Pediatric reference intervals for calculated LDL cholesterol, non-HDL cholesterol, and remnant cholesterol in the...

Increased prevalence of pediatric obesity and associated co-morbidities has heightened the concern for cardiovascular disease (CVD) risk later in life. Although the fasting lipid profile is traditionally used to assess CVD risk, the non-fasting lipid profile may simplify lipid testing and better predict CVD risk. Unfortunately, non-fasting lipid reference values are limited, particularly for children. The Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) has recruited thousands of healthy pediatric subjects to develop a pediatric reference interval database. Here, CALIPER reports pediatric reference intervals for non-fasting calculated low-density lipoprotein cholesterol (LDLc), non-high-density lipoprotein cholesterol (non-HDLc) and remnant cholesterol.

Non-fasting serum samples from the CALIPER cohort of community children and adolescents were previously analyzed for HDLc, total cholesterol, and triglycerides. These values were used to calculate LDLc, non-HDLc, and remnant cholesterol and subsequently establish reference intervals with corresponding 90% confidence intervals according to CLSI EP28-A3c guidelines. Reference intervals were also calculated using alternative statistical methods highlighted in recent literature.

All three lipid parameters required an age partition at 1 year due to wider reference intervals in the first year of life. LDLc and non-HDLc required sex partitioning for subjects 1-<10 years. Non-HDLc upper reference limit was higher than the 2011 National Heart, Lung, and Blood Institute (NHLBII) pediatric recommended cut-offs, suggesting elevated atherogenic lipoproteins in a proportion of apparently healthy pediatric subjects. The LDLc upper reference limit (10-<19 year partition) was the same as the NHLBI cut-off, potentially due to lower calculated LDLc values in the non-fasting state.

With the increased use of non-fasting lipid profiles, age- and sex-specific reference intervals and appropriate clinical decision limits are necessary for pediatric lipid monitoring. Our data supports the notion that appropriate decision limits, rather than reference intervals, should be used to interpret lipid levels in children as there is a high prevalence of hyperlipidemia in the apparently healthy pediatric population.