LONDON -- Cholesterol testing of toddlers or young children proved an effective screening method for familial hypercholesterolemia, according to a meta-analysis.
LONDON, Sept. 14 -- Cholesterol testing of toddlers or young children proved an effective screening method for familial hypercholesterolemia, according to a meta-analysis.
It identified about 96% of affected parents and provided the opportunity to prevent the disorder in two generations at once, David S. Wald, M.D., of the London School of Medicine and Dentistry, and colleagues, reported online in BMJ.
The parent who learns of these findings could start treatment immediately; treatment of the child, if needed, could be delayed until adulthood, they said.
The findings emerged from a meta-analysis of published data on total and LDL cholesterol in people with and without familial hypercholesterolemia according to age.
The analysis used 13 studies including 1,907 DNA or clinically confirmed cases of familial hypercholesterolemia and 16,221 controls. The main outcome measures were detection rates (sensitivity) in newborns and in age groups 1-9, 10-19, 20-39, 40-59, and ?60.
Serum cholesterol tests best discriminated between individuals with and without familial hypercholesterolemia in the 1-9 age group, when the detection rates with total cholesterol were 88%, 94%, and 96% for false positive rates of 0.1%, 0.5%, and 1% respectively. The results were similar for LDL cholesterol, the researchers said.
Cholesterol tests proved best for children ages one to nine when a high detection rate could be achieved with a false positive rate of 0.1%. On the other hand, screening performance was significantly reduced among newborns and young adults, the researchers said.
Among children nine or younger, the screening performance seemed to peak at one and two, on the basis of two studies that yielded a detection rate of 92% for total cholesterol for a 0.1% false positive rate, the researchers said.
There was no advantage in measuring LDLs over total cholesterol, except in newborns, when measuring LDL cholesterol yielded better detection.
Once an affected child is identified, measurement of cholesterol in each parent would determine which has familial hypercholesterolemia. The investigators said that applying a simple rule -- that the parent with the higher serum cholesterol concentration is the affected parent -- will pick up about 96% of parents with the disorder. In about one in 500 positive children, both parents will be affected, but this reduced the detection rate among parents by only 0.2%.
The researchers noted various complications and drawbacks of screening by DNA diagnosis, noting that DNA testing would miss 20% of affected parents of children who had an undetectable mutation. Screening without DNA diagnosis has the advantage of being simpler and less expensive, they said.
There are some practical challenges to implementing the screening strategy, the investigators wrote. Ideally, they said children would be screened at around 15 months of age, when they are scheduled for major immunizations.
The investigators said that at that stage of the child's development parents are especially receptive to ways of preventing disease in their child and may therefore be receptive to a family-based strategy to prevent the consequences of the same disorder within themselves and the family.
A simple means of blood sampling at the time of vaccination would be needed, they said. Also, systems would have to be developed to track affected children over time to ensure that appropriate treatment is started when they are older.
A strength of the proposed child-parent strategy is that the "population sweep" to identify index cases would not need to be repeated indefinitely.
If after about 30 years, the uptake of screening were high enough, the need to test children at 15 months would disappear because all or nearly all affected individuals would be known. Then it would be necessary to test only the children of families known to have the disorder, Dr. Wald said.
Affected adults, ages 20 to 39, have a 100-fold excess risk of dying of coronary heart disease. The strategy described here has the potential to prevent a major cause of coronary heart disease in young adults, he said.
The investigators made no attempt to define high cholesterol in children, noting that those levels often vary by population groups and between laboratories.