Sung Ji-Hee, Kim Jin-Ha, Kim Yejin, Choi Yun-Sun, Hong Siryeon, Choi Suk-Joo, Kim Jung-Sun, Roh Cheong-Rae, Oh Soo-Young
Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea (Drs Sung, JH Kim, Y Kim, YS Choi, Hong, SJ Choi, Roh, and Oh).
Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea (Dr JS Kim).
Am J Obstet Gynecol MFM. 2023 Apr;5(4):100886. doi: 10.1016/j.ajogmf.2023.100886. Epub 2023 Feb 4.
Antibiotic treatment in preterm pre-labor rupture of membranes can prolong the interval from membrane rupture to delivery and improve neonatal outcomes. However, the duration of antibiotic treatment for preterm pre-labor rupture of membranes has been rarely compared in prospective studies.
This study aimed to investigate the optimal duration of antibiotic treatment for pre-labor rupture of membranes. We performed a randomized controlled trial comparing neonatal morbidity and infantile neurologic outcomes between 2 groups of patients with preterm pre-labor rupture of membranes who received antibiotic treatment for 7 days or until delivery, respectively.
This prospective randomized study included patients who were diagnosed with preterm pre-labor rupture of membranes between 22+0 weeks and 33+6 weeks of gestation. The enrolled patients were randomly assigned to receive intravenous cefazolin (1 g dosage every 12 hours) and oral clarithromycin (500 mg dosage every 12 hours) either for 7 days or until delivery. The study protocol was registered at ClinicalTrials.gov under identifier NCT01503606. The primary outcome was a neonatal composite morbidity, and the secondary outcome was neurologic outcomes at 12 months of corrected age. We enrolled 151 patients and allocated 75 and 76 of them to the 7-day and until-delivery groups, respectively. Analysis was done by per protocol.
After excluding cases lost to follow-up and those with protocol violations, 63 (7-day regimen) and 61 (until-delivery regimen) patients with preterm pre-labor rupture of membranes and their babies were compared. There was no significant difference in the pregnancy outcomes, including gestational age at delivery and the interval from rupture of membranes to delivery, between the 2 groups. Among the neonatal outcomes, bronchopulmonary dysplasia, intraventricular hemorrhage, retinopathy of prematurity, necrotizing enterocolitis, and proven neonatal sepsis did not differ between the groups. However, the rates of respiratory distress syndrome (32.8% vs 50.8%; P=.039) and composite neonatal morbidities (34.4% vs 53.9%; P=.026) were lower in the until-delivery group than in the 7-day group. This difference remained statistically significant after a multivariable analysis adjusting for maternal age, twin pregnancy, antenatal corticosteroids treatment, gestational age at delivery, interval from rupture of membranes to delivery, and clinical chorioamnionitis. Infantile neurologic outcomes were evaluated in 71.4% of the babies discharged alive and did not differ between the groups.
Overall, the until-delivery regimen of cefazolin and clarithromycin in preterm pre-labor rupture of membranes led to a lower incidence of composite neonatal morbidity and respiratory distress syndrome than the 7-day regimen, and both regimens otherwise showed similar individual neonatal morbidities and infantile neurologic outcomes.
早产胎膜早破的抗生素治疗可延长从胎膜破裂到分娩的间隔时间，并改善新生儿结局。然而，前瞻性研究中很少比较早产胎膜早破抗生素治疗的持续时间。
本研究旨在探讨早产胎膜早破抗生素治疗的最佳持续时间。我们进行了一项随机对照试验，比较两组早产胎膜早破患者分别接受7天抗生素治疗或直至分娩后的新生儿发病率和婴儿神经学结局。
这项前瞻性随机研究纳入了妊娠22⁺⁰周至33⁺⁶周被诊断为早产胎膜早破的患者。入选患者被随机分配接受静脉注射头孢唑林（每12小时1g剂量）和口服克拉霉素（每12小时500mg剂量），疗程为7天或直至分娩。该研究方案已在ClinicalTrials.gov上注册，标识符为NCT01503606。主要结局是新生儿综合发病率，次要结局是矫正年龄12个月时的神经学结局。我们纳入了151例患者，分别将其中75例和76例分配到7天疗程组和直至分娩组。按方案进行分析。
在排除失访病例和违反方案的病例后，比较了63例（7天疗程）和61例（直至分娩疗程）早产胎膜早破患者及其婴儿。两组的妊娠结局，包括分娩时的孕周和从胎膜破裂到分娩的间隔时间，均无显著差异。在新生儿结局方面，两组间支气管肺发育不良、脑室内出血、早产儿视网膜病变、坏死性小肠结肠炎和确诊的新生儿败血症无差异。然而，直至分娩组的呼吸窘迫综合征发生率（32.8%对50.8%；P = 0.039）和新生儿综合发病率（34.4%对53.9%；P = 0.026）低于7天疗程组。在对产妇年龄、双胎妊娠、产前糖皮质激素治疗、分娩时的孕周、从胎膜破裂到分娩的间隔时间和临床绒毛膜羊膜炎进行多变量分析后，这种差异仍具有统计学意义。对存活出院婴儿中的71.4%进行了婴儿神经学结局评估，两组间无差异。
总体而言，早产胎膜早破患者使用头孢唑林和克拉霉素直至分娩的疗程比7天疗程导致的新生儿综合发病率和呼吸窘迫综合征发生率更低，且两种疗程的个体新生儿发病率和婴儿神经学结局相似。
