PEDIATRICS Vol. 105 No. 3 March 2000, pp. 637-638

COMMENTARY:
Cholesterol Screening in Children and Adolescents

The Committee on Nutrition of the American Academy of Pediatrics recently reiterated its recommendation that children and adolescents with a family history of high blood cholesterol or premature cardiovascular disease should be screened for high blood cholesterol.¹ In contrast, the American College of Physicians (ACP) does not recommend cholesterol screening in adults who may have familial hypercholesterolemia or other risk factors for coronary heart disease (CHD) until at least 25 to 30 years old in men and 35 to 40 years old in women.² Why the discrepant recommendations, and which ones should clinicians follow?

A review of the 2 sets of recommendations and their supporting documentation reveals a difference in the quality and quantity of evidence cited to support them. The ACP guideline is based on an exhaustive review of 45 clinical trials and 8 meta-analyses of cholesterol reduction. It includes projections of costs and of numbers-needed-to-treat to prevent 1 death in different risk groups.³ In contrast, the Committee on Nutrition statement primarily cites studies of cholesterol and arteriosclerosis in animals (7 references), cross-national comparisons (15 references), and studies of familial aggregation and tracking of cholesterol levels (16 references). The Committee on Nutrition does not quantify the costs or estimate the effects of the interventions it recommendsprecisely the numbers on which the ACP statement focuses. This turns out to be a key omission.

The Committee on Nutrition statement cites only 5 clinical trials of cholesterol-lowering interventions.^4-8 One trial, discussed below, was in children,⁸ the other 4^4-7 were studies of thousands of high-risk, middle-aged adults. Two of the adult trials^4,5 studied interventions that the committee recommends for children. The first trial, the Multiple Risk Factor Intervention Trial,⁴ tested a multifactorial intervention that included a cholesterol-lowering diet, blood pressure control, and smoking cessation counseling. Although this multifactorial intervention would likely overestimate benefits of dietary counseling alone, after 10.5 years the observed difference in CHD deaths was still small and not statistically significant (3.1% vs 3.4%; 2-tailed, P = .24). The second trial, the Lipid Research Clinics Coronary Primary Prevention Trial,^5,9 studied cholestyramine, a bile acid-binding resin recommended by the committee for treating children >10 years old with persistent high cholesterol levels. In the Lipid Research Clinics Coronary Primary Prevention Trial, the difference in CHD events approached statistical significance (2-tailed, P = .094). Even in these high-risk middle-aged men, however, the effect size was modest: it took an estimated 11 tons of cholestyramine to prevent 1 CHD death.¹⁰

The single clinical trial in children cited in the Committee on Nutrition statement is the Dietary Intervention Study in Children.⁸ The Committee devoted one half of its section on clinical trials to this study, without mentioning the magnitude of the effort required for the intervention or the size of its effect on blood cholesterol levels. To identify the 663 children that participated in the trial, the investigators needed to screen >44 000 children.⁸ For each enrolled child, the dietary intervention included 27 to 31 individual and group visits with nutritionists, behaviorists, and health educators and monthly telephone follow-up for 3 years. Despite this intensive effort, the observed difference in low-density lipoprotein-cholesterol levels between intervention and control groups, although statistically significant, was only 3.2 mg/dL.

The failure of the Committee to base its screening and treatment recommendations on estimates of the benefits, risks, and costs of the interventions it recommends may have harmful consequences. A 1995 survey of primary care physicians found that 76% of respondents screen at least some children for high blood cholesterol and that 17% screen all children.¹¹ A high proportion of these children, especially girls,¹² will have cholesterol levels exceeding those that the Committee calls acceptable. Among 5- to 9-year-old girls in the general population, for example, the prevalence of such levels is nearly 50%.¹³ Labeling these children as having high blood cholesterol levels and instituting a medically supervised treatment program as if they had a disease could contribute to a distorted view of the importance of childhood cholesterol levels and diet in determining heart disease risk. The excess risk associated with an elevated cholesterol level in childhood is small,¹⁴ the dietary treatment has little effect on blood cholesterol levels,^12,15 and the labeling could exacerbate an already high prevalence of eating disorders and fear of fat.^16-19 In a survey of fourth grade students in rural Iowa (n = 457), 46% of girls reported that they very often wish they were thinner and 21% very often feel guilty when they eat foods that might make them fat.¹⁸ Among South Carolina middle school girls (n = 1599), many had tried to lose weight by dieting (43%), fasting (11%), vomiting (6%), or taking diet pills (4%), laxatives (2%), or diuretics (2%).¹⁶ Identifying the 25% to 50% of these girls whose cholesterol levels are above the "acceptable" level and placing them on low-fat, low-cholesterol diets to reduce their risk of heart disease decades from now is not justified by a careful consideration of the likely risks and benefits.

How do physicians and parents manage children identified as having high cholesterol levels? The vast majority of primary care physicians initially recommend dietary management and follow-up.¹¹ In most cases, the parents do not comply, and their children simply do not keep their follow-up appointments.^20-22 However, in a recent survey ~16% of primary care physicians used drugs to treat high blood cholesterol levels in children.¹¹ The long-term safety of these medications is unknown, but we do know that they cause or promote cancer in rodents at only 2 to 45 times the exposures that humans receive.²³

In an era when time for office visits and resources for patient care are severely limited, when no intervention has been shown to be effective and safe for long-term use in children, and when labeling and medication use can lead to greater harms than benefits, childhood cholesterol screening is not justified. Clinicians should follow the recommendations of the ACP (and the US Preventive Health Services Taskforce²⁴) and defer cholesterol screening until adulthood.

Thomas B. Newman, MD, MPH
Departments of Epidemiology and Biostatistics, Pediatrics, and Laboratory Medicine
School of Medicine
University of California
San Francisco, CA 94143

Alan M. Garber MD, PhD
Department of Medicine
Stanford University School of Medicine and Veterans Affairs Palo Alto Health Care System
Palo Alto, CA 94304

FOOTNOTES

Received for publication Jun 14, 1999; accepted Nov 15, 1999.

Address correspondence to Thomas B. Newman, MD, MPH, Department of Epidemiology, University of California San Francisco, Box 0560, San Francisco, CA 94143. E-mail: newman{at}itsa.ucsf.edu

ABBREVIATIONS

ACP, American College of Physicians; CHD, coronary heart disease.

REFERENCES

1. American Academy of Pediatrics, Committee on Nutrition Cholesterol in childhood. Pediatrics 1998; 101:141-147 [Abstract/Free Full Text]
2. American College of Physicians. Guidelines for using serum cholesterol, high-density lipoprotein cholesterol, and triglyceride levels as screening tests for preventing coronary heart disease in adults. Ann Intern Med. 1996;124:515-517. Comments
3. Garber AM, Browner WS, Hulley SB. Cholesterol screening in asymptomatic adults, revisited. Ann Intern Med. 1996;124:518-531. Comments
4. The Multiple Risk Factor Intervention Trial Research Group. Mortality rates after 10.5 years for participants in the Multiple Risk Factor Intervention Trial: findings related to a priori hypotheses of the trial. JAMA. 1990;263:1795-1801. [Published erratum appears in JAMA. 1990;263:3151]. Comments
5. Lipid Research Clinics Program The Lipid Research Clinics Coronary Primary Prevention Trial results. I. Reduction in incidence of coronary heart disease. JAMA 1984; 251:351-364 [Abstract]
6. 4-8 Study Group Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study. Lancet 1994; 344:1383-1389 [CrossRef][Medline]
7. Shepherd J, Cobbe SM, Ford I, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group. N Engl J Med. 1995;333:1301-1307. Comments
8. DISC Collaborative Research Group Efficacy and safety of lowering dietary intake of fat and cholesterol in children with elevated low-density lipoprotein cholesterol. The Dietary Intervention Study in Children (DISC). JAMA 1995; 273:1429-1435 [Abstract]
9. Lipid Research Clinics Program The Lipid Research Clinics Coronary Primary Prevention Trial results. II. The relationship of reduction in incidence of coronary heart disease to cholesterol lowering. JAMA 1984; 251:365-374 [Abstract]
10. Toronto Working Group on Cholesterol Policy Asymptomatic hypercholesterolemia: a clinical policy review. J Clin Epidemiol 1990; 43:1028-1121 [Medline]
11. Kimm SY, Payne GH, Stylianou MP, Waclawiw MA, Lichtenstein C. National trends in the management of cardiovascular disease risk factors in children: second NHLBI survey of primary care physicians. Pediatrics. 1998;102(5). URL: http://www.pediatrics.org/cgi/content/full/102/5/e50
12. Newman TB, Garber AM, Holtzman NA, Hulley SB Problems with the report of the expert panel on blood cholesterol levels in children and adolescents. Arch Pediatr Adolesc Med 1995; 149:241-247 [Abstract]
13. National Cholesterol Education Program Report of the expert panel on blood cholesterol levels in children and adolescents. Pediatrics 1992; 89:515-584
14. Newman TB, Browner WS, Hulley SB The case against childhood cholesterol screening. JAMA 1990; 264:3039-3043 [Abstract]
15. Newman TB, Hulley SB Reducing dietary intake of fat and cholesterol in children. JAMA 1995; 274:1424-1425 [CrossRef][Medline]
16. Childress AC, Brewerton TD, Hodges EL, Jarrell MP The Kids' Eating Disorders Survey (KEDS): a study of middle school students. J Am Acad Child Adolesc Psychiatry 1993; 32:843-850 [Medline]
17. Shapiro S, Newcomb M, Loeb TB Fear of fat, disregulated-restrained eating, and body-esteem: prevalence and gender differences among eight- to ten-year-old children. J Clin Child Psychol 1997; 26:358-365 [CrossRef][Medline]
18. Gustafson-Larson AM, Terry RD Weight-related behaviors and concerns of fourth-grade children. J Am Diet Assoc 1992; 92:818-822 [Medline]
19. Kassirer JP, Angell M. Losing weightan ill-fated New Year's resolution. N Engl J Med. 1998;338:52-54. Editorial comment
20. Lannon CM, Earp J. Parents' behavior and attitudes toward screening children for high serum cholesterol levels. Pediatrics. 1992:1159-1163
21. Bachman RP, Schoen EJ, Stembridge A, Jurecki ER, Imagire RS. Compliance with childhood cholesterol screening among members of a prepaid health plan. Am J Dis Child. 1993;147:382-385. Comments
22. Nader PR, Yang M, Luepker RV, et al. Parent and physician response to children's cholesterol values of 200 mg/dL or greater: the Child and Adolescent Trial for Cardiovascular Health Experiment. Pediatrics. 1997;99(5). URL: http://www.pediatrics.org/cgi/content/full/99/5/e5
23. Newman TB, Hulley SB Carcinogenicity of lipid-lowering drugs. JAMA 1996; 275:55-60 [Abstract]
24. US Preventive Health Services Task Force. Guide to Clinical Preventive Services. 2nd ed. Baltimore, MD: Williams & Wilkins; 1996