BY KRISTA CONGER

Doctors should resume their vigilance in screening newborn infants for jaundice to combat the rising incidence of brain damage and death caused by severe forms of the disorder, say researchers at Stanford University Medical Center. An uncomplicated blood test to predict the likelihood of jaundice could easily be incorporated into the panel of tests for metabolic disorders required for all newborns, they add.

"It's a very simple thing to do," said Phyllis Dennery, MD, associate professor of pediatrics, noting that the test must be administered 24-48 hours after a baby's birth. By plotting the level of bilirubin -- the yellow pigment that causes jaundice -- against the time the sample was taken, physicians can reliably predict which infants are likely to experience severe jaundice after leaving the hospital, she said. "If we can help one or two babies out of a thousand, it would be worth it."

Dennery teamed with David Stevenson, MD, professor of pediatrics and (by courtesy) of gynecology and obstetrics, to write a review article about jaundice complications and treatment in the Feb. 22 issue of the New England Journal of Medicine.

Neonatal jaundice occurs when bilirubin, which is produced when the body disposes of excess red blood cells, builds up too quickly for disposal by the infant's immature liver. In adults and older infants the bilirubin is removed from the circulation by the liver and then excreted. Prior to birth, the placenta helps the fetus dispose of the bilirubin.

Most healthy full-term infants are able to get up to speed within a couple of days, but premature infants and babies with certain racial backgrounds or genetic risk factors sometimes have trouble dealing with the sudden onslaught. Within a few days, the skin and eyes of these babies begin to turn yellow as levels of the pigment increase.

Neonatal jaundice affects more than half the newborn babies in this country, according to the American Academy of Pediatrics. In most instances the condition resolves itself without treatment. But in rare cases the bilirubin levels are high enough to enter the brain and interfere with nerve cell signaling. If left untreated, the infant may die from prolonged exposure to the elevated levels.

Although cases of severe, prolonged jaundice are rare, Dennery said the incidence is increasing because of complacency among physicians and the early discharge of infants from hospitals. Currently, the only infants whose bilirubin levels are checked are those who show clinical signs of jaundice before leaving the hospital.

"There was a period before the mid-1980s when physicians were very aggressive with jaundice. But then some studies started coming out saying bilirubin neurotoxicity wasn't really a problem and they began to question their treatment practices," said Dennery. The studies suggested that severe complications from jaundice were rare and that low amounts of bilirubin in newborns might even be beneficial.

"Now physicians are less worried about it and are allowing severe jaundice to go untreated," she said.

The timing of jaundice onset also conflicts with standard hospital practices, she said. The severity of jaundice in a healthy, full-term infant usually peaks at about 72 hours, but many babies are discharged within 48 hours of their birth. Often, infants released early are not re-examined for two weeks, despite recommendations from the American Academy of Pediatrics that they undergo a follow-up exam two to three days after discharge, Dennery said.

Fortunately, she noted, jaundice is highly treatable. Most infants respond well to phototherapy in which banks of fluorescent lights are positioned close to the skin to break down the bilirubin into a water-soluble compound that is easier for the baby to excrete.

In especially severe cases of jaundice it may be necessary to repeatedly replace small volumes of the infant's own blood with red blood cells from a donor. This technique, called exchange transfusion, rapidly removes the excess bilirubin. But it is accompanied by serious risks and should only be employed after phototherapy has failed, Dennery said.

Dennery cautioned against treating neonatal jaundice with herbal compounds -- a practice common in China. The safety and purity of such herbs is not well documented and in some cases the herbs could make the condition worse, she said.

Asians, Native Americans and people from the Greek Isles are more likely to suffer from neonatal jaundice, although doctors aren't sure why. Infants born to mothers who had gestational diabetes or whose blood type is incompatible with that of the fetus are also at increased risk. Neonatal jaundice can also be caused by genetic factors influencing the levels of enzymes responsible for metabolizing bilirubin to an excretable form. Occasionally jaundice is associated with breast-feeding, but this can be easily remedied with proper breast-feeding techniques or with phototherapy, Dennery said.

She recommended that physicians carefully consider factors including race, complications during pregnancy and decreased milk intake when assessing the likelihood that an infant will develop jaundice. She added that doctors should strive to reassess all babies discharged early within two to three days of their release.

New technologies to determine bilirubin levels may soon make screening even easier and less invasive. Stevenson and his colleague, Henk Vreman, PhD, senior research scientist in pediatrics at Stanford, have developed a technique to measure exhaled carbon monoxide -- another byproduct of the breakdown of red blood cells -- which can help predict the levels of bilirubin in the blood. There is also a device that can assess bilirubin levels when pressed to the forehead, although it's not known whether such techniques have the same predictive power as the old-fashioned blood test.

Dennery said she hopes the new techniques and the growing tide of cautionary tales will help physicians overcome their reluctance to take elevated bilirubin levels seriously.

"We just want to make sure physicians know that elevated bilirubin levels may be harmful, and although it may not happen to too many kids, the consequences can be very severe -- including brain damage and death," she said.