Newborn and Early Infant Outcomes Following Maternal COVID-19 Vaccination During Pregnancy

Abstract

ImportanceThe study team previously showed that maternal mRNA COVID-19 vaccination during pregnancy confers protection against SARS-CoV-2 infection and COVID-19–related hospital admission in newborns and young infants. In this study, the study team evaluated newborn and early infant safety outcomes following maternal messenger RNA (mRNA) COVID-19 vaccination during pregnancy, for which there is limited comparative epidemiological evidence.ObjectiveTo determine if maternal mRNA COVID-19 vaccination during pregnancy is associated with adverse newborn and early infant outcomes.Design, Setting, and ParticipantsThis population-based retrospective cohort study took place in Ontario, Canada, using multiple linked health administrative databases. Singleton live births with an expected delivery date between May 1, 2021, and September 2, 2022, were included. Data were analyzed from January 2023 through March 2023.ExposureMaternal mRNA COVID-19 vaccination (1 or more doses) during pregnancyMain Outcomes and MeasuresSevere neonatal morbidity (SNM), neonatal death, neonatal intensive care unit (NICU) admission, neonatal readmission, and hospital admission up to 6 months of age. The study team calculated inverse probability of treatment weighted risk ratios (RRs) and fit weighted Cox proportional hazards regression models comparing outcomes in infants of mothers who received COVID-19 vaccination during pregnancy with those who received no COVID-19 vaccine doses before delivery.ResultsIn total, 142 006 infants (72 595 male [51%]; mean [SD] gestational age at birth, 38.7 [1.7] weeks) were included; 85 670 were exposed to 1 or more COVID-19 vaccine doses in utero (60%). Infants of vaccinated mothers had lower risks of SNM (vaccine exposed 7.3% vs vaccine unexposed 8.3%; adjusted RR [aRR], 0.86; 95% CI, 0.83-0.90), neonatal death (0.09% vs 0.16%; aRR, 0.47; 95% CI, 0.33-0.65), and NICU admission (11.4% vs 13.1%; aRR, 0.86; 95% CI, 0.83-0.89). There was no association between maternal vaccination during pregnancy and neonatal readmission (5.5% vs 5.1%; adjusted hazard ratio, 1.03; 95% CI, 0.98-1.09) or 6-month hospital admission (8.4% vs 8.1%; adjusted hazard ratio, 1.01; 95% CI, 0.96-1.05).Conclusions and RelevanceIn this population-based cohort study in Ontario, Canada, maternal mRNA COVID-19 vaccination during pregnancy was associated with lower risks of SNM, neonatal death, and NICU admission. In addition, neonatal and 6-month readmissions were not increased in infants of mothers vaccinated during pregnancy.

Neonatal Outcomes After COVID-19 Vaccination in Pregnancy

“…This study had findings concordant with smaller studies and had the advantage of evaluating specific neonatal diagnoses that were selected a priori as having biologically plausible links to COVID-19 vaccination. It also included information on BMI in pregnant individuals, a potentially important 12 The Canadian study also reported that infants of vaccinated individuals had lower risk of severe neonatal morbidity, defined as a composite consisting of 7 neonatal procedures and 15 different diagnoses, including gestational age and birth weight. 12 Accordingly, the selective contributions of pregnancy outcomes and specific neonatal outcomes to the association with vaccination in pregnancy were unresolved.…”

“…It is unlikely that mRNA COVID-19 vaccination during pregnancy directly reduces neonatal mortality, although others have suggested that such a protective effect is biologically plausible. 12 The vaccine does not seem to pass the placenta or induce placental inflammation, and could not be traced in cord blood. 25,26 The current study's results could not elucidate the mechanisms that explain why infants of vaccinated individuals had lower risks of some outcomes including mortality.…”

“…Previous studies have reported unchanged 11 or lower neonatal mortality 12,13 in exposed infants, and lower composite neonatal morbidity after vaccination during pregnancy. 12 A metaanalysis of 2 smaller studies reported lower rates of neonatal brain injury after vaccination during pregnancy. 14 The aim of this large population-based cohort study was to perform a comprehensive assessment of neonatal safety for mRNA COVID-19 vaccines.…”

“…Nevertheless, the power of this study exceeded that of previous investigations of neonatal outcomes. [11][12][13]31,32 Third, misclassification of some register data cannot be excluded, although the data sources have been found to be valid. 17 Fourth, no information was available on lifestyle factors, breastfeeding rates, or outcomes beyond the neonatal period.…”

“…Vaccination has not been associated with adverse pregnancy outcomes or higher admission rates to neonatal care, but information on neonatal outcomes is limited. Previous studies have reported unchanged or lower neonatal mortality in exposed infants, and lower composite neonatal morbidity after vaccination during pregnancy . A meta-analysis of 2 smaller studies reported lower rates of neonatal brain injury after vaccination during pregnancy …”