A Trial of Hyperimmune Globulin to Prevent Congenital Cytomegalovirus Infection

Publication Description
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 infon. 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.).

Primary Author
Hughes,B. L.
Clifton,R. G.
Rouse,D. J.
Saade,G. R.
Dinsmoor,M. J.
Reddy,U. M.
Pass,R.
Allard,D.
Mallett,G.
Fette,L. M.
Gyamfi-Bannerman,C.
Varner,M. W.
Goodnight,W. H.
Tita,A. T. N.
Costantine,M. M.
Swamy,G. K.
Gibbs,R. S.
Chien,E. K.
Chauhan,S. P.
El-Sayed,Y. Y.
Casey,B. M.
Parry,S.
Simhan,H. N.
Napolitano,P. G.
Macones,G. A.
Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network

Author Address
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(TRUNCATED)

Volume
385

Issue
5

Start Page
436

Other Pages
444

Publisher
Massachusetts Medical Society

Author Address
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(TRUNCATED)

PMID
34320288



Reference Type
Journal Article

Periodical Full
The New England journal of medicine

Publication Year
2021

Publication Date
29-Jul

Place of Publication
United States

ISSN/ISBN
1533-4406

Document Object Index
10.1056/NEJMoa1913569 [doi]

Accession Number
PMID: 34320288