以色列施耐德儿童医疗中心Keren Shahar-Nissan团队研究了万乃洛韦预防孕期母体原发性感染巨细胞病毒垂直传播的疗效。2020年9月12日，该研究发表在《柳叶刀》杂志上。

巨细胞病毒是一种常见的先天性感染，在早期原发性产妇感染后发病率很高。目前尚无有效方法来阻止病毒传染给胎儿。

为了确定万乃洛韦能否防止妊娠早期原发性感染孕妇将巨细胞病毒垂直传播给胎儿，研究组在以色列拉宾医疗中心进行了一项前瞻性、随机、双盲、安慰剂对照试验，招募18岁以上、在妊娠前后或孕早期确诊原发性巨细胞病毒感染的孕妇，将其随机分组，分别接受口服万乃洛韦或安慰剂进行治疗，直到孕21或22周进行羊膜穿刺术。主要终点为巨细胞病毒的垂直传播率。

2015年11月15日至2018年10月8日，研究组共招募了100名患者，排除10名，最终分析包括万乃洛韦组的45例患者（均为单胎）和安慰剂组的45例患者（43例单胎，2对双胞胎）。万乃洛韦组45例羊膜中有5例（11%）巨细胞病毒阳性，安慰剂组47例羊膜中有14例（30%）阳性，组间差异显著。在孕早期有原发性巨细胞病毒感染的受试者中，万乃洛韦组羊膜穿刺的阳性率为11%，显著低于安慰剂组（48%）。两组均未报告临床显著的不良事件。

总之，万乃洛韦可有效降低妊娠早期母体原发性感染后胎儿巨细胞病毒感染的风险。

附：英文原文

Title: Valaciclovir to prevent vertical transmission of cytomegalovirus after maternal primary infection during pregnancy: a randomised, double-blind, placebo-controlled trial

Author: Keren Shahar-Nissan, Joseph Pardo, Orit Peled, Irit Krause, Efraim Bilavsky, Arnon Wiznitzer, Eran Hadar, Jacob Amir

Issue&Volume: 2020/09/12

Abstract:

Background

Cytomegalovirus is a common congenital infection, with high morbidity after an early primary maternal infection. No effective means exist to prevent viral transmission to the fetus. We aimed to investigate whether valaciclovir can prevent vertical transmission of cytomegalovirus to the fetus in pregnant women with a primary infection acquired early in pregnancy.

Methods

This prospective, randomised, double-blind, placebo-controlled trial was done at the Infectious Feto-Maternal Clinic of Rabin Medical Center (Petach Tikvah, Israel). Pregnant women aged 18 years or older, with serological evidence of a primary cytomegalovirus infection acquired either periconceptionally or during the first trimester of pregnancy, were randomly assigned to oral valaciclovir (8 g per day, twice daily) or placebo from enrolment until amniocentesis at 21 or 22 gestational weeks. Randomisation was done separately for participants infected periconceptionally or during the first trimester and was done in blocks of four. Patients and researchers were masked to participant allocation throughout the entire study period. The primary endpoint was the rate of vertical transmission of cytomegalovirus. Statistical analyses were done according to per-protocol principles. The study was registered at ClinicalTrials.gov, NCT02351102.

Findings

Between Nov 15, 2015, and Oct 8, 2018, we enrolled and randomly assigned 100 patients to receive valaciclovir or placebo. Ten patients were excluded, five from each study group; therefore, the final analysis included 45 patients (all singletons) in the valaciclovir group and 45 patients (43 singletons and two sets of twins) in the placebo group. In the valaciclovir group, including both first trimester and periconceptional infections, five (11%) of 45 amniocenteses were positive for cytomegalovirus, compared with 14 (30%) of 47 amniocenteses in the placebo group (p=0·027; odds ratio 0·29, 95% CI 0·09–0·90 for vertical cytomegalovirus transmission). Among participants with a primary cytomegalovirus infection during the first trimester, a positive amniocentesis for cytomegalovirus was significantly less likely in the valaciclovir group (two [11%] of 19 amniocenteses) compared with the placebo group (11 [48%] of 23 amniocenteses; p=0·020. No clinically significant adverse events were reported.

Interpretation

Valaciclovir is effective in reducing the rate of fetal cytomegalovirus infection after maternal primary infection acquired early in pregnancy. Early treatment of pregnant women with primary infection might prevent termination of pregnancies or delivery of infants with congenital cytomegalovirus.

DOI: 10.1016/S0140-6736(20)31868-7

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31868-7/fulltext