Maternal, reproductive and perinatal factors and the risks of birth defects: traditional and emerging factors

Does an association exist between maternal, reproductive and perinatal factors, and the risks of major non-chromosomal birth defects?

This population-based cohort study included 1,126,058 naturally conceived singleton live births (21,644 with and 1,104,414 without a major non-chromosomal defect) who were born between 2004 and 2018 in New York, Texas, Massachusetts and North Carolina. All study children were linked to their respective state birth defect registries to identify major birth defects diagnosed within the first year of life, and to state death records. Children with chromosomal defects were excluded. Genitourinary defects were only evaluated in boys. Placental and bleeding issues included placenta previa, placental abruption, uterine bleeding and other excessive bleeding, and, at delivery, blood transfusion or unplanned hysterectomy. Adjusted odds ratios and 95% confidence intervals were modelled using logistic regression.

Among major non-chromosomal defects, the highest significant risks were with pre-gestational diabetes (adjusted OR 2.48, 95% CI 2.25 to 2.74), followed by placental or bleeding issues (adjusted OR 1.82, 95% CI 1.66 to 1.99); this pattern was also evident for congenital heart defects, blastogenesis defects, orofacial defects, gastrointestinal defects and musculoskeletal defects. Hypertension (pre-gestational and gestational), prior caesarean delivery, older maternal age and higher body mass index were also significant risk factors.

The risk factors most strongly associated with major non-chromosomal birth defects were pre-gestational diabetes and placental or bleeding issues; other significantly increased risks were hypertension (pre-gestational and gestational), prior caesarean delivery, older maternal age and pre-pregnancy body mass index 30 kg/m² or above.