New evidence for concern over the risk of birth defects from medications for nausea and vomitting of pregnancy

Abstract

ObjectivesThe aim of the study was to quantify the risk of major congenital malformations (MCM) associated with first-trimester exposure to antiemetics. Study Design and SettingUsing the Quebec Pregnancy Cohort (1998–2015), first-trimester doxylamine–pyridoxine, metoclopramide, and ondansetron exposures were assessed for their association with MCM. Generalized estimating equations were used to estimate odds ratios (OR), adjusting for potential confounders (aOR). ResultsWithin 17 years of follow-up, the prevalence of antiemetic use during pregnancy increased by 76%. Within our cohort, 45,623 pregnancies were exposed to doxylamine–pyridoxine, 958 to metoclopramide, and 31 to ondansetron. Doxylamine–pyridoxine and metoclopramide use were associated with an increased risk of overall MCM (aOR 1.07, 95% confidence interval [CI]: 1.03–1.11; 3,945 exposed cases) and (aOR 1.27, 95% CI: 1.03–1.57; 105 exposed cases), respectively. Doxylamine–pyridoxine exposure was associated with increased risks of spina bifida (aOR 1.87, 95% CI: 1.11–3.14; 23 exposed cases), nervous system (aOR 1.25, 95% CI: 1.06–1.47; 225 exposed cases), and musculoskeletal system defects (aOR 1.08, 95% CI: 1.02–1.14; 1,735 exposed cases). Metoclopramide exposure was associated with an increased risk of genital organ defects (aOR 2.26, 95% CI: 1.14–4.48; 10 exposed cases). No statistically significant association was found between ondansetron exposure and the risk of overall MCM. ConclusionFirst-trimester doxylamine–pyridoxine and metoclopramide exposure was associated with a significantly increased risk of overall and specific MCM.