Risk of malformation after ondansetron in pregnancy: An updated systematic review and meta‐analysis

Abstract

Ondansetron is increasingly used off label to treat nausea and vomiting during pregnancy. The main objective of this study was to evaluate the risk of major congenital malformations (MCM), cardiac defects and orofacial clefts associated with first trimester exposure to ondansetron using a meta‐analytic approach. MEDLINE, ClinicalTrials.gov and Scopus were searched until November 2019. All comparative cohort and case–control studies on MCM, cardiac or orofacial defects and use of ondansetron during pregnancy were included. A team of paired reviewers independently extracted data using a proprietary collaborative WEB‐based meta‐analysis platform (metaPreg.org). Pooled odd ratios with corresponding 95% CIs were calculated using random effects models. From 214 records initially retrieved, 12 studies were included. Using all available information to date, first trimester exposure to ondansetron was found to be associated with an increased risk of (a) ventricular septal defects (VSD) (OR 1.11, 95% CI 1.00–1.23; p < .05; n = 6 studies; I2 = 0%) and (b) oral clefts (OR 1.22, 95% CI 1.00–1.49; p < .05; n = 4 studies; I2 = 0%). No significant association was observed for the risk of cleft palate but, when excluding the study that contributed to the study heterogeneity, we found an OR of 1.48 (95% CI 1.19–1.84; p < .01; n = 5 studies; I2 = 0%). No statistically significant association was found for MCM, overall cardiac malformations, atrial septal defects and cleft lip with or without cleft palate. Exploratory investigations of other malformations showed an increased risk of diaphragmatic hernia, hypoplastic left heart and “respiratory system anomalies.”

Management of primary headaches during pregnancy, postpartum, and breastfeeding: A systematic review

“…NSAIDs, [38][39][40][41][42][43][44][45] two antiepileptics, [46][47][48] two β-blockers, [49][50][51] two calcium channel blockers, 50,52 two antiemetics (5-HT3 receptor antagonists), 53,54 two antipsychotics, 55,56 two antihistamines, 57,58 and one each assessed serotonin and norepinephrine reuptake inhibitors (SNRIs), 59,60 tricyclic antidepressants, 59,60 benzodiazepines, 61,62 corticosteroids, 63 oral magnesium, 64 triptans (5-HT1B/1D receptor agonists), 65 analgesics/antipyretics, 66 and intravenous magnesium. 67 Twelve SRs reported maternal adverse effects and 23 reported fetal/child adverse effects.…”

What changes in prescription patterns of antiemetic medications in pregnant women in France?

“…An offlabel use of ondansetron has also been observed for the treatment of hyperemesis gravidarum in the United States [5], where ondansetron prescriptions concerned 20% of pregnant women in 2014. However, a recent meta-analysis raised concerns about teratogenic risk of this drug, in particular risk of cardiac defect and orofacial clefts [12]. The French Authorities (ANSM) published warnings in December 2019 according to these potential risks [28]; a letter addressed to health professionals recalled that ondansetron can only be used in a context of cancer chemotherapy or radiation treatment and also recommended not to use ondansetron during the first trimester of pregnancy.…”

“…However, we know that exposure to domperidone may be responsible for cardiovascular adverse effects, in both children and adults, as mentioned in warnings published by the French Authorities (ANSM) in 2011 and 2014 [10,11]. Concerning ondansetron, a recent meta-analysis raised concerns about risks associated with exposure during the first trimester of pregnancy, in particular risk of cardiac septal defects and orofacial clefts [12]. The authors also fear a potential risk of diaphragmatic hernia, hypoplastic left heart, and "respiratory system anomalies.…”

Update on the Management of Breast Cancer during Pregnancy

“…Ondansetron is the most studied drug in this class and can be safely administered [66][67][68]. Two recent metanalyses confirmed the absence of increased risk of major malformations after ondansetron administration during the first trimester [69,70]. The histamine type 2 receptor (H2) antagonist, mostly used for premedication of taxanes, can be used to prevent allergic reactions without an increased risk of major malformations [71].…”