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Screening for Lipid Disorders in Children and AdolescentsUpdated Evidence Report and Systematic Review for the US Preventive Services Task Force

To identify the key insights or developments described in this article
1 Credit CME
Abstract

Importance  Lipid screening in childhood and adolescence can lead to early dyslipidemia diagnosis. The long-term benefits of lipid screening and subsequent treatment in this population are uncertain.

Objective  To review benefits and harms of screening and treatment of pediatric dyslipidemia due to familial hypercholesterolemia (FH) and multifactorial dyslipidemia.

Data Sources  MEDLINE and the Cochrane Central Register of Controlled Trials through May 16, 2022; literature surveillance through March 24, 2023.

Study Selection  English-language randomized clinical trials (RCTs) of lipid screening; recent, large US cohort studies reporting diagnostic yield or screen positivity; and RCTs of lipid-lowering interventions.

Data Extraction and Synthesis  Single extraction, verified by a second reviewer. Quantitative synthesis using random-effects meta-analysis.

Main Outcomes and Measures  Health outcomes, diagnostic yield, intermediate outcomes, behavioral outcomes, and harms.

Results  Forty-three studies were included (n = 491 516). No RCTs directly addressed screening effectiveness and harms. Three US studies (n = 395 465) reported prevalence of phenotypically defined FH of 0.2% to 0.4% (1:250 to 1:500). Five studies (n = 142 257) reported multifactorial dyslipidemia prevalence; the prevalence of elevated total cholesterol level (≥200 mg/dL) was 7.1% to 9.4% and of any lipid abnormality was 19.2%. Ten RCTs in children and adolescents with FH (n = 1230) demonstrated that statins were associated with an 81- to 82-mg/dL greater mean reduction in levels of total cholesterol and LDL-C compared with placebo at up to 2 years. Nonstatin-drug trials showed statistically significant lowering of lipid levels in FH populations, but few studies were available for any single drug. Observational studies suggest that statin treatment for FH starting in childhood or adolescence reduces long-term cardiovascular disease risk. Two multifactorial dyslipidemia behavioral counseling trials (n = 934) demonstrated 3- to 6-mg/dL greater reductions in total cholesterol levels compared with the control group, but findings did not persist at longest follow-up. Harms reported in the short-term drug trials were similar in the intervention and control groups.

Conclusions and Relevance  No direct evidence on the benefits or harms of pediatric lipid screening was identified. While multifactorial dyslipidemia is common, no evidence was found that treatment is effective for this condition. In contrast, FH is relatively rare; evidence shows that statins reduce lipid levels in children with FH, and observational studies suggest that such treatment has long-term benefit for this condition.

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CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.

Article Information

Accepted for Publication: May 20, 2023.

Corresponding Author: Janelle M. Guirguis-Blake, MD, Kaiser Permanente EPC, Department of Family Medicine, University of Washington, 521 Martin Luther King Jr Way, Tacoma, WA 98405 (jguirgui@uw.edu).

Author Contributions: Dr Guirguis-Blake had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Guirguis-Blake, Evans, Coppola.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Guirguis-Blake, Evans, Coppola.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Guirguis-Blake, Redmond.

Administrative, technical, or material support: Guirguis-Blake, Coppola, Redmond, Perdue.

Supervision: Guirguis-Blake, Evans.

Conflict of Interest Disclosures: None reported.

Funding/Support: This research was funded under contract 75Q80120D00004, Task Order 75Q80120F32001, from the Agency for Healthcare Research and Quality (AHRQ), US Department of Health and Human Services.

Role of the Funder/Sponsor: Investigators worked with USPSTF members and AHRQ staff to develop the scope, analytic framework, and key questions for this review. AHRQ had no role in study selection, quality assessment, or synthesis. AHRQ staff provided project oversight; reviewed the report to ensure that the analysis met methodological standards; and distributed the draft for peer review. Otherwise, AHRQ had no role in the conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript findings. The opinions expressed in this document are those of the authors and do not reflect the official position of AHRQ or the US Department of Health and Human Services.

Additional Contributions: We gratefully acknowledge the following individuals for their contributions to this project: Brandy Peaker, MD, MPH, and Tina Fan, MD, MPH (Agency for Healthcare Research and Quality); current and former members of the US Preventive Services Task Force who contributed to topic deliberations; and Jill Pope, BA, Melanie Davies, MAIS, and Elizabeth Webber, MS, for technical and editorial assistance at the Center for Health Research. Members of the USPSTF, peer reviewers, and federal partner reviewers did not receive financial compensation for their contributions.

Additional Information: A draft version of this evidence report underwent external peer review from 3 content experts (Stephen R. Daniels, MD, PhD, University of Colorado School of Medicine and Children’s Hospital Colorado; Juanita Redfield, MD, Kaiser Permanente Colorado [retired]; and Justin P. V. Zachariah MD, MPH, Baylor College of Medicine and Texas Children’s Hospital) and 5 individuals at USPSTF Federal Partner agencies (Office of Genomics and Precision Public Health and National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention; National Heart, Lung, and Blood Institute, National Institutes of Health). Comments were presented to the USPSTF during its deliberation of the evidence and were considered in preparing the final evidence review.

Editorial Disclaimer: This evidence report is presented as a document in support of the accompanying USPSTF Recommendation Statement. It did not undergo additional peer review after submission to JAMA.

AMA CME Accreditation Information

Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

  • 1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
  • 1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
  • 1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
  • 1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
  • 1.00 credit toward the CME [and Self-Assessment requirements] of the American Board of Surgery’s Continuous Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.

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