The authors' affiliations are listed in the Appendix.
N Engl J Med. 2014 Apr 3;370(14):1316-26. doi: 10.1056/NEJMoa1310214.
Congenital infection with human cytomegalovirus (CMV) is a major cause of morbidity and mortality. In an uncontrolled study published in 2005, administration of CMV-specific hyperimmune globulin to pregnant women with primary CMV infection significantly reduced the rate of intrauterine transmission, from 40% to 16%.
We evaluated the efficacy of hyperimmune globulin in a phase 2, randomized, placebo-controlled, double-blind study. A total of 124 pregnant women with primary CMV infection at 5 to 26 weeks of gestation were randomly assigned within 6 weeks after the presumed onset of infection to receive hyperimmune globulin or placebo every 4 weeks until 36 weeks of gestation or until detection of CMV in amniotic fluid. The primary end point was congenital infection diagnosed at birth or by means of amniocentesis.
A total of 123 women could be evaluated in the efficacy analysis (1 woman in the placebo group withdrew). The rate of congenital infection was 30% (18 fetuses or infants of 61 women) in the hyperimmune globulin group and 44% (27 fetuses or infants of 62 women) in the placebo group (a difference of 14 percentage points; 95% confidence interval, -3 to 31; P=0.13). There was no significant difference between the two groups or, within each group, between the women who transmitted the virus and those who did not, with respect to levels of virus-specific antibodies, T-cell-mediated immune response, or viral DNA in the blood. The clinical outcome of congenital infection at birth was similar in the two groups. The number of obstetrical adverse events was higher in the hyperimmune globulin group than in the placebo group (13% vs. 2%).
In this study involving 123 women who could be evaluated, treatment with hyperimmune globulin did not significantly modify the course of primary CMV infection during pregnancy. (Funded by Agenzia Italiana del Farmaco; CHIP ClinicalTrials.gov number, NCT00881517; EudraCT no. 2008-006560-11.).
人巨细胞病毒（CMV）先天性感染是发病率和死亡率的主要原因。2005 年发表的一项未对照研究显示，给原发性 CMV 感染的孕妇使用 CMV 特异性高免疫球蛋白，可使宫内传播率从 40%显著降低至 16%。
我们在一项 2 期、随机、安慰剂对照、双盲研究中评估了高免疫球蛋白的疗效。124 例妊娠 5 至 26 周、原发性 CMV 感染孕妇，在感染后 6 周内，随机分为高免疫球蛋白组或安慰剂组，每 4 周 1 次，直至妊娠 36 周或羊水中检测到 CMV。主要终点为出生时或通过羊膜穿刺术诊断的先天性感染。
123 例孕妇可进行疗效分析（安慰剂组 1 例孕妇退出）。高免疫球蛋白组先天性感染率为 30%（61 例孕妇的 18 例胎儿或婴儿），安慰剂组为 44%（62 例孕妇的 27 例胎儿或婴儿）（差异 14 个百分点；95%置信区间为 -3 至 31；P=0.13）。两组间或每组内病毒传播者与未传播者间，病毒特异性抗体、T 细胞介导的免疫应答或血液中病毒 DNA 水平均无显著差异。两组出生时先天性感染的临床结局相似。高免疫球蛋白组产科不良事件发生率高于安慰剂组（13%比 2%）。
在这项纳入 123 例可评估孕妇的研究中，高免疫球蛋白治疗并未显著改变妊娠期原发性 CMV 感染的进程。（由 Agenzia Italiana del Farmaco 资助；CHIP ClinicalTrials.gov 编号，NCT00881517；EudraCT 编号 2008-006560-11。）
