Screening for Lipid Disorders in Children: U.S. Preventive Services Task Force Recommendation Statement

U.S. Preventive Services Task Force (USPSTF)
Screening for Lipid Disorders in Children
Recommendation Statement

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This statement summarizes the current U.S. Preventive Services Task Force (USPSTF) recommendation on screening for lipid disorders in children.

This recommendation statement was first published in Pediatrics Electronic Pages. Select for copyright and source information.

The U.S. Preventive Services Task Force (USPSTF) is redesigning its recommendation statement in response to feedback from primary care clinicians. The USPSTF plans to release, later in 2007, a new, updated recommendation statement that is easier to read and incorporates advances in USPSTF methods. The recommendation statement below is an interim version that combines existing language and elements with a new format. Although the definitions of grades remain the same, other elements have been revised.


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Contents
Summary of Recommendation
Clinical Considerations
Other Considerations
Discussion
Recommendations of Others
References
Members of the USPSTF


Task Force Ratings
Strength of Recommendations and Quality of Evidence

Summary of Recommendation
•The USPSTF concludes that the evidence is insufficient to recommend for or against routine screening for lipid disorders in infants, children, adolescents, or young adults (up to age 20). This is a grade I Statement.


Rationale
Importance: There is good evidence that children with lipid disorders (dyslipidemia) are at risk for becoming adults with lipid disorders.

Detection: For children with familial dyslipidemia, the group most likely to benefit from screening, use of family history in screening may be inaccurate because of variability of definitions and unreliability of information. Serum lipid levels are accurate screening tests for childhood dyslipidemia, although many children with multifactorial types of dyslipidemia would have normal lipid levels in adulthood. Fifty percent of children and adolescents with dyslipidemia will have dyslipidemia as adults.

Benefits of detection and early intervention: a Trials of statin drugs in children with monogenic dyslipidemia (defined below in clinical considerations) indicate improved total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) measures. For children with multifactorial types of dyslipidemia, there is no evidence that diet or exercise interventions in childhood lead to improved lipid profiles or better health outcomes in adulthood.

Harms of detection and early treatment:Potential harms of screening may include labeling of children whose dyslipidemia would not persist into adulthood or cause health problems, although evidence is lacking. Adverse effects from lipid-lowering medications and low-fat diets, including potential long-term harms, have been inadequately evaluated in children.

USPSTF assessment: The USPSTF was unable to determine the balance between potential benefits and harms for routinely screening children and adolescents for dyslipidemia.
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a. Critical evidence gap.

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Clinical Considerations
•Dyslipidemias are abnormalities of lipoprotein metabolism and include elevations in TC, LDL-C, or triglycerides or deficiencies of HDL-C. These disorders can be acquired or familial; monogenic dyslipidemias are related to genetic conditions such as familial hypercholesterolemia in some individuals. Multifactorial dyslipidemias are due to risk factors including environmental factors (obesity, diet) or currently unidentified genetic factors. This recommendation applies to all asymptomatic individuals from birth to age 20.
•Because abnormal lipid levels have been strongly associated with the risk of coronary heart disease (CHD) events in adulthood, and early identification and lipid-lowering intervention in certain populations of adults can prevent CHD events, much attention has been directed at screening individuals for dyslipidemia at young ages (e.g., childhood). Among children and adolescents, 3 groups may be identified through screening:
1.Children with undiagnosed monogenic dyslipidemias such as familial hypercholesterolemia.
2.Those with undiagnosed secondary causes of dyslipidemia.
3.Those with multi-factorial dyslipidemia (polygenetic or related to risk-factors).
However, the clinical health benefits shown in adults identified and treated for dyslipidemia have not been studied in children, making the role of screening children uncertain.
•Children and adolescents with diabetes may be at especially high risk for dyslipidemia and cardiovascular events. Screening children and adolescents with diabetes for dyslipidemia has been recommended by other groups as a part of appropriate care for these children.
•The use of family history as a screening tool for dyslipidemia has variable accuracy largely because definitions of a positive family history and lipid threshold values vary substantially. Screening using family history as defined by the National Cholesterol Education Program (NCEP) and the American Academy of Pediatrics (AAP) has been shown to have high rates of false negative results.
•If clinicians choose to screen for dyslipidemia, the preferred screening tests are TC and HDL-C on nonfasting or fasting samples; calculating LDL-C requires fasting samples.
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Other Considerations
•Effectiveness of treatment interventions (diet, exercise, lipid lowering agents) in children with dyslipidemia (including multifactorial dyslipidemia) in improving health outcomes remains a critical research gap. Population-based screening studies or randomized controlled trials (RCTs) following children and adolescents into adulthood after treatment interventions will be necessary to assess universal lipid screening in childhood or adolescence.
•Rising rates of childhood overweight may lead to a higher prevalence of dyslipidemia in childhood and adulthood. Continued tracking of dyslipidemia in all age groups will be important as the epidemiology of obesity evolves.
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Discussion
Epidemiology
Dyslipidemias are disorders of lipoprotein metabolism and include elevations in TC, LDL-C, or triglycerides, or deficiencies of HDL-C. TC levels increase from birth, stabilize at approximately 2 years of age, peak before puberty, and then decline slightly during adolescence. Normal values for lipids in children and adolescents are currently defined according to population distributions of lipid levels from the Lipid Research Clinics (LRC) Prevalence Study conducted in the 1970s.1 Dyslipidemia is commonly defined as TC >200 mg/dL and LDL-C >130 mg/dL; these values correspond to the 95% percentile observed in the LRC study. More recent studies, including the National Health and Nutrition Examination Survey, indicate that age, sex, racial differences, and temporal trends shift these population-based cut points.2

Although dyslipidemia in adults is an established risk factor for CHD based on good quality evidence from long-term prospective studies, the CHD risk attributable to dyslipidemia during childhood is unknown. Indirect evidence from the Bogalusa Heart Study, a long-term epidemiologic study of risk factors for CHD from birth through 31 years of age, showed a correlation between lipid levels and arterial fat deposition seen at autopsy; however, such evidence does not directly link childhood lipid levels to health outcomes.3 Epidemiologic studies in children establish a strong statistical association between childhood overweight and dyslipidemia.2 Other risk factors for dyslipidemia include an established family history for common familial dyslipidemias including familial hypercholesterolemia, familial combined hypercholesterolemia, familial defective apoprotein B, and familial hypertriglyceridemia. Secondary causes of dyslipidemia include diabetes, nephrotic syndrome, and hypothyroidism.2

The USPSTF did not find direct evidence that screening for dyslipidemia leads to improvements in CHD-related mortality or overall mortality; therefore it reviewed the evidence on accuracy of screening tests including family history, efficacy of treatment, and harms of screening and treatment in children.

Accuracy of Screening Tests
TC and HDL-C can be measured on nonfasting venous or capillary blood samples, LDL-C requires fasting samples, and direct LDL-C can be measured on nonfasting venous samples. At least two measurements are necessary to ensure that true values are within 10% of the mean of the measurements. Fair-quality evidence shows that a value of TC minus HDL-C above the 95th percentile is 88% to 96% sensitive and 98% specific for detecting LDL-C >130 mg/dL.4-6 Although use of family history presents one potential method to target serum lipid screening to a group of children and adolescents with higher risk for dyslipidemia, its use is limited. Family history is time-consuming to elicit accurately, it has been variably defined in the literature, and its use as a screening tool has been shown to miss substantial numbers (30% to 60% in general) of children with elevated lipids. Family history definitions vary substantially among studies as do lipid detection thresholds; those studies that show higher sensitivities (~77%) have low specificities (≤55%).2 Population-based estimates of the number of children requiring serum lipid testing based on positive family history may range from 25% to 55%, depending on definitions of family history and serum LDL cut-off values.

Accurate screening tests in children would be useful if childhood dyslipidemia correlated with adult CHD health outcomes or with adult dyslipidemia as an intermediate outcome and if treatment improved CHD outcomes

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Screening for Lipid Disorders in Children: U.S. Preventive Services Task Force Recommendation Statement