Clinical practice guidelines are designed to provide a synthesis of evidence and to translate the evidence into graded recommendations; these recommendations may be helpful in improving clinical decision making [
12]. Paediatric guidelines for dyslipidaemia have undergone several modifications in recent years. The first paediatric guidelines for dyslipidaemia were published in 1992 by the National Cholesterol Education Program (NCEP) following guidelines for adults that were developed by the same NCEP [
13]. Although many of the recommendations were mainly based on expert opinion rather than on systematic evidence review, these guidelines were adopted by several paediatric scientific societies. Undoubtedly, these initial guidelines engendered some controversy; however, they were important for increasing the awareness of childhood dyslipidaemia and for stimulating the research on this important topic. Moreover, the cut-off points for acceptable, borderline and high plasma lipid concentrations based on percentiles from the Lipid Research Clinical Prevalence Study were the first to be presented [
14]. As new data and new evidence became available, organisations such as the American Heart Association (AHA) and the American Academy of Pediatrics (AAP) updated the original guidelines. In 1998, the AAP Committee on Nutrition produced a statement on cholesterol in childhood [
15], which was followed by an additional clinical report in 2008 [
16]. Furthermore, the AHA first published a consensus statement on dietary recommendations for children and then a scientific statement on drug therapy for high-risk lipid abnormalities in children and adolescents [
17,
18]. The most up-to-date guidelines for the management of childhood dyslipidaemia were published in 2011 by the National Heart Lung and Blood Institute (NHLBI) after performing a systematic review and grading the best available evidence [
3]. The 2011 Guidelines constitute a part of an integrated approach with a focus on all cardiovascular risk factors in children and adolescents; they represent a cornerstone for cardio-metabolic risk reduction and cardiovascular health in youth. As regards lipid abnormalities, the NHLBI Guidelines outlined the currently used references values for plasma lipid, lipoprotein and apolipoprotein concentrations in children and adolescents (
Table 1); moreover, they give recommendations concerning both lipid assessments in youth and the management of paediatric lipid disorders.
3.1. Non-Pharmacological Approaches
Although several pharmacological treatments are available or under development, current guidelines recommend healthy behaviours as the first-line treatment for childhood dyslipidaemia. It is important that healthy behaviours should be recommended for all children and adolescents; however, they should be strongly encouraged in those children with borderline or high plasma lipid and lipoprotein concentrations.
For children with an altered lipid profile, the initial management should consist of therapeutic lifestyle changes that focus on dietary modifications, daily physical activity, improving body weight and tobacco smoking cessation [
21]. Moreover, in order to prevent obesity in children, they should be encouraged to sleep for a decent amount of hours per day and to limit screen time (including television, cell phone, computer use, videogames, handheld electronics) to less than 2 h per day. In 2016, The AAP consensus groups recommended adequate daily hours of sleep (including naps) for children and adolescents, depending on their age [
22]. As regards sedentary activities, in a recent study, it was observed that every additional hour of watching television was correlated with increased triglycerides (TG) and decreased high-density lipoprotein (HDL-C) levels [
23]. Several possible reasons were proposed: among them, the lower energy expenditure and the increased intake of energy-dense foods (e.g., soft drinks, fast food) while watching television.
Although dietary treatment remains under debate, a modified diet can improve abnormal lipid profiles by inducing a lipid-lowering effect, mainly on triglycerides (TG) levels, but it also has a modest impact on total cholesterol (TC) and low-density lipoprotein (LDL-C). In adults, the PREDIMED study (the largest dietary prevention trial) demonstrated that the Mediterranean diet is beneficial in reducing the incidence of major cardiovascular events. Similarly, adherence to the Mediterranean diet in children may improve the carotid intima-media thickness test (CIMT), which is an early marker of atherosclerosis [
24,
25]. In view of these observations, it is likely that dietary modifications are relevant for the prevention of atherosclerotic cardiovascular disease in both children and adults. The specific dietary changes should emphasise decreasing total, trans and saturated fats; decreasing cholesterol amounts; and increasing the intake of fibre. The NCEP suggests two approaches for proposing a modified diet: the population approach is a group of recommendations for all youths in order to prevent an abnormal lipid profile and the atherosclerotic process. In contrast, the individual approach consists of suggestions for children with confirmed dyslipidaemia and an increased risk for cardiovascular disease. It is important to note that this latter approach uses a two-step nutritional change (CHILD-1 and CHILD-2) and that CHILD-1 recommendations coincide with those of the population approach [
26]. The recommended population diet, as well as the diet Cardiovascular Health Integrated Lifestyle Diet-1 (CHILD-1), should limit the total fat consumption to 20–30% of total calories, saturated fat intake to less than 10% of total calories and average cholesterol ingestion to less than 300 mg/day. Children should also avoid trans-fatty acids (<1%), preferring polyunsaturated fatty acids and monounsaturated fatty acids, which should be up to 10% and between 10 and 15% of total daily calories, respectively. It is also recommended to increase the intake of dietary fibre through whole grains, vegetables and fruit (five or more a day). For children at an increased cardiovascular risk and for children with confirmed dyslipidaemia who have failed to achieve the lipid goals after 3 months of the CHILD-1 diet, more intensive restrictions are needed. The Cardiovascular Health Integrated Lifestyle Diet-2 (CHILD-2) requires limiting saturated fat intake to less than 7% and cholesterol average ingestion to less than 200 mg/day [
3,
27]. The other step 1 recommendations should not be interrupted through the step 2 diet.
It is noteworthy that the NCEP recommends dietary modifications in children from 2 years of age: the first two years of life are critical for the development and the growth of children and it is important to provide them with an adequate amount of calories and nutrients [
28]. This also applies to children older than 2 years old and both CHILD-1 and CHILD-2 should ensure adequate daily caloric intake for normal growth and development: as a consequence, these diets should consist of 50–60% of total daily calories from carbohydrates and 10–20% from proteins [
27]. It is never suggested to limit protein consumption, while in children with elevated TG, it is recommended to decrease simple sugar consumption (including fruit juices and sugar drinks) and replace them with complex carbohydrates [
28].
For children with hypertriglyceridemia, an increase in omega-3 fatty acid dietary intake should also be encouraged by increasing the consumption of fish. Long-chain omega-3 fatty acids are also available in the form of unregulated fish oil products and prescription drugs; although it is not clear the exact mechanisms by which they reduce TG concentrations and limited data exist in children and adolescents, prescription products seem to lower TG levels and have been safely used in children [
20,
29,
30]. However, they lack the approval for use in children and should be used in consultation with a lipid specialist. For patients with increased LDL-C values, the CHILD-2 diet also recommends dietary adjuncts, such as plant stanol and sterol esters and water-soluble fibre psyllium. Plant sterol and stanol, when taken up to 2 g per day, were shown to inhibit intestinal cholesterol absorption, leading to a reduction in LDL-C levels by approximately 9% [
31].
Although the effectiveness of dietary changes is variable, it is important to remember that the above-mentioned dietary modifications are safe and well tolerated over time. Several studies, such as the Special Turku Coronary Risk Factor Intervention Project (STRIP) and the Dietary Intervention Study in Children (DISC) showed that reducing fat intake (total fat, saturated fat and cholesterol) was not significantly associated with changes in somatic growth, pubertal development, mean body mass index, nutritional sufficiency and psychological/social features [
32,
33]. Moreover, a recent study concluded that beneficial nutritional interventions can be safely introduced in youth and sustained over 20 years [
34].
Consultation with a registered nutritionist may help with promoting long-term adherence to a diet; a study of 1062 children (540 children in the intervention group and 522 controls) showed that repeated dietary counselling was helpful in reducing both saturated fat consumption and LDL-C concentrations [
35]. In addition, a paediatric dietitian plays a key role in setting goals, tracking progress, making dietary adjustments and educating parents about nutritional plans inside and outside of the home [
21]. It is important to set realistic short-term dietary goals and to consider social, parental and cultural factors in order to ensure the effective implementation of nutritional changes [
36]. It is also important that dietary modifications should never be portrayed as punitive, but rather in terms of the child’s education, and that adequate non-food-based rewards should be given when accomplishing the goals. Improving the quantity and the quality of nutrition is equally important: children with obesity often consume exaggerated portions and large quantities of non-nutritive but calorie-dense food. Common sources of non-nutritive foods include ultra-processed products, soft and energy drinks, snacks and fast food [
27]. The elimination of these foods and limitation of portion sizes should be strongly encouraged to improve the nutritional status. Furthermore, it is crucial that children and adolescents avoid skipping meals (in particular breakfast); in accordance with a retrospective, observational study, children who consumed fewer than two meals per day had higher levels of TC and LDL-C compared with those eating three times or more per day [
37].
In addition to nutritional changes, physical activity and weight reduction are the cornerstones of preventing and treating lipid abnormalities in children. Physical activity is associated with a variety of health benefits, both in healthy children and in youths with chronic disease [
38]. The benefits of physical activity were widely documented and include improved musculoskeletal, mental, behavioural and cardiovascular health. In particular, being physically active has a positive effect on cardiorespiratory fitness, serum glucose concentrations and insulin sensitivity, blood pressure, bone density and lipid profile [
39]. As a consequence, regular physical activity should always be encouraged in children with dyslipidaemia; it may be useful in lowering TC, TG and LDL-C levels, increasing HDL-C and, more importantly, it may assist with body fat and body mass index (BMI) reduction. Therefore, it is critical that all children and adolescents should engage in at least 1 h of moderate-to-vigorous physical activity every day [
3]. Interestingly, a study of 1235 adolescents showed a dose–response relationship between an increased number of minutes of physical activity and improved lipid concentrations (HDL-C and TG values) [
40]. It is important that physical activity is age appropriate, various (including unstructured and structured activities) and enjoyable to the child. Further recommendations are available in the 2018 Physical Activity Guidelines; these guidelines, released by the US Department of Health and Human Services, provide important guidance on the amounts and types of physical activity for multiple paediatric populations groups [
41].
Weight management is another important recommendation for children with an altered lipid profile and represents the primary treatment goal for obese or overweight children with dyslipidaemia. The excess adiposity adversely affects not only the lipid profiles but the entire cardio-metabolic health of young people [
42]; it is, therefore, necessary to maintain a healthy BMI. A 5 to 10% reduction in body weight through dietary modifications and increased physical activity is beneficial for reducing cardiovascular risk and improving lipid abnormalities. Via different mechanisms (improved insulin sensitivity, enhanced activity of lipoprotein lipase, reduced free fatty acids release from adipose tissues), weight loss is expected to increase the TG catabolism and removal by approximately 20% [
43,
44]. Only when obesity-related comorbidities (such as dyslipidaemia) are not sufficiently reduced with adequate weight reduction, they should be treated independently [
6].