Common virus wreaks havoc on VLBW infants

Rachel G. Greenberg, MD, MB, MHS

Many problems can arise in very low-birth-weight (VLBW) infants, but one common virus has been shown in a new study to increase hearing and respiratory problems, as well as extend hospital stays after birth.

“Preterm, very low-birth-weight infants who are infected with cytomegalovirus (CMV) after birth are at higher risk for significant morbidity at discharge from the neonatal intensive care unit (NICU),” says Rachel G. Greenberg, MD, MB, MHS, assistant professor of Neonatology at Duke University Medical Center, Durham, North Carolina, and co-author of the study.

The study,¹ published in JAMA Pediatrics, reveals that CMV is associated with a number of lasting effects.

“Historically, cytomegalovirus (CMV) acquired postnatally was thought to have no long-term sequelae for preterm infants,” Greenberg says. “Our study resulted in new findings-that postnatal CMV in preterm, very low-birth-weight (VLBW) infants was associated with increased risk of failed hearing screen, longer length of stay in the NICU, and decreased weight-for-age at discharge. We also confirmed our previous study showing an association between postnatal CMV infection and bronchopulmonary dysplasia.”

CMV packs a punch for preemies

Cytomegalovirus is common enough, infecting as many as 60% to 80% of children by adulthood in developing nations such as the United States. Most children are infected by age 3 years by the virus-a member of the herpesvirus family. Although the virus does not typically cause many symptoms in healthy individuals, it can hit young infants and individuals with weakened immune systems the hardest. It is the leading infectious cause of developmental impairment and hearing loss in the developed world, according to the study.

Historically, CMV was transmitted to hospitalized infants through blood transfusions, but modern healthcare practices have reduced this risk. Today, the most common exposure comes from the breast milk of CMV-infected mothers, as the virus remains in the body for life once an individual is infected. Whereas CMV is known to cause severe illness in VLBW infants, it was not previously believed to have any lasting effects. This study indicates otherwise.

Researchers investigated the effects of the virus in 273 VLBW infants with postnatal CMV compared with the same number of VLBW infants who were not infected with the virus across 302 NICUs between 2002 and 2016.

The research team found that 16.5% of VLBW infants with the virus failed their initial hearing screen compared with 9.2% of healthy VLBW infants. The virus was also associated with VLBW infants having their postnatal age at discharge increased by nearly 12 days, and decreased weights at discharge. The research team also associated the presence of the virus with bronchopulmonary dysplasia, according to the report. Overall, the VLBW infants in the study that were infected with the virus had an 80% relative increase in failing a hearing screen over VLBW infants without the virus.

The study found no increased association, however, between CMV and necrotizing enterocolitis, which Greenberg says is surprising.

“We were somewhat surprised that we did not find an association between postnatal CMV infection and necrotizing enterocolitis in preterm infants. Postnatal CMV infection is known to cause enteritis, and small previous studies have linked postnatal CMV infection to the development of necrotizing enterocolitis,” Greenberg says. “However, we think our finding can be explained by the fact that the incidence of necrotizing enterocolitis was very low in our study because we only considered postnatal infections occurring after the first 21 postnatal days.”

The study is the first to show the association between many of these problems and postnatal CMV, the study notes, and indicates that CMV is an important consideration in neurodevelopmental outcomes for preterm infants.

The study group had a lower overall incidence rate for CMV of 0.4% compared with other estimates of 6.5% across other NICUs, with 1.4% experiencing sepsis-like illness as a result of the virus. Screening for CMV rarely occurs, but rather is done after symptoms develop, the study notes.

Screenings and treatments needed

Greenberg says the study was not designed to investigate treatments but illustrates the need for more research.

“Our study was not designed to study treatment, but our findings underscore the need for prospective studies, ideally with long-term neurodevelopmental follow-up, to fully define the effects of postnatal CMV and evaluate whether antiviral treatment can improve outcomes,” Greenberg says. “The findings highlight the importance of screening for this infection in at-risk preterm infants when there is clinical suspicion. Given that this population of infants is already at high risk for neurodevelopmental impairment, we hope that our study will increase clinicians’ awareness of the long-term sequelae associated with postnatal CMV infection.”

References:

1. Weimer KED, Kelly MS, Permar SR, Clark RH, Greenberg RG. Association of adverse hearing, growth, and discharge age outcomes with postnatal cytomegalovirus infection in infants with very low birth weight. JAMA Pediatr. December 2, 2019. Epub ahead of print. Available at https://jamanetwork.com/journals/jamapediatrics/article-abstract/2755416. Accessed February 4, 2020.