Porreco Richard, Garite Thomas J, Combs C Andrew, Maurel Kimberley, Huls Christopher Kevin, Baker Susan, Fortner Kimberley B, Longo Sherri A, Nageotte Michael, Lewis David, Tran Lan
Obstetrix Medical Group of Colorado, Presbyterian St. Luke's Medical Center, Denver, CO (Dr Porreco).
Pediatrix Center for Research, Education, Quality and Safety, Sunrise, FL (Drs Garite and Combs and Ms Maurel); Department of Obstetrics and Gynecology, University of California, Irvine, Irvine, CA (Dr Garite); Sera Prognostics, Salt Lake City, UT (Dr Garite).
Am J Obstet Gynecol MFM. 2023 May;5(5):100896. doi: 10.1016/j.ajogmf.2023.100896. Epub 2023 Feb 14.
Preterm prelabor rupture of membranes is a leading cause of preterm birth and is responsible for 18% to 20% of perinatal deaths in the United States. An initial course of antenatal corticosteroids has been shown to reduce morbidity and mortality in patients with preterm prelabor rupture of membranes. For patients who remain undelivered for 7 days or more after the initial course of antenatal corticosteroids, it is uncertain whether a booster course of antenatal corticosteroids reduces neonatal morbidity or increases the infection risk. The American College of Obstetricians and Gynecologists has concluded that the current evidence is insufficient to make a recommendation.
This study aimed to evaluate if a single booster course of antenatal corticosteroids improves neonatal outcomes after preterm prelabor rupture of membranes.
We conducted a multicenter, placebo-controlled randomized clinical trial. The inclusion criteria were preterm prelabor rupture of membranes, gestational age of 24.0 to 32.9 weeks, singleton, initial antenatal corticosteroid course administered at least 7 days before randomization, and planned expectant management. Consenting patients were randomized in gestational age blocks to either receive booster antenatal corticosteroids (12 mg betamethasone every 24 hours for 2 days) or a saline placebo. The primary outcome was composite neonatal morbidity or death. A sample size of 194 patients was calculated to yield 80% power at P<.05 to detect a reduction in primary outcome from 60% in placebo group to 40% in antenatal corticosteroids group.
From April 2016 through August 2022, 194 patients consented and were randomized (47% of 411 eligible patients). Intent-to-treat analysis was performed on 192 patients (2 placebo patients left hospital, outcomes unknown). The groups had similar baseline characteristics. The primary outcome occurred in 64% of patients who received booster antenatal corticosteroids vs in 66% of patients who received the placebo (odds ratio, 0.82; 95% confidence interval, 0.43-1.57; gestational age-stratified Cochran-Mantel-Haenszel test). Individual components of the primary outcome and secondary neonatal and maternal outcomes were not significantly different between the antenatal corticosteroids and placebo groups. Specifically, chorioamnionitis (22% vs 20%), postpartum endometritis (1% vs 2%), wound infections (2% vs 0%), and proven neonatal sepsis (5% vs 3%) were not different between the groups.
A booster course of antenatal corticosteroids at least 7 days after the first antenatal corticosteroids course in patients with preterm prelabor rupture of membranes did not improve neonatal morbidity or any other outcome in this adequately-powered, double-blind randomized clinical trial. Booster antenatal corticosteroids did not increase maternal or neonatal infection.
胎膜早破是早产的主要原因，在美国占围产期死亡的18%至20%。已证实，初始疗程的产前糖皮质激素可降低胎膜早破患者的发病率和死亡率。对于在初始疗程的产前糖皮质激素治疗后7天或更长时间仍未分娩的患者，再次使用产前糖皮质激素是否能降低新生儿发病率或增加感染风险尚不确定。美国妇产科医师学会得出结论，目前的证据不足以给出推荐意见。
本研究旨在评估单次再次使用产前糖皮质激素是否能改善胎膜早破后的新生儿结局。
我们进行了一项多中心、安慰剂对照的随机临床试验。纳入标准为胎膜早破、孕龄24.0至32.9周、单胎、在随机分组前至少7天给予初始疗程的产前糖皮质激素，以及计划进行期待治疗。同意参与的患者按孕龄分组，随机接受再次使用的产前糖皮质激素（24小时一次，每次12mg倍他米松，共2天）或生理盐水安慰剂。主要结局为新生儿复合发病率或死亡。计算得出样本量为194例患者，在P<0.05时检验效能为80%，以检测主要结局从安慰剂组的60%降至产前糖皮质激素组的40%。
2016年4月至2022年8月，194例患者同意参与并被随机分组（411例符合条件患者中的47%）。对192例患者进行了意向性分析（2例接受安慰剂的患者出院，结局未知）。两组的基线特征相似。接受再次使用产前糖皮质激素的患者中64%出现主要结局，接受安慰剂的患者中这一比例为66%（比值比，0.82；95%置信区间，0.43 - 1.57；按孕龄分层的 Cochr an - Mantel - Haenszel检验）。产前糖皮质激素组和安慰剂组之间主要结局的各个组成部分以及次要的新生儿和母亲结局均无显著差异。具体而言，绒毛膜羊膜炎（22%对20%）、产后子宫内膜炎（1%对2%）、伤口感染（2%对0%）以及确诊的新生儿败血症（5%对3%）在两组之间并无差异。
在这项样本量充足的双盲随机临床试验中，胎膜早破患者在首次产前糖皮质激素疗程至少7天后再次使用该药物，并未改善新生儿发病率或任何其他结局。再次使用产前糖皮质激素并未增加母亲或新生儿感染。
