Long-term Risk for Type 1 Diabetes and Obesity in Early Term Born Offspring: A Systematic Review and Meta-Analysis.

CONTEXT: Prematurity increases the long-term risks for endocrine and metabolic morbidity of offspring, but there is uncertainty regarding the risks for early-term deliveries (370/7-386/7 weeks of gestation). OBJECTIVE: We aim to evaluate whether early-term deliveries increase the long-term risk for type 1 diabetes and obesity of offspring up to the age of 18 years compared with full-term children. PubMed, Medline, and EMBASE were searched. Observational cohort studies addressing the association between early-term delivery and long-term risk for type 1 diabetes and obesity, were included. Two independent reviewers extracted data and assessed risk of bias. Pooled relative risks (RRs) and heterogeneity were determined. Publication bias was assessed by funnel plots with Egger's regression line and contours, and sensitivity analyses were performed. RESULTS: Eleven studies were included following a screen of 7500 abstracts. All studies were scored as high quality according to the Newcastle-Ottawa Quality Assessment Scale. Early-term delivery was significantly associated with an increased risk for type 1 diabetes (RR 1.19, 1.13-1.25), while the association was weaker for overweight and obesity (RR 1.05, 0.97-1.12). It is challenging to determine whether the association between early-term births and long-term morbidity represents a cause and effect relationship or is attributable to confounders. Most of the included studies adjusted for at least some possible confounders. CONCLUSION: Compared with full-term offspring, early-term delivery poses a modest risk for long-term pediatric type 1 diabetes. Our analysis supports that, whenever medically possible, elective delivery should be avoided before 39 completed weeks of gestation.

Boosting maternal and neonatal anti-SARS-CoV-2 humoral immunity using a third mRNA vaccine dose.

BACKGROUND: To minimize COVID-19 pandemic burden and spread, 3-dose vaccination campaigns commenced worldwide. Since patients who are pregnant are at increased risk for severe disease, they were recently included in that policy, despite the lack of available evidence regarding the impact of a third boosting dose during pregnancy, underscoring the urgent need for relevant data. We aimed to characterize the effect of the third boosting dose of mRNA Pfizer BNT162b2 vaccine in pregnancy. METHODS: We performed a prospective cohort study of anti-SARS-CoV-2 antibody titers (n = 213) upon delivery in maternal and cord blood of naive fully vaccinated parturients who received a third dose (n = 86) as compared with 2-dose recipients (n = 127). RESULTS: We found a robust surge in maternal and cord blood levels of anti-SARS-CoV-2 titers at the time of delivery, when comparing pregnancies in which the mother received a third boosting dose with 2-dose recipients. The effect of the third boosting dose remained significant when controlling for the trimester of last exposure, suggesting additive immunity extends beyond that obtained after the second dose. Milder side effects were reported following the third dose, as compared with the second vaccine dose, among the fully vaccinated group. CONCLUSION: The third boosting dose of mRNA Pfizer BNT162b2 vaccine augmented maternal and neonatal immunity with mild side effects. These data provide evidence to bolster clinical and public health guidance, reassure patients, and increase vaccine uptake among patients who are pregnant. FUNDING: Israel Science Foundation KillCorona grant 3777/19; Research grant from the "Ofek" Program of the Hadassah Medical Center.

Long-term respiratory outcomes in early-term born offspring: a systematic review and meta-analysis.

OBJECTIVE: Newborns exhibit the lowest immediate respiratory morbidity rates when born at full term (39-40 completed weeks of gestation). We evaluated whether early-term deliveries (37 0/7 to 38 6/7 weeks of gestation) bear a substantial impact on overall and specific long-term respiratory outcomes of offspring up to the age of 18 years compared with full-term or later deliveries. DATA SOURCES: We searched PubMed, Medline, Embase, and relevant reference lists from January 2012 to May 2020. STUDY ELIGIBILITY CRITERIA: This systematic review and meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews guidelines and was registered on International Prospective Register of Systematic Reviews. Any observational or randomized human trials addressing the association between early-term delivery and long-term respiratory outcomes in the offspring, restricted to studies published in English, were included. The search included terms relating to gestational age, pediatric morbidity, and respiratory outcomes. We included studies assessing long-term respiratory disease (1-18 years) of offspring born early term compared with offspring born full term and later. METHODS: Here, 2 independent reviewers extracted data and assessed the risk of bias. Using a random-effect meta-analysis, pooled relative risk with their 95% confidence intervals and heterogeneity were determined. Publication bias was assessed using funnel plots with Egger regression line and contours, and sensitivity analyses were performed using Baujat plots. RESULTS: Overall, 14 studies were included after screening nearly 2500 abstracts. These studies included nearly 8 million patients and were subjected to qualitative and quantitative analyses. Early-term delivery significantly increased the risk of total respiratory morbidity in the offspring (relative risk, 1.20; 95% confidence interval, 1.16-1.26) compared with full-term delivery. The increased respiratory morbidity was attributed to obstructive airway diseases (relative risk, 1.19; 95% confidence interval, 1.12-1.27) and infectious respiratory diseases (relative risk, 1.22; 95% confidence interval, 1.17-1.29). Most studies were of acceptable quality. CONCLUSION: This comprehensive meta-analysis suggested that early-term delivery poses a risk of long-term pediatric respiratory morbidity compared with full-term delivery. Other factors throughout the years cannot be accounted for. Our study has added an important perspective to be considered when balancing the fetal, maternal, and neonatal risks associated with delivery timing.