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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
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(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.
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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
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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
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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.
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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.
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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
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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
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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)
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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
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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
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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.
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