Maternal Third-Trimester Vaccination Lowers Infant COVID-19 Hospitalization Risk

Optimizing Neonatal Passive Immunity Against Respiratory Viral Infection

Protecting infants from severe respiratory infections remains a critical priority, as neonates and premature infants face a significantly higher risk of severe COVID-19 outcomes compared to older children [1]. While maternal infection with SARS-CoV-2 is associated with increased risks of preterm birth and stillbirth [2], vaccination has emerged as a safe and effective strategy to mitigate these perinatal complications [3, 4]. Beyond direct maternal protection, the transfer of antibodies through the placenta and breast milk offers a potential mechanism for shielding immune-immature infants [5]. However, the durability of this passive immunity and the optimal window for maternal immunization to ensure infant protection have remained unclear. A new study now offers fresh insights into how the timing of maternal vaccination relative to conception dictates clinical outcomes for the infant.

Large-Scale Evaluation of Maternal mRNA Vaccination Timing

To determine how the timing of immunization influences neonatal outcomes, researchers conducted a retrospective cohort study of 78,644 infants born between July 1, 2021, and June 30, 2023, within the Kaiser Permanente Northern California healthcare system. The study examined the effectiveness of maternal messenger RNA (mRNA) SARS-CoV-2 vaccination administered either before or during pregnancy in preventing COVID-19 in infants from birth through 6 months of age. Maternal vaccination status was categorized into three primary groups: those vaccinated during pregnancy, those vaccinated during a prepregnancy interval, and those who remained unvaccinated. To capture the potential waning of immunity, the researchers further stratified the prepregnancy group into four distinct intervals: 0 to less than 3 months, 3 to less than 6 months, 6 to 12 months, and more than 12 months before the start of pregnancy. This granular approach allowed the team to pinpoint the exact duration of protective benefit, or lack thereof, across the gestational timeline.

Limited Utility of Prepregnancy Immunization for Neonatal Protection

The clinical burden of SARS-CoV-2 in early infancy was clearly defined within the study cohort, highlighting the vulnerability of patients in the first half-year of life. Among the 78,644 infants followed from birth, the researchers identified that 3,648 (4.6%) were diagnosed with COVID-19 infection before reaching 6 months of age. While the absolute risk of severe disease remained low, a critical subset of 76 infants (0.1%) required COVID-19–related hospitalization before age 6 months. These data points provide a baseline for understanding the vulnerability of neonates and young infants who are not yet age-eligible for direct vaccination and must rely on the transplacental transfer of maternal antibodies for protection. This passive transfer is the primary mechanism by which a mother’s immune system shares its pathogen-fighting proteins with the fetus through the umbilical cord.

Third-Trimester Dosing and Reduction in Severe Infant Outcomes

While prepregnancy vaccination showed no significant benefit for the neonate, the study found that maternal vaccination at any time during pregnancy provided measurable protection. The researchers conducted secondary analyses to evaluate vaccine effectiveness (the percentage reduction in disease incidence among vaccinated persons compared to unvaccinated persons) based on the specific trimester of pregnancy in which the vaccine was administered. For infants whose mothers were vaccinated at any point during gestation, the vaccine effectiveness was 7.5% (95% CI, -2% to 16.2%) against infant COVID-19 infection. Although the protection against mild infection was modest, the impact on severe disease was more pronounced, with maternal vaccination during pregnancy resulting in a vaccine effectiveness of 52.9% (95% CI, 11.1% to 75.1%) against infant COVID-19–related hospitalization. This suggests that while maternal antibodies may not always prevent colonization or mild illness, they are highly effective at preventing the lower respiratory tract involvement that necessitates inpatient care.

References

1. Choi JH, Choi S, Yun K. Risk Factors for Severe COVID-19 in Children: A Systematic Review and Meta-Analysis. Journal of Korean medical science. 2022. doi:10.3346/jkms.2022.37.e35

2. Baar JACV, Kostova EB, Allotey J, et al. COVID-19 in pregnant women: a systematic review and meta-analysis on the risk and prevalence of pregnancy loss. Human Reproduction Update. 2023. doi:10.1093/humupd/dmad030

3. Prasad S, Kalafat E, Blakeway H, et al. Systematic review and meta-analysis of the effectiveness and perinatal outcomes of COVID-19 vaccination in pregnancy. Nature Communications. 2022. doi:10.1038/s41467-022-30052-w

4. Carbone L, Trinchillo MG, Girolamo RD, et al. COVID-19 vaccine and pregnancy outcomes: A systematic review and meta-analysis.. International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics. 2022. doi:10.1002/ijgo.14336

5. Whited N, Cervantes J. Antibodies Against SARS-CoV-2 in Human Breast Milk After Vaccination: A Systematic Review and Meta-Analysis. Breastfeeding Medicine. 2022. doi:10.1089/bfm.2021.0353