CMV hyperimmune globulin during pregnancy does not lower risk of CMV infection, perinatal death: NEJM
USA: The administration of cytomegalovirus (CMV) hyperimmune globulin during pregnancy did not decrease the risk of congenital CMV infection or perinatal death among the offspring of women with primary CMV infection in pregnancy, reveals findings from a placebo-controlled, randomized trial. The findings of the study are published in the New England Journal of Medicine.
It is already known that primary CMV infection during pregnancy increases the risk of congenital infection and possible severe sequelae. It affects as many as 40,000 infants in the US annually and is associated with stillbirth, deafness, neonatal death, and motor and cognitive delay among symptomatic infants and children. Despite this, there is no established intervention for the prevention of congenital CMV infection.
Brenna L. Hughes and colleagues from the USA, therefore, aimed to assess whether CMV hyperimmune globulin prevents congenital CMV among women with evidence of primary infection early in pregnancy.
The trial included pregnant women with primary CMV infection diagnosed before 24 weeks gestation. They were randomly assigned to receive a monthly infusion of CMV hyperimmune globulin (at a dose of 100 mg per kilogram of body weight) or a 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.
A total of 206,082 pregnant women were screened for primary CMV infection before 23 weeks of gestation from 2012 to 2018; of the 712 participants (0.35%) who tested positive, 399 (56%) underwent randomization. The trial was stopped early for futility.
Key findings of the study include:
- Data on the primary outcome were available for 394 participants; a primary outcome event occurred in the fetus or neonate of 22.7% women in the group that received hyperimmune globulin and of 19.4% in the placebo group (relative risk, 1.17).
- 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), preterm birth occurred in 12.2% and 8.3%, respectively (relative risk, 1.47), and birth weight below the 5th percentile occurred in 10.3% and 5.4% (relative risk, 1.92).
- 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.
The 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, concluded the authors.
The study titled, "A Trial of Hyperimmune Globulin to Prevent Congenital Cytomegalovirus Infection," is published in the New England Journal of Medicine.