Hypertension in Pregnancy: Effect of Prenatal Care on Maternal and Infant Health

by

Forgive Avorgbedor

Program in Nursing Duke University

Date:_______________________ Approved:

___________________________ Diane Holditch-Davis, Supervisor/Co-Chair

___________________________

Elizabeth I. Merwin, Chair

___________________________ Lynne Lewallen

___________________________

James Blumenthal

___________________________ SeonAe Yeo

___________________________

Susan Silva

Dissertation submitted in partial fulfillment of the requirements for the degree of Doctor

of Philosophy in Nursing in the Graduate School

of Duke University

2017

ABSTRACT

Hypertension in Pregnancy: Effect of Prenatal Care on Maternal and Infant Health:

by

Forgive Avorgbedor

Program in Nursing Duke University

Date:_______________________

Approved:

___________________________ Diane Holditch-Davis, Supervisor/Co-Chair

___________________________

Elizabeth I. Merwin, Chair

___________________________ Lynne Lewallen

___________________________

James Blumenthal

___________________________ SeonAe Yeo

___________________________

Susan Silva

An abstract of a dissertation submitted in partial fulfillment of the requirements for the degree

of Doctor of Philosophy in Nursing in the Graduate School of

Duke University

2017

Copyright by Forgive Avorgbedor

2017

iv

Abstract Background. Hypertensive disorders (chronic hypertension,

preeclampsia/eclampsia, preeclampsia superimposed on chronic hypertension and

gestational hypertension) are present in 6% to 8% of pregnancies in the United States.

The number of women of childbearing age who will develop hypertension is increasing

due to the obesity epidemic and the increasing maternal age at pregnancy. In the United

States, 3 to 5% of pregnant women have chronic hypertension before pregnancy or are

diagnosed in the first 20 weeks of pregnancy. Chronic hypertension contributes to

pregnancy related hypertension and has negative effects on maternal and infant

outcomes including preterm birth and small for gestational age infants. Prenatal care is

one of the most important preventative public health measures used globally and in the

United States because the goal is to detect potential complications during pregnancy and

provide appropriate and timely interventions. However, not all pregnant women have

access to early prenatal care and adequate prenatal care. The benefits of prenatal care

for maternal and infant outcomes for women with hypertensive disorders during

pregnancy have not been described. Therefore, the purpose of this dissertation was to

examine the influence of chronic hypertension, pregnancy induced hypertension and

prenatal care on pregnancy outcomes for women and their infants.

Methods. First, a secondary data analysis of the 2009-2011 Pregnancy Risks

Assessment Monitoring System (PRAMS) dataset for North Carolina (Chapter 3) was

conducted to understand the effects of chronic hypertension and prenatal care on

v

maternal and infant outcomes in pregnant women. Second, to understand whether

preterm infants born to women with hypertensive disorders of pregnancy differ from

those of women without hypertensive disorders in terms of illness and development

characteristics, a secondary data analysis of a study of maternally administered

interventions for neonates was conducted in Chapter 4.

Results. In Chapter 3, the results indicated that women with chronic

hypertension have higher risks for pregnancy induced hypertension, preterm birth, and

small for gestational age infants. In addition, first trimester or adequate prenatal care

did not improve pregnancy outcomes for women with chronic hypertension as it did for

women without chronic hypertension. In Chapter 4, preterm infants of women with

hypertensive disorders are more likely to be small for gestational age than preterm

infants of women without hypertensive disorders.

Conclusion. Overall results showed that preterm infants of women with

hypertensive disorders are small for gestational age when compared to preterm infants

of women without hypertensive disorders. Also, prenatal care has no significant impact

on improving pregnancy and birth outcomes of women with chronic hypertension.

iv

Dedication

I would like to dedicate this dissertation to the blessed memory of my

grandmother Madam Veronica Kokui Malorku Seshie. She was a stark illiterate herself

but was committed and contributed to my early education. She encouraged me to go to

school on an empty stomach whenever she could not provide money or breakfast for

me. She always told me to run fast home after school and always promised that by the

time I returned from school, there would be food and she never disappointed me.

Danye (my mother as I affectionately called her) has contributed to and motivated me

tremendously to be who I am today. These days, your words remain with me even in

your absence and I constantly encourage myself to run toward success in times of

difficulty.

I would also like to dedicate this dissertation to family, friends and all who

contributed to any aspect of my life and to all who are struggling to beat the odds and be

useful people to society, that the Almighty God grants them his favor.

v

Table of Contents

Abstract .......................................................................................................................................... iv

List of Tables ............................................................................................................................... viii

List of Figures ................................................................................................................................ x

Acknowledgements ..................................................................................................................... xi

Chapter 1. Hypertension in Pregnancy: An Introduction ...................................................... 1

1.1 Hypertensive Disorders of Pregnancy .................................................................... 1

1.2 Effects of Prenatal Care on Women with Chronic HTN and their Infants ....................................................................................................................... 3

1.3 Purpose of the Dissertation ...................................................................................... 4

1.3.1 Chronic Hypertension in Pregnancy and maternal and infant outcomes: A Literature Review .................................................................. 4

1.3.2 Effects of Chronic Hypertension and Prenatal Care on Maternal and Infant Outcomes: Analysis of North Carolina PRAMS Data ............................................................................................................. 5

1.3.3 Preterm Infant Illness and Developmental Outcomes after Pregnancy with and without Hypertensive Disorders of Pregnancy .................................................................................................................. 6

1.3.4 Summary of Significant Findings ................................................................. 7

1.4 Conceptual Framework ............................................................................................. 7

Chapter 2. Chronic Hypertension in Pregnancy and Maternal and Infant Outcomes: A Literature Review ................................................................................................ 11

2.1 Chronic Hypertension in Pregnancy ..................................................................... 11

2.2 Methods ..................................................................................................................... 12

2.2.1 Data Extraction .............................................................................................. 13

2.3 Results ........................................................................................................................ 13

vi

2.4 Discussion ................................................................................................................. 24

2.4.1 Future Research ............................................................................................. 26

2.5 Conclusion ................................................................................................................ 27

Chapter 3. Effects of Chronic Hypertension and Prenatal Care on Maternal and Infant Outcomes: Analysis of North Carolina PRAMS Data ....................... 29

3.1 Methods ..................................................................................................................... 33

3.1.1 Study Sample and Measures ....................................................................... 35

3.2 Data Analysis ............................................................................................................ 37

3.3 Results ........................................................................................................................ 42

3.4 Discussion ................................................................................................................. 59

3.5 Strengths .................................................................................................................... 64

3.6 Limitations ................................................................................................................ 64

3.7 Conclusions ............................................................................................................... 65

Chapter 4. Preterm Infant Illness and Developmental Outcomes after Pregnancy with and without Hypertensive Disorders of Pregnancy ................................. 66

4.1 Hypertensive disorders of pregnancy .................................................................. 66

4.2 Methods ..................................................................................................................... 69

4.2.1 Design ............................................................................................................. 69

4.2.2 Sample ............................................................................................................ 70

4.2.3 Measures ......................................................................................................... 72

4.3 Data Analysis ............................................................................................................ 74

4.3.1 Statistical Power ............................................................................................ 77

4.4 Results ........................................................................................................................ 77

4.5 Supplemental Analyses ........................................................................................... 85

vii

4.6 Discussion ................................................................................................................. 88

4.7 Limitations ................................................................................................................ 91

4.8 Conclusions ............................................................................................................... 92

Chapter 5. Conclusions and Knowledge Acquired ............................................................... 93

5.1 Summary of Significant Findings in Chapter 3 ................................................... 93

5.2 Summary of Significant Findings in Chapter 4 ................................................... 95

5.3 Need to Upgrade Prenatal Care for Women with Chronic Diseases ........................................................................................................................... 97

5.4 Summary of this Dissertation Findings .............................................................. 101

5.5 Direction for Future Research .............................................................................. 102

Appendix A. Abbreviations and Their Meanings ............................................................... 104

References .................................................................................................................................. 105

Biography ................................................................................................................................... 120

viii

List of Tables Table 1.1. Adapted Concepts from Neuman’s Model and Study Variables ....................... 9

Table 2.1. Comparison Groups and Incidence of Chronic Hypertension in Pregnancy ..................................................................................................................................... 15

Table 3.1. Conceptual and Operationalization Definitions of Study Variables ....................................................................................................................................... 36

Table 3.2. Characteristics of Women without and with Chronic HTN .............................. 42

Table 3.3. Characteristics of the Infants of Women without and with Chronic HTN ............................................................................................................................... 43

Table 3.4. Descriptive Statistics of the Prenatal Care Measures and Study Outcomes ...................................................................................................................................... 44

Table 3.5. Logistic Regression of Chronic HTN and Study Outcomes .............................. 46

Table 3.6. Logistic Regression of Early Prenatal Care, Chronic HTN, and Study Outcomes .......................................................................................................................... 48

Table 3.7. Logistic Regression of the Adequacy of Prenatal Care, Chronic HTN, and Study Outcomes ....................................................................................................... 51

Table 3.8. Logistic Regression of Maternal Education, Chronic HTN, and Study Outcomes .......................................................................................................................... 53

Table 3.9. Logistic Regression of Maternal Age, Chronic HTN, and Study Outcomes ...................................................................................................................................... 56

Table 3.10. Logistic Regression: Ethnicity, Chronic HTN, and Study Outcome ....................................................................................................................................... 58

Table 3.11. Final Reduced Models: Summary of Significant Findings .............................. 60

Table 4.1. Descriptive Statistics for Characteristics of the Preterm Infants and Their Mothers ...................................................................................................................... 78

Table 4.2. Descriptive Statistics for Illness Outcomes Variables for Preterm Infants ............................................................................................................................ 80

Table 4.3. Logistic Regression Models for Infant Illness Outcomes ................................... 81

ix

Table 4.4. Descriptive Statistics for Physical Developmental Outcomes of Preterm Infants ............................................................................................................................ 82

Table 4.5. Descriptive Statistics for Physical Developmental Outcomes at Birth and 2 Months .................................................................................................................... 83

Table 4.6. Analysis of Covariance for Physical Developmental Outcomes of Preterm Infants at 2 Months ................................................................................................. 84

Table 4.7. Descriptive Statistics and General Linear Models, for preterm Infant Neurobehavioral Outcomes at 12 Months ................................................................... 85

Table 4.8. Supplemental Analysis: Descriptive Statistics for Illness Outcomes of Preterm Infants .................................................................................................... 86

Table 4.9. Supplemental Analysis: Descriptive Statistics for Physical Developmental Outcomes of Preterm Infants ........................................................................ 87

Table 4.10. Supplemental Analysis: Descriptive Statistics for Preterm Infants Neurobehavioral Outcomes ......................................................................................... 88

x

List of Figures Figure 1.1. Conceptual Framework of Chronic Hypertension in Pregnancy and its Relationship with Prenatal Care, Maternal and Infant Outcomes ........................................................................................................................................ 8

Figure 2.1. The Relationship between Maternal Risk Factors, Chronic HTN, Prenatal Care, Maternal, and Infant Outcomes ........................................................... 14

Figure 3.1. Schematic Representation of Study Aims and Variables. ................................ 37

Figure 3.2. Interaction between Chronic Hypertension (HTN) and First Trimester Prenatal Care on Pregnancy Induced Hypertension (PIH). ............................... 49

Figure 3.3. Interaction between Chronic Hypertension (HTN) and Maternal Education on Pregnancy Induced Hypertension (PIH). ...................................... 55

Figure 3.4. Interaction between Chronic Hypertension (HTN) and Maternal Age on Pregnancy Induced Hypertension (PIH). ................................................. 57

Figure 4.1. Study Sample Selection, Inclusion and Exclusion Criteria ............................... 71

xi

Acknowledgements I would like to thank the Almighty God for His grace and favour He has shown

me. I would like to extend my gratitude to the Duke University School of Nursing for a

gift of education. I would like to thank all my committee members, mentors, advisors,

teachers and colleagues who continue to support me in my education path. It takes a

village to raise a child and there is no doubt you did that. Very often people do not

reply emails from strangers but I am blessed with committee members outside my

department and my school who responded to my emails and are committed to nothing

but my success. I had a great privilege of working with two extraordinary dissertation

chairs, Diane Holditch-Davis and Elizabeth Merwin. They supported greatly and helped

me to develop skills beyond dissertation writing. Dr. Diane Holditch-Davis continued

to work tirelessly even in her retirement for me to reach this stage of my doctoral

education. Dr. Holditch-Davis, thank you for your tremendous work and may the

Almighty God reward you. I would also like to extend my greatest appreciation to my

other committee members Lynne Lewallen, James Blumenthal, SeonAe Yeo and Susan

Silva for their encouragement and always being available to provide guidance

I would also like to acknowledge Dr. Teresa Johnson who mentored me as a

McNair scholar and stimulated my interest in research and academia.

I would like to extend my sincere appreciation to my husband Mr. Christian

Beinpuo for all his contributions and encouragement over the years. You have been

supportive of my ambitions and success since I met you. As if you were God sent to help

xii

me through my education in the United States and you have done that through my

undergraduate education to my doctoral education. I do not have words to express my

appreciation but I can say thank you (barka, akpe).

To my mother Ms. Innocentia Tamakloe, you are always at the right place at the

right time. If you had not shown up on that faithfully Wednesday, a day before the end

of registration to write my final exam at high school, that would have been the end of

my education. But you came based on a mother’s instinct and saved me from a lifetime

disappointment. You may take it as a responsibility but to me it was a rebirth of my

education.

I would also like to extend my gratitude to Mr. Richard Sloane for guiding me

through data cleaning process. I walked to your office the summer of 2016 and I was not

very sure where to start. Although, you had few days left to the end of your contract,

you were committed to guiding me through the process before the end of your contract

and you did just that. I would also like to extend my heartfelt gratitude to my host Mr

Leonel Ac-Lumor in the United States.

I would like to thank anyone who gave me a push or a pull at anytime in my life.

If you pushed me, you made me to believe in myself. If you pulled me, you challenged

me to do better. I have a number of people who helped me I cannot mention all the

names. People who gave me food because I was hungry, drivers’ mates (bus conductor)

who declined my payment so that I can keep the money, food sellers who gave me fish

because I could not afford. A teacher and a neighbour who gave me ride to school on

xiii

his motorbike, I say thank you. Also a company bus drivers who dropped me at school

although I had no family member working in that company to qualify me to ride on the

bus. To those who gave me accommodations when I needed it most God richly bless

you. My tutor, Mr. Julien Kwashie Setor who believed in me and predicted I would be “

an educationist and a disciplinarian”. To all of you I say God richly bless you wherever

you are. Indeed, you are the village that raised a child like me.

Finally, I would like to extent my appreciation to North Carolina Department of

Health and Human Services Division of Public Health for granting me the permission to

use the Pregnancy Risk Assessment Monitoring System (PRAMS) data for Chapter 3 of

my dissertation. Also, the North Carolina PRAMS project coordinator, Fatma Simsek for

continuously clarifying information in the PRAMS the data set. I would also like to

acknowledge Holditch-Davis, Mother Administered Interventions for Neonates NIH

5R01 NR008418-04 and her entire research team for allowing me to use their data to

answer my research questions in Chapter 4 of this dissertation.

1

Chapter 1. Hypertension in Pregnancy: An Introduction

1.1 Hypertensive Disorders of Pregnancy

Hypertensive disorders (HDP) are present in about 10% of pregnancies in the

United States (Wagner, Barac, & Garovic, 2007; Zamorski & Green, 2001). Hypertensive

disorders are classified into four groups: chronic hypertension (HTN),

preeclampsia/eclampsia, preeclampsia superimposed on chronic HTN and gestational

HTN (Wagner et al., 2007; Zamorski & Green, 2001). The number of women of

childbearing age who will develop HTN is increasing due to the obesity epidemic and

increasing maternal age at pregnancy (Seely & Ecker, 2014; Sibai, 2007; Zhang, Meikle, &

Trumble, 2003). Chronic HTN (systolic blood pressure ≥140 mm Hg or diastolic blood

pressure ≥90 mm Hg [NHBPEP, 2000]) develops before pregnancy or is diagnosed in the

first 20 weeks of pregnancy. In the United States, 3 to 5% of pregnant women have

chronic HTN (ACOG, 2013). Chronic HTN contributes to pregnancy induced HTN

(PIH) (preeclampsia/eclampsia, and preeclampsia superimposed on chronic HTN),

which has negative effects on maternal and infant outcomes (Bramham et al., 2014;

Clausen & Bergholt, 2014).

The most common complications among women with chronic HTN are preterm

birth (delivery before 37 weeks gestation), small for gestational age (SGA) infants (birth

weights below the 10th percentile for babies of the same gestational age), preeclampsia

superimposed on chronic HTN (Chronic HTN with new onset of organ damage with or

without protein in urine or (ACOG, 2013). Placental abruption (early partial or full

2

separation of the placenta from the wall of the uterus that may result in bleeding and

early delivery) (Ananth, Peltier, Kinzler, Smulian, & Vintzileos, 2007; Ananth, Savitz, &

Williams, 1996; Sibai, 2002).

Women with chronic HTN are at higher risk of preterm delivery than women

without chronic HTN. Preterm births among women with chronic HTN are mostly

medically indicated because these women are at higher risk for preeclampsia (Chappell

et al., 2008). The prevalence of preeclampsia is 17 to 25% in women with chronic HTN

compared to 3 to 5% in women without chronic HTN (Chappell et al., 2008). Some

infants of women with chronic HTN were found to be SGA (Kase, Carreno, Blackwell, &

Sibai, 2013).

Another complication associated with women with chronic HTN is placental

abruption. Placental abruption is associated with 10% of preterm birth and 10-20% of

perinatal deaths (Tikkanen, 2011). Placental abruption is three times more likely among

women with chronic HTN than women without chronic HTN and often results in

preterm birth (Ananth et al., 2007; Ananth & Vintzileos, 2011).

The adverse health effects associated with chronic HTN provide a strong

rationale for identifying risk factors associated with chronic HTN. Currently, the

American Congress of Obstetricians and Gynecologists recommends that women with

chronic HTN undergo thorough counseling about the importance of blood pressure

control before conception and in early pregnancy (Seely & Ecker, 2014; Sibai, 2002; Sibai,

2007). Most studies on chronic HTN do not focus on pregnant women with chronic

3

HTN and studies focusing on pregnant women usually exclude women with chronic

HTN from the research sample because chronic HTN is considered an existing condition

that confounds other variables in pregnancy.

1.2 Effects of Prenatal Care on Women with Chronic HTN and their Infants

Prenatal care (receiving health care during pregnancy) is one of the most

important preventative public health measures used globally and in the United States

because the goal is to detect potential complications and provide appropriate and timely

interventions (Alexander & Kotelchuck, 2001; Kogan et al., 1998). Due to the

complications of chronic HTN, women with chronic HTN need careful monitoring

during early pregnancy (as defined as initiation of prenatal care in the first trimester).

Vintzileos et al. (2002) found that an absence of prenatal care increases preterm birth 2.8

times in both Black and White women. In addition, preterm delivery among women

with chronic HTN with and without prenatal care was 20.2% vs. 39.2% (Vintzileos,

Ananth, Smulian, Scorza, & Knuppel, 2002). Prepregnancy counseling and first

trimester and adequate prenatal care are key to early detection of pregnancy

complications (Seely & Ecker, 2014; Sibai, 2007).

However, not all pregnant women have access to early and adequate prenatal

care (determined by the time of prenatal care initiation and the number of prenatal

visits). African American and Hispanic women are less likely to access prenatal care.

Late or no prenatal care may lead to inadequate blood pressure control among pregnant

4

women with chronic HTN (Bouthoorn et al., 2012; Goodwin & Mercer, 2005; Gregory &

Korst, 2003; Wolf et al., 2004). White women who usually have better maternal and

infant outcomes than Blacks and Hispanics are most likely to have private insurance and

seek early prenatal care (Carr, Kershaw, Brown, Allen, & Small, 2013).

Although some women with chronic HTN prior to pregnancy may not

experience any complications during pregnancy, others may develop pregnancy

complications that lead to adverse infant outcomes (Seely & Ecker, 2014). This variation

in maternal and infant outcomes and effects of HDP lacks clear explanation. However,

prenatal care might be associated with lower risk for a number of poor outcomes.

Therefore, early initiation and adequate prenatal care may lead to early detection and

prevention of these complications.

1.3 Purpose of the Dissertation

The purpose of this dissertation was to develop a deeper understanding of the

influence of chronic HTN, PIH and prenatal care on pregnancy outcomes for women

and their infants

1.3.1 Chronic Hypertension in Pregnancy and maternal and infant outcomes: A Literature Review

The objective of Chapter 2 was to conduct a systematic literature review of the

incidence and prevalence of chronic HTN in pregnancy and effects of prenatal care on

maternal and infant outcomes.

5

1.3.2 Effects of Chronic Hypertension and Prenatal Care on Maternal and Infant Outcomes: Analysis of North Carolina PRAMS Data

The objective of Chapter 3 is to compare women with chronic HTN with women

without chronic HTN on maternal and infant characteristics and pregnancy

complications. This chapter utilizes the Phase Six (2009-2011) of the Pregnancy Risk

Assessment Monitoring System (PRAMS) data from North Carolina. The purpose of

this chapter was:

Aim 1. To compare women with chronic HTN and women without chronic HTN

on PIH, placental abruption and adverse birth outcomes (preterm birth and SGA) after

adjusting for known perinatal risk factors of maternal age, educational level, and

ethnicity/race.

Hypothesis 1: The rate of pregnancy-induced HTN, placental abruption, preterm

birth and SGA will be significantly higher among women with chronic HTN compared

to women without chronic HTN, after adjusting for maternal age, education level, and

ethnicity/race.

Aim 2. To explore whether early access to prenatal care or adequacy of prenatal

care has differential effects on rates of PIH, placental abruption and adverse birth

outcomes for women with chronic HTN compared to women without chronic HTN,

after adjusting for known perinatal risk factors of maternal age, educational level, and

ethnicity/race.

Hypothesis 2: Early access to prenatal care and/or adequacy of prenatal care will

6

be associated with a lower rate of PIH, placental abruption, preterm birth, and SGA in

women with chronic HTN compared to women without chronic HTN, after adjusting

for maternal age, education level, and ethnicity/race.

Aim 3. To explore the moderating effects of perinatal risk characteristics on PIH,

placental abruption and infant adverse birth outcomes for women with and without

chronic HTN.

Hypothesis 3: Perinatal risk factors (maternal age, educational level,

ethnicity/race) will have a greater influence on rate of PIH, placental abruption, preterm

birth, and SGA in women with chronic HTN than in women without chronic HTN.

1.3.3 Preterm Infant Illness and Developmental Outcomes after Pregnancy with and without Hypertensive Disorders of Pregnancy

The objective of Chapter 4 was to examine whether preterm infants born to

women with HDP differ from women without HDP in terms of illness and development

characteristics. Chapter 4 used data from a study of maternally administered

interventions for neonates (Holditch-Davis et al., 2014).

Aim 1. To compare illness severity (neurobiological risk, patent ductus

arteriosus, number of days on ventilator, intraventricular hemorrhage, infections,

gestational age and SGA) in preterm infants with a history of maternal HDP compared

to preterm infants with no history of maternal HDP, controlling for study intervention,

prenatal care and maternal history of diabetes.

Hypothesis 1: Preterm infants of mothers with HDP will be less healthy, as

7

measured by neurobiological risk, patent ductus arteriosus, number of days on

ventilator, intraventricular hemorrhage, infections, gestational age and SGA, than

preterm infants of mothers without HDP, after controlling for study intervention,

prenatal care, and maternal history of diabetes.

Aim 2. To compare infant physical development (head circumference, height,

and weight) and neurodevelopment (cognitive, language, and motor skills) in preterm

infants with a history of HDP relative to those with no history of HDP, controlling for

study intervention, prenatal care, and maternal history of diabetes.

Hypothesis 2: Infant development, as measured by head circumference, height,

weight at 2 months as well as cognitive, language, and motor skills at 12 months for

preterm infants of mothers with HDP will be slower than preterm infants of mothers

without HDP, after controlling for study intervention, prenatal care, and maternal

history of diabetes.

1.3.4 Summary of Significant Findings

Chapter 5 synthesizes the knowledge developed across the dissertation chapters.

1.4 Conceptual Framework

The relationship between chronic HTN, pregnancy related HTN and maternal

and infant outcomes is complex. Thus, in order to understand the effects of chronic

HTN among pregnant women, the Neuman Systems Model (NSM) guided the

conceptual framework (Figure 1.1) for Chapter 3 of this dissertation. The Neuman

Systems Model is centered on a wellness orientation, and a dynamic systems perspective

8

toward energy and variable interactions with the environment to mitigate possible harm

(stressors) (Neuman & Fawcett, 2002).

Figure 1.1. Conceptual Framework of Chronic Hypertension in Pregnancy and its Relationship with Prenatal Care, Maternal and Infant Outcomes

Table 1.1 shows the concepts adapted from the NSM and corresponding

variables. These concepts explain the relationships between the variables used in

Chapter 3 of this dissertation. The basic attributes of a pregnant woman consist of the

Stressors

⇒ Pregnancy

⇒ Chronic HTN

Intervention Secondary Prevention

⇒ Early access to prenatal care

⇒ Adequate prenatal care

Maternal Outcome v Pregnancy induced

hypertension

v Placental abruption

Infant Outcomes

v Preterm birth

v Small for gestational age

Maternal Characteristics ⇒ Maternal age

⇒ Education

⇒ Ethnicity/race

9

woman’s ethnicity/race, education level, which may have a direct relationship with the

woman’s age, which may have an effect on the pregnancy. Pregnancy is a natural

occurrence that brings significant biophysical changes. The changes are more

pronounced if the pregnant woman has a chronic condition such as chronic HTN.

Pregnant women with chronic HTN require monitoring to identify potential

complications for mother and fetus.

Table 1.1. Adapted Concepts from Neuman’s Model and Study Variables

Basic Structure

Stressor Secondary Prevention Reaction to the Stressor

1. Maternal Education

1. Chronic HTN

1. Early access (1st trimester) prenatal care

1. Maternal outcomes

2. Maternal age

2. Adequate prenatal care 2. Infant outcomes

3. Ethnicity

Chronic HTN as a stressor (a force that can have negative effects) may disturb

the pregnant woman’s equilibrium or normal physiology of pregnancy, which may lead

to negative physiological changes in the pregnant woman and her fetus. The pregnant

woman and the unborn fetus are interdependent individuals due to the anatomical and

physiological relationship between them. Chronic HTN can be viewed as a

physiological stressor, the negative effects of which can be modified with first trimester

prenatal care and adequate prenatal care.

Early and adequate prenatal care may also be seen as an intervention for chronic

10

HTN during pregnancy that might have protective effects. Initiating prenatal care in the

first trimester and continuous prenatal care visits until delivery may help minimize

pregnancy associated complications of chronic HTN. Chronic HTN complications

during pregnancy develop in the form of preeclampsia, low gestational age, SGA, low

birth weight and placental abruption (Sibai, 2002).

Chronic HTN is a stressor that may have a significant effect on maternal and fetal

health. The pregnancy complications experienced by the pregnant woman may be

transmitted to the fetal system because mother and fetus can be considered as separate

units that are interdependent. A pregnant woman with chronic HTN who develops

preeclampsia could also develop placental abruption that would deprive the fetus of

oxygen and nutrients resulting in an SGA infant and preterm birth.

In summary, a stressor can either be an intrapersonal or interpersonal force.

Interpersonal stressor is a force that transpires between individuals, and a mother with

chronic HTN may transmit pregnancy complications through the fetal system to affect

infant outcomes. In addition, infant health including gestational age at birth, being

small for gestational age, birth weight, placental abruption and fetal growth restriction

are considered reactions to the stressor. Therefore, chronic HTN during pregnancy is

the presumed antecedent of pregnancy complications.

11

Chapter 2. Chronic Hypertension in Pregnancy and Maternal and Infant Outcomes: A Literature Review

2.1 Chronic Hypertension in Pregnancy

Chronic hypertension (HTN) in pregnancy has significant negative effects on

maternal and infant health during and after pregnancy (Ankumah & Sibai, 2017).

Chronic HTN is one of the leading causes of maternal and perinatal mortality

worldwide with 12% of maternal deaths annually resulting from maternal complications

secondary to HTN (Moodley, 2007). In the US, approximately four million women give

birth each year and about 1-5% of pregnant women are diagnosed with chronic HTN

(Lawler, Osman, Shelton, & Yeh, 2007; Seely & Ecker, 2014; Sibai, 2002). The number of

pregnant women diagnosed with chronic HTN is rising because of the increasing

incidence of risk factors such as maternal age, obesity, and diabetes (Seely & Ecker, 2014;

Sibai, 2002; Sibai et al., 2000).

In comparison to women without chronic HTN, women with chronic HTN have

twice the risk of having pregnancy complications (Bramham et al., 2014). Chronic HTN

in pregnancy increases the risk for adverse birth outcomes including preterm births,

small for gestational age (SGA) infants and perinatal death and for maternal risk factors,

particularly placental abruption and preeclampsia, compared to women without chronic

HTN (Ferrer et al., 2000; Livingston, Maxwell, & Sibai, 2003; Sibai, 2002). Chronic HTN

also increases the mother’s risk for future cardiovascular disease (Garovic et al., 2010;

Rich-Edwards, Fraser, Lawlor, & Catov, 2014).

12

Pregnancies complicated with chronic HTN may require early prenatal care

monitoring because chronic HTN leads to adverse pregnancy outcomes (Seely & Ecker,

2011). Early prenatal care is key to early detection of pregnancy complications (Seely &

Ecker, 2014; Sibai, 2007). Prenatal care is one of the most important preventive public

health measures used globally and in the U.S because the goal is to detect potential

complications and provide appropriate and timely preventive interventions (Alexander

& Milton, 2001; Kogan et al., 1998).

Chronic HTN affects maternal and infant health immediately after birth and

these adverse outcomes can have long-term effects. However, the lack of evidence on

the effects of prenatal care on women with chronic HTN presents a significant challenge

for effective management of maternal risk factors before and during pregnancy. The

objective of this literature review was to conduct a systematic review on the effects of

chronic HTN in pregnancy and prenatal care on maternal and infant outcomes.

2.2 Methods

A literature search for this review was conducted using MEDLINE (PubMed)

and the Cumulative Index to Nursing and Allied Health Literature (CINAHL)

databases. Searches in MEDLINE and CINAHL were conducted using the following

terms: chronic HTN, prepregnancy HTN, chronic HTN in pregnancy hypertensive

disorders of pregnancy (HDP), prenatal care, and birth outcomes. The searches were

limited to English language articles in peer-reviewed journals. After full text review, 38

13

articles met the inclusion criteria (a. included women with chronic HTN in the sample

and b. defined chronic HTN) for this literature review. Articles were excluded if a.

chronic HTN was excluded, b. the relation between chronic HTN birth outcomes was

not addressed, c. chronic HTN was not focused on pregnant women, or d. the

manuscript was not research.

2.2.1 Data Extraction

The data were extracted from each article using a matrix method. Both

prospective and retrospective articles were included in the review. The findings from

each article were classified in terms of the incidence or prevalence of chronic HTN and

the consequences of chronic HTN for infant and maternal risk factors and outcomes.

Infant outcomes were defined as any outcome directly related to infant health and

maternal outcomes were any outcome that affected maternal health.

2.3 Results

The sample sizes in the articles included in this review ranged from 68 (Samuel

et al., 2011) to 56,494,634 (Bateman et al., 2012). Figure 2.1 shows potential variables that

might contribute to chronic HTN, maternal and infant outcomes commonly associated

with chronic HTN, and the role of prenatal care in moderating these outcomes. The

variables in the input box (see Figure 2.1) were examined in most of the studies and

were found to contribute to maternal and infant outcomes.

Although the risks associated with chronic HTN during pregnancy are known,

findings from this literature review indicated that maternal and infant outcomes such as

14

preeclampsia, placental abruption, preterm birth and SGA infants continue to be more

frequent among women with chronic HTN than women without chronic HTN.

Figure 2.1. The Relationship between Maternal Risk Factors, Chronic HTN, Prenatal Care, Maternal, and Infant Outcomes

Incidence and Prevalence of Chronic HTN in Pregnant Women. The incidence and

prevalence of chronic HTN varied across geographical areas and ethnicities/races. Table

2.1 details the incidence of chronic HTN studies that included both women with chronic

HTN and women without chronic HTN. Nationwide data in the US found the incidence

of chronic HTN in pregnancy between 1995 and 2008 was approximately 1.3% (Bateman

et al., 2012). Data from California indicated that the incidence of chronic HTN ranges

from 0.7-1% among pregnant women with single births (Gilbert, Young, & Danielsen,

2007; Yanit, Snowden, Cheng, & Caughey, 2012) and 1.2% in multiple gestation

pregnancies (Yanit et al., 2012). In another cohort study in California, the prevalence of

INPUT 1. Race/ethnicity 2. Maternal age 3. Previous

preeclampsia

Chronic HTN

OUTPUT 1. Maternal Outcomes 2. Infant Outcomes

MODERATOR Prenatal Care

15

Table 2.1. Comparison Groups and Incidence of Chronic Hypertension in Pregnancy

Authors and Year Country Year (s)

Comparison Group (s) Sample Size (N)

CHTN (%)

Ananth et al., 2007 USA 1995-2002 CHTN, No CHTN 30,189,949 0.73

Ankumah, Cantu, et al., 2014 USA BP =140–150/90–99, BP<140/90 BP=151–159/100–109�

759

NA

Barbosa et al., 2015 Brazil, 4 years CHTN, PE, Eclampsia, SPE/ Eclampsia

1,501 37.6

Bateman et al., 2012 USA, 1995-2008 CHTN, No CHTN 56,494,634 1.3

Bateman et al., 2014 USA, 2000-2007 CHTN, No CHTN 878,126 2.3

Broekhuijsen et al., 2015 Netherlands, 2002-2007 CHTN, No CHTN 988,389 0.3

Bryant et al., 2005 USA, 1998 CHTN, Pregnancy related HTN with no CHTN

1, 355 1.8

Carr et al., 2013 USA, 1978-2010 Hypertensive disorders, Ethnicity 279 19.4

Cruz et al., 2011 USA, 2002 and 2008 Mild CHTN, GHTN, Mild PE 27, 944 9.1

Ferrazzani et al., 2011 Italy, 1986-1995 CHTN, No CHTN, GHTN, PE, SPE

1, 965 16.0

Fridman et al., 2014 USA, California, 1999, 2002 and 2005

CHTN, Pregnancy related HTN 1, 551,017 0.8

Giannubilo et al., 2006 Italy, Ancona, 1999–2003 Mild CHTN, No CHTN 423 53

Gilbert et al., 2007 USA, California, 1991-2001 CHTN, No CHTN 4, 324, 904 0.69

Graham et al., 2007 USA, Mississippi, 1999-2003 CHTN, Ethnicity 202,931 1.6

16

Authors and Year Country Year (s)

Comparison Group (s) Sample Size (N)

CHTN (%)

Hu et al., 2016 China PE, SPE 850 0.2

Kase, Carreno, et al., 2013 USA, May 1991 to June, 1995 CHTN

765

NA

Lisonkova & Joseph, 2013 USA, Washington State, 2003- 2008

CHTN, Early-onset (<34 weeks) and Late-onset PE (>34 weeks)

456,668 1.2

Luke & Brown, 2007 USA, 1995–2000 CHTN, Parity, Maternal age groups

8, 079,996 NA

Madi et al., 2012 Brazil, March 1998 and February 2009

Chronic HTN, No HTN 5,945 5.5

Metz et al., 2014 USA, 1991 and 1995 CHTN, insulin-dependent diabetes, multiple gestation, previous PE

1,258 30.8

Moussa, Leon, et al., 2016 USA CHTN, SPE, SPE with severe features

774

NA

Odell et al., 2006 USA, Massachusetts CHTN, Haitian and African-American

16,578 2.2

Ono, Takagi, et al., 2013 Japan, 1 January 2006 and 31 December 2009,

Controlled HTN, Uncontrollable HTN, SPE. �

120

NA

Osmanagaoglu et al., 2004 Turkey, January 1992 to January 2003

CHTN, HELLP syndrome, SPE 147 16%

Pare et al., 2014 USA CHTN, PE in the exposed/ non exposed group

2,637 6.3

17

Authors and Year Country Year (s)

Comparison Group (s) Sample Size (N)

CHTN (%)

Prakash, Pandey, Singh, &Kar, 2006

India, July 2000-June 2002

CHTN PE, Eclampsia, HELLP syndrome, SPE

1,802

0.33

Roberts et al., 2005 Australia, 1 January 2000 and 31 December 2002

CHTN, PE, SPE, GHTN, No HTN 250,173 0.6

Sabol, de Sam Lazaro, et al., 2014

USA, California 2007–2012 CHTN, Race/ethnicity 21, 353 NA

Samadi et al., 2001 USA, 1979-1986 CHTN, Race/ethnicity 182,687 0.88

Samuel et al., 2011 USA, 1995–2005 CHTN, SPE 78,392 1.6

Savitz et al., 2014 USA, New York State, New York City, 1995–2004

CHTN, SPE, PE, GHTN 1,171,131 788,454

0.83 0.85

Sibai, Koch, et al., 2011 Brazil CHTN with or without prior PE 369 ANA

Tuuli et al., 2011 USA, January 1990 -December 2008

CHTN, SPE, PE, No CHTN 62,841 2.4

Vanek et al., 2004 Israel, 1988 and 1999 CHTN, No CHTN 113,156 1.6

Vigil-De Gracia et al., 2004 Spain, July 1996 and June 2001

CHTN, SPE 154 100

Yanit et al., 2012 USA, California, 2006 CHTN, No CHTN, Pregestational diabetes, CHTN /pregestational diabetes

532,088 1.0

18

Authors and Year Country Year (s)

Comparison Group (s) Sample Size (N)

CHTN (%)

Zetterstrom et al., 2005 Sweden, 1992- 1998 CHTN, No CHTN 681 515 0.5 Note: NA= Studies that included only women with chronic HTN or the percent of chronic hypertension was not indicated. CHTN =chronic hypertension, PE =preeclampsia; GHTN= gestational hypertension and SPE = preeclampsia superimposed on chronic hypertension

19

chronic HTN among pregnant women increased by 47.5% between 1999 and 2005

(Fridman et al., 2014). Between 1995 and 2004, the prevalence of chronic HTN in New

York and New York City was 0.83% and 0.85% respectively (Savitz, Danilack, Engel,

Elston, & Lipkind, 2014). One study in Mississippi found that 1.6% of the sample had

chronic HTN between 1999-2003 (Graham, Zhang, & Schwalberg, 2007). Another US

study found that the rate of chronic HTN between 1990-2008 was 2.4% (Tuuli,

Rampersad, Stamilio, Macones, & Odibo, 2011).

Chronic HTN in pregnancy is a global issue and the incidence of chronic HTN

varies among countries. Studies conducted outside the United States found a similar or

higher incidence of chronic HTN than those in the US. Chronic HTN had an incidence

of 5.5% among women who delivered between 1998 and 2009 in Brazil (Madi et al.,

2012). In Israel, 1.6% of the pregnant women had chronic HTN (Vanek, Sheiner, Levy, &

Mazor, 2004). In the Netherlands, 0.3% of pregnant women had chronic HTN

(Broekhuijsen et al., 2015). The incidence of chronic HTN is associated with severe

pregnancy morbidity and mortality (Gilbert et al., 2007).

Risk Factors Associated with Chronic HTN. Maternal race/ethnicity has a significant

relationship with chronic HTN and its associated pregnancy complications and adverse

birth outcomes. Black pregnant women were at higher risk of chronic HTN than White

and Hispanic women (Carr et al., 2013; Gilbert et al., 2007; Kase et al., 2013; Metz,

Allshouse, Euser, & Heyborne, 2014; Samadi, Mayberry, & Reed, 2001). The incidence of

chronic HTN among Black women was 2 times higher than the incidence in White

20

women. The incidence of chronic HTN among Black women was 1.64%, which was

more than that of White and Hispanic women combined (0.79 and 0.49 respectively)

(Gilbert et al., 2007). In two other studies that used data from low dose aspirin trial for

high-risk pregnant women (insulin-dependent diabetes, hypertension, multiple

gestation and previous preeclampsia), chronic HTN was found in nearly 66% of Black

women in comparison to only 34% in all other races/ethnicities combined together (Metz

et al., 2014); 61% of Black women had chronic HTN compared to 27% of White and 11%

of Hispanic women (Kase et al., 2013).

The pregnancy complications and adverse birth outcomes associated with

chronic HTN occur frequently among Black women and other ethnic minorities. The

percent of most adverse perinatal outcomes related to chronic HTN such as preterm

birth (Kase et al., 2013; Sabol et al., 2014), low birth weight infants (Kase et al., 2013),

intrauterine fetal demise and post-neonatal death were higher among Black women than

White women (Sabol et al., 2014). Black women were also more likely than White

women to develop preeclampsia, the most common negative maternal outcome

associated with chronic HTN (Bryant, Seely, Cohen, & Lieberman, 2005; Poon, Kametas,

Chelemen, Leal, & Nicolaides, 2010; Sabol et al., 2014; Samadi et al., 2001).

Women with chronic HTN are older than those without chronic HTN (Bateman

et al., 2012; Broekhuijsen et al., 2015; Madi et al., 2012). For women with chronic HTN,

advanced maternal age leads to negative infant outcomes such as low birth weight and

preterm birth (Luke & Brown, 2007; Madi et al., 2012). Women with chronic HTN and

21

older women are more likely to develop preeclampsia (Hu, Feng, Dong, & He, 2016;

Luke & Brown, 2007), eclampsia and postpartum hemorrhage (Broekhuijsen et al., 2015).

Maternal outcomes. Most of the adverse birth outcomes among women with

chronic HTN occur because of worsening blood pressure during pregnancy (Ankumah

et al., 2014; Kase et al., 2013; Odell et al., 2006; Samuel et al., 2011). The most common

complication associated with chronic HTN is preeclampsia superimposed on chronic

HTN. Preeclampsia is more serious among women with chronic HTN than in women

without chronic HTN (Ankumah et al., 2014; Bateman et al., 2012; Broekhuijsen et al.,

2015; Moussa et al., 2016; Osmanagaoglu, Erdogan, Zengin, & Bozkaya, 2004; Pare et al.,

2014; Samadi et al., 2001; Samuel, Lin, Parviainen, & Jeyabalan, 2011; Yanit et al., 2012;

Zetterstrom, Lindeberg, Haglund, & Hanson, 2005). Preeclampsia superimposed on

chronic HTN contributes to adverse outcomes (Zetterstrom et al., 2005). A higher

percentage (ranges from 8.7 to 28.7) of women with chronic HTN developed

preeclampsia compared to women without chronic HTN (Bateman et al., 2012; Bryant et

al., 2005; Gilbert et al., 2007; Lisonkova & Joseph, 2013; Moussa et al., 2016;

Osmanagaoglu et al., 2004; Pare et al., 2014; Samadi et al., 2001; Samuel et al., 2011; Yanit

et al., 2012; Zetterstrom et al., 2005).

Another pregnancy complication common among women with chronic HTN is

placental abruption. In comparison to women without chronic HTN, women with

chronic HTN were about 2-3 times more likely to be diagnosed with placental abruption

in pregnancy (Ananth et al., 2007; Gilbert et al., 2007; Hu et al., 2016; Yanit et al., 2012;

22

Zetterstrom et al., 2005). In addition, chronic HTN in pregnancy increases the risk of

morbidity and death in women (Cruz, Gao, & Hibbard, 2011; Gilbert et al., 2007;

Osmanagaoglu et al., 2004). Chronic HTN in pregnancy was also associated with an

increased risk for thrombotic events (Broekhuijsen et al., 2015; Cruz et al., 2011),

postpartum hemorrhage (Broekhuijsen et al., 2015; Vanek et al., 2004), uterine rupture

(Broekhuijsen et al., 2015) and cesarean section (Broekhuijsen et al., 2015; Gilbert et al.,

2007; Hu et al., 2016; Osmanagaoglu et al., 2004) than women without chronic HTN.

Infant outcomes. Chronic HTN is also related to significant infant health

complications. Infants born to women with chronic HTN are at significantly increased

risk for SGA (Ananth et al., 2007; Ferrazzani et al., 2011; Giannubilo, Dell'Uomo, &

Tranquilli, 2006; Madi et al., 2012), stillbirth or neonatal death (Barbosa et al., 2015; Madi

et al., 2012; Vanek et al., 2004), NICU admission or prolonged hospitalization (Madi et

al., 2012; Samuel et al., 2011; Vigil-De Gracia, Lasso, & Montufar-Rueda, 2004) and

preterm birth (Broekhuijsen et al., 2015; Ferrazzani et al., 2011; Graham et al., 2007; Kase

et al., 2013; Madi et al., 2012; Yanit et al., 2012).

Early delivery was more common among women with chronic HTN as result of

greater percent of these women developing preeclampsia, which led to NICU

admissions (Broekhuijsen et al., 2015; Cruz et al., 2011) and fetal death, than did women

without chronic HTN (Barbosa et al., 2015; Bateman et al., 2012; Cruz et al., 2011; Gilbert

et al., 2007; Roberts, Algert, Morris, Ford, & Henderson-Smart, 2005). Women with

chronic HTN had about 70% increased risk for preterm delivery (Broekhuijsen et al.,

23

2015). Preterm birth was significantly higher among women with chronic HTN than

women without chronic HTN, with the estimated rates of preterm delivery ranging from

10.7% to about 26% of studied samples (Broekhuijsen et al., 2015; Yanit et al., 2012).

Women with chronic HTN were also more likely to have preterm infants who

were also SGA (Kase et al., 2013). A higher percent of SGA infants occurred in pregnant

women with chronic HTN compared to women without chronic HTN (Ankumah et al.,

2014; Bateman et al., 2012; Broekhuijsen et al., 2015; Cruz et al., 2011; Ferrazzani et al.,

2011; Giannubilo et al., 2006; Osmanagaoglu et al., 2004; Yanit et al., 2012). According to

Yanit, Snowden, Cheng, and Caughey (2012), 18.3% of infants born to women with

chronic HTN were SGA compared to only 10.1% of infants of women without chronic

HTN. Preterm infants of women with chronic HTN also had low birth weight

(Broekhuijsen et al., 2015; Giannubilo et al., 2006).

Prenatal care. A growing number of mothers and infants are at risk for negative

outcomes because of the increasing prevalence of chronic HTN in pregnancy. Pregnant

women interact with the health care system through prenatal care. Barbosa et al. (2015)

conducted a study in Brazil that evaluated the impact of prenatal care on HPD in

association with maternal and infant outcomes. They found that the risk of maternal

death was 6 times higher when a mother had no prenatal care than when the women

received prenatal care, and inadequate prenatal care was also associated with increased

risk of maternal death (Barbosa et al., 2015). Incomplete or no prenatal care among

mothers with chronic HTN more than doubled the risks of stillbirth and neonatal deaths

24

(Barbosa et al., 2015). Although Haitian women with chronic HTN living in the USA

were more likely to initiate prenatal care in the first trimester and receive adequate

prenatal care compared to African American women with chronic HTN, the rate of low

birth weight was higher among Haitian women with chronic HTN (Odell et al., 2006).

Timely and effective management of chronic HTN may improve maternal and

infant outcomes. According to Ono et al. (2013), uncontrolled chronic HTN in

pregnancy predisposed women to be at high risk for preeclampsia. The infants of

women with chronic HTN, whether the women received treatment or not, were at 20-

30% increased risk for congenital malformations as compared to the infants of the

normotensive women (Bateman et al., 2014). Untreated HTN further increased the risk

of infant cardiac malformations (Bateman et al., 2014). A small increase in blood

pressure in women on blood pressure medication and women without blood pressure

medications resulted in increase in preterm birth, SGA, and preeclampsia (Ankumah et

al., 2014; Roberts et al., 2005). Controlling chronic HTN during pregnancy resulted in

better birth outcomes such as lower rates of preterm birth, LBW infants and NICU

admissions than experienced by women with uncontrolled HTN (Ono et al., 2013).

2.4 Discussion

The overall finding in this review was that maternal chronic HTN alone

increased the risks of adverse maternal and infant outcomes. This literature review

showed that the incidence of chronic HTN in pregnancy continues to increase

25

worldwide. Adverse maternal and infant outcomes were more severe when

preeclampsia was superimposed on chronic HTN as well as when maternal age was

greater. The most common birth and maternal outcomes associated with chronic HTN

in pregnancy were preeclampsia superimposed on chronic HTN, preterm birth, LBW

infants, placental abruption, and SGA infants. Rarer complication included congenital

malformations in the infant. The risk of adverse birth outcomes for women with chronic

HTN is high even without other pregnancy complications (McCowan, Buist, North, &

Gamble, 1996).

Using different comparison groups, some infant and maternal risk factors

(preeclampsia, preterm birth and placental abruption) have been found to be highly

associated with chronic HTN (Sibai et al., 2011). An earlier review indicated that women

with chronic HTN were at higher risk for perinatal mortality, placental abruption, and

SGA (Ferrer et al., 2000). Bramham et al. (2014) found that the incidence of chronic HTN

continued to increase and that adverse birth outcomes in women with chronic HTN

were more common than in women without chronic HTN.

The pregnancy outcomes of women with chronic HTN varied by race/ethnicity

and country of birth. The differences in pregnancy outcomes with chronic HTN may be

the result of other maternal risk factors such as obstetric history, medical history and

socioeconomic factors. Infants born to women with chronic HTN had more health

complications than infants born to women without chronic HTN. Confirming findings

of previous reviews (Bramham et al., 2014; Ferrer et al., 2000), this literature review

26

found that infants born to women with chronic HTN were more often preterm or SGA

than infants of women without chronic HTN. Further, infants of women with HTN

were more likely to be born through cesarean section or labor induction and to stay

longer in the hospital than infants born to women without chronic HTN.

2.4.1 Future Research

Both individual articles and literature reviews on chronic HTN in pregnancy

have demonstrated the risks associated with chronic HTN in pregnancy. Enough

evidence supports the association between chronic HTN and adverse maternal and

infant outcomes to move towards determining whether the current method of delivery

of prenatal care improves, prevents or minimizes the complications associated with

pregnancy and chronic HTN (Dayan, Lanes, Walker, Spitzer, & Laskin, 2016; Zhou et al.,

2016). Chronic HTN in pregnancy is complex; thus, understanding and managing

chronic HTN is essential.

There is a need for studies to focus on understanding the impact of prenatal care

for women with chronic HTN. Because this review also found that prenatal care could

potentially improve maternal and infant outcomes for women with chronic HTN.

However, only one article investigated the effect of prenatal care on women with HDP

(Barbosa et al., 2015). They concluded prenatal care improves maternal and infant

outcomes for women with HDP and no or inadequate prenatal care results in maternal

and neonatal death (Barbosa et al., 2015). They also suggested prenatal care is

inexpensive and focusing on the key roles and strategy of prenatal care could improve

27

maternal and infant outcomes

2.4.2 Limitations

Research on chronic HTN in pregnancy has limitations. The comparison groups

for the studies included in this review were different; the samples were compared to

either women without chronic HTN or other hypertensive groups. Lack of consistency

in the control groups limited generalizing about the complications associated with

chronic HTN. However, there was an indication that when chronic HTN is compared to

other hypertensive disorders, complications are more prevalent among women with

chronic HTN. The small number of intervention studies limits the empirically based

treatment options for women with chronic HTN.

Only limited research on the benefits of prenatal care for women with chronic

HTN has been conducted. The limitation of the only study conducted in this area was

that the influence of sociodemographic variables was not evaluated. Ultimately, more

research on prenatal care for women with chronic HTN is needed because prenatal care

appears to moderate the effects of chronic HTN on adverse maternal and infant

outcomes.

2.5 Conclusion

Chronic HTN and pregnancy complications are strongly associated. Both

maternal and infant outcomes were affected negatively by the presence of other

complicating factors (ethnicity, maternal age, history of previous pregnancy

28

complications). Sufficient evidence exists that early prenatal care and controlling

chronic HTN are necessary to curb adverse maternal and infant birth outcomes

associated with chronic HTN.

29

Chapter 3. Effects of Chronic Hypertension and Prenatal Care on Maternal and Infant Outcomes: Analysis of North Carolina PRAMS Data1

Chronic hypertension (HTN) is one of the leading maternal morbidities during

pregnancy and is associated with short- and long-term health problems for mothers and

their infants (Curtin, Gregory, Korst, & Uddin, 2015). Chronic HTN occurs in 1-5% of

pregnant women in the US (Livingston et al., 2003; Livingston & Sibai, 2001). According

to Child Health USA (2013), the prevalence of chronic HTN in pregnancy was 14.0 per

1,000 live births in 2011 and this disease mostly affected non-Hispanic Black women

(29.0 per 1,000 live births). Chronic HTN continues to increase among pregnant women

in the US partly due to increased maternal age (Curtin et al., 2015). As the average

maternal age for first time mothers increases, so does the incidence and prevalence of

chronic HTN, which often leads to adverse birth outcomes (Chan & Lao, 2008; Fretts,

2005; Luke & Brown, 2007; Wang, Tanbo, Abyholm, & Henriksen, 2011).

Adverse pregnancy and birth outcomes associated with chronic HTN are

prevalent (Bateman et al., 2012; Bramham et al., 2014). In comparison to women without

chronic HTN, women with chronic HTN have twice the risk for pregnancy

complications (Bramham et al., 2014). The adverse pregnancy and birth outcomes

include preterm birth (Broekhuijsen et al., 2015), small for gestational age (SGA) infants

1 PRAMS data used in this chapter was provided by North Carolina Department of Health and Human Services, Division of Public Health

30

(Ananth et al., 2007), placental abruption (Gilbert et al., 2007) and pregnancy related

HTN (Barbosa et al., 2015).

Worldwide, chronic HTN leads to pregnancy induced hypertension (PIH)

including preeclampsia (defined as HTN with new onset of organ damage with or

without protein in urine [ACOG, 2013]) a major cause of maternal mortality and infant

morbidity (Bramham et al., 2014; Chappell et al., 2008; Roberts et al., 2011; Schoenaker,

Soedamah-Muthu, & Mishra, 2014). In the United States, the rate of preeclampsia has

increased 25% in 20 years (Sibai et al., 2011). Women with chronic HTN are at greater

risk of superimposed preeclampsia than women without chronic HTN (Caughey,

Stotland, Washington, & Escobar, 2005; Chang et al., 2014; Tanaka et al., 2007). Thus,

women with chronic HTN need careful monitoring during pregnancy. For women

diagnosed with preeclampsia, the only cure is delivery to prevent progression. Thus,

preeclampsia alone contributes to about 15% of all preterm births (Sibai et al., 2011).

Women with chronic HTN experience other pregnancy complications that may

contribute to premature birth. Chronic HTN also predisposes pregnant women to

delivering small for gestational age (SGA; birth weight below the 10th percentile for

babies of the same gestational age) infants, as a result of decreased blood flow and

placental abruption (Catov, Nohr, Olsen, & Ness, 2008). Placental abruption is the early

separation of the placenta from the wall of the uterus that may result in bleeding and

early delivery (Seely & Maxwell, 2007). SGA infants are most common among women

whose pregnancies are complicated by preeclampsia (Ferrazzani et al., 2011). In

31

addition, chronic HTN may affect placental development, which can limit nutrition to

the fetus, thus causing uterine growth restriction and low birth weight (Savitz et al.,

2014; Seed et al., 2011; Seely & Maxwell, 2007).

In 2013, the prevalence of preterm birth and low birth weight in the U.S. were

11.4% and 8.0% respectively (Osterman, Kochanek, MacDorman, Strobino, & Guyer,

2015). Preterm births among women with chronic HTN may occur due to other

complications associated with chronic HTN. Preeclampsia, placental abruption, and

SGA infants associated with chronic HTN contribute to early delivery (Lawler et al.,

2007; Lecarpentier et al., 2013). SGA is particularly common among preterm infants

because preeclampsia is a precursor to both SGA infants and preterm birth (Clausson,

Cnattingius, & Axelsson, 1998). Despite extensive research on the causes of preterm

births, there is no clear understanding of how to prevent them because of the large

number of complications associated with preterm birth (Hamed, Alsheeha, Abu-

Elhasan, Abd Elmoniem, & Kamal, 2014).

Prenatal care is the most common intervention to prevent the complications

associated with chronic HTN in pregnancy (Rotundo, 2011). As a preventive measure,

prenatal care is intended to improve maternal and infant outcomes. The infant mortality

rate is higher if the mother did not receive first trimester prenatal care (Loggins &

Andrade, 2014). However, the benefits of prenatal care for pregnant women with

chronic HTN are under studied. The lack of attention to the benefits of prenatal care for

women with chronic HTN was raised as an issue almost two decades ago (Alexander &

32

Milton, 2001; Knuist, Bonsel, Zondervan, & Treffers, 1998). In their commentary on

prenatal care, Alexandra and Kotelchuck (2001) asserted that benefits of prenatal care

could differ among subgroups and that prenatal care may have a greater effect on

individuals from ethnic minority groups, with low SES backgrounds, or with chronic

illness.

Nevertheless, few studies have compared the effects of early, adequate prenatal

care with later or no prenatal care on birth weight, gestational age at birth and mode of

delivery for women with chronic HTN (Alexander & Milton, 2001; Knuist et al., 1998).

Determining whether prenatal care positively influences birth outcomes--preterm birth,

SGA infants, placental abruption and PIH—might lead to identifying ways to improve

care for women with chronic HTN.

The objective of this study was to determine whether early access to prenatal

care, adequacy of prenatal care and maternal risk factors moderate the effects of chronic

HTN on maternal and infant outcomes. This study was a secondary analysis of the

2009-2011 Pregnancy Risks Assessment Monitoring System (PRAMS) dataset for North

Carolina (NCSCHS, 2016). Specific aims and hypotheses tested were:

Aim 1. To compare women with chronic HTN to women without HTN on PIH,

placental abruption, and adverse birth outcomes (preterm birth and SGA) adjusting for

known perinatal risk factors of maternal age, educational level, and ethnicity.

Hypothesis 1: The rate of PIH, placental abruption, preterm birth, and SGA

infants would be significantly higher among women with chronic HTN than in women

33

without chronic HTN, after adjusting for maternal age, education level, and ethnicity.

Aim 2. To explore whether early access to prenatal care or adequacy of prenatal

care had differential effects on rates of PIH, placental abruption and adverse birth

outcomes for women with chronic HTN compared to women without chronic HTN,

adjusting for known perinatal risk factors of maternal age, educational level, and

ethnicity.

Hypothesis 2: Early access to prenatal care and/or adequacy of prenatal care

would lead to a greater decrease in the rate of PIH, placental abruption, preterm birth,

and SGA infants in women with chronic HTN than in women without chronic HTN,

after adjusting for maternal age, education level, and ethnicity.

Aim 3. To explore the moderating effects of perinatal risk characteristics on PIH,

placental abruption, and infant adverse birth outcomes for women with and without

chronic HTN.

Hypothesis 3: Perinatal risk factors (maternal age, education level, ethnicity)

would have a greater influence on rate of PIH, placental abruption, preterm birth, and

SGA infants in women with chronic HTN than in women without chronic HTN.

3.1 Methods

This secondary data analysis utilized the 2009-2011 Pregnancy Risk Assessment

Monitoring Surveillance (PRAMS) data from North Carolina (NC) (NCSCHS, 2016). The

PRAMS dataset compiles state-specific, population-based data to monitor maternal

34

behaviors, conditions and experiences before, during, and shortly after pregnancy

among women who deliver live-born infants (Shulman, Gilbert, & Lansky, 2006). The

women involved in the PRAMS are not representative of all pregnancies because only

pregnancies resulting in live births are included in the survey. Since 1987, PRAMS has

been one of the main surveillance initiatives of the Centers for Disease Control and

Prevention (CDC) to better understand the factors related to infant mortality and low

birth weight. According to the CDC, currently 47 states, New York City, Puerto Rico,

the District of Columbia and the Great Plains Tribal Chairmen’s Health Board

participate in PRAMS. About 1,700 new mothers from North Carolina are sampled

every year for the PRAMS (NCSCHS, 2016).

The PRAMS system uses a standardized data collection approach: birth

certificate data and questionnaire data. The two sources of data are combined to create

the PRAMS final analysis data set. The first questionnaire is usually mailed to women

2–6 months after they deliver a live infant. Selection of women is based on a stratified

sampling scheme applied to birth certificates each month (Shulman et al., 2006).

According to the CDC, some states were stratified based on low birth weight and other

states were stratified based on mother’s race or ethnicity. North Carolina stratified

based on low birth weight. A survey method of data collection is used and includes

mailed questionnaires with telephone follow-up.

PRAMS surveys consist of core questions for all 47 participating states and

optional standard and state-developed questions. All participants in the survey answer

35

standard questions: “At any time during 12 months before you got pregnant with your

new baby, did you do any of the following?”, “I visited a health care worker to be

treated for high blood pressure? No or Yes.“ “How many weeks or months pregnant

were you when you had your first visit for prenatal care?” (Shulman et al., 2006).

PRAMS data are revised periodically. The most recent Phase 6 data was analyzed in this

dissertation (2009-2011). For information on sampling method of PRAMS data in North

Carolina, see http://www.schs.state.nc.us/units/stat/prams/datacollect.htm.

3.1.1 Study Sample and Measures

North Carolina PRAMS respondents for the study period (2009-2011) consisted

of 5,526 women with live births. The exclusion criteria for this analysis were multiple

births and lack of data on chronic HTN. The sample for this secondary analysis was

2,917 women with a singleton birth and their infants. The number of the respondents

with chronic HTN was 292 (10%) and the number without chronic HTN was 2625 (90%).

The percentage of respondents who answered the questions relating to chronic HTN for

each year was similar, 1087 (37.3%) in 2009, 918 (31.5%) in 2010 and 912 (31.3%) in 2011.

The study compared women with and without chronic HTN. Chronic HTN was defined

as HTN before conception or diagnosis of HTN before 20 weeks gestation. Hypertensive

disorders were classified as chronic/prepregnancy HTN, pregnancy induced/gestational

HTN, preeclampsia and preeclampsia superimposed on chronic HTN (Abalos et al.,

2014). Table 3.1 lists and defines the key variables and their coding used to describe the

sample and address each aim. Figure 3.1 provides as schematic representation of the

36

study aims and study measures for each aim included in this secondary analysis.

Table 3.1. Conceptual and Operationalization Definitions of Study Variables

Variable Conceptual definition Operationalization Group: Chronic/Prepregnancy Hypertension (chronic HTN)

Received treatment for high blood pressure from healthcare provider 3 months before pregnancy, not including hypertension beginning during pregnancy

Chronic HTN before conception or diagnosis of hypertension before 20 weeks gestation, coded as chronic HTN: 1=Yes or 0=No (control)

Outcome: Pregnancy induced hypertension (PIH)

High blood pressure, hypertension (including pregnancy induced hypertension, preeclampsia, or toxemia) during pregnancy

PIH defined as having at least one of the listed hypertensive disorders during pregnancy, coded as PIH: 1=Yes or 0=No

Outcome: Small for gestational age (SGA)

Fetal growth restriction defined as an estimated infant birth weight less than the 10th percentile for gestational (Sibai, 2002)

SGA, coded as 1=Yes or 0=No

Outcome: Placental abruption

Premature separation of the placenta from the underlying myometrium resulting in pain, bleeding, and, potentially, clinically significant interruption of fetal gas and nutrient exchange (Lowe et al., 2009)

Placental abruption during current pregnancy, coded as 1=Yes or 0=No

Outcome: Preterm birth

Birth before 37 weeks gestation

Gestation at <37 weeks, coded as 1=Yes or No

Early prenatal care (1st trimester prenatal care)

Initiation of prenatal care during the first trimester

Respondents received prenatal care during the first trimester of pregnancy, coded as 1=Yes or 0=No

Adequate prenatal care (Adequacy of prenatal care)

Kessner Index measures the time of prenatal care initiation and the numbers of prenatal visits, coded as 2=adequate, 1=intermediate, 0=inadequate/no prenatal care (Kotelchuck, 1994).

Kessner Index recoded as: or 0=intermediate, inadequate, no prenatal care, no response 1=adequate

37

Variable Conceptual definition Operationalization Maternal age Mother’s age recorded on the birth

certificate Maternal age, in years

Maternal ethnicity Self-identified racial/ethnic category according to the U.S. Census definition/birth certificate ('Black', ‘White', ‘Hispanic’ and ‘Other’).

Ethnicity, categorized as 0=Non-Black 1=Black

Maternal education Number of years of attending formal education as recorded on the birth certificate

Maternal education, in years

Figure 3.1. Schematic Representation of Study Aims and Variables.

3.2 Data Analysis

Descriptive statistics were used to summarize the sample characteristics and

study measures for the total sample and for each group (chronic HTN versus control).

Prenatal care 1. Early Prenatal Care ⇒ (1st trimester prenatal care)

2. Adequacy Kessner Index

⇒ Adequate

⇒ Inadequate

Sample

i. 1. Women with chronic hypertension

ii. (Chronic HTN) 2. Women without chronic hypertension (Control)

Outcomes 1. Maternal Outcomes

⇒ Pregnancy induced hypertension

(PIH)

⇒ Placental abruption 2. Infant Outcomes ⇒ Preterm birth

⇒ Small for gestational age (SGA)

Perinatal Risk Factors ⇒ Ethnicity/race

⇒ Maternal education ⇒ Maternal age

AIM 1

AIM 2

AIM 3

38

Non-directional statistical tests were performed with the level of significance set at 0.05

for each test, including interaction effects. Data analyses were conducted using SAS 9.4

software (Cary, NC).

Sample characteristics. Chi-square/Fisher’s Exact Tests for categorical variables

and General Linear Models (GLMs, due to unequal sample sizes) for scalar measures

were used to test for group differences in the demographic/clinical characteristics of the

mothers and infants.

The known perinatal risk factors of maternal age, education level, and ethnicity

(Black, non-Black) were included as control variables (covariates) during the analysis of

Aims 1-2 and examined as key predictors of the outcomes in Aim 3. Other maternal

characteristics for which the chronic HTN and control groups differed significantly were

identified as potential covariates in the analytic models for Aims 1-3. The following

maternal characteristic variables were included as potential covariates in the initial

multivariable logistic regression models to examine predictors of the study outcomes:

(1) known perinatal risk factors - maternal age (years), education level (year categories),

and ethnicity (black/non-black) and (2) additional maternal characteristics for which the

chronic HTN and control group significantly differed - married (yes/no), BMI

(1=Underweight, 2=Normal, 3=Overweight, 4=Obese), prepregnancy diabetes (yes/no),

weight gain during pregnancy (pounds), gestational diabetes (yes/no), and smoked

during pregnancy (yes/no). For each of the logistic regression models used to address

the study aims, predictor and response variables were sorted in descending order

39

(binary: 1=yes vs. 0=no; continuous: highest to lowest values).

Aim 1 analysis. A logistic regression approach was used to test the hypothesis

that the rate of PIH, placental abruption, preterm birth, and SGA would be significantly

higher among women with chronic HTN than in women without chronic HTN, after

adjusting for maternal age, education level, and ethnicity. First, bivariate logistic

regression models were used to determine whether group predicted each outcome and

estimate the odds ratio (OR) and the 95% confidence interval (95% CI) for each outcome

when comparing women with chronic HTN to women without chronic HTN (control).

Each OR was used as an indicator of effect size and clinical significance. Next, a

multivariable logistic regression was performed on each outcome. This initial full model

included chronic HTN group, perinatal risk factors (maternal age, education level, and

ethnicity as covariates), and other identified maternal characteristic covariates as

explanatory variables. Finally, using an iterative manual backward elimination process,

the multivariable model for each outcome was reduced to a final model with chronic

HTN group regardless of statistical significance and only those covariates significant at

the 0.05 level.

Aim 2 analysis. A logistic regression approach was also applied to explore

whether early access to prenatal care and/or adequacy of prenatal care would lead to a

lower rate of PIH, placental abruption, preterm birth, and SGA in women with chronic

HTN than in women without chronic HTN, after adjusting for maternal age, education

level, and ethnicity. ORs and their 95% CIs were used to evaluate effect size. For each

40

outcome, separate analyses were conducted for prenatal care during the first trimester

and adequacy of prenatal care.

First, bivariate logistic regression models were used to determine whether the

prenatal care variable predicted each outcome. Next, a multivariable logistic regression

was performed on each outcome. This initial full model included the following

explanatory variable: the prenatal care variable, chronic HTN group, the interaction

between prenatal care variable and chronic HTN group, perinatal risk factors (maternal

age, educational level, and ethnicity as covariates), and other identified maternal

characteristic covariates. Using an iterative manual backward elimination process, the

multivariable model for each outcome was reduced to a final model that included the

prenatal care variable, chronic HTN group, and their interaction regardless of statistical

significance and covariates significant at the 0.05 level. The interaction term and its

components were retained in the final model so the question pertaining to the

differential effects of prenatal care in chronic HTN group relative to the control group

could be addressed.

Aim 3 analysis. Logistic regression was used to explore the moderating effects of

maternal perinatal risk factors on study outcomes. The goal was to determine whether

these perinatal risk factors (maternal age, education level, and ethnicity) had a greater

influence on rate of PIH, placental abruption, preterm birth, and SGA in women with

chronic HTN than in women without chronic HTN. Applying the definitions and

guidelines recommended by Kraemer and associates (2002), a risk factor would be a

41

moderator of an outcome if the variable interacted with the chronic HTN group variable.

On the other hand, a main effect of a risk factor in the absence of an interaction effect

would indicate that the factor was a non-specific predictor.

Separate analyses were performed for each perinatal risk factor and outcome.

The initial model for each risk factor included the following explanatory variables:

chronic HTN group, the perinatal risk factor of interest, its interaction chronic HTN

group, and perinatal risk factors and maternal characteristics as covariates. The

multivariable model for each outcome was then reduced to a final model using manual

backward elimination. The final model for each perinatal risk factor and outcome

included the risk factor variable, chronic HTN group, and their interaction regardless of

significance as well as covariates significant at the 0.05 level.

Statistical power. Power calculation indicated that a total sample size of 2917,

with 292 in the chronic HTN group and 2625 without chronic HTN (control group)

would provide at least 80% statistical power for each chronic HTN group comparison

conducted using logistic regression with level of significance set at 0.05 (two-tailed

tests). This determination was based on the assumption of a medium effect size for the

group comparison (OR=2.47 or higher) with 7 or fewer covariates in each final regression

model. The power calculations did not take into account multiple tests and multiple

outcomes.

42

3.3 Results

Sample characteristics. Table 3.2 summarizes maternal characteristics and Table

3.3 details infant characteristics of the total sample and by chronic HTN group. The

chronic HTN group had a significantly (1) higher percent of Blacks, (2) lower percent of

mothers with more than 12 years of education, (3) lower percent who were married, (4)

higher percent of mothers with a BMI above normal, (5) higher percent of mothers with

Table 3.2. Characteristics of Women without and with Chronic HTN

Maternal Characteristic

Total N = 2917

Control N = 2625

Chronic HTN

N = 292 p

Race, n (%) <.0011

White 1603 (61.1) 104 (35.6) Black 675 (23.1) 533 (20.3) 142 (48.6) Hispanic 372 (12.8) 342 (13.0) 30 (10.3) Other 163 (5.6) 147 (5.6) 16 (5.5)

Education, n (%), years <.0011 0-8 125 (4.3) 111 (4.2) 14 (4.8) 9-11 388 (13.3) 335 (12.8) 53 (18.3) 12 728 (25.0) 640 (24.4) 88 (30.3) 13-15 756 (26.0) 676 (25.8) 80 (27.6) 16 or greater 913 (31.4) 858 (32.8) 55 (19.0)

Married, n (%) 1769 (60.7)

1633 (62.2) 136 (46.6) <.001

Age, mean ± SD, years 27.7 ± 6.1 27.7 ± 6.0 27.8 ± 7.0 0.682 Body mass index (BMI), n (%) <.001

Underweight < 18.5 126 (4.6) 112 (4.6) 14 (5.3)

Normal 18.5-24.9 1377 (50.5)

1289 (52.3) 88 (33.2)

Overweight 25.0-29.9 618 (22.7) 555 (22.5) 63 (23.8) Obese 30.0+ 607 (22.3) 507 (20.6) 100 (37.7)

Pre-pregnancy diabetes, n (%) 244 (8.4) 79 (3.0) 165 (57.1) <.001

Insurance, n (%) 2208 (75.7)

1976 (75.3) 232 (79.45) 0.115

PROM, n (%) 123 (4.2) 108 (4.1) 15 (5.1) 0.411 Preterm labor, n (%) 745 (25.7) 649 (24.8) 96 (33.0) 0.003

43

Maternal Characteristic

Total N = 2917

Control N = 2625

Chronic HTN

N = 292 p

Fever during pregnancy, n (%) 51 (1.8) 48 (1.8) 3 (1.03) 0.1322 Infection kidney/bladder, n (%) 649 (22.3) 576 (22.0) 73 (25.1) 0.222 Caesarean, n (%) 996 (34.2) 884 (33.7) 112 (38.4) 0.111

Weight gain, mean ± SD, (LB) 29.0 ±

14.3 29.2 ± 14.2 26.3 ± 15.1 <.001

Gestational diabetes, n (%) 283 (9.8) 234 (9.0) 49 (16.9) <.001 Alcohol in Last 3 months of pregnancy, n (%) 204 (7.1) 189 (7.3) 15 (5.2) 0.178 Smoked during pregnancy, n (%) 322 (11.1) 279 (10.6) 43 (14.7) 0.035

Control=women without chronic hypertension (HTN). PROM=Premature rupture of membranes. General Linear Model (GLM) for scalar and chi-square/Fisher’s Exact Test for categorical variables; 1p-value for 2x2 chi-square test with categories collapsed: Race: black vs non-black; education: < 12 years vs > 12 years. 2Fisher’s Exact Test results.

Table 3.3. Characteristics of the Infants of Women without and with Chronic HTN

Infant Characteristics

Total

N = 2917

Control

N = 2625

Chronic HTN

N = 292 p

Birth weight, mean ± SD, g 2977.8 ±

827.3 3005.7 ±

819.7 2727.1 ± 853.8 <.001

Gestational age, mean ± SD, wk 37.5 ± 3.4 37.6 ± 3.4 36.8 ± 3.8 <.001

Birth weight, n (%), g <.001

Normal >= 2500 2017 (69.2) 1858 (70.8) 159 (54.5)

Low =< 2500 900 (30.9) 767 (29.2) 133 (45.6)

Female gender, n (%) 1481 (50.8) 1340 (51.1) 141 (48.3) 0.371

Infant living, n (%) 2805 (98.5) 2531 (98.6) 274 (97.2) 0.0671

Birth defect, n (%) 26 (0.9) 24 (0.9) 2 (0.68) 0.6921

NICU admission, n (%) 610 (21.2) 538 (20.8) 72 (25.2) 0.084

Hospital stay > 2 days, n (%) 1211 (42.2) 1055 (40.8) 156 (54.7) <.001

GLM for scalar and chi-square test for categorical variables; 1Fisher’s Exact Test results.

pre-pregnancy diabetes, (6) lower mean weight gain during pregnancy, (7) higher

percent of mothers with gestational diabetes, and (8) higher percent that smoked

44

during pregnancy. The chronic HTN infant group had a significantly (1) higher

percent of infants with a low birth weight, (2) a lower mean gestational age in weeks,

and (3) a higher percent of infants with a hospital stay of more than two days.

Prenatal care and study outcomes. Table 3.4 shows the prenatal care measures

(early prenatal care and adequacy of prenatal care), maternal outcomes (PIH and

placental abruption) and infant outcomes (preterm birth and SGA) for the total sample

and by chronic HTN groups. Although the chronic HTN group did not differ on the

percent of mothers with prenatal care during the first trimester (79.7% vs. 79.6%, χ2

=0.001, df=, p=0.982), the percent of women with inadequate prenatal care was

significantly higher in chronic HTN group when compared to the controls (32.5% vs.

21.5%, χ2 =18.489, df=1, p<.001).

Table 3.4. Descriptive Statistics of the Prenatal Care Measures and Study Outcomes

Total

N = 2917

Control

N = 2625

Chronic HTN

N = 292

p

Prenatal Care (PNC) Prenatal care during first trimester (n)

2892 2607 285 0.982

No, n (%) 590 (20.4) 532 (20.4) 58 (20.4) Yes, n (%) 2302 (79.6) 2075 (79.6) 227 (79.7)

Adequacy of prenatal care (n) 2917 2625 292 <.001 Adequate, n (%) 2259 (77.4) 2062 (78.6) 197 (67.5) Inadequate, n (%) 658 (22.6) 563 (21.5) 95 (32.5)

Study Outcomes Pregnancy Induced HTN (PIH) (n) 2905 2615 290 <.001

No, n (%) 2352 (81) 2182 (83.4) 170 (58.6) Yes, n (%) 553 (19.0) 433 (16.6) 120 (41.4)

Placental abruption (n) 2888 2600 288 0.934

45

Total

N = 2917

Control

N = 2625

Chronic HTN

N = 292

p

No, n (%) 2641 (91.5) 2378 (91.5) 263 (91.3) Yes, n (%) 247 (8.5) 222 (8.5) 25 (8.7)

Preterm birth (n) 2914 2622 292 0.001

No, n (%) 2269 (77.9) 2064

(78.7) 205 (70.2)

Yes, n (%) 645 (22.1) 558 (21.3) 87 (29.8) Small for gestational age (SGA) (n) 2909 2617 292 0.036

No, n (%) 2373 (81.6) 2148

(82.1) 225 (77.1)

Yes, n (%) 536 469 (17.9) 67 (23.0) Available data (N) and n/N (%) reported for this set of binary variables, p-values=logistic

regression.

Aim 1: Chronic HTN. Table 3.5 presents the bivariate logistic regression results

comparing the presence of each study outcome in women with chronic HTN group

relative to women without HTN (control). The bivariate results indicated that the

chronic HTN group relative to the control group had a significantly higher rate of PIH

(41.4% vs 16.6%, p<.001, OR=3.6), preterm birth (29.8% vs 21.3%, p<0.001, OR=1.6), and

SGA infants (23.0% vs 17.9%, p=0.036, OR=1.4). The two groups did not differ on

placental abruption rates (8.5% vs 8.7%, p=0.934). Table 3.5 also provides the results of

the final multivariable logistic regression model for each outcome. The final (reduced)

model included chronic HTN group and only those maternal characteristic covariates

significant at the 0.05 level after applying the covariate backward elimination

procedure. After adjusting for covariate effects, the chronic HTN group when

compared to the control group had a significantly greater likelihood of PIH (p<0.001,

46

Table 3.5. Logistic Regression of Chronic HTN and Study Outcomes

Model Outcome Explanatory Variable Wald χ2 p OR OR 95% CI

Bivariate PIH Chronic HTN 94.813 <.001 3.557 2.755, 4.592

Final PIH Chronic HTN 63.061 <.001 4.542 3.126, 6.598

Maternal education 4.158 0.042 1.116 1.004, 1.240

Marital status 12.985 0.003 0.655 0.520, 0.824

BMI 92.233 <.001 1.770 1.575, 1.988

Pre-pregnancy diabetes 6.635 0.010 0.563 0.364, 0.872

Weight gain 22.512 <.001 1.010 1.010, 1.024

Bivariate Placental abruption

Chronic HTN 0.007 0.934

1.018 0.661, 1.570

Final Placental abruption

Chronic HTN 0.011 0.917

0.976 0.615, 1.548

Maternal education 5.331 0.021 1.153 1.022, 1.301

Weight gain 7.047 0.008 0.987 0.977, 0.996

Bivariate Preterm Chronic HTN 10.923 0.001 1.570 1.202, 2.052

Final Preterm Chronic HTN 0.000 0.996 0.999 0.697, 1.431

Black 8.751 0.003 1.397 1.119, 1.743

Marital status 10.697 0.001 0.720 0.592, 0.877

Pre-pregnancy diabetes 4.810 0.028 1.521 1.046, 2.211

Weight gain 58.271 <.001 0.973 0.967, 0.980

Bivariate SGA Chronic HTN 4.387 0.036 1.364 1.020, 1.824

Final SGA Chronic HTN 2.323 0.127 1.287 0.930, 1.779

Maternal age 4.074 0.044 0.983 0.967, 1.000

BMI 15.428 <.001 0.788 0.699, 0.887

Smoked during pregnancy

55.643 <.001 2.746 2.106, 3.581

Weight gain 39.965 <.001 0.975 0.968, 0.983

Chronic HTN (chronic HTN/control); OR=odds ratio; 95% CI= 95% Confidence Interval; PIH=pregnancy induced hypertension; SGA=small for gestational age; black (black/non-black); marital status (married/not married); pre-pregnancy diabetes (yes/no); smoked during pregnancy (yes/no).

47

OR=4.5, 95% CI=3.1 to 6.6). More specifically, the odds of having PIH were 4.5 times

higher among women with chronic HTN than among women without chronic HTN.

After adjusting for covariates, the two groups did not differ on placental abruption,

preterm births, and SGA infants.

Aim 2a: Early prenatal care and chronic HTN. First, I examined the relationship

between early prenatal care and outcomes (Table 3.6). The bivariate logistic regression

indicated that women with prenatal care during the first trimester had higher PIH rates

(early prenatal care 19.78%, no early prenatal care 16.4%, p=0.060), higher placental

abruption rates (early prenatal care 9.0%, no early prenatal care 6.5%, p=0.0507), and

lower SGA infant rates (early prenatal care 17.5%, no early prenatal care 21.6%,

p=0.0211), but the differences in PIH and placental abruption were not significant.

Prenatal care during the first trimester, however, was not related to preterm birth (early

prenatal care 22.2%, no early prenatal care 22.1%, p=0.957).

Table 3.6 also shows the results of the final models with prenatal care during the

first trimester, chronic HTN group, their interaction, and covariates significant at the

0.05 level after applying the backward elimination procedure. Prenatal care during the

first trimester was no longer related to PIH, placental abruption, or SGA infants after

adjusting for the effects of other variables in the model. However, women with prenatal

care during the first trimester had a significantly greater likelihood of a preterm birth,

after controlling for other variables in the model.

48

Table 3.6. Logistic Regression of Early Prenatal Care, Chronic HTN, and Study Outcomes

Model Outcome Explanatory Variable Wald χ2

p OR OR 95% CI

Bivariate PIH PNC 1st Trimester 3.544 0.060 1.261 0.991, 1.606

Final PIH PNC 1st Trimester 1.085 0.298 1.169 0.958, 1.661

Chronic HTN 5.204 0.023 2.360 3.134, 6.667 PNC 1st Trimester

*Chronic HTN 4.362 0.037

--- ---

Marital status 11.006 <.001 0.696 0.562, 0.862 BMI 91.141 <.001 1.764 1.570, 1.982 Prepregnancy

diabetes 7.130 0.008

0.548 0.352, 0.852

Weight gain 23.425 <.001 1.017 1.010, 1.024

Bivariate Placental abruption

PNC 1st Trimester 3.819 0.051

1.430 0.999, 2.046

Final Placental abruption

PNC 1st Trimester 2.470 0.116

1.379 1.057, 2.409

Chronic HTN 1.764 0.184 0.256 0.493, 1.480 PNC 1st Trimester

*Chronic HTN 2.039 0.153

--- ---

Maternal age 4.377 0.036 1.024 1.002, 1.047 Weight gain 6.267 0.012 0.987 0.978, 0.997

Bivariate Preterm PNC 1st Trimester 0.003 0.957 1.006 0.809, 1.251

Final Preterm PNC 1st Trimester 4.111 0.043 1.303 1.025, 1.661 Chronic HTN 0.001 0.972 1.012 0.712, 1.464 PNC 1st Trimester

*Chronic HTN 0.001 0.977

--- ---

Black 10.261 <.001 1.440 1.152, 1.800 Marital status 13.435 0.002 0.684 0.559, 0.838 Prepregnancy

diabetes 5.152 0.023

1.547 1.061, 2.255

Weight gain 60.176 <.001 0.973 0.966, 0.980

Bivariate SGA PNC 1st Trimester 5.317 0.021 0.768 0.614, 0.961

49

Chronic HTN=chronic hypertension (chronic HTN/control); OR=odds ratio; 95% CI= 95% Confidence Interval; PIH=pregnancy induced hypertension; SGA=small for gestational age; PNC=Prenatal Care; PNC 1st Trimester (yes/no).

Figure 3.2. Interaction between Chronic Hypertension (HTN) and First Trimester Prenatal Care on Pregnancy Induced Hypertension (PIH).

The chronic HTN group when compared to the control group had a greater

likelihood of PIH (p=0.023, OR=2.4) after adjusting for early prenatal care main and

interaction effects as well as other covariates. The interaction between prenatal care

0

5

10

15

20

25

30

35

40

45

50

No Yes

PIH

(%)

First Trimester Prenatal Care

Control

Chronic HTN

Final SGA PNC 1st Trimester 0.960 0.327 0.875 0.689, 1.142 Chronic HTN 0.184 0.668 1.171 0.947, 1.822 PNC 1st Trimester*

Chronic HTN 0.120 0.729

--- ---

Maternal age 3.666 0.056 0.983 0.967, 1.000 BMI 15.450 <.001 0.786 0.698, 0.886 Smoked during

pregnancy 55.131 <.001

2.749 2.105, 3.591

Weight gain 38.348 <.001 0.976 0.968, 0.983

50

during the first trimester and chronic HTN was significant for PIH (p=0.037). The PIH

rate within each interaction subgroup was (1) no early prenatal care, chronic

HTN=27.6%; (2) no early prenatal care, control=15.1%; (3) early prenatal care, chronic

HTN=45.1%; and (4) early prenatal care, control=17.1% (Figure 3.2).

A posteriori simple effects conducted to further examine the interaction effect

indicated that PIH rates differed significantly between the chronic HTN and the control

groups among those without early prenatal care (χ2 =5.93, df=1, p =0.015) and with early

prenatal care (χ2 =101.52, df=1 p<.001). The ORs (95% CI) for PIH when comparing the

chronic HTN group to the control group in (a) women without early prenatal care was

2.360 (1.129 to 4.936) and (b) with early prenatal care was 5.328 (3.575 to 7.941).

The interaction term was not a significant predictor for the other outcomes.

Aim 2b: Adequacy of Prenatal Care and Chronic HTN. Table 3.7 presents the

bivariate regression results for prenatal care adequacy. Adequacy of prenatal care was

significantly associated with a lower preterm birth rate (adequate=21.3%, not

adequate=25.2%, p=0.033) and a lower SGA rate (adequate =17.6%, not adequate=21.2%,

p=0.036). Adequacy of prenatal care was not related to PIH (adequate=19.2%, not

adequate=18.5%, p=0.710) or placental abruption (adequate=8.3%, no adequate=9.6%,

p=0.301).

Table 3.7 also summarizes the results from the final model with prenatal care

adequacy, chronic HTN group, their interaction, and covariates significant at the 0.05

level. Women with adequate prenatal care were significantly less likely to have a

51

placental abruption. Adequacy of prenatal care was not related to the other outcomes

after adjusting for the effects of other variables in the model. Interestingly, prenatal care

adequacy was not related to placental abruption in the bivariate model.

Table 3.7. Logistic Regression of the Adequacy of Prenatal Care, Chronic HTN, and Study Outcomes

Model Outcome Explanatory Variable

Wald χ2 p OR OR 95% CI

Bivariate PIH Adequate PNC 0.138 0.710 1.043 0.834, 1.305

Final PIH Adequate PNC 0.216 0.642 0.936 0.762, 1.282 Chronic HTN 13.393 0.003 3.018 3.272, 6.981 Adequate PNC

*Chronic HTN 3.144 0.076

--- ---

Maternal education

3.995 0.046 1.115 1.002, 1.240

Marital status 13.457 0.002 0.649 0.515, 0.818 BMI 91.661 <.001 1.768 1.573, 1.987 Prepregnancy

diabetes 6.650 0.010

0.562 0.362, 0.871

Weight gain 22.978 <.001 1.017 1.010, 1.024

Bivariate Placental abruption

Adequate PNC 1.070 0.301

0.853 0.631, 1.153

Final Placental abruption

Adequate PNC 4.519 0.034

0.693 0.541, 1.031

Chronic HTN 1.464 0.226 0.557 0.633, 1.595 Adequate PNC

*Chronic HTN 1.863 0.172

--- ---

Maternal education

6.940 0.008 1.182 1.044, 1.338

Weight gain 6.733 0.010 0.987 0.977, 0.997

Bivariate Preterm Adequate PNC 4.568 0.033 0.801 0.654, 0.982

Final Preterm Adequate PNC 0.043 0.835 0.975 0.802, 1.254 Chronic HTN 0.492 0.483 0.815 0.712, 1.469

52

Model Outcome Explanatory Variable

Wald χ2 p OR OR 95% CI

Adequate PNC *Chronic HTN

0.832 0.362 --- ---

Black 8.934 0.003 1.402 1.123, 1.749 Marital status 10.554 0.001 0.718 0.588, 0.877 Prepregnancy

diabetes 4.874 0.027

1.525 1.048, 2.218

Weight gain 57.851 <.001 0.973 0.967, 0.980

Bivariate SGA Adequate PNC 4.384 0.036 0.794 0.639, 0.985

Final SGA Adequate PNC 0.082 0.774 0.962 0.748, 1.224 Chronic HTN 1.006 0.316 1.331 0.906, 1.779 Adequate PNC

*Chronic HTN 0.030 0.863

--- ---

Maternal age 3.707 0.054 0.983 0.967, 1.000 BMI 15.213 <.001 0.789 0.700, 0.889 Smoked during

pregnancy 54.652 <.001

2.733 2.094, 3.569

Weight gain 39.590 <.001 0.975 0.968, 0.983

Chronic HTN=chronic hypertension (chronic HTN/control); OR=odds ratio; 95% CI= 95% Confidence Interval; PIH=pregnancy induced hypertension; SGA=small for gestational age; PNC=Prenatal Care; adequacy of PNC (yes/no)

Women with chronic HTN when compared to the control had a greater

likelihood of PIH (OR=3.0), after adjusting for prenatal care adequacy main and

interaction effects as well as covariates in the model. No other outcomes were

significantly related to prenatal care adequacy. The prenatal care adequacy and chronic

HTN interaction did not significantly predict any outcomes.

Aim 3: Perinatal risk factors and chronic HTN. Tables 3.8-3.10 presents the logistic

regression results for perinatal risks factors and outcomes for the bivariate and final

53

models. Greater maternal education predicted lower preterm birth and lower SGA rates

in the bivariate analysis. When adjusted for other variables, neither maternal education

nor chronic HTN as main effects significantly predicted any of the outcomes (Table 3.8).

The interaction between maternal education and chronic HTN significantly predicted

PIH (Figure 3.3) but did not predict any other outcome. PIH rates steadily increased in

the chronic HTN group as the years of maternal education increased (0-8 years=21.4%; 9-

11 years =32.0%, 12 years =40.9%; 13-15 years=40.5%, and 16 or greater years=56.4%)

when compared to the control group (0-8 years=6.3%; 9-11 years =14.2%, 12 years

=19.7%; 13-15 years=18.3%, and 16 or greater years=15.3%) (all p<0.051) . The ORs (95%

Table 3.8. Logistic Regression of Maternal Education, Chronic HTN, and Study Outcomes

Model Outcome Explanatory Variable Wald χ2

P OR OR 95% CI

Bivariate PIH Maternal education 1.036 0.309 1.042 0.962, 1.129 Final PIH Maternal education 1.506 0.220 1.072 0.993, 1.226 Chronic HTN 0.557 0.456 1.503 3.262, 6.931 Chronic HTN*Maternal

education 4.678 0.031 --- ---

Marital status 13.368 0.003 0.651 0.517, 0.820 BMI 91.546 <.001 1.768 1.573, 1.986 Prepregnancy diabetes 5.918 0.015 0.581 0.375, 0.900 Weight gain 22.036 <.001 1.017 1.010, 1.024 Bivariate Placental

abruption Maternal education 2.547 0.111 1.098 0.979, 1.231

Final Placental abruption

Maternal education 3.487 0.062 1.128 1.024 1.304

Chronic HTN 1.210 0.271 0.391 0.621 1.567 Chronic HTN*Maternal

education 1.311 0.252 --- ---

54

Model Outcome Explanatory Variable Wald χ2

P OR OR 95% CI

Weight gain 7.121 0.008 0.986 0.977, 0.996 Bivariate Preterm Maternal education 15.008 <.001 0.864 0.803, 0.931

Final Preterm Maternal education 0.060 0.807 0.989 0.907, 1.080 Chronic HTN <.001 0.980 1.012 0.724, 1.504 Chronic HTN*Maternal

education 0.004 0.948 --- ---

Marital status 16.128 <.001 0.657 0.535, 0.806 Prepregnancy diabetes 5.888 0.015 1.587 1.093, 2.304 Weight gain 60.017 <.001 0.973 0.966, 0.980 Bivariate SGA Maternal education 16.927 <.001 0.848 0.784, 0.917 Final SGA Maternal education 2.286 0.131 0.927 0.849, 1.023 Chronic HTN 0.009 0.923 1.055 0.913, 1.808 Chronic HTN*Maternal

education 0.117 0.733 --- ---

BMI 17.369 <.001 0.777 0.690, 0.875 Smoked during

pregnancy 48.734 <.001 2.673 2.028, 3.522

Weight gain 37.845 <.001 0.976 0.968, 0.983

Chronic HTN=chronic hypertension (chronic HTN/control); OR=odds ratio; 95% CI= 95% Confidence Interval; PIH=pregnancy induced hypertension; SGA=small for gestational age; maternal education=descending, highest to lowest

CI) for PIH when comparing the chronic HTN group to the control group in (a) with 12

years of education was 3.758 (2.488 to 5.677) and (b) with 16 or greater years of

education was 6.922 (4.057 to 11.811). A posteriori simple effects analyses conducted to

further evaluate the interaction indicated that the chronic HTN group had significantly

higher PIH rates than the control group (χ2= 9.900, p<0.002) at each education level, with

the exception of 0-8 years of education (Fisher’s Exact p=0.086).

55

Figure 3.3. Interaction between Chronic Hypertension (HTN) and Maternal Education on Pregnancy Induced Hypertension (PIH).

Greater maternal age significantly predicted higher placental abruption and

lower SGA rates in the bivariate regression. After controlling for other variables,

increased maternal age continued to be associated with a greater likelihood of placental

abruption and decreased likelihood of SGA. In the final model, chronic HTN as a main

effect did not significantly predict any of the outcomes (Table 3.9). The interaction

between maternal age and chronic HTN significantly predicted PIH, but no other

outcomes (Figure 3.4). The PIH rates steadily increased in chronic HTN group as

maternal age increased (<18=26.9%; age 19-24=32.5%; age 25-30=41.9%; age 31-35=46.2%;

0

10

20

30

40

50

60

0-8 9-11 12 13-15 16 or greater

PIH

(%

)

Maternal Education (year)

Control

Chronic HTN

56

Table 3.9. Logistic Regression of Maternal Age, Chronic HTN, and Study Outcomes

Model Outcome Explanatory Variable Wald χ2

P OR OR 95% CI

Bivariate PIH Maternal age 0.255 0.614 0.996 0.981, 1.011

Final PIH Maternal age 3.189 0.074 0.982 0.969, 1.007 Chronic HTN 0.253 0.615 0.711 2.950, 6.307 Chronic HTN*Maternal age 8.311 0.004 --- --- Marital status 4.972 0.026 0.771 0.614, 0.969 BMI 88.479 <.001 1.751 1.558, 1.968 Prepregnancy diabetes 5.125 0.024 0.601 0.386, 0.934 Weight gain 22.953 <.001 1.017 1.010, 1.024

Bivariate Placental abruption

Maternal age 6.251 0.012 1.027 1.006, 1.049

Final Placental abruption

Maternal age 6.700 0.010 1.031 1.007, 1.052

Chronic HTN 0.240 0.624 1.619 0.622, 1.544 Chronic HTN*Maternal age 0.292 0.589 --- --- Weight gain 5.622 0.018 0.988 0.978, 0.998

Bivariate Preterm Maternal age 0.909 0.340 0.993 0.979, 1.007

Final Preterm Maternal age 0.045 0.832 1.002 0.989, 1.022 Chronic HTN 2.415 0.120 0.374 0.710, 1.455 Chronic HTN*Maternal age 2.946 0.086 1.037 1.000, 1.079 Marital status 19.016 <.001 0.635 0.518, 0.779 Prepregnancy diabetes 6.638 0.010 1.636 1.125, 2.378 Weight gain 61.509 <.001 0.973 0.966, 0.979

Bivariate SGA Maternal age 10.302 <.001 0.975 0.960, 0.990

Final SGA Maternal age 4.8682 0.027 0.980 0.965, 0.999 Chronic HTN 0.246 0.620 0.716 0.941, 1.797 Chronic HTN*Maternal age 0.819 0.366 --- --- BMI 15.837 <.001 0.785 0.696, 0.884 Smoked during pregnancy 55.309 <.001 2.738 2.100, 3.571 Weight gain 40.236 <.001 0.975 0.968, 0.983

Chronic HTN=chronic hypertension (chronic HTN/control); OR=odds ratio; 95% CI= 95% Confidence Interval; PIH=pregnancy induced hypertension; SGA=small for gestational age; maternal age= descending, oldest to youngest.

57

Figure 3.4. Interaction between Chronic Hypertension (HTN) and Maternal Age on Pregnancy Induced Hypertension (PIH).

age 36-40=55.9%; age 41-47= 66.7%) when compared to the control group (age 13-

17=21.3%; age 18-24 =19.1%; age 25-30=16.6%; age 31-35=12.3%; age 36-40=15.7%; age 40

or greater= 18.2%). The ORs (95% CI) for PIH when comparing the chronic HTN group

to the control group in (a) women with age 20 was 1.906 (1.247 to 2.913), (b) with age 30

was 4.399 (3.333 to 5.805) and (c) with 40 was 10.154 (5.919 to 17.418). A posteriori simple

effects analyses indicated that the chronic HTN group had significantly higher PIH rates

relative to the control group (p<0.005) at each age level, with the exception of the less or

equal 18 age category (p=0.529).

Black women when compared to non-black women had a higher rate of PIH

0

10

20

30

40

50

60

70

80

≤18 19-24 25-30 31-35 36-40 41-47

PIH

(%)

Maternal Age

Control

ChronicHTN

58

(Black: 27.4%); non-Black: 16.5%, p< 0.001) and preterm birth (Black: 31.0%; non-Black:

19.5%, p< 0.001) in the bivariate analysis. When controlling for other variables in the

final model, preterm birth was the only outcome for which this relationship remained

significant. Women with chronic HTN were significantly more likely to have PIH and

SGA infants after adjusting for other variables in the model (Table 3.10). There were no

statistically significant Black race or chronic HTN interaction effects.

Table 3.10. Logistic Regression: Ethnicity, Chronic HTN, and Study Outcome

Model Outcome Explanatory Variable Wald χ2

P OR OR 95% CI

Bivariate PIH Black 38.687 <.001 1.905 1.555, 2.333 Final PIH Black 2.142 0.143 1.227 0.943, 1.571 Chronic HTN 44.091 <.001 4.597 3.051, 6.665 Chronic HTN*Black 0.074 0.785 --- --- Marital status 4.971 0.026 0.777 0.623, 0.970 BMI 86.603 <.001 1.741 1.549, 1.957 Prepregnancy diabetes 7.709 0.006 0.538 0.347, 0.833 Weight gain 24.852 <.001 1.018 1.011, 1.025 Bivariate Placental

abruption Black

0.861 0.354 0.859 0.623, 1.184

Final Placental abruption

Black 0.943 0.332

0.833 0.580, 1.151

Chronic HTN 0.123 0.726 1.108 0.657, 1.702 Chronic HTN*Black 0.179 0.673 --- --- Weight gain 6.619 0.010 0.987 0.977, 0.997 Bivariate Preterm Black 39.020 <.001 1.855 1.528, 2.251 Final Preterm Black 9.759 0.002 1.461 1.136, 1.774 Chronic HTN 0.343 0.558 1.140 0.731, 1.556 Chronic HTN*Black 0.979 0.323 --- --- Marital status 10.505 0.001 0.722 0.593, 0.879 Prepregnancy diabetes 5.068 0.024 1.537 1.057, 2.234 Weight gain 58.141 <.001 0.973 0.967, 0.980 Bivariate SGA Black 0.275 0.600 1.061 0.851, 1.321 Final SGA Black 0.049 0.825 0.969 0.707, 1.200 Chronic HTN 4.919 0.027 1.626 1.011, 2.035 Chronic HTN*Black 2.443 0.118 --- ---

59

Chronic HTN=chronic hypertension (chronic HTN/control); OR=odds ratio; 95% CI= 95% Confidence Interval; PIH=pregnancy induced hypertension; SGA=small for gestational age; Black race (black/non-black)

3.4 Discussion

In this secondary analysis of PRAMS data, I examined PIH, placental abruption,

preterm births, and SGA infants in women with chronic HTN and compared them to

healthy controls without chronic HTN. My results indicated that women with chronic

HTN had higher rates of PIH, preterm birth and SGA infants but did not have a higher

rate of placental abruption. I also determined that receiving first trimester prenatal care

and having adequate prenatal care did not improve PIH, placental abruption, preterm

birth or SGA infants’ rates for women with chronic HTN compared to women without

chronic HTN. In addition, the results showed that maternal age and education

positively predicted PIH among women with chronic HTN. Black infants were at

greater risk for preterm birth than non-Black infants and the infants of women with

chronic HTN were at risk for SGA infants after adjusting for covariates (Table 3.11

summarizes the significant findings). In addition, the results showed maternal

education, prepregnancy diabetes, maternal weight gained during pregnancy, marital

status, BMI, ethnicity, maternal age and smoking during pregnancy increased the risks

Marital status 4.450 0.035 0.784 0.626, 0.983 BMI 16.872 <.001 0.778 0.690, 0.877 Smoke during

pregnancy 49.461 <.001

2.662 2.026, 3.497

Weight gain 39.535 <.001 0.975 0.968, 0.983

60

for PIH, placental abruption, preterm term birth and SGA infants.

The prevalence of chronic HTN among the sample was higher than the rate

reported in the literature previously (Fridman et al., 2014; Gilbert et al., 2007; Savitz et

al., 2014). However, although these studies were conducted in the US, their study

populations were not from North Carolina. The higher rate of chronic HTN in my study

is an indication that the rate of chronic HTN depends on the nature of the sample and

the location of the study population.

Table 3.11. Final Reduced Models: Summary of Significant Findings

Final Model Variables Nature of Relationship

Aim 1, 2a, 2b, 3c Chronic HTN Women with chronic HTN were more likely to have PIH.

Aim 3c Chronic HTN Women with chronic HTN were more likely to have a SGA infant.

Aim 2a Early PNC Women with PNC first trimester were more likely to have a preterm birth.

Aim 2a Early PNC interaction Women with PNC first trimester and chronic HTN were most likely to PIH.

Aim 2b PNC adequacy Women with inadequate PNC were more likely to have a placental abruption.

Aim 1, 2b Maternal education Women with more education were more likely to have PIH.

Aim 1, 2b Maternal education Women with more education were more likely to have a placental abruption.

Aim 3a Maternal education interaction

Women with more education and chronic HTN were most likely to have PIH.

Aim 1, 2a-b, 3b Maternal age Younger women were more likely to have a SGA infant.

Aim 2a, 3b Maternal age Younger women were less likely to have a placental abruption.

Aim 3b Maternal age interaction Older women with chronic HTN were most likely to have PIH.

61

Final Model Variables Nature of Relationship

Aim 1, 2a-b, 3c Black race Black women were more likely to have a preterm infant.

Aim 1, 2a-b, 3a-c Marital status Unmarried women were more likely to have PIH.

Aim 1, 2a-b, 3a-c Marital status Unmarried women were more likely to have a preterm birth.

Aim 1, 2a-b, 3a-c Pre-pregnancy BMI Women with greater BMI were more likely to have PIH.

Aim 1, 2a-b, 3a-c Pre-pregnancy BMI Women with greater BMI were less likely to have a SGA infant.

Aim 1, 2a-b, 3a-c Pre-pregnancy diabetes Women with pre-pregnancy diabetes were more likely to have a preterm birth.

Aim 1, 2a-b, 3a-c Pre-pregnancy diabetes Women with pre-pregnancy diabetes were less likely to have PIH.

Aim 1, 2a-b, 3a-c Pregnancy weight gain Women with greater weight gain were more likely to have PIH.

Aim 1, 2a-b, 3a-c Pregnancy weight gain Women with greater weight gain were less likely to have placental abruption.

Aim 1, 2a-b, 3a-c Pregnancy weight gain Women with greater weight gain were less likely to have a preterm infant.

Aim 1, 2a-b, 3a-c Pregnancy weight gain Women with greater weight gain were less likely to have a SGA infant.

Aim 1, 2a-b, 3a-c Smoked during pregnancy Women who smoked were more likely to have a SGA infant.

Aim 1 = chronic HTN with covariates; Aim 2a = Early prenatal care, chronic HTN, interaction, and covariates; Aim 2b = Adequacy of PNC, chronic HTN, interaction, and covariates, Aim 3a=maternal age, chronic HTN, interaction, and covariates; Aim 3b=maternal education, chronic HTN, interaction, and covariates; Aim 3c=ethnicity, chronic HTN, interaction, and covariates; interaction= interaction with chronic HTN.

Maternal demographic characteristics such as education, age, ethnicity and

marital status had effects on the rates of PIH, placental abruption, preterm birth and

SGA infants. My findings showed that women with chronic HTN were older; had more

years of education; and were at greater risk for PIH, placental abruption and having

SGA infants. Older women with chronic HTN may need extra monitoring during

62

pregnancy for better maternal and infant outcomes. These results are consistent with

previous studies (Luke & Brown, 2007; Madi et al., 2012). Black women were more

likely to have a preterm birth than other pregnant women, which is consistent with

earlier studies (Kase et al., 2013; Sibai et al., 2011).

Women with chronic HTN were more likely to develop PIH. High rates of PIH

among women with chronic HTN have been reported in earlier studies (Barbosa et al.,

2015; Bateman et al., 2012; Bryant et al., 2005; Zetterstrom et al., 2005). Preterm birth and

SGA were more prevalent among women with chronic HTN than in the control group.

Similar results were reported in previous studies (Ananth et al., 2007; Ferrazzani et al.,

2011; Kase et al., 2013).

The rate of placental abruption was similar when women with chronic HTN

were compared to women without chronic HTN. These results were not consistent with

existing literature because a positive association between chronic HTN and placental

abruption is very well established (Ananth et al., 2007; Ananth et al., 1996). However,

the rate of placental abruption among women with and without chronic HTN (8.7% vs

8.5%) reported here is higher that 1-2% reported in previous studies (Ananth et al.,

1996). Also, women who had placental abruption in a previous pregnancy were 10

times more likely to have placental abruption in current pregnancy than other women

(Ananth et al., 1996). Unfortunately, I was unable to control for placental abruption in

previous pregnancies because it was not reported in the secondary data I used.

Another finding was that early prenatal care did not reduce PIH, placental

63

abruption, or SGA infants among women with chronic HTN even after adjusting for

covariates. One previous study found that women who received first trimester care

were at risk for low birth weight infants (Odell et al., 2006), possibly because women

who were aware they were at elevated risk before pregnancy or women who

experienced unpleasant symptoms early in their pregnancy sought early prenatal care.

Also, in assessing the benefits of first trimester prenatal care for women with chronic

HTN, the severity of the HTN must be taken into consideration, but the secondary data I

used did not have a measure of the severity of chronic HTN. Early prenatal care did not

provide the same benefits for women with chronic HTN as for women without chronic

HTN. Thus, women with chronic HTN may need specialized care based on their

hypertensive status before or during pregnancy.

Adequate prenatal care also did not improve the rates of PIH, placental

abruption, preterm birth, or SGA infants for women with chronic HTN although the

results showed that adequate prenatal care improved infant outcomes (preterm birth

and SGA) for women without chronic HTN. Women with HDP without adequate

prenatal care were more likely to have severe clinical complications during pregnancy

(Barbosa et al., 2015). Surprisingly, receiving adequate prenatal care did not provide

similar benefits for women with chronic HTN in our study population. Odell et al.

(2006) also found that women with adequate prenatal care were at risk for delivering a

low birth weight infant. Thus, these findings may be suggesting that women with

chronic HTN do not benefit as much as women without chronic HTN do from receiving

64

adequate prenatal care. Prenatal care among women with chronic HTN needs more

investigation because pregnant women with chronic HTN may require a different form

of prenatal care to address their specific health needs.

3.5 Strengths

The strength of this study is that the sample size was sufficiently large to (a)

provide adequate statistical power to test for differences between the chronic HTN and

the control groups on the maternal and infant outcomes, (b) generate reliable estimates

of population parameters for women with singleton births and chronic HTN, and (c)

draw meaningful conclusions from the results. This study documents the prevalence of

chronic HTN in a population-based study including a large sample of African

Americans.

3.6 Limitations

A limitation of the PRAMS data set was that data were not available about the

chronic HTN history for all women with singleton births in the sample, which affected

the sample size and generalizability of the results. Another limitation was that in the

PRAMS data set, the different types of pregnancy related HTN were combined because

of the relatively low rates of each type. Thus, gestational HTN and preeclampsia could

not be individually analyzed. Finally, the prenatal care variables did not differentiate

between low-risk and high risk prenatal care.

65

3.7 Conclusions

In summary, women with chronic HTN were at greater risk for PIH, preterm

delivery and SGA infants than women without chronic HTN. Women with chronic

HTN did not derive the same benefits from first trimester prenatal care and adequate

prenatal care as women without chronic HTN. The rate of PIH, placental abruption,

preterm birth and SGA infants was not reduced among women with chronic HTN with

first trimester prenatal care and adequate prenatal care. The severity of HTN should be

determined before or during early pregnancy among women of childbearing age who

have chronic HTN to effectively manage the HTN during pregnancy to improve

maternal and infant outcomes. Women with chronic HTN may require specialized care

because first trimester prenatal care and adequate prenatal care did not appear to benefit

the women with chronic HTN as much as to women without chronic HTN.

66

Chapter 4. Preterm Infant Illness and Developmental Outcomes after Pregnancy with and without Hypertensive Disorders of Pregnancy2

4.1 Hypertensive disorders of pregnancy

Hypertensive disorders of pregnancy (HDP) (chronic or prepregnancy

hypertension (HTN) and pregnancy induced hypertension (PIH)--gestational HTN, and

preeclampsia/eclampsia) occur in 5 to 10% of pregnancies and these problems frequently

result in infant morbidity and death (Roberts et al., 2005; Sibai et al., 2000). Preterm

delivery (before 37 weeks gestation) and low birth weight less than 2500g are more

common in infants of women with HDP compared to infants of women without HDP

(Bramham et al., 2014; Roberts et al., 2005). In 2012, the prevalence of preterm birth and

low birth weight in the U.S. were 11.54% and 7.99%, respectively (Chandiramani, Joash,

& Shennan, 2010; Hamilton, Hoyert, Martin, Strobino, & Guyer, 2013). Infants of women

with HDP experience negative effects that may continue longer than the pregnancy, e.

g., prematurity or small for gestational age (SGA) (Savitz et al., 2014). The preterm

delivery rate is higher among women with HDP than women without HDP and infants

of women with HDP may be admitted to the NICU at a higher rate than infants born to

normotensive women (Broekhuijsen et al., 2015; Madi et al., 2012).

Preterm infants born to women with HDP may be at greater risk for postnatal

complications than other preterm infants. However, spontaneous patent ducts

2 The parent study was funded by NIH 5R01 NR009418

67

arteriosus (PDA) closure occurred more often in infants of mothers with history of HDP

(Koch et al., 2006). In addition, infants with spontaneous PDA closure were more likely

to be small for gestational age (SGA) and their mothers often experienced HDP (Koch et

al., 2006).

The highest risk factor for morbidity or mortality in premature infants, next to

the immature brain, is reduced lung function due to immaturity of the lungs (Hough et

al., 2016). Preterm infants born at 32 weeks gestation or less are at risk for impaired gas

exchange due to underdeveloped lungs (Joshi & Kootchar, 2007). Preterm infants are

also at risk for respiratory distress syndrome, which may lead to pneumonia and other

problems including heart failure (Chen et al., 2008). Respiratory dysfunction in preterm

infants may require mechanical ventilation to improve oxygenation, which may lead to

infection, pressure damage of lung and chronic lung disease (Cruz et al., 2011). Infants

born to women with HDP are also at higher risk for morbidity including severe

respiratory problems than women without HDP (Broekhuijsen et al., 2015; Barbosa et al.,

2015).

Another morbidity common in preterm newborns is intraventricular hemorrhage

(IVH). IVH is a result of bleeding in the lateral and third or fourth ventricles. IVH

occurs in about half of preterm infants, leading to adverse neurodevelopment and even

death, particularly after early onset IVH (Lu, Wang, Lu, Zhang, & Kumar, 2016). Early

onset IVH is usually associated with underlying factors including a lower gestational

age, low birth weight and preeclampsia (Lu et al., 2016; Osborn, Evans, & Kluckow,

68

2003). However, the rate of IVH was lower (14%) in infants of women with HDP

compared to 32% in infants of women without HDP (Dani et al., 2010).

Pregnant women with HDP experience more severe obstetric and perinatal

complications than women without HDP (Ferrazzani et al., 2011). However, the effects

on the preterm infants born to women with HDP are understudied. Therefore, the

objective of this study was to examine preterm infants whose mothers did or did not

have HDP in pregnancy and compare the infant’s illness and development outcomes.

The specific aims were:

Aim 1. To compare illness severity (neurobiological risk, patent ducts arteriosus,

number of days on ventilator, intraventricular hemorrhage, infections, gestational age

and SGA) in preterm infants with a history of maternal HDP to that of preterm infants

with no history of maternal HDP, controlling for study intervention, prenatal care and

maternal history of diabetes.

Hypothesis 1: Preterm infants of mothers with HDP are expected to be less

healthy, as measured by neurobiological risk, patent ducts arteriosus, number of days on

ventilator, intraventricular hemorrhage, infections, gestational age and SGA, than

preterm infants of mothers without HDP, after controlling for study intervention,

prenatal care, and maternal history of diabetes.

Aim 2. To compare infant physical development (head circumference, height,

and weight) and neurodevelopment (cognitive, language, and motor skills) in preterm

infants with a history of maternal HDP as compared to those with no history of maternal

69

HDP, controlling for study intervention, prenatal care, and maternal history of diabetes.

Hypothesis 2: Infant development, as measured by head circumference, height,

weight at 2 months as well as cognitive, language, and motor skills at 12 months, for

preterm infants of mothers with HDP is expected to be slower than preterm infants of

mothers without HDP, after controlling for study intervention, prenatal care, and

maternal history of diabetes.

4.2 Methods

4.2.1 Design

This exploratory secondary analysis examined differences in illness outcomes

and developmental outcomes in preterm infants born to women with HTN before or

during pregnancy (HDP) compared to women without HTN (control) using data from a

larger randomized controlled study, NIH 5R01 NR009418 (Holditch-Davis et al., 2014).

The original study compared three experimental interventions-- (1) the auditory–tactile–

visual–vestibular intervention (ATTV), (2) kangaroo care, and (3) an attention control

intervention of education about equipment needed for home care of preterm infants--on

maternal psychological well-being and the maternal infant relationship. (For detailed

information on the original data, see Holditch-Davis et al., 2014).

This secondary analysis used Study Group (HDP vs. control) as the independent

variable and examined the following outcomes: (1) infant illness outcomes were

collected at birth (gestational age, birth weight and SGA), at enrollment, when the babies

were no longer critically ill or no longer on ventilator (PDA, IVH) and at the first 30 days

70

(NBRS); (2) head circumference, height, and weight collected at birth and 2 months

corrected age; and (3) cognitive, language, and motor skills collected at 12 months

corrected age. Mothers and infants were enrolled during NICU admission. This study

was conducted primarily using enrollment data, which were obtained before the start of

the intervention, as well as data obtained at 2 and 6 months of age. The study

intervention was used as a covariate to prevent confounding the effects of the

interventions with the effects of HDP. Prenatal care was analyzed to determine whether

it had differential effects on women with HDP. Maternal history of diabetes was also

used as a covariate because women with HPD had higher rate of diabetes than in the

control women.

Study intervention, maternal prenatal care, and maternal history of diabetes

were incorporated as covariates in the analysis of the study outcomes due to their

possible influence on study outcomes. Additionally, maternal race and multiple births

were evaluated as covariates due to the significant study group differences on these

characteristics.

4.2.2 Sample

This analysis included participants (mothers and their preterm infants) from the

original study. The total sample included in this analysis was 221 mothers who had

data on HDP and their infants, with 80 (36%) in the HDP group and 141 (64%) in the

control group (Figure 4.1). Among the 36% of women with HDP, 14 (17.5%) had chronic

HTN, 43 (53.8%) had PIH and 23 (28.8%) had both chronic HTN and PIH.

71

Figure 4.1. Study Sample Selection, Inclusion and Exclusion Criteria

The sample was comprised of mothers who had singleton or multiple births (only one

infant from each multiple birth set was included in the original study) and whose

preterm infants had birth weights less than 1750g. Infants in the study included those

who had prenatal exposure to substances without symptoms or who experienced

Excluded N=19

I. One full term infant II. Eighteen missing

information on hypertensive disorders of pregnancy (HDP)

Analysis Sample: Singleton and multiple preterm infants and mothers of preterm infants N=221 HDP: N=80 Control: N=141

AIM 2

I. Birth and 2 months: Head circumference (HC), weight (WT) and height (HT) II. 12 months: cognitive, language and

motor development

AIM 1

I. Enrollment: o Patent ductus arteriosis (PDA) o Intraventricular hemorrhage (IVH) o Days on ventilator o Gestational age (GA) o Small for gestational age (SGA) II. During hospitalization: o Neurobiological Risk (NBRS) o Infections

Original Study N=240

72

postnatal neurological insults. The original study excluded infants who had congenital

neurological problems or symptoms of substance exposure. All mothers were eligible

except for women who could not participate in follow-up for 12 months; had history of

psychosis, bipolar disease or major depression at time of enrollment; or did not speak

English.

4.2.3 Measures

Sample Characteristics. Maternal and infant characteristics were obtained from

questionnaires at study enrollment and medical record review throughout

hospitalization. Maternal characteristics included sociodemographic measures, parity,

HDP, diabetes before pregnancy and gestational diabetes. Infant characteristics were

gender, birth weight in grams, gestational age, size for gestational age, surgeries, and

necrotizing enterocolitis (NEC). Study intervention, maternal prenatal care, and

maternal history of diabetes (gestational diabetes and/or prepregnancy diabetes) were

included as potential covariates in the analyses due to their possible influence on infant

outcomes.

Study Group. Hypertensive disorder of pregnancy (HDP) was defined as a

history of: chronic HTN and/or pregnancy induced HTN (gestational HTN or

preeclampsia during pregnancy). Information on HDP was obtained from infant

medical record reviews. Trained research assistants (who were nurses) initially

reviewed the medical record. The original hard copy was reviewed and the electronic

copy transcribed by the trained research assistants were reviewed separately and

73

compared. The control group included mothers without a history of HDP.

Infant Illness Outcomes. Infant illness outcomes at enrollment and during the

NICU hospitalization were obtained from the medical records by research staff. Infant

illness severity was measured using Neurobiological Risk Scale (Brazy, Goldstein,

Oehler, Gustafson, & Thompson, 1993). The items in this scale are scored on a 4-point

scale and used to determine the possible severity of insults to the brain through direct

injury or inadequate blood flow, oxygenation or nutrients. Seven neurological insults

are scored, with higher scores indicating more severe insults. Total scores of ≤4 are

considered low risk, scores of 5–7 intermediate risk and scores of 8–28 high risk for

abnormal outcomes (Brazy et al., 1993). Cronbach's alpha in this sample was 0.71

(Holditch-Davis et al., 2014). For this analysis, neurobiological risk (NBRS) was

dichotomized into low risk and high risk groups, with (a) 0 representing a score of 0 to 4

and (b) 1 indicating 5 or greater.

Patent ducts arteriosus (PDA) was assessed from medical record. The number of

days on mechanical ventilation was collected from medical record. Because the data

distribution was severely skewed, the natural log of the number days on ventilation

days +1 was derived to normalize the data for inclusion in the analytic models.

Intraventricular hemorrhage (IVH) was assessed as binary variable (Yes/No). The

number of infections was dichotomized into two groups (had an infection during

hospitalization or did not have) and SGA was also binary (yes, no). Finally, gestational

age at birth (GA), and birth weight (grams) were also obtained.

74

Infant Physical Development Outcomes. The developmental variables included (1)

head circumference in centimeters (cm), (2) height in cm, and (3) weight in grams. These

three indictors of infant growth were assessed at birth and 2 months corrected age.

Infant Developmental Outcomes. The Bayley Scales of Infant and Toddler

Development (BSID-III) (Bayley, 2003) was used for a standardized developmental

assessment to measure three components of infant development at 12 months: (1)

cognitive, (2) language, and (3) motor skills. A psychologist who was unaware of the

infant’s group assignment administered the BSID-III. The BSID-III is a standardized,

norm-referenced measure and a child’s performance is compared with normative data

from children of the same age (Bayley, 2003). The BSID-III is considered the gold

standard of infant and toddler assessment tools. It has good validity, including

predictive validity for cerebral palsy and mental retardation (Bayley, 2003; Spittle et al.,

2008). The BSID-III has shown acceptable reliability (Bayley, 2003). Internal consistency

ranged from .77 to .96 (Spittle et al., 2008). The standardized composite scores for each

of three domains were analyzed. Standard scores have a mean of 100 and a standard

deviation of 15, with higher score representing better performance.

4.3 Data Analysis

Descriptive statistics were used to describe maternal and infant characteristics,

and infant outcomes for the total sample and each study group (HDP and control).

Non-directional statistical tests were performed with level of significance set at 0.05.

75

The level of significance was not adjusted for the multiple tests and outcomes due to the

exploratory nature of this secondary analysis and to safeguard against Type II errors.

SAS Version 9.4 (SAS Institute Inc. Cary, NC) was used to conduct all analyses.

Analysis of variance and analysis of covariance models were conducted on

continuous outcomes using a General Linear Model (GLM) approach and a logistic

regression for binary outcomes. Odds ratios (OR) and eta-squared (η2) values along with

their 95% confidence interval (CI) were calculated to address effect size and clinical

significance.

Sample Characteristics. The study groups were compared on maternal and infant

characteristics using chi-square test (alternatively Fisher’s Exact Test) for categorical

characteristics and independent t-tests for continuous measures.

Covariates. The analyses of the outcomes included study group. Study

intervention, maternal prenatal care and maternal history of diabetes were included to

control potential effects on outcomes as well as significant maternal characteristics (see

Table 4.1) that were identified as a potential covariates in analyses of the sample

characteristics. Between-group sample characteristics significant at the 0.05 level were

controlled for as potential covariates.

Infant Illness Outcomes. First, a preliminary between-group analysis of all the

infant illness outcomes was conducted using chi-square tests for binary outcomes and

Wilcoxon Two-Samples Tests for continuous outcomes. A non-parametric approach

was used for the continuous measures for a preliminary analysis due to the non-

76

normality of data associated with count measures, such number of neurobiological risks.

Next, we conducted bivariate and multivariate logistic regression models to test for

between-group differences in the dichotomized infant illness outcomes, namely NBRS,

PDA, IVH, SGA, and infections, with and without covariates. GLMs were used to test

for between-group differences in the continuous outcomes, specifically log of days on

ventilator and birth gestational age (GA) with and without covariates. The final step

was to apply an iterative backward variable elimination method to reduce the model to

group and any covariates significant at the 0.05 level.

Developmental Outcomes. Infant head circumference (HC), height (HT), and

weight (WT) for the two groups were initially compared using independent t-tests to

examine group differences on these measures at birth and 2 months. The remaining

analyses were conducted on those infants with data available at both birth and 2

months. For this subset of infants, independent t-tests were used to compare differences

on these measures at each time point (birth and 2 months) in the HDP and control

groups. Next, GLMs were conducted to test for group differences on each 2-month

outcome, while controlling for the outcome at birth and other covariates. Finally, an

iterative backward variable elimination method was used to reduce the model to group,

the outcome at birth as a covariate, and any other covariates significant at the 0.05 level.

Neurodevelopmental outcomes (cognitive, language and motor skills) were

assessed at 12 months. Independent t-tests were used to evaluate between-group

difference on these measures. Next, a GLM approach was used to test group differences

77

with and without covariates. The final step was to reduce each multivariate model to a

final pragmatic model with group and significant covariates only.

4.3.1 Statistical Power

The total sample size of 221, with 80 in the HDP group and 141 in the control

group, provided at least 80% statistical power for each HDP-group analysis, assuming a

medium effect size and level of significance set at 0.05 for each individual two-tailed

test. The smallest clinically meaningful difference will be represented by (a) ORs for the

logistic regression of 2.47 and (b) values for eta-squared (η2) the GLMs of 0.06. The

power calculations did not take into account multiple tests and multiple outcomes due

to the exploratory nature of this initial set of analyses. Thus, the emphasis was placed

on the estimates of effect size.

4.4 Results

Sample Characteristics. Table 4.1 summarizes the maternal characteristics for the

total sample (N=221) and each study group (HDP: N=80; Control: N=141). Of 80 women

who had HDP, 37 (46.3%) had chronic HTN. Twenty-three (62%) of the women who

had chronic HTN developed PIH and 14 (38%) did not. The sample was comprised of

mostly Black women and their infants (68%), with the HDP group having a significantly

higher proportion of Black mothers than the control group (77.5% vs 63.1%, χ2=4.877;

df=1, p=0.027). Approximately 18% of sample were mothers with multiple birth, with

the percentage of multiple birth significantly lower in the HDP than in the control group

(10.0% vs 22.0%, χ2=5.046; df=1, p=0.025). Most women were first-time mothers (57%),

78

and only 33% reported being married. The mean age was 27.4 years, ranging

Table 4.1. Descriptive Statistics for Characteristics of the Preterm Infants and Their Mothers

Maternal Characteristic

N Total

N = 221 Control N = 141

HDP N = 80 p

Race, n (%) 221 0.0271 White 45 (20.4) 34 (24.1) 11 (13.8) African-American 151 (68.3) 89 (63.1) 62 (77.5) Hispanic 18 (8.1) 14 (9.9) 4 (5.0) Other 7 (3.2) 4 (2.8) 3 (3.8)

Multiple Births, n (%) 221 39 (17.7) 31 (22.0) 8 (10.0) 0.025 First-time mothers 212 120 (56.6) 74 (54.8) 46 (59.7) 0.487 Age, mean ± SD, yr 217 27.4 ± 6.1 27.13 ± 5.9 27.73 ± 6.6 0.486 Education, mean ± SD, yr 221 13.4 ± 2.3 13.5 ± 2.4 13.4 ± 2.1 0.667 Married, n (%) 215 70 (32.6) 43 (31.6) 27 (34.2) 0.699

Infertility, n (%) 220 9 (4.1) 7 (5.0) 2 (2.5) 0.4952

Study Intervention 221 0.776 ATTV 75 (33.9) 47 (33.3) 28 (35.0) Control 76 (34.4) 47 (33.3) 29 (36.3) Kangaroo 70 (31.7) 47 (33.3) 23 (28.8)

History of diabetes, n (%) 213 17 (8.0) 5 (3.6) 12 (16.2) <.001 Prenatal care, n (%) 220 204 (92.7) 130 (92.2) 74 (93.7) 0.687

Infant Characteristic

N Total

N = 221 Control N = 141

HDP N = 80

p

Birth weight, mean ± SD, g 221 1009.3 ± 331.3 1031.2 ± 332.2 970.9 ± 328.3 0.194 Female gender, n (%) 221 121 (54.8) 78 (55.3) 43 (53.8) 0.822 Infant surgery, n (%) 219 80 (36.5) 54 (38.9) 26 (32.5) 0.347 Necrotizing enterocolitis, n (%) 219 33 (15.1) 16 (13.7) 14 (17.5) 0.445

Control=Women without hypertensive disorders of pregnancy; HDP=Women with hypertensive disorders of pregnancy; p-value for two tailed test results; t-tests for continuous variables and chi-square tests for categorical variables; ATTV: Auditory, Tactile, Visual and Vestibular intervention; History of diabetes: chronic and gestational. 1 Race p-value is for a 2 x 2 chi-square test with group (HDP vs Control) by race (black vs non-black); 2Fisher’s Exact Test results due to low cell count.

from 17 to 43, and the mean years of education was 13.4 years, ranging from 8 to 20.

Seventeen mothers (8%) had a history of diabetes and 204 (93%) mothers reported

79

receiving prenatal care. The women and their infants were randomized to one of three

study intervention arms, with approximately 33% per arm. Table 4.1 presents the infant

characteristics for the total sample and each study group. Approximately 55% of the

infants were female, and the mean birth weight of the infants was 1009.2 grams (range:

410.0 to 1780.0). Among the infants, 37% had surgery and 15% had NEC.

Infant Illness Outcomes. Table 4.2 details the infant illness outcomes for the total

sample and study groups. The preliminary between-group comparisons indicated no

statistically significant differences on any illness variables (all p>0.05). Table 4.3 presents

the results from the logistic regression models and GLMs. Logistic regression analyses

on NBRS, PDA, IVH, and infections indicated no significant between-group differences

in the proportion of infants with these conditions. However, there were significant

between-group differences in the percentage of SGA infants. The HDP group had

higher percentage of SGA infants than the control group (SGA 31.7% versus 10.6%, p

< 0.001). In addition, the HDP group had lower rates of being high on the NBRS and

IVH than the control group (NBRS 28.8% versus 40.7%, p< 0.100; IVH 26.3% versus 37.9,

p< 0.100), but these differences were not significant. Race (Black, non-Black) was a

significant covariate for the NBRS outcome, with infants of Black mothers having a

lower rate of high-risk NBRS scores than the infants of non-Black mothers (29.1% versus

52.2%, p<0.001).

The HDP and control group did not differ significantly on days of mechanical

ventilation. Race was a statistically significant covariate for ventilator days, with infants

80

of Black mothers having a lower mean number of days on the ventilator than infants of

Table 4.2. Descriptive Statistics for Illness Outcomes Variables for Preterm Infants

Outcome

Total N = 221

Control N = 141

HDP N = 80

p

Number of neurobiological risks (n) 220 140 80 0.090 Median (25, 75th) 3.0 (1.0, 6.0) 3.0 (1.0,7.0) 2.0 (1.0,5.0) Minimum, Maximum 0.0, 17.0 0.0, 17.0 0.0, 15.0

Neurobiological risks (NBRS) (n) 220 140 80 0.076 No, n (%) 140 (63.6) 83 (59.3) 57 (71.3) Yes, n (%) 80 (36.4) 57 (40.7) 23 (28.8)

Patent ducts arteriosus (PDA) (n) 220 141 79 0.484 No, n (%) 124 (56.4) 77 (54.6) 47 (59.5) Yes, n (%) 96 (43.6) 64 (45.4) 32 (40.5)

Log of days on ventilator (n) 221 141 80 0.395 Median (25, 75th) 2.1 (0.7, 3.3) 2.2 (0.7, 3.3) 1.8 (0.3, 3.2) Mean (SD) 2.0 (1.4) 2.1 (1.4) 1.9 (1.5) Minimum, Maximum 0.0, 5.7 0.0, 5.7 0.0, 4.6

Small for gestational age (SGA), n (%)

40 (18.2) 15 (10.6) 25 (31.7) <.0011

Intraventricular hemorrhage (IVH) (n)

220 140 80 0.080

No, n (%) 146 (66.3) 87 (62.1) 59 (73.8) Yes, n (%) 74 (33.6) 53 (37.9) 21 (26.3)

Infection 220 140 80 0.976 No, n (%) 52 (23.6) 33 (23.6) 19 (23.8) Yes, n (%) 168 (76.4) 107 (76.4) 61 (76.3)

Birth gestational age, weeks (GA) (n)

221 141 80 0.099

Median (25, 75th) 27.0

(25.0, 29.0) 26.0

(25.0, 29.0) 28.0

(25.0,30.0)

Mean (SD) 27.2 (2.9) 27.0 (2.9) 27.7 (2.9) Minimum, Maximum 21.0, 35.0 21.0, 35.0 23.0, 35.0

p-value for chi-square test for binary outcomes and Wilcoxon Two-Sample Test for continuous outcomes. 1 2 x 2 chi-square test p-value (small versus appropriate/large gestational age). HDP= hypertensive disorders of pregnancy

non-Black mothers (Log mean+SD Black, 1.8 +1.4; non-Black, 2.5 +1.4, p<0.001, actual

mean+SD Black, 13.0+17.7; non-Black, 24.9+39.5). Infants in the HDP group had a greater

81

gestational age at birth than infants in the control group (Mean+SD: HDP, 27.7+2.9,

Table 4.3. Logistic Regression Models for Infant Illness Outcomes

OR= odds ratio for outcome comparing HDP/control; Partial η2= partial eta-squared; 95% CI = 95% Confidence Interval; Model=bivariate model with study group only or multivariate model with study group and any significant covariates. GLM Type III sums of squares results. HDP= hypertensive disorders of pregnancy

control, 27.0+2.9 weeks, p< 0.10) but this difference was not significant. Prenatal care had a

small, but statistically significant effect (η2 partial =0.0194, p=0.039). The mean birth gestational

Logistic Regression Model Outcome

Model Explanatory Variable

Wald χ2 (df=1)

p OR OR 95% CI

Neurobiological risk (NBRS)

Bivariate Study group 3.120 0.077 0.588 0.326, 1.060

Multivariate Study group 1.818 0.178 0.659 0.360, 1.208 Black 9.246 0.002 0.398 0.219, 0.720 Patent ducts arteriosus (PDA)

Bivariate Study group 0.491 0.484 0.819 0.469, 1.432

Small for gestational age (SGA)

Bivariate Study group 13.856 0.002 3.889 1.902, 7.950

Intraventricular hemorrhage (IVH)

Bivariate Study group 3.041 0.081 0.584 0.319, 1.069

Infection Bivariate Study group <.001 0.976 0.990 0.519, 1.889

General Linear Model (GLM)

Outcome

Model Explanatory Variable

F df,df p Partial η2

Partial η2 95% CI

Log of days on ventilator

Bivariate Study group 0.811,219 0.368 0.004 0.000, 0.036

Multivariate Study group 0.161,218 0.686 <.001 0.000, 0.024

Black 11.701,21

8 <.001 0.051 0.000, 0.117

Birth gestational age, weeks (GA)

Bivariate Study group 2.74 1,219 0.099 0.012 0.000, 0.056

Multivariate Study group 2.90 1,217 0.090 0.013 0.000, 0.058 Prenatal

care 4.30 1,217 0.039 0.019 0.000, 0.069

82

age was less for infants whose mothers received prenatal care than those whose mothers did

not (Mean+SD: prenatal care; 27.1+2.9, no prenatal care, 28.6+2.8).

Table 4.4 shows the descriptive statistics for the infant physical developmental

outcomes at birth and 2 months. The HDP and control groups did not differ significantly

on these measures at either assessment point. Descriptive statistics for infants with data

available at both assessment points are presented in Table 4.5. The mean infant height at 2

months tended to be less in the HDP group relative to the control group for the total

sample and the subsample with data at both assessment points but this difference was not

significant.

Table 4.4. Descriptive Statistics for Physical Developmental Outcomes of Preterm Infants

Measures Total

N = 221 Control N = 141

HDP N = 80 p

Head circumference at birth (n) 221 124 73 0.236

Median (25th, 75th percentile) 28.5 (27.0,

30.0) 28.5 (27.0, 30.0) 28.5 (27.0, 30.0)

Mean (SD) 28.4 (2.3) 28.2 (2.4) 28.7 (2.3) Minimum, Maximum 19.0, 34.5 19.0, 33.0 23.8, 34.5

Head circumference at 2 Months (n) 162 106 56 0.608

Median (25th, 75th percentile) 39.0 (38.0,

40.0) 39.0 (38.0,

41.0) 39.0 (38.0,

40.0)

Mean (SD) 39.3 (2.1) 39.3 (2.1) 39.1 (2.1) Minimum, Maximum 34.0, 46.0 34.0, 46.0 35.0, 46.0

Height at birth (n) 192 120 72 0.966

Median (25th, 75th percentile) 40.0 (38.0,

42.0) 40.0 (38.0,

42.5) 40.0 (38.0,

42.0)

Mean (SD) 39.8 (3.2) 39.8 (3.3) 39.8 (3.0) Minimum, Maximum 28.0, 46.5 28.0, 46.0 32.0, 46.5

Height at 2 Months (n) 157 101 56 0.097

Median (25th, 75th percentile) 56.5 (53.5,

58.5) 57.0 (54.0,

59.5) 56.0

(53.2,57.0)

83

Measures Total

N = 221 Control N = 141

HDP N = 80 p

Mean (SD) 56.3 (4.2) 56. 8(4.5) 55.6 (3.7)

Minimum, Maximum 43.5, 69.0 43.5, 69.0 47.0, 68.0 Weight at birth (kg) (n) 212 125 77 0.972

Median (25th, 75th percentile) 1.5 (1.2, 1.7) 1.5 (1.2,1.7) 1.4 (1.2,1.7) Mean (SD) 1.5 (0.4) 1.5 (0.4) 1.5 (0.4) Minimum, Maximum 0.7, 2.8 0.7, 2.4 0.8, 2.8

Weight at 2 Months (n) 168 110 58 0.280 Median (25th, 75th percentile) 4.9 (4.4,5.6) 5.0 (4.5,5.8) 4.8 (4.4, 5.4) Mean (SD) 5.0 (1.0) 5.1 (1.0) 4.9 (1.0) Minimum, Maximum 2.7,9.3 3.1, 8.2 2.7, 9.3

p-value results for t-test comparing infants of women with and without hypertensive disorders; HDP= hypertensive disorders of pregnancy

The analysis of covariance procedures using GLM for each 2-month outcome,

controlling for the same measure at birth and other potential covariates, were conducted

on the subsample with data at both time points. None of the other potential covariates

significantly influenced the 2-month outcomes and, therefore, they were omitted from

the final models. Table 4.6 presents the GLM results for each 2-month outcome, after

controlling for the same measure at birth. The results also indicated that the mean infant

height at 2 months was lower in the HDP group compared to the control group, after

covarying for height at birth (η2 partial =0.022, representing a small effect) but the

difference was not significant. Greater height at birth was a significant predictor of

greater height at 2 months.

Table 4.5. Descriptive Statistics for Physical Developmental Outcomes at Birth and 2 Months

Measures Total Control HDP p

Head circumference (n) 149 96 53

84

Measures Total Control HDP p

Birth: Mean (SD) 28.5 (2.3) 28.4 (2.5) 28.8 (1.9) 0.289

Month 2: Mean (SD) 39.4 (2.1) 39.5 (2.0) 39.2 (2.2) 0.383

Height (n) 139 88 51

Birth: Mean (SD) 40.0 (3.1) 40.0 (3.2) 40.0 (2.9) 0.993

Month 2: Mean (SD) 56.4 (4.3) 56.9 (4.4) 55.6 (3.8) 0.085

Weight (n) 161 104 57

Birth: Mean (SD) 1.5 (0.4) 1.5 (0.4) 1.5 (0.4) 0.722

Month 2: Mean (SD) 5.0 (1.0) 5.1 (1.0) 4.9 (1.0) 0.256

Note: Only infants with data available at both birth and 2 months were analyzed; p-value for t-test; HDP= hypertensive disorders of pregnancy.

Table 4.6. Analysis of Covariance for Physical Developmental Outcomes of Preterm

Infants at 2 Months

Partial η2= partial eta-squared; 95% CI = 95% Confidence Interval; Analysis of covariance using a General Linear Model approach for infants with data available at birth and 2 months; HDP= hypertensive disorders of pregnancy.

Table 4.7 provides descriptive statistics for the three neurodevelopmental

outcomes at 12 months and the analysis of variance and analysis of covariance results

2 Months Outcome Explanatory Variable

F df, df p Partial

η2

Partial η2 95% CI

Head Circumference (HC) Study group 0.83 1,146 0.365 0.006 0.000, 0.052

HC at birth 0.22 1,146 0.636 0.002 0.000, 0.037

Height (HT) Study group 3.09 1,136 0.081 0.022 0.000, 0.091

HT at birth 4.13 1,136 0.041 0.030 0.000, 0.103

Weight (WT) Study group 1.28 1,158 0.259 0.008 0.000, 0.056

WT at birth 0.02 1,158 0.891 0.001 0.000, 0.018

85

from the GLMs. The HDP and control groups did not differ significantly on the

neurodevelopmental outcomes with or without covariates. Prenatal care was not

included as a covariate because only four infants who were without prenatal care had

neurodevelopmental outcomes at 12 months. Covariates were not significantly

associated with any of the outcomes. Thus, the final models included study group only.

Table 4.7. Descriptive Statistics and General Linear Models, for preterm Infant Neurobehavioral Outcomes at 12 Months

12 Months Outcome

Total N = 221

Control N = 141

HDP N = 80

F df,df p Partial η2

Partial η2

95% CI

Cognitive n 155 99 56 1.25 1,153 0.265 0.008 0.000, 0.058

Mean (SD) 97.3 (16.5) 96.2 (17.1) 99.3 (15.4)

Min, max 49.0,135.0 49.0, 125.0 55.0, 135.0

Language n 153 97 56 1.02 1,151 0.314 0.007 0.000, 0.055

Mean (SD) 90.8 (14.9) 89.9 (14.9) 92.4 (14.8)

Min, max 47.0, 124.0 47.0,124.0 47.0, 121.0

Motor skills n 154 98 56 0.01 1,152 0.907 <.001 0.000, 0.017

Mean (SD) 89.8 (17.8) 89.7 (17.6) 90.1 (18.4)

Min, max 46.0, 121.0 46.0,121.0 46.0, 115.0

SD= Standard Deviation; Min, max = minimum, maximum; p-value for GLMs; Partial η2= partial eta-squared; 95% CI = 95% Confidence Interval; Model=bivariate model with study group only or multivariate model with study group and prenatal care as a covariate; HDP= hypertensive disorders of pregnancy.

4.5 Supplemental Analyses

Supplemental analyses were conducted whereby the HDP group was subdivided

86

into three groups: (1) chronic HTN, (2) PIH, and (3) both chronic HTN and PIH to the

control group. The analyses compared these three subgroups on each infant outcome.

Covariates were omitted and non-parametric Kruskal-Wallis test and Fisher’s Exact

were used due to the small sample sizes. No significant differences were observed (see

Tables 4.8-4.10).

Table 4.8. Supplemental Analysis: Descriptive Statistics for Illness Outcomes of Preterm Infants

HDP (N = 80)

Outcome Control N = 141

CHTN N= 14

PIH N = 43

CHTN & PIH

N = 23 p

Neurobiological risks (NBRS) (n) 140 14 43 23 0.186

No, n (%) 83 (59.3) 10 (71.4) 33 (76.7) 14 (60.9)

Yes, n (%) 57 (40.7) 4 (28.6) 10 (23.3) 9 (39.1)

Patent ducts arteriosus (PDA) 141 14 42 23 0.876

No, n (%) 77 (54.6) 9 (64.3) 24 (57.1) 14 (60.9)

Yes, n (%) 64 (45.4) 5 (35.7) 18 (42.9) 9 (39.1)

Log of days on ventilator 141 14 43 23 0.384

Median (25th, 75th percentiles) 2.2 (0.7, 3.3) 2.4 (0.7,3.9) 1.6 (0.7, 3.1) 1.1 (0.0, 3.3)

Intraventricular hemorrhage (IVH)

140 14 43 23 0.335

No, n (%) 87 (62.1) 10 (71.4) 33 (76.7) 16 (69.6)

Yes, n (%) 53 (37.9) 4 (28.6) 10 (23.3) 7 (30.4)

Infection 140 14 43 23 0.858

No, n (%) 33 (23.6) 4 (28.6) 11 (25.6) 4 (17.4)

Yes, n (%) 107 (76.4) 10 (71.4) 32 (74.4) 19 (82.6)

Birth gestational age, weeks (GA) 141 14 43 23 0.128

87

HDP (N = 80)

Outcome Control N = 141

CHTN N= 14

PIH N = 43

CHTN & PIH

N = 23 p

Median (25th, 75th percentiles) 26.0 (25.0,29.0)

26.0 (24.0,28.0)

28.0 (26.0, 30.0)

28.0 (25.0, 30.0)

CHTN=Chronic HTN disorder prior to the pregnancy only; PIH = Pregnancy induced hypertension without a prior history of HTN; 25th, 75th percentile; p-value for Fisher’s Exact Test for binary outcomes and Kruskal-Wallis Test for continuous outcomes; HDP= hypertensive disorders of pregnancy. Table 4.9. Supplemental Analysis: Descriptive Statistics for Physical Developmental

Outcomes of Preterm Infants

HDP (N = 80)

Outcome Control N = 141

CHTN N = 14

PIH N = 43

CHTN & PIH

N= 23

p

Head Circumference (HC) 124 12 41 20 0.772 Enrollment, median (25th, 75th)

28.5 (27.0, 30.0)

28.5 (27.8, 30.0)

28.5 (27.0, 30.5)

28.4 (27.2, 29.8)

Head Circumference (HC) 106 12 30 14 0.730

2 Months, median (25th, 75th)

39.0 (38.0, 41.0)

38.0 (38.0, 40.0)

39.0 (38.0, 40.0)

39.0 (38.0, 41.0)

Head Circumference (HC) 96 11 30 12 0.502

Difference median (25th, 75th)

11.0 (9.5, 13.0)

9.6 (9.5, 11.5)

10.5 (9.0, 12.0)

10.3 (7.8, 12.5)

Height (HT) 120 12 40 20

Enrollment, median (25th, 75th)

40.0 (38.0, 42.5)

39.2 (38.3, 40.3)

40.0 (37.8, 42.1)

40.0 (37.8, 41.5)

0.926

Height (HT) 110 12 31 15 0.327

2 Months, median (25th, 75th)

5.0 (4.5, 5.8)

4.8 (4.3, 5.7)

4.6 (4.1, 5.3)

4.9 (4.5, 5.5)

Height (HT) 88 11 28 12

Difference median (25th, 75th)

17.0 (14.0, 19.4)

16.6 (13.0, 18.0)

14.4 (12.5, 18.0)

15.3 (13.2, 17.3)

0.202

Weight (WT) 135 14 41 22 0.722

88

CHTN=Chronic HTN disorder prior to the pregnancy only; PIH = Pregnancy induced hypertension without a prior history of HTN; Difference score = 2 Months minus enrollment score; p-value for Kruskal-Wallis Test results.

Table 4.10. Supplemental Analysis: Descriptive Statistics for Preterm Infants

Neurobehavioral Outcomes

CHTN=Chronic HTN disorder prior to the pregnancy only; PIH = Pregnancy induced hypertension without a prior history of HTN; p-value for Kruskal-Wallis Test results

4.6 Discussion

The purpose of this secondary data analysis was to compare the differences

Enrollment, median (25th, 75th)

1.5 (1.2, 1.7)

1.4 (1.3, 1.8)

1.5 (1.2, 1.7) 1.3 (1.2, 1.6)

Weight (WT)) 110 12 31 15 0.327

2 Months, median (25th, 75th)

5.0 (4.5, 5.8)

4.8 (4.3, 5.7)

4.6 (4.1, 5.3)

4.9 (4.5, 5.5)

Weight (WT) 104 12 31 14 0.239

Difference median (25th, 75th) 3.5 (2.9, 4.2)

3.5 (2.9, 4.4)

3.2 (2.6, 4.0)

3.5 (3.2, 4.0)

HDP

N = 80

Month 12 Outcome Control N = 141

CHTN N = 14

PIH N = 43

CHTN & PIH N = 23 p

Cognitive 99 10 30 16 0.156

Median

(25th, 75th)

100.0

(85.0, 110.0)

97.5

(85.0, 100.0)

105.0

(95.0, 110.0)

100.0

(85.0, 107.5)

Language 97 10 30 16 0.310

Median

(25th, 75th)

91.0

(83.0, 100.0)

94.0

(71.0, 97.0)

95.5

(86.0, 106.0)

87.5

(79.0, 97.0)

Motor skills 98 10 30 16 0.335

Median

(25th, 75th)

94.0

(85.0, 100.0)

92.5

(70.0, 97.0)

95.5

(88.0, 107.0)

92.5

(83.5, 97.0)

89

between preterm infants of women with a history of HDP and those of women without

HDP on illness, physical development and neurodevelopmental outcomes. Overall, the

preterm infants of women with HDP were very similar to preterm infants of women

without a history of HDP except for the higher rate of SGA in the infants of women with

HDP. They did not differ on complications that influenced the gestational age at which

they are born or their health after birth. The infants included in this study were all

preterm infants from NICUs and were probably very sick. Thus, they represented a

highly select population. Preterm infants not requiring intensive care and full term

infants were omitted from both groups. The results also did not differ among the

different types of HDP (chronic HTN, PIH, and both chronic HTN and PIH) in our

supplemental analyses.

Infants born to women with HDP were more likely to be SGA than the infants of

the women without HDP. A higher risk for SGA infants among women with HDP is

consistent with findings from another study (Allen, Joseph, Murphy, Magee, & Ohlsson,

2004). The higher rate of SGA probably explains why the infants of women with HDP

had higher mean gestational ages even though their birth weights were lower than

infants of women without HDP.

In this secondary data analysis, the infants of women with and without HDP did

not differ on medical complications including the number of days of mechanical

ventilation. However, an earlier study found that women with a history of HDP had

infants who required more days of mechanical ventilation than infants of those of

90

women without a history of HTN (Cruz et al., 2011). The need for ventilators for infants

in both HPD and the control group maybe the same in this study because the samples

included were only preterm infants recruited from NICUs; whereas the other study

included all deliveries.

To the best of my knowledge, no study has compared preterm infants of women

with HDP and without HDP on physical and neurodevelopmental development.

Developmental delays are frequent complications of preterm birth (Adams-Chapman et

al., 2013). Preterm infants admitted to the NICU are at greater risk for

neurodevelopmental impairment (Myers & Ment, 2009) and developmental delay than

full term infants (Jackson, Needelman, Roberts, Willet, & McMorris, 2012). The lack of

significant differences between the preterm infants of women with HPD and control

women on physical and neurodevelopment suggested that despite a higher risk of being

SGA, the preterm infants of women with HPD developed at similar rates as infants of

women without HPD. Cognitive, language and motor development by 12 months

corrected age and growth measures at 2 months of infants of women with HDP and

without HDP had similar means. Thus, maternal history of HDP did not contribute

significantly to physical and neurodevelopmental changes among preterm infants

treated in an NICU.

Prenatal care and being born to non-Black women (ethnicity/ race) were

significant covariates. Infants born to non-Black women required more days on the

mechanical ventilator than did the infants of Black women. In addition, the findings

91

from this study indicated that ethnicity was more closely related to the need for

mechanical ventilation than maternal hypertensive status.

Interestingly, gestational age was higher for infants whose mothers did not have

prenatal care. This finding is not consistent with earlier studies (Vintzileos et al., 2002).

There may be several reasons to explain higher gestational age in women who did not

use prenatal care. It is likely that these women may have been very healthy and, thus,

did not seek prenatal care until they were in preterm labor.

4.7 Limitations

One limitation of the current study was that the effect sizes detected were lower

than the medium effect size predicted with the power analysis. Thus, the sample size

for the group of mothers with HDP and their infants was not sufficiently large to

provide 80% power to detect group differences and effect sizes when the level of

significance was set at 0.05.

The second limitation was that the preterm infants in this study belonged to a

selected group. Because the preterm infants both the HDP and the control groups were

recruited in the NICU, the sample excluded preterm infants that died and preterm

infants that did not require NICU admission. The results may not be representative of

all preterm infants because the sample analyzed was selective and also attrition bias

due to infant death and withdrawal from the original study may limit generalizability of

this study.

92

4.8 Conclusions

This study is the first study in which physical and neurodevelopmental

outcomes of infants born to women with history of HDP. This study examined the

short-term and long-term health of preterm infants born to women with history of HDP.

I found that preterm infants born to women with a history of HDP were more often

small for gestational age than infants of women without HDP. Although there is a need

to explore these outcomes further, I also concluded that preterm infants of women with

HDP will grow at the same rate as other preterm infants in their first 2 months of life.

93

Chapter 5. Conclusions and Knowledge Acquired The purpose of this dissertation was to develop an understanding of the

influence of hypertensive disorders (HDP) on pregnancy outcomes for women and their

infants and to describe the relationships among chronic hypertension (HTN), prenatal

care, and pregnancy outcomes. This chapter addresses significant findings from

Chapters 3 and 4; the influence of prenatal care on women with chronic diseases,

especially HTN; and the future direction of research about women of child bearing age

with chronic diseases.

5.1 Summary of Significant Findings in Chapter 3

The results from Chapter 3 indicated that women with chronic HTN had higher

rates of PIH, preterm birth and SGA infants but did not have a higher rate of placental

abruption. Chapter 3 of this dissertation also showed that with the exception of

placental abruption and without adjusting for the demographic variables, the rates of

PIH, preterm birth and SGA infants were higher among the women with chronic HTN

than women without chronic HTN. However, after adjusting for demographic

variables, only PIH was higher among the women with chronic HTN compared to

women without chronic HTN. The estimated odds of having PIH was 4.5 times greater

among the women with chronic HTN. First trimester prenatal care and adequate

prenatal care did not improve pregnancy outcomes more than was experienced by

women without chronic HTN. Perinatal risk factors--maternal education, maternal age

94

and ethnicity—were associated with a greater risk for poor maternal and infant

outcomes for women with chronic HTN as confirmed in previous studies (Bryant et al.,

2005; Poon et al., 2010; Sabol et al., 2014). The effect of demographic variables should be

considered when addressing issues related to improving pregnancy outcomes for

women with chronic HTN. As indicated in Chapter 3, maternal age, maternal education

level and ethnicity/race influenced both maternal and infant outcomes. Although health

care providers are already aware older women and minorities often have poor

pregnancy outcomes, educating these women on their risks and providing appropriate

guidance may improve their pregnancy outcomes. Some of the demographic variables

that differed between women with HTN and women without HTN such as maternal

BMI before pregnancy, pre-pregnancy diabetes and weight gain during pregnancy may

be modifiable. Thus, chronic HTN should not be managed without consideration of

modifiable behaviors that may help improve overall health outcomes for women with

chronic diseases.

Chronic HTN in pregnancy and its relation to pregnancy induced HTN is

complex. To understand this complex relationship and understand which other factors

influence adverse maternal and infant outcomes related to chronic HTN, the Neuman

Systems Model (NSM) provided the theoretical perspective for examining the effects of

chronic HTN on pregnancy complications and infant outcomes. In Chapter 3, the NSM

guided the examination of the relationship chronic HTN has with pregnancy related

HTN and pregnancy complications.

95

Women with chronic HTN have different maternal and infant pregnancy

outcomes than women without chronic HTN. The Neuman Systems Model was used to

define in the simplest form the relationships among chronic HTN, prenatal care and

other variables in pregnancy that might affect pregnancy complications and infant

outcomes. The Neuman Systems Model focuses on the core characteristics of human

system that stabilize the individual system (pregnant woman) and identified

sociocultural variables as one of the interacting variables. Using the NSM, maternal

demographic/sociocultural variables (education, age and ethnicity/race) that have

complex relationships with chronic HTN were identified and analyzed in association

with prenatal care. The Neuman Systems Model strengthened this study because

pregnancy was viewed through the lenses of maternal health before pregnancy, care

received during pregnancy, the benefits of care received and complications developed as

a result of maternal health before and during pregnancy.

The limitation of the NSM is that it may not be the best fitting model for women

with chronic diseases during pregnancy. The NSM helped to identify the variables

associated with chronic HTN and also identified prenatal care as an intervention.

However, the positive effects of prenatal care did not extend to women with chronic

HTN and their infants

5.2 Summary of Significant Findings in Chapter 4

The results from Chapter 4 indicated that the preterm infants of women with

96

HDP were very similar to preterm infants of women without a history of HDP. They

did not differ on complications that influenced the gestational age at which they are

born or their health after birth.

On the other hand, preterm infants of women with HDP from the NICU were

more often smaller for gestational age than other preterm infants. More research is

needed to determine the health conditions and optimal care for preterm infants of

women with HDP. Because not all preterm infants are admitted to the NICU, I

speculate that I was unable to determine the health conditions of preterm infants born to

women with hypertensive disorders and who received care outside the NICU. Preterm

infants may not need to be admitted to the NICU because of gestational age (late

preterm infants) or because they are healthy enough to be cared for in an intermediate

care facility (Hamilton, Hoyert, Martin, Strobino, & Guyer, 2013; Medoff Cooper et al.,

2012; Miles, Holditch-Davis, Schwartz, & Scher, 2007). These healthier preterm infants

may be more likely to be born to normotensive women. Infants of women with HDP

may need to have extra medical attention because maternal chronic diseases during

pregnancy may affect the health of preterm infants in ways that may not be immediately

known. Preterm infants of women with HDP need to be studied further with particular

attention to the location of care of the infants to better understand the health

complications of infants of women with HDP.

97

5.3 Need to Upgrade Prenatal Care for Women with Chronic Diseases

This dissertation also examined the effect of prenatal care on women with

chronic HTN. Women with HTN may benefit from prenatal care to improve infant

outcomes such as by preventing preterm birth. Prenatal care undoubtedly improves

maternal and infant outcomes for women without chronic diseases (Boss & Timbrook,

2001). Interestingly, the initial goal of prenatal care in the United States was to prevent

preeclampsia during pregnancy, which is the most common complication in women

with chronic HTN (Alexander & Korenbrot, 1995; Taussig, 1937). However, the goal has

evolved over the years to focus more on preventing low birth weight and infant

mortality (Alexander & Korenbrot, 1995; Behrman, 1985).

However, the benefits of prenatal care that are evaluated based on receiving first

trimester prenatal care and adequate prenatal care did not seem to have the same effect

on the population of women with chronic HTN, who are at risk for the most important

complications that prenatal care is intended to prevent, as on normotensive women. A

previous study also concluded that adequate prenatal care alone was not enough to

prevent adverse infant outcome such as low birth weight in pregnant women (da

Fonseca, Strufaldi, de Carvalho, & Puccini, 2014).

The effectiveness and benefits of prenatal care might vary among certain

subgroups including women with chronic illness (Alexander & Kotelchuck, 2001). The

results of this dissertation support the assertion that the current form of prenatal care is

98

not effective in preventing adverse maternal and infant outcomes for women with

chronic HTN. In Chapter 4 of this dissertation, 93.7% women with HDP received

prenatal care and likewise 92.2% of women without hypertensive disorders. However,

infants of women with HDP were more likely to be SGA despite receiving prenatal care.

In Chapter 3 of this dissertation, the success of prenatal care (first trimester prenatal care

and adequate prenatal care) did not benefit women with chronic HTN as intended.

Women of childbearing age continue to be vulnerable to pregnancy

complications because the number of women in their 30s and 40s giving birth continues

to increase (Sibai, 2002, 2007). In addition, women with chronic diseases at the time of

pregnancy are increasing as well (Sibai, 2002, 2007). The approach and method of

delivering prenatal care needs to change in order to provide effective care in response to

this shift to older women giving birth at a higher rate than 10 years ago. Pregnant

women with chronic diseases may need to see both a primary care provider and an

obstetrician to allow the primary care providers to focus on managing the chronic

disease. Without tailoring prenatal care to accommodate the health needs of women

with chronic illnesses like HTN, maternal and infant morbidity and mortality will

continue to increase. Health care providers managing women with chronic diseases

who have the potential to give birth should encourage these women to control their

chronic conditions prior to conception to minimize pregnancy complications.

The findings in this dissertation indicated that older women with chronic HTN

may need more attention during pregnancy than younger women because maternal age,

99

which also correlates with maternal level of education, is related to adverse maternal

and infant outcomes (Chapter 3). Although women who attend higher education may

be older before starting a family, these women might also have chronic diseases of

which they might not be aware. As a result, they need careful monitoring during

pregnancy. Providing anticipatory guidance on possible complications during and after

pregnancy as part of prenatal care would help women report signs and symptoms early

and receive timely medical attention.

Another finding consistent with previous studies (Ahern, Pickett, Selvin, & Abrams,

2003; Dole et al., 2004; Goldenberg, Culhane, Iams, & Romero, 2008; Vintzileos, Ananth,

Smulian, Scorza, & Knuppel, 2002) was that Black women were at greater risk for

preterm birth than non-Black women. The estimated odds of having preterm infants

among Black women was 1.5 times higher compared to non-Black women (Chapter 3)

regardless of their hypertensive status. Thus, prenatal care needs reevaluation to

improve pregnancy outcomes for Black women.

Chronic HTN in pregnancy is understudied because most studies focusing on

pregnancy and maternal and infant outcomes exclude women with chronic HTN.

Chronic HTN is considered a condition that might influence the results of those studies.

Because chronic HTN contributes to pregnancy related HTN and adverse birth

outcomes, chronic HTN might possibly have a greater influence on maternal and infant

outcomes than pregnancy related HTN. Despite the effects of chronic HTN on birth

outcomes of women and their infants, prenatal care, on which all women with and

100

without chronic HTN depend, does not appear to improve birth outcomes of women

with chronic HTN to the same degree as women without chronic HTN.

Over-reliance on prenatal care in its current one-size-fits-all form to solve all the

health problems of pregnant women may make prenatal care ineffective for women with

chronic diseases because health care providers may focus on fetal health more than

managing the mothers’ chronic diseases. Prenatal care serves as an entry point to the

health care system for most women (Misra & Guyer, 1998). However, pregnant women

and their health care providers should not continue to expect prenatal care alone to

resolve the effects of chronic diseases such as HTN (Hollowell, Oakley, Kurinczuk,

Brocklehurst, & Gray, 2011; Misra & Guyer, 1998; Moos, 2006).

The objective of prenatal care is to prevent diseases in pregnancy, rather than

managing existing diseases. Unfortunately, existing diseases and future diseases are

closely related. Thus, prenatal care delivery needs to be updated to closely monitor

chronic diseases to prevent future complications. Women who have chronic diseases

and are pregnant need to have a provider who can focus on managing the chronic

diseases. Having two different providers (obstetricians/midwives and primary care

providers including advanced practices nurses [APRNs]) during pregnancy may be

costly but might improve the health of mother and baby and reduce the burden on the

health care system, which may not become evident until after the baby is born ill and the

mother’s chronic disease worsens. Researchers need to explore the effectiveness of

managing pregnant women with chronic diseases by two different health care providers

101

and whether this care is cost effective.

5.4 Summary of this Dissertation Findings

In conclusion, women with chronic HTN were at greater risk for PIH, preterm

delivery and SGA infants than women without chronic HTN. Women with chronic

HTN did not derive the same benefits from first trimester prenatal care and adequate

prenatal care as women without chronic HTN. First trimester prenatal care and

adequate prenatal care did not reduce the rate of PIH, placental abruption, preterm birth

and SGA infants among women with chronic HTN. The severity of HTN needs to be

determined before or during early pregnancy to effectively manage the HTN during

pregnancy and prevent adverse pregnancy outcomes. Women with chronic HTN may

require specialized care because first trimester prenatal care and adequate prenatal care

did not appear to benefit them as much as women without chronic HTN. For older

women and women with chronic diseases, access to prenatal care alone is not enough to

effectively manage all aspects of their health or to improve their pregnancy outcomes.

Poor pregnancy outcomes for these women who often are well educated and part of the

work force will severely affect their families, the health care system and the country as a

whole.

This study examined the short-term and long-term health of preterm infants born to

women with history of HDP. I found that surviving preterm infants born to women

with a history of HDP were often small for gestational age. While there is a need to

102

explore this outcome further, this dissertation showed that preterm infants of women

with HDP would grow at the same rate as other preterm infants through 2 months

corrected age.

5.5 Direction for Future Research

Future research needs to focus on preterm infants born to women of HDP and

focus on the type of care (NICU or nursery) they received after birth in order to

understand whether preterm infants of women with HDP, admitted to the NICU or not,

are more likely to be small for gestational age than infants of normotensive mothers.

The difference between premature infants of mothers with and without HDP may be

more pronounced if the preterm infants of women without HDP were not as likely to

require intensive care as infants of women with HDP. As part of efforts to improve

prenatal care for women with chronic conditions like hypertensive disorders, studies

need to be designed to determine the benefits of a tailored prenatal care for women with

HDP to reduce the severe impact of HTN and improve overall health outcomes for

mothers and babies.

Pregnant women whether they are at low-risk or high-risk rely on prenatal care

for maintenance of their health and to minimize adverse birth outcomes. Because

prenatal care is key source of care and information for pregnant women, it is alarming

that prenatal care as it is currently provided is ineffective for women with chronic HTN.

Thus, research is needed on innovative and effective ways of providing care for this

103

subpopulation that continue increase as more women delay child birth.

Prenatal care is the initial point of contact to the health care system for most

women. Some women will be diagnosed with acute and chronic diseases such as HTN

at this point. Diagnoses of acute or chronic conditions may not resolve after giving

birth. Therefore, introducing these women to primary care providers during pregnancy

is necessary for continuity of care after pregnancy. This simple step may help prevent

future complications and manage chronic diseases effectively.

Some women diagnosed with HTN (gestational HTN and preeclampsia) for the

first time after 20 weeks gestation may continue to have elevated blood pressure post

pregnancy, which may lead to chronic HTN (Intapad & Alexander, 2013). Pregnancy

related HTN was also linked to future cardiovascular diseases (Magnussen, Vatten,

Smith, & Romundstad, 2009; Weissgerber et al., 2015) such as stroke (Wilson et al., 2003).

Researchers need to focus on appropriate interventions to minimize women developing

cardiovascular diseases after giving birth.

104

Appendix A. Abbreviations and Their Meanings

Abbreviations Definitions CHTN Chronic hypertension

GA Gestational age

HC Head circumference

HELLP Hemolysis, Elevated Liver enzymes, Low Platelet count

HDP Hypertensive disorders in pregnancy

HT Height

HTN Hypertension

IVH Intraventricular hemorrhage

NICU Neonatal Intensive Care Unit

NSM Neuman Systems Model

PE Preeclampsia

PIH Pregnancy induced hypertension

PNC Prenatal care

PRAMS Pregnancy Risks Assessment Monitoring System

SGA Small for gestational age

SPE Superimposed preeclampsia

WT Weight

105

References Abalos, E., Cuesta, C., Carroli, G., Qureshi, Z., Widmer, M., Vogel, J. P., & Souza, J. P.

(2014). Pre-eclampsia, eclampsia and adverse maternal and perinatal outcomes: a secondary analysis of the World Health Organization Multicountry Survey on Maternal and Newborn Health. BJOG: An International Journal of Obstetrics and Gynaecology, 121 Suppl 1, 14-24. doi:10.1111/1471-0528.12629

Adams-Chapman, I., Bann, C. M., Vaucher, Y. E., Stoll, B. J., Human Development

NICHD Neonatal Research Network, & Eunice Kennedy Shriver National Institute of Child Health (2013). Association between feeding difficulties and language delay in preterm infants using Bayley Scales of Infant Development. The Journal of Pediatrics, 163(3), 680-685. e683.

Ahern, J., Pickett, K. E., Selvin, S., & Abrams, B. (2003). Preterm birth among African

American and white women: a multilevel analysis of socioeconomic characteristics and cigarette smoking. Journal Epidemiology Community Health, 57(8), 606-611.

Alexander, G. R., & Korenbrot, C. C. (1995). The role of prenatal care in preventing low

birth weight. The Future of Children, 1995; 5:103-120. Alexander, G. R., & Kotelchuck, M. (2001). Assessing the role and effectiveness of

prenatal care: history, challenges, and directions for future research. Public Health Reports, 116(4), 306-316.

Allen, V. M., Joseph, K., Murphy, K. E., Magee, L. A., & Ohlsson, A. (2004). The effect of

hypertensive disorders in pregnancy on small for gestational age and stillbirth: a population based study. BMC Pregnancy and Childbirth, 4(1), 17. doi:10.1186/1471-2393-4-17

American College of Obstetricians and Gynecologists. (2013). Hypertension in

pregnancy. Report of the American College of Obstetricians and Gynecologists’ task force on hypertension in pregnancy. Obstetrics and gynecology, 122(5), 1122

Ananth, C. V., Peltier, M. R., Kinzler, W. L., Smulian, J. C., & Vintzileos, A. M. (2007).

Chronic hypertension and risk of placental abruption: is the association modified by ischemic placental disease? American Journal of Obstetric & Gynecology, 197(3), 273 e271-277. doi:10.1016/j.ajog.2007.05.047

Ananth, C. V., Savitz, D. A., & Williams, M. A. (1996). Pracental abruption and its

106

association with hypertension and prolonged rupture of membranes: A methodologic review and meta-analysis. Obstetrics & Gynecology, 88(2), 309-318.

Ananth, C. V., & Vintzileos, A. M. (2011). Ischemic placental disease: epidemiology and

risk factors. European Journal of Obstetrics & Gynecology and Reproductive Biology, 159(1), 77-82. doi:10.1016/j.ejogrb.2011.07.025

Ankumah, N. A., Cantu, J., Jauk, V., Biggio, J., Hauth, J., Andrews, W., & Tita, A. T.

(2014). Risk of adverse pregnancy outcomes in women with mild chronic hypertension before 20 weeks of gestation. Obstetrics & Gynecology, 123(5), 966-972. doi:10.1097/aog.0000000000000205

Ankumah, N. E., & Sibai, B. M. (2017). Chronic Hypertension in Pregnancy: Diagnosis,

Management, and Outcomes. Clinical Obstetrics and Gynecology, 60(1), 206-214. doi:10.1097/grf.0000000000000255

Barbosa, I. R., Silva, W. B., Cerqueira, G. S., Novo, N. F., Almeida, F. A., & Novo, J. L.

(2015). Maternal and fetal outcome in women with hypertensive disorders of pregnancy: the impact of prenatal care. Therapeutic Advances in Cardiovascular Disease, 9(4), 140-146. doi:10.1177/1753944715597622

Bateman, B. T., Bansil, P., Hernandez-Diaz, S., Mhyre, J. M., Callaghan, W. M., &

Kuklina, E. V. (2012). Prevalence, trends, and outcomes of chronic hypertension: a nationwide sample of delivery admissions. American Journal of Obstetric & Gynecology, 206(2), 134 e131-138. doi:10.1016/j.ajog.2011.10.878

Bateman, B. T., Huybrechts, K. F., Fischer, M. A., Seely, E. W., Ecker, J. L., Oberg, A. S., . .

. Hernandez-Diaz, S. (2014). Chronic Hypertension in Pregnancy and the Risk of Congenital Malformations: A Cohort Study. American Journal of Obstetric & Gynecology, 212(3), 337-e1. doi:10.1016/j.ajog.2014.09.031

Bayley N. (2003). Bayley Scales of Infant and Toddler Development. San Antonio, TX: The

Psychological Corporation. Boss, D. J., & Timbrook, R. E. (2001). Clinical obstetric outcomes related to continuity in

prenatal care. Journal of American Board Family Practice, 14(6), 418-423. Bouthoorn, S. H., Gaillard, R., Steegers, E. A., Hofman, A., Jaddoe, V. W., van Lenthe, F.

J., & Raat, H. (2012). Ethnic differences in blood pressure and hypertensive complications during pregnancy: the Generation R study. Hypertension, 60(1), 198-205. doi:10.1161/hypertensionaha.112.194365

107

Bramham, K., Parnell, B., Nelson-Piercy, C., Seed, P. T., Poston, L., & Chappell, L. C.

(2014). Chronic hypertension and pregnancy outcomes: systematic review and meta-analysis. British Medical Journal, 348, g2301. doi:10.1136/bmj.g2301

Brazy, J. E., Goldstein, R. F., Oehler, J. M., Gustafson, K. E., & Thompson, R. J., Jr. (1993).

Nursery neurobiologic risk score: levels of risk and relationships with nonmedical factors. Journal of Developmental and Behavioral Pediatrics, 14(6), 375-380.

Behrman, R. E. (1985). Preventing low birth weight: A pediatric perspective. The Journal

of Pediatrics, 107(6), 842-854. Broekhuijsen, K., Ravelli, A. C., Langenveld, J., van Pampus, M. G., van den Berg, P. P.,

Mol, B. W., & Franssen, M. T. (2015). Maternal and neonatal outcomes of pregnancy in women with chronic hypertension: a retrospective analysis of a national register. Acta Obstetricia et Gynecologica Scandinavica, 94(12), 1337-1345. doi:10.1111/aogs.12757

Bryant, A. S., Seely, E. W., Cohen, A., & Lieberman, E. (2005). Patterns of pregnancy-

related hypertension in black and white women. Hypertension in Pregnancy, 24(3), 281-290. doi:10.1080/10641950500281134

Carr, A., Kershaw, T., Brown, H., Allen, T., & Small, M. (2013). Hypertensive disease in

pregnancy: an examination of ethnic differences and the Hispanic paradox. Journal of Neonatal-Perinatal Medicine, 6(1), 11-15. doi:10.3233/npm-1356111

Catov, J. M., Nohr, E. A., Olsen, J., & Ness, R. B. (2008). Chronic hypertension related to

risk for preterm and term small for gestational age births. Obstetrics & Gynecology, 112(2 Pt 1), 290-296. doi:10.1097/AOG.0b013e31817f589b

Caughey, A. B., Stotland, N. E., Washington, A. E., & Escobar, G. J. (2005). Maternal

ethnicity, paternal ethnicity, and parental ethnic discordance: predictors of preeclampsia. Obstetrics & Gynecology, 106(1), 156-161. doi:10.1097/01.aog.0000164478.91731.06

Chan, B. C., & Lao, T. T. (2008). Effect of parity and advanced maternal age on obstetric

outcome. International Journal of Gynecology and Obstetrics, 102(3), 237-241. doi:10.1016/j.ijgo.2008.05.004

Chandiramani, M., Joash, K., & Shennan, A. H. (2010). Options and decision-making:

108

hypertensive disorders of pregnancy. Future Cardiology, 6(4), 535-546. doi:10.2217/fca.10.71

Chang, J. J., Strauss, J. F., 3rd, Deshazo, J. P., Rigby, F. B., Chelmow, D. P., & Macones, G.

A. (2014). Reassessing the impact of smoking on preeclampsia/eclampsia: are there age and racial differences? PLoS One, 9(10), e106446. doi:10.1371/journal.pone.0106446

Chappell, L. C., Enye, S., Seed, P., Briley, A. L., Poston, L., & Shennan, A. H. (2008).

Adverse perinatal outcomes and risk factors for preeclampsia in women with chronic hypertension a prospective study. Hypertension, 51(4), 1002-1009.

Chappell, L. C., Enye, S., Seed, P., Briley, A. L., Poston, L., & Shennan, A. H. (2008).

Adverse perinatal outcomes and risk factors for preeclampsia in women with chronic hypertension: a prospective study. Hypertension, 51(4), 1002-1009. doi:10.1161/hypertensionaha.107.107565

Chen, J.-M., Jeng, M.-J., Chiu, S.-Y., Lee, Y.-S., Soong, W.-J., Hwang, B., & Tang, R.-B.

(2008). Conditions associated with hypertension in a high-risk premature infant. Journal of the Chinese Medical Association, 71(9), 485-490.

Clausen, T. D., & Bergholt, T. (2014). Chronic hypertension during pregnancy. British

Medical Journal, 348, g2655. doi:10.1136/bmj.g2655 Clausson, B., Cnattingius, S., & Axelsson, O. (1998). Preterm and term births of small for

gestational age infants: a population-based study of risk factors among nulliparous women. British Journal of Obstetrics and Gynaecology, 105(9), 1011-1017.

Cruz, M. O., Gao, W., & Hibbard, J. U. (2011). Obstetrical and perinatal outcomes among

women with gestational hypertension, mild preeclampsia, and mild chronic hypertension. American Journal of Obstetrics and Gynecology, 205(3), 260 e261-269. doi:10.1016/j.ajog.2011.06.033

Curtin, S. C., Gregory, K. D., Korst, L. M., & Uddin, S. F. (2015). Maternal Morbidity for

Vaginal and Cesarean Deliveries, According to Previous Cesarean History: New Data From the Birth Certificate, 2013. National Vital Statistics Reports, 64(4), 1-13, back cover.

da Fonseca, C. R., Strufaldi, M. W., de Carvalho, L. R., & Puccini, R. F. (2014). Adequacy

of antenatal care and its relationship with low birth weight in Botucatu, Sao

109

Paulo, Brazil: a case-control study. BMC Pregnancy and Childbirth, 14, 255. doi:10.1186/1471-2393-14-255

Dani, C., Poggi, C., Bertini, G., Pratesi, S., Tommaso, M. D., Scarselli, G., & Rubaltelli, F.

F. (2010). Method of delivery and intraventricular haemorrhage in extremely preterm infants. The Journal of Maternal-Fetal & Neonatal Medicine, 23(12), 1419-1423.

Dayan, N., Lanes, A., Walker, M. C., Spitzer, K. A., & Laskin, C. A. (2016). Effect of

chronic hypertension on assisted pregnancy outcomes: a population-based study in Ontario, Canada. Fertility and Sterility, 105(4), 1003-1009. doi:10.1016/j.fertnstert.2015.11.039

Dole, N., Savitz, D. A., Siega-Riz, A. M., Hertz-Picciotto, I., McMahon, M. J., & Buekens,

P. (2004). Psychosocial factors and preterm birth among African American and White women in central North Carolina. American Journal of Public Health, 94(8), 1358-1365.

Ferrazzani, S., Luciano, R., Garofalo, S., D'Andrea, V., De Carolis, S., De Carolis, M. P., . .

. Caruso, A. (2011). Neonatal outcome in hypertensive disorders of pregnancy. Early Human Development, 87(6), 445-449. doi:10.1016/j.earlhumdev.2011.03.005

Ferrer, R. L., Sibai, B. M., Mulrow, C. D., Chiquette, E., Stevens, K. R., & Cornell, J.

(2000). Management of mild chronic hypertension during pregnancy: a review. Obstetrics & Gynecology, 96(5 Pt 2), 849-860.

Fretts, R. C. (2005). Etiology and prevention of stillbirth. American Journal of Obstetric &

Gynecology, 193(6), 1923-1935. doi:10.1016/j.ajog.2005.03.074 Fridman, M., Korst, L. M., Chow, J., Lawton, E., Mitchell, C., & Gregory, K. D. (2014).

Trends in maternal morbidity before and during pregnancy in California. American Journal of Public Health, 104 Suppl 1, S49-57. doi:10.2105/ajph.2013.301583

Garovic, V. D., Bailey, K. R., Boerwinkle, E., Hunt, S. C., Weder, A. B., Curb, D., . . .

Turner, S. T. (2010). Hypertension in pregnancy as a risk factor for cardiovascular disease later in life. Journal of Hypertension, 28(4), 826.

Giannubilo, S. R., Dell'Uomo, B., & Tranquilli, A. L. (2006). Perinatal outcomes, blood

pressure patterns and risk assessment of superimposed preeclampsia in mild chronic hypertensive pregnancy. European Journal of Obstetrics & Gynecology and Reproductive Biology, 126(1), 63-67. doi:10.1016/j.ejogrb.2005.06.042

110

Gilbert, W. M., Young, A. L., & Danielsen, B. (2007). Pregnancy outcomes in women with

chronic hypertension: a population-based study. Journal of Reproductive Medicine, 52(11), 1046-1051.

Goldenberg, R. L., Culhane, J. F., Iams, J. D., & Romero, R. (2008). Epidemiology and

causes of preterm birth. The Lancet, 371(9606), 75-84. Goodwin, A. A., & Mercer, B. M. (2005). Does maternal race or ethnicity affect the

expression of severe preeclampsia? American Journal of Obstetric & Gynecology, 193(3 Pt 2), 973-978. doi:10.1016/j.ajog.2005.05.047

Graham, J., Zhang, L., & Schwalberg, R. (2007). Association of maternal chronic disease

and negative birth outcomes in a non-Hispanic Black-White Mississippi birth cohort. Public Health Nursing, 24(4), 311-317. doi:10.1111/j.1525-1446.2007.00639.x

Gregory, K. D., & Korst, L. M. (2003). Age and racial/ethnic differences in maternal, fetal,

and placental conditions in laboring patients. American Journal of Obstetric & Gynecology, 188(6), 1602-1606; discussion 1606-1608.

Hamilton, B. E., Hoyert, D. L., Martin, J. A., Strobino, D. M., & Guyer, B. (2013). Annual

summary of vital statistics: 2010-2011. Pediatrics, 131(3), 548-558. doi:10.1542/peds.2012-3769

Hamed, H. O., Alsheeha, M. A., Abu-Elhasan, A. M., Abd Elmoniem, A. E., & Kamal, M.

M. (2014). Pregnancy outcomes of expectant management of stable mild to moderate chronic hypertension as compared with planned delivery. International Journal of Gynecology and Obstetrics, 127(1), 15-20. doi:10.1016/j.ijgo.2014.04.010

Holditch-Davis, D., White-Traut, R. C., Levy, J. A., O'Shea, T. M., Geraldo, V., & David,

R. J. (2014). Maternally administered interventions for preterm infants in the NICU: effects on maternal psychological distress and mother-infant relationship. Infant Behavior & Development, 37(4), 695-710. doi:10.1016/j.infbeh.2014.08.005

Hollowell, J., Oakley, L., Kurinczuk, J. J., Brocklehurst, P., & Gray, R. (2011). The

effectiveness of antenatal care programmes to reduce infant mortality and preterm birth in socially disadvantaged and vulnerable women in high-income countries: a systematic review. BMC Pregnancy and Childbirth, 11, 13. doi:10.1186/1471-2393-11-13

Hu, W. S., Feng, Y., Dong, M. Y., & He, J. (2016). Comparing maternal and perinatal

111

outcomes in pregnancies complicated by preeclampsia superimposed chronic hypertension and preeclampsia alone. Clinical and Experimental Obstetrics Gynecology, 43(2), 212-215.

Hypertension in pregnancy. Report of the American College of Obstetricians and

Gynecologists' Task Force on Hypertension in Pregnancy. (2013). Obstetrics & Gynecology, 122(5), 1122-1131. doi:10.1097/01.aog.0000437382.03963.88

Intapad, S., & Alexander, B. T. (2013). Future cardiovascular risk: Interpreting the

importance of increased blood pressure during pregnancy. Circulation, 127(6), 668-669. doi:10.1161/circulationaha.112.000677

Jackson, B. J., Needelman, H., Roberts, H., Willet, S., & McMorris, C. (2012). Bayley

scales of infant development screening test-gross motor subtest: Efficacy in determining need for services. Pediatric Physical Therapy, 24(1), 58-62.

Joshi, S., & Kotecha, S. (2007). Lung growth and development. Early Human Development,

83(12), 789-794. doi:10.1016/j.earlhumdev.2007.09.007 Kase, B. A., Carreno, C. A., Blackwell, S. C., & Sibai, B. M. (2013). The impact of

medically indicated and spontaneous preterm birth among hypertensive women. American Journal of Perinatology, 30(10), 843-848. doi:10.1055/s-0033-1333676

Knuist, M., Bonsel, G. J., Zondervan, H. A., & Treffers, P. E. (1998). Risk factors for

preeclampsia in nulliparous women in distinct ethnic groups: a prospective cohort study. Obstetrics & Gynecology, 92(2), 174-178.

Koch, J., Hensley, G., Roy, L., Brown, S., Ramaciotti, C., & Rosenfeld, C. R. (2006).

Prevalence of spontaneous closure of the ductus arteriosus in neonates at a birth weight of 1000 grams or less. Pediatrics, 117(4), 1113-1121. doi:10.1542/peds.2005-1528

Kogan, M. D., Martin, J. A., Alexander, G. R., Kotelchuck, M., Ventura, S. J., & Frigoletto,

F. D. (1998). The changing pattern of prenatal care utilization in the United States, 1981-1995, using different prenatal care indices. The Journal of the American Medical Association, 279(20), 1623-1628.

Kotelchuck, M. (1994). An evaluation of the Kessner Adequacy of Prenatal Care Index

and a proposed Adequacy of Prenatal Care Utilization Index. American Journal of Public Health, 84(9), 1414-1420.

112

Kraemer, H. C., Wilson, G. T., Fairburn, C. G., & Agras, W. S. (2002). Mediators and moderators of treatment effects in randomized clinical trials. Archives of General Psychiatry, 59(10), 877-883.

Lawler, J., Osman, M., Shelton, J. A., & Yeh, J. (2007). Population-based analysis of

hypertensive disorders in pregnancy. Hypertension in Pregnancy, 26(1), 67-76. doi:10.1080/10641950601147945

Lecarpentier, E., Tsatsaris, V., Goffinet, F., Cabrol, D., Sibai, B., & Haddad, B. (2013). Risk

factors of superimposed preeclampsia in women with essential chronic hypertension treated before pregnancy. PLoS One, 8(5), e62140. doi:10.1371/journal.pone.0062140

Lisonkova, S., & Joseph, K. S. (2013). Incidence of preeclampsia: risk factors and

outcomes associated with early- versus late-onset disease. American Journal of Obstetric & Gynecology, 209(6), 544 e541-544 e512. doi:10.1016/j.ajog.2013.08.019

Livingston, J. C., Maxwell, B. D., & Sibai, B. M. (2003). Chronic hypertension in

pregnancy. Minerva Ginecologica, 55(1), 1-13. Livingston, J. C., & Sibai, B. M. (2001). Chronic hypertension in pregnancy. Obstetrics and

Gynecology Clinics of North America, 28(3), 447-463. Loggins, S., & Andrade, F. C. (2014). Despite an overall decline in u.s. Infant mortality

rates, the black/white disparity persists: recent trends and future projections. Journal of Community Health, 39(1), 118-123. doi:10.1007/s10900-013-9747-0

Lowe, S. A., Brown, M. A., Dekker, G. A., Gatt, S., McLintock, C., McMahon, L. P., . . .

Paech, M. (2009). Guidelines for the management of hypertensive disorders of pregnancy 2008. Australian and New Zealand Journal of Obstetrics and Gynaecology, 49(3), 242-246.

Lu, H., Wang, Q., Lu, J., Zhang, Q., & Kumar, P. (2016). Risk factors for intraventricular

hemorrhage in preterm infants born at 34 weeks of gestation or less following preterm premature rupture of membranes. Journal of Stroke and Cerebrovascular Diseases, 25(4), 807-812. doi:10.1016/j.jstrokecerebrovasdis.2015.12.011

Luke, B., & Brown, M. B. (2007). Elevated risks of pregnancy complications and adverse

outcomes with increasing maternal age. Human Reproduction, 22(5), 1264-1272. doi:10.1093/humrep/del522

113

Madi, J. M., Araujo, B. F., Zatti, H., Rombaldi, R. L., Madi, S. R., de Zorzi, P., . . . Bampi, R. (2012). Chronic hypertension and pregnancy at a tertiary-care and university hospital. Hypertension in Pregnancy, 31(3), 350-356. doi:10.3109/10641955.2010.525279

Magnussen, E. B., Vatten, L. J., Smith, G. D., & Romundstad, P. R. (2009). Hypertensive

disorders in pregnancy and subsequently measured cardiovascular risk factors. Obstetrics & Gynecology, 114(5), 961-970.

Martin, J. A., Hamilton, B. E., Ventura, S. J., Osterman, M. J., Kirmeyer, S., Mathews, T.,

& Wilson, E. C. (2011). Births: final data for 2009. National vital statistics reports: from the Centers for Disease Control and Prevention, National Center for Health Statistics, National Vital Statistics System, 60(1), 1-70.

McCowan, L. M., Buist, R. G., North, R. A., & Gamble, G. (1996). Perinatal morbidity in

chronic hypertension. British Jounal of Obstetetric & Gynaecology, 103(2), 123-129. Medoff Cooper, B., Holditcheports: from the Centers for Disease Control and

Prevention, National Center for Health Statistics, National Vital Statistics System, 60s. niversity hospital. before pregnancy. t prenatal care Journal of Obstetric, Gynecologic & Neonatal Nursing, 41(6), 774-785.

Metz, T. D., Allshouse, A. A., Euser, A. G., & Heyborne, K. D. (2014). Preeclampsia in

high risk women is characterized by risk group-specific abnormalities in serum biomarkers. American Journal of Obstetrics & Gynecology. doi:10.1016/j.ajog.2014.04.027

Miles, M. S., Holditch-Davis, D., Schwartz, T. A., & Scher, M. (2007). Depressive

symptoms in mothers of prematurely born infants. Journal of Developmental & Behavioral Pediatrics, 28(1), 36-44.

Misra, D. P., & Guyer, B. (1998). Benefits and limitations of prenatal care: from counting

visits to measuring content. The Journal of the American Medical Association, 279(20), 1661-1662.

Moodley, J. (2007). Maternal deaths due to hypertensive disorders in pregnancy: Saving

Mothers report 2002-2004. Cardiovascular Journal of Africa, 18(6), 358-361. Moos, M. (2006). Prenatal care: limitations and opportunities. JOGNN: Journal of

Obstetric, Gynecologic & Neonatal Nursing, 35(2), 278-285. doi:10.1111/j.1552-6909.2006.00039.x

114

Moussa, H. N., Leon, M. G., Marti, A., Chediak, A., Pedroza, C., Blackwell, S. C., & Sibai,

B. M. (2016). Pregnancy Outcomes in Women with Preeclampsia Superimposed on Chronic Hypertension with and without Severe Features. American Journal of Perinatology. doi:10.1055/s-0036-1592134

Myers, E., & Ment, L. R. (2009). Long-term outcome of preterm infants and the role of

neuroimaging. Clinics in Perinatology, 36(4), 773-789, vi. doi:10.1016/j.clp.2009.07.008

Neuman, B. M., & Fawcett, J. (2002). The Neuman systems model: Upper Saddle River, NJ:

Pearson Education, Incorporated. Odell, C. D., Kotelchuck, M., Chetty, V. K., Fowler, J., Stubblefield, P. G., Orejuela, M., &

Jack, B. W. (2006). Maternal hypertension as a risk factor for low birth weight infants: comparison of Haitian and African-American women. Maternal and Child Health Journal, 10(1), 39-46. doi:10.1007/s10995-005-0026-2

Ono, Y., Takagi, K., Seki, H., Takai, Y., Samejima, K., Matsunaga, S., & Matsumura, H.

(2013). Neonatal outcome in infants of chronically hypertensive mothers. The Journal of Obstetrics and Gynaecology Research, 39(6), 1142-1146. doi:10.1111/jog.12041

Osborn, D. A., Evans, N., & Kluckow, M. (2003). Hemodynamic and antecedent risk

factors of early and late periventricular/intraventricular hemorrhage in premature infants. Pediatrics, 112(1 Pt 1), 33-39.

Osmanagaoglu, M. A., Erdogan, I., Zengin, U., & Bozkaya, H. (2004). Comparison

between HELLP syndrome, chronic hypertension, and superimposed preeclampsia on chronic hypertension without HELLP syndrome. Journal of Perinatal Medicine, 32(6), 481-485. doi:10.1515/jpm.2004.132

Osterman, M. J., Kochanek, K. D., MacDorman, M. F., Strobino, D. M., & Guyer, B.

(2015). Annual summary of vital statistics: 2012–2013. Pediatrics, peds. 2015-0434. Pare, E., Parry, S., McElrath, T. F., Pucci, D., Newton, A., & Lim, K. H. (2014). Clinical

risk factors for preeclampsia in the 21st century. Obstetrics & Gynecology, 124(4), 763-770. doi:10.1097/aog.0000000000000451

Poon, L. C., Kametas, N. A., Chelemen, T., Leal, A., & Nicolaides, K. H. (2010). Maternal

risk factors for hypertensive disorders in pregnancy: a multivariate approach.

115

Journal of Human Hypertension, 24(2), 104-110. doi:10.1038/jhh.2009.45 Prakash, J., Pandey, L. K., Singh, A. K., & Kar, B. (2006). Hypertension in pregnancy:

hospital based study. Jornal of the Association of Physicians of India, 54, 273-278. Report of the National High Blood Pressure Education Program Working Group on

High Blood Pressure in Pregnancy. (2000). American Journal Obstetrics & Gynecology, 183(1), S1-S22.

Rich-Edwards, J. W., Fraser, A., Lawlor, D. A., & Catov, J. M. (2014). Pregnancy

characteristics and women's future cardiovascular health: an underused opportunity to improve women's health? Epidemiologic Reviews, 36(1), 57-70. doi:10.1093/epirev/mxt006

Roberts, C. L., Algert, C. S., Morris, J. M., Ford, J. B., & Henderson-Smart, D. J. (2005).

Hypertensive disorders in pregnancy: a population-based study. Medical Journal of Australia, 182(7), 332-335.

Roberts, C. L., Ford, J. B., Algert, C. S., Antonsen, S., Chalmers, J., Cnattingius, S., . . .

Langridge, A. (2011). Population-based trends in pregnancy hypertension and pre-eclampsia: an international comparative study. British Medical Journal open, 1(1).

Rotundo, G. (2011). Centering pregnancy: the benefits of group prenatal care. Nursing for

Women's Health, 15(6), 508-517; quiz 518. doi:10.1111/j.1751-486X.2011.01678.x Sabol, B. A., de Sam Lazaro, S., Salati, J., Allen, A., Snowden, J., & Caughey, A. B. (2014).

Racial and ethnic differences in pregnancy outcomes in women with chronic hypertension. Obstetrics & Gynecology, 123(Suppl 1), 168S-169S. doi:10.1097/01.aog.0000447176.91016.01

Samadi, A. R., Mayberry, R. M., & Reed, J. W. (2001). Preeclampsia associated with

chronic hypertension among African-American and White women. Ethnicity & Disease, 11(2), 192-200.

Samuel, A., Lin, C., Parviainen, K., & Jeyabalan, A. (2011). Expectant management of

preeclampsia superimposed on chronic hypertension. Journal of Maternal-Fetal & Neonatal Medicine, 24(7), 907-911. doi:10.3109/14767058.2010.535874

Savitz, D. A., Danilack, V. A., Engel, S. M., Elston, B., & Lipkind, H. S. (2014). Descriptive

epidemiology of chronic hypertension, gestational hypertension, and

116

preeclampsia in New York State, 1995-2004. Maternal and Child Health Journal, 18(4), 829-838. doi:10.1007/s10995-013-1307-9

Schoenaker, D., Soedamah-Muthu, S. S., & Mishra, G. D. (2014). The association between

dietary factors and gestational hypertension and pre-eclampsia: a systematic review and meta-analysis of observational studies. BMC Medicine, 12(1), 157. doi:10.1186/s12916-014-0157-7

Seed, P. T., Chappell, L. C., Black, M. A., Poppe, K. K., Hwang, Y. C., Kasabov, N., . . .

North, R. A. (2011). Prediction of preeclampsia and delivery of small for gestational age babies based on a combination of clinical risk factors in high-risk women. Hypertension in Pregnancy, 30(1), 58-73. doi:10.3109/10641955.2010.486460

Seely, E. W., & Ecker, J. (2011). Clinical practice. Chronic hypertension in pregnancy.

New England Journal of Medicine, 365(5), 439-446. doi:10.1056/NEJMcp0804872 Seely, E. W., & Ecker, J. (2014). Chronic hypertension in pregnancy. Circulation, 129(11),

1254-1261. doi:10.1161/circulationaha.113.003904 Seely, E. W., & Ecker, J. (2014). Chronic Hypertension in Pregnancy. Circulation, 129(11),

1254-1261. Seely, E. W., & Maxwell, C. (2007). Chronic hypertension in pregnancy. Circulation,

115(7), e188-e190. Shulman, H. B., Gilbert, B. C., & Lansky, A. (2006). The Pregnancy Risk Assessment

Monitoring System (PRAMS): current methods and evaluation of 2001 response rates. Public Health Reports, 121(1), 74.

Sibai, B. M. (2002). Chronic hypertension in pregnancy. Obstetrics & Gynecology, 100(2),

369-377. Sibai, B. M. (2007). Caring for women with hypertension in pregnancy. The Journal of the

American Medical Association, 298(13), 1566-1568. doi:10.1001/jama.298.13.1566 Sibai, B. M., Caritis, S. N., Hauth, J. C., MacPherson, C., VanDorsten, J. P., Klebanoff, M.,

. . . Roberts, J. (2000). Preterm delivery in women with pregestational diabetes mellitus or chronic hypertension relative to women with uncomplicated pregnancies. The National institute of Child health and Human Development Maternal- Fetal Medicine Units Network. American Journal of Obstetrics & Gynecology, 183(6), 1520-1524.

117

Sibai, B. M., Koch, M. A., Freire, S., Pinto e Silva, J. L., Rudge, M. V., Martins-Costa, S., . .

. Spinnato, J. A., 2nd. (2011). The impact of prior preeclampsia on the risk of superimposed preeclampsia and other adverse pregnancy outcomes in patients with chronic hypertension. American Journal of Obstetrics & Gynecology, 204(4), 345 e341-346. doi:10.1016/j.ajog.2010.11.027

Spittle AJ, Doyle LW, Boyd R.N. (2008). A systematic review of the clinimetric

properties of neuromotor assessments for preterm infants during the first year of life. Developmental Medicine and Child Neurology, 50(4):254-266.

Tanaka, M., Jaamaa, G., Kaiser, M., Hills, E., Soim, A., Zhu, M., . . . McNutt, L. A. (2007).

Racial disparity in hypertensive disorders of pregnancy in New York State: a 10-year longitudinal population-based study. American Journal of Public Health, 97(1), 163-170. doi:10.2105/ajph.2005.068577

Taussig, F. J. (1937). The story of prenatal care: Presidential address. American Journal of

Obstetrics and Gynecology, 34(5), 731-739. Tikkanen, M. (2011). Placental abruption: epidemiology, risk factors and consequences.

Acta Obstetricia et Gynecologica Scandinavica, 90(2), 140-149. doi:10.1111/j.1600-0412.2010.01030.x

Tuuli, M. G., Rampersad, R., Stamilio, D., Macones, G., & Odibo, A. O. (2011). Perinatal

outcomes in women with preeclampsia and superimposed preeclampsia: do they differ? American Journal of Obstetrics and Gynecology, 204(6), 508 e501-507. doi:10.1016/j.ajog.2011.01.065

US Department of Health and Human Services. (2011).Child health USA 2013, Author:

Washington, DC. Vanek, M., Sheiner, E., Levy, A., & Mazor, M. (2004). Chronic hypertension and the risk

for adverse pregnancy outcome after superimposed pre-eclampsia. International Journal of Gynaecology & Obstetrics, 86(1), 7-11. doi:10.1016/j.ijgo.2004.03.006

Vigil-De Gracia, P., Lasso, M., & Montufar-Rueda, C. (2004). Perinatal outcome in

women with severe chronic hypertension during the second half of pregnancy. International Journal of Gynaecology & Obstetrics, 85(2), 139-144. doi:10.1016/j.ijgo.2003.12.002

Vintzileos, A. M., Ananth, C. V., Smulian, J. C., Scorza, W. E., & Knuppel, R. A. (2002).

118

The impact of prenatal care in the United States on preterm births in the presence and absence of antenatal high-risk conditions. American Journal of Obstetrics and Gynecology, 187(5), 1254-1257.

Vintzileos, A. M., Ananth, C. V., Smulian, J. C., Scorza, W. E., & Knuppel, R. A. (2002).

The impact of prenatal care in the United States on preterm births in the presence and absence of antenatal high-risk conditions. American Journal of Obstetrics and Gynecology, 187(5), 1254-1257.

Wagner, S. J., Barac, S., & Garovic, V. D. (2007). Hypertensive pregnancy disorders:

current concepts. The Journal of Clinical Hypertension (Greenwich), 9(7), 560-566. Wang, Y., Tanbo, T., Abyholm, T., & Henriksen, T. (2011). The impact of advanced

maternal age and parity on obstetric and perinatal outcomes in singleton gestations. Archives of Gynecology and Obstetrics, 284(1), 31-37. doi:10.1007/s00404-010-1587-x

Weissgerber, T. L., Turner, S. T., Mosley, T. H., Kardia, S. L., Hanis, C. L., Milic, N. M., &

Garovic, V. D. (2015). Hypertension in pregnancy and future cardiovascular event risk in siblings. Journal of the American Society of Nephrology, ASN. 2015010086.

Wilson, B. J., Watson, M. S., Prescott, G. J., Sunderland, S., Campbell, D. M., Hannaford,

P., & Smith, W. C. S. (2003). Hypertensive diseases of pregnancy and risk of hypertension and stroke in later life: results from cohort study. British Medical Journal, 326(7394), 845.

Wolf, M., Shah, A., Jimenez-Kimble, R., Sauk, J., Ecker, J. L., & Thadhani, R. (2004).

Differential risk of hypertensive disorders of pregnancy among Hispanic women. Journal of the American Society of Nephrology , 15(5), 1330-1338.

Yanit, K. E., Snowden, J. M., Cheng, Y. W., & Caughey, A. B. (2012). The impact of

chronic hypertension and pregestational diabetes on pregnancy outcomes. American Journal of Obstetrics and Gynecology, 207(4), 333 e331-336. doi:10.1016/j.ajog.2012.06.066

Zamorski, M. A., & Green, L. A. (2001). NHBPEP report on high blood pressure in

pregnancy: a summary for family physicians. American Family Physician, 64(2), 263-270, 216.

Zetterstrom, K., Lindeberg, S. N., Haglund, B., & Hanson, U. (2005). Maternal

119

complications in women with chronic hypertension: a population-based cohort study. Acta Obstetricia et Gynecologica Scandinavica, 84(5), 419-424. doi:10.1111/j.0001-6349.2005.00508.x

Zhang, J., Meikle, S., & Trumble, A. (2003). Severe maternal morbidity associated with

hypertensive disorders in pregnancy in the United States. Hypertension in Pregnancy, 22(2), 203-212. doi:10.1081/prg-120021066

Zhou, X., Niu, J. M., Ji, W. J., Zhang, Z., Wang, P. P., Ling, X. F., & Li, Y. M. (2016).

Precision test for precision medicine: opportunities, challenges and perspectives regarding pre-eclampsia as an intervention window for future cardiovascular disease. American Journal of Translational Research, 8(5), 1920-1934.

120

Biography Forgive Avorgbedor was born in the Volta Region of Ghana, specifically Keta

(Dzelukope) in 1981 to Ms. Innocentia Tamakloe and Mr. Godfred Avorgbedor. She is

married to Mr. Christian Beinpuo. She graduated from Mount Mary College of

Education, Somanya, Ghana before migrating to the United States in 2008. She enrolled

in the University of Wisconsin, Milwaukee in 2009 and obtained a Bachelors degree in

nursing with Cum Laude in 2012. Ms. Avorgbedor was a Ronald McNair scholar and

was an Undergraduate Research Fellow at the University of Wisconsin, Milwaukee. She

is currently a PhD candidate in the Duke University School of Nursing. Her doctoral

education was supported by Duke University. She also received summer fellowships

from Duke University Graduated School. Ms. Avorgbedor was inducted to Sigma Theta

Tau International Honor Society of Nursing in 2012.