美国阿拉巴马大学伯明翰分校Alan T.N. Tita团队研究了阿奇霉素预防计划顺产妇女败血症或死亡以及新生儿不良结局的效果。2023年2月9日出版的《新英格兰医学杂志》发表了这项成果。

阿奇霉素的使用可减少计划剖宫产妇女的母体感染，但其对计划阴道分娩妇女的影响尚不清楚。分娩时口服阿奇霉素是否会减少母体和后代败血症或死亡的发生率，还需要数据验证。

在这项多国、安慰剂对照的随机试验中，研究组将怀孕28周或以上的分娩妇女和计划阴道分娩的妇女随机分配至单次口服2 g阿奇霉素或安慰剂。两个主要结局分别为产妇败血症或死亡的复合结局，以及死产或新生儿死亡或败血症的复合结局。在中期分析中，数据和安全监测委员会建议为了产妇利益停止试验。

共有29278名女性接受了随机分组。阿奇霉素组产妇败血症或死亡的发生率显著低于安慰剂组（1.6% vs. 2.4%），相对风险为0.67，但死产或新生儿死亡或败血症的发生率相似（10.5% vs. 10.3%），相对风险为1.02。产妇主要结局的差异似乎主要由败血症的发生率（阿奇霉素组为1.5%，安慰剂组为2.3%）驱动，相对风险为0.65；两组全因死亡的发生率为0.1%（相对危险度为1.23）。

新生儿败血症发生率分别为9.8%和9.6%（相对危险度为1.03）。两组死产发生率均为0.4%（相对危险度为1.06）；两组新生儿在出生后4周内的死亡率均为1.5%（相对危险度为1.03）。阿奇霉素与较高的不良事件发生率无关。

研究结果表明，在计划阴道分娩的妇女中，单次口服阿奇霉素可显著降低产妇败血症或死亡的风险，但对新生儿败血症或死亡的影响甚微。

附：英文原文

Title: Azithromycin to Prevent Sepsis or Death in Women Planning a Vaginal Birth | NEJM

Author: Alan T.N. Tita, M.D., Ph.D.,, Waldemar A. Carlo, M.D.,, Elizabeth M. McClure, Ph.D.,, Musaku Mwenechanya, M.D.,, Elwyn Chomba, M.B., Ch.B.,, Jennifer J. Hemingway-Foday, M.P.H.,, Avinash Kavi, M.D.,, Mrityunjay C. Metgud, M.D.,, Shivaprasad S. Goudar, M.D.,, Richard Derman, M.D., M.P.H.,, Adrien Lokangaka, M.D., M.P.H.,, Antoinette Tshefu, M.D., Ph.D., M.P.H.,, Melissa Bauserman, M.D., M.P.H.,, Carl Bose, M.D.,, Poonam Shivkumar, M.D.,, Manju Waikar, M.D.,, Archana Patel, M.D., Ph.D.,, Patricia L. Hibberd, M.D., Ph.D.,, Paul Nyongesa, M.D.,, Fabian Esamai, M.B., Ch.B., M.P.H., Ph.D.,, Osayame A. Ekhaguere, M.B., B.S., M.P.H.,, Sherri Bucher, Ph.D.,, Saleem Jessani, M.B., B.S.,, Shiyam S. Tikmani, M.B., B.S.,, Sarah Saleem, M.B., B.S.,, Robert L. Goldenberg, M.D.,, Sk M. Billah, M.P.H.,, Ruth Lennox, M.B., Ch.B.,, Rashidul Haque, M.D.,, William Petri, M.D.,, Lester Figueroa, M.D.,, Manolo Mazariegos, M.D., M.P.H.,, Nancy F. Krebs, M.D.,, Janet L. Moore, M.S.,, Tracy L. Nolen, D.Ph.,, and Marion Koso-Thomas, M.D., M.P.H.

Issue&Volume: 2023-02-09

Abstract:

Background

The use of azithromycin reduces maternal infection in women during planned cesarean delivery, but its effect on those with planned vaginal delivery is unknown. Data are needed on whether an intrapartum oral dose of azithromycin would reduce maternal and offspring sepsis or death.

Methods

In this multicountry, placebo-controlled, randomized trial, we assigned women who were in labor at 28 weeks’ gestation or more and who were planning a vaginal delivery to receive a single 2-g oral dose of azithromycin or placebo. The two primary outcomes were a composite of maternal sepsis or death and a composite of stillbirth or neonatal death or sepsis. During an interim analysis, the data and safety monitoring committee recommended stopping the trial for maternal benefit.

Results

A total of 29,278 women underwent randomization. The incidence of maternal sepsis or death was lower in the azithromycin group than in the placebo group (1.6% vs. 2.4%), with a relative risk of 0.67 (95% confidence interval [CI], 0.56 to 0.79; P<0.001), but the incidence of stillbirth or neonatal death or sepsis was similar (10.5% vs. 10.3%), with a relative risk of 1.02 (95% CI, 0.95 to 1.09; P=0.56). The difference in the maternal primary outcome appeared to be driven mainly by the incidence of sepsis (1.5% in the azithromycin group and 2.3% in the placebo group), with a relative risk of 0.65 (95% CI, 0.55 to 0.77); the incidence of death from any cause was 0.1% in the two groups (relative risk, 1.23; 95% CI, 0.51 to 2.97). Neonatal sepsis occurred in 9.8% and 9.6% of the infants, respectively (relative risk, 1.03; 95% CI, 0.96 to 1.10). The incidence of stillbirth was 0.4% in the two groups (relative risk, 1.06; 95% CI, 0.74 to 1.53); neonatal death within 4 weeks after birth occurred in 1.5% in both groups (relative risk, 1.03; 95% CI, 0.86 to 1.24). Azithromycin was not associated with a higher incidence in adverse events.

Conclusions

Among women planning a vaginal delivery, a single oral dose of azithromycin resulted in a significantly lower risk of maternal sepsis or death than placebo but had little effect on newborn sepsis or death.

DOI: 10.1056/NEJMoa2212111

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2212111