Breast Milk Ingredient Could Prevent Deadly Colitis In Premature Infants
Premature birth can be a life-threatening condition for a newborn, but a new study from the University of Pittsburgh hopes to the tip the odds in favor of survival. It reports the development of a new therapy for a mystifying disease that has plagued neonatal wards for decades.
Nearly 1 in 14 premature babies in the US and Canada develops necrotizing entercolitis (NEC), a disease that causes intestinal tissue to wither away.
"Within about 10 days of birth, the baby starts to vomit and a few hours later, the belly becomes distended and discolored," said senior author Dr. David Hackam, professor of surgery at University of Pittsburgh School of Medicine. "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."
Previous studies have recognized that nourishing premature infants with breast milk reduces a child's chances for developing NEC. However in many cases, breast milk is not readily available, so standard practice is to provide nourishment with baby formula.
Dr. Hackam and his colleagues discovered that the life-saving component of breast milk is tied to the bacteria that reside within the baby's gut. Infants are born without gut bacteria, but are immediately colonized after birth, and breast milk is known to promote this process.
Humans are sometimes described as "planets of microbes," since trillions of bacteria reside within us, many of them beneficial. They can constitute as much as 1 to 3 percent of a person's body mass.
Depriving newborns of breast milk appears to upset the dynamics between "the bacterial settlers" and the neonate intestine, according to the study. It reports that cells in the gut's blood vessels produce a receptor — Toll-like receptor 4 (TLR4) — that is critical to this balance. Dr. Hackam's team found that premature babies have more TLR4 in their intestines than full-term newborns.
Too much TLR4 can trigger a reduction in nitric oxide, a chemical that is essential to blood flow. This subsequently constricts blood flow to the gut and suffocates the organ, which they demonstrated in mouse models of NEC.
They found that breast milk is enriched in sodium nitrate, which is naturally converted by gut bacteria into nitric oxide, which can both protect the intestinal lining and improve blood flow.
"When we gave formula supplemented with a sodium nitrate to the premature mice, we saw improved blood flow in the intestine, and NEC did not develop," said co-author and nitric oxide expert Dr. Mark Gladwin, who is also director of the University of Pittsburgh's Vascular Medicine Institute.
Drs. Hackam and Gladwin are testing the compound, which is FDA approved for other uses, in other models of NEC. They hope that one day it could be routinely added to formula for 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. "I look forward to one day putting myself out of business and having a therapy that truly saves these children."