Familial Hypercholesterolemia Biomarker Distribution in Dried Blood Spots

Abstract

To evaluate distribution profiles of total cholesterol (TC), lipoprotein cholesterol (LDL-C), and apolipoprotein B (apoB) as candidate markers of familial hypercholesterolemia (FH) in newborns, taking into consideration potential confounding factors, such as gestational age, birthweight, sex, and race. TC, LDL-C, and apoB were measured from 10,000 residual deidentified newborn dried blood spot cards. Concentrations for each biomarker were reported as multiples of the median (MoM), with emphasis on describing the 99th percentile values based on birth weight, gestational age, sex, and race. Seasonal variation of biomarkers was also explored. LDL-C and apoB had distribution curves with tails showing extreme elevation while the distribution of TC was less elevated and had the smallest range. Neonates born at early gestational age and low birth weight had significantly higher 99th percentile of MoM values for apoB but not TC or LDL-C. Differences in biomarker concentration based on sex and race were minimal. All biomarkers showed highest concentrations in the winter as compared with summer months. LDL-C and apoB had distribution curves supporting candidacy for neonatal FH screening. Future studies are needed to correlate newborn screening results with molecular testing to validate these two biomarkers, along with measured cholesterol levels later in childhood.