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

Birth Defects Res. 2023 Feb 1;115(3):275-289. doi: 10.1002/bdr2.2096. Epub 2022 Sep 27.


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.

Keywords: NVP medications; birth defects; birth defects etiology; nausea and vomiting of pregnancy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cleft Palate*
  • Craniosynostoses*
  • Female
  • Humans
  • Microphthalmos*
  • Nausea
  • Pregnancy
  • Pregnancy Complications* / drug therapy
  • Promethazine / therapeutic use
  • Pyridoxine / therapeutic use
  • Tetralogy of Fallot*
  • Vomiting


  • Promethazine
  • Pyridoxine