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Maternal prepregnancy body mass index and congenital heart defects: Preliminary results from the National Birth Defects Prevention Study, 1997-2003.
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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.
Body Mass Index • Body mass index (BMI) proxy for % body fat • Increasing prevalence of overweight and obesity
Obesity Trends* Among U.S. AdultsBRFSS,1990, 1998, 2006 (*BMI 30, or about 30 lbs. overweight for 5’4” person) 1998 1990 2006 No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30%
Prevalence among women 20-39 years of age (Ogden et al. 2006. JAMA)
Obesity and Pregnancy Outcomes • Several adverse pregnancy outcomes associated with obesity • Macrosomia (> 4000g or 4500g) • Large for gestational age (> 90th %ile) • Longer duration of labor • C-sections • Late fetal death
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
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)
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)
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.
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%)
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 79:714-727
Any heart defect (n=3390) Conotruncal defects (n=745) Tetralogy of Fallot (n=377) d-transposition of the great arteries (n=266) Atrioventricular septal defect (n=74) Anomalous pulmonary venous return (n=120) Total anomalous pulmonary venous return (n=100) Left ventricular outflow tract obstruction defects (n=552) Hypoplastic left heart syndrome (n=221) Coarctation of the aorta (COA) (n=207) Aortic stenosis (n=116) Right ventricular outflow tract obstruction defects (n=551) Pulmonary valve stenosis (n=400) Pulmonary atresia (n=74) Septal defects (n=1348) Ventricular septal defect (VSD) perimembranous (n=592) VSD muscular (n=138) Atrial septal defects (n=589) Atrial septal defect secundum (n=464) Atrial septal defect NOS (n=125) COA + VSD (n=101) ASD + VSD (n=263) Congenital Heart Defects(Simple, isolated)
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
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
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
Results: BMI Distribution 28-29%
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
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
Race/Ethnicity x BMI (Among Controls)*N (Row percents) 4764 * n=10 controls with missing race data
Missing BMI Data * Includes 1 CHD case and 2 controls missing race/ethnicity.