Despite attempts to find an intervention to prevent congenital cytomegalovirus (CMV) infection during pregnancy, researchers concluded that the administration of CMV hyperimmune globulin initiated before 24 weeks’ gestation did not lower the incidence of infection or perinatal death. Their trial was stopped early for futility, and results are published in The New England Journal of Medicine.
“Congenital cytomegalovirus (CMV) infection affects as many as 40,000 infants in the United States annually and is associated with stillbirth, neonatal death, deafness, and cognitive and motor delay among symptomatic infants and children. Among pregnant women with primary CMV infection, the incidence of fetal infection is estimated to be 35 to 40%, with approximately 10% of infected fetuses having symptoms at birth. Moreover, in approximately 20% of infants who have no evidence of infection at birth, neurologic deficits (most commonly deafness) that are attributable to CMV develop later in life,” wrote Brenna L. Hughes, MD, MSc, of Duke University School of Medicine, Durham, North Carolina, and colleagues from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.
Previous studies assessing the use of CMV hyperimmune globulin for the treatment and prevention of congenital infection in women with primary CMV infection during pregnancy have been inconclusive and inconsistent.
Therefore, Hughes et al conducted this multicenter, double-blind study, and included 394 women who tested positive for primary CMV infection before 23 weeks’ gestation. The primary outcome of the study was a composite of congenital CMV infection or fetal/neonatal death in cases where CMV testing was not done on the fetus/neonate.
The mean age of the women in both groups was 27-28 years, most were non-Hispanic White (64%-65.5%), most were married or living with partners (70%-73%), and most were between a mean of 15-16 weeks’ gestation when they were randomized to treatment with either hyperimmune globulin (100 mg/kg) or placebo. Infusions of hyperimmune globulin were administered monthly at a rate of 0.3 ml/kg/h until delivery and increased in increments only if there were no adverse reaction, to a maximum of 1.2 ml/kg/h or 75 ml/h, whichever was lower.
Among the 203 women who received hyperimmune globulin, a primary outcome event occurred in 22.7%, compared with 19.4% of those in the placebo group (RR: 1.17; 95% CI: 0.80-1.72; P=0.42). Researchers also found the following in comparing women treated with hyperimmune globulin vs placebo:
- 4.9% versus 2.6% of fetuses/neonates, respectively, died (RR: 1.88; 95% CI: 0.66-5.41).
- 12.3% versus 8.4% of women experienced a preterm birth (RR: 1.47; 95% CI: 0.81-2.67).
- 10.3% versus 5.4% had birth weight below the 5th percentile (RR: 1.92; 95% CI: 0.92-3.99).
No significant between-group differences were seen in secondary outcomes in mothers, including gestational diabetes, preeclampsia, placental abruption, and cesarean delivery.
A severe allergic reaction to the first infusion occurred in one participant in the hyperimmune group, and women in this group also had a higher incidence of headaches compared with placebo (28.6% versus 19.9%, respectively; RR: 1.44; 95% CI: 1.00-2.05) and shaking chills during infusion (6 versus 0).
“In this placebo-controlled, randomized trial involving women with primary CMV infection during early pregnancy, monthly infusions of CMV hyperimmune globulin did not prevent congenital CMV infection in their offspring. These findings contradict the conclusions of observational studies that suggested significant improvement in outcomes with the administration of CMV hyperimmune globulin,” concluded Hughes and colleagues. They added: “The percentage of women in the placebo group whose fetus or neonate had a primary outcome event (19.4%) was lower than we anticipated, as was the frequency of primary CMV infection among pregnant women screened for the trial. These findings are probably related to the fact that women with evidence of fetal infection at the time of randomization were not eligible for the trial.”
Other study limitations include only one screening of women during pregnancy, the possibility that CMV hyperimmune globulin was given to some participants after their fetuses were already infected, and the evaluation of neonatal outcomes only.
In pregnant women with CMV infection, 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.
This trial was stopped early for futility.
Liz Meszaros, Deputy Managing Editor, BreakingMED™
This study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Center for Advancing Translational Sciences. Behring provided the Cytogam and AlbuRx but had no other role in the trial.
Hughes reported receiving grants from NIH-NICHD during the conduct of the study; and has served on a scientific advisory board for MERCK outside the submitted work.
Cat ID: 190
Topic ID: 79,190,730,190,191,138,192,925