COMMENTARY

A Simple Solution to False-Positive Metabolic Screens in the NICU

Laura A. Stokowski, RN, MS

Disclosures

July 28, 2015

Stopping Parenteral Nutrition for 3 Hours Reduces False Positives in Newborn Screening

Tim-Aroon T, Harmon HM, Nock ML, Viswanathan SK, McCandless SE
J Pediatr. 2015 May 21. [Epub ahead of print]

False-Positive Newborn Metabolic Screens

False-positive newborn screening (NBS) results are a significant problem in neonatal care. A positive NBS result can provoke anxiety on the part of parents, require diligent follow-up, and sometimes lead to unnecessary evaluation to ascertain whether the infant has a true metabolic disorder. By far, the most false positives occur in the neonatal intensive care unit (NICU) among low-birth-weight (LBW) infants (birth weight < 1500 g) who receive parenteral nutrition (PN) within 24 hours of birth to prevent negative nitrogen balance and improve protein accretion and growth. Although a standard of care for LBW infants, starting PN early also coincides with the time that blood for the NBS is drawn. PN can cause false-positive or inconclusive NBS results by elevating amino acid concentrations in the blood sample, the most common cause of a false-positive NBS result.

A large retrospective cohort study was conducted to test a new strategy to reduce the rate of false-positive NBS results. Data from 12,567 consecutive births in one hospital between May 2010 and June 2013 were analyzed to determine the false-positive rate for amino acid levels in the NBS before and after a new NBS collection protocol was introduced in 2012. The protocol required that for LBW infants, the PN infusion was to be interrupted and replaced with an infusion containing the equivalent concentration of dextrose-containing fluids (same dextrose concentration as the infant's PN) for 3 hours before the infant's blood was drawn for the NBS. The rate of false-positive NBS results (defined as NBS results showing elevations of amino acid concentrations that, on further testing and evaluation, were not confirmed to indicate true metabolic disorders) was measured.

Out of the entire cohort, 39 infants (0.3%) had amino acid (methionine, phenylalanine, tyrosine, or arginine) concentrations above the state's cut-off values. In 38 infants, these were determined to be false-positive results, and one infant was diagnosed with maple syrup urine disease. The false-positive rate was highest in infants with the lowest birth weights. LBW infants accounted for 3.3% of the total study population but 89% of the false-positive results. No false-positive results for amino acid elevation occurred in infants who did not receive PN.

When the investigators compared LBW infants whose PN infusions had been stopped for 3 hours before the NBS was drawn, the new protocol had a dramatic effect on the false-positive rate. The false-positive rate for amino acids in the stop-PN group was significantly lower than in the early-PN group (3.1% vs 11.8%; P = .037). The stop-PN protocol produced a 74% reduction in the rate of false-positive amino acid NBS results. Similar reductions were seen in the number of "inconclusive" NBS results, in which elevations of more than one amino acid were seen. The stop-PN strategy also resulted in a significant cost savings ($17.27 per infant screened, or $192.54 for each false-positive NBS averted). The only extra cost taken into account for the stop-PN strategy was the cost of the 3-hour dextrose replacement fluid.

The investigators concluded that a new NBS blood collection, the 3-hour stop-PN protocol, can significantly reduce false-positive amino acid results on the NBS and the associated medical costs. They suggest that future research should determine whether less than 3 hours might be equally effective or whether a longer period of stopping PN might produce an even greater reduction in false-positive NBS results. Furthermore, methods to reduce other common false-positive NBS results in LBW infants (especially 17-hydroxyprogesterone concentrations and acylcarnitine profiles) are needed.

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