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Modification of the association between diabetes and birth defects by obesity, National Birth Defects Prevention Study, 1997–2011
Author(s) -
Tinker Sarah C.,
Gilboa Suzanne M.,
Moore Cynthia A.,
Waller D. Kim,
Simeone Regina M.,
Kim Shin Y.,
Jamieson Denise J.,
Botto Lorenzo D.,
Fisher Sarah C.,
Reefhuis Jennita
Publication year - 2021
Publication title -
birth defects research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.845
H-Index - 17
ISSN - 2472-1727
DOI - 10.1002/bdr2.1900
Subject(s) - medicine , obesity , odds ratio , diabetes mellitus , gestational diabetes , pregnancy , obstetrics , risk factor , confidence interval , pediatrics , endocrinology , gestation , biology , genetics
Background Maternal pregestational diabetes and obesity are risk factors for birth defects. Diabetes and obesity often occur together; it is unclear whether their co‐occurrence compounds birth defect risk. Methods We analyzed 1997–2011 data on 29,671 cases and 10,963 controls from the National Birth Defects Prevention Study, a multisite case‐control study. Mothers self‐reported height, pregestational weight, and diabetes (pregestational and gestational; analyzed separately). We created four exposure groups: no obesity or diabetes (referent), obesity only, diabetes only, and both obesity and diabetes. We estimated odds ratios (ORs) using logistic regression and the relative excess risk due to interaction (RERI). Results Among mothers with pregestational obesity without diabetes, modest associations (OR range: 1.1–1.5) were observed for neural tube defects, small intestinal atresia, anorectal atresia, renal agenesis/hypoplasia, omphalocele, and several congenital heart defects. Pregestational diabetes, regardless of obesity, was strongly associated with most birth defects (OR range: 2.0–75.9). Gestational diabetes and obesity had a stronger association than for obesity alone and the RERI (in parentheses) suggested additive interaction for hydrocephaly (1.2; 95% confidence interval [CI]: −0.1, 2.5), tetralogy of Fallot (0.9; 95% CI: −0.01, 1.8), atrioventricular septal defect (1.1; 95% CI: −0.1, 2.3), hypoplastic left heart syndrome (1.1; 95% CI: −0.2, 2.4), and atrial septal defect secundum or not otherwise specified (1.0; 95% CI: 0.3, 1.6; only statistically significant RERI). Conclusions Our results do not support a synergistic relationship between obesity and diabetes for most birth defects examined. However, there are opportunities for prevention by reducing obesity and improving glycemic control among women with pregestational diabetes before conception.