joseph r. biggio jr., m.d. consultant, cicatelli associates incorporated alabama department of...
TRANSCRIPT
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Joseph R. Biggio Jr., M.D.Consultant, Cicatelli Associates Incorporated
Alabama Department of Public Health
Montgomery, AL
March 2, 2009
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ObjectivesAt the conclusion of this lecture:
1. You should comprehend the rationale behind the definition of an optimal interpregnancy interval.
2. You should be able to explain the risks for both the infant and the mother of poorly timed pregnancies.
3. You should be able to identify topics for incorporation into family planning discussions that address:
a. Common misunderstandings about pregnancy prevention and preparation
b. Preconception health
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What is “Interpregnancy Interval”?
Variously definedTime from one delivery to nextTime from one event (miscarriage) to
delivery
Time from delivery/miscarriage to beginning of next pregnancyCalculated by determining time between
deliveries and subtracting the estimated length of gestation
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Interpregnancy Interval (IPI) for Practical Use
Period of time betweenLast delivery or pregnancy
lossAND
First day of the menstrual cycle in which conception occurs
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Why are we talking about this?
Increased perinatal mortality associated with short interpregnancy interval (IPI)Children’s Bureau Reports
Hughes , 1922Woodbury, 1925
Continued problem despite effective methods of prolonging this interval
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Why do we need to intervene?
More than 50% of infant mortality due to VLBWRacial disparity
Best predictor of VLBW delivery is prior history
Our best way of addressing infant mortality is to attempt to reduce risk factors indicated by prior adverse outcomes
Dunlop et al, Mat Child Health J, 2008
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Why might short interval matter?
Maternal depletion hypothesis More than 1 year required to replete maternal
resources essential for successful pregnancyWinkvist et al, J Pub Health, 1992
Adequate supply needed for balance between mother and fetus Biologic competition in setting of inadequacy Insufficient ability to support fetal growth and
development King, J Nutr, 2003
Maternal StressLockwood, Cur Opin Ob Gyn, 1994
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Birthweight and Maternal nutrition
Low weight women replete energy stores at expense of offspringFetal growth sustained only when food supply
sufficient for maternal weight gainFetus is more severely affected in terms of
lost weight than mother
Partitioning of energy supply influenced by initial maternal nutritional status
King, J Nutrition, 2003
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Two key nutrients: Folic acid & Iron
Folic acid Declines from mid-pregnancy to 3-6 months
postpartum Cell division Milk synthesis 20% of women low folate at 6 months
Iron Hemoglobin synthesis More than 1 gm for pregnancy requirements Stores low for months and poorly repleted
Smits, Lancet, 2001
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Effect of short IPI mitigated by folic acid supplementation
Folic acid usePre-conceptionPost-conception None
Birthweight and risk of IUGR directly related to both IPI and folic acid use
van Eijsden et al, Am J Clin Nutr, 2008
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Risk Factor, Surrogate, or Interaction?
Other predictors of poor infant outcomesAgeRaceEducationSocioeconomic statusMarital statusNumber of prior pregnanciesPrior pregnancy outcomes
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Is the association due to confounders?
Chicago
IPI ≤ 3months PTB rate 38%
Rate two-fold higher in African American vs. whites at all IPI
Adjusting for race, prior pregnancy history, education, smoking, and prenatal care, much of association dissipates
Ekwo and Moawad, Int J Epi, 1998
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Role of IPI modified by demographic variables
Unmarried women had a higher rate of SGA at all IPI IPI <12 months, 60% increase in SGA
Among women with IPI 12-35 months, conferred protection was lower in unmarried
Auger et al, BMC Preg Childbirth, 2008
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Why might long interpregnancy interval
matter?
Loss of physiologic adaptations
Revert to nulligravid state
Accrual of co-morbiditiesHypertensionObesityDiabetes
Zhu et al, AJOG, 2001
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Effects on Outcomes
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Effects on Infant OutcomesPremature birth
Low birthweight
Small for gestational age
Congenital anomalies
Infant death
Cerebral palsy
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Preterm Birth
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Preterm BirthIPI ≤ 8 months 2.3 fold increase in PTB
3.6 fold if < 4 monthsBasso et al, AJOG, 1998
Rate of preterm delivery inversely related to interval Interval <13 weeks, 1.9-fold increase in PTB
Klerman et al, AJPH, 1998
Interval <6 months Increase preterm birth < 34 weeksAdjusted for demographic, pregnancy historyOR 3.6; 95% CI 1.4-9.0
Rodrigues and Barros, EJOG, 2008
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Dose-dependent relationship between preterm birth and IPI
< 6 months IPI48% increase in PTB
6-12 months15% increase
Among those with prior PTB< 6 monthsOR 1.446-12 months OR 1.24
Even with prior term birth, women with IPI < 18 months had a higher rate of PTB
DeFranco et al, AJOG, 2007
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Preterm birth and IPI:Risk at both ends of the
spectrumRegistry of nearly 300,000 Hispanic
American births< 18 months
PTB < 32 weeks 26-47% increased risk
PTB < 38 weeks 14-20% increased risk
>59 monthsPTB < 32 weeks 45% increasePTB < 38 weeks 12% increase
Fuentes-Afflick and Hessol, O&G, 2000
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Interaction of Prior Pregnancy Outcome and IPI
IPI < 12 months, OR 1.3 for PTB
If prior PTB, PTB increased 4-fold IPI 18-48 months,
lowest risk for recurrence
If prior term delivery, PTB increased only with IPI <6 months
Hsieh et al, J SGI, 2005
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Low Birthweight and IUGR
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Birthweight and IPIShort IPI associated with reduction
in mean birthweight overallNorwegian registry1st and 2nd vs 2nd and 3rd births average
weight lower in subsequent pregnancyMost profound when IPI < 12 monthsErickson and Bjerkedal, J Epi Com Health, 1978
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Low birthweight, maternal weight, and short IPI
Brazil, case-control study IUGR
Short IPI more common in lower weight women
Adjusting for maternal weight, short IPI remained associated with IUGROR 1.38
Postulated less time to restore nutritional reserves
Ferraz et al, Am J Epi, 1988
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Other Perinatal Outcomes
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Impact of IPI on Perinatal Outcomes
Latin American Registry >1,000,000 pregnancies
Compared to 18-23 months, IPI <6, 6-11, and ≥60 months associated with Perinatal death LBW (<2500 gm) and VLBW (<1500 gm) PTB <37 and <32 weeks SGA
Increasing IPI to 18-59 months would decrease perinatal mortality by 15%
Conde-Agudelo et al, O&G, 2005
Post-abortion, IPI < 6 months LBW, PTB, PROM, anemia
Conde-Agudelo et al, Intl J OG, 2005
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Perinatal deathSwedish registry
Interval < 3 months1.9 fold increase
Interval >72 months1.5 fold increase
Stephansson et al, O&G, 2003
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Short IPI and Congenital Anomalies
Neural tube defects2-fold increased risk if livebirth ≤ 6
monthsNo appreciable effect if spontaneous
abortionInadequate replenishment of
micronutrients, especially folic acidTodoroff and Shaw, Am J Epi, 2000
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Adverse childhood outcomes and IPI
Disabling CPShorter IPI 16 vs. 23 months Controlling for infection, multiples, and
neonatal brain injury, IPI was associated with CP
Pinto-Martin et al, J Ped, 1998
Childhood allergies IPI > 24 months, 2-fold higher rate of
allergies? Etiology: larger family, cleanliness
Wegienka et al, J All Clin Immunol, 2004
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A cycle of adversityWomen with complicated 1st pregnancy
more likely to have an interpregnancy interval < 12 months IUGR, PTB, perinatal death
IPI < 6 months, associated withPTB < 32 weeksPTB < 36 weeksPerinatal death
Smith, Pell, & Dobbie, BMJ, 2003
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Effects of demographic factors
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Similar effects across racesMagnitude of increase associated with
short IPI similarRisk overall twice as high in AASGA OR 1.6 vs 1.3 ; PTB 1.4 vs 1.2
Shults et al, Epidemiology, 1999
Intervals < 7 months and > 60 monthsPTB IUGR Perinatal mortality
Kallan, Soc Biol, 1997
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Effects across US racial/ethnic groups
IPI ≤6 months50-80% increase in VLBW30-90% increase in PTB <32 weeks
8% of LBW and PTB related to short IPI in African Americans and Hispanics
4% in whites
Khoshnood et al, Am J Epi, 1998
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IPI matters even for low-risk women
Cohort with early care, education, non-smokers, age 20-34, prior term AGA deliveriesPTB and LBW increased with IPI ≤ 8 or ≥48 months
Adams et al, Paed Perinatal Epi, 1997
Military families with free access to healthcareShort IPI associated with PTB and LBWAfrican Americans <9 mon OR 2.65White <3 months OR 4.2
Rawlings et al, NEJM, 1995
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Women with delayed childbearing
Adverse outcomes increase with age VLBW (< 1500 gm) PTB
More likely to have short IPI Especially ≥ 35 yo and ≤ 6 months
Interval of 12-17 months, lowest risks for LBW PTB Fetal death
Nabukera et al, J Ob Gyn Res, 2008; Nabukera et al, Arch Gyn Ob, 2008
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What is “Optimal”? For whom?
Mother?
Infant?
Society?
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Utah Birth Certificate Study 173,000 births
16 confounding risk factors
IPI < 18 months, odds ratio for LBW 1.4 PTB 1.4 SGA 1.3
IPI >120 months, odds ratio for LBW 2.0 PTB 1.5 SGA 1.8
IPI 18-23 months, lowest risksZhu et al, NEJM, 1999
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Michigan Birth Certificate Study
435, 327 births; included 8 maternal risk factors
Risk highest at IPI < 3 months, lowest at 18-23 months
IPI < 6 months, odds ratio for LBW 1.5 PTB 1.3 SGA 1.3
IPI > 120 months, odds ratio for LBW 1.5 PTB 1.3 SGA 1.3
Zhu et al, AJOG, 2001
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Michigan linked-birth data565,816 births
Median IPI= 20 months
J-shaped association between IPI and LBW even controlling for confounders
Infants conceived <6 months weighed 200 gm less than those conceived at 18-23 months
Overall, 9.4% of LBW is due to suboptimal IPI
Zhu and Le, Matern Child Health J, 2003
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It’s not just for the baby…
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Maternal Effects of Interpregnancy Interval
450,000 women delivering singletons
Short IPI associated with increase in: Maternal death OR 2.5 3rd trimester bleeding OR 1.7 PROM OR 1.7 Endometritis OR 1.3 Anemia OR 1.3
Long IPI (>59 months) Pre-eclampsia, eclampsia OR 1.8
Conde-Agudelo et al, BMJ, 2000
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Short IPI and Uterine Rupture
With prior C/S, OR 3.9 for uterine ruptureMean IPI 10 months shorter in women with
uterine ruptureEsposito et al, AJOG, 2000
Interval < 6 monthsUterine rupture OR 2.66Major morbidity OR 1.95Blood transfusion OR 3.14
Stamilio et al, O&G, 2007
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Short IPI and uterine problems
Altered, insufficient wound healingSmooth muscle repairs slowlyEndometrial healing occurs with proliferation
of fibroblasts and connective tissueScar evolution continues for 6-12 months
Third trimester bleedingPoor remodeling of endometrial blood vesselsUteroplacental underperfusion
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Long IPI and labor dystocia650,000 births
examined
Labor dystocia increased with IPI > 2 years 4-5 years OR 1.15 6-7 years OR 1.25 8-9 years OR 1.30 10+ years OR 1.50
Zhu et al, AJOG, 2006
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Long IPI and Maternal Blood Pressure
Parous women have lower risk of pre-eclampsiaCardiovascular adaptations result in increased
vascular compliance in next pregnancyLower mean arterial pressure inversely
correlated with IPI—longer IPI, less MAP decrease
Effect disappears by 2-3 yearsMikolajczyk et al, Am J Epi, 2008
Risk of pre-e same as in nullip if IPI >6 yrsBasso et al, AJOG, 1997
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Whom should we focus our energies
on?
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Predictors of Short IntervalTwice as likely to have IPI < 12 months
MedicaidAge ≤ 20UnmarriedLess EducationRace
Duncan et al, MMWR, 1998
Age, education, race, marital status, number of prior pregnancies Individual level variables best predictors of IPI
Gold et al, Mat Child Health J, 2005
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Predictors of IPI450,000 womenShort interval
Young ageHistory of miscarriageFetal/neonatal deathLate prenatal careLower BMI
Long IntervalGreater BMIOlder ageChronic hypertension
Conde-Agudelo et al, BMJ, 2000
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Pregnancy Spacing
Tackling the problem and dispelling urban (and not-so urban)
myths
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If I am breastfeeding, I can’t get pregnant.
WRONG!
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I can’t pregnant until my periods start again.
WRONG AGAIN!
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Fertility in the Postpartum Period
Suppression of ovulation related to frequency and duration of breastfeedingNormal FSH, low LH levels with
decreased GnRH pulsations
Non-breastfeeding womenLH rises to normal by mean of 3 weeksFSH rise by 4 weeks
Glasier et al, Clin Endo, 1984
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Breastfeeding for birth control
Based on lactational amenorrheaHigh levels of prolactin maintainedAs estrogen and progesterone
decrease, FSH and LH increaseSuckling decreases amplitude and
frequency of GnRH pulsesNo LH surge and no ovulationFollicular development and ovulation
occur when suckling decreasesFFPRHC Guidance, J Fam Plan Repro Health Care, 2004
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Factors limiting effectiveness of lactational amenorrhea
Reduced frequency of breastfeedingMust be at least 6/day
Cessation of night feedingCannot have >6-10 hrs between sessions
Separation from infantIntroduction of supplemental feedingEffective at most only up until 6 monthsAfter first bleeding episode, risk of
pregnancy increasesFFPRHC Guidance, J Fam Plan Repro Health Care, 2004;
Gross et al, Aust NZ J Ob Gyn, 2002
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Menstrual bleeding and breastfeeding
Vaginal bleeding prior to 56 d of full breast feeding not usually a sign of return to fertility15% have signs of follicular development
although no ovulation until later
Menstrual bleeding usually precedes ovulation by 4 weeks
After 8 weeks, women with bleeding need contraception, especially if supplementing
Visness et al, O&G, 1997
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Return to fertilityWith exclusive breastfeeding
Menstruation 28 wk (15-48 wk)Ovulation 34 wk (14-51 wk)
Introduction of supplemental feeding correlates with resumption of menses and ovulation1st ovulation 155 days (67-252)50% of women have ovulation prior to
normal menses resumption
Wei and Yi, Chinese Med J, 2007
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An opportunity to improve outcomes from multiple angles
Family Planning and Preconception Counseling
Parts of the whole
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Family PlanningStatement of goals and rationale
Statement of patient intentions
Discussion of impact of desires on health outcomes
Options for contraception
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Preconception Counseling Goals: Prevention and Management
Ensure as healthy status as possible prior to pregnancyEspecially if benefit greatest with action
before conception or early pregnancyHealth promotion for woman and her
children EducationScreening and intervention to reduce risk
ComponentsModifiable risk factorsNon-modifiable risk factors
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Is there really a chance to make a difference?
38% of women with planned pregnancy had an indication for preconception counseling
66% of those with unplanned pregnancy had an indication for PCC
Adams et al, O & G, 1993
>50% of pregnancies in US unplanned
IOM, Best of Intentions, 1995
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Interpregnancy IntervalIf pregnant, it’s too late
Medical ConditionsThe greatest risk occurs before most
women present for prenatal carePost-conception 17d-56d (4-10 wk
menstrual age)—organogenesis
Folic AcidNeed repletion prior to neural tube closure
Why is it important to do it prior to pregnancy?
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Preconception InterventionsEvidenced-based improvement in outcomes
Folic acid
Alcohol use
Smoking
Maternal PKU
Diabetes
Obesity
Hypothyroidism
Accutane (Isotretinoins)
Anti-epileptics
Oral anticoagulants
Rubella
Hepatitis B
STDs
HIV/AIDS
CDC Preconception Care Work Group, MMWR 2006
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Proper PCCAllows decisions to be made to
attempt or avoid pregnancy
Influences timing of conception
Optimizes health status prior to conception
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Assessment of Risk FactorsScreening/Management of chronic
diseaseScreening/Treatment for
nutritional/dietary problemsScreening/Modification of risky behaviors
Substance abuseSexually transmitted disease screening
Screening/treatment for psychiatric, social issuesDomestic abuse
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Education on Non-modifiable Risk Factors
Prior obstetric historyPreterm birthPre-eclampsia
Genetic historyCongenital anomaliesGenetic disorders
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The easiest and fastest way to hit the points is through history
Reproductive history
Medical history
Family history
Nutritional history
Social history
Immunization history
Environmental/Occupational history
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March of Dimes website, Preconception Checklist
www.marchofdimes.com/professionals/19583_4182.asp
Remember:
• Education
• Health Promotion
• Screening and Intervention to Reduce Risk
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Reproductive History
Prior pregnanciesPreterm birthPre-eclampsiaPost-partum depressionGestational diabetesPeripartum cardiomyopathy
Prior Cesarean delivery
Infertility
Short pregnancy interval
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Prior Preterm BirthEtiology
Surveillance? Cervical length
17-alpha hydroxyprogesterone caproate—Delaluten
Vigilance
Appropriate spacing
Early prenatal care
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Medical History
Disorders that can adversely affect pregnancy outcome either directly or indirectly due to medicationsDiabetesLupusEpilepsy
Disorders that pregnancy can adversely affectCardiac disease
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Medication Exposure
Over the counter medicationsNSAIDSAlternative medicationsAppetite suppressants
Prescription medicationsAce InhibitorsCoumadinAnti-epilepticsAccutane
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Surgical History
Surgeries that change normal anatomic position or function of pelvic structuresBladder surgeries
Procedures that may be affected by increasing abdominal pressure or uterine growthGastric bypass
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Nutritional History: Maternal Diet, Weight & Exercise
Food fads
Pica
Dietary restrictions--PKU
Caffeine intake
Vitamin supplements
Eating disorders
Access to healthy food
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Maternal Weight
BMI associated with risk of adverse outcomesHypertensionMacrosomia/Shoulder dystociaGestational diabetesAbnormal labor/Cesarean sectionFetal anomaliesSpontaneous abortionThromboembolic disease
Exercise—type and amount
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Folic Acid and Birth DefectsNeural tube defect prevention
? Heart defects? Cleft lip/palate
MOD, 2000—82% of women would take folic acid; only 35% had it recommended
Cleves et al, 2004—23% of reproductive age women taking folic acid in gyn clinic
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Immunization and Infection History
Rubella
Varicella
Hepatitis B
Tetanus—every 10 years
Influenza
Pneumococcal, as indicated
Special OccupationCMVParvovirus
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Occupational, Environmental and Toxin Exposures
Substance AbuseTobacco—15%Alcohol—15%
drink during pregnancy; 2-3% problem drinkers
Illicit drugs
HomePetsLeadPesticidesHyperthermia
OccupationalSolventsRadiationMercury
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Family HistoryPrior child or other family member
with Congenital anomalySingle gene disorderMental retardation
Consanguinity
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Social Support & Domestic Violence
Increased demands of pregnancyFinancial PhysicalSocial
Birth spacing
Safe environmentPotential increase in domestic violence
during pregnancy
Post-partum demands
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Put it in writingSummary of Recommendations to
Patients
Folic acidRegular exerciseNormal body weightAvoid diet extremesLimit fish intakePrevent HIV/STDsAvoid alcohol, tobacco, drugsAchieve metabolic controlSeek early prenatal care
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Your goal is not to solve all the problems, but instead to identify ones that would benefit from additional
resources and evaluation!
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SummaryAn interpregnancy interval of 18-23 months has
the lowest risks for
Preterm birth
Low birthweight/SGA
Maternal Complications
Effective contraception is key in pregnancy spacing
Use family planning visits as opportunities to identify risk factors for adverse pregnancy outcomes
The best chance to improve pregnancy outcome is before pregnancy starts