COVID-19 Information Read the Latest
Children's Hospital is part of the UPMC family.
Our Sites
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.
Ranked #6 Nationally by U.S. News & World Report.
PITTSBURGH, PA - May 6, 2013 - An ingredient that naturally occurs in breast milk might be used to prevent premature babies from developing a deadly intestinal condition that currently is largely incurable, according to researchers at the University of Pittsburgh School of Medicine and Children's Hospital of Pittsburgh of UPMC in this week's online early edition of the Proceedings of the National Academy of Sciences.
The story begins with a baby who is born too early, meaning before 36 weeks gestation, said senior author David Hackam, M.D., Ph.D., Watson Family Professor of Surgery, Pitt School of Medicine, and co-director of the Fetal Diagnosis and Treatment Center at Children's Hospital. Once stable, typically the baby is fed with formula because often breast milk is not readily available to premature infants.
"Within about 10 days of birth, the baby starts to vomit and a few hours later, the belly becomes distended and discolored," Dr. Hackam said. "It becomes clear that the child has developed a major problem in his or her tummy, and an X-Ray will usually confirm the diagnosis of necrotizing enterocolitis, or NEC, in which the intestinal tissue is dying. We have no choice but to remove the dead parts of the intestine, but despite surgery, half of these preemie babies still die from the condition."
Dr. Hackam and his team noted NEC occurs when the intestines start getting colonized with bacteria, a process that occurs normally after birth. They focused on toll-like receptor 4 (TLR4), an immune protein that is involved in recognizing microbes and which they recently discovered plays a role in gut development. In the current work, Hackam and colleagues found that TLR4 is present in higher amounts in the blood vessel lining in preemies than in full-term babies.
The study shows that unlike normal mice, those bred to lack TLR4 in their blood vessels did not develop NEC in a model designed to induce the condition. The findings indicate that bacteria in the blood activate TLR4 leading to a reduction in nitric oxide, which in turn narrows blood vessels and decreases blood flow, Dr. Hackam said.
"This pathway can be dangerous when the preemie's immature gut becomes inflamed from exposure to the bacteria normally present in the intestine," he said. "Abundant TLR4 triggers a shutdown of the blood supply to the intestine, leading to tissue death or necrosis."
Premature babies who are nursed rather than formula-fed are more likely to survive NEC, so co-author and nitric oxide expert Mark Gladwin, M.D., chief, Division of Pulmonary Allergy and Critical Care Medicine, Pitt School of Medicine, and director of Pitt's Vascular Medicine Institute, and the team took a closer look at the components of breast milk.
They found that breast milk contains high levels of sodium nitrate, which is converted to nitrite by gut bacteria. Nitrite can be directly converted to the vasodilator nitric oxide, which can both protect the intestinal lining and improve blood flow.
"The additional nitrite appears to overcome the effects of TLR4 activation and corrects the blood flow problem," Dr. Gladwin said. "When we gave formula supplemented with a sodium nitrate and nitrite analog to the premature mice, we saw improved blood flow in the intestine, and NEC did not develop."
Drs. Hackam and Gladwin are testing the compound, which is FDA approved for other uses, in other models of NEC with the hope that it could be routinely added to formula fed to premature infants to prevent NEC.
"This condition is frightening for parents and frustrating for doctors because currently there is little we can do to treat it," said Dr. Hackam, a pediatric surgeon. "I look forward to one day putting myself out of business and having a therapy that truly saves these children."
Co-authors of the paper include researchers from the divisions of Pediatric Surgery, Newborn Medicine, and Pathology at Children's Hospital; the Division of Gastroenterology and the departments of Pediatrics, Pathology, and Surgery at Pitt School of Medicine.
The project was funded by National Institutes of Health grants GM078238, DK08752, GM053789, HL098032, HL096973 and HL103455; the Hartwell Foundation; the Institute for Transfusion Medicine; and the Hemophilia Center of Western Pennsylvania. Dr. Gladwin holds a patent for the use of nitrite salts in cardiovascular diseases and consults with Aires Pharmaceuticals.
Anita, Srikameswaran, 412-578-9193, SrikamAV@upmc.edu
Andrea Kunicky, 412-692-6254, andrea.kunicky@chp.edu
Children's Hospital's main campus is located in the Lawrenceville neighborhood. Our main hospital address is:
UPMC Children’s Hospital of Pittsburgh 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? Support the hospital by making a donation online, joining our Heroes in Healing monthly donor program, or visiting our site to learn about the other ways you can give back.