Efficient maternal to neonatal transfer of antibodies against SARS-CoV-2 and BNT162b2 mRNA COVID-19 vaccine.

BACKGROUNDThe significant risks posed to mothers and fetuses by COVID-19 in pregnancy have sparked a worldwide debate surrounding the pros and cons of antenatal SARS-CoV-2 inoculation, as we lack sufficient evidence regarding vaccine effectiveness in pregnant women and their offspring. We aimed to provide substantial evidence for the effect of the BNT162b2 mRNA vaccine versus native infection on maternal humoral, as well as transplacentally acquired fetal immune response, potentially providing newborn protection.METHODSA multicenter study where parturients presenting for delivery were recruited at 8 medical centers across Israel and assigned to 3 study groups: vaccinated (n = 86); PCR-confirmed SARS-CoV-2 infected during pregnancy (n = 65), and unvaccinated noninfected controls (n = 62). Maternal and fetal blood samples were collected from parturients prior to delivery and from the umbilical cord following delivery, respectively. Sera IgG and IgM titers were measured using the Milliplex MAP SARS-CoV-2 Antigen Panel (for S1, S2, RBD, and N).RESULTSThe BNT162b2 mRNA vaccine elicits strong maternal humoral IgG response (anti-S and RBD) that crosses the placenta barrier and approaches maternal titers in the fetus within 15 days following the first dose. Maternal to neonatal anti-COVID-19 antibodies ratio did not differ when comparing sensitization (vaccine vs. infection). IgG transfer ratio at birth was significantly lower for third-trimester as compared with second trimester infection. Lastly, fetal IgM response was detected in 5 neonates, all in the infected group.CONCLUSIONAntenatal BNT162b2 mRNA vaccination induces a robust maternal humoral response that effectively transfers to the fetus, supporting the role of vaccination during pregnancy.FUNDINGIsrael Science Foundation and the Weizmann Institute Fondazione Henry Krenter.

Prenatal exposure to preeclampsia as a risk factor for long-term endocrine morbidity of the offspring.

Objective: To analyze preeclampsia as a risk factor for pediatric endocrine disease. Study Design: A population-based cohort analysis comparing the risk of endocrine morbidity of children born between 1991-2014 to mothers with and without preeclampsia. Results: The study included 253,808 deliveries. Exposed offspring had significantly more endocrine hospitalizations (0.7% vs 0.4%; p < 0.001), specifically obesity (0.4% vs 0.2%, p < 0.001). While controlling for confounders, the exposed offspring had significantly more endocrine morbidity (OR 1.433 95% CI 1.115-1.841 p = 0.005). Conclusion: Preeclampsia is an independent risk factor for long-term endocrine disease of the offspring, specifically obesity.

In utero exposure to pre-eclampsia as an independent risk factor for long-term respiratory disease.

INTRODUCTION: Pre-eclampsia has a considerable effect on the intrauterine environment, yet not much is understood about how this impacts the respiratory health of the offspring. The aim of the present study is to determine if pre-eclampsia correlates with a higher incidence of respiratory disease in the offspring. METHODS: This cohort study assessed the differences in respiratory disease patterns between singletons born to mothers with and without pre-eclampsia. The study was conducted between 1991 and 2014 in a regional tertiary medical center. A generalized estimating equation (GEE) model was used to control for confounders and maternal clusters. RESULTS: 253 808 deliveries were included in the study. Of these, 3.0% were to mothers diagnosed with pre-eclampsia (n = 7660), 0.9% with severe pre-eclampsia (n = 2366), and 0.03% with eclampsia (n = 81). A significant linear association was noted between the severity of the pre-eclampsia (no pre-eclampsia, mild, severe pre-eclampsia, and eclampsia) and respiratory disease of the offspring (5.7%, vs 6.0% vs 7.3% vs 9.9%, respectively; P = .003). The offspring of mothers who developed pre-eclampsia had significantly higher rates of asthma (1.1%, vs 1.3% vs 1.4% vs 1.2% correspondingly; P = .018). In the GEE model, controlling for gestational diabetes, maternal age, gestational age, and length of follow up, pre-eclampsia was found to be an independent risk factor for respiratory morbidity in the offspring (adjusted odds ratio = 1.32; 95% confidence interval, 1.21-1.45). CONCLUSION: Exposure to maternal pre-eclampsia is an independent risk factor for long-term respiratory morbidity in the offspring. Specifically, the prenatal exposure to pre-eclampsia was significantly associated with asthma of the offspring.

Long-term neuropsychiatric morbidity in children exposed prenatally to preeclampsia.

INTRODUCTION: There are contradicting findings in the current literature regarding the association between in-utero exposure to preeclampsia and the long-term neuropsychiatric health of the offspring. The objective of this study is to assess whether prenatal exposure to preeclampsia increases the risk of long-term neuropsychiatric morbidity. METHODS: A retrospective population-based cohort study compared neuropsychiatric morbidity between singletons exposed and unexposed to preeclampsia. The study included all the singletons that were born between 1991 and 2014 in a single regional tertiary medical center. A generalized estimating equation (GEE) model was used to control for confounders and maternal clusters. RESULTS: Of the 253,808 singletons that met the inclusion criteria; 3.0% were born to mothers diagnosed with mild preeclampsia (n = 7660), 0.9% with severe preeclampsia (n = 2366) and 0.03% with eclampsia (n = 81). A significant linear association was noted between the severity of the preeclampsia (no preeclampsia, mild, severe preeclampsia and eclampsia) and the incidence of neuropsychiatric morbidity of the offspring (1.0%, vs. 1.2% vs. 1.9% vs. 1.2% respectively, p = 0.003). In a GEE model which was used to control for maternal clusters, gestational diabetes, maternal age, gestational age and time-to-event preeclampsia was found to be an independent risk factor for neuropsychiatric morbidity in the offspring (adjusted OR = 1.36; 95% CI 1.14-1.63). CONCLUSION: Offspring exposed prenatally to preeclampsia have a significantly higher risk of developing a neuropsychiatric morbidity during childhood.

Prenatal exposure to preeclampsia as an independent risk factor for long-term cardiovascular morbidity of the offspring.

INTRODUCTION: Preeclampsia is a leading cause of maternal and fetal morbidity and mortality. Regarding the offspring, little is known about the long-term complications. The objective of the current study is to assess whether in utero exposure to preeclampsia increases the risk of long-term cardiovascular morbidity in the offspring. MATERIALS AND METHODS: A population-based cohort study compared the incidence of cardiovascular disease between singletons exposed and unexposed to preeclampsia. Deliveries occurred between 1991 and 2014 in a regional tertiary medical center. A Cox proportional hazard model was used to control for confounders. RESULTS: During the study period 231,298 deliveries met the inclusion criteria; 4.1% of the births were to mothers diagnosed with preeclampsia, of which 3.2% with mild preeclampsia (n = 7286), 0.9% with severe preeclampsia (n = 2174) and 0.03% with eclampsia (n = 73). A significant linear association was noted between preeclampsia (no preeclampsia, mild preeclampsia, severe preeclampsia and eclampsia) and cardiovascular disease of the offspring (0.24%, vs. 0.33% vs. 0.51% vs. 2.73% respectively, p < 0.001 using the chi-square test for trends). In the offspring born at term, severe preeclampsia was found to be an independent risk factor for cardiovascular morbidity (adjusted HR = 2.32; 95% CI 1.15-4.67). In offspring born preterm, neither severe preeclampsia (adjusted HR = 1.36; 95% CI 0.53-3.48) nor mild preeclampsia (adjusted HR = 0.37; 95% CI 0.52-2.71) were associated with cardiovascular morbidity of the offspring. CONCLUSION: Exposure to severe maternal preeclampsia is an independent risk factor for long-term cardiovascular morbidity in the offspring born at term.

Prenatal exposure to gestational diabetes mellitus as an independent risk factor for long-term neuropsychiatric morbidity of the offspring.

BACKGROUND: The reported rates of gestational diabetes mellitus are constantly escalating and little is known about long-term complications in the offspring. Evidence from the field of epigenetics strongly advocates the need for research on the neuropsychiatric complications in offspring prenatally exposed to gestational diabetes mellitus. OBJECTIVE: We sought to assess whether in utero exposure to gestational diabetes mellitus increases the risk of long-term neuropsychiatric morbidity in the offspring. STUDY DESIGN: A population-based cohort study compared the incidence of hospitalizations due to neuropsychiatric disease between singletons exposed and unexposed to gestational diabetes mellitus. Deliveries occurred in the years 1991 through 2014 in a regional tertiary medical center. Perinatal deaths, multiple gestations, mothers with pregestational diabetes or lack of prenatal care, and children with congenital malformations were excluded from the study. A multivariate generalized estimating equation logistic regression model analysis was used to control for confounders and for maternal clusters. RESULTS: During the study period 231,271 deliveries met the inclusion criteria; 5.4% of the births were to mothers diagnosed with gestational diabetes mellitus (n = 12,642), of these 4.3% had gestational diabetes type A1 (n = 10,076) and 1.1% had gestational diabetes type A2 (n = 2566). During the follow-up period, a significant linear association was noted between the severity of the gestational diabetes (no gestational diabetes, gestational diabetes mellitus A1, gestational diabetes mellitus A2) and neuropsychiatric disease of the offspring (1.02% vs 1.36% vs 1.68%, respectively, P < .001). A Kaplan-Meier curve demonstrated that children born to women with gestational diabetes mellitus had higher cumulative incidence of neuropsychiatric morbidity. Using a generalized estimating equation multivariable logistic regression model, controlling for time-to-event, maternal age, gestational age at delivery, maternal obesity, maternal preeclampsia and fertility treatments, maternal gestational diabetes mellitus was found to be an independent risk factor for long-term neuropsychiatric disease of the offspring (gestational diabetes mellitus A1 [adjusted odds ratio, 1.83; 95% confidence interval, 1.53-2.19] and gestational diabetes mellitus A2 [adjusted odds ratio, 1.64; 95% confidence interval, 1.18-2.27]). Within the limits of our database, our findings also point to a possible association between in utero exposure to gestational diabetes mellitus and autistic spectrum disorder of the offspring (adjusted odds ratio, 4.44; 95% confidence interval, 1.55-12.69), which was found significant also after controlling for time-to-event, maternal age, gestational age at delivery, and offspring weight at birth. CONCLUSION: Exposure to maternal gestational diabetes mellitus is an independent risk factor for long-term neuropsychiatric morbidity in the offspring.