Continuing Education Activity

Obesity is a common health concern in pediatrics. It causes a myriad of comorbidities affecting every organ system of the child. Inadequate treatment leads to the tracking of obesity into adulthood and poor outcomes of this preventable disease. This activity reviews the evaluation and treatment of pediatric obesity and highlights the role of an interprofessional team in managing the patients with this condition.

Objectives:

• Describe the causes of polygenic versus monogenic obesity.
• Identify the role of leptin, ghrelin, and melanocortin in the neuroendocrine feedback in the pathophysiology of obesity.
• Outline the possible management strategies for an obese child.
• Summarize how coordination by the interprofessional team in the treatment of obesity will result in improved outcomes.

Introduction

Obesity is a serious and rampant health problem in children and adolescents. Obesity refers to increased adiposity. The criterion to define obesity is a Body Mass Index (BMI) of more than the 95th percentile for age and gender. Because the BMI vastly varies in children who are less than two years old, the weight for height more than the 95th percentile is used as the criterion rather than BMI.[1] 

Rising trends in the prevalence of obesity have been seen in the last few decades in the US, making it a public health concern.[2] Inadequate monitoring and treatment cause complications in childhood, translating into an increase in morbidity and mortality throughout adulthood.

Etiology

The etiology of obesity is multifactorial. Obesity originates from a complex interplay between various environmental, genetic, physical, and cultural factors. Environmental factors include the stress and anxiety levels at the family, school, and community settings.

Although genetic determinants play a significant role in variation in adiposity, the intake of excess calories in the face of less energy expenditure leads to the development of obesity.[3] There has been a shift in food preferences over the past decade due to marketing and the easy availability of high-calorie food like fast food and soda. The consumption of energy-dense food with a high glycemic index and high-carbohydrate beverages, larger portion sizes, and snacking between meals has been correlated with the drastic increase in obesity in industrialized nations.[4] 

The decline in physical activity and increased screen time (smartphones, computers, televisions) have further worsened the situation.[5] This notion has been further strengthened by studies showing a potential risk of increase in obesity during the current COVID-19 pandemic as the schools are closed, and thus the screen time and sedentary activities of children have catapulted.[6] 

Feeding patterns are culturally driven, and children tend to model their parents from a very young age. Studies have shown a positive influence of parental education and family meal structure in affecting nutritious food choices by their children. Factors like having meals as a family together, exposing the child to various food options, and avoiding watching television have effectively created a positive food environment and prevented obesity.[7] The amount of time spent by the child on television has been associated with increased, playing video games has been associated with distracted eating and obesity.[8]

Other crucial risk factors have been identified in recent studies as an effort to prevent rather than treat obesity. Perinatal factors influencing the risk for obesity include parental BMI in pregnancy, birth weight and nutrition of the child in the first 1000 days of life, breastfeeding (protective) versus formula feeding, catch-up growth, and weight gain in the first year. Environmental chemicals, microbiota, and adverse life experiences were also found to be potential risk factors.[9][10][11]

Polygenic obesity is much more common than monogenic obesity. With advances in genetic and molecular studies, the causes of monogenic obesity are being identified. MC4R (Melanocortin 4 receptor) and POMC(proopiomelanocortin) deficiency increase food-seeking behavior. Leptin and leptin receptor deficiency has been associated with early-onset extreme obesity.[12] Genetic syndromes like Prader Willi, Bardet-Beidl, Beckwith-Wiedmann, and Albright hereditary osteodystrophy have been associated with obesity.[13]

Secondary causes of obesity include endocrine, neurologic, psychologic, and drug-induced causes, which are also the differential diagnoses that need to be considered. The mechanism is thought to be hormonal imbalances that affect the satiety and food-seeking behavior of the individual.

Epidemiology

Between 1963–1965 and 1999-2000, the prevalence of obesity among children aged 6–11 years increased significantly from 4.2% to 15.3%.[14] Recent data from the National Health and Nutrition Examination Survey in 2015-2016 suggests a further increase. According to this survey, the prevalence of obesity in the US among 2-19 years olds is as high as 18.5%. The magnitude of the problem is extensive in adolescents, with the prevalence being 20.6% among 12- to 19-year-olds. Approximately 13.5 million adolescents suffer from obesity.[2] The risk for obesity in children varies significantly by ethnicity as well.

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 of 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 peptide yy, agouti-related peptide, and orexin also cause appetite stimulation, whereas Melanocortin and alpha-melanocyte-stimulating hormone promote satiety.[16][17] The deficiency of MCR4 has been associated with food-seeking behavior.[18]

Hence the balance between appetite stimulation and adiposity is maintained by the neuroendocrine interaction between gut, adipose tissue, and brain. Mutations in genes involved in secreting these hormones have been of interest in epigenetic modifications and are potential therapeutic targets.

History and Physical

History entails a thorough search for etiology and comorbidities. The etiology is suggested by reviewing previous growth charts of the child and tracing any abrupt changes in the trajectory of weight, height, and BMI. Behavior changes like extreme appetite and food-seeking behavior are seen in genetic diseases. A non-judgemental approach of questioning should be used to probe the details of the nutritional intake and energy expenditure of the child. Family history begins with identifying obese members. Exploration of the family feeding pattern, meal composition, snacking, and screen time dissects the cause of obesity. A 24-hour diet recall describing the number of servings of fruits, vegetables, and high-carbohydrate food in each meal helps assess the source of excess calorie intake. Duration and type of physical activity help in assessing energy expenditure. The history of Diabetes mellitus, Hypertension, Cardiovascular disease in a family member emphasizes the increased risk of developing the same in the child. Parental obesity is a major risk factor. The clinician should help the family understand that childhood obesity increases the risk of chronic diseases. Review of birth history for IUGR and increased catch-up growth are crucial.

History is a vital tool to rule out the secondary causes of obesity. History of head trauma preceding the onset of weight gain suggests a hypothalamic cause. Easy bruising, muscle weakness, fatigue, and central obesity indicate Cushing syndrome. Cold intolerance, dryness of skin, and swelling of the neck point towards hypothyroidism. A review of medications associated with obesity like prednisolone, antipsychotics (risperidone), and antiepileptic (valproate) is helpful to diagnose drug-induced obesity.[19] 

History suggestive of comorbidities includes polyuria, polydipsia for diabetes mellitus, headache, and vision changes (pseudotumor cerebri), painful limping and hip/knee pain (Blount disease and slipped capital femoral epiphysis), abdominal pain, vomiting, jaundice (gallbladder disease, non-alcoholic fatty liver disease), anxiety and depression, worsening school performance, bullying or being bullied (behavioral problems), shortness of breath, snoring and daytime sleepiness or fatigue (asthma and obstructive sleep apnea), irregular menses, hirsutism, and acne (PCOS).

Physical examination begins with an anthropological assessment of weight, height, and BMI (weight (kg) / height (m) squared) and a thorough systemic examination to screen for complications of obesity. General physical examination reviews for:[1]

• Facial and body dysmorphism, which suggests genetic disorders (Prader Willi- small hands and feet, hypotonia, Downs syndrome- upslanting eyes) and endocrine disorders (Cushing syndrome- moon face)
• Cognition impairment is also seen with these genetic syndromes
• Shorth stature (growth hormone deficiency, Albright hereditary osteodystrophy)
• Vision changes (papilledema- pseudotumor cerebri, retinitis dystrophy- Bardet-Biedl syndrome)
• Skin changes (acanthosis nigricans - thick, velvety skin on the nape of neck suggests insulin resistance, acne, and hirsutism)
• Tanner staging of sexual development premature adrenarche in obese girls).
• Screening for hypertension with appropriate sized cuff is important (PCOS), abdominal striae. 
• The clinician should look for shortness of breath and wheezing (asthma), abdominal tenderness, hepatomegaly (nonalcoholic fatty liver disease), hip and knee mobility restriction (slipped capital femoral epiphysis and Blount disease, respectively).
• Assessment of behavioral problems through checklists (child behavior checklist, children's behavioral inventory) covers the psychological aspect of the disease.

Evaluation

The primary care physician generally diagnoses obesity during health maintenance visits. The growth chart is reviewed for assessing onset, severity, and also hints towards the etiology.

• BMI trajectory helps define whether the onset of the problem was during sensitive periods (infancy, childhood, and adolescence) or abrupt. The adiposity rebound occurs between 3 and 7 years of age.
• Abrupt changes in BMI indicate personal or family stress and medical problems (tumor, trauma, hypothyroidism, drug-induced).
• Comparing the weight and height trajectories can be very useful. A young child who is taking excess calories shows a linear increase in both weight and height, whereas a disproportionate increase in weight only indicates sedentary periods and lower physical inactivity.
• An abrupt change in linear growth strongly implies endocrine problems.

Laboratory investigations focus on early detection of the comorbidities of obesity. They include:

• Serum lipid profile- LDL, HDL, Total cholesterol for dyslipidemia
• Fasting blood glucose and HbA1C are elevated in states of insulin resistance- Diabetes mellitus type-II, metabolic syndrome
• Liver function tests: ALT/AST are elevated in nonalcoholic fatty liver disease (NAFLD)
• LH/FSH, and free testosterone levels for polycystic ovarian syndrome (PCOS)
• Thyroid profile including TSH, free-T3, and free-T4 for hypothyroidism
• serum cortisol levels are elevated in Cushing syndrome
• Imaging: radiograph of hip and knee joints, ultrasound of abdomen and pelvis, CT/MRI brain to look for hypothalamic tumors.
• Polysomnography tests for obstructive sleep apnea and pulmonary function tests for obesity hypoventilation syndrome.
• Invasive tests are needed to assess the CSF opening pressure to diagnose pseudotumor cerebrii.

Treatment / Management

Behavioral interventions form the cornerstone in the management of pediatric obesity. Family-based interventions are aimed to improve BMI. They include measures like decreasing the number of sweetened beverages, fast food servings, and increasing the time spent in structured and unstructured physical activities. The physicians should make clear recommendations about the appropriate caloric intake of the child per day and the time spent in various types of structured and unstructured physical activities. Families are encouraged to plan their meals considering the preferences of the child and the nutritive value of food groups to ensure a balanced diet. exclusive parental participation rather than the participation of the child alone has been proven to be more effective.[20] Approaches like the traffic light diet plan can help decide a healthy food pattern as per their cultural beliefs and ethnicity.[21] 

Creating a positive food environment consists of incorporating healthy food choices by the authoritative family members and avoiding watching television while eating. These changes are mirrored by the family's children and have been successful in the prevention and treatment of obesity.[22][23] Motivational interviewing can help ascertain the patient's level of understanding regarding his problems and then develop strategies using his/her own values and thoughts to make changes.[24] Inclusion of the patients and their parents in goal-setting promotes the development of stimulus-control and self-monitoring of weight among children, which have proved to be sustainable and beneficial.

The Physical Activity Guidelines for Americans recommends 60 minutes or more of moderate-to-vigorous exercise for children aged 6 to 17 years, while children aged 3 to 5 years should be physically active throughout the day.[25] Concurrent aerobic plus resistance exercises have shown a tremendous impact on improving the metabolic profile of children and decrease the risk of cardiovascular events.[26] Changes towards increasing physical activity can include- walking to school, participating in sports, and exercising with family members in leisure time. Family physical activity has a better impact on the ability of the child to inculcate these life changes.[27]

The American Academy of Pediatrics (AAP) recommends a screen time restricted to less than 2 hours per day for greater than 2-year-olds. For children less than 2 years, it is recommended not to watch Television at all. Family involvement in engaging and encouraging physical activities in their leisure time can have a positive impact.

Pharmacological interventions are understudied. Orlistat is the only FDA-approved drug for obesity in less than 16 years. Orlistat is a pancreatic lipase inhibitor that promotes moderate weight loss by decreasing the absorption of fat. Adverse effects are mostly gastrointestinal, like flatulence, fatty-oily stools.[28] Other drugs like phentermine, topiramate, metformin, and exenatide have been evaluated by randomized controlled trials but not approved for pediatric use.[28] Experimental therapies include Hormone replacement therapy for patients with obesity, particularly in leptin and POMC deficiency in the adult population.[29]  Pharmacotherapy can help in the definitive treatment of underlying causes of secondary obesity like hypothyroidism and growth hormone deficiency.

The American Pediatric Surgical Association recommends surgical management for adolescents with near-complete skeletal maturity, BMI more than 40, and facing the medical complications of obesity after they have a failure of behavioral interventions for 6 months under the supervision of a multidisciplinary weight management program.[30] Bariatric surgery approaches include Adjustable gastric banding and Roux-en-Y. Adverse effects consist of postoperative malnutrition and vitamin deficiencies and iron and copper deficiency.

Differential Diagnosis

It is critical to dissect the history to look for secondary causes of obesity.

• Attenuated growth velocity points towards endocrine causes like hypothyroidism, hypothalamic tumor, growth hormone deficiency, and Cushing syndrome.
• A history of trauma is essential to rule out CNS injury leading to hypothalamic obesity. In such cases, usually, there is an abrupt change in growth trajectory following the inciting event.
• Genetic disorders are suggested by typical facial features, hyperphagia, neurodevelopmental delays and warrant DNA methylation studies to rule out Prader Willi syndrome. In addition, ocular abnormalities like retinal dystrophy and nystagmus are associated with Bardet- Beidl syndrome and Alstrom syndrome.
• Developmental delays should also raise the suspicion for congenital leptin deficiency and PCSK1 deficiency which can be identified by measuring serum leptin, proinsulin, and insulin level. MC4R deficiency is a cause of extremely early onset pediatric obesity and is diagnosed through molecular genetic studies.

Prognosis

Meta-analysis studies evaluating the efficacy of behavioral and family-based interventions on reducing childhood obesity have shown encouraging outcomes in preschool children. The reduction of screen time has emerged as an important strategy.[31] Early diagnosis and prompt interventions lead to a definite decline in the development of comorbidities and thus an excellent overall prognosis. As the burden of complications increases with severe obesity, the need to resort to pharmacological and surgical interventions is inevitable.

Complications

As discussed before, the comorbidities associated with severe obesity make management very challenging. Obesity impacts every organ system of the body, most common being cardiovascular and endocrine comorbidities. Dyslipidemia (decrease in HDL and increase in LDL and cholesterol) and hypertension increase the probability of adverse cardiovascular events. Central adiposity, in particular, causes metabolic imbalances leading to insulin resistance, metabolic syndrome, Polycystic ovarian syndrome (PCOS). The excess fat interferes with the liver's metabolic and synthetic functions, causing NAFLD and forms a nidus for the development of gallstones.

Orthopedic problems occur due to the increased pressure on growing bones due to the extreme bodyweight. Patients with Blount's disease present with knee pain, a limp, and severe bowing of both tibia is seen on X-ray. Slipped capital femoral epiphysis is also common where the child presents with hip pain instead and decreased internal rotation of the limb is evident on examination. Pulmonary complications include the development of asthma and obstructive sleep apnea. Patients may complain of shortness of breath, coughing, and exercise intolerance in asthma. Snoring, restlessness, and behavioral problems can indicate obstructive sleep apnea.

The psychological complications are rampant and have a profound impact on the child's day-to-day life; hence need to be addressed proactively. Interviewing in a non-judgemental manner with open-ended questions may help to bring out these aspects of the problem. In addition, the physician should evaluate the child for symptoms of anxiety, depression, worsening grades, and facing bullying at school. Pseudotumor cerebri is another serious neurological complication with relatively vague symptoms of headaches. The presence of vision changes and headaches strongly points towards the condition due to the development of papilledema. Initially, CT and MRI of the brain can be done, but the most definitive diagnostic test is measuring CSF opening pressure. It is also therapeutic and draining a large amount of CSF to relieve the pressure.

Consultations

Obesity in pediatrics is a reasonably challenging problem because inadequate diagnosis and treatment lead to tracking of childhood obesity, not adulthood causing comorbid illness. The primary care physician makes the initial diagnosis, but the subsequent management involves the consultation with an interprofessional team of specialists in a staged manner.[32]

• Stage 1 (prevention plus) of the management involves recommendations made by the primary care physician.
• Failure of improvement in 3 to 6 months warrants consideration of Stage 2 or structured weight management, which involves referral to dieticians.
• In stage 3, a comprehensive multidisciplinary team, including behavioral counselors, exercise specialists, and social workers, frequently contact the primary care provider to tackle the issue.
• In stage 4, the patient is referred to a tertiary care center with a pediatric weight management program, and pharmacological and surgical interventions are considered.

Deterrence and Patient Education

As family-based interventions have proved to be most successful and sustainable in managing pediatric obesity, educating families about positive-health-related behavior is a major determinant of the outcome. Encourage families to make conscious choices of healthy food options like minimizing salty and sugary snacks, candies and increasing fruits and vegetables to at least five servings daily. The importance of creating a positive food environment should be stressed- eating breakfast daily as a family in a fixed place and time and avoiding skipping the meals. Parents should be discouraged from using food as a reward.[33]

Parents are encouraged to engage in fun physical activities tailored to the child's capacity. Involving parents in setting goals related to diet and physical activity improves the efficacy. They can choose food options as per their cultural feeding pattern diet and their child's food preference.

Financial difficulties in the family may force parents to hold multiple jobs to support their children, which will be a major deterrent to family-based interventions. Children are more likely to consume a higher amount of high-calorie diet like fast food regularly and engage in lesser physical activity. It is important to understand barriers in following the medical team's recommendations in terms of behavioral and pharmacological intervention for a more patient-centered approach in management.[34]

Enhancing Healthcare Team Outcomes

Obesity is a serious public health concern in the United States, with an alarming increase in prevalence in the past few decades. The cause of primary obesity is an imbalance in nutritional intake versus energy expenditure. Secondary causes of obesity like endocrine problems, genetic causes, and head trauma need to be ruled out for deciding the appropriate line of management.

While the primary care physician makes the diagnosis based on the history, physical examination, and review of growth charts, it is equally important to consult with an interprofessional team of specialists, including dieticians, psychologists, behavioral counselors, exercise specialists, endocrinologists, neurologists, and surgeons. Nurse practitioners are a vital part of the interprofessional group. Continued and frequent motivation to both the parents and the child is needed to adopt positive health-related changes in their daily lives. These children require constant monitoring of weight and BMI to improve self-efficacy with the interventions. Dieticians can develop a range of low-energy-dense and balanced diet options to help parents make educated changes in feeding habits. Exercise specialists can make age-appropriate recommendations for exercise for the patient as well as family activities. Psychological problems play a major role in the development of maladaptive eating patterns, and thus the role of behavioral counselors and school-based health groups cannot be stressed enough.

The expertise of the interprofessional team in pediatric weight management programs is helpful when tertiary care intervention is considered. The role of pediatric surgeons becomes pivotal when the behavioral and pharmacologic interventions fail and bariatric surgery is considered. Consultations with endocrinology, neurology, and genetics can help when secondary causes of obesity are being evaluated.