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Developing a novel genetic assay to assess premature infants' readiness to feed orally

A new, noninvasive genetic test developed by a Tufts Medical Center researcher will present doctors with strong evidence of when premature babies are ready to feed on their own.

Every year, 500,000 premature infants are born in the United States, and most cannot feed by mouth.  The guidelines of the American Academy of Pediatrics require premature babies to remain in the Neonatal Intensive Care Unit (NICU) until they can feed on their own, either at their mother’s breast or by using a bottle with a special nipple.  Until they reach that milestone, most premature babies must feed passively through a small tube inserted into the stomach.

The inability of most premature babies to feed independently not only delays that magical day when mother and infant go home for the first time, but it also sends financial shockwaves throughout the U.S. health care system. For each day a baby stays in the NICU, the cost is $3,500. Multiply that figure by hundreds of thousands of infants, and annual costs soar to hundreds of millions of dollars annually.

In some cases, complications arise from trying to feed premature babies before they’re ready. These failed attempts lengthen the baby’s stay in the NICU, propelling the already astronomical costs even higher.  Often the cause behind these failed attempts is doctors’ need to rely on experience and judgment to determine oral feeding readiness, using subjective measures such as evaluating alertness, watching how intensely the infant sucks on a pacifier or observing oral motor skills.

Illuminating how babies’ complex feeding systems work helps doctors make real-time decisions

Neonatologist Jill L. Maron, MD, a neonatologist at The Tufts Medical Center in Boston, has witnessed first-hand the limitations of using only subjective measures alone to judge when a premature baby is ready to feed. Dr. Maron also is an investigator at the Mother Infant Research Institute (MIRI) at Tufts Medical Center, where her studies include seeking an objective method to determine oral feeding maturity. The evidence she analyzes is in an infant’s genes, and the genetic information she collects doesn’t even require the prick of a needle; it’s readily available in the baby’s saliva.

Dr. Maron envisions her noninvasive test will produce daily reports on oral feeding maturity that can be used by the baby’s neonatologist.  The test wouldn’t replace the doctor’s clinical judgment; it would supplement judgment with objective results based on analysis of genetic data.

“Our role would be to assess a baby at the bedside with a very safe, simple method and then the clinician would have a readout showing, ‘This is where your baby is today’,” Dr. Maron said. If the baby was not ready to feed, the report would indicate, “’This is where the limitation is; this is why your baby can’t feed.’ And neonatologists could also then use their own clinical judgment whether or not this was a baby they want to feed by mouth,” she added.

It has always been a goal of Dr. Maron’s to bring such diagnostic assays, or tests, into the NICU, where, according to her, the daily, unavoidable question is, ‘Is the baby eating?  Can the baby eat?’ And there’s no test to tell us, ‘Yes or no, and if not, why not?’’” Multiple organ systems are involved in feeding, such as the brain, the muscles of the mouth and throat, the stomach and the sense of smell.  The test results of Dr. Maron’s proposed assay could identify specific neonatal therapies to enhance oral feeding skills that are not fully functioning.

Dr. Maron’s research analyzing saliva samples of premature babies from birth to discharge home identified thousands of genes “…that can really help us understand what these genes are doing and how they’re relating to one another.  That’s when we realized [that on a genetic level] we captured a lot of the biological properties necessary to feed…” From that Eureka moment onward, Dr. Maron has gained the ability to measure the real-time development of interrelated feeding systems.

So far, Dr. Maron has identified dozens of genes that change between non-feeding and feeding states.  She has also found one gene primarily expressed in the hypothalamus, the brain’s hunger driver, which is 95% accurate in showing when a baby is too immature to feed.

Only a small group of researchers have focused on premature oral feeding readiness, and their progress, including Dr. Maron’s, has been made possible only by rapid advances in developmental biology and genetically based technology.  Dr. Maron estimates that honing in on the most predictive genetic feeding biomarkers, developing an effective, bedside assay, and getting FDA approval will take from five to 10 years. She said, “I believe we are just really at the tip of the iceberg of our knowledge.”

Dr. Maron’s test provides far-reaching benefits to babies and the health care system

The test has important benefits to babies, their families, hospitals, and society, according to Dr. Maron.  Her novel approach:
  • Supplements a subjective test that relies solely on a physician’s clinical judgment with an objective one.
  • Is safe, noninvasive, performed at the bedside using the baby’s saliva
  • Uses cutting edge nanotechnology identifying  a handful of genes in a saliva sample to observe the real-time development of complex systems needed for a baby to achieve oral feeding readiness
  • Would potentially decrease healthcare costs by hundreds of millions of dollars a year by discharging babies earlier from the NICU