Inactivated COVID-19 Vaccines in Peri-Pregnancy Period: Evaluation of Safety for Both Pregnant Women and Neonates.

Background: Pregnant women have been excluded from vaccination of COVID-19 due to the lack of strong clinical evidence, which may place pregnant women at greater risk of contracting COVID-19. We conducted this study in China to investigate the maternal and neonatal safety of inactivated COVID-19 vaccination administered during the peri-pregnancy period. Methods: This prospective observational cohort study enrolled pregnant women who received pregnancy care between January 1, 2021, and December 31, 2021. Pregnant women were categorized into vaccine group (n = 60) and control group (n = 60) based on whether they had received an inactivated COVID-19 vaccine within peri-pregnancy period. The primary outcomes were the incidence of maternal premature rupture of membranes (PROM) and neonatal adverse events, including induced labor/death, premature birth, low birth weight, and neonatal intensive care unit (NICU) admission and several secondary outcomes related to pregnant women and neonates. Inverse probability treatment weighting (IPTW) was employed to adjust for baseline covariates. Linear and logistic regression models were established after IPTW for continuous and binary outcomes, respectively. In sensitivity analysis, E-values were calculated and propensity score matching analysis and multivariate regression analysis used to demonstrate the robustness of IPTW results. Moreover, vaccination time subgroup analysis and medication subgroup analysis were conducted. Results: Out of 120 neonates delivered, there was no significant difference in PROM (25.42 % vs. 19.67 %, p = 0.438) or neonatal adverse events (11.86 % vs. 4.92 %, p = 0.148) between the vaccine and control groups. Moreover, among the secondary outcomes only serum alanine transaminase (ALT) at first trimester had a statistically significant difference between the groups, ALT levels were significantly higher in the vaccine group during the first trimester (20.67 +/- 20.34 vs. 13.05 +/- 9.43; RR: 5.38; p = 0.04). In sensitivity analysis, the Evalues calculated for the primary outcomes PROM and neonatal adverse events are 2.04 and 5.00 respectively. PSM analysis and multivariate regression analysis reached the same conclusion. The results of primary outcomes are both consistent across the vaccination time subgroup and medication subgroup. Conclusion: The sensitivity analysis illustrates the robustness of our results, so we can conclude that the vaccination of inactivated COVID-19 vaccine during the peri-pregnancy period is safe for both the pregnant woman and neonates no matter what time of vaccination and the use of medication. In addition, it is recommended to monitor ALT levels throughout the first trimester of pregnancy.