Specific birth defects in pregnancies of women with diabetes – National Birth Defects Prevention Study, 1997-2011

Abstract Background Diabetes is associated with an increased risk for many birth defects and is likely to have an increasing impact on birth defect prevalence due to the rise in diabetes in the United States in recent decades. One of the first analyses in which specific birth defects were assessed for their relationship with both pregestational and gestational diabetes used data from the initial six years of the National Birth Defects Prevention Study. That analysis reported strong associations for pregestational diabetes with several birth defects, but few exposures among some of the less common birth defects led to unstable estimates with wide confidence intervals. Since that analysis, the study continued to collect data for another eight years, including information on approximately 19,000 additional cases and 6,900 additional controls. Objectives Our objective was to use data from the National Birth Defects Prevention Study, the largest population-based birth defects case-control study in the United States, to provide updated and more precise estimates of the association between diabetes and birth defects, including some defects not previously assessed. Study Design We analyzed data on deliveries from October 1997 through December 2011. Mothers of case and control infants were interviewed about their health conditions and exposures during pregnancy, including diagnosis of pregestational (type 1 or type 2) diabetes before the index pregnancy or gestational diabetes during the index pregnancy. Using logistic regression, we separately assessed the association between pregestational and gestational diabetes with specific categories of structural birth defects for which there were at least three exposed case infants. For birth defect categories for which there were at least five exposed case infants, we calculated odds ratios adjusted for maternal body mass index, age, education, race/ethnicity, and study site; for defect categories with three or four exposed cases we calculated crude odds ratios. Results Pregestational diabetes was reported by 0.6 percent of mothers of control infants (71 / 11,447) and 2.5 percent of mothers of case infants (775 / 31,007). Gestational diabetes during the index pregnancy was reported by 4.7 percent of mothers of control infants (536 / 11,447) and 5.3 percent of mothers of case infants (1,653 / 31,007). Pregestational diabetes was associated with strong, statistically significant odds ratios (range: 2.5 to 80.2) for 46 of 50 birth defects considered. The largest odds ratio was observed for sacral agenesis (adjusted OR [aOR]: 80.2; 95% CI: 46.1, 139.3). A greater than 10-fold increased risk was also observed for holoprosencephaly (aOR: 13.1; 95% CI: 7.0, 24.5), longitudinal limb deficiency (aOR: 10.1; 95% CI: 6.2, 16.5), heterotaxy (aOR: 12.3; 95% CI: 7.3, 20.5), truncus arteriosus (aOR: 14.9; 95% CI: 7.6, 29.3), atrioventricular septal defect (aOR: 10.5; 95% CI: 6.2, 17.9), and single ventricle complex (aOR: 14.7; 95% CI: 8.9, 24.3).For gestational diabetes, statistically significant odds ratios were fewer (12 of 56) and of smaller magnitude (range: 1.3 to 2.1; 0.5 for gastroschisis). Conclusions Pregestational diabetes is associated with markedly increased risk for many specific births defects. Because glycemic control before pregnancy is associated with a reduced risk for birth defects, ongoing quality care for persons with diabetes is an important opportunity for prevention.