A Trial of Hyperimmune Globulin to Prevent Congenital Cytomegalovirus Infection

N Engl J Med. 2021 Jul 29;385(5):436-444. doi: 10.1056/NEJMoa1913569.

Abstract

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.).

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cytomegalovirus Infections / congenital*
  • Cytomegalovirus Infections / drug therapy
  • Cytomegalovirus Infections / mortality
  • Cytomegalovirus Infections / prevention & control
  • Double-Blind Method
  • Female
  • Fetal Death / etiology
  • Fetal Death / prevention & control
  • Fetal Diseases / prevention & control
  • Humans
  • Immunoglobulins, Intravenous / therapeutic use*
  • Incidence
  • Infant
  • Infant Mortality
  • Infant, Newborn
  • Infectious Disease Transmission, Vertical / prevention & control
  • Infusions, Intravenous
  • Pregnancy
  • Pregnancy Complications, Infectious / drug therapy*
  • Treatment Failure

Substances

  • Immunoglobulins, Intravenous
  • cytomegalovirus-specific hyperimmune globulin

Associated data

  • ClinicalTrials.gov/NCT01376778