A Trial of Hyperimmune Globulin to Prevent Congenital Cytomegalovirus Infection

Brenna L Hughes; Rebecca G Clifton; Dwight J Rouse; George R Saade; Mara J Dinsmoor; Uma M Reddy; Robert Pass; Donna Allard; Gail Mallett; Lida M Fette; Cynthia Gyamfi-Bannerman; Michael W Varner; William H Goodnight; Alan T N Tita; Maged M Costantine; Geeta K Swamy; Ronald S Gibbs; Edward K Chien; Suneet P Chauhan; Yasser Y El-Sayed; Brian M Casey; Samuel Parry; Hyagriv N Simhan; Peter G Napolitano; George A Macones; Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal–Fetal Medicine Units Network

doi:10.1056/NEJMoa1913569

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.

Authors

Brenna L Hughes¹, Rebecca G Clifton¹, Dwight J Rouse¹, George R Saade¹, Mara J Dinsmoor¹, Uma M Reddy¹, Robert Pass¹, Donna Allard¹, Gail Mallett¹, Lida M Fette¹, Cynthia Gyamfi-Bannerman¹, Michael W Varner¹, William H Goodnight¹, Alan T N Tita¹, Maged M Costantine¹, Geeta K Swamy¹, Ronald S Gibbs¹, Edward K Chien¹, Suneet P Chauhan¹, Yasser Y El-Sayed¹, Brian M Casey¹, Samuel Parry¹, Hyagriv N Simhan¹, Peter G Napolitano¹, George A Macones¹; Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal–Fetal Medicine Units Network

Collaborators

Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal–Fetal Medicine Units Network:
B Hughes, D Rouse, D Allard, E Werner, J Rousseau, L Beati, J Milano, J Lee, G Saade, A Salazar, L Pacheco, J Patel, D Carlson, K Smith, A Nounes, J DeVolder, G Mallett, W Grobman, A Peaceman, M Dinsmoor, K Paycheck, C Gyamfi-Bannerman, S Bousleiman, R Wapner, V Carmona, M Talucci, M Hoffman, A Vanneman, K Palomares, C Perez, L Plante, C Tocci, D Skupski, R Chan-Akeley, M Varner, K Hill, A Sowles, C Meadows, S Dellerman, L Hansen, S Esplin, W Goodnight, K Clark, J Thorp, S Timlin, C Beamon, H Byers, K Eichelberger, A Moore, A Tita, S Harris, L Harper, J Biggio, M Parks, J Sheppard, M Costantine, A Bartholomew, M Landon, J Iams, C Shellhaas, K Markham, B Rink, C Buhimschi, F Johnson, L Webb, D McKenna, K Fennig, K Snow, G Swamy, T Bishop, J Ferrara, R Gibbs, K Hale, K D Heyborne, J Phipers, E Chien, W Dalton, D Hackney, A Mayle, S Chauhan, F Ortiz, B Sibai, Y El-Sayed, C Willson, N Aziz, D Lyell, A Girsen, K Sherwi, B Casey, L Moseley, J Price, T Thomas, L Fay-Randall, A Sias, M Garcia, S Parry, J Craig, H Simhan, M Bickus, F Facco, M Birsic, P Napolitano, L Imbruglio, E Hemman, J Pates, L Foglia, E Thom, R Clifton, L Fete, L Mele, V L Flowers-Fanomezantsoa, T Boekhoudt, U Reddy, C Spong, S Pagliaro

Affiliation

¹ 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.).

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

A Trial of Hyperimmune Globulin to Prevent Congenital Cytomegalovirus Infection

Authors

Collaborators

Affiliation

Abstract

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MeSH terms

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