Antibiotic Timing in Previable Prelabor Rupture of Membranes Less Than 24 Weeks of Gestation.

OBJECTIVE: This study aimed to compare neonatal and maternal outcomes between immediate and delayed prophylactic antibiotic administration after previable prelabor premature rupture of membranes (PROM) less than 24 weeks of gestation. STUDY DESIGN: Retrospective cohort study of singleton pregnancies with PROM between 160/7 and 236/7 weeks of gestational age conducted at a single tertiary care referral center between June 2011 and December 2015. Patients with multiple gestations, fetal anomalies, those who elected augmentation, or with a contradiction to expectant management, such as suspected intra-amniotic infection or stillbirth, were excluded from the study. We compared pregnancy characteristics, maternal complications, and neonatal outcomes between women who received a course of antibiotics within 24 hours of PROM and women who received antibiotics after 24 hours of PROM. The primary outcome was neonatal survival to hospital discharge. Secondary outcomes included gestational age at delivery, time from PROM to delivery, neonatal birth weight, days in the neonatal intensive care unit (NICU), composite adverse neonatal outcomes, and maternal morbidity. RESULTS: Ninety-four women met inclusion criteria, 57 (61%) received antibiotics within 24 hours of PROM and 37 (39%) received antibiotics 24 hours after PROM. Baseline maternal characteristics were similar in both groups. The mean gestational age at PROM was similar between groups at 20.8 ± 2.3 weeks in the immediate antibiotics group and 20.6 ± 2.1 weeks in the delayed antibiotics group (p = 0.48). Compared with delayed antibiotic administration, immediate antibiotic administration was not associated with a significant difference in latency time from PROM to delivery, rate of stillbirth, days in an ICU, or adverse neonatal outcomes. Maternal outcomes also did not differ significantly between groups. Neonatal birth weight was lower in the immediate antibiotics group (p = 0.012). CONCLUSION: Our data suggest that there is no maternal or neonatal benefit to immediate administration of latency antibiotics compared with delayed administration. KEY POINTS: · Adverse neonatal outcomes did not differ based on timing of latency antibiotics for previable PROM.. · Maternal outcomes did not differ based on timing of latency antibiotics for previable PROM.. · Neonatal birth weight was lower in infants that received immediate antibiotics after previable PROM..

Histone H2A.Z subunit exchange controls consolidation of recent and remote memory.

Memory formation is a multi-stage process that initially requires cellular consolidation in the hippocampus, after which memories are downloaded to the cortex for maintenance, in a process termed systems consolidation. Epigenetic mechanisms regulate both types of consolidation, but histone variant exchange, in which canonical histones are replaced with their variant counterparts, is an entire branch of epigenetics that has received limited attention in the brain and has never, to our knowledge, been studied in relation to cognitive function. Here we show that histone H2A.Z, a variant of histone H2A, is actively exchanged in response to fear conditioning in the hippocampus and the cortex, where it mediates gene expression and restrains the formation of recent and remote memory. Our data provide evidence for H2A.Z involvement in cognitive function and specifically implicate H2A.Z as a negative regulator of hippocampal consolidation and systems consolidation, probably through downstream effects on gene expression. Moreover, alterations in H2A.Z binding at later stages of systems consolidation suggest that this histone has the capacity to mediate stable molecular modifications required for memory retention. Overall, our data introduce histone variant exchange as a novel mechanism contributing to the molecular basis of cognitive function and implicate H2A.Z as a potential therapeutic target for memory disorders.