(SLC-022) Safety of Nausea and Vomiting of Pregnancy Treatments: A US MotherToBaby Prospective Cohort Study

Background: Nausea and vomiting of pregnancy (NVP) affects up to 80% of pregnant individuals, yet the safety and efficacy of various treatments remain uncertain, leading to conflicting international guidelines.

Objectives: To compare the risk of adverse birth outcomes between mothers exposed to NVP medications and unmedicated mothers, with and without NVP.

Methods: A prospective, observational cohort study was conducted using data from the MotherToBaby Pregnancy Studies, which included live-born singleton pregnancies enrolled from February 22, 2016, to December 8, 2023. Pregnant women exposed to any NVP medications were compared to women with untreated NVP and women without NVP. Risk ratios (RR) of major congenital malformations, preterm delivery ( < 37.0 weeks), small for gestational age (SGA, ≤10th percentile), and neonatal intensive care unit (NICU) admissions were assessed. Propensity score-adjusted risk ratios with 95% confidence intervals were calculated using modified Poisson regression to assess the association between NVP treatments and adverse birth outcomes.

Results: The study included 2711 pregnant individuals: NVP treatment exposed (n=603), untreated NVP (n=1567), and no NVP (n=541). Major congenital malformations occurred in 6.12% (n=29) of the NVP treatment group, 5.04% (n=79) of the untreated NVP group, and 5.55% (n=30) of the no NVP group. Adjusted RR for treatment exposed was 1.23 (95% CI, 0.80-1.89) compared to untreated NVP and 1.05 (95% CI, 0.63-1.76) compared to no NVP. The rates of preterm birth were 8.62% (n=52) in the exposed group, 7.22% (n=113) in the untreated NVP group, and 7.95% (n=43) in the no NVP group. The adjusted RR of preterm birth was 1.21 (95% CI, 0.88-1.67) for treatment exposed compared to untreated NVP and 1.09 (95% CI, 0.74-1.61) compared to no NVP. The rates of infants being SGA were similar between groups, with adjusted RRs of 1.25 (95% CI, 0.90-1.74) for exposed women compared to untreated NVP and 1.42 (95% CI, 0.92-2.18) compared to no NVP. The risk of NICU admission was not increased for the exposed group. Doxylamine (n=345, 57.21%) and ondansetron (n=286, 47.43%) were the most used treatments. When the risks for adverse birth outcomes were evaluated separately for ondansetron, an increased risk of SGA was found, adjusted RR 1.80, (95% CI 1.23-2.60) compared to untreated NVP and 1.99 (95% CI 1.22-3.24) compared to no NVP.

Conclusions: No increased risk for major congenital malformations or other adverse birth outcomes was found in women treated with NVP medications compared to women with untreated NVP and women without NVP. The increased risk of SGA with ondansetron may be linked to the severity of NVP rather than the treatment itself.