Medications used to treat nausea and vomiting of pregnancy and the risk of selected birth defects

Abstract

Background Nausea and vomiting of pregnancy (NVP) occurs in up to 80% of pregnant women, yet its association with birth outcomes is not clear. Several medications are used for the treatment of NVP; however, data are limited on their possible associations with birth defects. Methods Using data from the National Birth Defects Prevention Study (NBDPS), a multi-site population-based case-control study, we examined whether NVP or its treatment was associated with the most common non-cardiac defects in the NBDPS (non-syndromic cleft lip with or without cleft palate (CL/P), cleft palate alone (CP), neural tube defects (NTDs), and hypospadias) compared to randomly-selected non-malformed live births. Results Among the 4524 cases and 5859 controls included in this study, 67.1% reported first trimester NVP, and 15.4% of them reported using at least one agent for NVP. Nausea and vomiting of pregnancy was not associated with CP or NTDs, but modest risk reductions were observed for CL/P (aOR=0.87, 0.77–0.98), and hypospadias (OR=0.84, 0.72–0.98). In regards to treatments for NVP in the first trimester, the following adjusted associations were observed with an increased risk: proton pump inhibitors and hypospadias (aOR=4.36, 1.21–15.81), steroids and hypospadias (aOR=2.87, 1.03–7.97), and ondansetron and CP (aOR=2.37, 1.18–4.76), while antacids were associated with a reduced risk for CL/P (aOR=0.58, 0.38–0.89). Conclusions Nausea and vomiting of pregnancy was not observed to be associated with an increased risk of birth defects, but possible risks related to three treatments (i.e. proton pump inhibitors, steroids and ondansetron), which could be chance findings, warrant further investigation.

Comparing Neonatal Outcome Following the Use of Ondansetron versus Vitamin B6 in Pregnant Females with Morning Sickness: A Randomized Clinical Trial

“…However, this sample size ruled out only a five-fold increased risk of major malformations and not any specific malformation. Moreover, the lack of other similar cohort studies precluded conducting a meta-analysis to increase the sample size (16). Besides, no previous reports were available on toxicity or teratogenicity of vitamin B6 during pregnancy.…”

Treatments for hyperemesis gravidarum and nausea and vomiting in pregnancy: a systematic review and economic assessment

“…One recent case-control study reported an increased risk of cleft palate (adjusted OR 2.37, 95% CI 1.18 to 4.76). 144 However, another Danish study, involving over 600,000 pregnancies, found no association with any adverse fetal outcomes. 145 Concerns have been raised regarding the risk of cardiac arrhythmias [time between start of the Q wave and of the T wave in the heart's electrical cycle (QT) prolongation] with large doses of i.v.…”

Ondansetron Use in Pregnancy and Birth Defects

“…The first, in 2012, was a review of data from the National Birth Defects Prevention Study in the United States (16). A total of 4524 cases and 5859 controls were examined, and the authors looked specifically at 3 birth defect categories: orofacial clefts, neural tube defects, and hypospadias.…”