Obesity in Pediatric Patients

Etiology

The etiology of obesity is multifactorial. Obesity originates from a complex interplay between genetic, biological, environmental, socioeconomic, and cultural factors. Genetics and biology are predetermined, but the remaining factors can be modified. These include the family's eating, sleeping, and exercise behaviors, access to healthy food at school and in the community, the availability of safe places for physical activity, and adverse childhood experiences. When energy intake in calories exceeds energy expenditure, weight gain results, eventually leading to obesity.[3] Genetic determinants play a lesser role. Food preferences have shifted in recent decades due to marketing and the availability of high-calorie processed foods like fast food and sugar-sweetened beverages. The consumption of these energy-dense foods, as well as super-sized portions and snacking, has been correlated with a drastic increase in obesity in industrialized nations.[4] 

Decreased physical activity and more screen time (smartphones, computers, televisions, and video games) contribute to the problem.[5] Studies show that obesity rates rose during the COVID-19 pandemic when schools were closed, and screen and sedentary time replaced active play and physical activities.[6] Feeding patterns are culturally driven, and children model their parents and families from a very young age. Studies demonstrate a positive influence of higher parental education and structured family meals on healthy food choices by children. Families eating together, exposing children to various nutritious food choices, and avoiding watching television during meals create a positive food environment that decreases the chance of developing obesity.[7] The amount of time spent by a child watching television and playing video games has been correlated with increased distracted eating and obesity.[8]

Other critical risk factors have been identified that may predispose to obesity. Perinatal and postnatal conditions that increase risk include elevated maternal BMI in pregnancy, large for gestational age birth weight, rapid weight gain in infancy and early childhood, and breastfeeding (protective) versus formula feeding. Environmental chemicals, microbiota, the early use of antibiotics, and adverse life experiences are also considered potential risk factors.[9][10][11]

Polygenic obesity and monogenic obesity are both uncommon but merit consideration. The former results from the interaction of several polygenic variants with environmental factors that increase the likelihood of obesity. Further genetic and molecular studies are needed to determine the clinical significance of these genetic variations. Monogenic obesity is severe with an early onset, usually due to an autosomal recessive mutation in the leptin-melanocortin pathway. MC4R (Melanocortin 4 receptor) and proopiomelanocortin deficiencies increase food-seeking behaviors in children. Leptin and leptin receptor deficiencies result in early-onset extreme obesity.[12] Genetic syndromes such as Prader Willi, Bardet-Beidl, Beckwith-Wiedmann, and Albright hereditary osteodystrophy are also associated with obesity.[13] Secondary etiologies of obesity include endocrine, neurologic, psychologic, and drug-induced causes, which should be considered when obesity onset is sudden or unexpected. The mechanism is thought to result from hormonal imbalances affecting satiety and food-seeking behaviors.

Epidemiology

Between 1963-1965 and 1999-2000, the prevalence of obesity among children aged 6 to 11 increased significantly from 4.2% to 15.3%.[14] Data from the National Health and Nutrition Examination Survey in 2015-2016 show the trend has continued. According to this survey, the prevalence of obesity in the United States for children and teens is 18.5%. The rate is even higher for adolescents, at 20.6% for 12 to 19-year-olds. Approximately 13.5 million American adolescents struggle with obesity.[2] Disparities exist across racial and ethnic groups, with non-Hispanic Black and Mexican American children having higher rates of obesity than non-Hispanic White children. Parental educational level and income, access to healthy food options, and availability of safe physical activity opportunities contribute to disparities in obesity prevalence. In addition, children with disabilities such as autism and intellectual disabilities are at higher risk for developing obesity. [American Academy of Pediatrics Clinical Practice Guidelines for Obesity 2023]

Pathophysiology

Appetite and satiety are controlled through neuroendocrine feedback mechanisms.

• Gastrointestinal hormones like ghrelin stimulate appetite, whereas GLP-1 (glucagon-like peptide-1), Peptide YY, CCK (cholecystokinin), and vagal neural feedback inhibit appetite and promote satiety.[15]
• Adipose tissue provides feedback on energy stores by adiponectin and leptin via satiety signals.
• These hormones provide feedback to the arcuate nucleus in the hypothalamus, which sends behavioral and autonomic outputs to the solitary tract nucleus in the brainstem, leading to gastrointestinal hormonal secretion.
• Neuropeptides in the brain, including peptide yy (PYY), agouti-related peptide (AgRP), and orexin, stimulate appetite, whereas melanocortin and alpha-melanocyte-stimulating hormones promote satiety.[16][17] A genetic deficiency of MCR4 has been associated with increased food-seeking behavior.[18]
• Lack of sleep has been shown to decrease circulating leptin levels and increase ghrelin levels, as well as self-reported hunger. Ghrelin is the "hunger hormone" that activates PYY and AgRP to stimulate appetite. 
• Neuroendocrine interaction between the gut, adipose tissue, and brain maintains the balance between appetite stimulation and adiposity. Mutations in genes involved in secreting these hormones have been of interest in epigenetic modifications and are potential therapeutic targets.

History and Physical

Evaluation of patients with obesity begins with a complete medical history and a careful physical examination to search for the etiology and the presence of comorbid conditions. This usually occurs during a well-child visit in the medical home but may also occur at problem-focused appointments. [American Academy of Pediatrics Clinical Practice Guidelines for Obesity 2023] The clinician should first inquire if the family or patient has concerns about the child's growth or weight. Next, history-taking begins with reviewing prenatal factors such as maternal weight gain during pregnancy or gestational diabetes that might increase the likelihood of obesity. Birth/perinatal history-taking includes inquiring about intrauterine growth retardation with rapid catch-up growth or a baby large for gestational age.

A non-judgmental approach should be used to probe the details of the child's nutritional intake and energy expenditure. Reviewing the family feeding patterns, meal composition, snacking, and screen time can aid in revealing the cause of excessive weight gain. A 24-hour diet recall listing the servings of fruits, vegetables, and high-carbohydrate and high-calorie foods in meals, snacks, and beverages can also provide valuable information. Noting the duration and type of physical activity helps assess energy expenditure.

A review of the height and weight growth charts for abrupt changes in the weight, height, and BMI trajectory may suggest an etiology. Extreme appetite and food-seeking behaviors are seen in some genetic conditions. The family history identifies others with obesity and obesity-related comorbid conditions. Genetic susceptibility may be present, especially if there are family members with severe obesity resulting in bariatric surgery or obesity affecting multiple generations. Diabetes, hypertension, or cardiovascular disease in a family member increases the risk of a child developing similar conditions. Parental obesity is another risk factor, likely related to the interplay of genetics, shared environment, and social determinants of health. Clinicians should help the family understand that childhood obesity increases the likelihood of progression to several chronic diseases. 

History may provide a vital clue to less common, secondary causes of obesity. Significant head trauma preceding the onset of sudden weight gain suggests a hypothalamic cause. Easy bruising, muscle weakness, fatigue, and central obesity may indicate Cushing syndrome. Cold intolerance, dry skin, and swelling of the anterior neck point to hypothyroidism. However, fewer than 1% of children with obesity are diagnosed with an endocrine cause, despite many families' belief that weight gain is due to a hormone imbalance. Reviewing medications associated with obesity, including steroids, antipsychotics (risperidone), and antiepileptics (valproate), helps evaluate drug-induced obesity.[19] 

History suggestive of comorbidities includes polyuria and polydipsia (diabetes mellitus), headache and vision changes (pseudotumor cerebri), painful limp and hip/knee pain (Blount disease and slipped capital femoral epiphysis), abdominal pain, vomiting, and jaundice (gallbladder disease, non-alcoholic fatty liver disease), anxiety and depression, worsening school performance, bullying or being bullied (behavioral or psychological problems), shortness of breath, snoring and daytime sleepiness or fatigue (asthma and obstructive sleep apnea), irregular menses, hirsutism, and acne (polycystic ovary syndrome/PCOS). Assessing behavioral and emotional concerns with validated screening tools such as the Patient Health Questionnaire-9 (PHQ-9) can aid in diagnosing psychological comorbidities. 

Physical examination begins with measuring height, weight, and blood pressure and calculating the BMI (weight (kg)/ height (m)²). Blood pressure should be measured with an appropriately sized cuff for accuracy, followed by a head-to-toe examination to identify potential causes and complications of obesity, including:

• Facial and body dysmorphism, suggestive of genetic disorders. Examples include almond-shaped eyes, hypogonadism, small hands and feet (Prader Willi syndrome), hypotonia, upward slanting eyes, short neck, transverse palmar creases (Down syndrome), round face, central obesity, excess fatty tissue of upper back between the shoulders (Cushing syndrome). 
• Cognitive impairment may indicate a genetic syndrome.
• Short stature is associated with hormone deficiencies and Albright hereditary osteodystrophy.
• Eye findings such as papilledema (pseudotumor cerebri), retinal degeneration, and nystagmus (Bardet-Biedl syndrome) should be followed up by a specialist. 
• Skin changes such as acanthosis nigricans (thick, darkened skin on the nape of the neck), acne, and hirsutism may indicate insulin resistance or PCOS. 
• Sexual maturity rating may reveal premature adrenarche in obese girls.
• The clinician should look for dyspnea and wheezing (asthma), abdominal tenderness or hepatomegaly (non-alcoholic fatty liver disease), and hip and knee mobility restriction (slipped capital femoral epiphysis and Blount disease, respectively).[1] 

Evaluation

The primary care clinician usually diagnoses obesity during health maintenance visits. The growth chart reveals the onset and severity of obesity and also provides clues about the etiology. The BMI trajectory helps identify a gradual increase during sensitive growth periods (infancy, childhood, and adolescence) versus an abrupt acceleration. Sudden changes in the BMI may indicate personal and family stress or medical problems related to tumors, trauma, hypothyroidism, or medications. Comparing the weight and height trajectories can be very useful. A young child taking in excess calories shows a linear increase in weight and height. In contrast, a disproportionate increase in weight only may indicate a sedentary lifestyle with low physical activity. A deceleration in linear growth over time implies endocrine problems such as hypothyroidism. 

Laboratory investigation focuses on the early detection of comorbidities. The risk increases with a child's age and with severe obesity. The prevalence of comorbidities varies by race and ethnicity. Black and Hispanic youth have a higher prevalence of pre-diabetes and type 2 diabetes mellitus (T2DM). Rates of non-alcoholic fatty liver disease (NAFLD) are higher in Hispanic children. These statistics are likely related to socioeconomic and environmental, not genetic factors. For children with obesity, evaluation for the presence of lipid abnormalities, pre-diabetes, diabetes, and hepatic dysfunction should begin at age 10. This includes a fasting lipid panel, fasting glucose, alanine transaminase, and aspartate transaminase every 2 years. If the fasting glucose is elevated, hemoglobin A1C (HbA1C) or a 2-hour plasma glucose level following an oral glucose tolerance test can be measured. For children aged 2 to 9 years, evaluation for lipid abnormalities is not required but may be performed, especially if there is a positive family history. In this age group, the risk of pre-diabetes, T2DM, and NAFLD is lower, so testing is not universally recommended. However, screening for glucose abnormalities or liver dysfunction is appropriate when there are physical examination findings such as acanthosis nigricans or a positive family history of diabetes.[American Academy of Pediatrics Clinical Practice Guidelines for Obesity 2023] 

When PCOS is suspected, testing for levels of luteinizing hormone, follicle-stimulating hormone, and testosterone should be performed. A thyroid hormone assessment is indicated for concerns about thyroid function and serum cortisol levels to diagnose Cushing syndrome. The following laboratory and imaging studies can be considered in unique circumstances. [American Academy of Pediatrics Clinical Practice Guidelines for Obesity 2023]

• Imaging: radiographs of hip and knee joints (slipped capital femoral epiphysis and Blount disease), ultrasound of abdomen and pelvis (PCOS), Computed tomography/magnetic resonance imaging of the brain (hypothalamic tumors)
• Polysomnography tests for obstructive sleep apnea and pulmonary function tests for asthma.
• Invasive procedures such as lumbar puncture to obtain CSF opening pressure for diagnosis of pseudotumor cerebri. 

Treatment / Management

Evidence supports treating obesity and comorbidities to achieve weight loss, prevent further weight gain, and improve complications of obesity. Guidelines do not recommend "watchful waiting." Clinicians must document the presence of obesity and carefully explain to caregivers the importance of treating obesity while avoiding stigmatizing the child. Asking permission to discuss the BMI and weight is helpful. Avoiding labels such as "obese child" and using words that are perceived as neutral, such as "unhealthy weight" or "gaining too much weight for age or height," are helpful. The focus should be on the child's health. [American Academy of Pediatrics Clinical Practice Guidelines for Obesity 2023]

Behavioral change forms the cornerstone in the management of pediatric obesity. Family-based interventions are aimed at decreasing BMI. These include limiting the number of sweetened beverages and fast food servings, eating more fruits and vegetables, and increasing the time spent being physically active. Clinicians should make clear recommendations about healthy foods and appropriate portions and encourage an active lifestyle with daily exercise. Merely saying "eat less and exercise more" is too simplistic. Families are encouraged to plan their meals, considering children's preferences and the nutrient value of foods to ensure a balanced diet.[20] (A1)

Evidence does not support any 1 specific diet for weight loss. Approaches like the "traffic light diet plan" can help families make healthy changes according to their cultural beliefs and ethnicity.[21] Another recommendation is the "5-2-1-0" guideline of 5 daily servings of fruits and vegetables, no more than 2 hours of screen time, at least 1 hour of physical activity, and no sugar-sweetened beverages. Primary care clinicians can suggest behaviors such as removing unhealthy food from the home, keeping a food diary, rewarding positive behavior changes, and writing down eating and exercise goals. Clinicians must be aware if a family experiences food insecurity and difficulty obtaining enough food or if the community or neighborhood lacks access to safe play and exercise activities. 

Creating a healthy food environment at home includes incorporating nutritious food choices for meals and snacks and avoiding TV watching while eating. Children model the adults in the home, and positive family changes can prevent and treat obesity.[22][23] Motivational interviewing helps ascertain the family's understanding of the health problems associated with obesity and guides them to adopt strategies using their values and thoughts.[24] Including patients and their parents in goal-setting promotes sustainable and beneficial behavior changes. (B3)

The Physical Activity Guidelines for Americans recommend 60 minutes or more of moderate-to-vigorous exercise for children aged 6 to 17, and children aged 3 to 5 years should be physically active throughout the day.[25] Both aerobic and resistance exercises have shown a positive effect on the metabolic profile of children and a decreased risk of cardiovascular events.[26] Increasing physical activity can include walking to school, participating in sports, unstructured outdoor play, and exercising with family members in leisure time. Family physical activity impacts adopting a healthy, active lifestyle more than if only the child is encouraged to change.[27](A1)

The American Academy of Pediatrics recommends screen time of less than 1 hour per day for children aged 2 to 5 years and 2 hours per day for older children. The American Academy of Pediatrics recommends no screen time for children younger than 2 years, except for video chats with friends and family. Children with more screen time are less likely to be physically active. Primary care clinicians, with limited resources and time, often find it challenging to provide the intensive behavior and lifestyle treatment recommended for patients with obesity. A structured weight management plan often includes motivational interviewing and a referral to a registered dietitian or nutrition specialist. The next step is a comprehensive multidisciplinary intervention with increased intensity and frequency of the behavior change component. This usually consists of an interprofessional team that provides up to 22 sessions over 3-12 months. Finally, some patients may benefit from tertiary care intervention for nutrition and exercise advice, behavior counseling, pharmacologic therapy, and consideration of bariatric surgery. 

No evidence supports weight loss medication as therapy alone, but it is recommended as an adjunct when intensive behavior interventions alone have failed. Many drugs used in adults are not FDA-approved for children, and further studies are ongoing. 

• Orlistat is an FDA-approved drug for children aged 12 years and older with obesity. It is a pancreatic lipase inhibitor that promotes mild to moderate weight loss by blocking fat absorption. Adverse effects, including flatulence, fecal urgency, and steatorrhea, limit usefulness. The dose is 120 mg orally 3 times daily.[28] 
• Metformin is approved for children aged 10 years and older to treat T2DM. It has not been approved for weight loss, although studies show a mild to modest weight reduction. It is also used to treat PCOS. It causes decreased hepatic glucose production, decreased gut glucose absorption, and increased insulin sensitivity. The dose begins at 500 mg orally, daily or twice daily, and can be increased to a maximum of 2500 mg per day. 
• Glucagon-like peptide-1 receptor agonists (GLP1s) decrease hunger by slowing gastric emptying and affecting central nervous system targets. Liraglutide, injected daily, is FDA-approved for children aged 12 or older with obesity. Exenatide, injected weekly, is approved for children aged 10-17 to treat T2DM. Adverse effects include nausea and vomiting. 
• Melanocortin 4 receptor (MC4R) agonists, such as setmelanotide, are FDA-approved for children aged 6 and older with rare genetic conditions such as proopiomelanocortin and leptin deficiency. It is injected daily to decrease appetite. Adverse effects include nausea and injection site reactions.[29]
• Phentermine and topiramate extended-release capsules are approved for weight loss in adults. Recent data show significant weight loss in teens and improved lipid profiles. However, the medication is not currently FDA-approved for children. Topiramate suppresses appetite but can cause cognitive slowing and is a known teratogen, so it must be prescribed cautiously for older teens. 
• Lisdexamfetamine is a stimulant sometimes used "off-label" in adults with obesity. It is approved for binge eating disorder treatment in adults but only for ADHD in pediatric patients. It may be helpful when a teen requires treatment for combined ADHD and obesity. 
(B3)

Weight loss surgery can be a safe and effective procedure for pediatric patients with severe obesity. Candidates include those whose BMI is greater than or equal to 35 kg/m² or 120% of the 95th percentile for age and gender, whichever is lower. The American Pediatric Surgical Association recommends surgical management for adolescents with near-complete skeletal maturity at risk for medical complications of obesity after a failure of intensive behavioral interventions in a multidisciplinary weight management program lasting at least 6 months.[30] 

Bariatric and metabolic surgeries include laparoscopic vertical sleeve gastrectomy and Roux-en-Y gastric bypass. Laparoscopic adjustable gastric band procedures are only approved for patients aged 18 or older and have worse long-term success and higher complication rates. Patients should be referred to comprehensive surgical centers with experience working with youth and their families. Like adults, pediatric bariatric patients can reduce their BMI and improve or resolve many obesity-related comorbid conditions, including hypertension, T2DM, dyslipidemia, and weight-related quality of life. Post-operative complications are usually minor, including nausea and dehydration, but up to a quarter of patients may require additional procedures in the following 5 years. Patients must undergo close follow-up and long-term monitoring for micronutrient deficiencies and malabsorption, and vitamin and mineral supplements may be required. [American Academy of Pediatrics Clinical Practice Guidelines for Obesity 2023]

Before bariatric and metabolic surgery, patients and their families are carefully evaluated and educated about the surgical risks and benefits so they can make informed decisions. The family must understand that lifestyle modifications are required following bariatric procedures and that surgery is not a "quick fix." The interprofessional surgical team also performs a comprehensive physiologic and psychosocial assessment to determine if the patient is a suitable surgical candidate.

Differential Diagnosis

It is essential to consider uncommon secondary causes of obesity and medical conditions associated with obesity. [American Academy of Pediatrics Clinical Practice Guidelines for Obesity 2023]

• Attenuated height growth velocity suggests endocrine causes like hypothyroidism, hypothalamic tumor, growth hormone deficiency, and Cushing syndrome.
• A history of significant head trauma requires ruling out CNS injury as the cause of hypothalamic obesity. In such cases, there is usually an abrupt change in the weight gain trajectory following the inciting event.
• The presence of hyperphagia, atypical facial features, and neurodevelopmental delays may indicate genetic disorders accompanied by obesity. DNA methylation studies can confirm Prader-Willi syndrome. Ocular abnormalities like retinal dystrophy and nystagmus are associated with Bardet-Beidl and Alstrom syndrome and warrant further investigation.
• Developmental delays in the presence of severe obesity should raise suspicion for rare conditions such as congenital leptin or PCSK1 deficiencies [31], which can be identified by measuring serum leptin, proinsulin, and insulin levels. MC4R deficiency is a cause of early-onset pediatric obesity and is diagnosed through molecular genetic studies.
• Idiopathic intracranial hypertension, also known as pseudotumor cerebri, is a rare but serious neurological condition most commonly affecting overweight or obese young women. Obesity does not cause idiopathic intracranial hypertension but is a typical association. Initial symptoms include vision changes and headaches. Papilledema may be present on physical examination. Computed tomography and brain magnetic resonance imaging can be performed, but the definitive diagnostic test measures the CSF opening pressure upon lumbar puncture.[32]

Prognosis

Meta-analysis of studies evaluating the efficacy of behavioral and family-based interventions in reducing childhood obesity have shown encouraging outcomes in preschool children. The reduction of screen time has emerged as a critical strategy.[33] Early diagnosis and prompt intervention lead to a decline in comorbidities and an improved overall prognosis. As the burden of complications increases with age and severity, early diagnosis and treatment offer the best chance for good health. When lifestyle changes and behavioral interventions fail, clinicians must refer patients for pharmacological and surgical interventions promptly. Without appropriate treatment, children with obesity likely become adults with obesity, at risk for long-term adverse health outcomes.  

Complications

Treating pediatric obesity and its comorbid conditions is challenging, time-consuming, and often frustrating for clinicians and families. Obesity impacts multiple organ systems, the most common being cardiovascular and endocrine.[34] Dyslipidemia (low HDL and high LDL and total cholesterol) and hypertension increase the probability of future adverse cardiovascular events. Central adiposity, in particular, causes metabolic imbalances leading to insulin resistance and metabolic syndrome and is associated with PCOS. Excess adipose interferes with the liver's metabolic and synthetic functions and is 1 possible cause of NAFLD. Obesity is also associated with an increased risk of gallstones.

Orthopedic problems occur more often when there is increased pressure on growing bones due to extreme body weight. The exact causes of Blount disease and slipped capital femoral epiphysis are likely multifactorial, but obesity is often present. Patients with Blount disease present with knee pain, a limp, and severe bowing of the tibias. Slipped capital femoral epiphysis is suspected when a child presents with hip pain and decreased internal limb rotation on examination.[35] Pulmonary comorbidities include asthma and obstructive sleep apnea. Asthmatic patients may complain of shortness of breath, cough, and exercise intolerance. Snoring, restlessness, daytime sleepiness, and behavioral problems can indicate obstructive sleep apnea. Pulmonary function tests and polysomnography may be warranted. 

The psychological complications of obesity can have a profound impact on a child's day-to-day life and should be addressed early. Interviewing children non-judgementally with open-ended questions may help them disclose any concerns. In addition, the clinician should ask about symptoms of anxiety or depression, worsening grades, or bullying at school. Professional counseling may be necessary to prevent the progression of psychological symptoms. [American Academy of Pediatrics Clinical Practice Guidelines for Obesity 2023]