Timing of Newborn Blood Collection Alters Metabolic Disease Screening Performance

Abstract

Blood collection for newborn genetic disease screening is preferably performed within 24–48 h after birth. We used population-level newborn screening (NBS) data to study early postnatal metabolic changes and whether timing of blood collection could impact screening performance. Newborns were grouped based on their reported age at blood collection (AaBC) into early (12–23 h), standard (24–48 h), and late (49–168 h) collection groups. Metabolic marker levels were compared between the groups using effect size analysis, which controlled for group size differences and influence from the clinical variables of birth weight and gestational age. Metabolite level differences identified between groups were correlated to NBS data from false-positive cases for inborn metabolic disorders including carnitine transport defect (CTD), isovaleric acidemia (IVA), methylmalonic acidemia (MMA), and phenylketonuria (PKU). Our results showed that 56% of the metabolites had AaBC-related differences, which included metabolites with either decreasing or increasing levels after birth. Compared to the standard group, the early-collection group had elevated marker levels for PKU (phenylalanine, Cohen's d = 0.55), IVA (C5, Cohen's d = 0.24), MMA (C3, Cohen's d = 0.23), and CTD (C0, Cohen's d = 0.23). These findings correlated with higher false-positive rates for PKU (P < 0.05), IVA (P < 0.05), and MMA (P < 0.001), and lower false-positive rate for CTD (P < 0.001) in the early-collection group. Blood collection before 24 h could affect screening performance for some metabolic disorders. We have developed web-based tools integrating AaBC and other variables for interpretive analysis of screening data.

Intervención de enfermería en tamiz metabólico neonatal: Revisión integrativa

“…Edad posnatal y recolección de muestra para tamiz metabólico neonatal: Para identificar metabolitos presentes en enfermedades metabólicas congénitas, esencialmente se realiza la toma de muestra de sangre entre el tercer y quinto día de vida del RN y se deposita en papel filtro específico para tamiz metabólico (7,9,13,(18)(19)(20)(21) . Se ha reportado la conveniencia de realizarse dentro de 24 a 48 h después del nacimiento, debido Sí a que antes de las 24 h de vida se han encontrado niveles elevados de marcadores de fenilalanina, hallazgos que se correlacionan con tasas más altas de falsos positivos para esta afección; además se puede perjudicar la detección de algunos trastornos metabólicos debido a la transición bioquímica del del neonato de un estado dependiente de la madre a un estado autónomo.…”

“…El momento de toma de muestra puede variar en RN prematuros, con bajo peso al nacer o con otras alteraciones al nacimiento (18) .…”

Comprehensive Evaluation of the NeoBase 2 Non-derivatized MSMS Assay and Exploration of Analytes With Significantly Different Concentrations Between Term and Preterm Neonates

“…The median ADO concentration is significantly higher in neonates with low birth weight [ 33 ]. In addition, the timing of blood collection affects analyte concentrations and thus the performance of NBS [ 11 , 34 ]. These results complicate the interpretation of metabolic status in preterm neonates and substantiate the requirement for a different cutoff for IEM screening.…”

Newborn Screening by Genomic Sequencing: Opportunities and Challenges

“…It is carried out with one or two samples [ 41 , 42 ]. Sampling beyond 24 h is generally required for optimal screening performance [ 43 ]. This has been found acceptable in newborn screening programmes world-wide.…”