Descriptive statistics and characteristics
Between December 15, 2020, and May 31,2022, we identified 62117 infants born at Kaiser Permanente Northern California (KPNC), an integrated health care delivery organization. Among these infants, we excluded 21918 (35.3%) based on maternal exclusion criteria and 10408 (16.0%) after applying infant exclusion criteria (Figure 1). The final study population included 30288 (48.8%) infants who were KPNC members at least 2 months after birth. The mean age at pregnancy onset was 31 years (standard deviation 4.66 years). Most mothers (66.15%) were between ages 25 and <35 years, and more than a quarter (27.26%) were of Asian race, 5.16% were Black, 24.45% were of Hispanic ethnicity and 37.57% were White. Among the infants in the cohort, 19179 (63.32%) of the mothers were unvaccinated during pregnancy, 1035 (3.42%) of the mothers received 1 dose of a mRNA COVID-19 vaccine, 9456 (31.22%) received 2 doses, and 618 (2.04%) received 3 doses during pregnancy (Table 1).
During the first 6 months of life, 940 (3.10%) infants tested positive for SARS-CoV-2 by polymerase chain reaction (PCR) test and 10 (0.03%) infants were hospitalized with a positive SARS-CoV-2 test.
Vaccine effectiveness: Primary design cohort analyses
During the Delta dominant period, the crude incidences of testing positive for SARS-CoV-2 during the first 2, 4 and 6 months of life were lower among infants whose mothers received at least 2 doses of mRNA COVID-19 vaccines during pregnancy (0.74, 1.38, and 1.55 infants per 100 person years [PY], respectively) than those whose mothers were not vaccinated during pregnancy (5.53, 5.18, and 4.83 infants per 100 PYs, respectively). After adjusting for covariates, vaccination during pregnancy significantly reduced risk of the infant testing SARS-CoV-2 positive by 85% (95% confidence interval [CI]: 67, 93) during the first 2 months of life, 64% (95% CI: 43, 78) during the first 4 months of life and 57% (95% CI: 36,71) during the first 6 months of life (Table 2). During the Omicron dominant period, vaccination during pregnancy reduced the risk of the infant testing SARS-CoV-2 positive by 22% (95% CI: -18, 48) during the first 2 months of life, 14% (95% CI: -10, 32) during the first 4 months of life, and 12% (95% CI: - 4, 26) during the first 6 months of life (Table 2).
In supplemental analyses by trimester of vaccination, receipt of the second dose during the second and third trimester reduced the risk of infants testing SARS-CoV-2 positive during the Delta dominant period by 91% (95% CI: 63, 98) and 87% (95% CI: 55, 96), respectively, during the first 2 months of life, by 60% (95% CI: 23, 79) and 70% (95% CI: 43, 84) during the first 4 months of life and by 65% (95% CI:33, 81) and 54% (95% CI: 27, 71) during the first 6 months of life (Table 3). We observed a similar pattern in vaccine effectiveness by trimester during the Omicron dominant period, however, estimates of vaccine effectiveness by trimester during the Omicron period were imprecise and much lower than during the Delta period (Table 3).
Over the entire study period, the crude rate of hospitalization with a SARS-CoV-2 positive test was lower during the first 6 months of life among infants whose mothers received at least 2 doses of mRNA COVID-19 vaccines during pregnancy compared with infants whose mothers were unvaccinated during pregnancy (21/100000 PY vs. 100/100000 PY). VE against hospitalization was not estimated because of the very small number of hospitalized cases. There were only 1 hospitalized case among the children of vaccinated mothers and 9 hospitalized cases among the children of unvaccinated mothers (Table 1).
Secondary analysis results using a test negative design (TND)
In the TND, we estimated that during the Delta predominant period, maternal vaccination reduced the infant’s risk of testing SARS-CoV-2 positive by 98% (95% CI:75, 100) during the first 2 months of life, 72% (95% CI: 55, 83) during the first 4 months of life, and 63% (95% CI: 45, 75) during the first 6 months of life (Supplemental Table). During the Omicron dominant period, maternal vaccination reduced the infant’s risk of testing SARS-CoV-2 positive by 55% (95% CI: 15, 76) during the first 2 months of life, 37% (95% CI:12, 55) during the first 4 months of life, and 40% (95% CI: 25, 53) during the first 6 months of life (Supplemental Table).