Anick Bérard1, Odile Sheehy2, Jessica Gorgui3, Jin-Ping Zhao2, Cristiano Soares de Moura4, Sasha Bernatsky4. 1. Research Center, CHU Sainte-Justine, 3175, Chemin de la Côte-Sainte-Catherine, Montréal, Québec H3T 1C5, Canada; Faculty of Pharmacy, University of Montreal, Pavillon Jean-Coutu, 2940, chemin de Polytechnique, Montréal, Québec H3T 1J4, Canada. Electronic address: anick.berard@umontreal.ca. 2. Research Center, CHU Sainte-Justine, 3175, Chemin de la Côte-Sainte-Catherine, Montréal, Québec H3T 1C5, Canada. 3. Research Center, CHU Sainte-Justine, 3175, Chemin de la Côte-Sainte-Catherine, Montréal, Québec H3T 1C5, Canada; Faculty of Pharmacy, University of Montreal, Pavillon Jean-Coutu, 2940, chemin de Polytechnique, Montréal, Québec H3T 1J4, Canada. 4. Faculty of Medicine, Department of Clinical Epidemiology, McGill University, Purvis Hall 1020 Pine Ave. West, Montréal, Québec H3A 1A2, Canada.
Abstract
OBJECTIVES: The aim of the study was 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 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. CONCLUSION: First-trimester doxylamine-pyridoxine and metoclopramide exposure was associated with a significantly increased risk of overall and specific MCM.
OBJECTIVES: The aim of the study was 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 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. CONCLUSION: First-trimester doxylamine-pyridoxine and metoclopramide exposure was associated with a significantly increased risk of overall and specific MCM.