The association of nausea and vomiting of pregnancy, its treatments, and select birth defects: Findings from the National Birth Defect Prevention Study

Background: Nausea and vomiting of pregnancy (NVP) occurs in approximately 70% of pregnant people. Treatments include pharmacologic and herbal/natural products. Research on the associations between NVP and its treatments and birth defects is limited.

Methods: We used data from the case-control National Birth Defects Prevention Study (1997-2011) to examine whether first-trimester NVP or its specific treatments were associated with 37 major birth defects. Odds ratios (aOR) and 95% confidence intervals (CIs) were adjusted for sociodemographic and reproductive factors.

Results: Mothers of 66.6% of 28,628 cases and 69.9% of 11,083 controls reported first-trimester NVP. Compared to no NVP, mothers with NVP had ≥10% reduction in risk of cardiac and noncardiac defects overall, and of 18 specific defects. Over-the-counter antiemetic use, compared to untreated NVP, was associated with ≥10% increase in risk for nine defect groups (heterotaxy, hypoplastic left heart syndrome [HLHS], aortic stenosis, cataracts, anophthalmos/microphthalmos, biliary atresia, transverse limb deficiency, omphalocele, and gastroschisis), whereas use of prescription antiemetics increased risk ≥10% for seven defect groups (tetralogy of Fallot, HLHS, spina bifida, anopthlamos/microphthalmos, cleft palate, craniosynostosis, and diaphragmatic hernia). We observed increased risks for promethazine and tetralogy of Fallot (aOR: 1.49, 95% CI: 1.05-2.10), promethazine and craniosynostosis (1.44, 1.08-1.92), ondansetron and cleft palate (1.66, 1.18-2.31), pyridoxine and heterotaxy (3.91, 1.49-10.27), and pyridoxine and cataracts (2.57, 1.12-5.88).

Conclusions: NVP does not increase risks of birth defects. Our findings that some treatments for NVP increase risk of specific birth defects should be investigated further before clinical recommendations are made.