Prenatal exposure to maternal BNT162b2 COVID-19 vaccination was not associated with adverse effects or poor outcomes in newborns, according to results of a population-based cohort study published in JAMA Pediatrics.
Researchers sourced data for this study from Maccabi healthcare services, a state-mandated health fund in Israel. The researchers evaluated all singleton live births (n=24,888) that occurred between March and September 2021, and outcomes of maternal COVID-19 mRNA vaccination were assessed through October 2021. The primary outcomes were the proportion of both preterm births and newborns who were small for gestational age (SGA), with differences assessed between newborns who were exposed vs unexposed to maternal vaccination. Exploratory outcomes after birth, including neonatal and postneonatal hospital admissions, congenital anomalies, jaundice requiring phototherapy, and all-cause mortality, were also assessed. Stabilized inverse probability of treatment weighting (IPTW) was used to balance baseline covariates between exposed and unexposed newborns, with propensity scores indicating the probability of prenatal COVID-19 vaccination. Propensity scores were estimated via logistic regression and included maternal age, timing of conception, parity, socioeconomic status, population subgroup, and maternal influenza immunization status.
Among all newborns included in the final analysis, 16,697 were prenatally exposed to maternal COVID-19 vaccination vs 7591 unexposed newborns. Of the exposed and unexposed newborns, the mean maternal age was 31.61 ± 5.22 and 30.49 ± 5.67 years, respectively. Among the exposed and unexposed newborns’ mothers, 10.6% and 11.4% had a BMI of 35 kg/m2 or greater (P =.03), 1.9% and 2.1% had gestational diabetes (P =.01), 10.7% and 11.1% had a high-risk pregnancy (P =.01), and 6.5% and 29.5% had SARS-CoV-2 infection before delivery, respectively.
After adjustment for propensity scores, no significant differences were noted between exposed and unexposed newborns in regard to the number of preterm births (risk ratio [RR], 0.95; 95% CI, 0.83-1.10). There also were no differences between the groups in regard to both the proportion of newborns who were SGA (RR, 0.97; 95% CI, 0.87-1.08) and those who had a low birth weight (RR, 0.89; 95% CI, 0.78-1.01). The risk for neonatal and postneonatal hospitalization was similar between the exposed vs unexposed newborns (RR, 0.99; 95% CI, 0.88-1.12 vs RR, 0.95; 95% CI, 0.84-1.07). In addition, no significant differences in the rate of all-cause mortality were observed between exposed and unexposed newborns (RR, 0.84; 95% CI, 0.43-1.72).
Similar findings were observed in a sensitivity analysis that excluded mothers who had SARS-CoV-2 infection before delivery, with the exception that exposure to maternal COVID-19 vaccination was associated with an increased risk for requiring phototherapy due to jaundice (RR, 1.46; 95% CI, 1.06-2.06).
The researchers used IPTW to compare a subset of newborns who were prenatally exposed to COVID-19 vaccination during the first trimester (n=2021) vs those who were unexposed (n=3580). No significant differences between exposed vs unexposed newborns were found in regard to the number of preterm births (RR, 0.87, 95% CI, 0.67-1.12) and newborns who were SGA (7.9% vs 6.9%; RR, 1.14; 95% CI, 0.92-1.40). They also assessed the risk for congenital malformations and found no significant differences between exposed and unexposed newborns (RR, 0.69; 95% CI, 0.44-1.04).
Limitations of this study included that only live births were assessed and its observational design. In addition, because the number of newborns exposed to maternal COVID-19 vaccination during the first trimester was underpowered, the outcomes of this study are primarily applicable to newborns who are exposed during the second and third trimesters.
Despite these limitations, the researchers concluded, “these findings contribute to current evidence in establishing the safety of BNT162b2 [maternal vaccination exposure in newborns] and can be used to inform pregnant patients, couples planning pregnancy, and counseling physicians.”
Goldshtein I, Steinberg DM, Kuint J, et al. Association of BNT162b2 COVID-19 vaccination during pregnancy with neonatal and early infant outcomes. JAMA Pediatr. 2022;e220001. doi:10.1001/jamapediatrics.2022.0001