This chapter will address the following American College of Graduate Medical Education competencies: patient care and medical knowledge.

Patient Care: Understanding assessment and treatment of obesity-related comorbidities is essential in caring for children with obesity. This chapter will help the pediatric health care provider carefully assess and screen for significant comorbidities so that measures can be taken to prevent additional organ system damage from occurring while the patient concurrently works to achieve a healthy weight. The identification of additional comorbidities can also build increased awareness and motivation in the patient and family to make healthy lifestyle changes.

Medical Knowledge: This chapter will help the pediatric health care provider apply knowledge about pathophysiology, comorbidities, epidemiology, psychosocial and behavioral factors influencing disease development and maintenance to patient care and research.

Childhood obesity affects all aspects of a child’s health. It is associated with psychosocial concerns such as attention deficit hyperactivity disorder (ADHD), disordered eating, depression and anxiety, low self-esteem, and lowered quality of life as well as with a constellation of chronic illnesses, traditionally thought to only affect adults. These include, but are not limited to, prediabetes and T2DM, hypertension (HTN), PCOS, nonalcoholic fatty liver disease, obstructive sleep apnea, hyperlipidemia, and acanthosis nigricans. There are also comorbidities of obesity found only in childhood such as Blount disease, slipped capital femoral epiphysis, premature adrenarche, and early puberty. Childhood obesity also increases the risk of adult obesity with all of the associated comorbidities including renal complications and cancer.¹

In children, as in adults, the combination of genes, environment, age, and lifestyle choices can act synergistically leading to unhealthy weight gain. The societal impact of the obesity epidemic is already palpable. The medical care costs of obesity in the United States were a staggering $147 billion in 2008.² It is expected that as the increasing population of children with obesity become adults with obesity, health care costs will continue to increase. We are still learning about the epidemiology, etiology, identification, and treatment of the many obesity-related disorders previously rarely diagnosed during childhood.

Attention deficit hyperactivity disorder

It should not be surprising that there is a significant relationship between obesity and ADHD. Core features of ADHD such as poor self-regulation, decreased ability to delay gratification, and impulsivity have been implicated as possible mechanisms underlying overeating and decreased physical activity. However, only a few studies have examined this relationship. A small study³ found in a sample of 26 children hospitalized for obesity that 15 met criteria for ADHD. In a meta-analysis, impulsivity was found to be higher among children with elevated weights than those within a healthy weight range.⁴ Hyperactivity and attention problems have also been consistently associated with adult obesity. ADHD has been associated with a 30% to 40% increased risk of adult obesity and conduct problems associated with a 40% to 60% increased risk of adult obesity.⁵ In individuals with ADHD, deficits in executive functioning, or the ability to self-regulate, were associated with greater body mass index (BMI) z-scores.⁶

Disordered eating

Disordered eating behaviors and relationships to food are not unusual in children and adolescents with obesity and may present in many ways and warrant a thorough evaluation.

Binge eating disorder has recently been included in the DSM-5 as a mental health condition and consists of eating a significantly large amount of food inappropriate to the situation, feeling out of control while eating, and distress over eating.⁷ A recent study⁸ examined binge eating symptoms in a group of adolescents presenting for obesity treatment. One-third of the sample endorsed significant binge eating. In addition, the study found binge eating to be correlated with higher BMIs, greater depressive symptoms, and lower self-esteem.

Emotional eating is defined as “eating in response to a range of negative emotions, such as anxiety, depression, anger, and loneliness, to cope with negative affect.”^9,10 Some studies have found emotional eating to be more prevalent among youth with obesity¹¹ and correlated with behavioral and mood symptoms.^11,12

Other areas of disordered eating have only been studied minimally in the pediatric literature, but may be clinically relevant and warrant assessment.

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  Refusing to eat certain foods or only eating a limited amount of food which may be seen more often in children on the autism spectrum¹³

  
  
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  Hiding or sneaking food

  
  
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  Night eating syndrome—eating an abnormally large portion of one’s daily calories after the evening meal or getting up to eat after falling asleep⁷

Mood symptoms

In examining mood symptoms, depressive and anxious symptoms have been found to be associated with obesity¹⁴ in addition to low self-esteem.¹⁵ Body dissatisfaction is also seen in youth with overweight.¹⁶ In one study¹⁷ examining psychopathology in 54 children aged 7 to 16 years with obesity, 50% of the sample was found to have some type of mental health concern, with depression and social phobia being the most frequent. Furthermore, these youth were more likely to have school difficulties and to not follow through with treatment recommendations.

It is important to note that the link between obesity and psychological symptoms may vary. It is likely that the associations between psychosocial correlates and obesity are mediated by other factors. For example, depression does not necessarily lead to obesity, nor does obesity necessarily lead to depression. Some studies have found depression to be a risk factor for obesity¹⁸; whereas other studies have found that those with depression may be more likely to engage in screen time and that screen time was associated with increased BMI.¹⁹ Further research is needed to definitively describe the relationship between depression and obesity. However, depression and mood symptoms are common and important to identify in youth with obesity.

In addition, the use of psychiatric medication to aid in mood and behavior management may also be associated with obesity. Several atypical antipsychotic medications (ie, olanzapine, aripiprazole, and risperidone) have been found to cause significant weight gain.²⁰ Clinically, families may report the onset of weight gain coincident with the child’s placement on psychiatric medication. This is important to monitor as children and adolescents may become nonadherent to psychiatric medication if they feel it is causing weight gain.

Quality of life

In one study, children and adolescents who had been referred to a hospital-based obesity program had a self-reported health-related quality of life (ie, physical, emotional, social, and school functioning) comparable to children and adolescents with cancer.²¹ Difficulties in the social domain are particularly salient in this population.^22,23 Weight-related teasing leads to higher levels of depression and unhealthy weight control behaviors.²⁴ In one study,²⁵ peer victimization was found to correlate with levels of depression and weight status. Parents, siblings, and other family members can also be a source of bullying and stigmatization that should be identified and addressed. Some examples of psychosocial assessment instruments are listed in Table 13-1.

Prediabetes and diabetes

The epidemic of childhood obesity has resulted in an increase in the population of youth with insulin resistance, insulin secretory abnormalities, and T2DM. The fetal environment may play a role in the future development of T2DM by inducing epigenetic changes that increase the likelihood of obesity and insulin resistance.³⁷ Before 1992, T2DM accounted for 4% of all new cases of diabetes in children younger than 19 years, rising to 16% in 1994.³⁸ Results of a multicenter study of diabetes in youth found a T2DM prevalence of 0.4 per 1000 in children aged 0 to 19 years. T2DM represented 6% of the cases of diabetes in non-Hispanic whites, 33% in African American, 40% in Asian or Pacific Islander, and 76% in native American youth. The incidence of T2DM for 10 to 14 year olds and 15 to 19 year olds is the highest among native Americans (25.3 and 49.4, respectively), followed by African Americans (22.3 and 19.4), Asian or Pacific Islanders (11.8 and 22.7), and Hispanics (8.9 and 17.0), and is low (3.0 and 5.6) among non-Hispanic whites.³⁹ The magnitude of T2DM in the pediatric population may be underestimated as illustrated in a recent report which found that 4% of adolescents with obesity referred to the Yale Pediatric Obesity Clinic between 1999 and 2001 had undiagnosed T2DM. In addition, 21% of children with obesity and 25% of adolescents with obesity evaluated in this clinic already had prediabetes.⁴⁰

Prediabetes, a term introduced by the American Diabetes Association, refers to the conditions in which blood glucose levels are higher than normal but are not high enough for a diagnosis of diabetes. Prediabetes applies to the stages previously known as impaired glucose tolerance and impaired fasting glucose. Individuals with prediabetes are at increased risk for developing T2DM, cardiovascular disease (CVD), and stroke. The current recommendations for the diagnosis of diabetes and prediabetes from the American Diabetes Association⁴¹ are summarized in Table 13-2.

The presentation of T2DM and prediabetes in children may be insidious and asymptomatic, and may only be identified by an incidental finding, such as glycosuria or hyperglycemia during an evaluation of a urinary tract infection or vaginal candidiasis. Patients can, however, present more acutely with the typical symptoms of diabetes, such as polyuria, polydipsia, weight loss, and fatigue. Patients with T2DM can also initially present in frank diabetic ketoacidosis or with hyperosmolar coma. Mortality and morbidity are high in this group of patients and a high index of suspicion and awareness of this condition by pediatric health care providers is warranted.⁴²

Complications associated with diabetes include increased risk of cardiovascular disease,⁴⁴ end-stage renal disease,⁴⁵ blindness,⁴⁵ and vascular insufficiency of the lower extremities.⁴⁶ The long-term effect of early onset T2DM in children on eventual morbidity and mortality is not yet known. Because the incidence of complications of diabetes increases with the duration of illness and inadequate control, it is likely that children with T2DM will develop complications at a younger age. These children may present with severe complications as they go into their third decade of life, which will have devastating consequences for these individuals and their potential progeny, as well as for the health care system.

Obstructive sleep apnea syndrome

OSAS results from partial or complete blockage of the upper airway during sleep. Obesity can produce several physiologic derangements that result in upper airway anatomic obstruction and poor gas exchange. Apneic episodes associated with OSAS produce brief arousals that may number in the hundreds per night, which results in interrupted sleep and daytime somnolence. OSAS can lead to hypoventilation, carbon dioxide retention, hypoxia, right ventricular hypertrophy and failure, and possibly pulmonary embolism.^{47, 48, 49} Symptoms suggestive of OSAS can include apneic periods, loud snoring, gasping or choking sounds while sleeping, daytime somnolence, morning headache, new-onset nocturnal enuresis, and excessive tiredness. Other adverse consequences of OSAS are increased blood pressure (BP), enuresis, daytime somnolence or hyperactivity, deficits in learning and memory function with resulting poor school performance,⁵⁰ and severe cardiopulmonary problems including cor pulmonale and pulmonary HTN. In extreme cases, this can result in death in the late second and third decades of life. Somnolence and fatigue caused by OSAS further impair the child’s ability to be physically active, may impair their ability to make healthy food choices, and worsen psychological conditions and symptoms, which in turn predisposes them to worsening obesity and creates a vicious cycle.

Obesity is a well-known risk factor for OSAS in adults. There is mounting evidence that OSAS is also a considerable problem in children with obesity, with a prevalence as high as 60%.⁵¹ In one study of children with obesity undergoing polysomnography, it was observed that 46% had OSAS.⁵² Likewise, in another study OSAS was observed in 59% of children with obesity undergoing evaluation for symptoms of sleep disordered breathing.⁵³ Yet another study reported that 55% of children scheduled for bariatric surgery for morbid obesity had OSAS.⁵⁴ The American Academy of Pediatrics (AAP) in its technical report concludes that obesity is an independent risk factor for snoring and OSAS,⁵⁰ and some studies report that the severity of OSAS parallels the severity of obesity.^55,56

Hypertension

The association between obesity and HTN in children has been widely described across ethnic and racial groups. All studies report higher BP and/or higher prevalence of HTN in children with obesity compared to lean children.⁵⁷ A study in school-aged children found that children with BMI greater than 85th percentile had a prevalence of HTN of only 2.6%, in comparison to 10.7% in children with BMI greater than 95th percentile, and that the prevalence of elevated BP and/or HTN rose with each successive increase in BMI percentile, even within the presumably normal range of BMI.⁵⁸ This correlation has been reported independently of race, gender, or age.⁵⁸

The pathogenesis of HTN in obesity seems to be related to sympathetic nervous system hyperactivity, which induces increased heart rate and BP variability, increased levels of plasma catecholamines, and neural manifestations, such as increased peripheral sympathetic nerve traffic. Insulin resistance has also been implicated in the pathogenesis of obesity-related HTN in children as well as altered vascular structure and function. Because HTN in children puts youth at risk for elevated BP in adulthood,^59,60 further enhancing their risk for CVD, identification and treatment of HTN in all children, especially in those with obesity, is essential. The definition of HTN in children with obesity is the same as that for children without obesity; thus, a BP percentile for age, gender, and height less than 90th percentile is normal. Prehypertension is defined as a BP percentile of 90th percentile or greater to less than 95th percentile. Stage 1 HTN is a systolic or diastolic pressure at 95th percentile or greater for age, gender, and height through the 99th percentile plus 5 mm Hg. Stage 2 HTN is a systolic and/or diastolic BP greater than the 99th percentile plus 5 mm Hg. Elevated readings should be documented on 3 or more separate occasions for diagnosis. If the child has a reading at greater than 99th percentile for systolic or diastolic pressure, immediate further evaluation and/or treatment should be undertaken.⁶¹

Nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) includes a range of diseases, varying in severity from simple liver steatosis to nonalcoholic steatohepatitis, which may progress to cirrhosis and ultimately liver failure. Cirrhosis due to obesity is soon expected to pass alcoholic cirrhosis as the most common cause of liver failure in adults.⁶² The prevalence of NAFLD among children with obesity is not well known but as the prevalence of childhood obesity continues to increase, the incidence of NAFLD is also increasing. An autopsy study reported that fatty liver was found in 38% of children with obesity, which is consistent with other reports from similar clinical populations. NAFLD is more common in boys and children of Asian (10.2%) and Hispanic background (11.8%). African American children had the lowest rates of NAFLD at 1.5%, and fatty liver is currently the most common form of pediatric liver disease.^{63, 64, 65}

NAFLD is characterized by mild-to-moderate elevation of serum aminotransferases, a hyperechoic liver on ultrasound and histological characteristics similar to alcoholic liver disease. Classical histological findings that characterize NAFLD in children are steatosis, ballooning, inflammation, and fibrosis.⁶⁶ The pattern of the distribution of pediatric NAFLD histological lesions is frequently different from that of adults. Children with NAFLD typically do not report any symptoms specific to these conditions. Thus, suspicion of this condition is typically raised by finding elevation of aspartate transaminase (AST) and alanine transaminase (ALT), and through elimination workup for other causes of elevated liver enzymes. A liver ultrasound can show signs of fatty infiltration; however, the definite diagnosis of NAFLD is by biopsy. It is important to involve a hepatologist or pediatric gastroenterologist to determine the need for liver biopsy.⁶⁷ Other causes of liver disease such as viral and autoimmune hepatitis, celiac disease, drug toxicity, Wilson disease, and other metabolic and genetic diseases should be considered in the clinical and laboratory evaluation.

It is thought that chronic overnutrition that leads to obesity may create an inflammatory cycle that promotes insulin resistance and hepatic lipid deposition. Components of the current American diet thought to contribute to the development of NAFLD are saturated fats, particularly trans-fats, fructose, animal protein sources, specifically branched chain amino acids, and alcohol.⁶⁸

Gallbladder disease

Increased cholesterol turnover leads to lithogenic bile, predisposing individuals with obesity to gallbladder calculi. Cholelithiasis has been reported to be 3 times more common in individuals with morbid obesity than in normal individuals. A study published in 2012 evaluated a large multiethnic and diverse pediatric population in southern California and reported that boys with extreme obesity have a 3-fold higher odds of gallstone disease, and girls with extreme obesity have almost an 8-fold higher odds of gallstone disease. Girls who used oral contraceptives had even higher odds. As in adults, increased risk for gallstone disease, including female sex, Hispanic ethnicity, obesity, and oral contraceptive use was also found in this pediatric population.⁶⁹

Functional gastrointestinal disorders

Several studies suggest that obesity is a risk factor for functional gastrointestinal (GI) disorders among children. For example, a study comparing a group of children referred to a GI practice to age- and sex-matched children seen in a local primary care practice found that the patients with GI complaints as a whole and by disease subgroup were more likely to have obesity. Constipation, gastroesophageal reflux, irritable bowel syndrome, encopresis, and functional abdominal pain were common complaints.⁷⁰ Another study found similar results, with obesity present in 22.4% of the patients with constipation compared with 11.7% of controls.⁷¹ None of these studies proved causality between obesity and these GI disorders, merely an association.

Studies in adults have shown correlations between obesity and gastro-esophageal reflux disease (GERD). Evidence exists of a dose–response relationship between erosive esophagitis and BMI.⁷² Herbella et al⁷³ showed that patients with obesity with GERD had normal or hypertensive esophageal motility, and Wu et al⁷⁴ found a correlation between greater BMI and waist circumference and increased numbers of transient relaxations of the lower esophageal sphincter. Higher BMI also has been correlated with greater intragastric pressure and gastroesophageal pressure gradient.⁷⁵

Obesity has also been reported to be associated with poor outcome and disability at long-term follow-up in children with functional abdominal pain.⁷⁶ More research is needed to investigate the causality of increased GI disorders among children with obesity as well as the effect of weight loss on these conditions.

Polycystic ovary syndrome

PCOS is the most common cause of androgen excess in female adolescents with hyperandrogenemia. It is also the most common endocrinopathy in women of childbearing age, with reported prevalence rates ranging from 5% to 10%.^{77, 78, 79, 80} These patients usually present with menstrual irregularities, infertility, hirsutism and acne, and often also have obesity.^78,81 Insulin resistance is present in the majority of adolescents with PCOS, although the relationship between insulin resistance and hyperandrogenism is complex. Lower levels of insulin induced by treatment result in decreased androgen levels. On the other hand, hyperandrogenism may contribute to decreased sensitivity to insulin. Obesity worsens the clinical presentation of PCOS by increasing insulin resistance and further elevating ovarian and adrenal androgens and unbound testosterone. Women with PCOS have an increased risk for T2DM, cardiovascular disease, and infertility.^{77, 78, 79, 80}

Premature adrenarche and early puberty

Children with obesity tend to be taller, and are more likely to have advanced bone age and earlier physical maturation than normal weight children.⁸² Although the determinants of initiation of puberty and menarche remain controversial, a hypothesis to explain the possible link between increased adipose body mass and pubertal development involves leptin, a hormone whose systemic levels parallel the size of the fat mass in a given individual. Adipose tissue and leptin increase during puberty. Leptin probably has a role in puberty initiation at the hypothalamic level, and higher leptin levels in children with obesity may lead to earlier puberty.

Orthopedic complications

A variety of orthopedic complications can present in a child with obesity. Blount disease results from overgrowth of the medial aspect of the proximal tibial metaphysis, leading to bowing of the legs. Approximately two-thirds of children with Blount disease also have obesity.

Another serious orthopedic complication found in children with obesity is slipped capital femoral epiphysis. This condition results from the slipping of the epiphysis of the proximal femur off the metaphysis posteriorly and medially.⁸³ Clinically, the condition presents with decreased hip mobility, limp, and often with referred pain to the knee and is diagnosed radiologically. About 50% to 70% of affected children have obesity.^84,85 Many adolescents with obesity also complain of foot pain and fallen arches. Well-fitting shoes with good arch support and sometimes arch inserts can be very helpful for children with obesity. Like other comorbidities of obesity, orthopedic problems further impair physical activity and promote additional weight gain.

Asthma

The prevalence of asthma, like the prevalence of obesity, is increasing among children. Even though at the present time their causal association remains controversial, there is consensus that there is a pervasive interaction between obesity and asthma. While exercise-induced bronchospasm may cause a limitation of physical activity and resultant obesity, obesity also causes or enhances bronchial hyperreactivity to exercise and may predispose to asthma. In addition, there is evidence that the morbidity secondary to asthma is enhanced in inner-city children with obesity. These children have more severe asthma symptoms, use more medications, and visit the emergency department more often than children with normal weight and asthma.⁸⁶ Good asthma preventive management is key to prevent asthma exacerbations from resulting in limitations to a child’s physical activity.

Cardiovascular disease

CVD complications associated with obesity include HTN, dyslipidemia, left ventricular hypertrophy, and pulmonary HTN (typically secondary to prolonged OSAS). All are well-known risks for CVD. The presence of multiple CVD risk factors in an individual is associated with early mortality.⁵⁷ Diabetes alone is a major risk factor, equivalent in its impact to the presence of a patient experiencing a previous cardiovascular event.^87,88 This is particularly alarming considering the increasing number of children with obesity diagnosed with T2DM and HTN simultaneously. As a result, the American Heart Association has issued a “call to action” to address this problem and has reclassified obesity as a major modifiable risk factor for coronary heart disease.⁸⁹

A study of adolescent girls found that almost 11% of white girls with overweight and 65% of black girls with overweight had 3 CVD risk factors compared with a frequency of 0.8% in girls with healthy weight.⁹⁰ Similar findings have been reported for boys.⁹¹ Other studies have reported actual end-organ injury in children. For example, left ventricular hypertrophy, left atrial enlargement, congestive heart failure, and stroke were found in children with HTN.^92,93 BMI correlated directly with the presence of cardiovascular abnormalities independently of other variables. A case of myocardial infarction and dissection of the right coronary artery has been reported in a 17-year-old adolescent with obesity and T2DM.⁹⁴

Evidence of childhood obesity affecting the risk for CVD was shown in the Harvard Growth Study, which revealed a 2-fold increase in the rate of death from CVD for males who were overweight during adolescence.⁵⁹ In addition, the Bogalusa heart study found that children with a BMI above the 85th percentile were more likely to have abnormal levels of cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL) and triglycerides, and high BP than normal weight children.⁹⁵ The expert panel appointed by the National Heart, Lung, and Blood Institute to develop cardiovascular health guidelines for pediatric care providers concluded that the scientific evidence linking elevated BMI to cardiovascular risk factors and morbidity is strong and well supported.⁹⁶

If not addressed, the epidemic of childhood obesity may reverse the trend of decreasing mortality from CVD achieved during the last 5 decades in the United States. Therefore, screening and treatment of cardiovascular risk factors need to be considered in children and adolescents suffering from obesity.

Renal complications

The kidney is another organ that obesity can affect. Marked proteinuria due to focal segmental glomerulosclerosis (FSGS) has been found in African American adolescents with severe obesity.⁹⁷