Periviable Premature Rupture of Membranes-Maternal and Neonatal Risks: A Systematic Review and Meta-analysis.

OBJECTIVE: Periviable premature rupture of membranes (PROM) counseling should describe maternal and neonatal outcomes associated with both immediate delivery and expectant management. Unfortunately, most published data focuses on neonatal outcomes and maternal risk estimates vary widely. We performed a meta-analysis to describe outcomes associated with expectant management compared with immediate delivery of periviable PROM. STUDY DESIGN: We performed a search on PubMed, MEDLINE, Web of Science, PROSPERO, Cochrane library, and ClinicalTrials.gov utilizing a combination of key terms. Published clinical trials and observational cohorts were included if published after 2000. Publications were selected if they included maternal and/or neonatal outcomes for both expectant management and immediate delivery. Gestational age range was limited from 14 to 25 weeks. The primary outcome was maternal sepsis. Secondary outcomes included chorioamnionitis, hemorrhage, laparotomy, and neonatal survival. Pooled risk differences (RDs) were calculated for each outcome using a random-effects model. Publication bias was assessed using funnel plots and Harbord test. RESULTS: A total of 2,550 studies were screened. After removal of duplicates and filtering by abstract, 44 manuscripts were reviewed. A total of five publications met inclusion for analysis: four retrospective and one prospective. Overall, 364 (68.0%) women underwent expectant management and 171 (32.0%) underwent immediate delivery. Maternal sepsis was significantly more frequent in the expectant group (RD, 4%; 95% confidence interval, 2-7%) as was chorioamnionitis (RD: 30%; p < 0.01) and any laparotomy (RD: 28%; p < 0.01). Neonatal survival in the expectant group was 39% compared with 0% in the immediate group (p < 0.01). CONCLUSION: Women who undergo expectant management following periviable rupture of membranes experience significantly increased risks of sepsis, chorioamnionitis, and laparotomy. Overall, 39% of neonates survive to discharge. Knowledge of these risks is critical to counseling patients with this diagnosis. KEY POINTS: · Expectant management associated with 4% increased risk of sepsis.. · Expectant management associated with 30% increased risk of chorioamnionitis.. · A total of 39% of neonates survived to discharge with expectant management..

Neonatal respiratory morbidity in the early term delivery.

OBJECTIVE: The purpose of this study was to evaluate the risk of respiratory morbidity in neonates delivered at "early term" (37-38 weeks) compared with those delivered at 39 weeks. STUDY DESIGN: We conducted a retrospective cohort study of singleton deliveries from 37(0/7) to 39(6/7) weeks' gestation. Our primary outcome was composite respiratory morbidity. RESULTS: Of 2273 deliveries at 37-39 weeks, 51% (n = 1169) delivered in the early term period. Infants delivered at 37-38 weeks had a 2-fold increased risk of respiratory distress syndrome, oxygen use, continuous positive airway pressure use, and composite respiratory morbidity (risk ratio [RR], 2.9; 95% confidence interval [CI], 1.0-7.9; oxygen usage RR, 2.0; 95% CI, 1.4-2.9; continuous positive airway pressure RR, 1.9; 95% CI, 1.1-3.2; composite respiratory morbidity RR, 2.0; 95% CI, 1.4-2.8). CONCLUSION: The 2-fold increased risk of composite respiratory morbidity of infants in the early term period supports the urgency for limiting nonindicated deliveries to ≥ 39 weeks' gestation.

The allosteric enhancer PD81,723 increases chimaeric A1/A2A adenosine receptor coupling with Gs.

PD81,723 {(2-amino-4,5-dimethyl-3-thienyl)-[3-(trifluromethyl)-phenyl]methanone} is a selective allosteric enhancer of the G(i)-coupled A1 AR (adenosine receptor) that is without effect on G(s)-coupled A2A ARs. PD81,723 elicits a decrease in the dissociation kinetics of A1 AR agonist radioligands and an increase in functional agonist potency. In the present study, we sought to determine whether enhancer sensitivity is dependent on coupling domains or G-protein specificity of the A1 AR. Using six chimaeric A1/A2A ARs, we show that the allosteric effect of PD81,723 is maintained in a chimaera in which the predominant G-protein-coupling domain of the A1 receptor, the 3ICL (third intracellular loop), is replaced with A2A sequence. These chimaeric receptors are dually coupled with G(s) and G(i), and PD81,723 increases the potency of N6-cyclopentyladenosine to augment cAMP accumulation with or without pretreatment of cells with pertussis toxin. Thus PD81,723 has similar functional effects on chimaeric receptors with A1 transmembrane sequences that couple with G(i) or G(s). This is the first demonstration that an allosteric regulator can function in the context of a switch in G-protein-coupling specificity. There is no enhancement by PD81,723 of G(i)-coupled A2A chimaeric receptors with A1 sequence replacing A2A sequence in the 3ICL. The results suggest that the recognition site for PD81,723 is on the A1 receptor and that the enhancer acts to directly stabilize the receptor to a conformational state capable of coupling with G(i) or G(s).