Neonatal birth parameters of positive newborns at PKU screening as predictors of false-positive and positive results at recall-testing

Abstract

Methods: Phenylalanine concentration was measured with a uorometric multitask plate counterWallac 1420 VICTOR F (Perkin Elmer, Finland) and the uorescent ninhydrine method (EG&G Wallac neonatal phenylalanine kit) using a recall cut-off level >120 mmol/l (2 mg/dl) of phenylalanine on dried blood spots. A multivariate logistic regression analysis was performed to evaluate the predictive role that body parameters (sex, gestational age, parity, weight, length and head circumference) of positive newborns at PKU screening had on false-positive and positive results at recall PKU tests. Results:The risk of false-positive results is higher (~48%) in females than in males. Moreover, for each 100g of body weight reduction, the risk of false positive is around 4.2% higher. The risk of con rmation increased by 39% per week of gestational age. Conclusions:In conclusion, our results suggest that preterm or low-birth-weight neonates recalled at the rst investigation are more likely to be due to false-positives, whereas the risk of con rmation is higher in at-term neonates. By implication, the phenylalanine cut-off value for premature or low-body-weight infants could be higher.

Reduction in newborn screening metabolic false-positive results following a new collection protocol

“…5,6,12,19 Our results do, however, agree with others who have demonstrated a higher FPR in premature infants or in those admitted to a NICU. [6][7][8][9]20 The results also indicate that an increased FPR can be expected with a lower birth weight as has been shown by others. 4,[7][8][9]20 The highest FPR was seen in infants with a birth weight <1,000 g when compared with the other birth weight groups.…”

“…[6][7][8][9]20 The results also indicate that an increased FPR can be expected with a lower birth weight as has been shown by others. 4,[7][8][9]20 The highest FPR was seen in infants with a birth weight <1,000 g when compared with the other birth weight groups. This is likely related to hepatic immaturity, which delays the detoxification ability of the liver.…”

“…[6][7][8][9] In an effort to minimize possibly missing a true disorder for all conditions included in the NBS program, some programs have implemented guidelines that recommend obtaining a second or third sample at different ages. 10,22 The study protocol we investigated, which involved interrupting TPN and reducing FPRs, could also be incorporated into a multiple specimen collection program avoiding parenteral anxiety and the potential risk of delaying the diagnosis of a metabolic disorder that could result from waiting until the patient is completely off TPN to collect an additional sample.…”

“…Various medical therapies, including total parenteral nutrition (TPN), provided in the NICU and the liver immaturity of the preterm infant's metabolic system contribute to higher rates of presumptive positive NBS results in this group. [6][7][8][9] This population requires special planning and investigation into the best practice for collecting the NBS specimen in a manner to reduce the potential of a false-positive result (FPR), a result that is out of the range established by the NBS laboratory (presumptively positive), and additional testing confirms that no disorder exists. However, despite the importance of this problem, there is limited literature about how to decrease the FPR in the NICU population.…”

Diagnosis, classification, and genetics of phenylketonuria and tetrahydrobiopterin (BH4) deficiencies

“…Where screening is carried out in maternity wards, the blood sample is usually obtained between days 2 and 5; in general, however, screening is carried out mostly between the ages of 2 and 7 days [4]. In the U.S., samples are typically obtained at 24-48 h. A commonly used Phe cut-off level for diagnosis of PKU is 120-130 μmol/L (with a Phe/Tyr ratio N2), with TMS employed [5].…”