Lipid disorders in children

Pediatric dyslipidemia is a condition characterized by abnormal lipid values in children and adolescents. Affecting approximately 20% of individuals aged 6–19 years, it is most commonly caused by obesity, though familial dyslipidemias are also an important cause. Affected individuals are usually asymptomatic, but severe dyslipidemia may manifest with xanthomas or clinical signs of atherosclerotic cardiovascular disease (ASCVD). Screening involves a targeted approach starting at 2 years for children with risk factors (e.g., obesity, family history of premature ASCVD) and possibly a universal approach for all children between ages 9–11 and 17–21 years. Diagnosis is confirmed if the average of two fasting lipid panels, taken 2–12 weeks apart, shows abnormal levels of LDL, non-HDL, and/or triglycerides. Management begins with lifestyle interventions such as dietary changes and regular exercise. If lipid levels remain elevated after 6 months of lifestyle changes, pharmacotherapy may be necessary. Referral to a lipid specialist is indicated for very high lipid levels or suspected familial hypercholesterolemia.

For individuals ≥ 20 years, see “Lipid disorders in adults.”

Approximately 20% of individuals aged 6–19 years have abnormal lipid values. ^[1]

Epidemiological data refers to the US, unless otherwise specified.

• Obesity (most common cause)
• Familial dyslipidemias
• Other causes: See “Secondary causes of dyslipidemia.”

• Family history ^[2][3][4]
  • Parent with total cholesterol ≥ 120 mg/dL or known dyslipidemia
  • First- or second-degree relative with premature ASCVD ^[2]
• High risk factors ^[2][3][4]
  • BMI ≥ 97th percentile
  • Pediatric hypertension meeting criteria for pharmacotherapy
  • Diabetes
  • Kawasaki disease with coronary aneurysms
  • Heart transplant
  • Chronic kidney disease (including kidney transplant)
  • Cigarette smoking
• Moderate risk factors ^[2][3][4]
  • BMI 95–96th percentile
  • Pediatric hypertension not meeting criteria for pharmacotherapy
  • Kawasaki disease with regressed coronary aneurysms
  • Nephrotic syndrome
  • Inflammatory conditions: SLE, JIA
  • HIV
  • HDL < 40 mg/dL

Other conditions, especially cardiac conditions, may also increase risk and affect management. ^[3]

• Dyslipidemia is usually asymptomatic.
• Patients with severe dyslipidemia (e.g., those with homozygous familial dyslipidemia) may present with: ^[5][6][7]
  • Xanthomas (cutaneous, interdigital, tendinous)
  • Clinical ASCVD
• See “Clinical features of dyslipidemias” for additional information.

Methods ^[2][3][4][8]

• Targeted screening: recommended for all children if risk factors are present
  • Starting at 2 years of age, screen for risk factors for pediatric dyslipidemia at well-child visits. ^[8]
  • When risk factors are first recognized, obtain a lipid panel (preferably fasting). ^[2][3][4]
  • If the lipid panel is normal and risks persist, repeat the lipid panel regularly (e.g., every 3–5 years) throughout childhood. ^[3][4]
• Universal lipid panel screening: recommended by some societies in addition to targeted screening ^[2][4][9]
  • First screening: once between 9 and 11 years
  • Second screening: once between 17 and 21 years

For individuals with a family history suggesting premature ASCVD and/or inherited hyperlipoproteinemia, obtain a screening lipid panel as early as 2 years of age. ^[10]

Interpretation ^[2][3][4][8]

• Abnormal nonfasting lipid panel results in children
  • Total cholesterol > 200 mg/dL
  • Non-HDL > 145 mg/dL
  • HDL < 45 mg/dL
• Abnormal FLP results in children
  • LDL measurements
    • Elevated: ≥ 130 mg/dL
    • Borderline: 110–129 mg/dL
  • Non-HDL measurements
    • Elevated: ≥ 145 mg/dL
    • Borderline: 120–144 mg/dL
  • Triglyceride measurements
    • Children aged 10–19 years
      • Elevated: ≥ 130 mg/dL
      • Borderline: 90–129 mg/dL
    • Children aged < 10 years
      • Elevated: ≥ 100 mg/dL
      • Borderline: 75–99 mg/dL

If screening results are abnormal, proceed to diagnostics for pediatric dyslipidemia to confirm the diagnosis.

Diagnose dyslipidemia if the average of two FLPs, obtained 2–12 weeks apart, meets criteria for abnormal FLP results in children.

• Hypercholesterolemia is diagnosed with either LDL (most common) or non-HDL measurements.
• Hypertriglyceridemia is diagnosed with triglyceride levels.

Pediatric dyslipidemia most commonly involves moderately to severely elevated triglycerides, normal to mildly elevated LDL, reduced HDL, and obesity. ^[2]

Initial management ^[2][3][4]

• Educate patients and caregivers on the risk of complications of dyslipidemia.
• Thoroughly assess for risk factors for pediatric dyslipidemia.
• Immediately refer to a pediatric lipid specialist for:
  • LDL ≥ 250 mg/dL
  • Average triglyceride level ≥ 500 mg/dL or a single triglyceride level ≥ 1000 mg/dL ^[2]
  • Suspected or confirmed familial hypercholesterolemia (FH) ^[3]
  • Complex and/or multiple risk factors (e.g., significant cardiac history) ^[2][3]
• Initiate lifestyle interventions to address modifiable risk factors.
  • Dietary changes
    • Start CHILD-1 diet and refer to a dietician.
    • If no improvement after 3 months, escalate to the CHILD-2 diet.
  • Counseling on regular exercise
  • Counseling on smoking cessation, if applicable
• Optimize treatment of underlying conditions.

Ongoing management of pediatric dyslipidemia ^[2][3][4]

Recheck an FLP after 6 months of lifestyle interventions to guide further management.

• Persistent hypercholesterolemia
  • Start statin therapy for children based on LDL level and risk factors, i.e., for any of the following:
    • LDL ≥ 250 mg/dL (immediate referral to a lipid specialist)
    • LDL 190–249 mg/dL regardless of risk factors
    • LDL 160–189 mg/dL with either
      • A positive family history
      • ≥ 1 high risk factor for pediatric dyslipidemia and either 2 moderate risk factors or clinical ASCVD
    • LDL 130–159 mg/dL with either
      • ≥ 2 high risk factors for pediatric dyslipidemia
      • 1 high risk factor and either 2 moderate risk factors or clinical ASCVD
  • Continue CHILD-2-LDL diet and lifestyle changes for either of the following:
    • LDL 130–189 mg/dL with no risk factors; repeat FLP every 6 months
    • LDL < 130 mg/dL regardless of risk factors; repeat FLP every 12 months
• Persistent hypertriglyceridemia
  • Refer to a lipid specialist for either of the following:
    • Triglycerides ≥ 500 mg/dL (immediate referral)
    • Triglycerides 200–499 mg/dL and non-HDL ≥ 145 mg/dL and LDL < 130 mg/dL
  • Continue CHILD-2 diet and lifestyle interventions for any of the following:
    • Triglycerides 200–499 mg/dL and non-HDL < 145 mg/dL: Consider adding omega-3-fish oil.
    • Triglycerides elevated but < 200 mg/dL : Intensify CHILD-2-TG diet , weight loss, and repeat FLP in 6 months.
    • Triglycerides < 100 mg/dL if < 10 years or < 130 mg/dL if 10–19 years; repeat FLP every 12 months.

Statin therapy for children ^[2][3][4]

• Indications
  • First-line pharmacotherapy for elevated LDL in individuals > 10 years
  • Specialists may consider statin therapy for patients with hypertriglyceridemia.
• Initiation: Start at a low dose and uptitrate after 3 months based on FLP results and tolerability. ^[2]
• Monitoring studies
  • Baseline studies: Obtain creatine kinase, ALT, and AST.
  • Following initiation or dose change: Obtain FLP, ALT, AST 4 weeks later.
  • Stable dose ^[2]
    • Check FLP, ALT, and AST in 8 weeks
    • Then every 3–4 months in the first year
    • Then every 6 months
  • If symptoms of myopathy develop, stop the statin and check a creatine kinase level.
• Referral indications: not meeting treatment goals despite optimal therapy

Statin therapy is not routinely recommended for children < 10 years of age but may be considered by a specialist. ^[2] Statins are contraindicated in pregnancy. Counsel individuals who can become pregnant on highly effective contraception methods. ^[2]

Advanced management

Specialists may consider the following:

• Alternative or adjunctive pharmacotherapy ^[2][3][4]
  • Hypercholesterolemia: ezetimibe, bile acid sequestrant, PCSK9 inhibitors, LDL apheresis
  • Hypertriglyceridemia: fibrate (off-label), niacin, and/or omega-3 fatty acids
• Genetic testing: for familial dyslipidemia genetic variants in the patient and possibly family members ^[10]

• At every well-child visit, discuss:
  • Pediatric lifestyle recommendations (e.g., counseling on regular exercise, limited screen time)
  • Pediatric nutrition
• Children with risk factors for dyslipidemia: Recommend the CHILD-1 diet.