A formula for survival

An experimental synthetic ''amniotic'' fluid shows promising results in helping premature infants thrive.

By SUSAN ASCHOFF, Times Staff Writer
© St. Petersburg Times
published December 24, 2002

Cathy Zenko could not have known her tiny son, born 12 weeks early and weighing 21/4 pounds, would advance the cause of science.

Zenko was just beginning to sort out the tubes and monitors snaking from her day-old baby when two doctors approached her at a Gainesville hospital to ask if Tyler could receive a teaspoon or two of an experimental liquid to keep his digestive tract healthy.

Tyler Zenko is now 2 1/2 years old and thriving.

The Alachua boy also is Patient 1 in the newly published study titled "Tolerance of Simulated Amniotic Fluid in Premature Neonates."

"Thank you, Tyler. You were the first," wrote study co-author Dr. Darlene Calhoun on the copy she sent last week to his mom.

Of the 4-million babies born in the United States every year, 60,000 are delivered prematurely, after 32 weeks or less in the womb and weighing under 3 pounds. A ventilator helps them breathe, an incubator keeps them warm and a tube stuck in a vein gives them nourishment.

But even as medical advances keep preemies alive, doctors still do not know what causes many of their physical difficulties.

Calhoun and Dr. Robert Christensen, St. Petersburg neonatologists specializing in blood disorders, unexpectedly found one of those answers five years ago while working at the University of Florida. They discovered receptors in the small intestine for two growth factors found in amniotic fluid. Since babies swallow amniotic fluid when in the womb, perhaps preemies continued to need it.

"We basically uncovered a piece of what nature does for these babies and we think it should be duplicated," Christensen says.

Christensen is chairman of the pediatrics department at the University of South Florida School of Medicine. He and Calhoun moved to USF-St. Petersburg last year to fill distinguished chairs in pediatrics.

Their patients are the youngest in All Children's Hospital.

Preemies cannot digest formula or breast milk. Many cannot suck or swallow properly. In their first days or weeks of life, they are fed intravenously. With no nourishment passing through the digestive tract, deterioration of the small intestine begins within hours of birth and impedes feeding when the baby is stronger.

In the womb, a fetus does not swallow its food, either. Nutrients are delivered through the placenta and umbilical cord.

But the fetus drinks amniotic fluid -- 8 to 10 ounces per kilogram of body weight per day, says Christensen. That's the equivalent of 5 gallons for an adult.

"Amniotic fluid is thought of as just being a cushion for the baby. In fact, it's hugely dynamic," he says.

Years before Tyler Zenko became Patient 1, Christensen and Calhoun examined the small intestine, particularly the fingerlike projections called villi that line the interior and absorb nutrients and water needed by the body. Here they found their clue. Receptors on the villi matched two growth factors found in amniotic fluid.

They could stimulate growth of the villi and keep preemies' intestines healthy, they theorized, if they gave them amniotic fluid outside the womb.

Producing synthetic amniotic fluid proved relatively simple, says Christensen. The growth factors, granulocyte colony-stimulating factor and erythropoietin, have been synthesized for years to treat certain kinds of anemia and low white-blood-cell counts.

For preemies, the proportions were concentrated in an odorless, colorless, flavorless solution patented by UF and called Safe Start.

"We wanted to call it Gator SAFE," says Christensen, referring to UF's popular sports drink Gatorade.

Researchers at UF and Shands at UF medical center, USF and Tampa General Hospital, Shands Jacksonville, and the Arnold Palmer Hospital for Women and Children in Orlando tested Safe Start on 30 premature infants ages 25 to 31 weeks.

They began with Tyler Zenko in June 2000.

"The first morning when I got to see him (after he was born), Dr. Christensen and Dr. Calhoun were there" in the neonatal unit, Cathy Zenko says. Her son was on a ventilator and fighting a lung infection. Still, she and her husband, Frank Zenko, agreed to the doctors' request that Tyler receive yet another treatment, this one experimental.

"It's such a small amount," she said of the Safe Start fed to Tyler through a tube down his throat.

The babies in the study were divided into three groups and given from 1 to 5 teaspoons of Safe Start per day for three days. Researchers watched for adverse reactions, from diarrhea and bloating to blood-pressure changes. Three babies were taken off the solution, largely because of unrelated complications. The remainder showed no ill effects.

Calhoun and Christensen are seeking funding for further testing, most likely on monkeys, to document Safe Start's positive effect on the intestines. They hope the patented solution will someday be commercially available to all preemies.

"Preemies will be looking at shorter time in the hospital," predicts Christensen. The length of their high-cost stay is largely determined by an infant's ability to steadily gain weight.

Cathy Zenko says she will save the published report for Tyler, so he can one day learn about his early brush with invention.

"There was never a moment to think," she adds, "that he wasn't going to make it."

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