Pickens C Austin, Sah Samyukta, Chandrappa Rahul, Isenberg Samantha L, Courtney Elya R, Lim Timothy, Chace Donald H, Lee Rachel, Cuthbert Carla, Petritis Konstantinos
Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, 4770 Buford Hwy NE, S110-3, Atlanta, GA 30341, USA.
Capitainer Inc., East Providence, RI 02914, USA.
Int J Neonatal Screen. 2024 Dec 10;10(4):81. doi: 10.3390/ijns10040081.
Parenteral nutrition (PN) is a nutrient solution administered intravenously (IV) to premature babies. PN causes elevations of some amino acids in blood samples that are also biomarkers used in newborn screening (NBS). Therefore, PN status must be annotated by clinicians on dried blood spot (DBS) cards to reduce NBS laboratory burdens associated with potential false results; however, NBS laboratories continue to receive DBSs with misannotated PN status. N-acetyltyrosine (NAT), a water-soluble tyrosine analog used to increase tyrosine bioavailability in PN solutions, can be used as a blood-based biomarker of PN administration in NBS assays. Residual DBS specimens and manufactured DBSs were used in analyses. The assay was developed and validated using flow injection analysis tandem mass spectrometry (FIA-MS/MS) for the detection of NAT. NAT was only present in neonate DBSs with annotated PN administration and was multiplexed into first-tier newborn screening assays. NAT was highly correlated with amino acids present in PN solutions, such as arginine, leucine, methionine, phenylalanine, and valine. In our sample cohort, we determined an NAT cutoff could aid the identification of misannotated neonates administered PN. We also report the Amadori rearrangement product valine-hexose (Val-Hex) was quantifiable in neonates administered PN, which we suspect forms in the PN solution and/or IV lines. Here, we present the first known use of NAT as a biomarker of PN administration, which is currently being piloted by two U.S. NBS laboratories. NAT and Val-Hex can aid the identification of misannotated DBSs from neonates administered PN, thus decreasing false positive rates.
肠外营养（PN）是一种通过静脉注射（IV）给早产儿使用的营养液。PN会导致血样中某些氨基酸水平升高，而这些氨基酸也是新生儿筛查（NBS）中使用的生物标志物。因此，临床医生必须在干血斑（DBS）卡片上标注PN状态，以减轻NBS实验室与潜在假结果相关的负担；然而，NBS实验室仍不断收到PN状态标注错误的DBS样本。N - 乙酰酪氨酸（NAT）是一种用于提高PN溶液中酪氨酸生物利用度的水溶性酪氨酸类似物，可在NBS检测中用作PN给药的血液生物标志物。分析中使用了剩余的DBS标本和人工制造的DBS样本。该检测方法采用流动注射分析串联质谱（FIA - MS/MS）开发并验证，用于检测NAT。NAT仅存在于标注了PN给药的新生儿DBS样本中，并被纳入一级新生儿筛查检测。NAT与PN溶液中存在的氨基酸，如精氨酸、亮氨酸、蛋氨酸、苯丙氨酸和缬氨酸高度相关。在我们的样本队列中，我们确定了一个NAT临界值有助于识别PN给药标注错误的新生儿。我们还报告称，在接受PN治疗的新生儿中可定量检测到Amadori重排产物缬氨酸 - 己糖（Val - Hex），我们怀疑它在PN溶液和/或静脉输液管中形成。在此，我们首次展示了将NAT用作PN给药生物标志物的应用，目前美国的两个NBS实验室正在进行试点。NAT和Val - Hex有助于识别接受PN治疗新生儿的DBS样本标注错误，从而降低假阳性率。
