Newborn Sleeping

Preemie gut may hinge on amniotic fluid

U. PITTSBURGH (US) — Lack of exposure to amniotic fluid could be the reason that preterm infants are more susceptible to a serious gastrointestinal inflammatory disease.

In an early online report in the Proceedings of the National Academy of Sciences, researchers from the Children’s Hospital of Pittsburgh and University of Pittsburgh School of Medicine show that feeding amniotic fluid to young mice reduced the risk of necrotizing enterocolitis (NEC) in an experimental model, suggesting new therapeutic avenues for warding off the deadly condition.

Senior author David Hackam, professor of surgery at Pitt School of Medicine, and co-director of the Fetal Diagnosis and Treatment Center at Children’s Hospital, notes that NEC is the leading cause of death from gastrointestinal disease in babies, and most commonly affects those who are born six to eight weeks too early. Twelve to 15 percent of all premature babies develop NEC.

“The disease occurs when these tiny babies are about two to three weeks of age,” he said. “At first, they are a little sick, but seem OK. Then, often without warning, they stop tolerating their feeds, their bellies become swollen and, in many cases, they become critically ill within hours. When I operate on them, I see patches of dead intestinal tissue that needs to be removed. It is devastating for families.”

The causes of NEC are not well understood, he adds. In previous research, his team determined that a molecular switch called Toll-lie receptor 4 (TLR4) was turned on in intestinal tissue affected by NEC.

Healthy infants born at term have relatively low levels of TLR4 in the gut. The protein is important in fending off infection because it is involved in the recognition of bacteria, leading the researchers to posit that unlike in healthy newborns, something goes wrong with the TLR4 response when preemies get colonized with normal gut flora.

“One big difference between a 34-week-old baby developing in its mother’s uterus and one in the neonatal intensive care unit is that the first one is floating in and swallowing amniotic fluid,” Hackam says.

“Early delivery means that exposure to the fluid is gone, so we speculated that components of the fluid could help prevent NEC by keeping TLR4 in check.”

In the study, the researchers showed that injecting small amounts of amniotic fluid into the intestine of premature mice, or feeding the fluid to them, stopped NEC from developing. That’s because the fluid is rich in epidermal growth factor (EGF), a wound healing protein; when the researchers removed it from the fluid or blocked or removed the EGF receptor on intestinal cells, amniotic fluid no longer had a protective effect.

“It appears that EGF in amniotic fluid is able to shut off TLR4 activity and prevent NEC,” Hackam says. “Perhaps if we one day banked amniotic fluid after premature delivery, we could give it to newborns at risk for the problem. We also could identify a drug that inhibits TLR4 activity to try to save these babies.”

The research team includes lead author Misty Good, assistant professor of pediatrics at University of Pittsburgh School of Medicine, and others from Children’s Hospital and University of Pittsburgh School of Medicine.

The study was funded by National Institutes of Health, the Children’s Hospital of Pittsburgh Foundation, and the Hartwell Foundation.

More news from University of Pittsburgh: http://www.news.pitt.edu/

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  1. LHoggins

    Could breastmilk protect the gut cells helping to shut off TLR4 activity?

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