The aim of this multicenter retrospective cohort study was to examine the impact of maternal age on perinatal outcomes in multiparas, stratified according to maternal age in one- and two-year increments. The analysis involved 302,484 multiparas who delivered between the years 2003 and 2021 in four university-affiliated obstetrics departments. Maternal age was considered both as a continuous variable and in two-year intervals, as compared with a comparison group of parturients aged 25–30 years. The study focused on cesarean delivery and neonatal intensive care unit (NICU) admission as primary outcomes. The findings revealed that cesarean delivery rates increased as maternal age advanced, with rates ranging from 6.7% among 25–30 year olds, rising continuously from 13.5% to 19.9% between the age strata of 31 and 42, to exceeding 20% among those aged ≥ 43 years (p < 0.01 for each stratum when compared to 25–30 year old group). Similarly, NICU admission rates rose from 2.7% in the comparison group to 6% in parturients aged 45–46 years (p < 0.01 for each stratum when compared to 25–30 year old group). The study highlights the association between incrementally advanced maternal age and increased rates of maternal and neonatal complications, necessitating global awareness of these implications for family planning decisions and maternal care.

In early 2023, when Omicron was the variant of concern, we showed that vaccinating pregnant women decreased the risk of severe COVID-19 related complications, and maternal morbidity and mortality. To analyze the impact of COVID-19 during pregnancy on newborns and the effects of maternal COVID-19 vaccination on neonatal outcomes, when Omicron was the variant of concern. INTERCOVID-2022 is a large, prospective, observational study, conducted in 40 hospitals across 18 countries, from November 27, 2021 (the day after the World Health Organization declared Omicron the variant of concern) to June 30, 2022, to assess the effect of COVID-19 in pregnancy on maternal and neonatal outcomes, as well as vaccine effectiveness (VE). Women diagnosed with laboratory-confirmed COVID-19 in pregnancy were compared with two 'non-diagnosed', unmatched women recruited concomitantly and consecutively in pregnancy or at delivery. Mother/newborn dyads were followed until hospital discharge. Primary outcomes were a neonatal positive test for COVID-19, severe neonatal morbidity index (SNMI), severe perinatal morbidity and mortality index (SPMMI), preterm birth, neonatal death, referral to neonatal intensive care unit (NICU), and diseases during the neonatal period. VE was estimated adjusted by maternal risk profile. We enrolled 4707 neonates born to 1577 (33.5%) mothers diagnosed with COVID-19 and 3130 (66.5%) non-diagnosed mothers. Amongst diagnosed mothers, 642 (40.7%) were not vaccinated, 147 (9.3%) were partially vaccinated, 551 (34.9%) were completely vaccinated, and 237 (15.0%) also had a booster vaccine. Neonates of booster-vaccinated mothers had less than half (RR=0.46; 95%CI=0.23, 0.91) the risk of being diagnosed with COVID-19 compared to those of unvaccinated mothers; they also had the lowest rates of preterm birth, medically-indicated preterm birth, respiratory distress syndrome and number of days in NICU. Newborns of unvaccinated mothers had double the risk of neonatal death (RR=2.06; 95% CI=1.06, 4.00) compared to those of non-diagnosed mothers. Vaccination was not associated with any congenital malformations. Although all vaccines provided protection against neonatal test positivity, newborns of booster-vaccinated mothers had the significantly highest VE (64%; 95% CI=10-86%); VE was not as high for mRNA vaccines only. VE against moderate/severe neonatal outcomes was much lower: 13% in the booster-vaccinated group (all vaccines), and 25% and 28% in the completely and booster-vaccinated groups, respectively (mRNA vaccines only). Vaccines were fairly effective in protecting neonates when given to pregnant women 100 days (14 weeks) or less before birth; thereafter, the risk increased and was much higher after 200 days (29 weeks).. Finally, none of the neonatal practices studied, including skin-to-skin contact and direct breastfeeding, increased the risk of infecting newborns. When Omicron was the variant of concern, newborns of unvaccinated mothers had an increased risk of neonatal death. Neonates of vaccinated mothers had a decreased risk of preterm birth and adverse neonatal outcomes. As the protective effect of COVID-19 vaccination decreases with time, to ensure that newborns are maximally protected against COVID-19 mothers should receive a vaccine or booster dose no more than 14 weeks before the expected date of delivery.

Infants are at a higher risk of Coronavirus Disease 2019 (COVID-19)-related hospitalizations compared to older children. In this study, we investigated the effect of the recommended third maternal dose of BNT162b2 COVID-19 vaccine during pregnancy on rates of infant COVID-19-related hospitalizations. We conducted a nationwide cohort study of all live-born infants delivered in Israel between 24 August 2021 and 15 March 2022 to estimate the effectiveness of the third booster dose versus the second dose against infant COVID-19-related hospitalizations. Data were analyzed for the overall study period, and the Delta and Omicron periods were analyzed separately. Cox proportional hazard regression models estimated hazard ratios and 95% confidence intervals (CIs) for infant hospitalizations according to maternal vaccination status at delivery. Among 48,868 live-born infants included in the analysis, rates of COVID-19 hospitalization were 0.4%, 0.6% and 0.7% in the third-dose, second-dose and unvaccinated groups, respectively. Compared to the second dose, the third dose was associated with reduced infant hospitalization with estimated effectiveness of 53% (95% CI: 36–65%). Greater protection was associated with a shorter interval between vaccination and delivery. A third maternal dose during pregnancy reduced the risk of infant hospitalization for COVID-19 during the first 4 months of life, supporting clinical and public health guidance for maternal booster vaccination to prevent infant COVID-19 hospitalization.

The Centers for Disease Control (CDC) recommend a third dose of COVID-19 vaccine for pregnant women, although data regarding effectiveness during pregnancy are lacking. This national, population-based, historical cohort study of pregnant women in Israel, delivering between August 1, 2021 and March 22, 2022, aims to analyze and compare the third and second doses’ vaccine effectiveness in preventing COVID-19-related hospitalizations during pregnancy during two COVID-19 waves (Delta variant in the summer of 2021 and Omicron, BA.1, variant in the winter of 2022). Time-dependent Cox proportional-hazards regression models estimate the hazard ratios (HR) and 95% confidence intervals (CI) for COVID-related outcomes according to vaccine dose, and vaccine effectiveness as 1-HR. Study includes 82,659 and 33,303 pregnant women from the Delta and Omicron waves, respectively. Compared with the second dose, the third dose effectively prevents overall hospitalizations with SARS-CoV-2 infections, with estimated effectiveness of 92% (95% CI 83–96%) during Delta, and enhances protection against significant disease during Omicron, with effectiveness of 92% (95% CI 26–99%), and 48% (95% CI 37–57%) effectiveness against hospitalization overall. A third dose of the BNT162b2 mRNA COVID-19 vaccine during pregnancy, given at least 5 months after the second vaccine dose, enhances protection against adverse COVID-19-related outcomes.

Hybrid immunity, acquired through vaccination followed or preceded by a COVID-19 infection, elicits robust antibody augmentation. We hypothesize that maternal hybrid immunity will provide greater infant protection than other forms of COVID-19 immunity in the first 6 months of life. We conducted a case-control study in Israel, enrolling 661 infants up to 6 months of age, hospitalized with COVID-19 (cases) and 59,460 age-matched non-hospitalized infants (controls) between August 24, 2021, and March 15, 2022. Infants were grouped by maternal immunity status at delivery: Naïve (never vaccinated or tested positive, reference group), Hybrid-immunity (vaccinated and tested positive), Natural-immunity (tested positive before or during the study period), Full-vaccination (two-shot regimen plus 1 booster), and Partial-vaccination (less than full three shot regimen). Applying Cox proportional hazards models to estimate the hazard ratios, which was then converted to percent vaccine effectiveness, and using the Naïve group as the reference, maternal hybrid-immunity provided the highest protection (84% [95% CI 75-90]), followed by full-vaccination (66% [95% CI 56-74]), natural-immunity (56% [95% CI 39-68]), and partial-vaccination (29% [95% CI 15-41]). Maternal hybrid-immunity was associated with a reduced risk of infant hospitalization for Covid-19, as compared to natural-immunity, regardless of exposure timing or sequence. These findings emphasize the benefits of vaccinating previously infected individuals during pregnancy to reduce COVID-19 hospitalizations in early infancy.

Research using artificial intelligence (AI) in medicine is expected to significantly influence the practice of medicine and the delivery of health care in the near future. However, for successful deployment, the results must be transported across health care facilities. We present a cross-facilities application of an AI model that predicts the need for an emergency caesarean during birth. The transported model showed benefit; however, there can be challenges associated with interfacility variation in reporting practices.