|
| A) | 85th percentile for age and sex | ||
| B) | 90th percentile for age and sex | ||
| C) | 95th percentile for age and sex | ||
| D) | 97th percentile for age and sex |
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].
| A) | Class 1 obesity | ||
| B) | Healthy weight | ||
| C) | Severe obesity | ||
| D) | Overweight |
PEDIATRIC WEIGHT STATUS CLASSIFICATION
| Category | Definition (as BMI Percentile for Age and Sex) |
|---|---|
| Underweight | BMI <5th percentile |
| Healthy weight | BMI 5th to 84th percentile |
| Overweight | BMI 85th to 94th percentile |
| Obesity | BMI ≥95th percentile or BMI ≥30 kg/m2 (class 1 obesity) |
| Severe obesity | BMI ≥120% of the 95th percentile or BMI ≥35 kg/m2 (class ≥2 obesity) |
| A) | Both decreased modestly, consistent with the adult trend | ||
| B) | Obesity stabilized while severe obesity increased sharply | ||
| C) | Both increased, while adult obesity prevalence declined | ||
| D) | Both remained unchanged during the COVID-19 pandemic |
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].
| A) | Non-Hispanic White | ||
| B) | Non-Hispanic Asian | ||
| C) | Non-Hispanic Black | ||
| D) | Hispanic |
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].
| A) | 10% to 30% | ||
| B) | 20% to 45% | ||
| C) | 50% to 90% | ||
| D) | 60% to 100% |
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) | 2 to 3 times higher | ||
| B) | 5 to 8 times higher | ||
| C) | Up to 15 times higher | ||
| D) | Up to 30 times higher |
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].
| A) | Obese children consume significantly more calories than their normal-weight peers | ||
| B) | BMI levels increased between 1988 and 2006 even when holding caloric intake and physical activity constant | ||
| C) | Physical activity levels declined in parallel with rising obesity rates since the 1980s | ||
| D) | Genetic factors have changed substantially since the 1980s, explaining rising rates |
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].
| A) | directly increasing caloric intake through appetite stimulation via the gut. | ||
| B) | altering adipose tissue, liver, pancreas, GI tract, and brain development, shifting the metabolic set point. | ||
| C) | reducing total energy expenditure through disruption of thyroid function only. | ||
| D) | increasing sedentary behavior via effects on the central nervous system. |
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]:
Exposure to obesogens can alter adipose tissue, liver, pancreas, GI tract, and brain development and function, changing the set point for control of metabolism.
Obesogens can determine how much food is needed to maintain homeostasis, increasing susceptibility to obesity.
Obesogens can act via epigenetic mechanisms, early development exposure is the most sensitive time to impact weight gain.
| A) | Insulin deficiency and low birth weight without metabolic risk | ||
| B) | Hyperinsulinemia and insulin resistance | ||
| C) | Elevated GLP-1 with accelerated linear growth | ||
| D) | Low cortisol with impaired glucocorticoid receptor signaling |
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].
| A) | Lower birth weight and reduced risk for metabolic syndrome | ||
| B) | Normal adiposity with increased risk for autoimmune disease | ||
| C) | Greater offspring body fat, higher childhood BMI, and increased cardiometabolic risk | ||
| D) | Delayed puberty with reduced risk of type 2 diabetes |
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].
| A) | MC4R | ||
| B) | POMC | ||
| C) | LEP | ||
| D) | PCSK1 |
CLINICAL CHARACTERISTICS OF MONOGENIC AND SYNDROMIC OBESITIES
| Disease | Abnormalities | ||
|---|---|---|---|
| Growth | Endocrine | Other Clinical | |
| Monogenetic Obesity | |||
| Leptin deficiency | Absence of pubertal growth spurt | Hypogonadotropic hypogonadism, hypothyroidism | Frequent infections due to altered immune function |
| Leptin receptor deficiency | |||
| MC4R deficiency | Increased lean mass and accelerated linear growth | Hyperinsulinemia | Hypotension |
| POMC deficiency | Accelerated childhood growth | ACTH deficiency, hypothyroidism | Red/orange hair, fair skin in non-Hispanic White patients |
| PCSK1 variation | Failure to thrive in early infancy | ACTH deficiency, hypothyroidism, hypoglycemia | Intractable recurrent diarrhea |
| SRC1 deficiency | Not reported | Impaired leptin-induced POMC, low testosterone and gonadotropin levels, PMOS | Fractures from minor incidents, liver fibrosis, diabetes/insulin resistance |
| Syndromic Obesity | |||
| Albright hereditary osteodystrophy | Short stature | PHP, hyperparathyroid levels | Hypocalcemia, subcutaneous ossifications, other skeletal and developmental anomalies |
| Alström syndrome | Short stature | Insulin resistance, type 2 diabetes, hypothyroidism, hypogonadism, hyperandrogenism (females) | Hearing loss, vision impairment, renal failure, hepatic dysfunction, cardiomyopathy |
| Bardet-Biedl syndrome | Rapid weight gain in early childhood through adolescence | Hypogonadism | Visual impairment, cognitive disabilities, polydactyly, liver dysfunction, renal failure |
| Prader-Willi syndrome | Poor feeding, failure to thrive, hypotonia in infancy | Hypogonadism | Dysmorphia, intellectual disability, behavioral disorders |
| SIM1 deficiency | Neonatal hypotonia and feeding difficulty | Hypogonadism | Developmental delay, facial dysmorphism |
| SH2B1 deficiency | Reduced height | Insulin resistance | Delayed speech and language development |
| 16p11.2 deletion | Not reported | Hyperinsulinemia | Developmental delay; intellectual, communication and socialization disability |
| ACTH = adrenocorticotropic hormone; MC4R = melanocortin-4 receptor; PMOS = polyendocrine metabolic ovarian syndrome; PCSK1 = prohormone convertase subtilisin/kexin 1; PHP = pseudohypoparathyroidism; POMC = proopiomelanocortin; SH2B1 = SRC-homology-2B adaptor protein 1; SIM1 = single-minded homolog 1; SRC1 = steroid receptor coactivator 1. | |||
| A) | Prader-Willi syndrome | ||
| B) | Alström syndrome | ||
| C) | Bardet-Biedl syndrome | ||
| D) | SIM1 deficiency |
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].
| A) | Binge eating episodes followed by feelings of guilt and purging | ||
| B) | Preference for high-fat foods without overall increase in caloric intake | ||
| C) | Prolonged time to satiation, brief satiety, food preoccupation, and distress when food is denied | ||
| D) | Nighttime eating with normal daytime appetite and standard meal sizes |
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].
| A) | Released by adipocytes post-prandially to signal satiation | ||
| B) | Acts on POMC neurons to suppress food intake after meals | ||
| C) | Is the only orexigenic gut hormone, activating NPY neurons to increase food intake | ||
| D) | Stimulates insulin secretion from pancreaticβ-cells in response to elevated glucose |
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].
| A) | approximately equal to the general pediatric population. | ||
| B) | slightly elevated, affecting fewer than 5% of children with class 1 obesity. | ||
| C) | greater than 10% in school children with obesity, compared with 0.0.8% to 3.2% in normal-weight peers. | ||
| D) | predominantly a complication of severe obesity only, with no significant association with class 1 obesity. |
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].
| A) | it is exclusively insulin-dependent and does not respond to oral medications. | ||
| B) | β-cell function declines at nearly double the annual rate seen in adult type 2 diabetes. | ||
| C) | youth with type 2 diabetes have lower rates of associated comorbidities than adults. | ||
| D) | it is primarily caused by immune-mediated destruction of β-cell rather than insulin resistance. |
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].
| A) | Hypertension, dyslipidemia, insulin resistance, and obesity | ||
| B) | Hypotension, hyperglycemia, elevated HDL-C, and low triglycerides | ||
| C) | Hyperglycemia, low LDL-C, elevated GLP-1, and increased adiponectin | ||
| D) | Obesity, low testosterone, elevated leptin, and adrenal insufficiency |
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].
| A) | NAFLD is primarily a disease of adolescence and rarely affects children younger than age 9. | ||
| B) | NAFLD is less aggressive in children than adults and rarely progresses to NASH. | ||
| C) | Nearly 25% of children with NAFLD have NASH, and 7% to 10% may develop cirrhosis. | ||
| D) | NAFLD prevalence is equal between boys and girls across all obesity classes. |
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].
| A) | Fasting insulin level | ||
| B) | Lateral neck x-ray | ||
| C) | Overnight polysomnography | ||
| D) | Pulmonary function testing |
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].
| A) | Improved peer relationships secondary to increased social engagement around food | ||
| B) | Higher rates of depression, poor self-esteem, alienation, and disordered eating, with greater impact in teenage females | ||
| C) | Equivalent psychological impact across all age groups and both sexes | ||
| D) | Psychosocial effects that uniformly resolve once obesity is treated |
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) | Class 1 obesity | ||
| B) | Class 2 obesity | ||
| C) | Class 3 obesity | ||
| D) | Overweight with metabolic risk |
PEDIATRIC OBESITY SEVERITY CLASSIFICATION
| Category | Definition (as BMI Percentile for Age and Sex) |
|---|---|
| Class 1 obesity | BMI 95th percentile to 119% of the 95th percentile (%BMIp95 1.0–1.19 times the 95th percentile) |
| Class 2 obesity | BMI 120–139% of the 95th percentile or BMI 35–39.9 kg/m2 (whichever is lower) (%BMIp95: 1.2–1.39 times the 95th percentile) |
| Class 3 obesity | BMI >140% of the 95th percentile or BMI ≥40 kg/m2 (whichever is lower) (%BMIp95 ≥1.4 times the 95th percentile) |
| A) | Obesity onset at age 12, normal parents' weight, and BMI at the 96th percentile | ||
| B) | Severe obesity onset before age 5, hyperphagia, and normal-weight biological parents | ||
| C) | Moderate obesity with hypertension and dyslipidemia in a 15-year-old | ||
| D) | Overweight with ADHD and binge eating in a 10-year-old female |
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.
| A) | Hypothyroidism | ||
| B) | Cushing syndrome | ||
| C) | Insulin resistance | ||
| D) | POMC deficiency |
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.
| A) | A mean BMI reduction of 5 kg/m2, representing a major clinical benefit | ||
| B) | Statistically and clinically significant BMI reductions of 3 to 4 units compared to control | ||
| C) | Statistically significant but clinically negligible BMI reductions compared to usual care | ||
| D) | No difference in BMI compared to usual care across all study durations |
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].
| A) | Any child with class 1 obesity who has failed 6 months of lifestyle modification therapy | ||
| B) | Patients age 13 or older with class 2 or greater obesity | ||
| C) | Patients age 16 or older with class 3 obesity only | ||
| D) | Adolescents of any age with type 2 diabetes regardless of BMI classification |
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].
| A) | Class 2 or 3 polygenic obesity unresponsive to lifestyle modification therapy | ||
| B) | Any genetic obesity diagnosed by clinical presentation regardless of genotype | ||
| C) | Prader-Willi syndrome and hypothalamic obesity unresponsive to GLP-1 receptor agonists | ||
| D) | Monogenic obesity due to POMC, PCSK1, or LEPR deficiency, or Bardet-Biedl syndrome |
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].
| A) | Blocking dietary fat absorption in the GI tract and increasing fecal fat excretion | ||
| B) | Inhibiting norepinephrine reuptake in the hypothalamus and stimulating dopamine release | ||
| C) | Reducing appetite via hypothalamic GLP-1 receptors, delaying gastric emptying, and decreasing reward-driven eating | ||
| D) | Directly inhibiting leptin resistance in the arcuate nucleus by blocking pro-inflammatory cytokines |
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].
| A) | Mean BMI change of -5.2% vs -0.6%, a treatment effect of -4.6% | ||
| B) | Mean BMI change of -16.1% vs +0.6%, a treatment effect of -16.7% | ||
| C) | Mean BMI change of -8.4% vs +1.3%, a treatment effect of -9.7% | ||
| D) | Equivalent BMI reductions to liraglutide with fewer gastrointestinal adverse effects |
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%.
| A) | Age 10 years of age or older; contraindicated in patients with ADHD | ||
| B) | Age 12 years of age or older; contraindicated in patients with pregnancy risk or use of unreliable contraception | ||
| C) | Age 16 years of age or older; contraindicated in patients with a history of seizures | ||
| D) | Age 18 years of age or older; contraindicated in patients with controlled hypertension |
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].
| A) | ADHD stimulant therapy is contraindicated in obesity due to cardiovascular risks | ||
| B) | ADHD treatment is a lower priority and should be deferred until weight loss is achieved | ||
| C) | ADHD, obesity, and binge eating disorder share pathophysiology involving impaired dopaminergic activity and executive function; stimulant treatment reduces obesogenic behaviors and BMI | ||
| D) | Treating ADHD improves school performance but has no demonstrated effect on weight or eating behaviors |
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].