Children's Hospital is part of the UPMC family.
Be safe anytime, anywhere.
To find a pediatrician or pediatric specialist, please call 412-692-7337 or search our directory.
A resource for our network of referring physicians.
For more information about research, please call our main office at 412-692-6438.
Children's Hospital is ranked One of America's Best Children's Hospitals.
PITTSBURGH, PA - June 25, 2012 - Lack of exposure to amniotic fluid could be the reason that preterm infants are more susceptible to the gastrointestinal inflammatory disease known as necrotizing enterocolitis (NEC), according to researchers at Children’s Hospital of Pittsburgh of UPMC and the University of Pittsburgh School of Medicine. In an early online report in the Proceedings of the National Academy of Sciences, they show that feeding amniotic fluid to young mice reduced the risk of NEC in an experimental model, suggesting new therapeutic avenues for warding off the deadly condition.
Senior author David Hackam, M.D., Ph.D., Watson Family Professor of Surgery, Department of Surgery, Pitt School of Medicine, and co-director of the Fetal Diagnosis and Treatment Center at Children’s Hospital, noted 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 added. 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,” Dr. Hackam said. “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,” Dr. Hackam said. “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, M.D., assistant professor of pediatrics, 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 grants R01GM078238 and RO1DK08752, and by the Children’s Hospital of Pittsburgh Foundation and the Hartwell Foundation.
Anita Srikameswaran, 412-578-9193, SrikamAV@upmc.edu
Marc Lukasiak, 412-692-7919, Marc.Lukasiak@chp.edu
Children's Hospital's main campus is located in the Lawrenceville neighborhood. Our main hospital address is:
Children’s Hospital of Pittsburgh of UPMC
One Children’s Hospital Way
4401 Penn Ave.
Pittsburgh, PA 15224
In addition to the main hospital, Children's has many convenient locations in other neighborhoods throughout the greater Pittsburgh region.
With myCHP, you can request appointments, review test results, and more.
For questions about a hospital bill call:
To pay your bill online, please visit UPMC's online bill payment system.
Interested in giving to Children's Hospital? Visit Children's Hospital of Pittsburgh Foundation's website to make a donation online.