Nancy A. Melville

June 07, 2012

June 7, 2012 (Thessaloniki, Greece) — About 9% of children with congenital cytomegalovirus infection (CMV) develop moderate to severe outcomes; however, only a small percentage of those who are asymptomatic at birth have disease progression after age 2, even if they develop symptoms before age 2, according to a large study presented here at the European Society for Paediatric Infectious Diseases 30th Annual Meeting.

The findings come from 2 studies that looked at more than 50,000 births from 1977 to 1986 — one conducted in Malmö, Sweden, and the other conducted in London, United Kingdom.

The researchers identified 176 congenitally infected infants — 76 (4.6 per 1000 births) in Sweden and 100 (3.2 per 1000 births) in the United Kingdom. They also selected 214 control subjects for the study. Subjects were followed until age 5.

Examination indicated that 5% (9 of 176) of neonates with congenital CMV were symptomatic. Symptoms included hepatomegaly or splenomegaly, tachypnea, and hypertonia or microcephaly.

Among the children followed until age 5, 83% (126 of 151) had no developmental problems, 7% had mild problems, 3% had moderate problems, and 6% had severe impairment (P = .36).

Among children who were symptomatic neonatally, 56% (5 of 9) had some impairment, as did 14% (20 of 142) of those who were asymptomatic (P = .007).

"Interestingly, all of the moderate to severe complications were identified in the first year of life; only mild complications were reported later on," said lead author Claire L. Townsend, PhD, from the Medical Research Council Centre of Epidemiology for Child Health, University College London Institute of Child Health in the United Kingdom.

Dr. Townsend noted that at least half of the children with moderate to severe complications were born to mothers who had preexisting immunity. The mothers of 8 of 14 children with moderate to severe outcomes had probable or confirmed nonprimary infection.

In all of the patients, serious outcomes were identified by age 2; only 3 children had mild developmental impairment that was first identified after age 2. Four control subjects had sequelae.

Earlier Studies of Long-term Sequelae

Population-based studies indicate that the incidence of congenital CMV is about 3 to 5 per 1000 births, but the incidence can be over 1% in some populations, Dr. Townsend noted.

The disease can cause childhood disability (including sensorineural hearing loss), motor impairment (such as cerebral palsy), and cognitive and visual problems.

Dr. Townsend explained that according to previous studies, up to 85% to 90% of children born with congenital CMV tend to be asymptomatic at birth; of those, about 10% to 15% go on to develop long-term sequelae. Patients who are symptomatic at birth are much more likely to go on to develop problems, and approximately 40% to 60% develop long-term complications.

These findings are valuable in providing insight into the natural history of CMV and the appropriate comprehensive follow-up, Dr. Townsend said.

"In these 2 studies, we identified very little evidence of progression of disease," she noted. "Even in Western European settings, where maternal prevalence is around 15% to 17%, secondary and nonprimary maternal infection can result in moderate to severe disability."

"These natural history data are important for considering prevention of congenital CMV and the balances of risk and benefits in looking at treatments for CMV," she said.

Results Encouraging, But More Research Needed

"The need to evaluate congenital CMV cases over a long term has been pressing; this study offers valuable insights for the treatment of such cases," according to Paolo Manzoni, MD, from the Department of Neonatology and the Neonatal Intensive Care Unit at S. Anna Hospital in Torino, Italy.

"It is not easy to obtain such long-term data," he told Medscape Medical News. "The findings are not totally consistent with current knowledge and need to be further confirmed, but these are great numbers," he said.

"If supported in additional studies, the findings can help take some of the fear out of the consequences of congenital CMV infection."

The condition is often treated with acyclovir or ganciclovir, but inconsistencies around the world make management a challenge, Dr. Manzoni noted.

"The protocols for a specific regimen in management vary from country to country, so there is more uncertainty," he said. "There are no strong prospective trials assessing the benefits of treating CMV in infants infected since birth, compared with no treatment, so the data are inconsistent and the strategies are not the same at different centers."

Dr. Townsend and Dr. Manzoni have disclosed no relevant financial relationships.

European Society for Paediatric Infectious Diseases (ESPID) 30th Annual Meeting. Presented May 9, 2012.

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