Passive Immunization During Pregnancy for Congenital Cytomegalovirus Infection

N Engl J Med. 2005 Sep 29;353(13):1350-62. doi: 10.1056/NEJMoa043337.


Background: Currently, there is no effective intervention for a primary cytomegalovirus (CMV) infection during pregnancy.

Methods: We studied pregnant women with a primary CMV infection. The therapy group comprised women whose amniotic fluid contained either CMV or CMV DNA and who were offered intravenous CMV hyperimmune globulin at a dose of 200 U per kilogram of maternal weight. A prevention group, consisting of women with a recent primary infection before 21 weeks' gestation or who declined amniocentesis, was offered monthly hyperimmune globulin (100 U per kilogram intravenously).

Results: In the therapy group, 31 women received hyperimmune globulin, only 1 (3 percent) of whom gave birth to an infant with CMV disease (symptomatic at birth and handicapped at two or more years of age), as compared with 7 of 14 women who did not receive hyperimmune globulin (50 percent). Thus, hyperimmune globulin therapy was associated with a significantly lower risk of congenital CMV disease (adjusted odds ratio, 0.02; 95 percent confidence interval, -infinity to 0.15; P<0.001). In the prevention group, 37 women received hyperimmune globulin, 6 (16 percent) of whom had infants with congenital CMV infection, as compared with 19 of 47 women (40 percent) who did not receive hyperimmune globulin. Thus, hyperimmune globulin therapy was associated with a significantly lower risk of congenital CMV infection (adjusted odds ratio, 0.32; 95 percent confidence interval, 0.10 to 0.94; P=0.04). Hyperimmune globulin therapy significantly (P<0.001) increased CMV-specific IgG concentrations and avidity and decreased natural killer cells and HLA-DR+ cells and had no adverse effects.

Conclusions: Treatment of pregnant women with CMV-specific hyperimmune globulin is safe, and the findings of this nonrandomized study suggest that it may be effective in the treatment and prevention of congenital CMV infection. A controlled trial of this agent may now be appropriate.

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • Adult
  • Amniotic Fluid / virology
  • Analysis of Variance
  • Cytomegalovirus / genetics
  • Cytomegalovirus / isolation & purification
  • Cytomegalovirus Infections / congenital
  • Cytomegalovirus Infections / prevention & control
  • Cytomegalovirus Infections / therapy*
  • DNA, Viral / analysis
  • Female
  • Fetal Diseases / prevention & control
  • Fetal Diseases / therapy*
  • HLA-DR Antigens
  • Humans
  • Immunization, Passive*
  • Immunoglobulins / therapeutic use*
  • Immunoglobulins, Intravenous
  • Infant, Newborn
  • Killer Cells, Natural
  • Logistic Models
  • Lymphocyte Count
  • Male
  • Pregnancy
  • Pregnancy Complications, Infectious / therapy*
  • Prospective Studies


  • DNA, Viral
  • HLA-DR Antigens
  • Immunoglobulins
  • Immunoglobulins, Intravenous
  • cytomegalovirus-specific hyperimmune globulin