Body mass index (BMI) is a surrogate marker of adiposity calculated as weight (kg)/height² (m²). Pediatric weight classification is BMI-based (Table 1). Obesity is defined as BMI at or above the 95th percentile, or ≥2 standard deviations above the median relative to children and teens of the same age and biological sex [1,29].

The COVID-19 pandemic was associated with increases in obesity, but this may have been limited to children. Between 2017–2018 and 2021–2023, adult obesity prevalence dropped 2.5% and severe obesity stabilized, but pediatric obesity increased 8.5% and severe obesity increased 12.8% [36].

In 2017–2020, obesity (19.7% overall) affected 14.7 million youth, increased with age among 2- to 5-year-olds (12.7%), 6- to 11-year-olds (20.7%), and 12- to 19-year-olds (22.2%), and was higher among Hispanic (26.2%) and non-Hispanic Black (24.8%) Americans than non-Hispanic White (16.6%) and non-Hispanic Asian (9.0%) Americans [37].

Shared genetics and family environment both contribute to heritability. The genetic heritability of BMI and adiposity has been separately estimated by twin studies (50% to 90%), nuclear families (30% to 50%), and adoption studies (10% to 35%). In a population with the entire range of BMI, the genetic component accounts for 40% to 50% of variability in BMI and adiposity overall and is higher in obese and severely obese (60% to 80%) than normal-weight (~30%) persons [38].

A child's risk of obesity is 2- to 3-fold higher with obesity in one biological parent and up to 15-fold with obesity in both parents, suggesting involvement of intergenerational transmission [29,39]. Assortative mating, or sexual selection based on phenotypic similarity (e.g., fatness) may increase the concentration of obesity alleles among people in the upper range of BMI distribution over time. Spouse concordance for obesity confers a 20-fold higher risk for obesity in adult offspring vs those of normal-weight parents [38].

In the dominant EBM, energy imbalance resulting in obesity is caused by overeating and insufficient exercise; we gain weight because we eat more calories than we burn [8]. If the uptake in calorie-dense food is greater than the energy expenditure, it is expected that the accumulation of fat will increase in direct proportion to this imbalance [42].

The EBM paradigm of the obesity epidemic has become conventional wisdom, but different lines of evidence challenge its validity, and EBM cannot explain or address the following.

Between 1999–2000 and 2017–2018 as adult obesity increased 28% and severe obesity increased 92%, caloric intake decreased, activity energy expenditure increased, and adults showed clear evidence of dietary improvement with increased healthy fats and plant sources of protein, and decreased sugar intake [8,43].

Between 1988 and 2006, despite weekly physical activity increasing 47% in men and 120% in women, BMI was up to 2.3 kg/m² higher in 2006 than in 1988 for an equivalent amount of energy intake or physical activity; in other words, BMI increased even when holding carbohydrate and fat intake and physical activity constant [44].

Obesogens alter energy metabolism by disrupting signaling pathways that regulate energy intake and expenditure, nutrient handling, and adipose biology. Obesogens can be naturally occurring (e.g., heavy metals, viruses), anthropogenic (e.g., plastics, household chemicals, personal care products, insecticides, prescription drugs), or food components (e.g., non-nutritive sweeteners, fructose, trans-fats, preservatives), any of which can increase adiposity via endocrine or nonendocrine mechanisms. Exposures can occur via food, air, water, and placental transmission [49].

As endocrine-disrupting chemicals, obesogens fundamentally contribute to the obesity epidemic by shifting energy balance to promote adipose accumulation and metabolic disease. This evidence led to the obesogen hypothesis, which states [50]:

Small for gestational age newborns are typically hyperinsulinemic and insulin resistant at birth, exhibit rapid catch-up growth in infancy, and develop obesity in childhood with persistent insulin resistance and later development of metabolic syndrome [9]. Early rapid weight gain confers a nearly 4-fold greater risk for developing overweight or obesity from childhood to adulthood [40].

Maternal metabolic factors before and during pregnancy adversely affect offspring growth or adiposity in utero and after birth, increasing risk for cardiometabolic disease into adulthood. Maternal obesity and diabetes are associated with high birth weight and higher BMI during childhood, and excess adipose tissue accumulation [40].

Up to 13% of children referred to tertiary centers for suspected underlying medical causes of obesity show monogenic obesity. The prevalence of genetic obesities is underestimated because diagnosis requires genotyping and analysis of genetic variants; Bardet-Biedl syndrome is the exception [41].

Hyperphagia, a core feature of genetic obesities, is an extreme unsatisfiable drive to eat, with food-seeking behaviors such as eating quickly, negotiating for more food, and sneaking, stealing, or hiding food. Hyperphagia may be extreme and constant, manifesting as prolonged time to satiation, brief duration of satiety, protracted hunger, preoccupation with food, distress if denied food, and/or eating more than optimal quantities of food. Intolerance of food restriction and conflicts over food limits can cause substantial negative consequences for patients and caregivers [7,58].

The incretin hormones GLP-1 and GIP stimulate insulin secretion to regulate glucose homeostasis. GLP-1 also acts centrally to reduce appetite by activating satiety pathways, and in the stomach to delay gastric emptying [7]. Ghrelin, the only orexigenic gut hormone, signals the need for increased food intake [60].

Hypertension prevalence is more than 10% in school children with obesity, compared with 0.8% to 3.2% among normal-weight peers; severe obesity confers a four-fold greater risk of hypertension [14]. Hypertension is strongly associated with high BMI and is also linked to hyperinsulinemia [88].

Hyperinsulinemia and glucose dysregulation are key features of pediatric obesity. Type 2 diabetes is preceded by a progressive decline in β-cell function and an increase in insulin resistance. When the insulin release can no longer compensate for the insulin resistance, type 2 diabetes occurs [81].

Type 2 diabetes is a significant comorbidity of childhood obesity and an aggressive disease in children. The ≥20% decline in β-cell function per annum, nearly double the rate in adult type 2 diabetes, can progress, sometimes rapidly, to diabetic complications of NAFLD, dyslipidemia, PMOS, and nephropathy [90]. Pediatric type 2 diabetes is also highly treatment-resistant; the odds of disease progression despite intervention are more than 50% [15].

Metabolic syndrome, an adverse metabolic phenotype with hypertension, dyslipidemia, insulin resistance, and obesity, is directly linked to target organ damage, cardiovascular disease (CVD), and all-cause mortality in adults. Metabolic syndrome is increasingly common in children with obesity, with the same core elements as in adults [91]. The pathogenesis involves interactions between obesity, insulin resistance, and inflammation, along with hyperinsulinemia and oxidative stress [14,88].

Among children with NASH, 83% have a BMI ≥97th percentile. Nearly 25% of children with NAFLD have NASH, and 7% to 10% may develop cirrhosis and end-stage liver disease [14,94]. The disease course in childhood is more severe than in adults, and pediatric NAFLD imposes a long-term cardiometabolic burden with increased morbidity and mortality in early adulthood [92]. Hepatocellular carcinoma and cardiovascular complications are life-threatening comorbidities of both NAFLD and NASH [95].

Obstructive sleep apnea is deeply intertwined with obesity and hypertension. Obesity is the primary driver of adolescent obstructive sleep apnea and hypertension. Obstructive sleep apnea impairs sleep, thus increasing food consumption and weight gain. Increased obstructive sleep apnea severity is also associated with more frequent and severe hypertension [99]. Neurocognitive deficits and excessive daytime sleepiness are common in obese children with obstructive sleep apnea. Obstructive sleep apnea is diagnosed with polysomnography [89]. Obesity hypoventilation syndrome may represent a long-term consequence of obstructive sleep apnea and is associated with a high mortality rate. Aggressive therapy is warranted for obese children with this syndrome [88].

Psychosocial consequences of childhood obesity are common and include alienation, distorted peer relationships, poor self-esteem, distorted body image, anxiety, depression, and disordered eating patterns. The risk of psychosocial morbidity increases with age and is greater among teenage females than males [89]. It remains unclear whether psychological morbidities are the cause or consequence of obesity, whether both originate from common susceptibility factors that promote weight gain and psychological disturbances, and/or are further aggravated by obesity-related stigmatization and bullying. Nonetheless, regular screening with early intervention is essential [100].

A comprehensive evaluation of a child or adolescent with obesity should begin with a detailed medical history, including relevant prenatal, birth, growth, developmental, medical, psychosocial, and medication histories [100,103]. The birth history should assess for maternal diabetes and whether the patient was large or small for gestational age. Growth history is also important, particularly early-onset obesity occurring before 5 years of age with hyperphagia, which may suggest monogenic obesity, and a history of failure to thrive during infancy, which may be associated with Prader-Willi syndrome. The history should also identify previous CNS injury or hypothalamic tumors that may contribute to weight gain or obesity.

The musculoskeletal examination should evaluate for bowed legs, which may be associated with Blount disease, and for a limp, which may indicate slipped capital femoral epiphysis. Skin findings may include acanthosis nigricans, a marker of insulin resistance, and hirsutism, severe acne, or both, which may suggest PMOS. Finally, overall mood and affect should be evaluated. A flat affect, chronic fatigue, and sleep problems may be associated with depression.

Furthermore, despite the extensive investment in time and resources, any weight improvement is usually short-lived, and intensive lifestyle modification therapy seldom provides clinically significant and durable weight loss [28,54,106,107]. A Cochrane review evaluated 70 randomized controlled trials of lifestyle modification therapy in children 6 to 11 years of age with obesity. At longest follow-up, the mean difference between lifestyle modification therapy vs usual care or no treatment was -0.06 units in BMI z score, -0.53 kg/m² in BMI, and -1.45 kg in weight; all three mean differences were statistically significant but clinically negligible [109].

In 2023, the AAP published their first clinical practice guideline on the evaluation and treatment of pediatric obesity. Patients 13 years of age or older with severe obesity should be referred to multidisciplinary pediatric bariatric surgery centers for metabolic and bariatric surgery evaluation. However, the AAP also states that age should not be the sole determinant of eligibility for metabolic and bariatric surgery [11].

Setmelanotide is approved for chronic weight management in all patients 6 years of age or older with monogenic obesity or syndromic obesity due to POMC, PCSK1, or LEPR deficiency; or Bardet-Biedl syndrome [134].

Endogenous glucagon-like peptide 1 (GLP-1) is an incretin hormone with multifactorial direct and indirect effects on energy and glucose metabolism. GLP-1 promotes insulin secretion from pancreatic β-cells and reduces glucagon secretion from pancreatic β-cells, improving insulin sensitivity and suppressing hepatic glucose production. GLP-1 also inhibits postprandial gastric emptying and duodenal peristalsis, thereby reducing appetite and food intake [142].

The landmark STEP Teens trial randomized 201 adolescents 12 to 17 years of age (mean BMI: 37 kg/m²) to semaglutide or placebo for 68 weeks [130]. Semaglutide (vs placebo) led to superior change in BMI (-16.1% vs +0.6%), weight (-16.3% vs +2.6%), and subjects with weight loss ≥10% (62% vs 8%), ≥15% (53% vs 5%), and ≥20% (37% vs 3%). The primary endpoint, BMI change, showed a treatment effect of -16.7%.

Phentermine/topiramate extended release (ER) is an anti-obesity medication approved as Qsymia. These agents remain important off-label considerations. Phentermine was approved in 1959 as short-term (≤12 weeks) obesity treatment in patients older than 16 years of age before obesity was understood as a chronic disease requiring long-term treatment. Phentermine has been among the most widely prescribed anti-obesity medication in adults for decades. Its efficacy, minimal side effects, and low-cost accessibility have also made phentermine the most widely prescribed anti-obesity medication (off-label) in patients 16 years of age or younger or longer than 12 weeks [19,164].

ADHD, BED, and loss-of-control eating disorder (LOC-ED) are prevalent in pediatric obesity [5]. ADHD is characterized by persistent, functionally damaging levels of hyperactivity, inattention, distractibility, and impulsivity [1,188]. ADHD in children increases obesity prevalence by 40% to more than 100% [189,190,191]. The 29% prevalence of ADHD in teen candidates for metabolic and bariatric surgery is six-fold greater than the general population [193]. Children with ADHD demonstrate significantly lower birth weight and are significantly more likely to have obesity at 5 years of age onward [190].