A Trial of Hyperimmune Globulin to Prevent Congenital Cytomegalovirus Infection.


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
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

436-444

Subventions

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
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Organisme : NICHD NIH HHS
ID : UG1 HD027915
Pays : United States
Organisme : NICHD NIH HHS
ID : UG1 HD087192
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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.

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Auteurs

Brenna L Hughes (BL)

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.).

Rebecca G Clifton (RG)

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.).

Dwight J Rouse (DJ)

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.).

George R Saade (GR)

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.).

Mara J Dinsmoor (MJ)

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.).

Uma M Reddy (UM)

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.).

Robert Pass (R)

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.).

Donna Allard (D)

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.).

Gail Mallett (G)

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.).

Lida M Fette (LM)

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.).

Cynthia Gyamfi-Bannerman (C)

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.).

Michael W Varner (MW)

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.).

William H Goodnight (WH)

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.).

Alan T N Tita (ATN)

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.).

Maged M Costantine (MM)

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.).

Geeta K Swamy (GK)

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.).

Ronald S Gibbs (RS)

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.).

Edward K Chien (EK)

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.).

Suneet P Chauhan (SP)

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.).

Yasser Y El-Sayed (YY)

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.).

Brian M Casey (BM)

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.).

Samuel Parry (S)

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.).

Hyagriv N Simhan (HN)

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.).

Peter G Napolitano (PG)

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.).

George A Macones (GA)

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.).

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