Routine screening of newborns for familial hypercholesterolemia (FH) is feasible with first-tier biochemical testing followed by reflex second-tier genetic testing, according to a cross-sectional study published Oct. 29 in JAMA Cardiology.

Amy L. Peterson, MD, MS, et al., collected residual dried blood spot (DBS) specimens from newborns in Wisconsin from 2021-2022 and tested them for biomarkers that suggested high risk for FH as a first step toward development of multitier newborn screening for FH. Specifically, they collected total cholesterol, LDL-C and apolipoprotein B (ApoB) between 24 and 72 hours after birth and identified combinations that accounted for the greatest variance. Then they tested a subset for pathogenic variants in eight genes associated with FH.

Results showed that DBS samples were acquired from 10,004 of 59,927 newborns (mean age, 27.8 hours; 49% females). Principal component analysis from the specimens tested indicated the combination of LDL-C and ApoB accounted for the largest variance; 768 specimens were selected for genetic testing.

Findings also revealed that 16 pathogenic or likely pathogenic variants for FH were identified, yielding a prevalence of one in 625 (1.6 per 1,000; 95% CI, 0.91-2.60 per 1,000) newborns in the cohort. Pathogenic variants were dispersed throughout the full range of Mahalanobis scores chosen for genetic testing.

Peterson and colleagues note that although "further refinement and validation are needed before implementation, ... routine newborn screening for FH would substantially increase diagnosis of this common, potentially fatal, yet readily treatable condition while providing opportunities for cascade screening."

In an accompanying editorial comment, Daniel J. Rader, MD, and Sarah Schmidt, MD, write that the study results support including FH in newborn screening; however, "the lipidology and pediatric cardiology communities will need to become more involved" for this "to ever become a reality."