Screening for Familial Hypercholesterolemia in 5000 Neonates: A Recall Study

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Abstract
To investigate the feasibility of screening for familial hypercholesterolemia, apolipoprotein B (Apo B) levels were determined in dried blood spot samples on neonatal screening cards from 5000 consecutively born neonates, by radial immunodiffusion assay. The 103 infants with Apo B levels in the top 2% were recalled for repeat dried blood spot Apo B determinations. Forty-five of the 103 infants were retested, and serum lipid profiles and Apo B levels were determined for both parents of 43 of these infants, and for the mother only for the other two infants. The recalled “top 2%” group had a higher proportion of females, a higher mean birth weight, a higher mean gestational age and a higher proportion of infants sampled initially on day 5 than in the total screened population, consistent with our previously determined influence of these factors on Apo B levels at screening. The retested group (n = 45) was representative of the total recalled group (n = 103) with respect to Apo B levels at screening, sex, birth weight, gestational age, and age at sampling for screening. The infants' mean ± SD age at retesting was 12.3 ± 3.3 months. Their mean Apo B value on retesting was 0.65 ± 0.20 g/liter of whole blood (range 0.30 to 1.16 g/liter). Two fathers had had coronary bypass surgery by the age of 40 and had type II lipid profiles and elevated serum Apo B levels. For both, their child had elevated Apo B levels at recall (both 1.05 g/liter of whole blood). Another five mothers and five fathers had type II lipid profiles (total and low-density lipoprotein cholesterol more than 95th percentile for their age and sex), and in four of these their child also had elevated Apo B levels at recall (≥0.70 g/liter of whole blood). Another eight infants had recall Apo B levels of more than 0.70 g/liter, of whom two had only had one parent with low-density lipoprotein cholesterol more than the 90th percentile suggesting genetically determined elevated levels. Despite the arbitrary cutoff point, a total of six of the 45 infants retested had strong indications of having the gene for familial hypercholesterolemia. This gives an estimated frequency of between one in 365 and one in 830 in the total population screened, which is comparable with the reported frequency of one in 500. We conclude that screening for familial hypercholesterolemia using this method is feasible, but that a further study using a cutoff point that takes into account the factors that affect Apo B levels at screening would be useful.