Objective-Obesity is a risk factor for congenital heart defects (CHD), but whether risk is independent of abnormal glucose metabolism is unknown. Data on whether overweight status increases risk is also conflicting.Research Design and Methods-We included 121815 deliveries from a cohort study, the Consortium on Safe Labor, after excluding women with pregestational diabetes as recorded in the electronic medical record. CHD were identified via medical record discharge summaries. Adjusted odds ratios (OR) for any CHD were calculated for prepregnancy body mass index (BMI) categories of overweight (25 to <30 kg/m 2 ), obese (30 to <40 kg/m 2 ), and morbidly obese (≥40 kg/m 2 ) compared to normal weight (18.5 to <25 kg/m2) women, and for specific CHD with obese groups combined (≥30 kg/m 2 ). A sub-analysis adjusting for oral glucose tolerance test (OGTT) results where available was performed as a proxy for potential abnormal glucose metabolism present at the time of organogenesis.Results-There were 1388 (1%) infants with CHD. Overweight (OR=1.15 95% CI: 1.01-1.32), obese (OR=1.26 95% CI: 1.09, 1.44), and morbidly obese (OR=1.34 95% CI: 1.02-1.76) women had greater odds of having a neonate with CHD than normal weight women (P< 0.001 for trend). Obese women (BMI ≥30 kg/m 2 ) had higher odds of having an infant with conotruncal defects (OR=1.34 95%CI: 1.04-1.72), atrial septal defects (OR =1.22 95% CI: 1.04-1.43), and ventricular Users may view, print, copy, download and text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms Dr. S. Katherine Laughon, Epidemiology Branch, NICHD, National Institutes of Health, 6100 Executive Blvd., Room 7B03, Rockville, MD 20852, Tel: 301-435-6935, laughonsk@mail.nih.gov. Supplementary information is available at the journal's website. Duality of interestThe authors report no conflicts of interest. Conclusion-Increasing maternal weight class was associated with increased risk for CHD. In obese women, abnormal glucose metabolism did not completely explain the increased risk for CHD; the possibility that other obesity-related factors are teratogenic requires further investigation. HHS Public Access