In experiments with mice, infection with a common virus that can be transmitted from mother to fetus before birth significantly worsens necrotizing enterocolitis (NEC), an often fatal complication of premature birth, reports a team led by Johns Hopkins Children’s Center investigators.

The new findings regarding cytomegalovirus (CMV) advance the search for better treatments for NEC — a relatively rare condition but still the most common emergency intestinal complication among preemies. Up to nearly 10% of premature infants develop NEC, a disease characterized by severe inflammation of the intestinal lining that ultimately kills this tissue. About a third of babies with NEC die from it, and survival rates have remained unchanged over the past three decades.

“The impact of NEC on premature infants and their families is great, and is made worse by the fact that people often hear about NEC for the first time only after their loved one is diagnosed with it,” says David Hackam, surgeon-in-chief and co-director of  Johns Hopkins Children’s Center.

“Surprisingly, we often don’t actually know what causes NEC in the first place,” he adds. “By identifying its connection with cytomegalovirus infection, we have now identified an important trigger for NEC, which could save the lives of premature infants who develop this condition.”

An estimated 40% – 80% of people worldwide are chronically infected with CMV, a virus in the herpes family that doesn’t usually cause symptoms in healthy people but is a common cause of hearing loss and other organ-damaging birth defects when transmitted from mother to fetus during pregnancy. Fetuses acquire CMV from infected mothers during gestation in 30%–50% of cases.

In a neonatal mouse model of NEC with CMV that Hackam and his colleagues developed, the researchers found that mice harboring CMV had significantly worse intestinal tissue damage and higher mortality rates than those without the virus.

In experiments with mouse tissue, Hackam and team zeroed in on the immune protein toll-like receptor 4 (TLR4). They found that mice genetically altered to produce no TLR4 in their intestines had significantly lower NEC severity even with CMV infection, suggesting that this protein could be a good target for developing drugs against NEC.

If animal and human studies confirm the CMV-NEC connection, another treatment option might be to administer adenosine, commonly sold as a dietary supplement, the scientists report. Adenosine is a precursor of ATP, a molecule that cells use for fuel. When the researchers gave mice with NEC and CMV adenosine, it significantly reduced NEC severity. The team plans to investigate these ideas in future studies.