Congenital CMV: No Benefit With Hyperimmune Globulin Therapy

Veronica Hackethal, MD

April 03, 2014

Treatment with hyperimmune globulin for primary cytomegalovirus (CMV) infection during pregnancy is no better than placebo, according to a study conducted by researchers in Italy and published in the April 3 issue of the New England Journal of Medicine.

"This controlled study did not show a significant reduction in the rate of transmission of CMV infection among women receiving hyperimmune globulin as compared with women receiving placebo," write Maria Grazia Revello, MD, from the Department of Obstetrics and Gynecology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Policlinico San Matteo, University of Pavia, Italy, and colleagues. "Moreover, this study showed no effect of hyperimmune globulin on the activity of neutralizing antibodies."

Congenital CMV infection affects about 0.6% of all newborns in the United States and European Union and can cause sequelae such as sensorineural hearing loss and cognitive and motor defects in about 20% of those infected, according to the article. Previous studies suggested a reduction in congenital CMV infection and improved infant outcomes among women given hyperimmune globulin during pregnancy.

This phase 2 study, called the Congenital HCMV Infection Prevention (CHIP) trial, used a randomized, placebo-controlled, double-blind design and took place at 11 centers in Italy from June 2009 to November 2011. During the study, 124 pregnant women who acquired primary CMV infection between 5 and 26 weeks' gestation were randomly assigned within 6 weeks of presumably acquiring the infection to receive either hyperimmune globulin or placebo (0.9% saline solution) intravenously. The women received treatments every 4 weeks until 36 weeks' gestation, detection of CMV in the amniotic fluid, or spontaneous termination of pregnancy.

The researchers diagnosed CMV based on seroconversion. Onset of infection was based on clinical symptoms. For asymptomatic seroconversion, the researchers assumed onset to be halfway between the last seronegative serum sample and the first seropositive sample.

Overall transmission rate was 30% (18/61) in the treatment group vs 44% (27/62) in the placebo group (95% confidence interval, −3 - 31 percentage points; P = .13). No significant differences were found between women who transmitted the virus and those who did not for virus-specific antibodies, T-cell-mediated immune response, or viral DNA in the blood. The treatment group had a higher percentage of obstetrical adverse events than placebo, but the difference did not reach statistical significance (13% vs 2%; P = .06).

Clinical outcomes at birth were similar between groups regarding prematurity, low birth weight, and other abnormalities (microcephaly, jaundice, hearing deficits, and other symptoms or birth defects).

The investigators caution that the study may have been too small to show a treatment effect, although 2 ongoing phase 3 trials may do so.

"These findings do not support the explanation that hyperimmune globulin could act by reducing the maternal or placental viral load through a direct neutralization effect," the authors conclude. "[T]reatment with hyperimmune globulin did not significantly modify the course of primary CMV infection during pregnancy."

This research was supported by a grant from Agenzia Italiana del Farmaco. Full conflict-of-interest information is available on the journal's Web site.

New Engl J Med. 2014;370:1316-1326. Abstract

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