Baby steps
Pediatrics Nationwide magazine | Spring/Summer 2014
By Kelli Whitlock Burton
Clinicians and scientists have been studying necrotizing enterocolitis, or NEC, for decades and here’s what they know for sure: Some premature infants get it. Some don’t. Some who get it need surgery. Some don’t. Some who get it will survive. Some won’t. The ability to predict disease severity remains, researchers say, frustratingly elusive.
“The biggest challenge with NEC is that you’ve got a whole neonatal intensive care unit full of preemies and only a few out of 100 are going to get it and you don’t know which ones,” says Lawrence Moss, MD, surgeon-in-chief at Nationwide Children’s Hospital and a founding member of a multicenter research consortium that’s studying NEC, an infection and inflammation of the intestinal walls. About 2,000 to 4,000 infants get the disease each year, making it the most common gastrointestinal illness in neonatal intensive care units. NEC is either managed with medicine and diet or with surgery, depending on severity.
“If we could figure out which babies with NEC are going to progress and need surgery and which ones are likely to do well with medical management,” Dr. Moss says, “we’d have a much better chance of helping these patients.”
The consortium has taken the first step in that direction by developing an algorithm to predict disease severity that uses both biologic and clinical markers. In a series of studies published late last year, the team identified seven protein biomarkers found in urine that are either up- or down-regulated in patients with NEC. They also created a checklist of 27 risk factors to help predict disease progression.
They analyzed urine samples for the biomarkers and calculated risk factors for 119 premature infants at five hospitals around the country. Looking only at clinical criteria, the researchers accurately predicted disease severity just 40 percent of the time. But when they combined the presence of the proteins with the risk factors, their prediction rate rose to 100 percent.
“The diagnosis of NEC is very subjective, so having an objective test that could catch the disease early could have a meaningful impact on how babies are treated,” says Karl Sylvester, MD, an associate professor of surgery at Lucile Packard Children’s Hospital in Palo Alto, Calif., and lead author of the studies. “We are continuing to evaluate molecular markers that would speak to an infant’s predisposition for disease.”
These studies offer a snapshot of the proteins at one stage in each patient’s disease. The next step will be to look at protein levels over the course of the illness, information that could help scientists pinpoint what triggers NEC in the first place.