Effectiveness of childhood universal screening for familial hypercholesterolaemia: systematic review

Background

Familial hypercholesterolaemia (FH) is an inherited condition characterised by very high lifelong levels of low-density lipoprotein cholesterol leading to an increased risk of atherosclerotic cardiovascular disease (CVD). In the context of impactful preventive public health, CVDs are gaining growing attention. FH remains a condition with a high prevalence yet is underdiagnosed. Unless detected by cascade testing or opportunistically, FH is often only identified after a cardiovascular event. To inform decision-making, this systematic review evaluates whether universal screening for FH in children is clinically effective and safe.

Methods

Electronic searches were conducted in November 2025 across seven databases from inception, supplemented by grey literature searches. Outcomes of interest were case characteristics, morbidity, mortality, surrogate markers, safety, quality of life, and resource use. Population-based observational studies were considered. Screening, data extraction and quality were independently performed by two reviewers.

Results

Of 7,758 records identified and 299 full texts screened, 18 publications on 10 studies met the inclusion criteria. No comparative studies of universal screening were identified. Substantial heterogeneity was observed in the context, screening methods, and populations screened. Screening ages ranged from 1 to 17 years old. Screening typically occurred alongside existing health checks, using non-fasted capillary samples for cholesterol testing, and genetic confirmation. Across four studies, 5% to 8% of children exceeded screening thresholds and required further testing. FH prevalence was reported as 1 in 413 (Slovenia), 1 in 273 (England), and 1 in 150 (Australian pilot). No studies reported safety, morbidity, mortality, resource use or quality of life in children.

Conclusions

Universal screening may help identify FH in children but a lack of long-term comparative evidence of effectiveness limits interpretation.

Key messages

• There is a lack of long-term comparative evidence on effectiveness of universal screening for FH. However, available evidence suggests that universal screening may help identify FH in children.

• The substantial heterogeneity in context, methods, and populations, alongside lack of long-term outcomes across studies limits comparison of the effectiveness of universal FH screening in children.