Artificial amniotic fluid aimed at aiding digestion in premature infants

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GAINESVILLE, Fla. — Researchers report the first premature babies to receive an experimental artificial amniotic fluid patented by University of Florida scientists appear to tolerate the solution, which was given orally in hopes it will help the infants’ digestive system develop properly so they can eventually handle regular feedings.

Very-low-birthweight babies, some born nearly four months before their due dates often weighing less than two pounds, are almost universally unable to digest human milk or formula. In their first days or weeks they are fed intravenously, which typically causes their intestines to degenerate from disuse-making feeding even more difficult when they later graduate to breast or bottle.

Ultimately, infants can require surgery to remove damaged portions of the digestive tract. Some become candidates for experimental bowel transplantation or even die. Most develop related problems with lifelong consequences, said Dr. Martha Sola, an assistant professor of pediatrics at UF’s College of Medicine.

“Clearly, in utero their intake is not formula,” said Sola, UF’s liaison for future studies of the artificial amniotic fluid. “So even breast milk, which is much better than artificial formula of any sort, is not what their intestines should be seeing at that physiologic age. This work aims to mimic what the intestines at that age are functionally prepared to handle, which would be amniotic fluid.”

Researchers at UF, the University of South Florida, Shands at UF medical center, Shands Jacksonville and the Arnold Palmer Hospital for Women and Children in Orlando tested the artificial amniotic fluid-a flavorless, colorless, odorless electrolyte-based solution developed at UF known as SAFE START-in 30 preterm babies whose gestational ages ranged from 25 to 31 weeks. Their findings appeared in the October issue of the Annals of Pharmacotherapy.

While in the womb, a fetus swallows amniotic fluid constantly-about 200 to 300 milliliters per kilogram of their weight every day. The growth factors contained in the fluid prompt normal development of the fetal intestine, said Dr. Robert D. Christensen, former chief of neonatology at UF’s College of Medicine and now chairman of pediatrics at USF’s College of Medicine.

“To translate this to somebody our size, it would be like an adult swallowing five gallons of fluid per day,” said Christensen, also physician-in-chief at All Children’ s Hospital in St. Petersburg. “If you were to drink five gallons of something a day you’d have to be constantly swallowing it. That’s what babies do-they constantly swallow amniotic

fluid, and if they don’t, the bowel doesn’t develop. It’s the old adage ‘use it or lose it.’ If you don’t use the intestinal tract, you lose whatever function is present.”

The SAFE START solution has no nutritive or caloric value but contains growth factors essential to normal intestinal development, Christensen said. Animal studies in mice and rats have shown these hormones-granulocyte colony-stimulating factor and erythropoietin-stimulate the growth of villi, the intestine’s fingerlike projections that absorb nutrients from food.

“This is the first such solution that’s been developed-that’s the exciting part,” Christensen said. “Our hypothesis is that by providing them with simulated amniotic fluid, we prevent the intestinal atrophy that otherwise would occur.”

Each year, an estimated 60,000 low-birthweight babies are born in the United States, said Dr. Darlene A. Calhoun, a former UF faculty member who worked with Christensen and others to develop the solution. Researchers have yet to determine the best way to feed these infants, said Calhoun, now the associate chairman for research at USF’s Children’s Research Institute.

“Feeding these babies is a nightmare,” she said. “We lose babies from problems with their gut as a result of feeding. It’s a very complex process; unfortunately, we still don’t know a lot about it.”

In the study, funded in part by the National Institutes of Health and the Children’s Miracle Network, 30 preterm babies were separated into three groups of 10 each. Babies in each group were given varying amounts of the artificial amniotic fluid at room temperature through a small stomach tube or from a bottle every three hours for a three-day period. The maximum amount babies received each day was equivalent to about four teaspoons. Most tolerated the feedings well; only three did not complete all 24 doses. One had extra fluid in the stomach, one developed abdominal distention and a third became ill with an unrelated heart condition.

Researchers plan to seek federal approval to conduct large-scale multicenter studies to test the safety and effectiveness of the artificial amniotic fluid, which is not yet commercially available, Christensen said.

In addition to degeneration of the intestines, prolonged intravenous feedings also place babies at increased risk of infection, which endangers their lives, lengthens hospitalization and hikes health-care costs, Calhoun said. If neonatal intensive care unit stays could be shortened by just one day per patient, the annual savings to the health-care system would approach $250 million just in the United States, she said. The length of these stays is often determined by how well babies gain weight, which hinges on how soon they begin tolerating full feedings.

“We hope that by using the solution we might be able to shorten hospitalization by a couple days,” she said. “The impact is huge, both financially to the health-care system in addition to the outcomes of these really precious babies.”

Recent research advances have translated into major improvements in the care of premature infants, said Dr. Pam Kling, an assistant professor of pediatrics at the University of Wisconsin-Madison.

“But because the mechanisms behind feeding intolerance in premature infants are so difficult to study, we have experienced essentially no advances in treating feeding intolerance,” Kling said. “This study may be a first step.”