LAUSR

OBJECTIVE To quantify the risk of major congenital malformations (MCM) associated with first-trimester exposure to antiemetics. STUDY DESIGN AND SETTING Using 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). RESULTS Within 17 years of follow-up, the prevalence of antiemetic use during pregnancy increased by 76%. Within our cohort, 45,623 pregnancies 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%CI: 1.03-1.11; 3945 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; 1735 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 significant association was found between ondansetron exposure and the risk of overall MCM. CONCLUSION First-trimester doxylamine-pyridoxine and metoclopramide exposure was associated with a significantly increased risk of overall MCM.