Informed consent

If you’re a parent facing the decision of whether or not to let your child or teen be screened for dyslipidemia (blood “cholesterol”), before you respond with “Why not?”, you may want to know the recommendations of the expert committee of the U.S. Preventive Services Task Force.

The USPSTF performed a systematic review of 25 years of evidence — 266 published studies — and released its report several weeks ago. Despite the importance of this information for millions of parents, it received virtually no media attention.

As previously reviewed, guidelines calling for cholesterol screening don’t have sweeping support — which is a very different picture from that presented by the media and most consumer literature. In fact, expert organizations without industry ties recommend against widespread screening and treating blood lipid levels, especially in growing children and teens. In this new position statement, the USPSTF said: “No professional organization recommends universal screening for dyslipidemia in children or adolescents.”

The organization at the forefront of promoting cholesterol screening and treatment is the National Cholesterol Education Program (NCEP) and its guidelines are followed by the American Heart Association (AHA) and American Academy of Pediatrics (AAP). NCEP recommends screening all children and adolescents with a family history of premature heart disease or dyslipidemia, or any young person considered to have “risk factors” or who is “overweight” — which, all told, describes most kids.

[I put risk factors in quotations because a risk assessment tool has not been studied or developed for children and risk factors such as “overweight...diet, physical inactivity, and aerobic capacity/fitness have not been evaluated sufficiently to determine their usefulness as screening tools alone or in combination,” according to the evidential review conducted for the USPSTF led by Dr. Elizabeth M. Haney, M.D., at the Oregon Evidence-based Practice Center, Department of Medical Informatics and Clinical Epidemiology in Portland.]

But, if you read the detailed walk-through of the evidence behind the AHA’s recently-released guidelines for lipid management in young people, you already know there is no evidence for any long-term health benefits in keeping lipid levels to recommended low levels, there is no evidence to support that young people over the AHA’s arbitrary cutoffs for “high” cholesterol levels are at any risk [except perhaps those with the extremely rare disorders, such as genetic/familial hypercholesterolemia], and that there is no evidence it is safe to give young people statins for decades. The AHA didn’t even look at the evidence for potential risks of lowering cholesterol levels in healthy children.

So, it won’t come as a surprise that the just-released findings of the USPSTF differ from the guidelines of NCEP, the AAP, and the AHA. The USPSTF experts examined randomized, control clinical trials and all available evidence, carefully considering ten key questions concerning the effectiveness, risks and accuracy of screening; the effectiveness and risks of diet, drug and exercise interventions for managing cholesterol and preventing cardiovascular disease; and if reducing blood cholesterol levels in youth reduces the risk of high cholesterol and cardiovascular disease in adulthood.

Their first sentence concisely summed things up:

SUMMARY OF RECOMMENDATIONS

The U.S. Preventive Services Task Force (USPSTF) concludes that the evidence is insufficient to recommend for or against routine screening for lipid disorders in infants, children, adolescents, or young adults (up to age 20). [Evidence for effectiveness] is lacking, of poor quality, or conflicting and the balance of benefits and harms cannot be determined.

Elevated lipid levels in growing children and teens do not predict high levels in adulthood, they found, as “many children with multifactorial types of dyslipidemia [will] have normal lipid levels in adulthood.” Of course, when “high” levels among kids are found, then people want to do something about them. But, they reported: “There is no evidence that diet or exercise interventions in childhood lead to improved lipid profiles or better health outcomes in adulthood.”

More than that, cholesterol interventions are not benign. The systematic evidence review for the USPSTF looked at 81 controlled and noncontrolled clinical studies just on the question of cholesterol management and found “a variety of adverse effects of drug, diet, exercise, and combination therapy in children and adolescents.”

Getting kids to eat low-fat diets is the intervention most popular with “healthy eating” advocates, but the USPSTF not only found lack of effectiveness, but evidence for harm: “Nineteen studies of dietary fat restriction reported effects on growth, nutrient intake, laboratory safety parameters, or other adverse effects. Twelve studies reported normal height growth...In one study, growth failure occurred in 8 (20%) of 40 children with dyslipidemia, 3 (7.5%) of whom had nutritional dwarfing and no progression of puberty....There have been three reports of growth retardation and nutritional dwarfing in children on unmonitored [low-fat] diets; however, there are several reports of normal growth during monitored low-fat diet interventions.”

Let’s take a moment to look more closely at the evidence on dietary interventions. Medscape, in its review of the USPSTF findings for physicians, may have left the impression that there is a paucity of evidence to answer the question of whether there is efficacy for screening and managing lipid levels, but it is more accurate to say there is a paucity of evidence in support for any efficacy.

The USPSTF examined 16 clinical trials just on diet and exercise interventions to treat dyslipidemias, lasting from two months to seven years. Going down the line, all of the clinical studies reported no change to total cholesterol levels, with only three exceptions. Two of those papers were found to be of poor quality: one involved children eating one box of fiber cereal a day for three weeks and then two boxes a day for a total of 12 weeks; the other only measuring temporary blood lipid changes during weight loss among 56 fat children over 6 months. Only one clinical trial reported effectiveness in reducing total and LDL-cholesterol levels long-term: the Dietary Intervention Study in Children (DISC). A closer look finds it wasn’t actually effective, either:

Published in 1995, DISC was a randomized controlled clinical trial conducted at six centers around the country involving 673 kids, ages 8 to 10 years old, and lasted three years. The intervention and control group were well matched. The dietary goals in the intervention group were to reduce total fat to less than 28% of total calories, less than 8% saturated fat, and no more than 150 mg cholesterol in a balanced, healthy diet. It involved intense intervention with the entire family that consisted of dietary assessments; a personalized eating program; group and personal sessions led by nutritionists, behaviorists and health educators — six weekly and five biweekly group sessions, and two individual visits of children with their family members during the first six months; four group and two individual sessions during the second six months; and four to six group and individual sessions during the second and third years, with monthly telephone contacts between sessions; blood tests and physical examinations. The intervention group maintained the diet well, consistently taking in less fat and calories than the control group.

After three years, there was a “significant difference in the LDL-cholesterol levels” (the primary endpoint) between the intervention and control groups of .... only 0.08 mmol/L. There was no difference in HDL-cholesterol or LDL:HDL ratios, but there was a small increase in triglycerides among the intervention kids.

And, in contrast to popular wisdom that children’s weight gain can be controlled by a “healthy” low-fat diet: despite following a diet lower in fat and calories, there was no difference in the average weights, BMI, body fat as measured by skinfold thickness, waist-to-hip ratio, or blood pressures between the two groups after three years. There was, however, a difference in the nutrients the children took in. The “lower fat intake was associated with lower levels of calcium, zinc, magnesium, phosphorus, vitamin E, vitamin B-12, thiamine, niacin, and riboflavin.”

Among the studies that found no effect of diet on blood lipids that the USPSTF examined was this same DISC study group after a longer follow-up of 7 1/2 years, with 87.5% still participating. “Dietary adherence was well-maintained by the intervention group,” although the differences between the groups decreased slightly over time. Still, by year 5 and at final 7-year follow-up, there was no difference in total, LDL- or HDL-cholesterol levels among the groups (although mean triglyceride levels were 3 mg/dL higher in the intervention group). The researchers observed that pubertal changes have the strongest impact on blood lipids and “sexual maturation had a stronger effect than diet.” The nutrient intakes among the teens were not evaluated on follow-up.

And despite the intervention group eating 98 to 148 kcal/day less than the control group, even after years there was no significant difference in the children’s average weights or BMI (with differences of a mere 0.1 kg), or any relationship between their measurements or body fat and their dietary fat intakes.

Like adults, getting lipid levels down to the AHA-recommended low levels cannot be achieved through diet and exercise, and means a lifetime of prescription medications for most people. But parents need to know, and the USPSTF experts emphasized, that “drug treatments for dyslipidemia in children have been studied only in children with FH [familial hypercholesterolemia] or FCH [familial combined hyperlipidemia], the population for whom these drugs are Food and Drug Administration–approved.” Cholesterol lowering drugs are not only not approved by the FDA for other uses in children, but it is not known if or how their effectiveness for these rare, extreme conditions “translate to children with milder and/or nonmonogenic dyslipidemia.”

Medicating children is especially problematic, the USPSTF found: “Lipid-lowering agents have been shown to cause elevations in creatine kinase and liver-function tests (statins), gastrointestinal adverse effects, and decreased absorption of vitamins and minerals (bile-acid resins)....Two studies of niacin reported increased liver enzyme levels (6 of 21 children in one study) and multiple other symptoms such as flushing, abdominal pain, nausea, and headache. There are also case reports of hepatitis and hepatotoxicity with the use of niacin.... The adverse effects of long-term use of lipid-lowering agents (eg, for 20 years) have not been studied.”

The focus on childhood obesity has raised interest in screening children for “risk factors” believed to be associated with heart disease, but the available clinical evidence fails to support that lipid screening or interventions among young people reduce the incidences of cardiovascular-related health problems during childhood or adulthood. While population-wide screening is being proposed, there is no clinical evidence that it is warranted or effective in healthy children. Reading statements carefully reveals weenie words speculating only that screening kids “could lead to interventions or treatments that could prevent or delay adult dyslipidemia and heart disease.” That takes population-wide screening into the realms of experimental research.

Parents still have a choice on behalf of their children, however, to give or withhold consent for their participation. In all research involving human subjects, Good Clinical Practice regulations, adopted worldwide, include human rights protections for study participants. An essential part is the ethical and moral obligation of investigators to fully inform participants of the status of the research, risks and benefits, so they can freely give an informed consent. Known as the Declaration of Helsinki — born from the human experimentation war crimes tried during the Nuremberg trial in Germany in 1946 — it concludes that “the interest of science and society should never take precedence over considerations related to the well-being of the subject.”

This basic principle seems to be being forgotten in many of today’s public health initiatives that encompass widespread unproven, unsound and potentially risky screenings, measuring and initiatives, such as those to address childhood obesity. This may sound like a melodramatic point to raise... until we think about it, especially in light of the one-sided information readily available to most consumers.

When parents face whether to give their consent for their children to be tested and subjected to interventions — be it BMI, fitness, diet or lipids — they deserve to have all available information on the evidence so that they can make an informed decision on what is best for their children.

© 2007 Sandy Szwarc