(101) Effectiveness of pre-pregnancy maternal SARS-CoV-2 vaccination in preventing COVID-19 in infants

Background: SARS-CoV-2 vaccination during pregnancy reduces risk of COVID-19 in infants, with the highest protection seen in the first two months of life. It is unknown whether maternal vaccination prior to pregnancy similarly protects infants against COVID-19.

Objectives: To determine the effectiveness of pre-pregnancy maternal SARS-CoV-2 vaccination on risk of infant COVID-19.

Methods: This cohort study used electronic health record data of mother-infant pairs who were members at delivery/birth in Kaiser Permanente Northern California’s integrated health system. The study included mothers age 16-50 years and their infants born July 1, 2021 - June 30, 2023, and excluded mothers vaccinated with non-mRNA SARS-CoV-2 vaccines. The exposure was maternal vaccination status, categorized – according to the most recent SARS-CoV-2 mRNA vaccination up to 14 days prior to delivery – as vaccinated during pregnancy, vaccinated during one of four pre-pregnancy intervals, or unvaccinated (reference). The outcome was COVID-19 in infants from 0-2, 2-4, and 4-6 months of life, defined by positive SARS-CoV-2 PCR or rapid antigen test, or ICD diagnostic code. We used Cox regression to examine the association of maternal vaccination status with infant’s risk of COVID-19 in risk sets defined by infant birthdate and age in days, adjusting for maternal age, insurance type, pre-pregnancy BMI, diabetes, hypertension, neighborhood deprivation index, breastfeeding, and maternal COVID-19 infection history. We calculated vaccine effectiveness was as (1-HR)x100%.

Results: There were 3648 COVID-19 cases among 78644 infants, of which 943/21087 (4.5%) were born to SARS-CoV-2 unvaccinated mothers; 36/1963 (1.8%) infants of mothers vaccinated >12 months pre-pregnancy onset; 187/7268 (2.6%) infants of mothers vaccinated 6-12 months pre-pregnancy; 217/6134 (3.5%) infants of mothers vaccinated 3-6 months pre-pregnancy; 404/7930 (5.1%) infants of mothers vaccinated < 3 months pre-pregnancy; and 1861/34262 (5.4%) infants of mothers vaccinated during pregnancy. After covariate adjustment, maternal vaccine effectiveness during infants’ first 2 months of life was 37.8% (95% CI 24.8-48.6) for vaccination during pregnancy, 11.3% (-15.6-32.0) for vaccination < 3 months pre-pregnancy, 10.9% (-21.3-34.5) for 3-6 months pre-pregnancy, and 17.6% (-18.4-42.7) for 6-12 months pre-pregnancy. Vaccination regardless of pre-birth interval was not protective against COVID-19 for infants aged 2-4 or 4-6 months.

Conclusions: Over 2 years when multiple SARS-CoV-2 variants circulated, maternal vaccination during pregnancy provided some protection against COVID-19 in early infancy, but vaccination prior to pregnancy did not appear to be protective. More research is needed to determine impacts of differences in unvaccinated and vaccinated populations, and effects of maternal COVID-19 and hybrid immunity.