A multicountry study to establish rates for pregnancy and neonatal outcomes in low- and middle-income regions.

BACKGROUND: Maternal vaccines can reduce the burden of diseases for both mother and neonate. The development and implementation of such vaccines require a thorough interpretation of safety data and standardized disease case definitions. This study aimed to evaluate the current rates for adverse pregnancy outcomes, maternal and neonatal events of interest (EOIs) that will be informative for preparing future phase III clinical trials on maternal vaccines conducted in low- and middle-income countries and further assisting in safety data interpretation (e.g., monitoring potential safety signals in clinical trials, and/or helping with the causality assessments of adverse events following immunization).

METHODS: We performed a prospective cohort study on healthy 18-45-year-old women, with singleton, low-risk pregnancies, with a gestational age of ≥240/7 weeks at enrollment and ≤276/7 weeks at first visit, and their neonates. The study was conducted between 2019-2021 in 10 countries that were considered low- and middle-income countries by the World Bank Group at the time the study was designed. All pregnancy-related outcomes and maternal EOIs occurring from enrollment up to 42 days post-delivery and neonatal EOIs occurring within the first 28 days after birth were recorded.

RESULTS: Of 2311 pregnant women and 2181 neonates enrolled, 2222 and 2094 were included in the analyses, respectively. Most livebirths (2088 [94.0%]) were without apparent congenital anomalies. Preterm delivery (166 [7.5%]), non-reassuring fetal status (137 [6.2%]), and hypertensive disorders of pregnancy (125 [5.6%]) were the most frequently reported EOIs related to pregnancy. The most frequent neonatal EOIs were low birthweight (including very low birthweight) (156 [7.4%]), preterm birth (141 [6.7%]), small for gestational age (111 [5.3%]), and congenital anomalies (103 [4.9%], including mainly major external structural defects, as well as detected internal and functional defects). Overall, there were similar frequencies in pregnancy outcomes, pregnancy-related and neonatal EOIs across countries, although some variation in the reporting rate was noted.

CONCLUSION: This multicountry study contributes to establishing the most recent background rates for pregnancy outcomes, maternal and neonatal EOIs in low- and middle-income regions. The clinical relevance in the context of the safety assessment in future trials will be applied.

TRIAL REGISTRATION: NCT03614676 (03/08/2018).