Abstract This doctoral research explores the impact of maternal SARS-CoV-2 mRNA vaccination during pregnancy, focusing on its efficacy in generating immune responses, transplacental antibody transfer, and the subsequent immunity conferred to newborns. The study aims to address gaps in understanding the duration and effectiveness of maternal-derived neonatal immunity while assessing the roles of breastfeeding, maternal booster doses, and postnatal infections in shaping antibody kinetics over a 9-month postpartum period. Background The emergence of SARS-CoV-2 created significant health challenges, especially for pregnant women, who are at higher risk of severe complications compared to non-pregnant individuals. Despite initial vaccine hesitancy stemming from the exclusion of pregnant women in clinical trials, subsequent observational studies have confirmed the safety and efficacy of mRNA vaccines in this population. Vaccination not only reduces maternal morbidity but also leverages transplacental antibody transfer to provide passive immunity to neonates, a crucial protection mechanism during their immunologically immature early life. Methodology This prospective observational study recruited 98 pregnant women who received at least one dose of an mRNA COVID-19 vaccine during different trimesters. Maternal and neonatal antibody levels were assessed at birth (T0), and at 3, 6, and 9 months postpartum (T1–T3). Blood samples were analyzed using chemiluminescent microparticle immunoassay (CMIA) to quantify IgG antibodies against SARS-CoV-2's spike protein. Antibody kinetics were studied in relation to vaccination timing, breastfeeding practices, and postnatal infections. Participants were monitored for vaccine-related adverse events, SARS-CoV-2 exposure, and health outcomes. Findings Maternal vaccination induced robust immune responses, with efficient transplacental transfer of IgG antibodies observed. The study highlights several critical insights: 1. Timing of Vaccination: Antibody levels in both mothers and newborns were significantly higher when vaccination occurred in the second or third trimester. Third-trimester vaccinations resulted in the highest antibody titers in neonates, emphasizing the importance of late-pregnancy immunization. 2. Antibody Durability: Neonatal antibody levels peaked at birth and declined significantly over the first 9 months. However, antibodies were detectable in most infants at 9 months, indicating prolonged, albeit waning, immunity. 3. Impact of Breastfeeding: Breastfed infants exhibited a slower decline in antibody levels compared to formula-fed or mixed-fed infants, underscoring the complementary protective role of breast milk. 4. Role of Booster Doses: Booster doses administered postpartum in mothers significantly increased maternal antibody titers, enhancing neonatal immunity when breastfeeding was continued. 5. Postnatal Infections: Neonates exposed to SARS-CoV-2 showed a slower decline in antibody levels, suggesting an active adaptive immune response even in early infancy. Safety and Clinical Outcomes The study confirmed the safety of maternal vaccination, with no severe adverse effects reported among participants. Neonates exhibited good health outcomes, with no severe COVID-19 cases or hospitalizations observed. These findings reinforce the benefits of vaccination in preventing severe disease in both mothers and infants. Discussion The study contributes valuable insights into optimizing maternal immunization strategies. It validates the efficacy of mRNA vaccines in eliciting maternal immune responses and facilitating efficient antibody transfer. Furthermore, it highlights the synergistic effects of vaccination timing, breastfeeding, and booster doses in enhancing neonatal immunity. Key implications include the necessity of late-trimester vaccinations to maximize antibody transfer and the potential of booster doses to sustain maternal immunity, benefiting breastfeeding infants. The findings also underscore the need for continued research into the mechanisms of antibody transfer, the role of placental receptors, and the influence of maternal cytokines on neonatal immunity. Conclusion Maternal vaccination against SARS-CoV-2 is a pivotal intervention for protecting pregnant women and their newborns. By providing passive immunity, it reduces neonatal susceptibility to COVID-19 during the critical early months of life. The study advocates for broader public health strategies promoting vaccination during pregnancy, emphasizing its dual benefits for maternal and neonatal health. Future research should explore alternative vaccination schedules, the durability of neonatal antibodies, and the integration of maternal vaccination into routine obstetric care.
COVID-VACCINES IN PREGNANCY: MATERNAL AND NEONATAL RESPONSE OVER THE FIRST 9 MONTHS AFTER DELIVERY
PROTO, ALICE
2025
Abstract
Abstract This doctoral research explores the impact of maternal SARS-CoV-2 mRNA vaccination during pregnancy, focusing on its efficacy in generating immune responses, transplacental antibody transfer, and the subsequent immunity conferred to newborns. The study aims to address gaps in understanding the duration and effectiveness of maternal-derived neonatal immunity while assessing the roles of breastfeeding, maternal booster doses, and postnatal infections in shaping antibody kinetics over a 9-month postpartum period. Background The emergence of SARS-CoV-2 created significant health challenges, especially for pregnant women, who are at higher risk of severe complications compared to non-pregnant individuals. Despite initial vaccine hesitancy stemming from the exclusion of pregnant women in clinical trials, subsequent observational studies have confirmed the safety and efficacy of mRNA vaccines in this population. Vaccination not only reduces maternal morbidity but also leverages transplacental antibody transfer to provide passive immunity to neonates, a crucial protection mechanism during their immunologically immature early life. Methodology This prospective observational study recruited 98 pregnant women who received at least one dose of an mRNA COVID-19 vaccine during different trimesters. Maternal and neonatal antibody levels were assessed at birth (T0), and at 3, 6, and 9 months postpartum (T1–T3). Blood samples were analyzed using chemiluminescent microparticle immunoassay (CMIA) to quantify IgG antibodies against SARS-CoV-2's spike protein. Antibody kinetics were studied in relation to vaccination timing, breastfeeding practices, and postnatal infections. Participants were monitored for vaccine-related adverse events, SARS-CoV-2 exposure, and health outcomes. Findings Maternal vaccination induced robust immune responses, with efficient transplacental transfer of IgG antibodies observed. The study highlights several critical insights: 1. Timing of Vaccination: Antibody levels in both mothers and newborns were significantly higher when vaccination occurred in the second or third trimester. Third-trimester vaccinations resulted in the highest antibody titers in neonates, emphasizing the importance of late-pregnancy immunization. 2. Antibody Durability: Neonatal antibody levels peaked at birth and declined significantly over the first 9 months. However, antibodies were detectable in most infants at 9 months, indicating prolonged, albeit waning, immunity. 3. Impact of Breastfeeding: Breastfed infants exhibited a slower decline in antibody levels compared to formula-fed or mixed-fed infants, underscoring the complementary protective role of breast milk. 4. Role of Booster Doses: Booster doses administered postpartum in mothers significantly increased maternal antibody titers, enhancing neonatal immunity when breastfeeding was continued. 5. Postnatal Infections: Neonates exposed to SARS-CoV-2 showed a slower decline in antibody levels, suggesting an active adaptive immune response even in early infancy. Safety and Clinical Outcomes The study confirmed the safety of maternal vaccination, with no severe adverse effects reported among participants. Neonates exhibited good health outcomes, with no severe COVID-19 cases or hospitalizations observed. These findings reinforce the benefits of vaccination in preventing severe disease in both mothers and infants. Discussion The study contributes valuable insights into optimizing maternal immunization strategies. It validates the efficacy of mRNA vaccines in eliciting maternal immune responses and facilitating efficient antibody transfer. Furthermore, it highlights the synergistic effects of vaccination timing, breastfeeding, and booster doses in enhancing neonatal immunity. Key implications include the necessity of late-trimester vaccinations to maximize antibody transfer and the potential of booster doses to sustain maternal immunity, benefiting breastfeeding infants. The findings also underscore the need for continued research into the mechanisms of antibody transfer, the role of placental receptors, and the influence of maternal cytokines on neonatal immunity. Conclusion Maternal vaccination against SARS-CoV-2 is a pivotal intervention for protecting pregnant women and their newborns. By providing passive immunity, it reduces neonatal susceptibility to COVID-19 during the critical early months of life. The study advocates for broader public health strategies promoting vaccination during pregnancy, emphasizing its dual benefits for maternal and neonatal health. Future research should explore alternative vaccination schedules, the durability of neonatal antibodies, and the integration of maternal vaccination into routine obstetric care.File | Dimensione | Formato | |
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https://hdl.handle.net/20.500.14242/197792
URN:NBN:IT:UNIMI-197792