Newborn Screening for Familial Hypercholesterolemia Using Liquid Chromatography Tandem Mass Spectrometry-Based Free Cholesterol Measurements.

Abstract

To describe the feasibility of free cholesterol (FC) measurement from dried blood spots (DBS) obtained during regular newborn screening in a pilot project in the Euroregion Pomerania, aimed ultimately to enhance the rates of familial hypercholesterolemia diagnoses. DBS from 7973 babies born in 2019 and included in the "Innovative Polish-German Cross-Border Program for Early Diagnosis and Treatment of Rare Diseases in Newborns - RareScreen" project were analyzed. The FC concentration was measured in each DBS using liquid chromatography tandem mass spectrometry and the distribution was examined. The FC concentration determined in the study sample ranged between 0.005 and 1.521 mmol/L (0.19 and 58.89 mg/dL), with a median of 0.709 mmol/L (27.4 mg/dL). There was no strong appearance of effects attributable to the newborn's sex, gestational age, birth weight, or age at sampling on the FC concentration. The 99.5% percentile for the FC concentration was 1.159 mmol/L (44.8 mg/dL). Our study demonstrated the feasibility of large-scale measurements of FC in DBS from newborns using liquid chromatography tandem mass spectrometry in a central study laboratory. The FC concentration was similar across selected demographic and clinical conditions of the newborns. FC may represent a novel marker for screening of lipid abnormalities but needs to be validated in future studies.