Pediatric Lipid Disorders in Clinical Practice Workup

Updated: Jan 29, 2015
  • Author: Henry J Rohrs, III, MD; Chief Editor: Stuart Berger, MD  more...
  • Print

Laboratory Studies

Lipid testing

Lipids can be routinely measured individually as TC, TGs, or HDL-C. Using these measurements and the Friedewald equation when TG levels are less than 400 mg/dL, LDL-C can be calculated. Direct LDL measurements allow LDL-C determination on specimens when the TG level is 400 mg/dL or higher and do not require a fasting specimen. However, direct LDL-C measurements have no advantage (and add needless expense) when the TGs levels are less than 400 mg/dL

Children should be on their regular diet for 4-6 weeks before lipid testing. Recent changes in diet that may change lipid levels are an indication to delay testing. Measurements of TC and HDL-C do not need to be performed in the fasting state. However, isolated TG measurements and lipid profile measurements should follow an overnight fast of least 8 hours, preferably 12-14 hours.

Recent severe illness (eg, hospitalization within the last 4-6 wk) is a contraindication to lipid testing because significant stress can also lead to transient decreases in lipid levels or transient lipid abnormalities (eg, hypertriglyceridemia following diabetic ketoacidosis). During acute illness, lipids should not be measured unless hypertriglyceridemia is believed to be the underlying cause of the disease (eg, pancreatitis). Lipoproteins are negative acute phase reactants and their concentrations decline within 24 hours of severe acute stress. In adults, intraindividual variation in TC over the course of one year is reported to be ±8% (range 4-11%). Intraindividual variation in TG is 13-41%, whereas HDL-C varies by 4-12%. Standing TC levels are 8-12% higher than recumbent values because of a decrease in intravascular fluid that leaks into the interstitial space. The use of anticoagulants in sample tubes may lower TC levels by 3% or less.

Historically, an overnight fast was deemed necessary before lipid screening, but adult data suggest nonfasting lipids may be appropriate for initial screening for cardiovascular risk. [3, 4, 5, 6, 7] A large, cross sectional study was performed in children to assess differences in lipid values based on fasting status. [8] Mora found that although statistically significant differences existed in nonfasting lipid levels, these differences were not clinically significant, with more than 95 percent of children falling into the same classification category whether lipids were fasting or nonfasting.

Non-HDL cholesterol (ie, the TC minus the HDL-C) has been shown to be an excellent measure of risk for cardiovascular disease in adults. Both of the major non-HDL lipoproteins (LDL and VLDL) are the apoprotein-B – containing lipoproteins.


National Cholesterol Education Program

The goal of the National Cholesterol Education Program (NCEP) created in 1985 by the National Heart, Lung, and Blood Institute (NHLBI) is to educate both the public and medical professionals about the benefits of lowering cholesterol levels so as to reduce the risk for coronary heart disease. Current pediatric guidelines for cholesterol screening are based on a consensus report published in 1992 (modified in 2001). [9, 10, 11, 12]

Abnormalities in lipid levels were initially defined as concentrations at or above the 95th percentile for TC, TGs, and LDL-C for age and sex, whereas low HDL-C concentrations were defined as lower than the 5th percentile for age and sex (see Table 3 below). Many of these cutoffs have been modified by the NCEP to define healthy or desirable levels and not merely levels outside of a certain concentration range defined statistically.

The NCEP has not defined desirable and undesirable TG levels for children and adolescents. For adults, the NCEP has defined desirable TG levels as less than 150 mg/dL, mildly elevated levels as 150-199 mg/dL, elevated levels as 200-499 mg/dL, and levels of 500 mg/dL or higher as very high.

At the University of Florida, hypertriglyceridemia in children is defined as TG levels at or above 125 mg/dL. This value of 125 mg/dL is easy to remember and approximates the mean 95th percentile for TGs in boys and girls across childhood and adolescence. Functionally mild hypertriglyceridemia in children is defined in this clinic as TG levels of 125-299 mg/dL, modest hypertriglyceridemia as TG levels of 300-499 mg/dL, marked hypertriglyceridemia as TG levels of 500-999 mg/dL, and massive hypertriglyceridemia as TG levels of 1000 mg/dL or higher. These cutoffs can be used when determining treatment approaches to hypertriglyceridemia. Desirable and undesirable fasting lipid levels in children and adults are listed in Table 3, below.

Table 3. NCEP Lipid Assessments for Children and Adults (Open Table in a new window)

Children (< 20 y) Desirable level (mg/dL) Borderline level (mg/dL) Undesirable level (mg/dL)
TC < 170 170-199 ≥200
LDL-C < 110 110-129 ≥130
HDL-C* >45 35-45 < 35
TG < 125 ... ≥125
Adults (≥20 y) Desirable level (mg/dL) Borderline level (mg/dL) Undesirable level (mg/dL)
TC < 200 200-239 ≥240
LDL-C§ < 130 130-159 ≥160
HDL-C|| ≥40 ... < 40
TGs < 150 150-199 ≥200
* This was not established by NCEP; these values were the adult cutpoints used at the time that the pediatric NCEP guidelines were established.

This was not established by NCEP; a TG level of 125 mg/dL approximates the mean 95th percentile for TGs in boys and girls during childhood and adolescence.

In March of 2001, cutoff points for desirable and undesirable cholesterol, HDL-C, and other levels were revised in the Adult Treatment Panel III (ATPIII). [12]

§ The optimal LDL-C concentration is less than 100 mg/dL; in patients with cardiovascular disease or diabetes, the optimal LDL-C level is less than 70 mg/dL.

|| If the HDL-C level is 60 mg/dL or higher, one risk factor for coronary heart disease can be subtracted in adults.


National Heart, Lung, and Blood Institute

In 2011, the National Heart, Lung, and Blood Institute (NHLBI) released pediatric lipid screening and cardiovascular health recommendations. [13] These guidelines agree with most of those from the NCEP but are more specific, recommending precise ages and more aggressive repeat testing and therapy in high-risk patients. The evidence-based recommendations suggest no routine lipid screening before age 8 years.

In children aged 2-8 years who are considered to be at higher risk (eg, children with a family history of early cardiovascular disease or a parent with a TC level of 240 mg/dL or higher or known dyslipidemia; children with diabetes, hypertension, or a BMI ≥95th percentile; children who smoke cigarettes), fasting lipid profiles should be obtained on two separate occasions and the results averaged. Universal screening is recommended for low-risk individuals at age 9-11 years and again at age 17-21 years.

These recommendations for universal screening, while controversial, recognize the preponderance of evidence that high LDL-C levels are a significant contributor to heart disease, although they do not consider the lack of evidence as to whether the benefits of lifelong treatment with lipid-lowering drugs outweigh the treatment risks. [13]

American Association for Clinical Endocrinology

The American Association for Clinical Endocrinology (AACE) included optimal apoprotein-B levels in their most recent dyslipidemia guidelines. [14] According to the AACE, for patients at risk for coronary artery disease (CAD), including individuals with diabetes, apoprotein-B levels should be less than 90 mg/dL, whereas patients with established CAD or diabetes who have one or more additional risk factors should have an apoprotein-B level of less than 80 mg/dL. Optimal apoprotein-B levels have not yet been established for children.