Ondansetron exposure during pregnancy is not associated with risk of congenital malformations: evidence from a meta-analysis

Ondansetron is widely used drug for treatment of morning sickness and hyperemesis gravidarum. However, whether exposure to ondansetron during pregnancy is associated with risk of congenital malformations or not remains debatable. The present meta-analysis was performed for published cohort/registry-based studies which evaluated the association between ondansetron exposure and risk of congenital malformations. Major congenital malformations were considered as the primary outcome measure. Specific abnormalities like cardiac malformation, septal defect, cleft lip/palate, hypospadias, and genitourinary abnormalities were considered as secondary outcome measures along with spontaneous abortion/miscarriage, stillbirth, preterm delivery, and low birth weight babies. Pooled analysis was done using the Mantle-Hanzle method, random effect model and were expressed as odds ratio (OR) with 95% CI. Fourteen studies were included in systematic review. There was no significant difference for major congenital malformations [n=12; OR: 1.12 (95% CI: 0.93-1.36), I2=96], septal defect [n=5; OR: 1.39 (95% CI: 1.01-1.91), I2=48%], cleft lip/palate [n=3; OR: 1.11 (95% CI: 0.80-1.53), I2=41%] between ondansetron exposed and control arms. However, a greater number of events were found in control arm than intervention arm for cardiac defect [n=7; OR: 1.26 (95% CI: 1.09-1.45), I2=71%; p=0.002]. We also observed a greater number of events for stillbirth and pre-term labour in control arm than in intervention arm with OR: 1.57 (95% CI: 1.24-1.97); p=0.0001 and OR: 1.33 (95% CI: 1.05-1.69); p=0.02, respectively. This meta-analysis concludes that ondansetron exposure during pregnancy is not associated with any increased risk of major congenital malformations, septal /cardiac defect, cleft lip/palate, spontaneous abortion/miscarriage, stillbirth, pre-term labour and low birth weight babies