Meijer Nils W F, Maase Rose E, Hall Patricia L, Visser Wouter F, Koop Klaas, Bosch Annet M, Heiner-Fokkema M Rebecca, de Sain-van der Velden Monique G M
Section Metabolic Diagnostics, Department of Genetics, University Medical Center Utrecht, Lundlaan 6, 3584 EA Utrecht, The Netherlands.
Reference Laboratory for Neonatal Screening, Center for Health Protection, National Institute for Public Health and the Environment (RIVM), 3720 BA Bilthoven, The Netherlands.
Metabolites. 2025 Sep 22;15(9):634. doi: 10.3390/metabo15090634.
: Dutch newborn screening is an important public health program designed to detect conditions early in life, enabling timely interventions that can prevent mortality, morbidity, and long-term disabilities. However, the program also faces certain challenges. One such issue is obtaining and maintaining a high positive predictive value (PPV); another is that newborn screening (NBS) in the Netherlands is intended for all newborn babies until the age of six months. This means comparing infants at different ages may introduce variability that complicates data interpretation. To support the optimization of the program, we systematically analyzed population-level tandem mass spectrometry (MS/MS) data to explore postnatal metabolic changes. : We evaluated the impact of covariates-including birth weight, gestational age, age at blood collection, and biological sex-on metabolite profiles using retrospective newborn screening (NBS) data. Special emphasis was placed on the combined effects of these covariates. The analysis was based on data from 985,629 newborns collected between 2018 and 2024. : Specifically, (extremely) preterm infants exhibit altered levels of several amino acids and acylcarnitines. Moreover, we observed multiplicative effects of gestational age and birth weight on several metabolic markers. Biological sex however, does not have an impact. The largest impact of the age of sampling was observed on the C0/C16+C18 ratio, which may impact screening performance for CPT1 deficiency. : Covariate-adjusted reference values could improve the performance of the Dutch newborn screening.
荷兰新生儿筛查是一项重要的公共卫生项目，旨在尽早发现疾病，以便及时进行干预，预防死亡、发病和长期残疾。然而，该项目也面临一些挑战。其中一个问题是获得并维持较高的阳性预测值（PPV）；另一个问题是荷兰的新生儿筛查（NBS）适用于所有6个月以下的新生儿。这意味着比较不同年龄的婴儿可能会引入变异性，使数据解读变得复杂。为支持该项目的优化，我们系统地分析了人群水平的串联质谱（MS/MS）数据，以探索出生后的代谢变化。
我们使用回顾性新生儿筛查（NBS）数据评估了协变量（包括出生体重、胎龄、采血年龄和生物学性别）对代谢物谱的影响。特别强调了这些协变量的综合影响。分析基于2018年至2024年间收集的985,629名新生儿的数据。
具体而言，（极）早产儿表现出几种氨基酸和酰基肉碱水平的改变。此外，我们观察到胎龄和出生体重对几种代谢标志物有相乘效应。然而，生物学性别没有影响。采血年龄对C0/C16 + C18比值的影响最大，这可能会影响肉碱棕榈酰转移酶1（CPT1）缺乏症的筛查性能。
经协变量调整的参考值可以提高荷兰新生儿筛查的性能。
