A Common-Sense Solution

December 3, 2015

Simple innovation reduces problematic false positives in newborn screening for genetic disorders 

Innovations in Pediatrics - Fall 2015 - View Full PDF


Division Chief, Pediatric Genetics, UH Rainbow Babies & Children’s Hospital; Assistant Professor of Pediatrics, Case Western Reserve University School of Medicine

Fifty years ago, an infant with undiagnosed phenylketonuria (PKU) would progress from normal to severely intellectually disabled in just about a year, as the genetic condition took its toll. Newborn screening for genetic conditions has changed that equation.

“As a public health program, newborn screening has been incredibly successful,” says geneticist Shawn E. McCandless, MD, Division Chief of Pediatric Genetics at University Hospitals Rainbow Babies & Children’s Hospital. “Today, we have adults living with PKU and thriving. Following the prescribed treatment isn’t easy, but it is effective.”

Still, the relatively high number of false positives generated during testing remains a challenge for newborn screening programs. “In the field, we recognize that the false positives in newborn screening are what inhibit the development of new programs,” Dr. McCandless says. “The more false positives you have, the more you lose public support for the program because parents and pediatricians just don’t think it’s worth it.” 

At UH Rainbow Babies & Children’s Hospital and UH MacDonald Women’s Hospital, a collaborative effort has identified a simple innovation addressing this issue. After the UH Rainbow Babies & Children’s Hospital NICU staff noticed that they were seeing an increasing number of false positive results for amino acids measured during newborn screening, they met with the genetics team and lab services and identified a likely cause: the new protocol calling for high-protein parenteral nutrition solution to be immediately given to all infants admitted to the NICU. In response, the group proposed replacing the protein-containing solution with simple dextrose solution for three hours before the newborn screening heel prick test, done at 24 hours of age. 

Data collected from more than 12,000 infants born at UH MacDonald Women’s Hospital over three years suggest that the innovation is working. Infants whose protein- containing parenteral nutrition was stopped for three hours before newborn screening showed a 74 percent reduction in the false positive rate for amino acids, compared with infants who received the standard protein-containing solution. 

“It was a big, dramatic difference,” Dr. McCandless says. 

Importantly, there were no reports of serious complications or hyperglycemia during the three-hour solution-replacement window, nor was there any apparent difference in hospital outcome. The group published these results recently in The Journal of Pediatrics.

For Dr. McCandless, these findings point to the need for continuous quality improvement in newborn screening protocols. This can be done by addressing the physiological circumstances that can affect the screening marker, as in this case. But it can also be accomplished by gaining a better understanding of what ‘normal’ screening values are for low birthweight (LBW) infants. 

“LBW babies account for the vast majority of false positives,” Dr. McCandless says. “There are a variety of reasons for that, but the main reason is that we don’t have good data on the appropriate normal ranges for those kids. We need to set the cut-off point such that we don’t miss any abnormal results. If we had better data, we’d be able to pinpoint a more accurate cut-off point.”

The new protocol also highlights the importance of collaboration across disciplines, Dr. McCandless says.

“There’s this long tradition of collaboration and collegiality at Rainbow, where people really do talk to each other. With new technologies and new facilities and growth, people may have fewer physical interactions on a day-to-day basis. You have to work harder to keep those lines of communication open. But it’s actually invaluable, and this is a great example of it.”

For more information, contact Dr. McCandless at Peds.Innovation@UHHospitals.org

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