Newborn metabolic screening yields false positives in preemies

By Anne Harding

NEW YORK (Reuters Health) - Testing premature infants for inborn errors of metabolism using cutoffs for healthy term infants results in a high rate of false positives, according to new findings published online in Pediatrics Monday.

"While most of these babies ultimately will normalize their metabolism and as the testing goes along they will screen perfectly fine, in the early days they are going to test abnormal if you use the same criteria that you use for a term baby," said study coauthor Dr. Alan Spitzer, senior vice president and director of The Center for Research, Education and Quality at Pediatrix in Sunrise, Florida, in a telephone interview.

"In the neonatal unit we have to look at screening differently," added Dr. Reese Clark, vice president and co-director of the center and a co-author of the study.

Currently, hospitals are required to send samples taken for newborn screening to a state laboratory, Dr. Spitzer added, and tests for premature babies often come back as false positives. "That needs to be followed up. That's a substantial demand that's placed on the caregivers of those patients . . . and it produces obviously anxiety for the families who have to be told your child's had an abnormal screening test," he said.

To better characterize metabolic profile test results in premature infants, Dr. Spitzer and his colleagues gathered data on 995 babies born between 23 and 31 weeks' gestation. All of the infants underwent testing within 24 hours of birth and again at days 7, 28, and 42, or at discharge. A total of 3,579 samples were taken, with amino acid or acylcarnitine alerts reported on 251 samples from 214 infants. The proportion of metabolic profiles that were abnormal changed over time: 12% at birth, 29% at 23 to 26 weeks' gestational age; 17% at 29 to 31 weeks' gestational age; and 2% at day 28.

However, none of the infants in the study had any inborn errors of metabolism.

"The basic concept here was to try to come up with a set of normal values for the premature infant and show that those values change over the course of time," Dr. Spitzer said. Added Dr. Clark: "What we're really trying to provide is a standard for the state to use."

Most neonatologists already understand that metabolic abnormalities are common in premature infants, Dr. Clark noted, but the pediatricians who provide follow-up care to these babies may not. "We're trying to make the general practicing public aware of the problem," he said.

Waiting to do newborn screening until a baby's metabolism matures is not a good option, according to Dr. Spitzer, because this would mean missing a crucial early window for intervention if a baby does turn out to have a true metabolic abnormality.

Dr. Dennis Dietzen, an associate professor of pediatrics at the Washington University School of Medicine in St. Louis and director of the Core Laboratory at St. Louis Children's Hospital, reviewed the study for Reuters Health.

"I think that this paper brings some definition to what everybody already knows, that premature infants have physiology and biochemistry that's very different from term infants, but we didn't know how different," he said. "These babies have very low blood volume, so the fact that they could do this is pretty impressive. The execution of this study was really probably quite difficult. The size of it is very impressive as well."

While the study provides valuable background on screening test values for premature infants, Dr. Dietzen added, it has limitations, including the fact that values were based on testing of dried blood spots. Hospital core labs test plasma, not blood spots, he explained. "It takes a little bit more to translate that into everyday practice for these really, really tiny babies."

To accurately diagnose metabolic errors in premature infants, according to Dr. Dietzen, it will be necessary to obtain values from preemies who actually have these disorders, which is a major challenge because they are so rare. "In preemies it's very difficult to make a definitive biochemical diagnosis. The data may be suggestive, but in these situations there are probably going to be genetic investigations that have to happen to make that diagnosis," he said.

SOURCE: http://bit.ly/1jl2d0c

Pediatrics 2014.

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