A Trial of Hyperimmune Globulin to Prevent Congenital Cytomegalovirus Infection.
Adult
Cytomegalovirus Infections
/ congenital
Double-Blind Method
Female
Fetal Death
/ etiology
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
Journal
The New England journal of medicine
ISSN: 1533-4406
Titre abrégé: N Engl J Med
Pays: United States
ID NLM: 0255562
Informations de publication
Date de publication:
29 07 2021
29 07 2021
Historique:
entrez:
28
7
2021
pubmed:
29
7
2021
medline:
19
8
2021
Statut:
ppublish
Résumé
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. 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. 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. 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.).
Sections du résumé
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.).
Identifiants
pubmed: 34320288
doi: 10.1056/NEJMoa1913569
pmc: PMC8363945
mid: NIHMS1729242
doi:
Substances chimiques
Immunoglobulins, Intravenous
0
cytomegalovirus-specific hyperimmune globulin
129L90A25N
Banques de données
ClinicalTrials.gov
['NCT01376778']
Types de publication
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
436-444Subventions
Organisme : NICHD NIH HHS
ID : U10 HD040500
Pays : United States
Organisme : NICHD NIH HHS
ID : U10 HD040544
Pays : United States
Organisme : NICHD NIH HHS
ID : UG1 HD034116
Pays : United States
Organisme : NICHD NIH HHS
ID : UG1 HD040560
Pays : United States
Organisme : NICHD NIH HHS
ID : UG1 HD053097
Pays : United States
Organisme : NICHD NIH HHS
ID : U10 HD040485
Pays : United States
Organisme : NICHD NIH HHS
ID : U10 HD034116
Pays : United States
Organisme : NICHD NIH HHS
ID : UG1 HD068258
Pays : United States
Organisme : NICHD NIH HHS
ID : U10 HD040560
Pays : United States
Organisme : NICHD NIH HHS
ID : U10 HD040545
Pays : United States
Organisme : NICHD NIH HHS
ID : U01 HD036801
Pays : United States
Organisme : NICHD NIH HHS
ID : UG1 HD027869
Pays : United States
Organisme : NICHD NIH HHS
ID : U10 HD068268
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Organisme : NICHD NIH HHS
ID : UG1 HD087230
Pays : United States
Organisme : NICHD NIH HHS
ID : UG1 HD027915
Pays : United States
Organisme : NICHD NIH HHS
ID : UG1 HD087192
Pays : United States
Organisme : NICHD NIH HHS
ID : UG1 HD040544
Pays : United States
Organisme : NICHD NIH HHS
ID : UG1 HD034208
Pays : United States
Organisme : NICHD NIH HHS
ID : UG1 HD040512
Pays : United States
Organisme : Eunice Kennedy Shriver National Institute of Child Health and Human Development
ID : (HD40500, HD36801, HD53097, HD40512, HD40485, HD34
Organisme : NICHD NIH HHS
ID : U10 HD027869
Pays : United States
Organisme : NICHD NIH HHS
ID : U10 HD027915
Pays : United States
Organisme : NICHD NIH HHS
ID : U10 HD068282
Pays : United States
Organisme : NICHD NIH HHS
ID : UG1 HD040545
Pays : United States
Organisme : NICHD NIH HHS
ID : UG1 HD040485
Pays : United States
Organisme : NICHD NIH HHS
ID : UG1 HD068268
Pays : United States
Organisme : NICHD NIH HHS
ID : U10 HD034208
Pays : United States
Organisme : NICHD NIH HHS
ID : U10 HD053097
Pays : United States
Organisme : NICHD NIH HHS
ID : U10 HD068258
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000040
Pays : United States
Organisme : NICHD NIH HHS
ID : UG1 HD040500
Pays : United States
Organisme : NICHD NIH HHS
ID : UG1 HD068282
Pays : United States
Organisme : NICHD NIH HHS
ID : U10 HD040512
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001873
Pays : United States
Organisme : NICHD NIH HHS
ID : U10 HD036801
Pays : United States
Organisme : NICHD NIH HHS
ID : U24 HD036801
Pays : United States
Investigateurs
B Hughes
(B)
D Rouse
(D)
D Allard
(D)
E Werner
(E)
J Rousseau
(J)
L Beati
(L)
J Milano
(J)
J Lee
(J)
G Saade
(G)
A Salazar
(A)
L Pacheco
(L)
J Patel
(J)
D Carlson
(D)
K Smith
(K)
A Nounes
(A)
J DeVolder
(J)
G Mallett
(G)
W Grobman
(W)
A Peaceman
(A)
M Dinsmoor
(M)
K Paycheck
(K)
C Gyamfi-Bannerman
(C)
S Bousleiman
(S)
R Wapner
(R)
V Carmona
(V)
M Talucci
(M)
M Hoffman
(M)
A Vanneman
(A)
K Palomares
(K)
C Perez
(C)
L Plante
(L)
C Tocci
(C)
D Skupski
(D)
R Chan-Akeley
(R)
M Varner
(M)
K Hill
(K)
A Sowles
(A)
C Meadows
(C)
S Dellerman
(S)
L Hansen
(L)
S Esplin
(S)
W Goodnight
(W)
K Clark
(K)
J Thorp
(J)
S Timlin
(S)
C Beamon
(C)
H Byers
(H)
K Eichelberger
(K)
A Moore
(A)
A Tita
(A)
S Harris
(S)
L Harper
(L)
J Biggio
(J)
M Parks
(M)
J Sheppard
(J)
M Costantine
(M)
A Bartholomew
(A)
M Landon
(M)
J Iams
(J)
C Shellhaas
(C)
K Markham
(K)
B Rink
(B)
C Buhimschi
(C)
F Johnson
(F)
L Webb
(L)
D McKenna
(D)
K Fennig
(K)
K Snow
(K)
G Swamy
(G)
T Bishop
(T)
J Ferrara
(J)
R Gibbs
(R)
K Hale
(K)
K D Heyborne
(KD)
J Phipers
(J)
E Chien
(E)
W Dalton
(W)
D Hackney
(D)
A Mayle
(A)
S Chauhan
(S)
F Ortiz
(F)
B Sibai
(B)
Y El-Sayed
(Y)
C Willson
(C)
N Aziz
(N)
D Lyell
(D)
A Girsen
(A)
K Sherwi
(K)
B Casey
(B)
L Moseley
(L)
J Price
(J)
T Thomas
(T)
L Fay-Randall
(L)
A Sias
(A)
M Garcia
(M)
S Parry
(S)
J Craig
(J)
H Simhan
(H)
M Bickus
(M)
F Facco
(F)
M Birsic
(M)
P Napolitano
(P)
L Imbruglio
(L)
E Hemman
(E)
J Pates
(J)
L Foglia
(L)
E Thom
(E)
R Clifton
(R)
L Fete
(L)
L Mele
(L)
V L Flowers-Fanomezantsoa
(VL)
T Boekhoudt
(T)
U Reddy
(U)
C Spong
(C)
S Pagliaro
(S)
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2021 Massachusetts Medical Society.
Références
Clin Infect Dis. 2006 Oct 15;43(8):994-1000
pubmed: 16983610
Pediatrics. 2010 Feb;125(2):e214-24
pubmed: 20100760
N Engl J Med. 1992 Mar 5;326(10):663-7
pubmed: 1310525
J Matern Fetal Neonatal Med. 2019 Feb;32(4):617-625
pubmed: 28978246
Vox Sang. 2015 Jul;109(1):71-8
pubmed: 25766313
Matern Child Health J. 1999 Dec;3(4):225-31
pubmed: 10791363
JAMA. 1986 Oct 10;256(14):1904-8
pubmed: 3020264
J Clin Virol. 2008 Mar;41(3):192-7
pubmed: 18054840
Clin Obstet Gynecol. 1982 Sep;25(3):563-76
pubmed: 6290121
Rev Med Virol. 2007 Jul-Aug;17(4):253-76
pubmed: 17579921
Ultrasound Obstet Gynecol. 2019 Mar;53(3):383-389
pubmed: 29947159
Rev Med Virol. 2007 Sep-Oct;17(5):355-63
pubmed: 17542052
N Engl J Med. 2014 Apr 3;370(14):1316-26
pubmed: 24693891
Prenat Diagn. 2008 Jun;28(6):512-7
pubmed: 18509871
N Engl J Med. 2005 Sep 29;353(13):1350-62
pubmed: 16192480