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Maternal prepregnancy body mass index and
congenital heart defects Preliminary results
from the National Birth Defects Prevention Study,
1997-2003
Adolfo Correa, Suzanne M. Gilboa, Lilah M.
Besser, Lorenzo Botto, Sonja A. Rasmussen, D. Kim
Waller, Charlotte A. Hobbs, Mario Cleves, Tiffany
Riehle-Colarusso
National Center on Birth Defects and
Developmental Disabilities
Disclaimer The findings and conclusions in this
presentation have not been formally disseminated
by CDC and should not be construed to represent
any agency determination or policy.
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Body Mass Index

• Body mass index (BMI) proxy for body fat
• Increasing prevalence of overweight and obesity

Obesity Class NHLBI Cutpoints (kg/m2) IOM Cutpoints (kg/m2)
Underweight lt18.5 lt19.8
Normal 18.5 - 24.9 19.8 - 26.0
Overweight 25.0 - 29.9 gt26.0 - 29.0
Obesity I 30.0 - 34.9 gt29.0
II 35.0 - 39.9
Extreme obesity III gt40
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Obesity Trends Among U.S. AdultsBRFSS, 1990,
1998, 2006
(BMI ?30, or about 30 lbs. overweight for 54
person)
1998
1990
2006
No Data lt10 1014
1519 2024 2529
30
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Prevalence among women 20-39 years of age (Ogden
et al. 2006. JAMA)
Years Overweight or obesity BMI gt 25 Obesity BMI gt 30 Extreme obesity BMI gt 40
1999-2000 54.4 28.3 6.0
2001-2002 54.7 29.8 5.0
2003-2004 51.7 28.9 8.0
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Obesity and Pregnancy Outcomes

• Several adverse pregnancy outcomes associated
  with obesity
• Macrosomia (gt 4000g or 4500g)
• Large for gestational age (gt 90th ile)
• Longer duration of labor
• C-sections
• Late fetal death

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Obesity and Birth Defects

• Obesity is a risk factor for structural birth
  defects, most consistently, for neural tube
  defects (NTDs)
• Naeye, 1990
• Waller et al., 1994
• Shaw et al., 1996
• Watkins et al., 1996
• Werler et al., 1996
• Källén, 1998
• Waller et al., 2007

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Obesity and CHD

• Association with congenital heart defects (CHD)
  in the aggregate
• NBDPS data 1997-2002 (Waller et al. 2007)
• Overweight 1.13 (1.01-1.26)
• Obese 1.40 (1.24-1.59)
• Prospective cohort 1984-1987 (Moore et al. 2000)
• Obese PR 0.89 (0.35-2.2)

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Obesity and CHD

• Specific CHD phenotypes associated with body mass
  index
• Shaw et al., 2000
• Two California case-control studies (1987-1989
  1989-1991)
• Watkins and Botto, 2001
• Atlanta Birth Defects Case Control Study
  (1968-1980)
• Watkins et al., 2003
• Atlanta Birth Defects Risk Factor Surveillance
  Study (1993-1997)
• Cedergren and Källén, 2003
• Swedish medical registries (1992-2001)

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Research Objectives

• To investigate the relation between prepregnancy
  body mass index and the occurrence of congenital
  heart defects among women without pregestational
  diabetes.
• To investigate possible effect measure
  modification by gestational diabetes, folic acid
  supplement intake, and race/ethnicity.

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National Birth Defects Prevention Study

• Population-based case-control design
• AR, CA, GA (CDC), IA, MA, NC, NJ, NY, TX, UT
• October 1,1997 - December 31, 2003
• Cases live births, stillbirths, or terminations
• Controls live births from vital records or
  hospital data
• Computer-assisted telephone interview
• Participation CHD cases (72) Controls (69)

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CHD Classification Two Axes

• Axis 1 Heart complexity (Heart)
• Simple One primary cardiac lesion
• Association At least two distinct cardiac
  lesions
• Complex
• Axis 2 Extra-cardiac malformations (Baby)
• Isolated No major extra-cardiac defects
• Multiple Presence of major extra-cardiac
  defects
• Syndrome
• Complex

Botto LD, et al. 2007. Seeking causes
Classifying and evaluating congenital heart
defects in etiologic studies. Birth Defects Res
Part A Clin Molec Teratol 79714-727
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Congenital Heart Defects(Simple, isolated)

• Right ventricular outflow tract obstruction
  defects (n551)
• Pulmonary valve stenosis (n400)
• Pulmonary atresia (n74)
• Septal defects (n1348)
• Ventricular septal defect (VSD) perimembranous
  (n592)
• VSD muscular (n138)
• Atrial septal defects (n589)
• Atrial septal defect secundum (n464)
• Atrial septal defect NOS (n125)
• COA VSD (n101)
• ASD VSD (n263)

• Any heart defect (n3390)
• Conotruncal defects (n745)
• Tetralogy of Fallot (n377)
• d-transposition of the great arteries (n266)
• Atrioventricular septal defect (n74)
• Anomalous pulmonary venous return (n120)
• Total anomalous pulmonary venous return (n100)
• Left ventricular outflow tract obstruction
  defects (n552)
• Hypoplastic left heart syndrome (n221)
• Coarctation of the aorta (COA) (n207)
• Aortic stenosis (n116)

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Exclusions

• Exclusion of cases with complex heart or baby
  classification
• N 358 cases
• Exclusion of mothers with pregestational
  diabetes
• Type 1 or 2 diabetes diagnosed any time before,
  during, or after index pregnancy, or at unknown
  date
• N 185 cases N 26 controls
• Exclusion of those with missing BMI
• N 230 cases N 208 controls

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Exposure and Covariates

• Self-reported height and weight converted to body
  mass index and categorized (NHLBI)
• Potential confounders
• Maternal age, race/ethnicity, education, parity,
  smoking (B1-P1), supplemental folic acid intake
  (B1-P1), hypertension during pregnancy, household
  income
• Study center conditional logistic regression

B1-P1 refers to the month before conception
through the end of first month of pregnancy
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Analysis

• Analysis restricted to CHD outcomes with at least
  50 isolated cases
• Simple and multiple logistic regression
• Assessment of effect measure modification using
  interaction terms and stratified models
• Presentation of results for simple, isolated CHD

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Results BMI Distribution
BMI category (kg/m2) Simple, isolated cases (n3390) Controls (n4774)
N () N ()
lt 18.5 172 (5.1) 285 (6.0)
18.5 24.9 1794 (52.9) 2707 (56.7)
25.0 29.9 809 (23.9) 1056 (22.1)
gt 30.0 615 (18.1) 726 (15.2)
28-29
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Results Main Effects
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Results GDM Stratification
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Results Race/Ethnicity Stratification
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Study Limitations

• Self-reported BMI
• Potential misclassification of exposure due to
  underestimation of weight and overestimation of
  height
• Missing data
• BMI data is missing more frequently among
  Hispanic mothers (due to missing height)
• Incomplete case ascertainment among elective
  terminations
• Quality of ultrasound visualization is poorer
  among obese mothers

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Conclusions

• Overweight status and obesity are associated with
  increased risk for selected CHD
• Underweight status appears to be unassociated
  with CHD
• Gestational diabetes during index pregnancy may
  modify the effect of overweight and obesity
• May reflect role of undiagnosed type 2 diabetes
• Some evidence of effect measure modification of
  both overweight status and obesity by Hispanic
  ethnicity

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Supplemental Slides
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Race/Ethnicity x BMI (Among Controls)N (Row
percents)
R/E Underweight Average weight Overweight Obese Total
NHW 169 (5.7) 1769 (59.5) 616 (20.7) 419 (14.1) 2973
NHB 32 (5.5) 278 (47.9) 143 (24.7) 127 (21.9) 580
Hispanic 52 (5.5) 493 (52.0) 146 (25.9) 158 (16.7) 949
Other 31 (11.8) 161 (61.5) 49 (18.7) 21 (8.0) 262
4764
n10 controls with missing race data
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Age x BMI (Among Controls)N (Row percents)
Maternal age Underweight Average weight Overweight Obese Total
lt 20 65 (12.4) 324 (61.7) 89 (17.0) 47 (8.9) 525
20-24 90 (8.6) 538 (51.6) 247 (23.7) 168 (16.1) 1043
25-29 55 (4.4) 687 (55.5) 290 (23.4) 206 (16.6) 1238
30-34 56 (4.3) 747 (57.6) 288 (22.2) 206 (15.9) 1297
gt 35 19 (2.8) 411 (61.3) 142 (21.2) 99 (14.8) 671
4774
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Missing BMI Data
Race/Ethnicity CHD Cases (n228) Controls (n205)
Race/Ethnicity Missing N () Missing N ()
NHW 26 (11.4) 18 (8.8)
NHB 13 (5.7) 2 (1.0)
Hispanic 182 (79.8) 170 (82.9)
Other 6 (2.6) 13 (6.3)
Includes 1 CHD case and 2 controls missing
race/ethnicity.