Obesity Effects on Child Health

Issues of Concern

Etiology and Pathophysiology

The complex interaction of individual and environmental factors plays a crucial role in developing obesity. The most important factors contributing to childhood obesity are summarized below. 

Environmental Factors

Changes in the environment in the past few decades in terms of easy access/ affordability of high-calorie fast food, increased portion size, increased intake of sugary beverages, and sedentary lifestyles are associated with increased incidence of obesity.[10] Increasing use of electronic devices [television, tablets, smartphone, videogames] by children has led to limited physical activity, disruption of the sleep-wake cycle, depression of metabolic rate, and poor eating patterns.[11]

Feeding patterns in infancy have a long-term effect on developing obesity later on in life. It has been shown that breastfeeding in the first year of life is inversely associated with weight gain and obesity.[12] This association was much more significant if the child was exclusively breastfed compared to having added formula or solid food. Despite concerns about the risk for obesity in preterm and SGA infants receiving calorie and protein supplementation, it has been shown to improve catch-up growth without increasing the risk of obesity.[13] High protein intake in the initial two years of life has also been postulated to increase weight gain later in childhood. 

Biological Factors

There is a complex interaction between the neural, hormonal, and gut-brain axis affecting hunger and satiety. Hypothalamus regulates appetite and is influenced by key hormones, ghrelin, and leptin. Ghrelin is released from the stomach and stimulates hunger (orexigenic), whereas leptin is mainly secreted from adipose tissue and suppresses appetite (anorexigenic). Several other hormones like neuropeptide Y and agouti-related peptide stimulate hunger, while pro-melanocortin and α-melanocyte-stimulating hormone suppress hunger.[14] These hormones control energy balance by stimulating the hunger and satiety centers in the arcuate nucleus of the hypothalamus through various signaling pathways. Stress-related psychiatric disorders with associated abnormal sleep-wake cycles can also lead to increased ghrelin levels and, in turn, increase appetite.

The gut microbiome includes the trillions of microorganisms that inhabit the human gut. Alterations in the gut microbiome can lead to weight gain through numerous pathways.[15] The dominant gut florae are Firmicutes and Bacteroidetes (90%), Proteobacteria, Actinobacteria, and Fusobacteria. These bacteria have a symbiotic relationship with their host. They can be affected by various factors, such as gestational age at birth, premature rupture of membranes, mode of delivery of the infant, type of feeding, feeding practices, and antibiotics usage. The maturation of gut flora occurs from birth to adulthood and is determined by various genetic factors, diet, lifestyle, and environment. Gut microbiota helps maintain the mucosal barrier, nutrient digestion (especially the synthesis of short-chain fatty acids), and immune response against pathogens. The imbalance of the gut microbiome (dysbiosis), leading to increased production of short-chain fatty acids, has been linked to developing obesity and other medical conditions, such as type 2 Diabetes Mellitus, Metabolic syndrome, anxiety, and depression.[16]

Genetic Factors

Obesity can be either monogenic, syndromic, or polygenic types. Monogenic obesity is uncommon, occurring in 3% to 5% of obese children.[17] Mutations in genes for leptin, leptin receptor, proopiomelanocortin, and melanocortin-4 receptor can lead to obesity. Monogenic type presents in early childhood with unusual feeding behaviors and severe obesity.

Genetic syndromes causing severe obesity include

1. Prader Willi syndrome: Early growth faltering followed by hyperphagia and increased weight gain by 2 to 3 years. The mild or moderate cognitive deficit, microcephaly, short stature, hypotonia, almond-shaped eyes, high-arched palate, narrow hands/feet, delayed puberty are common features.
2. Alstrom syndrome: Blindness, deafness, acanthosis nigricans, chronic nephropathy, type 2 diabetes, cirrhosis, primary hypogonadism in males, and normal cognition are common features in Alstrom syndrome.
3. Bardet Biedl syndrome: Intellectual disability, hypotonia, retinitis pigmentosa, polydactyly, hypogonadism, glucose intolerance, deafness, and renal disease are the features in Bardet Biedl syndrome.
4. Other syndromes include Beckwith-Weideman syndrome and Cohen syndrome.

Polygenic obesity is much more common and is caused by a complex interaction between multiple genetic variants and the environment known as gene-environment interaction (GEI). When a child with genotype variants conferring risk for obesity interacts with various environmental factors predisposing to obesity, there is a tendency for decreased physical activity, increased food intake, and body fat storage. Early life environment starting with maternal nutrition during the prenatal or early postnatal period and early childhood adverse environmental or psychosocial stressors can lead to epigenetic changes leading to obesity.

Endocrine Factors

Endocrine causes constitute less than 1% of cases of obesity in children.[18] It is usually associated with mild to moderate obesity, short stature, or hypogonadism. These include cortisol excess [steroid medications or Cushing syndrome], hypothyroidism, growth hormone deficiency, and pseudohypoparathyroidism.

Medications

Numerous medications can cause weight gain. These include antiepileptics, antidepressants, antipsychotics, diabetes medications [insulin, sulfonylureas, thiazolidinediones], glucocorticoids, progestins, antihistamines [cyproheptadine], alpha-blockers [terazosin], and beta-blockers [propranolol]. Close monitoring for excessive weight gain should be done when any of these medications are used in children.

Toxins

Endocrine-disrupting chemicals, such as bisphenol A and dichlorodiphenyltrichloroethane, have been hypothesized to predispose to obesity by modulating estrogen receptors and possibly metabolic programming.[19]

Viruses

Few studies in animal models have proven that obesity can be triggered by infection with adenovirus. However, human studies have found conflicting results.

Clinical Significance

Childhood obesity significantly impacts both physical and psychological health. Obesity can lead to severe health conditions, including non-insulin-dependent diabetes, cardiovascular problems, bronchial asthma, obstructive sleep apnea (OSA), hypertension, hepatic steatosis, gastroesophageal reflux (GER), and psychosocial issues. The preventive and therapeutic interventions in childhood obesity are crucial in decreasing the burden of comorbid health conditions.

Metabolic Syndrome

Metabolic syndrome, also named syndrome X, is a cluster of risk factors specific for cardiovascular diseases such as hypertension, glucose intolerance, dyslipidemia, and abdominal obesity that commonly occur in obese children or adolescents. Insulin resistance, hyperinsulinemia, and oxidative stress are the underlying factors contributing to metabolic syndrome.[20] 

Dyslipidemia

Atherogenic dyslipidemia is common in obese children and adolescents. A fasting lipoprotein level needs to be obtained in all children with obesity. Elevated triglycerides (TG) and Free fatty acid (FFA) levels, decreased HDL (high-density lipoprotein) cholesterol levels, and normal or mildly increased serum LDL (low-density lipoprotein) cholesterol levels are common findings in childhood obesity.[21] Hyperinsulinemia and insulin resistance in childhood obesity promotes hepatic delivery of FFA for triglyceride synthesis and sequestration into TG-rich lipoproteins.[22] 

Glucose Intolerance

Childhood obesity quadruples the risk of developing glucose intolerance and non-insulin-dependent diabetes mellitus (NIDDM or Type 2 diabetes). Over 85% of children with NIDDM are either overweight or obese at diagnosis.[23] Acanthosis nigricans is an increased pigmentation and thickness of the skin in intertriginous folds, and it is usually associated with glucose intolerance in children and adolescents. Fasting insulin and glucose should be included in the evaluation of childhood obesity. The risk factors for type 2 non-insulin-dependent diabetes and metabolic syndrome include, 

• children with BMI 85th to 95th percentile along with,
• immediate family history of type 2 diabetes 
• signs of insulin resistance such as acanthosis nigricans, dyslipidemia, hypertension, and polycystic ovarian syndrome.
• Children with BMI >95th percentile regardless of family history or associated features.[24] 

Hypertension

The most significant risk factor for pediatric hypertension is the high body mass index. One-fourth of obese children can have hypertension. Adipocyte is not only a storage depot for fat but is also an active endocrinological cell. The pro-inflammatory adipokines (leptin, resistin, and IL-6) lead to an increase in sympathetic nervous system (SNS) activation, which preferentially impacts the renal vascular beds.[25] Hypertension risk in childhood obesity can also be explained due to hyperinsulinemia. Hyperinsulinemia causes hypertension through secondary mechanisms such as increased renal sodium retention, increased intracellular free calcium, and increased SNS activity.[26] Dietary therapy, along with exercise, effectively decreases blood pressure. 

Hepatic Steatosis 

Pediatric liver disease is a severe complication of childhood obesity. Obesity-related non-alcoholic fatty liver disease (NAFLD) spectrum includes fatty liver, steatohepatitis, cirrhosis, and hepatocellular carcinoma.[27] Hyperinsulinemia in childhood obesity plays a significant role in contributing to hepatic steatosis. Gradual weight loss with regular exercise and diet with less refined carbohydrates and low-fat help normalize hepatic enzymes and resolve hepatic steatosis.[28]  

Cholelithiasis

The prevalence of cholelithiasis is high among adolescents with obesity, and the association is more robust in girls than in boys. Increased cholesterol synthesis and cholesterol saturation of bile contribute to cholelithiasis among adolescents with obesity.[29][29] Cholelithiasis occurs even more frequently with weight reduction. Almost half of the cases of cholecystitis in adolescents may be associated with obesity. 

Asthma

Overweight or obese children have been observed to have a higher prevalence of asthma and asthma exacerbations. The link between asthma and obesity is mediated through abnormal inflammatory and oxidant stress, chest restriction with airway narrowing, and obesity-related comorbidities such as obstructive sleep apnea and gastroesophageal reflux.[30] 

Idiopathic Intracranial Hypertension 

Idiopathic intracranial hypertension (IIH) is an uncommon disease of childhood and adolescence characterized by increased intracranial pressure without any identifiable cause. Almost half of the children who present with this syndrome may be obese and also have more IIH symptoms at onset.[31] The disease is characterized by elevated intracranial pressure. IIH presents with headaches and may lead to severe visual impairment or blindness. The potential for visual impairment indicates the need for aggressive treatment of obesity in patients with IIH.

Sleep Apnea

Obesity and overweight are crucial risk factors for obstructive sleep apnea (OSA). Neurocognitive deficits and excessive daytime sleepiness are common among obese children with sleep apnea.[32] Obesity hypoventilation syndrome may represent a long-term consequence of sleep apnea and is associated with a high mortality rate. Aggressive therapy is warranted for obese children with this syndrome. Obesity management such as increased physical activity and a healthy diet are recommended for OSA treatment, as well as surgical procedures, if appropriate. 

Orthopedic Complications

Fractures, musculoskeletal discomfort, and lower extremity malalignment such as Blount disease and slipped capital femoral epiphyses are more common in overweight than non-overweight children and adolescents.[33] Blount disease is a disorder of the proximal tibial growth plate, which results in progressive bowing of the tibia. Although the prevalence of Blount disease is low, approximately two-thirds of Blount disease patients may be obese. Slipped capital femoral epiphysis occurs due to epiphyseal plate disruption. Between 30% and 50% of patients with slipped capital femoral epiphysis are overweight.  

Polycystic Ovary Disease 

Obesity is frequently associated with polycystic ovary disease (PCOD). Up to 30% of women with PCOD may be obese. Hyperandrogenism and hyperinsulinemia often accompany PCOD. Obesity increases the risk of PCOD through insulin resistance and compensatory hyperinsulinemia, which increases androgen production and decreases sex hormone-binding globulin, thereby increasing the bioavailability of androgen. Adolescents with PCOD are at increased risk for metabolic syndrome and glucose intolerance. Weight loss represents an important therapeutic target in obese adolescents with PCOD. 

Persistence of obesity into adulthood

About 15% to 30% of adults with obesity were also obese in their childhood or adolescence.[34] The cardiovascular risk factors present in obese children or adolescents usually persist into adulthood. The change in body fat in obese adolescents can be a reasonable mediator contributing to the excess morbidity and mortality in later adulthood. 

Psychosocial impact 

Children with obesity or overweight are more likely to experience low self-esteem and depression during adolescence. Negative psychological experiences trigger emotional eating, leading to an ongoing obesity-depression cycle. Children who are overweight or obese face bullying at school and are excluded from competitive physical activities. Overall, children with obesity have less social interaction and spend more time in sedentary activities. Numerous studies have confirmed the association of childhood obesity with ADHD and anxiety disorders.[35]

Eating Disorders

Children with overweight or obesity have a high prevalence of disordered eating behaviors, increasing the risk of developing eating disorders. The majority of adolescents with restrictive eating disorders report a history of obesity in the past. Binge eating increases the risk of obesity and type 2 diabetes.[36] Appropriate evaluation for eating disorders should be performed during the treatment planning of childhood obesity. 

Academic Performance 

Children who are obese and have comorbid health problems like diabetes, asthma, or sleep apnea miss school more frequently, thereby affecting their school performance negatively.

Enhancing Healthcare Team Outcomes

Prevention is the best intervention to decrease the prevalence of obesity. The pediatrician should explore the risk of obesity and overweight during every clinical visit for all children.  

• Both bottle-fed and breastfed infants are at risk of overfeeding. However, overfeeding is more prevalent among bottle-fed infants. Exclusive breastfeeding and delayed initiation of solid foods may reduce the future risk of overweight. 
• Skim milk is a safe replacement for whole milk after two years of age. Parents or caretakers should never use food like sweets for a reward. The entire family should have a balanced diet that comprises less than 30 percent of calories from fat. AAP recommends consuming a variety of vegetables and fruits, whole grains, proteins, low-fat dairies and decreasing the intake of sodium, saturated fats, and refined sugars beginning at the age of two years.[37]
• An essential step in preventing obesity is reducing sedentary time. Limit the screen time, including television, video games, or mobile, not more than 2 hours per day for more than six-year-old children and not more than 1 hour per day for 2-6 years of age group. AAP strongly recommends not allowing kids less than two years to have screen time.[38]
• Encourage physical activity for children. Children aged 3 to 5 years should be active throughout the day. Children and adolescents ages 6 to 17 years should be physically active for at least 60 minutes every day.[39]
• As per CDC, 60% of middle school kids and 70% of high school kids do not meet the standard sleep recommendations. AAP recommends that children aged 1 to 2 years sleep 11 to 14 hours per day, children 3 to 5 years sleep 10 to 13 hours, children 6 to 12 years sleep 9 to 12 hours, and adolescents aged 13 to 18 years should regularly sleep 8 to 10 hours.[40] Avoiding heavy meals close to bedtime, being physically active throughout the day, and removing electronic devices in the bedroom will help to get better sleep.  

The pediatrician should explore for associated morbidity in all obese children. The detailed assessment in obese children should include assessing cardiac comorbidities, orthopedic complications, and psycho-social complications.

1. Reasonable weight-loss goals should be initially 5 to 10 pounds (2 kg to 4.5 kg) or a rate of 1 to 4 pounds (0.5 to 2 kg) per month.
2. Dietary management: Dieticians provide dietary prescriptions mentioning the total calories per day and recommended percentage of calories from carbohydrates, protein, and fat. The Traffic Light Plan is one method of providing dietary management. The Traffic Light Plan classifies foods as green (low energy density), yellow (moderate energy density), and red (high energy density). These categories help children in adopting healthier eating patterns.[41] The dietician plays a significant role in guiding the diet plan for the patients.
3. Physical activity: As per the fitness level, begin the physical activity with the goal of 30 minutes/day in addition to any school activity. Treatment should target gradually increasing the activity to 60 minutes per day. An exercise physiologist, along with the physician, can help the patients to achieve their target physical activity.
4. Behavior modification: Primary care-based behavioral interventions such as self-monitoring, nutritional education, improvement of eating habits, increasing physical activity, attitude change, and rewards help manage childhood obesity.
5. Family involvement: Review overall family activity and television viewing patterns and always involve parents in nutrition counseling. Family-based behavioral treatment is the most robust intervention for childhood obesity.[41]
6. Psychotherapy:  Behavioral therapy and Cognitive therapy are commonly used by the psychologist in the management of obesity. Behavioral therapy trains patients to act differently around food, and cognitive therapy trains patients how to change their thoughts and emotions related to food.
7. None of the anorexiant medications are FDA approved for use in childhood obesity. Orlistat is the only FDA-approved medication for use in adolescents. 
8. Surgical procedures like gastric bypass have not been studied sufficiently in children to advise their use. 

An interprofessional team that provides a holistic and integrated approach can help achieve the best possible outcomes. Collaboration, shared decision making, and communication are key elements for a good outcome. Multidisciplinary teams include a primary physician, a dietician, a nurse or nurse practitioner, a clinical exercise physiologist, and a psychologist. The interprofessional team can provide a comprehensive weight loss program that benefits the patients.