A randomized trial of hyperimmune globulin to prevent congenital cytomegalovirus

Maria Grazia Revello, Tiziana Lazzarotto, Brunella Guerra, Arsenio Spinillo, Enrico Ferrazzi, Alessandra Kustermann, Secondo Guaschino, Patrizia Vergani, Tullia Todros, Tiziana Frusca, Alessia Arossa, Milena Furione, Vanina Rognoni, Nicola Rizzo, Liliana Gabrielli, Catherine Klersy, Giuseppe Gerna

Research output: Contribution to journalArticle

191 Citations (Scopus)

Abstract

BACKGROUND: Congenital infection with human cytomegalovirus (CMV) is a major cause of morbidity and mortality. In an uncontrolled study published in 2005, administration of CMV-specific hyperimmune globulin to pregnant women with primary CMV infection significantly reduced the rate of intrauterine transmission, from 40% to 16%. METHODS: We evaluated the efficacy of hyperimmune globulin in a phase 2, randomized, placebo-controlled, double-blind study. A total of 124 pregnant women with primary CMV infection at 5 to 26 weeks of gestation were randomly assigned within 6 weeks after the presumed onset of infection to receive hyperimmune globulin or placebo every 4 weeks until 36 weeks of gestation or until detection of CMV in amniotic fluid. The primary end point was congenital infection diagnosed at birth or by means of amniocentesis. RESULTS: A total of 123 women could be evaluated in the efficacy analysis (1 woman in the placebo group withdrew). The rate of congenital infection was 30% (18 fetuses or infants of 61 women) in the hyperimmune globulin group and 44% (27 fetuses or infants of 62 women) in the placebo group (a difference of 14 percentage points; 95% confidence interval, -3 to 31; P = 0.13). There was no significant difference between the two groups or, within each group, between the women who transmitted the virus and those who did not, with respect to levels of virus-specific antibodies, T-cell-mediated immune response, or viral DNA in the blood. The clinical outcome of congenital infection at birth was similar in the two groups. The number of obstetrical adverse events was higher in the hyperimmune globulin group than in the placebo group (13% vs. 2%). CONCLUSIONS: In this study involving 123 women who could be evaluated, treatment with hyperimmune globulin did not significantly modify the course of primary CMV infection during pregnancy.

Original languageEnglish
Pages (from-to)1316-1326
Number of pages11
JournalNew England Journal of Medicine
Volume370
Issue number14
DOIs
Publication statusPublished - 2014

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Globulins
Cytomegalovirus
Placebos
Cytomegalovirus Infections
Infection
Pregnancy
Pregnant Women
Fetus
Parturition
Viruses
Amniocentesis
Viral DNA
Amniotic Fluid
Double-Blind Method
Confidence Intervals
Morbidity
T-Lymphocytes
Mortality
Antibodies

ASJC Scopus subject areas

  • Medicine(all)

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A randomized trial of hyperimmune globulin to prevent congenital cytomegalovirus. / Revello, Maria Grazia; Lazzarotto, Tiziana; Guerra, Brunella; Spinillo, Arsenio; Ferrazzi, Enrico; Kustermann, Alessandra; Guaschino, Secondo; Vergani, Patrizia; Todros, Tullia; Frusca, Tiziana; Arossa, Alessia; Furione, Milena; Rognoni, Vanina; Rizzo, Nicola; Gabrielli, Liliana; Klersy, Catherine; Gerna, Giuseppe.

In: New England Journal of Medicine, Vol. 370, No. 14, 2014, p. 1316-1326.

Research output: Contribution to journalArticle

Revello, MG, Lazzarotto, T, Guerra, B, Spinillo, A, Ferrazzi, E, Kustermann, A, Guaschino, S, Vergani, P, Todros, T, Frusca, T, Arossa, A, Furione, M, Rognoni, V, Rizzo, N, Gabrielli, L, Klersy, C & Gerna, G 2014, 'A randomized trial of hyperimmune globulin to prevent congenital cytomegalovirus', New England Journal of Medicine, vol. 370, no. 14, pp. 1316-1326. https://doi.org/10.1056/NEJMoa1310214
Revello, Maria Grazia ; Lazzarotto, Tiziana ; Guerra, Brunella ; Spinillo, Arsenio ; Ferrazzi, Enrico ; Kustermann, Alessandra ; Guaschino, Secondo ; Vergani, Patrizia ; Todros, Tullia ; Frusca, Tiziana ; Arossa, Alessia ; Furione, Milena ; Rognoni, Vanina ; Rizzo, Nicola ; Gabrielli, Liliana ; Klersy, Catherine ; Gerna, Giuseppe. / A randomized trial of hyperimmune globulin to prevent congenital cytomegalovirus. In: New England Journal of Medicine. 2014 ; Vol. 370, No. 14. pp. 1316-1326.
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abstract = "BACKGROUND: Congenital infection with human cytomegalovirus (CMV) is a major cause of morbidity and mortality. In an uncontrolled study published in 2005, administration of CMV-specific hyperimmune globulin to pregnant women with primary CMV infection significantly reduced the rate of intrauterine transmission, from 40{\%} to 16{\%}. METHODS: We evaluated the efficacy of hyperimmune globulin in a phase 2, randomized, placebo-controlled, double-blind study. A total of 124 pregnant women with primary CMV infection at 5 to 26 weeks of gestation were randomly assigned within 6 weeks after the presumed onset of infection to receive hyperimmune globulin or placebo every 4 weeks until 36 weeks of gestation or until detection of CMV in amniotic fluid. The primary end point was congenital infection diagnosed at birth or by means of amniocentesis. RESULTS: A total of 123 women could be evaluated in the efficacy analysis (1 woman in the placebo group withdrew). The rate of congenital infection was 30{\%} (18 fetuses or infants of 61 women) in the hyperimmune globulin group and 44{\%} (27 fetuses or infants of 62 women) in the placebo group (a difference of 14 percentage points; 95{\%} confidence interval, -3 to 31; P = 0.13). There was no significant difference between the two groups or, within each group, between the women who transmitted the virus and those who did not, with respect to levels of virus-specific antibodies, T-cell-mediated immune response, or viral DNA in the blood. The clinical outcome of congenital infection at birth was similar in the two groups. The number of obstetrical adverse events was higher in the hyperimmune globulin group than in the placebo group (13{\%} vs. 2{\%}). CONCLUSIONS: In this study involving 123 women who could be evaluated, treatment with hyperimmune globulin did not significantly modify the course of primary CMV infection during pregnancy.",
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AU - Revello, Maria Grazia

AU - Lazzarotto, Tiziana

AU - Guerra, Brunella

AU - Spinillo, Arsenio

AU - Ferrazzi, Enrico

AU - Kustermann, Alessandra

AU - Guaschino, Secondo

AU - Vergani, Patrizia

AU - Todros, Tullia

AU - Frusca, Tiziana

AU - Arossa, Alessia

AU - Furione, Milena

AU - Rognoni, Vanina

AU - Rizzo, Nicola

AU - Gabrielli, Liliana

AU - Klersy, Catherine

AU - Gerna, Giuseppe

PY - 2014

Y1 - 2014

N2 - BACKGROUND: Congenital infection with human cytomegalovirus (CMV) is a major cause of morbidity and mortality. In an uncontrolled study published in 2005, administration of CMV-specific hyperimmune globulin to pregnant women with primary CMV infection significantly reduced the rate of intrauterine transmission, from 40% to 16%. METHODS: We evaluated the efficacy of hyperimmune globulin in a phase 2, randomized, placebo-controlled, double-blind study. A total of 124 pregnant women with primary CMV infection at 5 to 26 weeks of gestation were randomly assigned within 6 weeks after the presumed onset of infection to receive hyperimmune globulin or placebo every 4 weeks until 36 weeks of gestation or until detection of CMV in amniotic fluid. The primary end point was congenital infection diagnosed at birth or by means of amniocentesis. RESULTS: A total of 123 women could be evaluated in the efficacy analysis (1 woman in the placebo group withdrew). The rate of congenital infection was 30% (18 fetuses or infants of 61 women) in the hyperimmune globulin group and 44% (27 fetuses or infants of 62 women) in the placebo group (a difference of 14 percentage points; 95% confidence interval, -3 to 31; P = 0.13). There was no significant difference between the two groups or, within each group, between the women who transmitted the virus and those who did not, with respect to levels of virus-specific antibodies, T-cell-mediated immune response, or viral DNA in the blood. The clinical outcome of congenital infection at birth was similar in the two groups. The number of obstetrical adverse events was higher in the hyperimmune globulin group than in the placebo group (13% vs. 2%). CONCLUSIONS: In this study involving 123 women who could be evaluated, treatment with hyperimmune globulin did not significantly modify the course of primary CMV infection during pregnancy.

AB - BACKGROUND: Congenital infection with human cytomegalovirus (CMV) is a major cause of morbidity and mortality. In an uncontrolled study published in 2005, administration of CMV-specific hyperimmune globulin to pregnant women with primary CMV infection significantly reduced the rate of intrauterine transmission, from 40% to 16%. METHODS: We evaluated the efficacy of hyperimmune globulin in a phase 2, randomized, placebo-controlled, double-blind study. A total of 124 pregnant women with primary CMV infection at 5 to 26 weeks of gestation were randomly assigned within 6 weeks after the presumed onset of infection to receive hyperimmune globulin or placebo every 4 weeks until 36 weeks of gestation or until detection of CMV in amniotic fluid. The primary end point was congenital infection diagnosed at birth or by means of amniocentesis. RESULTS: A total of 123 women could be evaluated in the efficacy analysis (1 woman in the placebo group withdrew). The rate of congenital infection was 30% (18 fetuses or infants of 61 women) in the hyperimmune globulin group and 44% (27 fetuses or infants of 62 women) in the placebo group (a difference of 14 percentage points; 95% confidence interval, -3 to 31; P = 0.13). There was no significant difference between the two groups or, within each group, between the women who transmitted the virus and those who did not, with respect to levels of virus-specific antibodies, T-cell-mediated immune response, or viral DNA in the blood. The clinical outcome of congenital infection at birth was similar in the two groups. The number of obstetrical adverse events was higher in the hyperimmune globulin group than in the placebo group (13% vs. 2%). CONCLUSIONS: In this study involving 123 women who could be evaluated, treatment with hyperimmune globulin did not significantly modify the course of primary CMV infection during pregnancy.

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