巨细胞病毒免疫球蛋白预防先天性巨细胞病毒感染的临床试验
A Trial of Hyperimmune Globulin to Prevent Congenital Cytomegalovirus Infection.
机构信息
From the Department of Obstetrics and Gynecology, Brown University, Providence, RI (B.L.H., D.J.R., D.A.); George Washington University Biostatistics Center, Washington, DC (R.G.C., L.M.F.); the University of Texas Medical Branch, Galveston (G.R.S.), the University of Texas Health Science Center at Houston, Children's Memorial Hermann Hospital, Houston (S.P.C.), and the University of Texas Southwestern Medical Center, Dallas (B.M.C.); Northwestern University, Chicago (M.J.D., G.M.); Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD (U.M.R.); Columbia University, New York (C.G.-B.); the University of Utah Health Sciences Center, Salt Lake City (M.W.V.); the University of North Carolina at Chapel Hill, Chapel Hill (W.H.G.), and Duke University, Durham (G.K.S.) - both in North Carolina; the Department of Pediatrics (R.P.), University of Alabama at Birmingham (A.T.N.T.), Birmingham; Ohio State University, Columbus (M.M.C.), the University of Colorado School of Medicine, Anschutz Medical Campus, Aurora (R.S.G.); Case Western Reserve University, Cleveland (E.K.C.); Stanford University, Stanford, CA (Y.Y.E.-S.); the University of Pennsylvania, Philadelphia (S.P.), and the University of Pittsburgh, Pittsburgh (H.N.S.); Madigan Army Medical Center, Joint Base Lewis-McChord, WA (P.G.N.); and Washington University, St. Louis (G.A.M.).
出版信息
N Engl J Med. 2021 Jul 29;385(5):436-444. doi: 10.1056/NEJMoa1913569.
BACKGROUND
Primary cytomegalovirus (CMV) infection during pregnancy carries a risk of congenital infection and possible severe sequelae. There is no established intervention for preventing congenital CMV infection.
METHODS
In this multicenter, double-blind trial, pregnant women with primary CMV infection diagnosed before 24 weeks' gestation were randomly assigned to receive a monthly infusion of CMV hyperimmune globulin (at a dose of 100 mg per kilogram of body weight) or matching placebo until delivery. The primary outcome was a composite of congenital CMV infection or fetal or neonatal death if CMV testing of the fetus or neonate was not performed.
RESULTS
From 2012 to 2018, a total of 206,082 pregnant women were screened for primary CMV infection before 23 weeks of gestation; of the 712 participants (0.35%) who tested positive, 399 (56%) underwent randomization. The trial was stopped early for futility. Data on the primary outcome were available for 394 participants; a primary outcome event occurred in the fetus or neonate of 46 of 203 women (22.7%) in the group that received hyperimmune globulin and of 37 of 191 women (19.4%) in the placebo group (relative risk, 1.17; 95% confidence interval [CI] 0.80 to 1.72; P = 0.42). Death occurred in 4.9% of fetuses or neonates in the hyperimmune globulin group and in 2.6% in the placebo group (relative risk, 1.88; 95% CI, 0.66 to 5.41), preterm birth occurred in 12.2% and 8.3%, respectively (relative risk, 1.47; 95% CI, 0.81 to 2.67), and birth weight below the 5th percentile occurred in 10.3% and 5.4% (relative risk, 1.92; 95% CI, 0.92 to 3.99). One participant in the hyperimmune globulin group had a severe allergic reaction to the first infusion. Participants who received hyperimmune globulin had a higher incidence of headaches and shaking chills while receiving infusions than participants who received placebo.
CONCLUSIONS
Among pregnant women, administration of CMV hyperimmune globulin starting before 24 weeks' gestation did not result in a lower incidence of a composite of congenital CMV infection or perinatal death than placebo. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Center for Advancing Translational Sciences; ClinicalTrials.gov number, NCT01376778.).
背景
孕妇原发性巨细胞病毒（CMV）感染有导致先天性感染和可能出现严重后遗症的风险。目前尚无预防 CMV 先天性感染的既定干预措施。
方法
在这项多中心、双盲试验中，在妊娠 24 周前诊断为原发性 CMV 感染的孕妇被随机分配每月接受一次 CMV 免疫球蛋白（剂量为 100 毫克/千克体重）或匹配的安慰剂输注，直至分娩。主要结局是胎儿或新生儿如果未进行 CMV 检测，则发生先天性 CMV 感染或胎儿或新生儿死亡的复合结局。
结果
2012 年至 2018 年，共有 206082 名孕妇在妊娠 23 周前筛查原发性 CMV 感染；在 712 名（0.35%）检测结果阳性的参与者中，有 399 名（56%）进行了随机分组。由于无效，试验提前终止。394 名参与者有主要结局数据；在接受免疫球蛋白组中，203 名妇女中有 46 名（22.7%）和安慰剂组中 191 名妇女中有 37 名（19.4%）的胎儿或新生儿发生了主要结局事件（相对风险，1.17；95%置信区间 [CI]，0.80 至 1.72；P=0.42）。免疫球蛋白组中 4.9%的胎儿或新生儿死亡，安慰剂组中 2.6%（相对风险，1.88；95%CI，0.66 至 5.41），早产分别为 12.2%和 8.3%（相对风险，1.47；95%CI，0.81 至 2.67），出生体重低于第 5 百分位分别为 10.3%和 5.4%（相对风险，1.92；95%CI，0.92 至 3.99）。免疫球蛋白组中有 1 名参与者首次输注时发生严重过敏反应。接受免疫球蛋白治疗的参与者在接受输注时头痛和寒战的发生率高于接受安慰剂的参与者。
结论
在孕妇中，在妊娠 24 周前开始使用 CMV 免疫球蛋白治疗并未导致先天性 CMV 感染或围产期死亡的复合发生率低于安慰剂。（由美国国立儿童健康与人类发育研究所和国家转化医学推进中心资助；临床试验.gov 编号，NCT01376778。）
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