Obesity in children: clinical guidelines

List of Abbreviations

BP – blood pressure

AH – arterial hypertension

ACTH – adrenocorticotropic hormone

ALT – alanine aminotransferase

AST – aspartate aminotransferase

BPDS – biliopancreatic diversion

VGP – vertical gastroplasty

GB – gastric bypass

DBP – diastolic blood pressure

BMI – body mass index

IR – insulin resistance

IRI – immunoreactive insulin

AHI – apnea-hypopnea index

IGF-1 – insulin-like growth factor 1

CT – computed tomography

LH – luteinizing hormone

HDL – high-density lipoproteins

LDL – low-density lipoproteins

MRI – magnetic resonance imaging

NAFLD – non-alcoholic fatty liver disease

GSD – gallstone disease

NPMD – neuropsychological and motor development

OGTT – oral glucose tolerance test

PTH – parathyroid hormone

POMC – pro-opiomelanocortin

LSG – laparoscopic sleeve gastrectomy

SBP – systolic blood pressure

BBS – Bardet-Biedl syndrome

OSA – obstructive sleep apnea

GH – growth hormone

SHBG – sex hormone-binding globulin

DM – diabetes mellitus

PWS – Prader-Willi syndrome

TSH – thyroid-stimulating hormone

US – ultrasound examination

FSH – follicle-stimulating hormone

ECG – electrocardiography

EchoCG – echocardiography

SDS – standard deviation score

T3 – triiodothyronine

FT4 – free thyroxine

T2D – type 2 diabetes mellitus

Terms and Definitions

Simple (constitutional-exogenous, idiopathic) obesity – obesity associated with excessive caloric intake under conditions of physical inactivity and genetic predisposition.

Hypothalamic obesity – obesity associated with the presence and treatment of hypothalamic and brainstem tumors, radiation therapy for brain tumors and hemoblastosis, head trauma, or stroke.

Iatrogenic obesity – obesity associated with long-term use of medications (glucocorticoids, antidepressants, etc.)

Syndromic obesity – obesity developing in chromosomal and other genetic syndromes (Prader-Willi, fragile X, Alström, Cohen, Down, pseudohypoparathyroidism, etc.)

Monogenic obesity – obesity developing as a result of a gene mutation (leptin, leptin receptor, melanocortin 3 and 4 receptor, pro-opiomelanocortin, proprotein convertase subtilisin/kexin type 1, neurotrophic receptor tyrosine kinase 2 / tropomyosin receptor kinase B).

Insulin resistance – impaired insulin action and cellular response in insulin-sensitive tissues at pre-, post-, and receptor levels, leading to chronic metabolic alterations and accompanied initially by compensatory hyperinsulinemia.

Body mass index – an index calculated as body weight in kilograms divided by the square of height in meters, which provides an indirect estimate of body fat mass.

Physical activity – any bodily movement produced by skeletal muscles that results in energy expenditure exceeding resting levels.

Moderate-intensity physical activity – physical activity accompanied by an increased heart rate, a feeling of warmth, and mild shortness of breath.

Vigorous-intensity physical activity – physical activity accompanied by increased sweating and rapid breathing.

Basal metabolic rate — energy expenditure required to maintain vital body functions (i.e., respiration, circulation, etc.). Defined as the amount of calories the body expends at rest without physical activity.

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Obesity is a heterogeneous group of hereditary and acquired diseases associated with excessive accumulation of adipose tissue in the body [1,2]

1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)

Obesity is a multifactorial disease resulting from a specific interaction of genetic and non-genetic causes. The role of "heredity" in the development of obesity is proven by the different incidence of this disease in various ethnic groups and a higher concordance in the development of the pathology in monozygotic twins.

The most common type of obesity, associated with excessive caloric intake in conditions of physical inactivity and genetic predisposition, is constitutional-exogenous (simple, idiopathic) obesity.

The largest study to date on the genetic influence on BMI (Genetic Investigation of Anthropometric Traits - GIANT), based on a genome-wide association study, identified 97 chromosomal loci associated with the development of obesity. In total, the alleles of these chromosomal segments account for 2.5 to 20% of the total BMI variability [3]. Furthermore, a comparative analysis of the study results separately for children and adults showed extensive overlap of risk alleles for overweight and obesity across all groups; thus, to date, there is no molecular genetic explanation for early and late-onset obesity [4,5]. Therefore, simple obesity is a polygenic disease. However, according to modern concepts, the contribution of each individual gene to obesity predisposition is relatively small.

Modern studies on the features of the quantitative and qualitative development of adipose tissue itself ¾ both brown and white, hormones, and active substances secreted by it ¾ appear promising.

Taking into account the features of the development of modern society, among the main risk factors for overweight and obesity are unbalanced diet, physical inactivity, lack of dietary and rest routine, emotional stress, the influence of education and family traditions, changes in the intestinal microbiocenosis, and social influences (aggressive marketing of unhealthy foods). Thus, despite the fact that constitutional-exogenous obesity is a disease with a genetic predisposition, the likelihood of its development and the degree of its manifestation largely depend on lifestyle and dietary habits.

The genetic component is decisive for monogenic and certain syndromic forms of obesity [6]. Much less frequently, obesity in childhood and adolescence is associated with the use of medications (e.g., glucocorticosteroids, antidepressants, neuroleptics (antipsychotics), antiepileptic drugs) or the presence of diseases (hypothalamic and brainstem tumors, radiation therapy for brain tumors and hemoblastoses, head trauma, stroke, hypercortisolism, hypothyroidism, and other neuroendocrine disorders, chromosomal abnormalities).

1.3 Epidemiology of the Disease or Condition

The prevalence of childhood obesity worldwide has been increasing rapidly over the past 40 years, acquiring an epidemic trend. Thus, the prevalence of obesity in girls between 1975 and 2016 increased from 0.7 to 5.6%; in boys, from 0.9 to 7.8%, while the total number of obese children globally reached 124 million by 2016 [7].

One of the most negative trends can be considered the increasing number of overweight young children. According to WHO estimates, existing trends could result in 70 million children under 5 years of age being obese by 2025 [8].

According to the results of a national population-based study involving more than 5 thousand children aged 5, 10, and 15 years, the prevalence of overweight among children was 19.9%, and obesity was 5.7%. The highest prevalence of overweight (28.9%) and obesity (9.6%) was noted among 10-year-old boys; the minimum was in the subgroup of 15-year-old girls (11.5 and 2.2%, respectively) [9].

According to a meta-analysis (65 studies) involving over 350 thousand children and adolescents, the prevalence of obesity and overweight in the Russian Federation is 25.3%. The authors also demonstrate that over the past 15 years, the number of overweight and obese children in the Russian Federation has tended to increase, with the growth being driven primarily by an increase in the proportion of infants and preschool children [10].

In 2007, the WHO Regional Office for Europe launched the Childhood Obesity Surveillance Initiative (COSI), aimed at determining the causes of overweight and developing and implementing nutrition and physical activity standards in school-aged children. A 2017–2018 study conducted in Moscow within this initiative, involving 2,166 7-year-old children, revealed overweight in 27% of boys and 22% of girls, and obesity in 10% and 6% of children, respectively [11].

Taking into account the age of the subjects, it can be stated that global trends are also observed in our country ¾ we have shifted from obesity as predominantly an adolescent condition to the problem of overweight in preschool and early school-aged children.

1.4 Features of Coding the Disease or Condition

E66.0 Obesity due to excess energy intake

E66.1 Drug-induced obesity

E66.2 Extreme obesity with alveolar hypoventilation

E66.8 Other forms of obesity

E66.9 Obesity, unspecified

E67.8 Other specified hyperalimentation

Examples:

(E66.0) Constitutional-exogenous obesity, grade III. Dyslipidemia. Impaired glucose tolerance.

(E89.3) Craniopharyngioma, post-surgical status. Hypothalamic morbid obesity. Hypopituitarism.

(E66.8) Monogenic obesity due to proopiomelanocortin deficiency, grade II. Secondary adrenal insufficiency.

(E67.8) Prader-Willi syndrome: grade III obesity, psychomotor retardation. Status post orchidopexy (05.2013). Dyslipidemia.

1.5 Classification of the disease or condition

Classification of obesity in children (V.A. Peterkova, O.V. Vasyukova, 2014 [1,2]):

1. By etiology:

   simple (constitutional-exogenous, idiopathic) — obesity associated with excessive caloric intake in conditions of physical inactivity and genetic predisposition;

   hypothalamic — obesity associated with the presence and treatment of hypothalamic and brainstem tumors, radiation therapy for brain tumors and hemoblastoses, head trauma, or stroke;

   obesity in neuroendocrine diseases (hypercortisolism, hypothyroidism, etc.);

   iatrogenic obesity (caused by long-term administration of corticosteroids, antidepressants, and other drugs);

   monogenic obesity — due to mutations in genes for leptin, leptin receptor, type 3 and 4 melanocortin receptors, proopiomelanocortin, proprotein convertase subtilisin/kexin type 1, neurotrophic tyrosine kinase receptor type B (TrkB; see Table 2);

   syndromic obesity (associated with chromosomal aberrations, genomic imprinting disorders, other genetic syndromes — Prader-Willi, fragile X, Alström, Cohen, Down, pseudohypoparathyroidism, etc.; see Table 3).

2. By the presence of complications and comorbid conditions:

   carbohydrate metabolism disorders (impaired glucose tolerance, impaired fasting glucose, insulin resistance, diabetes mellitus),

   non-alcoholic fatty liver disease (fatty hepatosis and steatohepatitis as the conditions most frequently encountered in children),

   dyslipidemia,

   arterial hypertension,

   delayed puberty,

   precocious puberty,

   hyperandrogenism syndrome,

   apnea-hypopnea syndrome,

   musculoskeletal disorders (Blount's disease, osteoarthritis, spondylolisthesis, etc.),

   cholelithiasis

3. By degree of obesity:

   BMI SDS 2.0 – 2.5 ¾ grade I

   BMI SDS 2.6 – 3.0 ¾ grade II

   BMI SDS 3.1 – 3.9 ¾ grade III

   BMI SDS ≥ 4.0 ¾ morbid

1.6 Clinical presentation of the disease or condition

The clinical picture is determined by the etiopathogenetic form of obesity. The largest group, accounting for up to 98–99% of all cases of obesity, is simple (constitutional-exogenous, idiopathic) obesity. Disease onset is most often after the age of 5 years or during puberty. As a rule, obesity progresses gradually, against the background of good (often accelerated) growth rates. The presence of striae, follicular keratosis, polyphagia, acanthosis nigricans, arterial hypertension, etc. does not always correlate with the degree of obesity. The presence of overweight and obesity in relatives (parents, grandparents) is characteristic.

Hypothalamic obesity in most cases has a rapidly progressive character, developing after surgery (radiation therapy), and less frequently ¾ precedes the period of diagnosis. In cases of craniopharyngioma, most patients are characterized by slowed growth rates; for gliomas — symptoms of precocious puberty; neurological complaints (headaches, visual impairment) depend on the location and progression of the tumor. Children with hypothalamic obesity often exhibit sleep-wake rhythm disorders and behavioral disturbances.

It should be particularly noted that the "hypothalamic syndrome of puberty" encountered in Russian-language literature and practice is not hypothalamic obesity, but rather simple constitutional-exogenous obesity with comorbid conditions.

In monogenic forms, obesity debuts in the first months and years of life, while the majority of syndromic forms are characterized by psychomotor developmental delay.

• Screening for monogenic and syndromic forms of obesity is recommended for children with early-onset obesity (under 5 years of age) accompanied by prominent polyphagia, especially in the presence of a strong family history of obesity [1, 6, 12].

Level CLevel 5Level of recommendation evidence C (reliability level of evidence – 5).

Syndromic forms of obesity are characterized by an early onset of obesity and its rapid progression. Most syndromic forms are distinguished by a moderate to severe neurodevelopmental delay, dysmorphic features, and organ-specific developmental anomalies. To date, at least 30 obesity-associated syndromes have been studied (the best known are listed in Table 1). Syndromic obesity can be caused by mutations in either a single gene (Alström syndrome, Cohen syndrome) or multiple genes (Bardet-Biedl syndrome), as well as by chromosomal rearrangements and/or imprinting disorders (Prader-Willi syndrome, Albright hereditary osteodystrophy).

Prader-Willi syndrome (PWS) is the most frequent syndromic form of obesity, occurring in 1 out of 10,000–30,000 newborns. The development of PWS is caused by disrupted gene expression of the paternal allele on chromosome 15 (microdeletion, maternal uniparental disomy, imprinting center mutations, chromosomal translocations). The diagnosis can be suspected prenatally based on reduced fetal motor activity, whereas neonatal hypotonia with the absence of the suck reflex is such a significant clinical sign of the syndrome that it allows for diagnosis right in the maternity hospital, especially when combined with characteristic phenotypic stigmata (dolichocephaly, acromicria, thin lips with down-turned corners, almond-shaped eyes, strabismus) and signs of hypogonadism (external genitalia hypoplasia, cryptorchidism) in newborns [13]. In the neonatal period, due to feeding difficulties, children with PWS may lag in weight, whereas from 2 years of age, the second period characteristic of the syndrome is observed, accompanied by excessive weight gain, increased interest in food, hyperphagia leading to morbid obesity. Psychomotor developmental delay is observed in almost all children with PWS. Hypothalamic dysfunction underlies many manifestations of the syndrome (hyperphagia, temperature and pain dysregulation, endocrinopathies including growth hormone deficiency, hypogonadism, hypothyroidism, and central adrenal insufficiency). DNA methylation using methylation-specific polymerase chain reaction (PCR) is a highly specific diagnostic method that allows for confirming or excluding the diagnosis of PWS [14].

Bardet-Biedl syndrome (BBS) is an autosomal recessive disorder characterized by obesity, retinitis pigmentosa, polydactyly, intellectual disability, hypogonadism, and renal pathology (renal developmental anomalies, renal failure). The prevalence of this pathology is 1:160,000. At least 25 different genes are involved in the development of BBS, as well as in the development and functioning of cilia (primary cilia), which are primarily sensory organelles and participate in signaling pathways, including the regulation of eating behavior. BBS is considered a ciliopathy, and the mechanisms of obesity development in BBS are still being studied [15].

Pseudohypoparathyroidism type 1A is characterized by a combination of parathyroid hormone resistance and a specific phenotype known as Albright hereditary osteodystrophy (AHO). AHO combines specific (brachydactyly, subcutaneous calcifications) and non-specific manifestations (obesity, short stature, round face, intellectual disability). Pseudohypoparathyroidism type 1A develops as a result of post-receptor signal transduction impairments from the receptor to the cell, with the most frequent cause being inactivating mutations of the GNAS gene, leading to decreased expression and function of the stimulating alpha-subunit of the G protein (Gas). The disease is characterized by an autosomal dominant inheritance pattern. The GNAS gene is tissue-specifically imprinted, and Gas is produced in a number of tissues (somatotrophs, gonads, thyroid gland, proximal renal tubules) solely from the maternal allele. In most tissues, Gas is expressed biallelically, but even 50% protein activity may be insufficient in certain tissues, thereby developing the AHO phenotype. Due to these expression features of GNAS, if the mutation is inherited from the mother, both AHO and parathyroid hormone (PTH) resistance develop, and resistance to TSH, gonadotropic hormones, and somatoliberin may also be observed [16]. When the GNAS mutation affects the paternal allele, Gα expression from the maternal allele is preserved; therefore, as a rule, only specific phenotypic features of Albright osteodystrophy develop (see Table 1).

In a study by Edson Mendes de Oliveira et al., exome sequencing of 2,548 children with severe obesity identified 22 children with genetic variants in the GNAS gene. In 16 children, the effect of GNAS mutations on signaling via the melanocortin-4 receptor (MC4R), which couples with Gas and is crucial for appetite and weight regulation, was investigated. Gas triggers one of two signaling pathways from the MC2R and MC4R melanocortin receptors, mediating ACTH effects in the former case and contributing to basal metabolic regulation in the latter. Energy homeostasis regulation is mediated through melanocortin type 4 receptors (MC4R). All this explains the mechanism of obesity development in pseudohypoparathyroidism, which is mediated by the resistance of these receptors [17].

Table 1

Syndromic forms of obesity

Monogenic forms of obesity are extremely rare, characterized by an early onset (from the first months of life up to 1 year) and polyphagia. Most patients have normal neuropsychological development (see Table 2). Monogenic forms of obesity develop due to a mutation in one of the genes encoding proteins of the leptin-melanocortin system. This system is key in the regulation of eating behavior and energy metabolism; it is activated by leptin (LEP), which is secreted by adipocytes, but exerts its effect via the leptin receptor (LEPR) of the arcuate nuclei of the hypothalamus, leading to the activation of pro-opiomelanocortin (POMC). Under the action of the prohormone convertase 1 (PC1) enzyme, adrenocorticotropic hormone (ACTH) and α-melanocyte-stimulating hormone (α-MSH) are formed from POMC, which in turn activates the MC4R receptor in the paraventricular nuclei, leading to satiety signaling. The PC1 enzyme cleaves prohormones at basic amino acid pairs, leaving C-terminal basic residues, which are removed by carboxypeptidase E (CPE). Brain-derived neurotrophic factor (BDNF) and its receptor (TrkB) are also involved in the regulation of the MC4R signaling pathway, and the SIM 1 (single-minded homolog 1) gene encodes a transcription factor involved in the development of the supraoptic and paraventricular nuclei [15].

Table 2

Monogenic forms of obesity

Leptin deficiency

Congenital leptin deficiency is a rare syndrome characterized by morbid obesity from the first months of life accompanied by severe hyperphagia and low, undetectable leptin levels. These patients are characterized by hypogonadotropic hypogonadism, growth hormone deficiency, central hypothyroidism, and children with leptin deficiency also frequently suffer from respiratory infections due to T-cell hypofunction.

Leptin receptor deficiency

Characterized by a clinical picture similar to leptin deficiency; however, a distinctive laboratory feature of this syndrome is an elevated serum leptin level.

POMC deficiency

The combination of rapidly progressive morbid obesity, increased appetite, and adrenal insufficiency with undetectable serum cortisol and ACTH levels is characteristic of proopiomelanocortin deficiency. POMC deficiency leads to hyperphagia and early-onset obesity due to the loss of melanocortin signaling at the melanocortin-4 receptor (MC4R). In the postnatal period, the newborn develops adrenal insufficiency (secondary, due to ACTH deficiency, since POMC is its precursor) characterized by hypoglycemia, prolonged jaundice, and a predisposition to severe infections. Due to the lack of melanocyte-stimulating hormone (MSH) action on melanocortin-1 receptors, most such children have pale skin and red hair.

Prohormone convertase 1 (PC1) deficiency

Mutations in this enzyme lead to impaired cleavage of multiple prohormones, such as pro-gonadotropin-releasing hormone, proinsulin, pro-thyrotropin-releasing hormone, and POMC, contributing to the development of GH deficiency, secondary hypocortisolemia, hypothyroidism, and hypogonadism. The inability to cleave POMC is a probable mechanism for the development of obesity in such patients. Intestinal dysfunction and postprandial hypoglycemia are explained by impaired maturation of gastrin, glucagon, glucagon-like peptide-1, and insulin (elevated proinsulin levels) in PC1 deficiency.

Brain-derived neurotrophic factor (BDNF) and its receptor (TrkB) deficiency

The development and differentiation of central and peripheral nervous system neurons depend on neurotrophic factors (neurotrophins) secreted by target tissues. Neurotrophin signaling occurs via the specific activation of tyrosine kinase B receptors. A heterozygous mutation in the NTRK2 gene encoding tyrosine kinase B (TrkB) was identified in an 8-year-old boy with severe developmental delay (impaired short-term memory, stereotypic behavior), impaired pain sensitivity, and severe obesity.

Mutation in the SIM1 gene

A de novo translocation between chromosomes 1 and 6 was detected in a girl with a body weight of 47 kg at the age of 5.5 years [18]. The mutation leads to a disruption in the SIM1 gene, the human homolog of the Drosophila Single-minded (Sim) gene, which regulates neurogenesis. The SIM1 gene encodes a transcription factor involved in the formation of the paraventricular and supraoptic nuclei. A deletion of the 6q16.2-6q16.3 region has been identified in patients with obesity and Prader-Willi-like phenotype [19].

MC4R deficiency

Mutations in the MC4R gene are the most frequent monogenic cause of obesity. Patients with MC4R deficiency are characterized by increased appetite and obesity combined with a high growth rate. Along with excess fat mass, MC4R gene mutations are characterized by an increase in lean mass and bone mineral density, which is why such individuals often appear "broad-boned." Patients with MC4R deficiency exhibit higher fasting insulin concentrations compared to children of the same age, sex, and BMI. Homozygous mutations are much rarer than heterozygous ones and feature more pronounced clinical symptoms [20]. Adult patients exhibit less pronounced hyperphagia and hyperinsulinemia than children with the same mutation.

Neuroendocrine diseases are rare causes of childhood obesity and are characterized by specific clinical signs. For instance, hypercortisolism is characterized by decreased growth velocity along with progressive obesity, whereas the appearance of dry skin, cold intolerance, and fatigue may indicate the presence of hypothyroidism.

2. Diagnostics, medical indications and contraindications for diagnostic methods

Criteria for establishing the diagnosis/condition:

As a diagnostic criterion for overweight and obesity in children, it is recommended to determine the standard deviation score of the body mass index (BMI SDS).

In accordance with WHO recommendations, obesity in children and adolescents aged 0 to 19 years should be defined as a BMI equal to or greater than +2.0 BMI SDS, and overweight from +1.0 to +2.0 BMI SDS. Normal body weight is diagnosed when BMI values are within ± 1.0 BMI SDS [1, 21, 22].

The WHO website presents new growth and weight reference values for children in the form of tables and curves for ages 0–5 years (http://who.int/childgrowth/standards/ru/) and ages 5–19 years (https://www.who.int/tools/growth-reference-data-for-5to19-years/indicators/bmi-for-age) (see Appendix G1, G2).

Additionally, for the diagnosis of overweight and obesity in children, WHO software tools Anthro (for ages 0–5 years) and AnthroPlus (for ages 5–19 years) for personal computers can be used (https://www.who.int/tools/growth-reference-data-for-5to19-years/application-tools).

Since directly assessing the amount of adipose tissue in the body is difficult, the most informative approach is determining BMI, which is calculated as the ratio of body weight in kilograms to the square of a person's height expressed in meters. It has been proven that BMI correlates with body fat mass in both adults and children. According to WHO criteria, in adults, a BMI of 18.5–24.9 corresponds to normal body weight, 25–29.9 to overweight, and obesity is diagnosed at a BMI above 30. Criteria for overweight in children are determined using percentile tables or BMI standard deviation scores (SDS). These take into account not only height and weight, but also the child's sex and age. This is because BMI values in children change as the child develops: high in the first year of life, decreased in early childhood (2–5 years), and gradually increasing during puberty, which generally reflects the dynamics of adipose tissue.

These standards share a common principle: percentiles must be symmetrical relative to the median (the 50th percentile). The WHO uses standard deviations of –1, –2, –3 SDS, the median, and +1, +2, +3 SDS.

2.1 Complaints and Anamnesis

Taking the medical history involves identifying birth weight, age of obesity onset, psychomotor development, family history of obesity (including parental height and weight), type 2 diabetes mellitus, and cardiovascular diseases, growth and weight dynamics, presence of neurological complaints (headaches, visual disturbances), snoring (≥ 3 nights per week), and sleep apnea.

2.2 Physical Examination

• All children with obesity and overweight are recommended to undergo height measurement, height SDS, weight measurement with BMI SDS calculation, waist circumference measurement, and assessment of subcutaneous fat distribution [1, 22, 23, 24, 25, 26].

Level CLevel 5Level of recommendation evidence C (reliability level of evidence – 5).

• All children with obesity and overweight are recommended to have their blood pressure (BP) measured on peripheral arteries to detect arterial hypertension, with evaluation taking into account sex, age, and height [1, 12, 23, 27, 28]:

Level CLevel 5Level of recommendation evidence C (reliability level of evidence – 5).

• To diagnose arterial hypertension detected during routine measurement, 24-hour ambulatory blood pressure monitoring is recommended [23, 27, 28].

Level CLevel 5Level of recommendation evidence C (reliability level of evidence – 5).

Comments:

Measurement and subsequent evaluation of blood pressure (BP) are carried out in accordance with the “Clinical Guidelines for Arterial Hypertension in Children” of the Russian Ministry of Health and the guidelines for the diagnosis, treatment, and prevention of arterial hypertension in children and adolescents developed by experts from the Association of Pediatric Cardiologists of Russia and the Russian Medical Society on Arterial Hypertension [27, 28].

In children and adolescents, the following are distinguished: normal BP, high normal BP, and stage 1 and 2 arterial hypertension. Blood pressure levels are evaluated using percentile tables that take into account the patients' sex, age, and height

Normal BP – systolic blood pressure (SBP) and diastolic blood pressure (DBP) whose level is ≥10th and <90th percentile of the population BP distribution curve for the corresponding age, sex, and height.

High-normal BP is defined as SBP and/or DBP whose level is ≥90th and <95th percentile of the population BP distribution curve for the corresponding age, sex, and height, or ≥120/80 mm Hg (even if this value is <90th percentile).

Arterial hypertension is defined as a condition in which the average SBP and/or DBP level, calculated from three separate measurements, is ≥ the 95th percentile value of the population BP distribution curve for the corresponding age, sex, and height.

If SBP and DBP levels fall into different categories, the stage of AH is determined by the higher value of the two parameters.

In children and adolescents, 2 stages of AH are distinguished:

Stage 1 – average SBP and/or DBP levels from three measurements equal to or exceeding the 95th percentile values established for the given age group, provided that they exceed the 99th percentile by no more than 5 mm Hg.

Stage 2 (severe) – average SBP and/or DBP levels from three measurements exceeding the 99th percentile values by more than 5 mm Hg, established for the given age group.

• In all children with obesity and overweight, for screening of obesity-associated diseases, it is recommended to determine the presence and nature of striae, follicular keratosis, acanthosis nigricans, androgen-dependent dermopathy (in girls – hirsutism, acne, oily seborrhea) [1, 12, 23, 24]:

Level CLevel 5Level of recommendation evidence C (reliability level of evidence – 5).

• In all children with obesity and overweight, for an objective assessment of the child's condition, it is recommended to evaluate the stage of sexual development using the Tanner scale (Appendix H3) [1, 12, 23, 24]:

Level CLevel 5Level of recommendation evidence C (reliability level of evidence – 5).

• In all children with obesity and overweight, to identify genetic syndromes associated with obesity, it is recommended to identify characteristic specific phenotypic features (see Table 2) [1, 12, 23, 25]:

Level CLevel 5Level of recommendation evidence C (reliability level of evidence – 5).

2.3 Laboratory Diagnostics

• In all patients with obesity, for the purpose of complication screening, it is recommended to perform a general clinical biochemical blood test to detect lipid metabolism disorders, with determination of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity in the blood in combination with an ultrasound examination of the abdominal organs (liver) [23, 27, 28, 29, 30].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5). Comments:

To diagnose dyslipidemia in all patients, the levels of total cholesterol, high- and low-density lipoprotein cholesterol, and triglycerides in the blood are determined. Criteria for optimal, elevated, high, and low values of lipids and lipoproteins in children and adolescents have been established (see Table 3)

The diagnosis of dyslipidemia is established in the presence of 2 or more "high" and/or "low" parameters:

• Cholesterol ³ 5.2 mmol/L

• Triglycerides > 1.3 (for children under 10 years); ³ 1.7 (for children over 10 years) mmol/L

• HDL ≤ 0.9 (boys) and ≤ 1.03 (girls) mmol/L

• LDL ³ 3.0 mmol/L

Table 3

Classification of serum lipid and lipoprotein levels in children and adolescents [31, 32]

Determination of ALT and AST activity in combination with liver ultrasound is recommended for all patients with obesity to screen for non-alcoholic fatty liver disease. Fatty hepatosis occurs in 25-45% of adolescents with obesity; with the duration of obesity, liver damage may also progress: steatohepatitis, fibrosis, cirrhosis. Thus, in the USA, non-alcoholic fatty liver disease is the most common cause of cirrhosis in adolescents and the most frequent indication for liver transplantation in adults [33].

ALT activity exceeding the upper limit of normal established for a given laboratory in children with ultrasound signs of NAFLD in the absence of other causes of cytolytic syndrome (viral, metabolic liver damage, etc.) is regarded as a manifestation of steatohepatitis [29]. In dubious cases, reliable diagnosis of non-alcoholic steatohepatitis is possible only after morphological examination of liver tissue.

• In all patients with obesity over 10 years of age, to detect carbohydrate metabolism disorders, it is recommended to perform a glucose tolerance test (OGTT) with determination of fasting glucose and at 120 minutes [34, 35, 36].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5).

Comments:

Conditions for the test: in the morning on an empty stomach, following an 8-14 hour fast, the patient drinks glucose at a rate of 1.75 g of dry substance per 1 kg of body weight, but not more than 75 g, dissolved in 250 ml of water. For three days prior to the test, the patient is recommended to consume a diet containing at least 250-300 g/day of carbohydrates and maintain normal physical activity.

Evaluation of the OGTT (performed based on blood plasma glucose levels):

• Normoglycemia is a fasting glucose level of less than 6.1 mmol/L and a 2-hour post-standard OGTT glucose level of less than 7.8 mmol/L.

• Impaired fasting glucose: fasting glucose level is 6.1 – 6.9 mmol/L;

• Impaired glucose tolerance: glucose level at 2 hours of OGTT corresponds to 7.8 – 11.1 mmol/L.

The diagnosis of DM in children is established if

1. Fasting glucose level ³ 7.0 mmol/L; fasting state is defined as no caloric intake for at least 8 hours^a, or

2. Glycemia level 2 hours after standard OGTT ³ 11.1 mmol/L, or

3. There are classic symptoms of diabetes mellitus (polyuria, polydipsia, unexplained weight loss) combined with a random blood glucose determination ³ 11.1 mmol/L. A "random" measurement is considered to be a glucose level determined at any time of day regardless of the time of the last meal, or

4. Glycated hemoglobin (HbA1c) > 6.5% ^b. The test is recommended to be performed in a certified laboratory (using a method approved by the National Glycohemoglobin Standardization Program and standardized in accordance with the Diabetes Control and Complications Trial (DCCT)).

a - In the absence of overt hyperglycemia, a diagnosis of DM made on the basis of these criteria must be confirmed by repeat tests.

b - A level of less than 6.5% does not exclude the possibility of diagnosing DM based on glucose levels.

It is not advisable to test blood glucose levels using glucometers for the diagnosis of carbohydrate metabolism disorders, since glucometers do not have sufficient accuracy for a definitive diagnosis and may lead to diagnostic errors [34].

In clinically manifest DM, performing an OGTT is not recommended; carbohydrate metabolism disorders can be diagnosed using fasting glycemia parameters, postprandial levels, or levels throughout the day, as well as by determining glycated hemoglobin.

Performing an OGTT in children with obesity under 10 years of age is indicated if the child has additional risk factors: clinical signs of insulin resistance (acanthosis nigricans), gestational diabetes in the mother, DM in 1st- and 2nd-degree relatives, suspicion of congenital syndromes associated with early development of DM, etc., and is decided on an individual basis in each case [35].

According to epidemiological studies, individuals with impaired fasting glucose and impaired glucose tolerance constitute a risk group for the development of type 2 diabetes mellitus, and these carbohydrate metabolism disorders are regarded as "prediabetes".

2.4 Instrumental Diagnostics

• For screening of NAFLD and cholelithiasis in children and adolescents with obesity, it is recommended to perform an abdominal ultrasound examination (comprehensive) [1, 29, 30, 33, 37].

Level CLevel 5Level of recommendation evidence C (reliability level of evidence – 5).

Comments:

Instrumental diagnostic methods are leading in establishing the diagnosis of NAFLD and cholelithiasis. Ultrasound examination helps detect hepatic steatosis and the presence of calculous cholecystitis with a sufficiently high accuracy. Diagnostic ultrasound signs of fatty hepatosis include hepatomegaly, heterogeneity of the parenchyma, attenuation of the ultrasound signal in the distal parts of the liver, and depletion of the vascular pattern.

The "gold standard" for diagnosing NAFLD is percutaneous liver biopsy under ultrasound guidance. However, its widespread use, especially in pediatric practice, is limited due to the invasiveness of the technique.

• Nighttime polysomnography is recommended for children and adolescents with obesity who present with clinical signs of obstructive sleep apnea syndrome (OSAS): excessive daytime sleepiness, snoring during sleep, and episodes of breathing cessation during sleep [1, 12, 23, 26, 38, 39].

GPP BLOE 3Grade of Recommendation B (Level of Evidence – 3).

• Cardiorespiratory (respiratory) monitoring is recommended as an alternative diagnostic method for OSAS in children and adolescents with obesity [26, 38, 39, 40].

GPP BLOE 3Grade of Recommendation B (Level of Evidence – 3).

Comments:

Obstructive sleep apnea syndrome (OSAS) is characterized by sleep-related breathing disorders in the form of prolonged partial upper airway obstruction and/or complete intermittent obstruction (obstructive apnea), which disrupts normal pulmonary ventilation during sleep and impairs sleep quality [26]. Excessive fat deposition in the pharynx, neck, chest, and abdominal regions, fat infiltration of the diaphragm, increased muscle relaxation during sleep, and tonsillar and adenoidal hypertrophy contribute to the development of obstructive sleep apnea syndrome [38]. Obesity is an independent risk factor for OSAS [39]. The prevalence of OSAS in overweight and obese children reaches 38% compared to 3% in the general population [40]. Moderate and severe OSAS is associated with an increased risk of cardiovascular, metabolic, cognitive, and emotional-behavioral disorders in children [41–45].

Nighttime polysomnography is the "gold standard" for diagnosing obstructive sleep apnea and includes the analysis of sleep architecture and the respiratory disturbance index (RDI; apnea-hypopnea index) to determine the severity of OSAS. Cardiorespiratory (respiratory) monitoring also records respiratory parameters and allows for the assessment of the RDI, but it does not include the analysis of sleep stages. Therefore, this study is not recommended for patients with sleep disorders [26, 38].

2.5 Other Procedures

• An assessment of actual dietary intake using the 24-hour dietary recall method with a food diary is recommended for all children and adolescents with obesity and overweight in order to prescribe or adjust medical nutrition therapy [1, 12, 23].

Level CLevel 5Level of recommendation evidence C (reliability level of evidence – 5).

Comments: Nutritional status assessment is of great clinical significance as it contributes to the timely identification of risk groups for obesity and overweight, as well as other nutrition-related diseases. Evaluating dietary status in clinical practice for children and adolescents is useful both for selecting and assessing the effectiveness of diet therapy and pharmacotherapy.

Various methods are used to assess actual dietary intake and changes in nutritional status, including the 24-hour dietary recall method (maintaining a food diary) and the food frequency questionnaire method.

The method of recording food intake using a food diary is the most accurate and reliable for assessing actual intake. Its disadvantages include being labor-intensive and its potential impact on the patient's habitual diet.

• Additional investigations (hormonal profile testing, brain MRI, molecular genetic, and cytogenetic methods) in children and adolescents with obesity are recommended only when hypothalamic, syndromic, endocrine, or monogenic forms of obesity are suspected [1, 12, 23, 28].

Level CLevel 5Level of recommendation evidence C (reliability level of evidence – 5).

Comments:

Hormonal tests are performed strictly according to indications.

Evaluation of blood thyroid-stimulating hormone (TSH) and serum free thyroxine (FT4) levels is advisable when hypothyroidism is suspected; assessment of serum total cortisol, blood adrenocorticotropic hormone (ACTH), and blood leptin levels is indicated when monogenic obesity associated with proopiomelanocortin or leptin deficiency is suspected; measurement of total cortisol and ACTH in the blood, their circadian rhythm, urinary free cortisol, and dexamethasone suppression tests** are indicated when endogenous hypercortisolism is suspected; and measurement of parathyroid hormone and proinsulin in the blood is indicated when syndromic forms of obesity (pseudohypoparathyroidism, prohormone convertase 1 deficiency) are suspected.

Measurement of blood insulin-like growth factor I (IGF-1) is indicated when hypothalamic obesity is suspected. Measurement of blood prolactin is indicated when hypothalamic obesity is suspected, as well as in girls with menstrual irregularities. Assessment of serum luteinizing hormone, serum follicle-stimulating hormone, total testosterone, sex hormone-binding globulin, and anti-Müllerian hormone in the blood is performed in cases of hyperandrogenism syndrome, dysmenorrhea in girls, and puberty disorders in boys.

Measurement of blood aldosterone, blood renin, and urinary metanephrines and normetanephrines is indicated to clarify the genesis of newly detected arterial hypertension in an obese patient, depending on clinical manifestations.

Brain MRI is indicated when hypothalamic obesity is suspected.

Gene mutation analysis and cytogenetic testing (karyotyping) are performed when monogenic and syndromic forms of obesity are suspected. A characteristic feature of syndromic obesity is the presence of pronounced neurological symptoms—psychomotor developmental delay, intellectual disability, etc. In such cases, consultation with a neurologist and a geneticist, along with genetic testing tailored to the clinical picture and phenotypic features, is advisable.

• Routine determination of TSH to rule out endocrine causes of obesity in children and adolescents is not recommended [46].

Level CLevel 5Level of recommendation evidence C (reliability level of evidence – 5).

Comments:

According to the European Thyroid Association guidelines for the management of subclinical hypothyroidism, an elevated TSH level ranging from 5 to 7 mIU/L in obese children and adolescents is in the vast majority of cases a consequence rather than a cause of obesity and does not warrant levothyroxine sodium hormone therapy [46].

• Consultations (examinations) with specialists—cardiologist, obstetrician-gynecologist, ophthalmologist, medical psychologist, psychiatrist, somnologist, otorhinolaryngologist, nutritionist, and others—are recommended for overweight and obese children and adolescents when comorbid conditions are identified, such as arterial hypertension, menstrual irregularities, depression, OSAS, etc. [1, 12, 23, 26, 28].

Level CLevel 5Level of recommendation evidence C (reliability level of evidence – 5).

• Assessment of insulin resistance (IR) in children and adolescents with obesity is performed based on strict indications and is not recommended in routine clinical practice [1, 12, 23].

Level CLevel 5Level of recommendation evidence C (reliability level of evidence – 5).

Comments:

The "gold standard" for diagnosing IR is the euglycemic-hyperinsulinemic clamp, as well as the frequently sampled intravenous glucose tolerance test evaluated using the minimal Bergman model [47, 48].

Unfortunately, these tests are not applicable in everyday practice because they are quite time-consuming, expensive, and invasive, requiring specially trained medical personnel and complex statistical data processing.

In everyday practice, the values of stimulated insulin release and the Matsuda index, determined from glucose tolerance test data, hold the greatest diagnostic significance for assessing IR in obese children and adolescents [49]. To reduce the invasiveness of the study and minimize the risk of hemolysis, placing an intravenous catheter is preferred. Fasting blood immunoreactive insulin (IRI) and blood glucose levels are measured, as well as at 30, 60, 90, and 120 minutes following a glucose load, to calculate the Matsuda index:

Matsuda = 10000 / √(IRI0 × Gl0 × IRImed × Glmed),

where IRI is immunoreactive insulin in µIU/mL, and Gl is glucose in mg/dL. IRI0 and Gl0 are fasting plasma insulin and glucose; IRImed and Glmed are the mean insulin and glucose levels during the OGTT. Index values below 2.6 indicate the presence of insulin resistance [50, 51].

It should be noted that due to the controversial nature of IR assessment and the current lack of officially approved effective pharmacotherapy for this condition, insulin resistance evaluation should be performed selectively and is not mandatory in routine clinical practice. Indications for performing a glucose tolerance test with IR assessment include previously diagnosed carbohydrate metabolism disorders, a burdened family history (type 2 diabetes mellitus, hyperandrogenism, etc.), the presence of objective markers of insulin resistance such as acanthosis nigricans or pronounced hyperpigmentation of skin folds in the neck, axillary, or inguinal regions, and clinical signs of hyperandrogenism.

• For children and adolescents with obesity and overweight, in order to assess body composition, it is recommended, whenever possible, to determine the percentage ratio of water, muscle, and adipose tissue using bioelectrical impedance analysis [52–56].

GPP CLOE 4Grade of Recommendation C (Level of Evidence – 4).

Comments:

Bioelectrical impedance analysis of body composition is based on measuring the electrical resistance of tissues (impedance) when a low-intensity electric current passes through them, and makes it possible to estimate the amount of fat mass and fat-free mass, as well as total body water (body composition). In terms of the accuracy of the obtained results, bioelectrical impedance analysis approaches the data obtained by X-ray densitometry. The advantages of the method are the absence of radiation exposure and the possibility of follow-up monitoring over time. There are reference standards for assessing the studied body composition parameters depending on sex, age, and ethnicity, as well as the type of analyzer used [52, 53].

The study is advisable for maintaining the patient's motivational adherence to treatment and for assessing changes in body composition parameters over time, but it is not mandatory.

• To personalize the ongoing diet therapy in children and adolescents with obesity and overweight, it is recommended, whenever possible, to study basal metabolic rate indicators using indirect resting calorimetry [57, 58].

Level CLevel 5Level of recommendation evidence C (reliability level of evidence – 5).

Comments:

In order to increase the effectiveness of obesity treatment in children and adolescents, nutritionists actively use the determination of resting energy expenditure and macronutrient metabolism, which are among the leading components of personalized diet therapy. The main method for studying basal metabolism is currently indirect resting calorimetry. This technique is recommended by the American Dietetic Association and the American Academy of Pediatrics as the preferred method for assessing basal metabolism in children and adolescents.

At the same time, given the high cost of the method and the need for additional training of the physician to perform this study, the assessment of basal metabolism is feasible at large centers equipped with a specialized endocrinology department; it is not mandatory.

3. Treatment, including drug and non-drug therapies, diet therapy, and pain management

Lifestyle modification (diet therapy, increased physical activity, and behavioral therapy for eating habits) in children and adolescents with obesity or overweight, as well as in their family members, forms the basis of obesity therapy and prevention. If lifestyle modification is ineffective, pharmacological agents may be used, the list of which in children and adolescents is currently limited to orlistat. Bariatric surgery is another treatment method for morbid complicated obesity in adolescents.

The goal of obesity treatment in children and adolescents is, in the short term, to maintain the BMI SDS value (over 6–12 months of follow-up); in the long term, to decrease the BMI SDS value, achieve "overweight" and "normal weight" categories, ensure normal physical and somatic development of the child, develop independence and motivation for self-monitoring of eating behavior, and prevent obesity-associated comorbid conditions.

3.1 Diet therapy

• To control body weight in children and adolescents with obesity and overweight, it is recommended to establish and maintain healthy eating standards taking into account age-related characteristics [12, 57, 59, 60, 61].

GPP ALOE 1Grade of Recommendation A (Level of Evidence – 1).

Comments:

The current trend in pediatric obesity dietetics is an age-appropriate normocaloric diet with a sufficient amount of protein, carbohydrates, vitamins, and micronutrients, and the necessary minimum of fats, tailored to the child's taste preferences.

All types of diets—hypocaloric, ketogenic, low-fat, low-glycemic index, etc.—are alternative treatment options, used according to indications and often in specialized departments.

This is due to several factors. Firstly, current research has shown that long-term use of restrictive diets leads to nutritional status disorders, which is undesirable in children. Secondly, the initial daily caloric intake in children and adolescents with obesity is quite high, and its abrupt restriction is accompanied by an increase in the sense of hunger, which leads to a loss of motivation, failure to follow these recommendations, and loss of compliance.

Necessary conditions for effective treatment:

• restriction of sweet beverages: a ban (consumption of no more than 1 serving no more than 1 time per week) on not only sweet carbonated drinks, but also juices, compotes, and fruit drinks, while allowing drinking water as desired by the child,

• restriction of sweet fruits to 1 serving (100 g) per day,

• meals at least 4 times a day, mandatory breakfast,

• prohibition of sweet dairy products,

• control of portion size/quantity. To visually demonstrate desired portion sizes, "healthy eating plates" are now widely used. If the child wants a second serving of lunch/dinner, allow it 20 minutes after the first one, provided that regular meals (at least 4 times a day) are maintained

• enrichment of the diet with vegetables (for young children—300 g, for adolescents—400 g per day, with a restriction on using potatoes in such quantities as the sole vegetable), dietary fiber, and whole-grain products

• teaching children to eat slowly, without computer/television/mobile device distractions.

3.2 Physical activity and prevention of a sedentary lifestyle

• Children and adolescents aged 6 to 17 years with obesity and overweight are recommended daily moderate- to high-intensity physical activity (including as part of a prescribed exercise therapy program) totaling at least 60 minutes [61, 62, 63].

Level CLevel 5Level of recommendation evidence C (reliability level of evidence – 5).

• High-intensity physical activity (including as part of a prescribed exercise therapy program) is recommended to be included in the mandatory hour of daily physical activity and performed at least three times a week [62, 63].

Level CLevel 5Level of recommendation evidence C (reliability level of evidence – 5).

Comments: Regular physical activity is an important component of a healthy lifestyle. Scientific research has shown that physical activity has a significant positive effect on the health status of children and adolescents, in particular on the risk of overweight, obesity, and type 2 diabetes mellitus, as well as on the musculoskeletal system. In recent decades, physical activity among children and adolescents has been declining, which significantly increases the likelihood of developing overweight and obesity that can lead to cardiovascular diseases, cancer, and osteoporosis later in life. Conversely, good physical development and a high level of physical activity in children and adolescents are associated with a lower risk of these diseases.

According to global WHO recommendations, adequate physical activity for children and adolescents aged 6–17 years implies daily sessions lasting at least 60 minutes a day. Physical activity exceeding 60 minutes a day provides additional health benefits. The recommended daily duration of physical activity (60 minutes or more) can be accumulated throughout the day through shorter bouts of activity (e.g., 2 times a day for 30 minutes). Bouts of moderate- to high-intensity physical activity lasting at least 10 minutes are considered minimally effective.

Light-intensity physical activities include: household chores (ironing, tidying, cleaning), leisurely walking (3–4 km/h); moderate-intensity activities include drawing, moderate (4–6 km/h) and brisk walking (over 6 km/h), doubles tennis, golf, cycling (16–19 km/h); high-intensity activities include aerobics, cycling (19–22 km/h), swimming (45 m/min), singles tennis, and running (9 to 14 km/h).

Depending on its frequency, duration, and intensity, physical activity is divided into three categories: low, moderate, and high (Table 4)

Table 4.

Classification of physical activity

• Children aged 1–4 years are recommended various types of physical activity of any intensity totaling at least 180 minutes per day for the prevention of overweight and obesity [64].

Level CLevel 5Level of recommendation evidence C (reliability level of evidence – 5).

Comments:

According to the 2019 WHO guidelines on physical activity, sedentary behaviour and sleep for children under 5 years of age, specific definitions for the duration of physical activity have been developed for various age groups [64]. Physical activity for young children refers to various games: for example, lying on the floor with toys, crawling, baby gymnastics, etc. If the infant cannot crawl yet, it is recommended to spend at least 30 minutes a day in the prone position (tummy time).

• Children at 1 year of age are not recommended to have screen time [64].

Level CLevel 5Level of recommendation evidence C (reliability level of evidence – 5).

• Children aged 1 to 4 years are not recommended to have more than 1 hour of screen time per day [64].

Level CLevel 5Level of recommendation evidence C (reliability level of evidence – 5).

Comments:

WHO guidelines for children under 5 years limit the time spent by a young child in restraint devices and in front of a smartphone or TV screen (e.g., watching cartoons on TV or portable devices, playing smartphone games, etc.).

Parents should use the time the child spends in restraint devices, excluding sleep, for communication: reading fairy tales, reciting poems, singing songs. Restraint devices refer to various cradles, strollers, child safety seats, or carriers.

• For children and adolescents with obesity and overweight, in order to prevent hypokinesia, it is recommended to reduce inactive time spent in front of a television or computer monitor to 2 hours a day or less [63, 65, 66, 67].

Level CLevel 5Level of recommendation evidence C (reliability level of evidence – 5).

Comments:

Hypokinesia is an important predisposing factor for the development of overweight, obesity, and cardiovascular pathology in children and adolescents. Low physical activity is observed in 64–75% of adolescents. It is necessary to reduce the time spent on physically inactive pastimes: television, video films, computer games, and web surfing. From the first day and throughout the first month, screen time is recommended to be reduced by 30 minutes, from the second month by 45 minutes, from the 3rd month by 60 minutes, and so on.

• All children and adolescents with obesity and overweight as part of forming a "healthy lifestyle" are recommended to normalize their sleep schedule [64, 68, 69, 70].

GGR BLOC 1Grade of Recommendation B (Level of Evidence – 1).

Comments:

Sleep duration, bedtime and wake-up time, sleep quality (sleep architecture, subjective satisfaction with sleep), and efficiency (sleep latency or sleep onset speed and sleep continuity) affect body weight and appetite [69]. It is important to note that a late bedtime is associated with an increased risk of obesity and an increase in BMI SDS, regardless of wake-up time [69, 70].

Sleep deprivation and non-compliance with the daily routine contribute to changes in the secretion of a number of hormones (leptin, ghrelin, cortisol, growth hormone, decreased melatonin levels), lead to a decrease in daily physical activity, increased appetite, and consumption of high-calorie foods [68, 69].

The 2019 WHO guidelines define sleep duration in children [64]. Thus, for children under one year of age, sleep duration is 14–17 hours (at 0 to 3 months of age) or 12–16 hours (at 4 to 11 months of age), including daytime naps. For children aged 1 to 2 years, sleep duration is 11–14 hours, including daytime naps. For children aged 3 to 4 years, sleep duration is 10–13 hours.

The optimal sleep duration for early school-age children (5–13 years) is 9–11 hours per day, and for adolescents (14–18 years) 8–10 hours per day [69].

3.3 Pharmacotherapy

• The use of pharmacotherapy (in combination with lifestyle modifications) in children and adolescents with obesity is recommended from 12 years of age when measures aimed at forming a healthy lifestyle lasting at least 1 year are ineffective [12, 71].

GPP ALOE 1Grade of Recommendation A (Level of Evidence – 1).

Comments:

Medical therapy for obesity in adolescents is limited. Medications approved for the treatment of obesity in children older than 12 years globally and in the Russian Federation are liraglutide and orlistat.

• Children older than 12 years with obesity, as an adjunct to a healthy diet and physical activity when lifestyle modification measures lasting at least 1 year are ineffective, may be recommended therapy with liraglutide [72, 73].

Level of Evidence BLevel of Confidence 2Level of recommendation B (level of evidence – 2).

Comments:

Liraglutide is a glucagon-like peptide-1 (GLP-1) analogue. At the hypothalamic level, liraglutide, by activating GLP-1 receptors, enhances satiety signals and weakens hunger signals, thereby reducing food intake. In addition, liraglutide glucose-dependently stimulates insulin secretion and reduces glucagon secretion. The efficacy and safety of liraglutide in adolescents with obesity aged 12–17 years were evaluated in the SCALE TEENS randomized clinical trial. Liraglutide reduced body weight (on average by 2.7 kg compared to weight gain in the placebo group +2.1 kg), reduced the BMI SDS value more (by 0.25) than placebo (0.02); a greater achievement of 5% and 10% weight loss by patients was also noted in the liraglutide group compared to placebo [72, 73].

The drug is administered subcutaneously once daily at any time, regardless of meals, into the abdomen, thigh, or upper arm. The starting dose is 0.6 mg daily, followed by standard dose titration according to the instructions: the dose is increased by 0.6 mg at intervals of at least one week. The drug dose should be increased until a value of 3.0 mg (therapeutic dose) or the maximum tolerated dose is reached. Among side effects, dyspeptic symptoms (decreased appetite, nausea, vomiting, constipation, diarrhea) are described, which usually occur in the first weeks of treatment, are transient in most cases, and do not require discontinuation of therapy.

• Children older than 12 years when measures aimed at forming a healthy lifestyle lasting at least 1 year are ineffective may be recommended the intake of orlistat [12, 71].

Level of Evidence BLevel of Confidence 2Level of recommendation B (level of evidence – 2).

Comments:

Orlistat is an inhibitor of gastric and pancreatic lipases, which are involved in the hydrolysis of triglycerides and are necessary for the absorption of fats in the small intestine. As a result of the drug's action, the breakdown of dietary fats is impaired and their absorption is reduced. After drug withdrawal, its action rapidly terminates, and lipase activity is restored. The efficacy of orlistat in the complex therapy of obesity in adolescents has been evaluated in controlled clinical trials. According to these studies, the average weight change in the orlistat group ranged from +0.53 kg (12 months of therapy, 12 months of observation, 539 adolescents) [74] to –6.9 kg (6 months of therapy, 60 patients) [75]. Orlistat is prescribed at 1 capsule (120 mg) before main meals; the maximum daily dose is 360 mg (3 capsules, 1 capsule 3 times a day). The duration of treatment can range from 3 months to 12 months.

• Metformin** is not recommended for the treatment of obesity in children without complications and comorbid conditions [24, 71, 76–79].

Level CLevel 5Level of recommendation evidence C (reliability level of evidence – 5).

Comments:

Metformin** belongs to the biguanide group of hypoglycemic drugs for the treatment of diabetes mellitus. The use of metformin** in pediatric practice is approved in the age group older than 10 years with a diagnosed type 2 diabetes mellitus [76–78]. Meta-analyses demonstrate a moderate positive effect of metformin**, mainly manifested in the stabilization of weight and BMI SDS, as well as a reduction in fat mass and an improvement in the metabolic profile and insulin resistance in children and adolescents with obesity [24, 71, 78, 79].

Treatment with metformin** does not negatively affect lean mass and does not lead to a decrease in growth rates in adolescents [77].

It is important to note that treatment with metformin** in children and adolescents is not accompanied by the development of lactic acidosis, which has been described in adults [80].

According to updated data presented by the International Consortium for Childhood and Adolescent Endocrinology regarding the diagnosis and management of polycystic ovary syndrome in adolescents, metformin** has a favorable short-term (6 months) effect on the course of polycystic ovary syndrome (PCOS) in overweight and obese patients and can be used as monotherapy.[x] Metformin** therapy reduces the frequency of anovulation and testosterone levels in non-obese patients with PCOS and can also be used as monotherapy. The daily dose of metformin** in adolescents ranges from 0.5 to 2 g [24]. The use of metformin** as adjuvant therapy for PCOS (in combination with combined oral contraceptives) is beneficial in patients with obesity combined with carbohydrate metabolism disorders (impaired glucose tolerance, diabetes mellitus, insulin resistance). Long-term use of metformin** may lead to vitamin B12 deficiency, especially in high-risk groups (history of bariatric surgery, type 2 diabetes mellitus, vegetarianism, history of pernicious anemia), making it advisable to monitor this parameter during treatment [81].

Thus, off-label metformin** therapy is most advisable in the group of patients with hyperandrogenism and menstrual irregularities who are at risk for developing PCOS.

The mechanism by which metformin** promotes weight loss remains not fully understood to date. The main effects of metformin** include inhibition of gluconeogenesis and hepatic glucose production, increased sensitivity of liver tissue, skeletal muscle, and adipocytes to insulin action, partly by inducing the expression of glucose transporters (GLUT-1 and GLUT-4). The glucose-lowering action of metformin** is mediated primarily through the formation of insulin receptor substrate 2, which is found in the highest concentration in the liver.

At the beginning of treatment, gastrointestinal side effects are possible: flatulence, nausea, abdominal distention, loose stools, and a metallic taste in the mouth. Cases of lactic acidosis have also been reported during metformin** therapy. The risk of lactic acidosis is not affected by the duration of treatment, the dosage of metformin**, or the patient's age and sex. However, the probability of lactic acidosis increases in the presence of renal or hepatic impairment.

• Children with Prader-Willi syndrome may be recommended #somatropin** therapy [84].

Level of Evidence BLevel of Confidence 2Level of recommendation B (level of evidence – 2).

Comments:

The drug #somatropin** is approved by the Food and Drug Administration (FDA) for the treatment of children with Prader-Willi syndrome (PWS). According to numerous studies, #somatropin** therapy, especially when initiated at an early age (before the development of obesity), leads to an improvement in anthropometric parameters and body composition (decrease in fat mass and increase in muscle mass), which may help reduce the risk of obesity in these patients (provided that diet and physical activity regimens are followed) [84].

Before and during #somatropin** therapy, an assessment of anthropometric parameters, the condition of the adenotonsillar system, bone age, blood insulin-like growth factor I (IGF-1) levels, and carbohydrate metabolism parameters (blood glucose testing, plasma insulin testing, glycated hemoglobin testing) is performed. Given the potential effect of #somatropin** on the hypertrophy of the lymphoid tissue of the pharyngeal ring and the worsening of sleep-disordered breathing parameters with the risk of apnea, polysomnography is recommended both before and during therapy, especially in the first 3–6 months of #somatropin** treatment. The average daily dose of #somatropin** for the treatment of PWS is 1 mg/m²/day, but it is recommended to start therapy, especially in young children, with lower doses (0.5 mg/m²/day) followed by titration to the average daily dose under the control of IGF-1 values, avoiding exceeding the reference ranges [79, 84]. In young children with PWS (under 2 years of age), #somatropin** therapy at lower doses (0.6 mg/m²/day) showed efficacy similar to that of standard therapeutic doses (1 mg/m²/day) and was characterized by a lower number of side effects at the initial stage of treatment [84, 85]. Contraindications for prescribing #somatropin** in patients with Prader-Willi syndrome include severe complicated obesity, uncompensated diabetes mellitus, severe apnea, active malignancies, and psychotic disorders [79, 84].

Currently, drug therapy for certain monogenic forms of obesity—congenital leptin deficiency, leptin receptor deficiency, and pro-opiomelanocortin deficiency—is being investigated worldwide in clinical trials [86,87,88].

Recent studies show that lifestyle modification interventions, including educational programs for overweight and obese patients, as well as pharmacotherapy to reduce obesity in children and adolescents, have short-term efficacy. Therefore, the treatment of obesity in children and adolescents must be long-term.

3.4 Surgical treatment

• Surgical treatments for obesity (bariatric surgery) may be recommended in adolescents with morbid obesity only if the following conditions are met [12, 89,90,91]:

• BMI >35 kg/m² combined with clinically significant comorbid metabolic disorders (non-alcoholic steatohepatitis, type 2 diabetes mellitus, obstructive sleep apnea syndrome, Blount's disease, severe arterial hypertension);

• BMI >40 kg/m² (BMI SDS > 4.0 for sex and age) regardless of the presence of complications;

• Completed or nearly completed physical development (partial or complete closure of growth plates), attainment of Tanner stages 4-5 of sexual maturity;

• Documented failure of conservative obesity treatment methods for 6 months in specialized centers;

• Absence of mental illness, psychological or behavioral disorders that may hinder adequate compliance with postoperative recommendations (including those due to syndromic and hypothalamic forms of obesity);

• Willingness/ability of the adolescent and their family members to undergo long-term and regular postoperative follow-up

Level CLevel 5Level of recommendation evidence C (reliability level of evidence – 5).

Comments: Surgical treatments for morbid obesity (bariatric surgery) in adolescents have been gaining popularity worldwide over recent decades. The main advantages of bariatric surgery are rapid weight loss, improvement in metabolic parameters, and quality of life in patients with morbid obesity. According to the clinical guidelines of the International Endocrine Society, bariatric surgery is the treatment of choice for morbid complicated obesity in adolescents.

Laparoscopic approach is preferred in adolescent obesity surgery as the least invasive. Bariatric operations are divided into three groups: restrictive (gastric-limiting), malabsorptive (bypass), and combined. Restrictive operations aim to reduce stomach volume. Weight loss in this case occurs by limiting the amount of food consumed and achieving early satiety during meals. The most common gastric-limiting operations include laparoscopic adjustable gastric banding (LAGB) (currently LAGB is used extremely rarely) and laparoscopic sleeve gastrectomy (LSG). Combined operations include various modifications of laparoscopic Roux-en-Y gastric bypass (RYGB) with an alimentary limb anastomosis.

Currently, there are several consensus statements on metabolic surgery in adolescents with morbid obesity: clinical guidelines for the surgical treatment of morbid obesity in adolescents under the auspices of the International Pediatric Endosurgery Group (IPEG); European interdisciplinary clinical guidelines for the surgical treatment of morbid obesity under the auspices of the Bariatric Study Collaborative Group (BSCG); and recommendations of the pediatric working group of the American Society for Metabolic and Bariatric Surgery (ASMBS) (see Table 5).

According to a meta-analysis of 23 studies involving 637 adolescents who underwent various bariatric procedures, the mean BMI reduction at one year was 13.5 kg/m² (8 studies, 256 patients). When analyzing the effectiveness of various surgical techniques, the minimum weight loss was observed with adjustable gastric banding (AGB) (Δ BMI = 10.5 kg/m² — 11 studies, 271 patients), and the maximum with Roux-en-Y gastric bypass (RYGB) (Δ BMI = 17.2 kg/m² — 8 studies, 256 patients). For sleeve gastrectomy (SG), the mean BMI reduction was 14.5 kg/m² (3 studies; 90 patients) [92].

Currently, prospective studies reflecting data on the safety of bariatric surgery in adolescents have been published [93,94]. According to Inge et al. (277 patients; mean age 17 years), 19 adolescents (6.8%) underwent reoperation within 30 days after elective bariatric surgery. Readmission due to dehydration was required in 36 patients. Furthermore, 66% of all surgeries in this study were RYGB; 28% were SG, and 6% were AGB. All operations were performed laparoscopically. The highest number of complications was registered after RYGB [52]. Subsequent follow-up of this patient group for 3 years demonstrated that weight loss is sustained and persists throughout the 3-year follow-up period. It was also shown that over the entire follow-up period, 13% of children required reoperation [95]. Based on the analysis of 5-year dynamic follow-up of 81 children (aged 13 to 18 years) from the Swedish National Adolescent Registry after laparoscopic RYGB, it was shown that the mean BMI reduction during treatment was 13 kg/m² and was achieved two years after surgical treatment. Further dynamic follow-up shows a slight increase in BMI in the group of operated children.

Table 5.

International Consensuses on Bariatric Surgery in Adolescents

Over a five-year follow-up period, 20 adolescents (25%) required reoperations, half of which were laparoscopic cholecystectomies for calculous cholecystitis developed due to rapid and significant weight loss [96].

According to 94% of studies included in the systematic review and meta-analysis, surgical treatment of obesity demonstrated statistically significant advantages regarding weight loss and type 2 diabetes remission [98]. Moreover, it is important to note that patients who had diabetes for less than 5 years achieved long-term remission in 76% of cases, whereas among those with diabetes for more than 5 years, only 21% did [99].

Numerous data from prospective cohort studies have been obtained regarding the favorable effect of bariatric surgery on the reversal of metabolic disorders associated with obesity in adolescents. Weight loss in adolescents is accompanied by a significant improvement in carbohydrate and lipid metabolism parameters, a decrease in liver transaminase levels, and a reduction in the severity of obstructive sleep apnea syndrome. In addition, there is a substantial improvement in quality of life and a reduction in patients' psychological distress during dynamic follow-up [95,96,97].

SG and RYGB can be considered safe and effective methods for treating severe obesity in children. When deciding which procedure to use, consideration of vitamin deficiency complications, operative time, and the need for reoperation should be of paramount importance. The risk of reoperation is significantly higher with biliopancreatic diversion and adjustable gastric banding than with the other two procedures, making this choice less desirable. Reliable studies have shown that SG is as effective as RYGB in weight loss and comorbidity improvement. Thus, SG has gained universal acceptance and has become the most commonly performed procedure in adolescents [100].

Although the use of bariatric surgery in adolescents has increased in recent years, only a small fraction of children who have indications and are expected to derive significant health benefits are referred for surgical treatment [101].

All adolescents after bariatric surgery require monitoring of vitamin and micronutrient levels for the timely diagnosis of deficiencies. Calcium and vitamin D deficiencies develop most frequently in this patient group, leading to secondary hyperparathyroidism and osteoporosis if not corrected in a timely manner. Iron, folic acid, and other vitamins (thiamine, pyridoxine, cyanocobalamin), as well as fat-soluble vitamins, are also frequently registered [95,96,97].

Long-term clinical follow-up is a mandatory requirement and should be conducted in specialized centers under the supervision of a pediatric and bariatric surgeon, pediatrician/pediatric endocrinologist, and psychologist.

Conditions for performing bariatric surgery in children:

To determine the feasibility of bariatric surgery, the child must be consulted by a pediatric endocrinologist involved in pediatric weight loss programs. Before referral for surgical treatment, the specialist must ensure that the child has undergone weight loss programs and has been consulted by a psychologist or psychiatrist.

Bariatric procedures in children should be performed in pediatric surgical departments. The unit must be equipped with specialized equipment and instruments for bariatric surgery. The staff must have experience working with bariatric patients.

Consent for bariatric surgery:

When deciding on the feasibility of performing bariatric surgery in a child, the possibility of disagreements between the parent(s) and the adolescent must be taken into account. A thorough assessment of the understanding of obesity issues and bariatric surgery by both parents and adolescents must be conducted. Bariatric surgery should only be performed if both the parent and the adolescent consent to the procedure. In cases where the child lacks decision-making capacity, they must demonstrate the ability to make lifestyle changes following bariatric surgery, and only then should bariatric surgery be considered. Parents and the multidisciplinary team must decide that bariatric surgery is the best course of action for the child.

Special cases: In cases of Prader-Willi syndrome (PWS), the expected weight loss is less than in children without syndromic obesity [102]. Alqahtani et al. published a study involving 24 children with and without PWS, which confirmed the results of weight regain after sleeve gastrectomy (SG) in patients with PWS. At the same time, the use of SG proved to be safe and effective, demonstrating a sustained BMI reduction of 10 points over 5 years [103].

3.5 Anesthesia

Not applicable.

4. Medical Rehabilitation and Sanatorium-Resort Treatment

Specific measures of rehabilitation and sanatorium-resort treatment have not been developed.

5. Prevention and Dispensary Observation

• Children and adolescents with overweight and obesity are recommended routine clinical follow-up by a pediatrician/pediatric endocrinologist, including monitoring of anthropometric parameters, BMI assessment, and actual dietary intake [12,23,61].

Level CLevel 5Level of recommendation evidence C (reliability level of evidence – 5).

Comments:

The pediatrician monitors preschool and early school-age children with overweight or metabolically uncomplicated obesity. Infants under one year of age are monitored by a pediatrician on a monthly basis. This includes monitoring of anthropometric parameters and BMI SDS. If obesity develops, a consultation with a pediatric endocrinologist is indicated.

Toddlers (1–3 years) are monitored by a pediatrician every 3–6 months. If obesity develops, a consultation with a pediatric endocrinologist is also indicated, and in the presence of concomitant delayed psychomotor development, a genetics consultation is recommended.

Clinical follow-up of preschool and early school-age children with overweight can be performed by either a pediatrician or a pediatric endocrinologist. The most important component of such follow-up remains the assessment of the dynamics of anthropometric parameters, BMI SDS, evaluation of the child's lifestyle, and a detailed discussion with the parents. Monthly visits are required for the first 3 months, followed by visits every 6–12 months (if there is positive progress).

Clinical follow-up of adolescents with obesity requires a consultation with a pediatric endocrinologist. Screening for comorbid conditions is mandatory. Follow-up is performed monthly for the first 3 months, followed by every 6 months (if there is positive progress). Children with complicated obesity are monitored by a pediatric endocrinologist every 3–6 months. If complications persist, the scope of examinations and subspecialist consultations is determined individually.

When body weight normalizes, children are monitored by the pediatrician at scheduled intervals designated for healthy children (Health Group I).

• For the prevention of obesity in children, it is recommended to actively screen for overweight at the age of 2 to 9 years and conduct patient education schools for overweight and obese patients [12,23,61].

Level CLevel 5Level of recommendation evidence C (reliability level of evidence – 5).

6. Organization of Medical Care

Indications for hospitalization in a medical organization:

1) Form: elective; setting: inpatient, day hospital:

a. Comprehensive screening for complications when outpatient evaluation is not feasible;

b. Comprehensive treatment including the School for Overweight and Obese Patients (day hospital) when outpatient treatment and education are not feasible;

c. When planning bariatric surgery

2) Form: emergency, urgent; setting: inpatient: not applicable. If emergency conditions develop associated with the worsening of comorbid diseases (hypertensive crisis, acute abdomen in cholelithiasis, apnea), the patient must be hospitalized in a specialized department according to the primary emergency condition.

Indications for patient discharge from a medical organization

1) Form: elective; setting: inpatient, day hospital:

a. Performance of planned examination/treatment.

2) Form: emergency, urgent; setting: inpatient: stabilization of a life-threatening condition.

7. Additional Information

No additional information available.

Criteria for Evaluating the Quality of Medical Care

References

Appendix A1. Working Group Composition

LEADERS:

Valentina A. Peterkova – Academician of the Russian Academy of Sciences, Professor, Doctor of Medical Sciences, Scientific Supervisor of the Institute of Pediatric Endocrinology, National Medical Research Center for Endocrinology of the Russian Ministry of Health, Head of the Department of Pediatric Endocrinology and Diabetology, Institute of Higher and Continuing Professional Education, National Medical Research Center for Endocrinology of the Russian Ministry of Health, Chief freelance pediatric specialist endocrinologist of the Russian Ministry of Health.

Olga B. Bezlepkina – D.Sc. in Medicine, Deputy Director of the Center – Director of the Institute of Pediatric Endocrinology, National Medical Research Center for Endocrinology of the Russian Ministry of Health, Professor at the Department of Pediatric Endocrinology and Diabetology, Institute of Higher and Professional Continuing Education, National Medical Research Center for Endocrinology of the Russian Ministry of Health.

TEXT AUTHORS:

Olga V. Vasyukova – Ph.D. in Medicine, Leading Researcher at the Institute of Pediatric Endocrinology and Head of the Center for Treatment and Prevention of Metabolic Diseases and Obesity, National Medical Research Center for Endocrinology of the Russian Ministry of Health.

Pavel L. Okorokov – Ph.D. in Medicine, Senior Researcher at the Institute of Pediatric Endocrinology, National Medical Research Center for Endocrinology of the Russian Ministry of Health.

Oleg A. Malievsky – D.Sc. in Medicine, Professor at the Department of Hospital Pediatrics, Bashkir State Medical University of the Russian Ministry of Health, Chief freelance pediatric endocrinologist of the Volga Federal District.

Alexander E. Neymark – Ph.D. in Medicine, Surgeon, Head of the Research Laboratory of Metabolic Surgery, Leading Researcher, Associate Professor at the Almazov National Medical Research Centre.

Evgeny A. Zorin – Ph.D. in Medicine, Surgeon, Head of the Surgical Department, Medical and Rehabilitation Center of the Russian Ministry of Health.

Yuri I. Yashkov – D.Sc. in Medicine, Head of the Obesity Surgery Service, CELT JSC, Honorary President of the Russian National Association of Bariatric Surgeons.

Yulia V. Burmitskaya – Ph.D. in Medicine, Pediatric Endocrinologist, Somnologist at the Center for Treatment and Prevention of Metabolic Diseases and Obesity, National Medical Research Center for Endocrinology of the Russian Ministry of Health.

Daria A. Kopytina – Pediatric Endocrinologist, National Medical Research Center for Endocrinology of the Russian Ministry of Health.

REVIEWERS:

Bashnina Elena Borisovna — Doctor of Medical Sciences, Professor at the Department of Endocrinology named after Academician V.G. Baranov, North-Western State Medical University named after I.I. Mechnikov, Chief freelance pediatric endocrinologist of the North-Western Federal District.

Galkina Galina Aleksandrovna — Doctor of Medical Sciences, Head of the Pediatric Endocrinology Department, Research Institute of Obstetrics and Pediatrics, Rostov State Medical University of the Russian Ministry of Health, Chief freelance pediatric endocrinologist of the Rostov Region, Chief freelance pediatric endocrinologist of the Southern Federal District.

Kolodkina Anna Aleksandrovna — Head of the Department of Hereditary Diseases and Early-Onset Endocrinopathies, Institute of Pediatric Endocrinology, National Medical Research Center for Endocrinology of the Russian Ministry of Health, Candidate of Medical Sciences.

Kostrova Irina Borisovna — Head of the Pediatric Endocrinology Department, Children's Republican Clinical Hospital named after N.M. Kuraev, Chief freelance pediatric endocrinologist of the Republic of Dagestan, Chief freelance pediatric endocrinologist of the North Caucasian Federal District.

Elena V. Nagaeva – Head of the Department of Thyroidology, Somatic and Reproductive Development Disorders, Institute of Pediatric Endocrinology, National Medical Research Center for Endocrinology of the Russian Ministry of Health, D.Sc. in Medicine.

Elena E. Petryaikina – D.Sc. in Medicine, Director of the Russian Children's Clinical Hospital, Pirogov Russian National Research Medical University of the Russian Ministry of Health, Chief freelance pediatric endocrinologist of Moscow, Chief freelance pediatric endocrinologist of the Central Federal District.

Galina N. Svetlova – Deputy Chief Physician, National Medical Research Center for Endocrinology of the Russian Ministry of Health, Pediatric Endocrinologist, Ph.D. in Medicine.

Tatyana E. Taranushenko – D.Sc. in Medicine, Head of the Department of Pediatrics, Institute of Postgraduate Education, V.F. Voino-Yasenetsky Krasnoyarsk State Medical University of the Russian Ministry of Health, Chief freelance pediatric endocrinologist of Krasnoyarsk Krai, Chief freelance pediatric endocrinologist of the Siberian Federal District.

Chugunov Igor Sergeevich — Head of the Pediatric Endocrine Tumor Department, Institute of Pediatric Endocrinology, National Medical Research Center for Endocrinology of the Russian Ministry of Health, Candidate of Medical Sciences

Conflict of interest: the authors of the clinical guidelines declare no conflict of interest.

For final editing and quality control, the guidelines were re-analyzed by the working group members, who concluded that all expert comments and feedback had been taken into account and the risk of systematic bias in guideline development was minimized.

Appendix A2. Methodology for Developing Clinical Guidelines

Methods used for evidence collection/selection: electronic database search.

Description of methods used for assessing the quality and strength of evidence: the evidence base for the guidelines included publications from the Cochrane Library, EMBASE, MEDLINE, and PubMed databases. Literature search depth was 15 years.

Methods used to assess the quality and strength of evidence:

expert consensus;

assessment of significance in accordance with the rating scheme.

Methods used for evidence analysis:

reviews of published meta-analyses;

systematic reviews with evidence tables.

Description of methods used for evidence analysis

When selecting publications as potential sources of evidence, the methodology used in each study is examined to ensure its validity. The result of this examination affects the level of evidence assigned to the publication, which in turn affects the strength of the recommendations.

To minimize potential bias, each study was evaluated independently. Any discrepancies in evaluations were discussed by the full panel of authors. If a consensus could not be reached, an independent expert was involved.

Evidence tables: compiled by the authors of the clinical guidelines.

Methods used to formulate the recommendations: expert consensus.

Good Practice Points (GPPs–)

Recommended good clinical practice is based on the clinical experience of the authors of these guidelines.

Economic analysis

Cost analysis was not performed, and pharmacoeconomic publications were not analyzed.

Recommendation validation method

External expert review.

Internal expert review.

Description of the recommendation validation method

The draft of these recommendations was reviewed by independent experts who were primarily asked to comment on how comprehensible the interpretation of the evidence underlying the recommendations is.

Feedback was obtained from primary care physicians (pediatric endocrinologists) regarding the clarity of the presentation of these guidelines and their assessment of the importance of the proposed recommendations as a tool for daily practice.

All comments received from the experts were thoroughly systematized and discussed by the members of the working group (authors of the recommendations). Each item was discussed individually.

Consultation and peer review

The draft recommendations were reviewed by independent experts who were primarily asked to comment on the clarity and accuracy of the interpretation of the evidence base underlying the recommendations.

Working Group

For the final revision and quality control, the recommendations were re-evaluated by the members of the working group, who concluded that all comments and feedback from the experts had been taken into account and the risk of bias in the development of the recommendations was minimized.

Key recommendations

The strength of recommendations (1–5) based on the corresponding levels of evidence (A–C) (Table P1 and Table P2) is provided alongside the text of the recommendations.

Target audience for these clinical guidelines:

1. Pediatric endocrinologists;

2. Pediatricians;

3. General practitioners.

Table 1. Level of Evidence (LoE) grading scale for diagnostic methods (diagnostic interventions)

Table 2. Level of Evidence (LoE) grading scale for prevention, treatment, and rehabilitation methods (preventive, therapeutic, and rehabilitative interventions)

Table 3. Grade of Recommendation (GoR) scale for prevention, diagnostic, treatment, and rehabilitation methods (preventive, diagnostic, therapeutic, and rehabilitative interventions)

Procedure for updating clinical guidelines.

The mechanism for updating clinical guidelines provides for their systematic revision at least once every three years, as well as upon the emergence of new evidence-based medicine data on the diagnosis, treatment, prevention, and rehabilitation of specific diseases, or in the presence of justified additions/comments to previously approved clinical guidelines, but no more frequently than once every 6 months.

The decision to update is made by the Russian Ministry of Health based on proposals submitted by non-profit medical professional organizations. The formulated proposals must take into account the results of a comprehensive assessment of drugs and medical devices, as well as the results of clinical approbation.

Appendix A3. Reference Materials

1. Order of the Russian Ministry of Health No. 851n dated November 9, 2012, "On Approval of the Standard of Primary Health Care for Children with Obesity" (Registered with the Ministry of Justice of Russia on February 28, 2013, No. 27399)

2. Order of the Russian Ministry of Health No. 677n dated November 7, 2012, "On Approval of the Standard of Specialized Medical Care for Children with Obesity" (Registered with the Ministry of Justice of Russia on January 17, 2013, No. 26564)

Assessment scales, questionnaires, and other patient status evaluation tools provided in the clinical guidelines

Appendix 1. BMI normative values for children aged 0 to 5 years (WHO).

Source: (http://who.int/childgrowth/standards/ru/) Purpose: for assessing normal body weight, overweight, and obesity severity.

Appendix 2. BMI normative values for children aged 5 to 19 years (WHO).

Source: https://www.who.int/tools/growth-reference-data-for-5to19-years/indicators/bmi-for-age

Purpose: for assessing normal body weight, overweight, and obesity severity.

Appendix 3. Stages of sexual development according to the Tanner scale.

3. Stages of breast development and pubic hair growth in girls according to Tanner

Figure 1. Stages of breast development and pubic hair growth in girls according to Tanner.

Breasts: Stage 1: pre-pubertal breasts, glandular tissue is absent, areola diameter < 2 cm, areolas are pale. Stage 2: breasts and areolas protrude as a cone without distinct contours, areolar pigmentation appears. Stage 3: areola is deeply pigmented, protruding as a second cone above the breast tissue. Stage 4: mature breast, only the nipple projects.

Pubic hair: Stage 1: no hair growth. Stage 2: sparse pigmented hair growth on the labia majora. Stage 3: hair becomes darker and coarser, located across the pubic symphysis. Stage 4: complete pubic hair distribution.

3. Stages of sexual development in boys according to Tanner

Figure 2. Stages of sexual development in boys. Stage 1: no hair growth; testes, scrotum, and penis are pre-pubertal. Testicular volume 2–3 ml. Stage 2: sparse pigmented hair growth around the base of the penis; scrotum enlarges, becomes slightly pigmented. Testicular volume 4 ml. Stage 3: hair becomes darker and coarser, located across the pubic symphysis; elongation of the penis begins; scrotal skin begins to fold. Testicular volume 10 ml. Stage 4: complete pubic hair distribution, but no spread to the thighs or lower abdomen; penis continues to elongate; glans diameter increases; external genitalia become pigmented. Testicular volume – 12 ml or more. Stage 5: adult "diamond-shaped" hair distribution pattern; external genitalia reach maximum size. Testicular volume – 15 ml or more.

Appendix B. Physician Action Algorithms

Appendix C. Patient Information

Recommendations for overweight children and adolescents.

The best diet for weight loss is healthy eating!

BASIC HEALTH RULES

1. LIFESTYLE

• Make a daily schedule for the week (sleep, breakfast, school, lunch, computer, meeting friends, extracurricular activities or clubs, tutor, dinner, "doing nothing", helping around the house, reading for pleasure, etc.) and try to follow it: regularity is the key to success.

• Parental support: ask your parents to help you (even if they are also overweight and sure that it is fine and you have no problems), phrase your request correctly: if you have questions you would like to discuss with a doctor, ask your parents to make an appointment; prepare food for you to take to school as a snack; go for a walk with you, sign you up for a club, or go to a workout together; organize weekly (ideally ¾ daily) family lunches or dinners.

• Adequate sleep: healthy sleep should last at least 8–9 hours; those who want to lose weight need to sleep soundly at least from midnight (24:00) to 6:00 AM, so try to be in bed by 22:00 – 22:30.

• Meal schedule should not cause hunger: to lose weight, you need to eat more frequently (breakfast, lunch, dinner, and two snacks) but in smaller portions. Learn to pack a snack for school.

• You can skip dinner if you wish. But breakfast is a must in your life!

• While eating ¾ food only. Do not read, watch TV, or sit at the computer. This way you will happily avoid overeating.

• What is eaten and drunk during the day must correspond to your activity level. Therefore, you need to eliminate the habit of consuming the main part of food at night, and try to stop eating 2-3 hours before bedtime. Exclude "on-the-go" eating and fast food: hot dogs, chips, sandwiches, fried foods.

• Watching TV, working and playing on the computer — no more than 1-2 hours a day!

• Gradualness — no starvation or super-diets! Weight loss should be gradual, no more than 500 g per week.

• “Don't eat your feelings”: it's better not to "eat away" unpleasant situations, anxieties and worries at school or at home under a pillow, but rather "talk them through" in a conversation with parents and friends; if necessary, ask your parents to take you to a psychologist.

• Be sure to monitor your weight. It is best to weigh yourself in the morning, before eating, once a week. Don't forget to record your weight. Rejoice at every lost kilogram and every kilogram not gained.

2. PHYSICAL EXERCISE

• The main principle — move!

• Remember that for effective weight loss, physical exercise must be daily, lasting at least 60 minutes.

• Go to aerobics, shaping, fitness, aqua aerobics, the swimming pool, or simply walk.

• Don't like sports — go dancing.

• Help around the house — wash dishes, floors, dust.

• If you have time, walk to school and back instead of taking a bus or subway.

3. NUTRITION

• All sweet drinks (this includes not only carbonated beverages, but also all store-bought juices and iced teas) are undesirable! Firstly, it is harmful, and secondly, it is sweet. It is best to drink plain or mineral water, tea and coffee with 1 teaspoon of sugar, lemon or milk, berry infusions (rose hip), optionally — fresh fruit compote without sugar, 0.5 - 1 glass of freshly squeezed fruit juice (apple, orange, berries) diluted 1/3 with water, or vegetable juice.

• Eat porridge for breakfast: oatmeal with apples, raisins, millet porridge with pumpkin, buckwheat porridge with milk. Buckwheat with meat for breakfast is also very good. The thing is that porridges contain "complex" carbohydrates (unlike the "simple" carbohydrates found in your favorite buns) and give you the necessary energy until lunch. Also suitable for breakfast are rolled oats (not cornflakes!), which can be mixed with kefir, milk, or fruit.

• Fall in love with fruits and vegetables: apples (good baked), citrus fruits (grapefruit, orange, unsweetened tangerines), berries (fresh and frozen), pineapple, cabbage (white cabbage, cauliflower, Brussels sprouts, etc.), cucumbers, pumpkin, tomatoes, zucchini, eggplant (all strictly non-fried), green beans and green peas, herbs (lettuce, parsley, celery, dill), baked or boiled potatoes. Exclude: bananas, pears, grapes, dates, dried fruits, nuts and seeds, chips, fried and French fries.

• Do not get carried away with sweet yogurts and curd desserts: most of them contain a lot of sugar and starch. Forget about glazed curd bars and curd mass. Allowed: cottage cheese up to 5% fat, natural yogurt, kefir, fermented baked milk, sour milk.

• Try to eat fish or meat dishes regularly. Dietary meat varieties include chicken, veal, turkey, and beef. Avoid: sausages, frankfurters, small sausages, canned fish in oil, smoked fish.

• Limit your intake of sweets to 1 serving per day. Try to replace candies with fruits and berries. Preferred (rarely, in small amounts): marmalade, pastille, marshmallow — instead of chocolate and halva, sorbet — instead of ice cream.

Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools

Information is not available.