Background Preterm premature rupture of membranes (PPROM), which is associated with vaginal dysbiosis, is responsible for up to one-third of all preterm births. Consecutive ascending colonization, infection, and inflammation may lead to relevant neonatal morbidity including early-onset neonatal sepsis (EONS). The present study aims to assess the vaginal microbial composition of PPROM patients and its development under standard antibiotic therapy and to evaluate the usefulness of the vaginal microbiota for the prediction of EONS. It moreover aims to decipher neonatal microbiota at birth as possible mirror of the in utero microbiota. Methods As part of the PEONS prospective multicenter cohort study, 78 women with PPROM and their 89 neonates were recruited. Maternal vaginal and neonatal pharyngeal, rectal, umbilical cord blood, and meconium microbiota were analyzed by 16S rRNA gene sequencing. Significant differences between the sample groups were evaluated using permutational multivariate analysis of variance and differently distributed taxa by the Mann–Whitney test. Potential biomarkers for the prediction of EONS were analyzed using the MetaboAnalyst platform. Results Vaginal microbiota at admission after PPROM were dominated by Lactobacillus spp. Standard antibiotic treatment triggers significant changes in microbial community (relative depletion of Lactobacillus spp. and relative enrichment of Ureaplasma parvum) accompanied by an increase in bacterial diversity, evenness and richness. The neonatal microbiota showed a heterogeneous microbial composition where meconium samples were characterized by specific taxa enriched in this niche. The vaginal microbiota at birth was shown to have the potential to predict EONS with Escherichia/Shigella and Facklamia as risk taxa and Anaerococcus obesiensis and Campylobacter ureolyticus as protective taxa. EONS cases could also be predicted at a reasonable rate from neonatal meconium communities with the protective taxa Bifidobacterium longum, Agathobacter rectale, and S. epidermidis as features. Conclusions Vaginal and neonatal microbiota analysis by 16S rRNA gene sequencing after PPROM may form the basis of individualized risk assessment for consecutive EONS. Further studies on extended cohorts are necessary to evaluate how far this technique may in future close a diagnostic gap to optimize and personalize the clinical management of PPROM patients. Trial registration NCT03819192, ClinicalTrials.gov. Registered on January 28, 2019.

Vaccination in the SARS-CoV-2 pandemic is important, especially to protect pregnant women and the unborn. In 2021, the messenger RNA (mRNA)-based vaccines BNT162b2 (BioNTech/Pfizer) and mRNA-1273 (Moderna), and the vector-based vaccine AZD1222 (AstraZeneca) were approved for use in Germany. 1 Vaccination for pregnant women was considered after weighing the individual benefits and risks of the vaccines without preference for a vaccine type. 1 After national guidelines discouraged the use of AZD1222 in those under 60 years of age, 1 mRNA-based boost vaccination was recommended. In this study we intend to evaluate antibody kinetics following heterologous vaccination in pregnant women in comparison to their newborns as well as to a healthy nonpregnant control group. STUDY DESIGN:We recruited 3 pregnant participants (gestational age at primary vaccination between 21 and 28 weeks) and 25 nonpregnant control participants at the Jena University Hospital. They were observed after prime vaccination with AZD1222 and boost vaccination 12 weeks thereafter with either BNT162b2 or mRNA-1273. Ethical approval was obtained for the same (Jena University Hospital ethics commission ref.: 2021-2078). The anti-Spike immunoglobulin G (IgG) antibody levels were determined in the serial serum samples (before and 1, 2, 3, 4, 5, 8, and 16 weeks after prime

Introduction A common problem in the treatment of threatened preterm birth is the timing and the unrestricted use of antenatal corticosteroids (ACS). This study was performed to evaluate the independent effects of the distinct timing of antenatal corticosteroids on neonatal outcome parameters in a cohort of very low (VLBW; 1000 – 1500 g) and extreme low birth weight infants (ELBW; < 1000 g). We hypothesize that a prolonged ACS-to-delivery interval leads to an increase in respiratory complications. Materials and Methods Main data source was the prospectively collected single center data for the German nosocomial infection surveillance system (KISS) between 2015 and 2018. Multivariate regression analysis was performed to determine independent effects of the ACS-to-delivery interval on the need for ventilation, surfactant or the occurrence of bronchopulmonary dysplasia, neonatal sepsis or necrotizing enterocolitis. Subgroup analysis was performed for ELBW and VLBW neonates. Results A total of 239 neonates were included. We demonstrate a significantly increased risk of respiratory distress characterized by the need for ventilation (OR 1.045; CI 1.011 – 1.080) and surfactant administration (OR 1.050, CI 1.018 – 1.083) depending on the ACS-to-delivery interval irrespective of other confounders. Every additional day between ACS and delivery increased the risk for ventilation by 4.5% and for surfactant administration by 5%. Subgroup analysis revealed significant differences of respiratory complications in VLBW infants. Conclusions Our data strongly support the deliberate use and timing of antenatal corticosteroids in pregnancies with threatened preterm birth versus a liberal strategy. When given more than 7 days before birth, each day between application and delivery increases is relevant concerning major effects on the infant. Especially VLBW preterm neonates benefit from optimal timing.

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