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Screening for Lipid Disorders in Children: US Preventive Services Task Force Recommendation Statement

2007; American Academy of Pediatrics; Volume: 120; Issue: 1 Linguagem: Inglês

10.1542/peds.2006-1812

1098-4275

Ned Calonge, Diana B. Petitti, Thomas G. DeWitt, Leon Gordis, Kimberly D. Gregory, Russell Harris, Kenneth W. Kizer, Michael L. LeFevre, Carol Loveland‐Cherry, Lucy N. Marion, Virginia A. Moyer, Judith K. Ockene, George F. Sawaya, Albert L. Siu, Steven M. Teutsch, Barbara P. Yawn,

Obesity and Health Practices

The US Preventive Services Task Force (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) (I recommendation).There is good evidence that children with lipid disorders (dyslipidemia) are at risk for becoming adults with lipid disorders.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.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.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.The USPSTF was unable to determine the balance between potential benefits and harms for routinely screening children and adolescents for dyslipidemia.Dyslipidemias are disorders of lipoprotein metabolism and include elevations in TC, LDL-C, or triglyceride levels or deficiencies of HDL-C. TC levels increase from birth, stabilize at ∼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 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 95th percentile observed in the Lipid Research Clinics 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.2Although dyslipidemia in adults is an established risk factor for CHD on the basis of 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.2The 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.TC and HDL-C levels can be measured on nonfasting venous or capillary blood samples, LDL-C measurement requires fasting samples, and direct LDL-C can be measured on nonfasting venous samples. At least 2 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 a 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%–60%, in general) of children with elevated lipid levels. 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 who require serum lipid testing on the basis of positive family history may range from 25% to 55%, depending on definitions of family history and serum LDL cutoff 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. Serial correlations between lipid levels measured in individual children over time vary on the basis of the type of lipid level followed. On the basis of the evidence from 23 prospective cohort studies, correlations have been found to be higher for TC (r = 0.38–0.78) and LDL-C (r = 0.4–0.7) levels than for HDL-C (r = 0.0–0.8) and triglyceride (r = 0.1–0.58) levels, and good-quality evidence indicates that ∼40% to 55% of children with elevated TC and LDL levels will continue to have elevated lipid levels on follow-up into adolescence and early adulthood.2 No studies examine tracking of lipid levels in those with risk factors for dyslipidemia (eg, childhood overweight).Treatment of childhood dyslipidemia has been shown to be effective in lowering lipid levels in select populations; however, no studies have addressed the effect of treatment on childhood or adult health outcomes (eg, CHD events). In those children with diagnosed monogenic dyslipidemia, a condition that has been associated with premature CHD events, no RCTs are likely be completed to provide health outcomes in untreated controls. In this population of children with familial monogenic dyslipidemias (familial hypercholesterolemia or familial combined hyperlipidemia), good-quality evidence based on a meta-analysis of 9 RCTs demonstrated the effectiveness of statins in reducing intermediate outcomes: TC and LDL (percent mean reduction [95% confidence limits] from meta-analysis of trials: 24.4% [19.5, 29.2] for TC and 30.8% [24.1, 37.5] for LDL in 8 studies).2 Fair evidence based on 2 fair-quality trials shows that bile-acid–binding resins reduce lipid levels in children with monogenic dyslipidemia.7,8 RCTs of diet supplements (psyllium, oat, garlic extract, and sterol margarine) and advice show marginal improvements in lipid levels in children with monogenic dyslipidemia.2 There is fair-quality evidence that dietary counseling is associated with minimal improvements in lipid levels in children with monogenic and multifactorial dyslipidemias; however, these improvements may not be sustained after the counseling intervention ceases.9–15 There are no studies of physical activity interventions in those with monogenic dyslipidemia and fair-quality evidence in those with multifactorial dyslipidemia based on a meta-analysis of 6 trials that showed that physical activity interventions were associated with minimal to no improvement in lipid levels in children with multifactorial dyslipidemia (percent mean reduction [95% confidence limits] from meta-analysis of trials: 0% [−5.6, 5.6] for TC and 3.1% [−7.7, 1.5] for LDL-C reduction in 4 studies).2There is poor-quality evidence on the adverse effects of screening. There are conflicting reports about behavioral difficulties in screened children and reports of parental noncompliance with recommendations for diet and follow-up. Studies have shown no increases in anxiety among screened children and adolescents.2 Fair-quality evidence on the harms of treatment is based on 81 controlled and noncontrolled studies of treatment that reported a variety of adverse effects of drug, diet, exercise, and combination therapy in children and adolescents.2 Lipid-lowering agents have been shown to cause elevations in creatine kinase and liver-function tests (statins), gastrointestinal adverse effects, and decreased absorption of vitamins and minerals (bile-acid resins). The adverse effects of long-term use of lipid-lowering agents (eg, for >20 years) have not been studied. There have been 3 reports of growth retardation and nutritional dwarfing in children on unmonitored diets; however, there are several reports of normal growth during monitored low-fat diet interventions.2 Physical activity interventions have had no reported harms in children without monogenic dyslipidemia, but an exaggerated blood pressure response was seen in children with monogenic dyslipidemias who were undergoing physical activity intervention.No professional organization recommends universal screening for dyslipidemia in children or adolescents. The NCEP report of the Expert Panel on Blood Cholesterol Levels in Children and Adolescents recommends selective screening for children and adolescents with a family history of premature CHD or at least 1 parent with a high TC level (TC ≥ 240 mg/dL) in the context of regular health care. Optional cholesterol testing may be recommended in children and adolescents who are judged to be at higher risk independent of family history or parental hypercholesterolemia (eg, those who are overweight or have high-fat diets).The American Academy of Pediatrics’ recommendations are based on this NCEP report and concur with its screening recommendations.16 The American College of Obstetricians and Gynecologists concurs with the NCEP recommendations for screening in adolescents.17 In 2003, the American Heart Association recommended performing targeted screening of fasting lipids in children >2 years of age with a family history of dyslipidemia or premature cardiovascular disease and in children for whom family history is unknown and other risk factors are present.18 In a 2007 update, the American Heart Association recommended, in addition, screening children who are overweight or obese.19The USPSTF grades its recommendations according to 1 of 5 classifications (A, B, C, D, and I) reflecting the strength of evidence and magnitude of net benefit (benefits minus harms). The USPSTF grades the quality of the overall evidence for a service on a 3-point scale (good, fair, poor).Evidence includes consistent results from well-designed, well-conducted studies in representative populations that directly assess effects on health outcomes.Evidence is sufficient to determine effects on health outcomes, but the strength of the evidence is limited by the number, quality, or consistency of the individual studies, generalizability to routine practice, or indirect nature of the evidence on health outcomes.Evidence is insufficient to assess the effects on health outcomes because of limited number or power of studies, important flaws in their design or conduct, gaps in the chain of evidence, or lack of information on important health outcomes.The following were the members of the USPSTF at the time this recommendation was finalized (for a list of current USPSTF members, go to www.ahrq.gov/clinic/uspstfab.htm): Ned Calonge, MD, MPH, chair, USPSTF (chief medical officer and state epidemiologist, Colorado Department of Public Health and Environment, Denver, CO); Diana B. Petitti, MD, MPH, vice-chair, USPSTF (senior scientific advisor for health policy and medicine, regional administration, Kaiser Permanente Southern California, Pasadena, CA); Thomas G. DeWitt, MD (Carl Weihl professor of pediatrics and director of the Division of General and Community Pediatrics, Department of Pediatrics, Children's Hospital Medical Center, Cincinnati, OH); Leon Gordis, MD, MPH, DrPH (professor, Epidemiology Department, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD); Kimberly D. Gregory, MD, MPH (director, Women's Health Services Research and Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA); Russell Harris, MD, MPH (professor of medicine, Sheps Center for Health Services Research, University of North Carolina School of Medicine, Chapel Hill, NC); Kenneth W. Kizer, MD, MPH (president and chief executive officer, National Quality Forum, Washington, DC); Michael L. LeFevre, MD, MSPH (professor, Department of Family and Community Medicine, University of Missouri School of Medicine, Columbia, MO); Carol Loveland-Cherry, PhD, RN (executive associate dean, Office of Academic Affairs, University of Michigan School of Nursing, Ann Arbor, MI); Lucy N. Marion, PhD, RN (dean and professor, School of Nursing, Medical College of Georgia, Augusta, GA); Virginia A. Moyer, MD, MPH (professor, Department of Pediatrics, University of Texas Health Science Center, Houston, TX); Judith K. Ockene, PhD (professor of medicine and chief of the Division of Preventive and Behavioral Medicine, University of Massachusetts Medical School, Worcester, MA); George F. Sawaya, MD (associate professor, Department of Obstetrics, Gynecology, and Reproductive Sciences and Department of Epidemiology and Biostatistics, University of California, San Francisco, CA); Albert L. Siu, MD, MSPH (professor and chairman, Brookdale Department of Geriatrics and Adult Development, Mount Sinai Medical Center, New York, NY); Steven M. Teutsch, MD, MPH* (executive director, Outcomes Research and Management, Merck & Company, Inc, West Point, PA); and Barbara P. Yawn, MD, MSc (director of research, Olmstead Research Center, Rochester, MN).