This case-control study included data on deliveries that had estimated due dates from July 1999 to June 2004. Cases were liveborn, stillborn (fetal deaths at greater than 20 weeks gestation), and prenatally diagnosed, electively terminated pregnancies with birth defects that occurred to women residing in the California counties of Los Angeles, San Francisco, and Santa Clara.
Case information was abstracted from multiple hospital reports and medical records, following established procedures. 20
Medical records were reviewed by a clinical geneticist. Infants with trisomies were ineligible. Case groups included spina bifida, anencephaly, d-transposition of the great arteries, and tetralogy of Fallot. The latter 2 were confirmed by echocardiography, cardiac catheterization, surgery, or autopsy. Ascertainment of spina bifida and anencephaly ended with an estimated due date of 30 June 2003; ascertainment of d-transposition of great arteries, tetralogy of Fallot, and controls ended with estimated due date of 30 June 2004. Nonmalformed, liveborn controls were selected randomly from birth hospitals to represent the population from which the cases were derived.
Mothers were eligible for interview if they were the biologic mother and carried the pregnancy of the study subject, they were not incarcerated, and their primary language was English or Spanish. Maternal interviews were conducted using a standardized, computer-based questionnaire in English or Spanish, primarily by telephone, no earlier than 6 weeks after the infant’s estimated due date. Information solicited from women included height, prepregnant weight, age, race/ethnicity, educational level, history of overweight, weight gain patterns (weight gain in hips, waist or both), weight change in year before pregnancy (gained ≥5 lbs, lost ≥5 lbs, or both), and family history (affected first degree relative) of any of the 4 studied birth defects. Queries specific to the periconceptional period (2 months before through 2 months after conception) included use of folic-acid containing vitamin supplements, diabetes (gestational, type I, and type II), seizure medication use, dieting to lose weight, use of treatments for weight loss, and weight change pattern (gained ≥5 lbs, lost ≥5 lbs, or both in first 2 months of pregnancy). Body mass index (BMI) was estimated for each woman based on reported prepregnant weight and height (kg/m2). Obesity was defined as BMI ≥30.
The interview also included a modified version of the National Cancer Institute’s Health Habits and History Questionnaire, a well-known, semi-quantitative food frequency questionnaire with demonstrated reliability and validity.21,22
The food frequency questionnaire was modified to include ethnic foods appropriate to a diverse study population. This questionnaire provided information on dietary folate and energy intake.
In total, 659 case mothers (80% of eligible) and 700 control mothers (77% of eligible) were interviewed. Eleven percent of case mothers and 12% of control mothers could not be located and the remainder declined to participate. The median time between estimated date of delivery and interview completion was 10 months for cases and 8 months for controls. The 659 cases included 147 with anencephaly, 191 with spina bifida, 181 with tetralogy of Fallot, and 142 with d-transposition of great arteries (1 case had 2 eligible diagnoses- anencephaly and tetralogy of Fallot).
We estimated relative risks using odds ratios (ORs) and 95% confidence intervals (CIs), using SAS 9.1 (SAS Institute, Cary, NC). Models were constructed to assess effects associated with continuous measures of BMI, as well as the categorical designation of obese (BMI ≥3 kg/m2) compared with normal BMI of 18.5 to 24.9 kg/m2. Covariates in analyses included maternal race/ethnicity (Latina, foreign-born; Latina, US-born; white, non-Latina; Black, non-Latina; Asian; other), education (<12; 12; 13–15; >15 years), age (<25; 25–29; 30–34; and >34 years), weight-related factors described above, periconceptional vitamin supplement use (yes or no), dietary folate intake (µg/d), and total energy intake (kcal/d).