Draft Recommendation Statement
Lipid Disorders in Children and Adolescents: Screening
December 21, 2015
Recommendations made by the USPSTF are independent of the U.S. government. They should not be construed as an official position of the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.
Dyslipidemia, a genetic or multifactorial disorder of lipoprotein metabolism, is defined by elevations in total cholesterol, low-density lipoprotein (LDL) cholesterol, non–high-density lipoprotein (HDL) cholesterol, and/or triglycerides, as well as lower HDL cholesterol. Elevations in total, LDL, and nonHDL cholesterol are associated with risk of cardiovascular disease in adults, as is lower HDL cholesterol and, to a lesser extent, elevated triglycerides.
Heterozygous familial hypercholesterolemia occurs in approximately 1 out of every 200 to 500 persons in North America and Europe.1 Familial hypercholesterolemia is variably defined in the literature but generally includes highly elevated LDL cholesterol levels (e.g., ≥190 mg/dL), genetic mutation, or both.
Alternatively, dyslipidemia can be multifactorial, with both polygenic and environmental determinants, including obesity. Multifactorial dyslipidemia includes elevated LDL cholesterol (≥130 mg/dL), total cholesterol (≥200 mg/dL), or both that are not the result of familial hypercholesterolemia.2 Obesity is associated with slight elevations in LDL cholesterol; it is more strongly related to elevated triglycerides and lower HDL cholesterol.
Recent estimates from the National Health and Nutrition Examination Survey (NHANES) indicate that 7.8% of children ages 8 to 17 years have elevated total cholesterol (≥200 mg/dL) and 7.4% of adolescents ages 12 to 19 years have elevated LDL cholesterol (≥130 mg/dL).1, 3, 4
The rationale for screening for lipid disorders in children and adolescents is that early identification and treatment of elevated LDL cholesterol could delay the atherosclerotic process and thereby reduce the incidence of premature ischemic cardiovascular events in adulthood.
The USPSTF found inadequate evidence on the quantitative difference in diagnostic yield between universal and selective screening for familial hypercholesterolemia or multifactorial dyslipidemia.
Benefits of Early Detection and Treatment
The USPSTF found inadequate direct evidence on the benefits of screening for familial hypercholesterolemia or multifactorial dyslipidemia.
The USPSTF found adequate evidence from short-term trials (≤2 years) that pharmacotherapy results in substantial reductions in LDL and total cholesterol in children with familial hypercholesterolemia. One short-term pharmacotherapy trial reported a reduction in carotid intima–media thickness. The USPSTF found inadequate evidence to address whether short-term pharmacotherapy leads directly to a reduced incidence of premature cardiovascular disease (e.g., myocardial infarction or stroke). The USPSTF found inadequate evidence on the association of changes in intermediate lipid outcomes or noninvasive measures of atherosclerosis in children and adolescents with incidence of or mortality from relevant adult health outcomes.
The USPSTF found inadequate evidence on the benefits of lifestyle modification or pharmacotherapy interventions in children and adolescents with multifactorial dyslipidemia in improving intermediate lipid outcomes or atherosclerosis markers or in reducing incidence of premature cardiovascular disease.
Harms of Early Detection and Treatment
The USPSTF found inadequate evidence to assess the harms of screening for familial hypercholesterolemia or multifactorial dyslipidemia. The USPSTF found inadequate evidence to assess the long-term harms of treatment of familial hypercholesterolemia in children or adolescents. Long-term evidence on the treatment of familial hypercholesterolemia was limited to one study of statins. Short-term statin use was generally well tolerated in children and adolescents with familial hypercholesterolemia, with transient adverse effects (such as elevated liver enzymes). Treatment with bile-sequestering agents was commonly associated with gastrointestinal symptoms and poor palatability. The USPSTF found inadequate evidence to assess the harms of treatment of multifactorial dyslipidemia in children or adolescents. One study of a low-fat, low-cholesterol dietary intervention in children with multifactorial dyslipidemia showed no harms.
The USPSTF concludes that the current evidence is insufficient and that the balance of benefits and harms of screening for lipid disorders in asymptomatic children and adolescents younger than age 20 years cannot be determined.
Patient Population Under Consideration
This recommendation applies to asymptomatic children and adolescents younger than age 20 years without a known diagnosis of a lipid disorder.
In addition to screening in children and adolescents younger than age 20 years, the USPSTF also systematically searched for evidence on the effects of screening for lipid disorders in adults ages 21 to 39 years. The USPSTF found no evidence that screening in young and middle-aged adults improves short- or long-term cardiovascular outcomes; thus, the USPSTF has no recommendation for this age group.
Suggestions for Practice Regarding the I Statement
Potential Preventable Burden
Heterozygous familial hypercholesterolemia is an autosomal dominant disorder that causes severe elevations in LDL cholesterol, resulting in early atherosclerotic lesions. It is generally asymptomatic in childhood and is rarely associated with cardiovascular events in the first two decades of life.1 The burden of familial hypercholesterolemia is due to premature cardiovascular events in adulthood. Studies conducted before statin use became common suggest that the condition is associated with a cumulative incidence of ischemic heart disease in 1 out of 6 men and 1 out of 10 women by age 40 years. By age 50 years, 25% of women and 50% of men with untreated familial hypercholesterolemia will experience clinical cardiovascular disease.4 Coronary artery disease occurs in 50% of men by age 50 years and 30% of women by age 60 years.5, 6 Coronary artery disease–related mortality is increased in adults younger than age 60 years with familial hypercholesterolemia. Among adults surviving to age 60 years, the risk of coronary heart disease approaches that of the general population.1, 7
Multifactorial dyslipidemia includes elevated LDL cholesterol (≥130 mg/dL) or total cholesterol (≥200 mg/dL) that is not a result of familial hypercholesterolemia.2 Several longitudinal studies have documented an association between childhood lipid levels in this range and measures of atherosclerosis. Studies show that tracking lipid levels from childhood and adolescence to adulthood cannot predict which individuals will have elevated LDL or total cholesterol as adults.2 In addition, the association between multifactorial dyslipidemia in childhood and adolescence and clinical cardiovascular disease in adulthood is unknown.
Most children with elevated lipid levels will not progress to a clinically important lipid disorder or develop premature cardiovascular disease and are therefore subject to overdiagnosis. Screening could result in the labeling of children with a “nondisease,” parental or child anxiety, or unnecessary or harmful testing and treatment. The adverse effects of long-term use of lipid-lowering pharmacotherapy and lifestyle modification (including diet and physical activity) have not been adequately studied.
Generally, screening rates for dyslipidemia in children and adolescents seen in primary care have been low. According to the National Ambulatory Medical Care Survey, 2.5% of well-child visits in 1995 included lipid testing, and 3.2% included it in 2010.8 Claims data from health insurance plans report rare use of lipid-lowering pharmacotherapy in 8- to 20-year-olds. Among more than 13 million children, 665 initiated lipid-lowering therapy, for an incidence rate of 2.6 prescriptions per 100,000 person-years (95% CI, 0.1 to 2.7).9
Normal lipid values for children and adolescents are currently defined by population distributions of lipid levels from the Lipid Research Clinics Prevalence Study, conducted in the 1970s.2, 10 In 1992, the National Cholesterol Education Program (NCEP) proposed fixed threshold values to define dyslipidemia in children (total cholesterol of ≥200 mg/dL, LDL cholesterol of ≥130 mg/dL, or both). These values are slightly lower than the 95th percentile observed in the Lipid Research Clinics Prevalence Study for both boys and girls at nearly all ages, although there are some age-related variations in adolescence.2, 11
Cholesterol levels vary by sex and with age throughout childhood. Total cholesterol levels increase from birth, stabilize at approximately age 2 years, peak before puberty, and then decline slightly during adolescence.2, 12 The accepted cutoff values for elevated LDL and total cholesterol may overidentify or underidentify children and adolescents, depending on age and sex.2 Abnormal lipid levels in youth are based on population distributions, not associations with health outcomes. It is unclear to what degree elevated lipid levels in children and adolescents younger than age 20 years are associated with future disease risk.
Elevated lipid levels track modestly into adulthood, making it difficult to predict which children and adolescents will continue to have elevated cholesterol in adulthood.2, 13, 14 Longitudinal studies suggest that elevated LDL cholesterol in adolescence predict elevated LDL cholesterol 15 to 20 years later, with a positive predictive value of 32.9% to 37.3%, and lower predictive values among younger children.15
Serum (or plasma) total and HDL cholesterol do not change appreciably according to a fasting or nonfasting state. Serum LDL cholesterol levels may be calculated using the Friedewald formula: LDL cholesterol = total cholesterol − (triglycerides/5) − HDL cholesterol. Because accurate calculation depends on triglyceride levels, fasting serum testing is required. Direct LDL cholesterol measurement does not require fasting and is preferred when triglyceride levels are greater than 400 mg/dL.2 Recent guidelines on screening for dyslipidemia in children recommend initial screening for either LDL or nonHDL cholesterol.16
Screening strategies for dyslipidemia in clinical practice include selective or universal screening. Selective screening is based on family history of dyslipidemia or premature cardiovascular disease. Universal screening is based only on age. Cascade screening is a common screening strategy for familial hypercholesterolemia in other countries. Cascade screening involves case-finding among relatives of patients with confirmed familial hypercholesterolemia and testing for genetic variants identified in the first affected relative (i.e., the proband). However, the U.S. health system does not currently have the infrastructure to implement cascade screening.2
Treatment of Dyslipidemia
Interventions for dyslipidemia include lifestyle modification (e.g., changes in diet and physical activity) and pharmacotherapy (e.g., statins, bile-sequestering agents, or inhibitors of cholesterol absorption).
The USPSTF recommends that clinicians screen for obesity in children age 6 years or older and offer them or refer them to a comprehensive, intensive behavioral intervention (B recommendation).17 The USPSTF found insufficient evidence on screening for primary hypertension in asymptomatic children and adolescents to prevent subsequent cardiovascular disease in childhood or adulthood (I statement).18 These recommendations are available on the USPSTF Web site (www.uspreventiveservicestaskforce.org).
Research Needs and Gaps
Randomized trials of screening programs are needed to assess the benefits and harms of combined screening and treatment programs for familial hypercholesterolemia in children and adolescents. For both familial hypercholesterolemia and multifactorial dyslipidemia, long-term, controlled treatment trials of lipid-lowering medications, supplements, dietary interventions, or combinations thereof are needed to assess harms, as well as effectiveness in improving intermediate and health outcomes in adulthood.1, 2 These trials should be conducted in racially and ethnically diverse U.S. populations. In the absence of randomized, controlled trials of screening programs, treatment studies in patients with screen-detected multifactorial dyslipidemia would be informative. In addition, longitudinal studies would help to better understand the association of intermediate outcomes in childhood and adolescence with premature myocardial infarction and stroke in adulthood.1, 2
With these studies, it may be possible to consider age- and sex-specific—rather than fixed—cutoff values to define thresholds for abnormal total and LDL cholesterol.2
Burden of Disease
Estimates from the 2011–2012 NHANES show a prevalence of elevated total cholesterol in children ages 8 to 17 years of 7.8%, and estimates from the 2007–2010 NHANES show a prevalence of elevated LDL cholesterol in adolescents of 7.4%. These are likely overestimates of the true prevalence of dyslipidemia due to within-person variability. Repeat testing is needed to reliably identify children and adolescents with elevated lipid levels.2-4, 10
Much attention has been directed at screening for dyslipidemia in childhood and adolescence because of the following: atherosclerosis starts in youth; lipid levels in youth are associated with the extent of atherosclerosis in adulthood; familial hypercholesterolemia is associated with premature ischemic cardiovascular disease; short-term treatment of familial hypercholesterolemia with statins substantially lowers LDL cholesterol and, based on one study, improves measures of atherosclerosis; abnormal lipid levels in adulthood have been strongly associated with the risk of coronary heart disease events; and early identification and intervention with cholesterol-lowering therapy in certain populations of adults can prevent such events.
Screening in children and adolescents may identify youth with undiagnosed familial hypercholesterolemia or multifactorial dyslipidemia. However, the clinical health benefits and risks among children and adolescents identified and treated for dyslipidemia have not been sufficiently studied, making the role of screening in children and adolescents uncertain.
Scope of Review
To update its 2007 recommendation,19 the USPSTF commissioned two systematic evidence reviews on screening for lipid disorders in children and adolescents (age <20 years). Based on public comment on the draft research plan, the USPSTF decided to conduct two separate reviews: one on screening for familial hypercholesterolemia and the other on screening for multifactorial dyslipidemia. The review on familial hypercholesterolemia focused on heterozygous familial hypercholesterolemia. Homozygous familial hypercholesterolemia and secondary causes of dyslipidemia (such as diabetes, nephrotic syndrome, or hypothyroidism) were outside the scope of the review.
Accuracy of Screening Tests
The review identified two fair-quality studies of universal screening for familial hypercholesterolemia. Both studies took place in school settings. The first study, the Coronary Artery Risk Detection in Appalachian Communities (CARDIAC) Project, was a universal screening program (n=81,156) in West Virginia schools intended to identify the prevalence of cardiac risk factors, such as obesity, dyslipidemia, hypertension, and glucose intolerance.20 The second study was a Danish screening study (n=2,085) that measured apolipoprotein levels as a screening test for familial hypercholesterolemia. No studies on selective screening for familial hypercholesterolemia were identified.1, 21
The CARDIAC Project reported a diagnostic yield of about 1.3 cases per 1,000 persons screened when familial hypercholesterolemia was diagnosed based on a LDL cholesterol level greater than 155 mg/dL, total cholesterol level greater than 260 mg/dL, or both, plus DNA evidence of a genetic mutation in a first- or second-degree relative.20 The Danish study identified 10 subjects based on laboratory testing and a family history consistent with familial hypercholesterolemia, for a diagnostic yield of 4.8 cases per 1,000 persons screened.1, 21
No studies on selective screening for multifactorial dyslipidemia were identified.
An Ohio study (n=6,500) used a nonfasting total cholesterol threshold of 200 mg/dL or greater to universally screen for multifactorial dyslipidemia in children and adolescents. The prevalence of elevated nonfasting total cholesterol was 8.5%. After confirmatory testing using a fasting LDL cholesterol threshold of 130 mg/dL or greater, the positive predictive value was 77% and the diagnostic yield was 5.8%.2, 22
Population-based studies suggest that approximately 8% to 11% of children and adolescents would screen positive using the NCEP nonfasting total cholesterol threshold of 200 mg/dL or greater. Point estimates of the prevalence of elevated total cholesterol from three large, population-based U.S. studies were combined with the positive predictive value derived from the Ohio study to simulate diagnostic yield (screening yield x positive predictive value of the initial screen). Simulated diagnostic yield ranged from 4% to 12% for different age and body mass index subgroups. Subgroups with the highest diagnostic yield were children with obesity (12.3%) and overweight (8.9%), children ages 9 to 11 years (7.2%), and adolescents ages 16 to 19 years (7.2%).2
Effectiveness of Early Detection and Treatment
No direct evidence was found that reported on selective or universal screening and intermediate or health outcomes in children or adolescents with familial hypercholesterolemia.
Thirteen randomized, blinded trials (n=1,789) examined the effectiveness of lipid-lowering medications in children and adolescents. No evidence on the effectiveness of dietary supplements or lifestyle interventions on intermediate outcomes in children with familial hypercholesterolemia was found. The 13 fair- to good-quality trials included eight trials of statins, three trials of bile-sequestering agents, and two trials of a cholesterol absorption inhibitor.1
Trials included 54 to 248 participants whose ages ranged from 6 to 18 years (mean age range, 8 to 15 years). Both sexes were well represented. When reported, the majority of study participants were white. The trials were conducted in countries with a high Human Development Index (>0.9). Study participants were patients at tertiary-care lipid clinics. Trial duration ranged from 6 weeks to 2 years, with most lasting less than 1 year. All trials excluded participants with homozygous familial hypercholesterolemia, secondary dyslipidemia, or use of medications that could affect lipid levels. Familial hypercholesterolemia was defined on the basis of elevated fasting lipid levels and family history, using various standard criteria.1
Statin trials included pravastatin, simvastatin, lovastatin, atorvastatin, and rosuvastatin. They reported statistically significant reductions in LDL cholesterol from baseline, with most effect sizes ranging from 20% to 40% compared with placebo. Due to the variability in medication, dosage, and duration of treatment, data were not pooled across trials.1
Dose response was seen in two studies of pravastatin and rosuvastatin. The greatest effect on LDL cholesterol was in a trial of rosuvastatin. In that trial, the only statin study in which treatment targets were reported, only 12% to 41% of participants reached the target LDL cholesterol of less than 110 mg/dL, with greater effects at higher doses. Participants who received the highest dose (20 mg/day) had a 50% reduction (least mean square estimate) from baseline in LDL cholesterol compared with 1% in the control group (p<0.001). The effects of statins on HDL cholesterol were mixed, with some studies reporting minimal improvement and others showing no change. Trials that evaluated total cholesterol found reductions of 20% to 30% from baseline compared with placebo. One trial of pravastatin reported a 2.0% reduction in carotid intima–media thickness in the treatment group compared with a 1.0% increase in the control group. The mean change in carotid intima–media thickness differed significantly between groups (p=0.02).1
Three trials of bile-sequestering agents (colesevelam, cholestyramine, and colestipol) reported more modest effects on LDL and total cholesterol, with similar effect sizes across studies. The study of colesevelam showed a dose response. Only 3.2% to 7.9% of participants reached target LDL cholesterol of 110 mg/dL or less, with greater effects at higher doses.1
One drug, an intestinal cholesterol absorption inhibitor (ezetimibe; studied in two randomized, controlled trials), also showed smaller effects on LDL cholesterol in a trial of combination therapy with simvastatin. Ezetimibe reduced LDL cholesterol by 54% compared with 38% using simvastatin alone. In a trial assessing ezetimibe monotherapy compared with placebo, ezetimibe reduced LDL cholesterol by 28% (95% CI, -31 to -25) from baseline compared with a negligible change in the placebo group.1
No evidence was found on lifestyle modification alone or dietary supplements as treatment of familial hypercholesterolemia in children or adolescents. No evidence was found on the effectiveness of interventions in childhood or adolescence on cardiovascular outcomes in adulthood. There was also a lack of evidence on the association between intermediate outcomes in childhood or adolescence and health outcomes in adulthood among those with familial hypercholesterolemia.1
No direct evidence was found that evaluated selective or universal screening and intermediate or health outcomes in children or adolescents with multifactorial dyslipidemia.2
There is also a lack of evidence on the effectiveness of treatment in childhood on adult health outcomes. However, two trials were found that addressed the effectiveness of treatment on intermediate outcomes in children with multifactorial dyslipidemia.2
A good-quality trial, Dietary Intervention Study in Children (n=663), evaluated a modified NCEP Step II diet (low-fat and low-cholesterol) delivered using an intensive multiyear, family-based counseling intervention in children ages 8 to 10 years.23 Study participants had a mean baseline LDL cholesterol level of 131 mg/dL, which is close to the minimum threshold for dyslipidemia. Outcomes were evaluated at 1, 3, and 5 years after randomization, at the end of the trial (about 8 years after randomization), and 9 years after the end of the trial (about 17 years after randomization). The intervention resulted in statistically significant reductions in mean LDL and total cholesterol in the intervention versus control groups at 1 and 3 years. The mean adjusted between-group difference was greatest in year 1 (total cholesterol, -6.1 mg/dL; LDL cholesterol, -4.8 mg/dL; p<0.001) and smaller, but still statistically significant, in year 3 (total cholesterol, -3.3 mg/dL [p=0.04]; LDL cholesterol, -3.3 mg/dL [p=0.02]). However, the groups did not differ significantly at year 5, 7, or 18.2, 23
A small, fair-quality trial (n=32) of 30 g per day of flaxseed supplementation found no effect at 4 weeks on total or LDL cholesterol in children ages 8 to 18 years with moderate to severe dyslipidemia.2, 24
One high-quality, longitudinal study (n=9,245) of adolescents and young adults (ages 12 to 39 years) from the NHANES evaluated the association between mortality before age 55 years and several cardiovascular risk factors, including lipid levels. In multivariate models, neither highly elevated cholesterol (total cholesterol ≥240 mg/dL) nor moderately increased total cholesterol (200 to 239 mg/dL) was independently associated with death (all causes and endogenous causes) when both sexes were combined. Extremely elevated cholesterol (total cholesterol ≥240 mg/dL) was associated with a greater risk of death (endogenous causes) before age 55 years (relative hazard, 2.58 [95% CI, 1.31 to 5.08]) in females only. However, this estimate was based on a small number of deaths.25
A good-quality trial suggests that a low-fat, low-cholesterol diet with intensive counseling has a modest effect on LDL cholesterol in children and adolescents with multifactorial dyslipidemia,2, 23 but the effect dissipates with time. No evidence was found on dietary supplements for the treatment of multiple dyslipidemia in children or adolescents. No evidence was found on the effectiveness of interventions in childhood or adolescence on cardiovascular outcomes in adulthood. There was also a lack of evidence on the association between intermediate outcomes in childhood or adolescence and health outcomes in adulthood among persons with multiple dyslipidemia.2
Potential Harms of Screening and Treatment
No studies reported on the harms of screening for familial hypercholesterolemia in children and adolescents. Evidence was available from short-term trials of medication use in children and adolescents with familial hypercholesterolemia. The USPSTF evaluated 18 fair- to good-quality trials (n=2,210) for the harms of treatment of familial hypercholesterolemia in children and adolescents, including 13 trials of statins, three trials of bile-sequestering agents, and two trials of a cholesterol absorption inhibitor (ezetimibe). Most were applicable to the U.S. primary health care setting. Study duration mostly ranged from 8 weeks to 2 years; the longest was 10 years.1 Bile-sequestering agents were commonly associated with gastrointestinal symptoms and poor palatability. Statins were well tolerated; elevated liver enzyme or creatine kinase levels or both were observed in some studies but were transient. Ten trials evaluated the effects of statin use on growth or sexual maturation and found no reported abnormalities. Ezetimibe was well tolerated in short-term studies.1
Overall, evidence of treatment harms was limited to only one long-term study. The study was a 10-year cohort followup of a 2-year trial of pravastatin followed by continued statin use over the intervening years. Sex hormone levels were measured in young adult siblings (mean age, 24 years). Young men with familial hypercholesterolemia had lower dehydroepiandrosterone sulfate levels, within normal ranges, compared with their unaffected siblings. However, this difference is of unknown clinical significance.26
No studies were found that reported on the harms of screening for multifactorial dyslipidemia in children and adolescents.
The only trial that evaluated harms of treatment in children with multifactorial dyslipidemia was the Dietary Intervention Study in Children, which evaluated a dietary intervention combined with behavioral counseling in children with multifactorial dyslipidemia. This good-quality trial demonstrated no harms in anthropometric, laboratory, psychosocial, or sexual maturation measures during the trial or long-term followup (18 years), suggesting that low-fat, low-cholesterol dietary interventions may not be harmful in children.2
Estimate of Magnitude of Net Benefit
The USPSTF found inadequate evidence on the quantitative difference in diagnostic yield between universal and selective screening approaches. There is inadequate evidence on the effectiveness and harms of long-term treatment and the harms of screening. The USPSTF also found inadequate evidence on the association between changes in intermediate outcomes (e.g., lipid levels or noninvasive measures of atherosclerosis) and improvements in adult cardiovascular health outcomes. Therefore, the USPSTF concludes that the evidence on the benefits and harms of screening for lipid disorders in children and adolescents younger than age 20 years is insufficient and that the balance of benefits and harms cannot be determined.
How Does the Evidence Fit With Biological Understanding?
Left untreated, familial hypercholesterolemia leads to premature clinical atherosclerotic cardiovascular events in adulthood resulting from long-term exposure to elevated serum cholesterol. Cardiovascular events rarely occur in the first two decades of life, typically taking place during the fourth decade. Because of the lack of evidence on the long-term benefits and harms of medication, it is not known whether there is benefit to initiating treatment in childhood versus later in adolescence or adulthood. It is also not known if improvement in intermediate outcomes results in improvement in adult health outcomes.
Multifactorial dyslipidemia in childhood and adolescence is a risk factor for future atherosclerosis in adulthood. Although elevated lipid levels can continue into adulthood, they do so inconsistently, making it difficult to predict which children and adolescents will have elevated cholesterol as adults. The relationship between dyslipidemia in adults and coronary heart disease in adults has been well established; however, the association between multifactorial dyslipidemia in childhood and adolescence and future disease risk in adulthood is unknown.
This recommendation updates the 2007 USPSTF recommendation on screening for lipid disorders in children, adolescents, and young adults. This recommendation is similar to the previous recommendation in that the evidence to assess the balance of benefits and harms of screening for lipid disorders remains insufficient.
The National Heart, Lung, and Blood Institute’s Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents16 and the American Academy of Pediatrics’ Bright Futures27 recommend universal screening before adolescence (ages 9 to 11 years) and again after puberty (ages 17 to 21 years). Selective screening (e.g., based on family history and other risk factors) is recommended for younger children starting at age 2 years. The American Academy of Family Physicians28 states that there is insufficient evidence to recommend for or against routine screening for lipid disorders in infants, children, adolescents, or young adults (up to the age of 20 years). The U.K. National Screening Committee29 indicates that there is insufficient evidence to recommend universal screening, though a project is currently underway to evaluate cascade screening.
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2. Lozano P, Henrikson NB, Dunn J, et al. Lipid Screening in Childhood for Detection of Multifactorial Dyslipidemia: A Systematic Evidence Review for the U.S. Preventive Services Task Force. Evidence Synthesis No. 140. AHRQ Publication No. 14-05204-EF-1. Rockville, MD: Agency for Healthcare Research and Quality;2015.
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15. Magnussen CG, Raitakari OT, Thomson R, et al. Utility of currently recommended pediatric dyslipidemia classifications in predicting dyslipidemia in adulthood: evidence from the Childhood Determinants of Adult Health (CDAH) study, Cardiovascular Risk in Young Finns Study, and Bogalusa Heart Study. Circulation. 2008;117(1):32-42.
16. Expert Panel on Integrated Guidelines for Cardiovascular Health Risk Reduction in Children and Adolescents, National Heart Lung and Blood Institute. Expert panel on integrated guidelines for cardiovascular health and risk reduction in children and adolescents: summary report. Pediatrics. 2011;128(Suppl 5):S213-56.
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18. U.S. Preventive Services Task Force. Screening for primary hypertension in children and adolescents: U.S. Preventive Services Task Force recommendation statement. Pediatrics. 2013;132(5):907-14.
19. U.S. Preventive Services Task Force. Screening for Lipid Disorders in Children: U.S. Preventive Services Task Force Recommendation Statement. 2007. Accessed at http://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/lipid-disorders-in-children-screening on 15 December 2015.
20. Cottrell L, John C, Murphy E, et al. Individual-, family-, community-, and policy-level impact of a school-based cardiovascular risk detection screening program for children in underserved, rural areas: the CARDIAC Project. J Obes. 2013;2013:732579.
21. Skovby F, Micic S, Jepsen B, et al. Screening for familial hypercholesterolaemia by measurement of apolipoproteins in capillary blood. Arch Dis Child. 1991;66(7):844-7.
22. Garcia RE, Moodie DS. Routine cholesterol surveillance in childhood. Pediatrics. 1989;84(5):751-5.
23. Obarzanek E, Hunsberger SA, Van Horn L, et al. Safety of a fat-reduced diet: the Dietary Intervention Study in Children (DISC). Pediatrics. 1997;100(1):51-9.
24. Wong H, Chahal N, Manlhiot C, et al. Flaxseed in pediatric hyperlipidemia: a placebo-controlled, blinded, randomized clinical trial of dietary flaxseed supplementation for children and adolescents with hypercholesterolemia. Pediatrics. 2013;167(8):708-13.
25. Saydah S, Bullard KM, Imperatore G, et al. Cardiometabolic risk factors among U.S. adolescents and young adults and risk of early mortality. Pediatrics. 2013;131(3):e679-86.
26. Kusters DM, Avis HJ, de Groot E, et al. Ten-year follow-up after initiation of statin therapy in children with familial hypercholesterolemia. JAMA. 2014;312(10):1055-7.
27. American Academy of Pediatrics. Recommendations for Preventive Pediatric Health Care. 2015. Accessed at https://www.aap.org/en-us/professional-resources/practice-support/Periodicity/Periodicity%20Schedule_FINAL.pdf on 15 December 2015.
28. American Academy of Family Physicians. Clinical Preventive Service Recommendation: Lipid Disorders, Infants, Children, Adolescents, and Young Adults. 2007. Accessed at http://www.aafp.org/patient-care/clinical-recommendations/all/lipid-disorders.html on 15 December 2015.
29. U.K. National Screening Committee. The UK NSC Recommendation on Familial Hypercholesterolaemia Screening in Children. 2015. Accessed at http://legacy.screening.nhs.uk/familialhypercholesterolaemia-child on 15 December 2015.