Pediatric Obesity Algorithm® 2018-2020

Pediatric Obesity Algorithm®

2018-2020

Disclaimer The Pediatric Obesity Algorithm, was developed to assist health care professionals in medical decision making in the management and care of patients with overweight and obesity. The Pediatric Obesity Algorithm is not intended to be a substitute for a medical professional's independent judgment and should not be considered medical advice. The content herein is based on the medical literature and the clinical experience of obesity medicine specialists. In areas regarding inconclusive or insufficient scientific evidence, the authors used their professional judgment.

The Pediatric Obesity Algorithm is a working document that represents the state of obesity medicine at the time of publication. OMA encourages medical professionals to use this information in conjunction with, and not as a replacement for, their best clinical judgment. The presented recommendations may not be appropriate in all situations. Any decision by practitioners to apply these guidelines must be made in light of local resources and individual patient circumstances.

Permissions The Obesity Medicine Association owns the copyright to the Obesity Algorithm but invites you to use the slide set. Access to the Obesity Algorithm content and/or permission for extensive quoting or reproducing excerpts and for the reproduction and use of copyrighted text, images, or entire slides will not be granted until the requestor has signed the copyright consent and permission agreement available at www.ObesityAlgorithm.org. OMA reserves the right to deny a request for permission to use the Obesity Algorithm.

Chair: Suzanne E. Cuda, MD, FAAP, FOMA

Co-authors: Administrative Assistance: Marisa Censani, MD Lauren Rieck Madeline Joseph, MD, FAAP, FACEP Nancy T. Browne, MS, PPCNP-BC, CBN, FAANP Valerie O’Hara, DO, FAAP

Citation: Cuda S, Censani M, Joseph M, Browne N, O’Hara V. Pediatric Obesity Algorithm, presented by the Obesity Medicine Association. www.obesitymedicine.org/childhood-obesity. 2018-2020. www.obesitymedicine.org/childhood-obesity (Accessed = Insert date)

To provide health care professionals an algorithm to guide the treatment of children and adolescents with increased body fat, based upon scientific evidence, supported by the medical literature, and derived from the clinical experiences of members of the Obesity Medicine Association.

The Pediatric Obesity Algorithm was derived from input by volunteer OMA members consisting of:

• Academicians • Clinicians • Researchers

The Pediatric Obesity Algorithm did not receive industry funding, had no input from industry, and the authors received no payment for their contributions.

The Pediatric Obesity Algorithm 2018/2020 is intended to be a “living document” updated as needed. It is intended as an educational tool to assist in the translation of medical science and the clinical experience of the authors towards assisting health care professionals improve management of their pediatric patients with overweight and obesity.

This algorithm is not intended to be interpreted as “rules” and/or directives regarding medical care of an individual patient.

While it is hoped many clinicians may find this algorithm helpful, the final decision regarding the optimal care of the patient with overweight or obesity is dependent upon the individual clinical presentation, and the judgment of the clinician who is tasked with directing a treatment plan that is in the best interest of the patient.

Overall Management Goals...... 8 Co-Morbidities...... 61 Epigenetics...... 9 Behavioral Health Problems Associated with Obesity. . . . . 78 Assessment...... 17 Eating Disorders...... 84 Obesity as a Disease...... 27 Miscellaneous Topics...... 89 Differential Diagnosis...... 29 Social Consequences...... 97 Review of Symptoms...... 31 Pharmacology...... 103 Diagnostic Work Up...... 33 Medication Related Weight Gain...... 107 Physical Examination...... 37 Appendices...... 116 Nutritional Recommendations...... 41 Appendix A: Staged Treatment Approach...... 117 Food Insecurity...... 45 Appendix B: Resources/Tools...... 121 Management...... 47 References...... 126 Activity Recommendations...... 58 Disclosures...... 154

Pediatric patient with overweight or obesity

Develop healthy habits Improve health & Improve body and lifestyle patterns quality composition through adulthood of life

Prevent future adverse Improve body image health consequences and self esteem

Small for Gestational Age Infants Very Low Birth Weight Infants Large for Gestational Age Infants (Intrauterine Growth Restriction) (Premature infants) • Tobacco abuse during • Mothers with preconception • Undergo significant periods of pregnancy BMIs > 30 kg/m2 undernutrition following birth • Commonly leave the NICU at a • Use of folic acid may • Mothers with excessive smaller size than counterparts attenuate the effect gestational weight gain who remained in utero • Insufficient gestational • Gestational diabetes • Undergo a period of catch-up weight gain mellitus growth when they are provided with high nutrient formula or fortified human milk • Have higher levels of visceral fat suggesting a set up for higher incidence of CV disease and T2DM • Often receive prolonged courses of antibiotics • Highly stressed

10 Pediatric Obesity Algorithm®. ©2018-2020 Obesity Medicine Association. Reference/s: [1] The Maternal Resource Hypothesis: Each generation produces larger and more metabolically compromised mothers Less maternal disease (as compared to past generations) + decreased physical activity + improved nutrition increased maternal BMI and adiposity

Increased maternal insulin resistance  stimulates fetal pancreatic beta cells and adipocyte hyperplasia

Adipocyte hyperplasia establishes a competitive dominance over other tissues

Intense postprandial insulin response and the relative number of adipocytes is so large that the competitive dominance of adipocytes is inevitable and obesity unavoidable

Maternal Insulin Resistance C section delivery Neonatal Intestinal Microbiome

• Maternal insulin resistance (IR), not • “Iatrogenic Artificial Selection” • Before delivery through first 2 years prepregnancy BMI, with or without • Larger infants secondary to of life glucose intolerance predicts weight excessive fetal growth leads to • Colonization of the neonatal biome gain and adiposity in infant from 0- larger infant head circumferences may be due to transvaginal 12 months leading to increased number of C migration of organisms or trans- • Genes for lipid, amino acids, and section deliveries location from the maternal GI tract inflammatory pathways unregulated • Increased numbers of C sections • Obesity in pregnancy associated with maternal IR has facilitated the survival of larger with higher levels of Bacteroides, • Maternal IR causes specific defects infants and the mothers who Clostridium and Staphylococcus in maternal skeletal muscle that can produced them (associated with increased energy persist for 12 months after birth, • C section delivery is strongly harvest from diet) and lower levels increasing risk for T2DM in mother associated with childhood obesity of bifidobacterium than normal and higher risk in future • The frequency of C section births is weight pregnancies greatest in the population that is the • Intestinal colonization of infants most inactive, sedentary and obese delivered by C section closely related to maternal skin microbes, vs vaginally delivered infants, which resemble vaginal microbes

Exposure to Environmental Toxins Postnatal Exposures (First 1000 days)

• Microbes associated with low dose • Bottle fed penicillin exposure can induce • Early introduction of complementary obese phenotype foods • Nutrients i.e. Folate, methionine, • Maternal and paternal diets high in choline, betaine, vitamin B12 can CHOs, low in fruits and vegetables change DNA methylation status • Coercive feeding or reward feeding • Bioactive food components • Poor parental role models (curcumin, genistein, retinoic acid) • Inappropriate amount of sleep and can cause micro RNAs to down physical activity regulate target RNA

Childhood Exposure to Antibiotics Epidemiological Evidence Microbiota Modification

• 33% of pregnancies • Antibiotic mediated promotion of • Germ free animals (no • 45% of neonates exposed in growth in animals widely microbiota) require 30% more prenatal period practiced calories to maintain their body • Mothers with overweight more • Effect on children: greater if mass likely to receive antibiotics prescribed before 6 months of • Gut microbiota allow host to • Antibiotic treatment highest with age, boys > girls, higher digest otherwise indigestible C section cumulative orders associated complex plant polysaccharides to with progressive weight gain monosaccharides and short • 88% of premature and low birth chain fatty acids weight • Antibiotic use increases height by 0.04 cm per month and weight by • Animals in overweight category • By age 2, 3 antibiotic courses 23.8 g/month compared to have a 50% reduction in • By age 10, 10 courses placebo Bacteroides and a proportional • By age 20, 17 courses increase in Firmicutes • Also exposed through the food • Antibiotics change the milieu, chain disrupt immune defenses at the intestinal border, resulting in increased inflammatory and metabolic disorders

Effects on Mitochondria Effect on the Microbiome Circumstantial Evidence

• Antibiotics both decrease • Early exposure is • Strong association in the number of associated with resistance meta-analyses for the mitochondria and impair developing in probiotic association between their function microorganisms antibiotic exposure in early • Mitochondria are important • Intestinal microbiota life and childhood in maintaining energy exposed to antibiotics adiposity metabolism show reduced diversity • Strong dose-response • Evidence suggests that • Data from animal studies relationship between antibiotics cause shows antibiotic induced antibiotic exposure and mutations in the changes in gut microbiota childhood adiposity mitochondrial genome can result in fat • Mitochondrial genome accumulation by changing shares common pathways host metabolism with bacteria

Incidence and Impact of Breast Feeding Complementary Feeding Physical Associations Activity • 18% of pregnancies • GDM infants fed milk from • Associated with an increase in • Physical activity • Glycemic status of the mother biological mothers during 1st week protein intake from 5% (breast milk) levels are similar usually returns to normal by of life had higher body weight at 2 to 25% of diet among non GDM day 15 postpartum years of age than GDM infants fed • Higher protein intake in early life and GDM • Being born to a mother with donor milk from non GDM women associated with higher BMI at 2 children but the both GDM and overweight indicating that 1st week of life is years impact of similar has the highest risk for critical period for nutritional • Added sugar intake enhances amounts of childhood obesity programming preference for sweet foods activity on a high • Maternal hyperglycemia  Possibly due to breast milk • Early complementary feeding (<13 risk population is leads to fetal composition that is altered weeks) associated with greater unknown hyperinsulinemia which by glycemic status but caloric intake at 22 weeks increases fetal growth and normalizes through time • Early complementary feeding not birth weight • Hispanic low income children known to be different in non GDM • Higher birth weight strongly exposed to GDM required breast vs GDM infants but may associated with childhood feeding duration of >12 months to exacerbate already elevated risk obesity reduce obesity prevalence for childhood obesity

Weight Assessment by Age Group and Disease Severity

Weight Assessment for Children ages 0-2 years

BMI percentile in Children Ages 2-20 years

BMI for Children with Severe Obesity Ages 2-20 years

Measurement Tool

. Growth charts for infants . are available through the BMI is not used CDC and the WHO until 2 years of age . CDC is based on a cohort of mostly . To assess weight white American children, mostly non status in an infant, breast fed use weight for . WHO is based on length children from diverse racial and ethnic backgrounds, mostly breast fed

Body Mass Index Percentile Ages 2 to 20 Years

Underweight Healthy Weight Overweight Obesity Severe Obesity < 5th percentile 5-84th percentile 85-94th 95-99th BMI > 120th% of th percentile percentile or BMI the 95 percentile or BMI > 35 kg/m2 > 30

Caveat: Not all patients with BMI 85% or above have excess adiposity, and many children and adolescents with BMI < 5% are healthy and do not need treatment. The CDC recommends using the WHO growth charts to monitor growth for infants and children ages 0 to 2 years of age in the U.S. and using the CDC growth charts for children age 2 years and older.

Indications Definition BMI z Score • System to express severe obesity • Expanded definition of severe • BMI z score should not be used to in youth as a percentage above obesity includes Class I, II, and III assess BMI changes among the 95th percentile obesity children with BMIs > 120% of the • Statistically: unsmoothed 99th • Class I obesity (>95th percentile 95th percentile percentile similar to 120% of the to <120% of the 95th percentile) • High BMI z scores are 95th percentile of BMI for age • Class II obesity (>120% to compressed into a narrow range, • 2012, new growth charts created <140% of the 95th percentile) or which can result in a clinically to augment Centers for Disease a BMI > 35 to < 39, whichever significant reduction in BMI being Control & Prevention (CDC) lower represented by a small reduction charts allowing clinicians to track • Class III obesity (>140% of the in BMI z score and visualize BMI values in 95th percentile) or BMI > 40, • Changes in the % of the 95th children with severe obesity over whichever lower. percentile is the preferred metric th the 99 percentile. • Class I obesity = 95th-99th to use in the management of • These growth charts define a percentile or Obesity children with severe obesity child/adolescent’s BMI as a th • The same BMI z value maps to th • Class II & III = > 99 percentile “percentage of the 95 or Severe Obesity substantially different levels of percentile”(%BMIp95) %BMIp95 depending on age and sex

Definition As Compared To Adult Recommendations

2 • BMI ≥ 120 % of the 95th • The inclusion of an • BMI 35 kg/m is a higher th absolute BMI threshold threshold than BMI percentile (1.2 x 95 2 percentile) (35 kg/m ) aligns the ≥120% of the 95th pediatric definition with percentile among most or class II obesity in adults, children, but it is a • An absolute BMI ≥35 a high-risk category of somewhat lower kg/m2, whichever is obesity associated with threshold (and therefore lower based on age early mortality in adults expands the population and sex that is categorized as severely obese) among boys ≈18 years and older and girls ≈16 years and older.

Endocrine/Immune Physical Psychological Response Response Response

Adiposopathy Fat Mass Disease Quality of Life - Impaired fasting glucose -Asthma - Isolation from peers - Metabolic Syndrome - Immobility - Decrease in ability to - Hypertension - Lipomastia participate in normal childhood - Menstrual Dysfunction (girls) - Tissue Compression (sleep activities - Early Puberty (girls) apnea, GERD, HTN) - Subject to bullying - Delayed Puberty (boys) - Lack of social/age - NAFLD - Tissue Friction (intertrigo) - Stress on weight-bearing appropriate relationships - Dyslipidemia - Anxiety/depression - Insulin Resistance joints - Slipped capital femoral - Binge eating disorder - Type 2 DM - Night eating disorder - Increased uric acid, epiphysis, Blount’s disease, - Bulimia microalbuminuria scoliosis, osteoarthritis) - Gynecomastia - Cholecystitis

Linear growth in pre-pubertal and pubertal children Developmental delay; suspect syndromal obesity Consistent or accelerated linear growth Decreased linear growth - Can be associated with decreased linear growth - Evaluation dependent on presentation and family history - Consider exogenous obesity; - Consider endocrinopathy - Refer to genetics nutritional origin - Test for TSH, Free T4, - Consider precocious puberty if dexamethasone suppression secondary sexual development at test, 24-hour urinary free < 8 yrs. for girls (breast development) cortisol if indicated and < 9 yrs. for boys (enlarged testicular size) - Consider bone age

Symptoms Related Co-Morbidity Nervousness, school avoidance, social Depression, anxiety, bullying inhibitions Fatigue, Muscle aches Vitamin D deficiency Polyuria, polydipsia, fatigue, nocturia Type 2 Diabetes (T2DM)

Headaches, facial numbness Idiopathic Intracranial Hypertension (Pseudotumor cerebri) Skin pigmenting, skin tags Insulin resistance (IR) Daytime somnolence, loud snoring, witnessed Obstructive sleep apnea(OSA) apnea Abdominal pain, indigestion Gastroesophageal reflux disease (GERD), gall bladder disease, constipation Hip or knee pain Slipped capital femoral epiphysis (SCFE), early osteoarthritis In-toeing, leg bowing, mild knee pain Blount’s disease

Family History/Prenatal Feeding Miscellaneous Factors

• Maternal/Paternal • Duration of exclusive • Amount of screen time obesity breast feeding • Juice • Gestational DM/Weight • Timing of early gain introduction of • Sugar Sweetened complementary foods Beverages • Siblings with obesity • Early introduction of • Sleep duration • Birth Weight (small or cereal (<6 months of large for gestational age age)

• Family Hx of Early CVD

Toddler Early Childhood Puberty Adolescent (Age 1-4) (Age 5-9 years) (Age 10-14 years) (Age 15-18 years years)

Exercise Active Play Vigorous Exercise for 60 min or more every day Feeding Food as reward or Family Meals Modified meals or punishment Eating out pack lunch Diversity in diet Fast food/Sugar Continue to Sweetened challenge Beverages vegetables and fruits Miscellaneous Screen time Bullying Sedentary Time Snoring Parents as role Sleep Duration models

Infancy Toddler Early Childhood Puberty Adolescent (0-24 months) (Age 2-4 years) (Age 5-9 years) (Age 10-14 years) (Age 15-18 years)

Weight>Length BMI > 95th percentile BMI > 95th percentile BMI > 95th percentile BMI > 95th percentile Or Or Or Or > 85th percentile with 2 or > 85th percentile with 2 > 85th percentile with 2 > 85th percentile with 2 more risk factors (24-48 or more risk factors or more risk factors or more risk factors months)

- Fasting Blood Glucose and/or HbA1c - Fasting Lipid Panel/Non fasting if fasting not feasible - ALT, AST, consider GGT - Consider 25 OH Vitamin D - Consider Sleep Study - Consider Liver Ultrasound - Consider Uric Acid - Consider fasting serum insulin - Consider Urine Microalbumin/Creatinine ratio - Consider C-peptide, hs-CRP

Gynecomastia

Tonsillar Hypertrophy Steatosis and Increased Abdominal Visceral Fat

Increased echogenicity

VF 5.43 cm

Pictures taken with consent of patients Blount’s Disease

Birth- 4 months 4-6 months 6-8 months 8-10 months 10-12 months

Breast milk and/or 8 to 12 feedings 4 to 6 feedings 3 to 5 feedings 3 to 4 feedings 3 to 4 feedings fortified infant formula *2 to 6oz per feeding *4 to 6oz per feeding *6 to 8oz per feeding *7 to 8oz per feeding *24-32oz per day (18-32oz per day) (27-45oz per day) (24-32oz per day) (24-32oz per day) Cereal, breads, None None 2-3 servings of iron- 2-3 servings of iron- 4 servings of iron-fortified starches fortified baby cereal fortified baby cereal bread or other soft (serving= 1 to 2 Tbsp) (serving= 1 to 2 Tbsp) starches or baby cereal (serving= 1 to 2 Tbsp) Fruits and Vegetables None None Offer plain, cooked, 2-3 servings (1 to 2 4 servings (2 to 3 Tbsp) mashed, or strained Tbsp) of soft, cut-up, daily of fruits and baby foods and mashed vegetables. No juice. vegetables and fruits. vegetables and fruits Avoid combination daily. No juice. foods. No juice. Meats and Other None None Begin to offer plain- Begin to offer well 1 to 2oz daily of soft, Protein Sources cooked meats. Avoid cooked, soft, finely finely cut or chopped combination dinners. chopped meats. meat or other protein foods

While there is no comprehensive research indication which complimentary foods is best to introduce first, focus should be on first foods that are higher in iron and zinc such as pureed meats and fortified-iron rich foods.

12-23 months 2-3 years 3-4 years Milk and Milk Products 2 cups/day (whole milk or milk 2 to 2.5 cups/day 2.5-3 cups/day products) Serving: 1 cup of milk or cheese, 1 ½ oz of natural cheese, 1/3 cup shredded cheese Meat and Other Protein Foods 1 ½ oz/day 2oz/day 2-3oz/day

Serving: (1oz equivalent) = 1oz beef, poultry, fish, ¼ cup cooked beans, 1 egg, 1Tbsp peanut butter*, ½ oz of nuts* *peanut butter and nuts may be a choking hazard under the age of three

Breads, Cereal, and Starches 2 oz/day 2 oz/day 2-3 oz/day

1 oz = 1 slice whole grain bread, ½ cup cooked cereal, rice, pasta or 1 cup dry cereal Fruits 1 cup/day 1 cup/day 1-1 ½ cups/day Serving: 1 cup of fruit or ½ cup dried fruit; NO JUICE Vegetables 3/4 cup/day 1 cup /day 1-1 ½ cups/day (non-starchy vegetables to include sources of vitamin C and A) Serving: (1 cup equivalent) = 1 cup of raw or cooked vegetables; 2 cups of raw leafy green greens Fats and Oil Do not limit* 3 teaspoons 3-4 teaspoons/day *Low-fat products are not recommended under the age of 2 Miscellaneous none none none desserts, sweets, soft drinks, candy, jams, jelly

5-9 years 10-14 years 15-18 years

Milk and Milk Products 2.5-3 cup/day 3 cups/day 3 cups/day

Serving: 1 cup of milk or cheese, 1 ½ oz of natural cheese, 1/3 cup shredded cheese; encourage low-fat dairy sources Meat and Other Protein Foods 4-5oz/day 5oz/day 5-6oz/day

Serving: (1oz equivalent) = 1oz beef, poultry, fish, ¼ cup cooked beans, 1 egg, 1Tbsp peanut butter*, ½ oz of nuts

Breads, Cereal, and Starches 5-6oz/day 5-6oz/day 6-7oz/day Fruits 1 ½ cups/day 1 ½ cups/day 1 ½- 2 cups Serving: 1 cup of fruit or ½ cup dried fruit Vegetables 1 ½ -2 cups/day 2-3 cups/day 3+ cups/day (non-starchy vegetables to include sources of vitamin C and A: broccoli, bell pepper, tomatoes, spinach, green beans, squash) Serving: (1 cup equivalent)= 1 cup of raw or cooked vegetables; 2 cups of raw leafy green greens Fats and Oil 4-5 tsp/day 5 tsp/day 5-6 tsp//day Miscellaneous none none none desserts, sweets, soft drinks, candy, jams, jelly

Background Health Impact Screening Tool/Recommendations •21% of children meet USDA •Depression, anxiety, toxic stress •Screening Tool definition of FI • 4-36 months: high risk for •Hunger Vital Sign: •7.5 million American families lack developmental problems. •1. Within the past 12 months, we consistent access to adequate, • FI •More likely to be iron deficient (Yes or No) •Poverty, un/under employment not •Pre-Adolescent boys: lower bone •2. Within the past 12 months, the food only factors density we bought just didn’t last and we didn’t have money to get more. (Yes or No) •Greater risk: children in immigrant •Lower cognitive indicators, families, families headed by single dysregulated behavior, emotional women, less education, large distress •Recommendations families, parental separation or •Adolescents: higher risk for dysthymia •1.Screen for FI with 2 question divorce. /suicidal ideation. validated tool •16% of low-income households do •Health effects of FI may persist beyond •2.Be familiar with community, state, not receive federal support early life into adulthood. Including: DM, and federal resources hyperlipidemia, and CV disease. •Poverty associated with obesity. •3.Be aware of nutritional content of •Environmental realities: presence of these resources •FI disproportionately threatens full grocery, increased fast food. •4.Be aware of factors that increase certain populations at high risk for Intermittent access to adequate food – vulnerability for FI obesity. results in unhealthy eating patterns •5.Advocate and increased stress

For a list of resources see Appendix B SNAP = Supplemental Nutrition Assistance Program; Reference/s: [30] [31] [32] [33] [34] [35] 46 WIC = Special Supplemental Nutrition Program for Women, Infants, and Children [36] [37] [38] [39] [40] [41] [42] [43] [44] Pediatric Obesity Algorithm®. ©2018-2020 Obesity Medicine Association. Management

Portion Control CHO Restricted Low Glycemic Low Fat or Balanced or Reduced Index Elimination • Tolerance is high • Adherence to • Tolerance is high • Tolerance is high • Used mostly in • Useful in diet is • Small amount of • Limited trials: in 3 fast food or toddlers and approximately weight loss RCT small reduction cafeteria type young children 50% • Decreases in BMI, total and LDL settings • Small amount of • Weight loss is postprandial Cholesterol • No clear weight loss moderate to glucose • No weight loss or evidence for good response, slows minimal effectiveness • Lowers fasting insulin secretion, • No difference • Weight loss is insulin and and delays between low fat & low small to triglyceride gastric emptying glycemic in reduction moderate levels leading to longer of steatosis • Tolerance is high • Amount of satiety • Not same as protein is not • Favorable for elimination diets associated with high fasting for food effect on muscle insulin level allergies/intolera sparing nce

• Current evidence suggests that improved weight status can be achieved in children and adolescents with overweight or obesity irrespective of the macronutrient distribution of a reduced-energy diet.

• Tailoring the macronutrient content to target specific cardio-metabolic risk factors, such as a low-carbohydrate diet to treat insulin resistance, may be possible.

• No screen time • Exclusive breastfeeding for 6-12 • No TV in bedroom months • Allow infant to feed themselves • Appropriate formula feeding • Do not force/finish foods when infant ingestion for age indicating refusal Behavior • Delay complementary foods until 6 • 12-18 Hours of sleep Intake months and Sleep • No juice/sugar sweetened beverages • No fast food • No desserts

Activity • Keep active in playpen/floor • Encourage direct interaction with parents as much as possible • No media

Weight/length percentile Weight/length percentile Weight/length percentile Weight/length percentile appropriate crossing lines exceeding 85th for age exceeding 95th for age • Exclusive breast • Exclusive breast • Exclusive breast • Exclusive breast feeding for as long as feeding for as long as feeding for as long as feeding for as long as possible, possible possible possible complementary foods • If formula feeding, • If formula feeding, • If formula feeding, at 6 months review dietary history, reduce intake to lower reduce intake to lower • No media if no complementary limits, 24 oz/day, limits, 24 oz/day, 3 foods, intake 27-47 feedings should be times per day, minimal oz/day, if every 4-5 hours for < 6 intake of complementary foods months, 3 times per complementary food (after 6 months of age) day for > 6 months. after 6 months of age, intake 24-32oz/day Review appropriate consider excluding • No media intake of cereal complementary foods • No media after 6 months of age, consider limiting cereal • No media

• Routine sleep pattern • No TV in bedroom • 11-14 hours of sleep • All meals at the table/highchair • Three meals plus snack(s) • Parents as role models • 3 servings of protein (1-3oz)/day • Food not used as reward Behavior • 2-2.5 cups dairy/day • Parents should not be over controlling Intake and Sleep • 3 servings non-starchy vegetables • Family Based Therapy (3/4 cup to 1 ½ cups)/day • Fruit 1 cup /day • Dessert only on special occasion • No sugar sweetened beverages • No fast food Activity • Age appropriate portion sizes • Praise for trying new foods • Active play almost constantly • Minimal sedentary time • No screen time < 2 years, < 1 hour/day 2-4 years

BMI < 85th BMI 85th-95th BMI 95th-120th BMI > 120th percentile percentile percentile percentile

• 1-1.5 cups each of • 1-1.5 cups each of • Restricted CHO/LGI • Restricted fruits and fruits and • <1 hour of screen CHO*/LGI** vegetables/day vegetables/day time/day • Screen time 50% of • <2 hours screen • 1-2 hours of screen • Reduce sedentary active time up to 1 time/day if 2-4 years time/day if 2-4 years activity hour/day • Free play for as many • Free play for as many • Free play for as many • Reduce sedentary hours as possible/day hours as possible/day hours as possible/day activity • No sugar sweetened • No sugar sweetened • No sugar sweetened • Free play for as many beverages beverages beverages hours as possible/day • No sugar sweetened beverages

• Minimize obesogenic • Three meals; 1-2 snacks medications especially SGAs* • 3 servings of protein/day • Treat asthma with controller • 2-3 servings of dairy/day meds to minimize systemic • 4-5 servings non-starchy steroid use vegetables Pharmac- Intake • Consider ACE inhibitor for ology • Dessert only on special occasion persistent hypertension • No sugar sweetened beverages • No fast food • Age appropriate portion sizes • Praise for trying new foods • Screen time <1-2 hours Behavior • Consider low glycemic Activity • Routine sleep pattern and Sleep index/reduced carbohydrate diet • No TV in bedroom • 11-14 hours of sleep • All meals at the table • Moderate - vigorous activity for 60 • Parents as role models minutes or greater each day; Can • Parenting style should not be overly controlling be organized or not • Sleep study if severe obesity and/or symptoms • Tonsillectomy and adenoidectomy if indicated

BMI < 85th BMI 85th-95th BMI 95-120th BMI >120th percentile percentile percentile percentile

• 1.5-2 cups of fruits • 1.5-2 cups each of • Restricted CHO/LGI • Restricted CHO/LGI and 3+ cups fruits and 3+ cups • < 1 hour of screen • Screen time 50% of vegetables /day vegetables/day time/day active time up to 1 • < 2 hours screen • < 1-2 hours of screen • Reduce sedentary hour/day time/day time/day activity • Reduce sedentary • At least 60 min of • At least 60 min of • At least 60 min of activity age appropriate age appropriate age appropriate • At least 60 min of activity/day activity/day activity /day age appropriate • No sugar sweetened • No sugar sweetened • No sugar sweetened activity /day beverages beverages beverages • No sugar sweetened beverages

• Orlistat (Xenical) FDA approved for • 3 meals; 1-2 nutritious snacks > age 12 • 3 servings of protein/day • Minimize obesogenic medications • 3 servings of dairy/day especially SGAs • 4-5 servings of non-starchy vegetables • Treat asthma with controller meds • Dessert only on special occasion to minimize systemic steroid use • No sugar sweetened beverages • Consider ACE inhibitor for Pharmac- Intake • No fast food persistent hypertension ology • Age-appropriate portion sizes • Metformin FDA approved for T2DM • Allow child to leave food on plate > age 10

• Screen time less than 1-2 hours/day • 10-12 hours of sleep Behavior • Vigorous activity for 60 minutes or • Routine sleep pattern Activity more daily. Can be organized or not and Sleep • No TV in bedroom • Monitor for changes in decreased • Parenting style should not be overly activity level controlling • Decrease non academic sedentary • Peer groups become increasing important time as much as possible • All meals at table with family and encourage socialization • Recommend meal and exercising tracking

• Orlistat (Xenical) > age 12, • 3 meals; nutritious snacks Phentermine approved for > age 16 • 3 servings of protein/day • Minimize obesogenic medications • 3 servings of dairy/day especially SGAs* • 4-5 servings of non-starchy • Treat asthma with controller meds vegetables to minimize systemic steroid use • Dessert only on special occasion Pharmac- Intake • Consider ACE inhibitor for ology • No sugar sweetened beverages persistent hypertension • No fast food • Metformin FDA approved for T2DM • Age-appropriate portion sizes > age 10 • Allow adolescent to leave food on plate • Screen time less than one hour/day Behavior Activity • 10-12 hours of sleep and Sleep • Vigorous activity for 60-90 minutes • Routine sleep pattern or more daily • No TV in bedroom • Planned intervention with structured • Parenting style should not be overly physical activity controlling • Decrease non academic sedentary • Friends and relationships are important time as much as possible • Recommend meal/exercising tracking or monitoring

Infants (0-12 months) Toddlers (12-36 months) Young Children (3-5 yrs) Older Children (5-12 yrs)

•Interaction with caregivers •30 minutes of structured •60 minutes of structured •60 minutes, and up to several dedicated to exploring physical activity each day. physical activity each day. hours, of age-appropriate movement and the •At least 60 minutes per day •At least 60 minutes of physical activity on all, or most environment of unstructured physical unstructured physical activity days. •Setting that encourages and activity •Opportunity to develop •Should include moderate and stimulates movement •Opportunity to develop fundamental motor skills that vigorous physical activity with experiences and active play the majority of the time spent movement skills that will will serve as the building in activity that is intermittent for short periods of time serve as the building blocks blocks for future motor several times a day for future motor skillfulness skillfulness and physical •Several bouts of physical •Promote skill development in and physical activity activity activity lasting 15 minutes or more each day. movement •Access to indoor and •Access to indoor and •Should participate each day in •Environment should meet or outdoor areas for performing outdoor areas for performing a variety of age-appropriate exceed recommended safety large-muscle activities large-muscle activities physical activities designed to standards for performing •Caretakers should promote •Caregivers should promote achieve optimal health, large-muscle activities movement skills by providing movement skills by providing wellness, fitness, and •Structured and unstructured activity and physical opportunities for structured performance benefits. physical activity movement experiences and unstructured physical •Extended periods (two hours activity or more) of inactivity are discouraged, especially during the daytime hours.

9-13 Years 14-18 Years Aerobic/Endurance Vigorous intensity: Running Running Bicycle riding Dancing Sports: soccer or swimming Swimming Bicycle riding

Bone-Building Basketball Running Tennis Jumping Running

Muscle Strengthening Push-ups Use of free-weights of 15-20 pounds with Use of resistance bands high repetitions

Active Play Football Yoga Basketball Dance Ice Hockey Running Volleyball Walking Individual sports: Cycling Tennis Household chores Track & Field Competitive or noncompetitive sport Running Swimming Dance

Prevalence/Diagnosis Evaluation Treatment

Prevalence •Ambulatory blood pressure monitoring • Primary treatment is weight loss: Diet and • 3.8-24.8% of adolescents with obesity have HTN recommended due to prevalence of white lifestyle interventions before medication • 2 fold increase BMI 95-98th %ile coat HTN and masked HTN • Low Na (<1500 mg/day) or DASH diet • 4 fold increase BMI >99th %ile •Screen for glucose intolerance and • For Stage 1 HTN lifestyle intervention for 6-12 • Three separate measurements at least one week months apart dyslipidemia • Physical activity beneficial: moderate to •Sleep history vigorous, 30-60 min 5 days or more a week Diagnosis •Further studies not necessary unless • < 13 years use normative data (slide xxx) • Restrict only Stage 2 from high static • Elevated BP = avg sys and dia BP > 90th and < 95th history of chronic kidney disease or other competition until BP is controlled percentile renal disorders • Pharmacotherapy if Stage 1 not controlled after • Hypertension = avg sys and dia BP > 95th percentile •If unresponsive to lifestyle intervention, 12 months or symptomatic or Stage 2 in on repeated obtain ECHO prior to starting medication combination with lifestyle intervention •If there is a possible secondary cause, • Pharmacotherapy • > 13 years • Begin with single agent at the low end of the • Elevated BP = sys 120-129 mm Hg, dia < 80 mm Hg consider renal US, electrolytes, CBC, creatinine, renin and aldosterone dosing range • Stage 1 Hypertension = sys > 130--139 mm Hg, dia • ACE inhibitor, Angiotensin II Receptor Blocker, 80-89 mm Hg Ca Channel Blocker or thiazide diuretic • Stage 2 Hypertension = > 140/90 mm Hg • Increase dose every 2-4 weeks until BP is • Obesity associated with increased risk for normalized • Masked HTN (Clinic BP <95th percentile but • Thiazide diuretic is usually the second agent ambulatory BP >95th percentile) • Circadian variability: up to 50% do not experience the expected nocturnal BP dip

62 Reference/s: [60] [61] [62] Pediatric Obesity Algorithm®. ©2018-2020 Obesity Medicine Association. [63] [64] New (2017) Clinical Practice Guideline (CPG) for Screening and Management of HTN and Children with Obesity

Issues Associations between HTN General Guidelines and Children with Obesity • New normative data was based on •Associations between children with •Diet and lifestyle interventions are the normal weight children, thus the obesity and HTN include cornerstone, but 7% of children with cut off values for the categories of •Graded increase in rate of HTN with elevated BP progress to HTN “elevated or >90th percentile, Stage increasing waist circumference •Children with obesity and HTN can 1 or >95th percentile, and Stage 2 •Lack of circadian variability of blood participate in competitive sports once or >95th percentile + 12 mm Hg pressure target levels for BP are reached are lower than older CPGs •Up to 50% do not experience the (normative values) •Children with obesity and Stage 2 HTN • Problem: The proportion of children expected nocturnal dip •Development of HTN as an adult should be restricted from high static with obesity and HTN is now higher sports (wrestling, weight lifting, boxing) based on the lowering of the •Acute, severe HTN requires immediate normative values •HTN in children with obesity is frequently accompanied by evaluation dyslipidemia and disordered glucose •Ambulatory blood pressure monitoring metabolism, all of which contribute to can be an objective method to evaluate greater increases in CV risk treatment •Severe OSA is commonly associated with HTN in children with obesity

BP, mm Hg Boys Girls Age Systolic Diastolic Systolic Diastolic 1 98 52 98 54 2 100 55 101 58 3 101 58 102 60 4 102 60 103 62 5 103 63 104 64 6 105 66 105 67 7 106 68 106 68 8 107 69 107 69 9 107 70 108 71 10 108 72 109 72 11 110 74 111 74 12 113 75 114 75 >13 120 80 120 80

Diagnosis Evaluation Treatment Clinical Finding

• IIH is also known as • Idiopathic intracranial • Preserving vision and One study in 606 adults with pseudotumor cerebri (PTC), hypertension (IIH) is defined controlling symptoms are obesity: benign intracranial as elevated intracranial the goals of therapy • incidence of 2.8% with hypertension (BIH), and pressure without clinical, • Variable response to all abnormalities on non- pseudotumor cerebri radiological or laboratory therapies. mydriatic fundus syndrome. evidence of a cause. • Ventricular/lumbar photographs • IIH can lead to permanent • Full neurological peritoneal shunts may lower • 0.6% incidence of visual impairment or examination usually with intracranial pressure, asymptomatic optic disc blindness. imaging and spinal tap preserve vision, and relieve edema • A strong association • Full eye examination for other symptoms. • Headaches, visual loss, between childhood obesity papilledema or loss of visual • Some case reports of including blind spots, poor and increased risk of field success with weight loss peripheral (side) vision, pediatric IIH. after RYGB. double vision, and short • The incidence of IIH in • Loss of as little as 6% of temporary episodes of youth with obesity is lower body weight has been noted blindness. in prepubertal children than to reduce intracranial in adolescents. pressure.

Definition Things to Follow Things to Avoid

• Sleep hygiene is a variety of • Keep bedtimes and wake times consistent • High stimulation activities just different practices and habits every day of the week. Late weekend nights or before bed, such as watching TV, that are necessary to have sleeping-in can throw off a sleep schedule for or playing video games good nighttime sleep quality days. • Spending lots of non-sleep time in and full daytime alertness. • Bedtime should follow a predictable sequence bed. This also includes if a child is of events, such as brushing teeth and reading awake in bed tossing and turning: a story. get out of bed to do a low • Having physical exercise early in the day can stimulation activity (e.g., reading), help with sleep time. then return to bed later. • Worry time should not be at bedtime. Children • Intake of caffeine (sodas, with this problem can try having a “worry time” chocolate, tea, coffee) in the scheduled earlier to think about and discuss afternoons/evenings. their worries with a parent. • For the best night’s sleep, most • Security objects at bedtime are often helpful people should avoid strenuous for children who need a transition to feel safe. workouts close to bedtime. • When checking on a child at night, checks should be “brief and boring.”

National Sleep Foundation (hours) Not Recommended (hours)* Newborn 14-17 < 11 or >19 Infants 12-15 < 10 or >18 Toddler 11-14 < 9 or > 16 Preschool 10-13 < 8 or > 14 School-Aged 9-11 < 7 or > 12 Teenager 8-10 < 7 or > 11 Young Adult 7-9 < 7 or > 9 Adult 7-9 < 7 or > 9

Older Adult (+ 65) 7-8 < 7 or > 8

Diagnosis Evaluation Treatment Clinical Findings

• Prevalence : 3-16% • Sleep study if severe to • Sleep hygiene • Decrease in mean verbal IQ scores, global IQ Primary • Snoring without apnea or rule/out apnea or counseling scores, selective attention scores, sustained Snoring hypopnea, hypercapnia, hypopnea, hypercapnia, attention scores, memory index . hypoxemia, high arousal hypoxemia, high arousal • Direct correlation between number of mild index, disruption of normal index, disruption of desaturations (3%)/arousals & severity of sleep architecture or normal sleep neurocognitive deficits daytime symptoms • Characterized as benign; linked to neuropsychological impairments.

Restless • Insomnia with “creepy or • Diagnosis of exclusion • Sleep hygiene • Autosomal dominant, sensorimotor disorder leg crawling” feeling in the • No single test can counseling • 2/3 of children may have low levels of serum ferritin; syndrome arms and legs at night diagnose RLS • Dopamine agonists iron is a cofactor in synthesis of dopamine. (RLS) • Insomnia accompanied by • Low iron levels are • Oral iron • Restless legs syndrome and attention deficit an urge to move the limbs suggestive • Clonazepam disorder are associated. • EMG and possible muscle • Gabapentin • Interferes with going to sleep and staying asleep biopsy to rule out other • May be accompanied by daytime fatigue, neuro-muscular disease inattentiveness, or frank sleepiness. • Dopamine deficiency implicated in the pathogenesis

Diagnosis Evaluation Treatment Clinical Findings

Delayed Sleep • Habitually unable to fall asleep • History of circadian • “Bright light” therapy: • Habitually unable to fall asleep before 2-3 am Phase before 2-3 am sleep pattern provide 2700-10 000 lux of • Prefer to wake in the late morning or early afternoon. . Syndrome • Neurological sleep disorder in which • Perform sleep logs bright light via a light box for • Higher likelihood of HLA DR1 and the occasional familial a person's sleep/wake cycle is and wrist 20-30 minutes immediately clustering of delayed sleep phase syndrome suggest a delayed with respect to the external actigraphy after waking leading to a genetic predisposition. day/night cycle • Evaluate for gradual phase • Delayed sleep phase syndrome linked to polymorphisms • Normal sleep if sleeps freely but secondary effects advancement (shifting back) in Period gene.15. very sleepy if conforming to of chronically poor of the sleep onset time at • Onset: typically adolescence, boys>girls conventional sleep-wake schedules. sleep night. . • 0.5-1 mg melatonin about 5.5 hours before sleep onset • Stimulant drugs to counter residual daytime sleepiness

Obesity • Awake chronic hypercapnia (PaCO2 • Evaluate for • Weight loss • May have central respiratory control system abnormality Hypoventilation >45 mm Hg) + Obesity concurrent OSA • Respiratory support as with decreased responsiveness to CO2 rebreathing, Syndrome • Excessive work of breathing and (90% chance) indicated, including CPAP hypoxia, or both. increased CO2 production • Sleep study:O2 • Inspiratory muscle strength and resting tidal volumes • Abnormal central ventilatory drive Sats, CO2 levels, decreased and obesity and apnea • Leptin deficiency/resistance may contribute to OHS by • Other disorders should be ruled out episodes reducing ventilatory responsiveness leading to CO2 Also known as Pickwickian • Cardiac and retention. Syndrome pulmonary work up • Pulmonary HTN more common & severe than in OSA. if symptomatic

Diagnosis Evaluation Treatment Clinical Finding

• Upper airway becomes • Sleep study • Tonsillectomy and History: blocked repeatedly • AHI 1-1.5 mild adenoidectomy (T&A) if • Snoring or disrupted during sleep, reducing • AHI 1.5-5.0 indicated sleeping or completely stopping moderate • Repeat sleep study > 6- • Daytime sleepiness airflow • AHI > 5.0 severe 8 weeks post op • Hyperactivity • OSA may be a cause of • Evaluation by ENT for • Weight loss (other • Audible pauses in obesity and not a obstruction recommended breathing consequence alone • Titration of O2 treatment should be • Nocturia saturation used pending weight • Consider EKG/ECHO loss) • Consider Ferritin level • Routine sleep pattern • Assess blood pressure, features of metabolic syndrome which in combination with OSA increase CV risk

Diagnosis Evaluation Treatment Clinical Findings • HbA1c > 5.7% but < 6.5% • Fasting blood glucose • Restricted carbohydrate • Reversible intermediate x 2 measurements • Consider fasting insulin, diet phase of altered glucose • FBG >100 mg/dl but may be falsely low if • Adolescent studies have metabolism in < 126 mg/dl on repeat disease severe or mildly shown increase in insulin progression from normal measurements elevated during pubertal sensitivity with intensive glucose tolerance to (impaired fasting glucose) growth spurt diet and exercise induced T2DM • 2 hour oral glucose • 2 hour OGTT weight loss tolerance test (OGTT) for • Major clinical predictors of • Consider Metformin for • Acanthosis nigricans, blood glucose >140 mg/dl prediabetes to type 2 HbA1c > 5.8% when hyperpigmentation in but < 200 mg/dl (impaired diabetes mellitus (T2DM) compliant with diet axillae, umbilicus, groin, glucose tolerance) progression: severe popliteal fossae obesity, impaired glucose • Skin tags tolerance, and ethnicity • High risk ethnic groups include African Americans, Mexican Americans, Native Hawaiians, American Indians, Pacific Islanders and Asian Americans

Diagnosis Evaluation Treatment Pharmacology • Although any dyslipidemia • Fasting lipid profile every 3-6 • Weight loss: Aggressive diet • The dyslipidemia of obesity is can co-exist with obesity, months if abnormal and lifestyle intervention not usually treated with obesity is directly associated • May monitor with non fasting • Restricted medication but the following with: TG >100 mg/dl if <10 lipid profile if more feasible CHO/LGI/Elimination diet applies to other dyslipidemias yrs, > 130 mg/dl if >10 yrs or • Family history of premature • Decreased saturated fat diet which may co-exist with the HDL <50 mg/dl if female, <40 cardiovascular disease (May for LDL >130 mg/dl dyslipidemia of obesity mg/dl if male help differentiate dyslipidemia • HDL may increase with • Statin for FC or LDL > • If pattern of dyslipidemia is of obesity from heterozygous exercise, especially vigorous 190mg/dl and failure to different than high TG/low familial hypercholesterolemia) exercise respond to weight HDL, pursue work up and • Consider genetic testing for loss/phytosterols/ increased treatment per NHLBI persistent elevations of LDL fiber guidelines and consider >190 mg/dl, TG > 500 mg/dl • Phytosterols 2 grams per day referral to Lipidologist to achieve an LDL < 130 mg/dl • Increased fiber to 12 grams per day to achieve an LDL < 130 mg/dl • Omega-3 to 1-4 grams per day to achieve TG < 100 mg/dl

Diagnosis Evaluation Treatment • Elevated BMI: thickening of the carotid • CV damage already apparent in • Intensive lifestyle modifications intima is associated with increased BMI childhood (autopsies) • Exercise programs (aerobic and • If Metabolic Syndrome (MetS) is used as • Elevated systolic and/or diastolic blood resistance training) a predictor, individual components are pressure: > 140/90 mm Hg associated • Regular exercise over 6 mos more reliable than presence or absence with early CV disease restored endothelial function of MetS • Increased severity of obesity is and improved cIMT in children • Male sex is a risk predictor for CV correlated with increased CV risk as with obesity disease at all weight categories measured by components of the • Improved CRF associated with • MetS identifies children between 8-14 metabolic syndrome up until BMI of reduction in CVD mortality years at increased risk for T2DM and 140% of the 95th percentile when risk • Although treatment with statins and early subclinical atherosclerosis: risk is plateaus hypertensive medications in adults is 15 fold • Carotid intima-media thickness (cIMT) associated with decreased incidence • Traditional biomarkers in adults such as 0.07 mm greater in age/height matched of MI and stroke and predicted by LDLc may not be as reliable in children children with obesity vs normal weight declines in acceleration of cIMT, no • Increased LA, LV, LV mass, epicardial • Maximal or submaximal exercise testing intervention studies with medication fat associated with early CVD is a strong predictor of CVD have been done in children

Diagnostic Criteria: Diagnostic Criteria: Evaluation Treatment Modified NCEP-ATP III* International Diabetes Federation • Age 12-19 years • Central obesity + 2 risk factors • Fasting plasma glucose • Children with lifestyle • 2003 Cook criteria with • Age 10-16 years >100mg/dL intervention (physical activity, modification of fasting blood WC ≥ 90th percentile for age • Fasting lipid panel: triglycerides nutrition education, and behavior glucose (FBS) criterion to 2003 and sex; adult cut-off if lower and HDL therapy) found to have ADA criterion of > 100 mg/dl as SBP ≥ 130 or DBP ≥85 mmHg • Waist circumference (WC) significant decrease of MS abnormal. TG ≥ 150 mg/dl • Systolic (SBP) and diastolic prevalence and improvement of • The presence of any 3 of the HDL< 40 mg/dl blood pressure (DBP) blood pressure, waist following: FBS ≥ 100 mg/dl • Birth History: Metabolic circumference, and 2 hour TG ≥ 100 mg/dL • Age >16 years syndrome (MS) has been glucose values on OGTT HDL ≤ 10th percentile for WC≥94 cm for males; ≥80 cm associated with birth weight, compared to children with age and sex for females** maternal obesity, and gestational obesity without intervention. FBS ≥100mg/dL SBP ≥ 130 or DBP ≥85mmHg diabetes mellitus • Degree of weight loss (BMI SDS WC (cm) ≥ 90th percentile or previously diagnosed HTN - Children LGA at birth and reduction >0.5) associated with for ethnicity, age and sex ≥ 150 mg/dl or treatment for exposed to intrauterine improvement of prevalence of BP (mmHg) ≥ 90th percentile hypertriglyceridemia environment of diabetes or all MS components. for age, height, and sex <40 mg/dl for males; <50 mg/dl maternal obesity at increased for females or tx for low HDL risk. *NCEP-ATP III: National Cholesterol ≥ 100 mg/dl or known T2DM **Asians and Central and South American: ≥ Education Program Adult Treatment Panel 90 cm in males III

Diagnosis Diagnosis PCOS Evaluation Treatment Menstrual Irregularity • Excessive weight gain • Oligomenorrhea/ • Prolactin, estradiol, • Symptomatic and can be associated with amenorrhea and clinical consider LH/FSH individualized menstrual irregularity or biochemical • T4/TSH • Oral contraceptive pills • Irregular menses: Less hyperandrogenism with • Free testosterone, total (OCPs) is first line than 21 days or > 45 frequent presence of: testosterone, DHEA-S, treatment for most days interval, treat for > 3 obesity, glucose sex hormone binding Progestin monotherapy is month intervals or less intolerance, dyslipidemia, globulin an alternative if OCPs than 9 cycles in 12 and OSA • Early morning 17-OH are contraindicated months at gynecological • PCOS can present in progesterone • Lifestyle modification and age > 18 months and lean adolescents and • Provera challenge if dietary control HCG negative those with obesity oligomenorrhea • Consider Metformin: • Not every adolescent with • Consider pelvic US most effective in obesity and menstrual • Consider 2 hour OGTT combination with weight irregularity has PCOS loss • Hirsutism (may or may • Metformin clearly not be clinically evident) indicated for abnormal glucose tolerance

Diagnosis Evaluation Treatment Blount’s Disease • Early walking (before the age of 12 • AP and Lateral views of the tibia • Surgical correction months) in a severely obese child • Dome-shaped metaphysis, open growth plate and disruption of the continuity between the lateral borders of the epiphysis and metaphysis, with inferomedial translation of the proximal tibial epiphysis

Slipped Capital Femoral • Hip pain or limp: consider referred • AP and Lateral views of the hips • Surgical emergency (In situ Epiphysis pain to groin, knee, limb • Ultrasound pinning) • M:F = 1.5:1 • Degree of severity depends on • Intertrochanteric osteotomy • Age of onset Males = 12.7-13.5 years avascular necrosis and/or • Age of onset Females = 11.2-12 instability years

Scoliosis • Physical findings may be obscured • Shoulder height asymmetry or use • Determine whether curve is by obesity of a scoliometer in addition to the great enough to require surgery • Increased curve magnitude at traditional Adam Forward Bend (> 45 degrees) presentation Test

Diagnosis Evaluation Treatment Clinical Findings • Screen: severe obesity or • Imaging Technology: • Intensive Life Style Clinical Signs: family history NAFLD Liver Ultrasound Treatment Often asymptomatic ALT- 2X normal (NAFLD) MRI and MR • Improved diet and exercise Acanthosis nigricans ALT > 80 Nonalcoholic spectroscopy • Remove SSBs Hepatomegaly steatohepatitis (NASH) CT Scan Epidemiology: • Medications: more common Transient Elastography Most common liver • Diagnosis of exclusion (Fibroscan) • No currently available disease in US children R/o genetic/metabolic, MR Elastography medications or 40+% children with medications, dietary, Liver Biopsy : Gold supplements are obesity infections Standard recommended Male > Female • ALT • Elevated AST & GGT with • Consider: Hispanic > Caucasian Currently best screening normal ALT suggests Vitamin E & Asian > Blacks test diagnosis other than NAFLD Probiotics At Risk Population: Limitations: LFTs can be • Follow-up screening for Emerging therapies overweight and obese normal NAFLD when initial is normal: • If NAFLD, screen for OSA, insulin resistance, Persistently elevated ALT: repeat q 2-3 years if risk prediabetic, diabetic, DM,HTN, dyslipidemia further evaluation/other factors are same; sooner dyslipidemia, central causes of chronic if clinical risk factors • Liver transplant in adiposity hepatitis. increase advanced cases panhypopituitarism Family history of NAFLD and/or NASH

Reference/s: [125] [126] [127] [128] [129] [130] [131] 77 [132] [133] [134] [135] [136] [137] [138] [139] [140] Pediatric Obesity Algorithm®. ©2018-2020 Obesity Medicine Association. Behavioral Health Problems and Children with Obesity

Attention Deficit Hyperactivity Syndrome Depression

Emotional Eating Anxiety

Characteristics Associations Evaluation Treatment/Medication • Theoretical hypotheses • Difficulty in planning as a • ADHD or inattention presents • Physical activity is a mediating factor • Impulsivity and consequence of at ages 7-8 • Social play may alleviate ADHD inattention: risk factors inattentiveness often • Assess level of physical symptoms in children for weight gain and expressed by skipping activity • Address academic performance as ADHD breakfast and lunch. • Inattention is associated with ongoing poor performance is • Reward deficiency • Binge eating is one of the reduced levels of physical associated with obesity in hypothesis manifestations of impulsivity activity in childhood and adolescence • Insufficiency of • Patients with ADHD can suffer associated with obesity in • There is association of un-medicated dopamine from short sleep duration due adolescence ADHD with higher BMIs during • In children < 10 yrs, ADHD to insomnia leading to delayed • Assess for co-existing childhood compared with those associated with lower not onset of melatonin conduct disorder, an without ADHD or ADHD treated with higher BMI • ADHD is highly associated with additional risk factor stimulants. • Strongest association is other psychiatric disorders • Starting stimulants at younger age between ADHD and including seasonal depression, and longer duration associated with adolescent females but overall anxiety. slower BMI growth earlier in effect is very small • Short sleep duration, binge childhood but a more rapid rebound • Preadolescent boys are the eating, and skipping meals to higher BMIs later biggest group diagnosed with are all associated with ADHD and in that group the obesity. association with obesity is very small

Association Evaluation Treatment

• Children with OB/OW • Girls more likely to suffer from • Combination of obesity and significantly more likely to have depression than boys depression (as well as other depression • Diagnosis of depression and mood disorders) is strongly • More severe depression in the antidepressant usage are associated with an increased most obese groups independently associated with risk for early CVD (5 fold) • Increase in use of social media BMI trajectory over time • Depression should be associated with an increase in • Antidepressants more than twice considered as big a risk factor body dissatisfaction as likely to be prescribed to low for early CVD as obesity • Peer victimization, bullying and SES children especially in combination with teasing increase with obesity • Bidirectional association between components of the metabolic status and are strongly depression and obesity syndrome associated with depression • Bariatric surgery: initial • Depression strongly associated improvement in depression with with physical inactivity and binge weight loss but return of eating symptoms with weight regain

Diagnosis Evaluation Treatment Clinical Findings

Differential Diagnosis Screening tools • Routine screening for Prevalence • Generalized anxiety • SCARED anxiety in children and • General population: 20-25% disorder • QOL measures---not always adolescents presenting for of youth • Social anxiety specific for anxiety obesity management • Odds of having severe disorder If positive: Referral to mental Counseling: obesity vs obesity were 5x • Specific phobias health professional who may • CBT higher for those with anxiety use • Mindfulness Based • Anxiety with increased BMI • SAFA Scale Score: has Psychotherapies >F than in M subscales for age ranges • Psychodynamic • Social anxiety: strong • The Hospital Depression Psychotherapy association with obesity in and Anxiety Index-self- Psychotherapy elementary aged pts with assessment scale • Fluoxetine severe obesity > obesity > • Zoloft adolescent population • Venlafaxine • May be a barrier to seeking obesity treatment

Etiology Diagnosis/Evaluation Treatment Clinical Finding • Hx of high dietary restraint Diagnosis • Should not focus on calorie- • F>M but low prevalence • Poor interoceptive (feelings • Eating in response to negative restricted diet but on emotion in children of hunger/satiety) emotions or stress regulation skills • Usually emerges in awareness • Prior dieters at higher risk • Dialectical behavior therapy with adolescence • Alexithymia or emotion • Associated with PTSD, adult modules on mindfulness, • Associated with dysregulation and childhood trauma emotion regulation and distress depression • Reversed hypothalamic exposure or emotional abuse tolerance • Genetic loading pituitary adrenal (HPA) • Emotional eaters shift negative combined with parental stress axis(normal emotions narrowly to food cues psychological control response to stress is loss of appetite) • May be the outcome of Evaluation inadequate parenting or • DEBQ (Dutch Eating Behavior depressive feelings in Questionnaire) interaction with genetic susceptibility • May be a mediator between depression and obesity

Binge Eating Night Eating Syndrome

Sleep Related Eating Bulimia Nervosa Disorder

Diagnosis Evaluation Treatment Clinical Finding

Prevalence: BED occurs with at least 3 Cognitive Behavioral Therapy Clinical Findings: • 30% patients with obesity qualifiers: Interpersonal psychotherapy • Recurrent episodes of eating • 0.7-4% general population • Eating too rapidly Dialectical Behavior Therapy an abnormally large amount • 1.5 X more likely female • Eating until feels too full or sick Pharmacotherapy of food population • Eating large portions when one Agents that help with BED and Weight Loss: • Recurrent inappropriate Average age of onset is not hungry • Topiramate (not FDA approved) compensatory behavior in • Late adolescents- early 20s • Eating alone because one feels Agents for BED and possible related weight loss (more order to prevent weight gain. Pathophysiology: shame about portions study needed): • Binge episodes cause Pathological overeating related to: • Feeling disgust or guilty after • Vyvanse distress • Dysfunction of dopamine (DA) binge eating • Not FDA-approved for isolated BED in • Consists of feeling out of and norepinephrine systems. • Binge Eating at least 1 X /week children control while eating larger • Food stimulation results in for at least 3 months • Approved for treatment of ADHD (ages 6- amounts of food than most abnormal DA responses in pts 17) people would eat in 2 hours with obesity. • Inhibits reuptake of DA and norepinephrine • Self-evaluation is influenced • Methylphenidate-mediated • Elicits release of monoamine by body share and weight inhibition of DA transport neurotransmitters likely altering pathologic • Two Subtypes: results in greater increases in BE. 1. Purging DA levels within caudate in • Agents that help with BED symptoms without 2. Non-purging patients with obesity and BED weight loss: (Some associated with weight gain) compared to obesity/non BED • Tricyclic Agents population. • SSRIs • SSNRIs

Diagnosis Evaluation Treatment Challenges • Recurrent episodes of • Self report by patient • Medical complications: electrolyte • Since patients hide eating an objectively • Patient is ashamed and imbalance, esophageal tears, gastric symptoms, diagnosis is large amount of food with tries to keep diagnosis a disruption, infertility, dental decay difficult an associated loss of secret • Psychological treatment: • Patients often conceal control • Adolescents are • Cognitive behavioral therapy their inappropriate • Inappropriate susceptible population • Integrative cognitive-effective compensatory behavior compensatory • Prevalence: 1-1.5% for therapy even after treatment behavior(self induced strict criteria, much higher • Medication: only one medication trial • High index of suspicion vomiting, misuse of for subthreshold (N=13) of fluoxetine in conjunction with when adolescents laxatives or diuretics, presentations CBT in adolescents with obesity and present with mood or fasting , or excessive • Median age is 12.4 years overweight showing limited efficacy anxiety disorders exercise) • 41% report purging • Studies of psychotherapeutic approaches • High level of comorbidity • Overvaluation of shape • Strong association with have been inconclusive • Can occur at ANY weight and weight mood (50%) and anxiety • Minimum frequency of (66%) disorders once per week over 3 • 53% with suicidal ideation months • Subthreshold presentations common

NES vs BED vs SRED Prevalence/Evaluation Treatment Clinical Findings/Diagnosis

NES vs BED • Prevalence: • Anti-Depressants: • 1st described in 1955: delay in the • Although 7-24% NES pts also meet BED, still a • 1.5% general population SSRIs circadian intake of food with 25% or different diagnosis • 10-20% in pts with obesity more of intake in evening or night • In BED pts eat large amounts in one sitting, in NES • Evaluation • Cognitive Behavioral • Wake up 2x/week plus 2 qualifiers: pts eat smaller amounts throughout the night • Night Eating Diagnostic Questionnaire Therapy • Morning anorexia • NES also associated with nocturnal anxiety, not so • Provides clinically useful • Strong urge to eat between with BED diagnostic categories • Melatonin dinner and bed and/or night NES vs SRED • Night Eating Questionnaire • Sleep onset/insomnia • Timing of nocturnal eating: SRED occurs during slow • Provides convenient global • Relaxation Techniques 4+nights/week wave sleep, no disturbance prior to falling asleep, score for NES severity • Belief that one must eat to NES occurs between dinner onward and during • Possible genetic link: PER1 gene--- get to sleep wakeful periods, Frequently NES patients have possibly involved in controlling your • Mood frequently depressed insomnia body clock and/or mood worse in • State of consciousness during nocturnal eating: • Defect in this gene could evening SRED patients have partial or complete amnesia for cause NES • Awareness and recall of eating episodes, NES patients can recall eating, • Diagnosis of exclusion eating episodes occur during wakefulness • Substance abuse • Present for 3 months • Rate of comorbid sleep disorders present in those • Other medical disorders • Increased risk with obesity, other ED, with nocturnal eating: 80% of SRED patients have • Medication anxiety, depression, and emotional or associated comorbid sleep disorders (RLS, PLMS, • Other psychiatric disorders substance abuse somnambulism) • Sleep Study • Some studies found increased • Food Type: SRED patients frequently consume non preference for CHO due to food items, can injure themselves during neurochemical responses (cortisol, eating/cooking, NES patients eat food, not at risk of melatonin, serotonin, tryptophan injury transport changes)---possibly self medicating properties

Diagnosis Evaluation Treatment Clinical Findings • Rule out underlying causes of SRED, Sleep study: Discontinue medications that can be -SRED is a parasomnia — abnormal activity or medications, concurrent psychiatric dxs. • 50-70% somnambulism triggers. behavior that occurs while falling asleep, sleeping • Review sleep-related questions: sleep Hx • 25% PLMS • Stop or change medications that may be or waking up. • Complete questionnaire to determine sleep- • 10-14% OSA contributing -Episodes of SRED occur in the first half of the wake pattern / level of daytime sleepiness. • 5-6% where nocturnal • Treat other sleep disorders. night and include: • Information from your sleep partner, parent or eating was observed – • Treat other associated sleep disorders • Frequent episodes, generally nightly, of other household members may be helpful. occurred during NREM such as sleepwalking, restless legs eating and drinking in an out-of-control Differential Diagnosis: sleep syndrome or obstructive sleep apnea. manner • Nocturnal Eating Disorder Medications that may be associated Safety strategies. • Impaired consciousness while preparing and • Kleine-Levin Syndrome with SRED • Safely and gently coax back to bed eating food • Dissociative disorder • Zolpidem, triazolam, amitriptyline, without using restraint or awakening. • Little or no memory of these actions the next • Bulimia nervosa w/ nocturnal eating olanzapine, risperidone Strategies may also include changes to morning • Binge Eating Disorder Assess for associations with: your sleep routine. • Eating high-carbohydrate and high-fat foods Prevalence: 5% general population -OSA, sleepwalking, narcolepsy and Medications: or odd combinations of food 9-17% in patients with other restless legs syndrome Pramipexole • Possibly eating inedible or toxic substances, eating disorders -Hypnotic sleep medications, i.e. Topiramate such as frozen foods, coffee grounds, Age of Onset: late teens early 20s zolpidem, antidepressants or Fluoxetine cleaning solutions or cigarette butts Gender: 65% female, >40% also have antipsychotics Lifestyle and home remedies • Possibly experiencing injuries or engaging in overweight -A daytime eating disorder, ie.e BN/AN • Keep sleep area and kitchen safe dangerous food preparation activities Causes: -Stress, anxiety or depression • Consider storing foods eaten during a • Not being easily awakened or redirected • Exact mechanism unknown -A first-degree relative — a parent, SRED episode outside the kitchen or during the episode • often occurs in people with history of child or sibling — with sleep-related placing locks on cabinets and the fridge. • Experiencing a negative impact on your sleepwalking, and stress eating disorder or sleepwalking • Develop regular sleep and wake times. health from the nighttime eating -Experiencing sleep deprivation • Go to bed and get up at the same time each day, including weekends. • Get enough sleep every night. • . Avoid alcohol and tobacco

Genetic Syndromes Bariatric Surgery

Vitamin D Deficiency

•Hypotonia at birth, difficult feeding followed hyperphagia, hypogonadism, MR, deletion of Prader Willi Syndrome q11-13 region

Bardet-Biedl Syndrome •Retinitis pigmentosa, polydactyly, MR, hypogonadism, renal abnormalities

Fragile X Syndrome •Macro-orchidism, MR, prominent jaw, large ears

Albrights Hereditary Osteodystrophy •Short stature, skeletal defects, resistance to several hormones

Alstrom Syndrome •Photophobia, nystagmus, deafness, blindness, diabetes

•Hypogonadism, intense hyperphagia, absence of growth spurt, T-immune dysfunction, Congenital Leptin Deficiency frequent infections

•Hyperphagia and early-onset obesity; adrenal crisis due to ACTH deficiency, POMC Deficiency hypopigmentation

MC4R Deficiency •Increased linear growth and final height, severe hyperinsulinemia

• Chromosome 8q22 mutation. Obesity (central only- thin arms and legs), MR, head/face defects Cohen Syndrome (small jaw, shortened philtrum, high raised palate). Some children have seizures and deafness.

Presentation Special Behaviors Diagnosis Complications Characteristics Treatment

•Small and •Voracious and •Diagnosis: Paternal •Scoliosis •Hypotonia, poor •Calorie control and unusually floppy at insatiable appetite, chromosome 15q •Sleep Apnea suck, characteristic behavioral birth which often leads to partial deletion or •Osteoporosis facial features management obesity, usually unexpression •Almond shaped •Infertility due to •Bitemporal •Growth hormone starts around 2 eyes, thin upper •70% with paternal lack of narrowing of the therapy and years lips, thin facies allele deletion, 25% development of head, almond replacement of sex •Low muscle mass, •Severe behavioral with maternal secondary sexual shaped eyes, hormones at small hands and problems disomy, and 5% characteristics elongated face, and puberty feet with translocation or thin upper lip •Delayed motor other structural •May have relatively development abnormalities normal weight until •Intellectual and 2-5 years of age, speech delay then rapid weight gain •Ketotic at levels of carbohydrate intake that are higher than normally expected •Hunger control

Bardet-Biedl Syndrome Cohen Syndrome Alstrom Syndrome POMC Deficiency

• Ciliopathic genetic • Chromosome 8q22 • Very rare- ALMS 1 • Hyperphagia and early- disorder mutation mutation onset obesity; adrenal • Obesity, visual problems • Obesity (central only- • Childhood obesity, crisis due to ACTH including loss of vision, thin arms and legs), blindness and hearing deficiency; polydactyly, MR, head/face defects loss hypopigmentation hypogonadism (small jaw, shortened • Photophobia, • Often mental retardation area between the nose nystagmus, deafness and kidney failure and upper lip, high • Can have endocrine raised palate) issues such as type II • Some children have diabetes, high insulin, seizures and deafness and high triglycerides

Albright’s Hereditary Congenital Leptin Fragile X MC4R Deficiency Osteodystrophy Deficiency Syndrome

• MC4R mutations are • Short stature, skeletal • Hypogonadism, intense • Macro-orchidism, the most common defects, resistance to hyperphagia, absence mental retardation, monogenic form of several hormones of growth spurt, T- prominent jaw, large obesity. immune dysfunction, ears frequent infections • Increased linear growth and final height, increased fat mass, severe hyperinsulinemia

Diagnosis Significance Treatment Special considerations • Deficiency defined by • Fat soluble vitamin • Children aged 1–18 Children with obesity, Institute of Medicine and essential for skeletal years: malabsorptive syndromes, Endocrine Society clinical health in growing children • 1.) 2000 IU/d of vitamin or on medications affecting practice guidelines as • Important role for bone D2 or vitamin D3 for at vitamin D metabolism serum 25-hydroxyvitamin health through the least 6 weeks or (i.e. anticonvulsants, D [25(OH)D] < 20 ng/mL absorption of calcium • 2.) 50,000 IU of vitamin glucocorticoids, antifungals, from small intestine D2 or D3 once a week for and antiretrovirals) may • Available in diet and at least 6 weeks to require 2 to 3 times the through synthesis from achieve a blood level of dose of vitamin D to achieve sunlight 25(OH)D above 20 ng/ml, the same serum 25(OH)D followed by maintenance levels as children without therapy of 600-1000 IU/d these conditions

Outcomes (3 year Teen Labs Recommendations Indications Study) •Indications for adolescents mirror the •Mean percent weight loss=27% • Adolescents undergoing MBS need to be followed in weight management clinic pre and NIH recommendations for adults: •74% normalized blood pressure postoperatively; preferably American College of •BMI ≥40 kg/m2 •66% normalized lipid levels Surgeons MBSAQIP recommendations or •Greater than 50% with T2DM in including sensitivity training. 2 • Vertical sleeve gastrectomy (VSG) most •BMI ≥35 kg/m with significant remission common operation with adolescents; both current comorbidities including •57% low ferritin levels Roux-en-Y Gastric Bypass and VSG similar severe OSA, T2D, hypertension. •8% Vitamin B12 deficiency risk/benefit • Screened for micronutrient deficiencies at •16% Vitamin A deficiency baseline and ongoing after MBS. •In adolescents, use of percentile BMI •No change in vitamin D deficiency • Obesity is a chronic disease requiring values are used along with existing (37% before and after MBS multimodal therapies and treatment by a severe medical conditions and/or multidisciplinary weight management team debilitating quality of life. which can provide surgical, pharmacologic, behavioral, nutritional interventions and activity recommendations. •MBS considered for youth with severe • Counseled females about increased fertility with obesity: BMI > 120% of the 95th weight loss percentile. • All adolescents counseled risk/benefit and provided informed consent along with family/guardian

Adverse Childhood Bullying Experiences

Weight Stigma Quality of Life

Diagnosis Evaluation Treatment Clinical Findings • Adverse childhood The Adverse Childhood • Implement approaches to prevent • Creates dangerous levels of experiences (ACEs) as Experience (ACE) and recognize Adverse stress. potentially traumatic events Questionnaire is a 10- Childhood Experiences (ACEs) • ACEs are associated with Positive ACE history with: item self-report measure and mitigate their impact through negative behavioral and health • Negative, lasting effects on developed for the ACE building resilience. outcomes, such as obesity, health and self esteem. study to identify childhood • Proactively support safe, stable alcoholism, and depression • Experiences ranging from experiences of abuse and and nurturing family relationships • Specific ACEs predictive of physical, emotional, or sexual neglect. (SSNRs), teach resilience, and obesity in childhood and abuse to parental divorce or intervene early to promote adolescence include: the incarceration of a parent healing of the trauma and stress • Death of parent or guardian. associated with disruptions in • family economic hardship SSNRs • Sexual abuse • Utilize connection between • Witnessing domestic ACEs, social issues, and violence mental/physical health to inform • Physical abuse social programs and health • Weight gain may be protective policies that support prevention mechanism used by ACE and recovery from ACE events. survivors against further abuse

Definition Epidemiology Consequences Treatment

• Involves intentional, • Being overweight or obese is • Weight-based teasing in • Talk to patients/don’t blame and largely one of the most common children with obesity may child unprovoked, efforts reasons that children and contribute to negative • Don’t encourage children to to harm another adolescents are teased or emotional consequences, fight back (physically) • Can be physical or bullied at school academic failure, and peer • Telling the child to ignore the verbal, and direct or • Verbal teasing was the most rejection bullying may cause escalation. indirect frequent type of victimization • Risk of depression/low • Bystanders may be affected in • Involves repeated reported by adolescents with self-esteem in children that they don’t often know how negative actions by obesity, followed by relational with obesity is substantial to respond one or more against aggression, cyberbullying and even after controlling for Consult mental health if the child another physical aggression other factors including has: • Involves an • Boys with obesity were duration of obesity • severe depression, anxiety, or imbalance of significantly more likely to have • Psychological sequelae suicidality physical or dual role of bully-victim, which are a consequence of • particular difficulty in psychological power has the highest psychosocial victimization & not simply discussing the bullying implications among the bullying of weight status • severe impairment in daily roles, whereas girls with obesity activities were mainly victims

Forms Settings Health Consequences Recommendations • Bullying • School • Emotional • Positive role modeling • Teasing • Peers • Physical • Appropriate language (person • Victimization • Educators • Psychological first) • Home • Social • Clinical management of • Relational • Parents • Academic comorbidities • Verbal Abuse • Family members • Unhealthy eating • Counseling • Physical Abuse • Media behaviors • Behavioral health • Cyberbullying • Healthcare Providers • Decreased activity screening • All disciplines • Increased weight • Coping with stigma • Prevalence: • Work stress • >70 % • Healthy behaviors • Advocacy

Assessment Health Consequences Recommendations Impact of Weight Quality of Life-Kids • Psychosocial • Interventions: screen and treat mood and (IWQOL-Kids©) Tool • Depression social problems: address family/friend • 4 Domains: physical • Low self-esteem support for healthy eating. comfort, body-esteem, • Altered eating patterns • Improvements may be due to treatment social life, family relations • Sleep disturbances program itself and not exclusively to Pediatric Quality of Life Inventory • Increased cardiometabolic reductions in BMI; however, improved (PedsQL™) Tool abnormalities may decrease QOL HRQOL seen with sustained weight loss • Domains: Physical, scores • BMI may not directly relate to improved Emotional, Social, School • Inverse relationship between lower QOL but may be associated through other Parent-proxy tools are available QOL scores and increased BMI factors, including child social problems. • Perform comprehensive biopsychosocial assessment when providing treatment to youth with obesity and their families.

Orlistat (Xenical) Metformin Topiramate Phentermine • FDA approved in children •FDA approved in children with • Not FDA approved in • FDA approved in children > 12 years T2DM > 10 years children for weight loss >16 years for weight loss • Weight loss is small •Provides very modest • Has been used for • Has been used in reduction in BMI when • Side effects preclude combined with lifestyle seizure control in adolescents usage in most patients. interventions over short time children for years • Weight loss is small to • May cause oily stools •May have a role in • May control cravings moderate. prediabetes and/or strong • Can cause cleft palate in • May cause anxiety, family hx of T2DM fetus. tremors, slightly •Dose in adolescents, if increased blood pressure tolerated, should be at the • May cause paresthesias maximum recommended dose of extremities, cognitive of 1,000 mg twice daily to take disruption (confusion, advantage of the effect of difficulty concentrating) decreasing appetite •May prolong duration of time before onset of T2DM •May cause gastrointestinal upset especially in first few weeks, can be managed with dose titration

Byetta/Bydureon Bupropion Vyvanse

•FDA status: not approved for pediatric •FDA status: not approved for pediatric use •FDA approved for ADHD in children in use •MOA: aminoketone class of antidepressants, 2007, not for weight loss •MOA: slows gastric motility, unrelated to SSRIs. Moderates the levels and •FDA approved for BED in adults in 2015 suppresses appetite activity of neurotransmitters norepinephrine and (50-75 mg/day), not for weight loss dopamine, exactly how it works to treat •Reduction of BMI (4%) and body •MOA: LDX hydrolyzes to release the depression uncertain. active drug, d-amphetamine which inhibits weight in adolescents with severe •Black Box warning for worsening of depression in obesity in small RCT of 10 mcg BID. reuptake of dopamine and/or NE and pts 18-24 yrs. of age. enhances release of DA, NE, and Slight rebound of BMI after down •May increase risk of seizures – particularly in pts serotonin. LDX may decrease titration of dose, then recovery when with epilepsy, eating disorder such as bulimia or pathological overeating and therefore tx dose increased again anorexia nervosa. BED. •Preliminary evidence suggests that •Indications: •SE: decreased appetite, insomnia, HA, GI higher doses for prolonged periods of •Depression upset, irritability, monitor for CV changes time may be necessary for weight •Seasonal Affective Disorder (increased BP/pulse) loss •Smoking Cessation (Zyban) •Contraindications: MAOI use •Wellbutrin and Weight Loss •Scheduled II controlled drug: •Unlike other antidepressants it is not associated •Prescribing rules apply as with other with weight gain stimulants •Not FDA approved for weight loss

Contrave Qsymia Liraglutide •FDA approved for weight loss with BMI > •FDA status: not approved for pediatric use •Not FDA approved for weight loss in 30 or BMI >27 with at least one weight- •Combination of phentermine and adolescents, approved at 3.0 mg for adults related condition. topiramate •Treatment emergent adverse events: GI •MOA: reuptake inhibitor of Norepinephrine •Black box warning for worsening of disorders (abdominal pain), hypoglycemia and dopamine (Wellbutrin) and opioid depression in pts 18-24 yrs: •In small study of children with obesity with antagonist (naltrexone) www.fda.gov/bbs/topics/AN prediabetes, significant reduction in FBG •4.8% weight loss in trial over placebo – •Contraindications: pregnancy, glaucoma, and 2 hour postprandial glucose noted study duration 1 yr. hyperthyroidism, monoamine oxidase •Advantages: greater weight loss, food inhibitors within 14 days, hypersensitivity or addiction, long term data idiosyncrasy to sympathomimetic amines •Common Side effects: Nausea, •Adverse reactions: paraesthesia, dizziness, constipation, headache, vomiting and dysgeusis, insomnia, constipation, dry dizziness mouth, suicidal ideation, possible seizures •Concerns: Worsening depression and/or if medication discontinued abruptly suicidal ideation in youth •Warnings: fetal toxicity, metabolic acidosis •Contraindications: uncontrolled HTN, •Avoid: pregnancy, alcohol. Activities Seizure disorders, anorexia or bulimia, drug requiring concentration until establishing or alcohol withdrawal, MAOI usage effect (if any) on these activities

Significant Small to Neutral Weight Loss Weight Gain Weight Gain (neutral to mild) Guanfacine Atomoxetine Lisdexamfetamine ADHD Amphetamine Methylphenidate Valproate Pregabalin Carbamazepine Lamotrigine Topiramate Vigabatrin Gabapentin Oxocarbazepine Levetoracetam Zonisamide Anti-Seizure Phenytoin Felbamate

Amitriptyline Gabapentin Timolol Zonisamide Divalproex Metoprolol Levetiracetam Topiramate Migraine Flunarizine Propranolol

Insulin and analogs GLP-1 Receptor Agonists Diabetic Medications Metformin

Glucocorticoids Benzodiazepines Gleevac Statins Other Medications Depo Provera Antihistamines (Cyproheptadine) Carvedilol Oral Contraceptive Pills Reference/s: [262] [266] [258] [267] [268] [269] [270] [271] 109 [272] [273] [274] [275] [276] [277] [278] [279] [280] [281] Pediatric Obesity Algorithm®. ©2018-2020 Obesity Medicine Association. [282] [283] [284] [285] [286] Review of Medications: Psychiatric

Significant Weight Gain Small to Neutral Weight Gain Weight Loss Clozapine Aripiprazole Olanzapine Haloperidol Antipsychotics Chlorpromazine Ziprasidone Quetiapine Risperidone Special considerations: “Youth may be particularly sensitive to weight gain, especially with olanzapine, as well as extrapyramidal side effects and metabolic changes.” Many of the medications listed here have only been well studied in adults Paroxetine* Lithium Venlafaxine Bupropion* Amitriptyline Desipramine Fluvoxamine Olanzapine Imipramine Sertraline Citalopram Duloxetine Trazodone Nortriptyline Escitalopram Fluoxetine Antidepressants Doxepin Mirtazapine

Valproate Topiramate Mood Stabilizers Lithium Gabapentin Lorazepam Anxiolytics Diazepam Oxazepam *Black box warning

Incidence and Risk Factors for Weight Risk factors for Treatment of Associations Gain Diabetes Complications • Antipsychotic prescriptions in • Adolescents are at greater • The atypical antipsychotic • Metformin may be effective in children have increased risk than adults medications risperidone and decreasing weight gain significantly over the past 2 • Specific Medication: highest aripiprazole are FDA associated with atypical decades. weight gain with olanzapine, approved for use in autism antipsychotic use. • The prescriptions are mainly then clozapine, risperidone spectrum disorder (ASD) in • Dosing: Metformin can be for second generation and aripiprazole. young children: as young as titrated up to 500 mg twice Antipsychotics. • Differences according to 5 (risperidone) or 6 daily for children aged 6 to 9 • Up to 80% of children show diagnosis: Autism treated (aripiprazole) years. years and 850 mg twice daily significant weight gain with SGAs had greater weight • Both of these medications for those 10 to 17 years gain. can cause weight gain, and • Tolerability: Metformin is well • Older, lower baseline BMI z- greater cumulative exposure tolerated by children and score, males and dx of mood is associated with increased adolescents with ASD disorder were associated with risk for diabetes. more SGA-induced weight gain

Incidence and Risk Factors for Weight Special Considerations Treatment of Associations Gain Complications • In the last 2 decades, > 11 • Weight gain occurring in 40% • Topiramate and zonisamide • Weight gain with the AEDs is new AEDs have been of children on VPAs. are the 2 AEDs causing not only a cosmetic problem introduced to the market. • 38% of VPA-treated gained weight loss. but also a risk for obesity- • Several AEDs are associated >10% of their BW compared • Topiramate significantly related vascular disorders. with weight gain such as with 8% treated with reduced adiponectin, • As AEDs may influence gabapentin, pregabalin, lamotrigine. leptin/adiponectin ), and weight, physicians have to valproic acid (VPA) and • Hyperinsulinemia markedly increase the serum properly select and vigabatrin and to some extent /hyperleptinemia common level of adiponectin, characterize the suitable carbamazepine (CBZ). with VPA, marked in epileptic increases energy AED as an initial step or • Others are weight neutral children who gained weight. metabolism, resulting in modify the existing AED if it such as lamotrigine (LTG), Alterations not seen with weight loss since adiponectin compromises patient’s levetiracetam, and phenytoin CBZ or LTG. play a significant role in health. or associated with slight • MOA: ↑ insulin and metabolic regulations. weight loss as, e.g., insulin/glucose with VPA felbamate. possibly stimulating appetite.

Incidence and Risk Factors for Weight Gain Special Treatment of Associations Consideration Complications • Positive association Drug Class/DrugWeight Change • Topiramate is, generally, • Recognizing and avoiding with headache and a well-tolerated migraine trigger factors of migraines as obesity among Anti-depressants therapy in children that is well as a suitable therapy children Amitriptyline ↑ ↑ ↑ Calcium channel blockers weight negative. strategy that is not weight • Migraine is ↑ in those Verapamil ↔ • Treatment starts at 15 positive may give the child with with obesity. Risk ↑ Flunarizine ↑ ↑ mg/day and it is migraines the chance for a with ↑ obesity status. Nortriptyline ↑ ↑ increased during an 8 good quality of life. • Overlap between Protriptyline ↓ week-period to 2 to 3 • Psychological and physical migraine Venlafaxine, Duloxetine ↔ ↓ mg/kg daily (Max dose is triggers include: stress, pathophysiology, Anti-convulsants 200 mg/day). anxiety, worry, depression, central and peripheral Divalproex sodium ↑ ↑ ↑ • Side effects: fatigue, fever, illness, poor pathways regulating Lamotrigine ↔ gastroenteritis, sleep habits, irregular meals, feeding. Gabapentin ↑ concentration difficulty, fasting, hypoglycemia, and • Specifically, Topiramate ↓ ↓ somnolence or even dehydration. neurotransmitters like β-Blockers cognitive impairment. • An important part of the serotonin, peptides Propranolol ↑ • Due to the low dose prophylactic treatment in such as orexin, and Nadololol ↔ required for treatment of pediatric migraine is the adipocytokines Metoprolol ↑ migraine, Topiramate can psychological support. (adiponectin and Serotonin antagonists be a good choice for the leptin) may have roles Cyproheptadine ↑ ↑ ↑ pediatric population due in both feeding and to its efficacy and the low migraine. frequency of side effects

Incidence and Risk Factors for Weight Special Consideration Treatment of Associations Gain Complications • Mood stabilizers medications • Data regarding body • There is a resurgence of • Some reports indicated that are medications that are off- composition and fasting interest in lithium treatment of topiramate may be useful as label for the treatment of metabolic effects of mood bipolar disorders due to its an add-on therapy to induce bipolar disorder in children stabilizers in pediatric bipolar unique anti-suicidal and weight loss in patients who and adolescents. disorder are sparse. neuro-protective effects. have experienced • Mood stabilizers can be • Combining antipsychotics • Lithium may be less effective psychotropic-induced weight divided into traditional agents with mood stabilizers seems than risperidone for treating gain. lithium, valproate, and to lead to greater weight gain chronic mixed/manic • Amantadine appears to carbamazepine and newer than treatment with one or symptoms in young children stabilize weight gain related agents, including the two mood stabilizers. but comparable to to psychotropic medications. anticonvulsants lamotrigine, anticonvulsants. However, in It also may help decrease oxcarbazepine, topiramate, comparison, risperidone was BMI with continued and gabapentin. associated with higher weight amantadine usage but • Newer medications are often gain and prolactin levels than controlled trials in lacking to used as second-line choices lithium. date. behind atypical antipsychotics for overall efficacy.

Valproic Acid Lithium SSRIs SNRIs • Weight gain seen • Risk of weight gain is • Fluoxetine, paroxetine, • Mirtazapine and during first 3 months of high sertraline Trazadone treatment • F>M • Most commonly used • F>M • F>M • No direct effect on lipids medication for • Unfavorable effect on • Pathogenic mechanism treatment of depression triglycerides and LDL unknown in adolescents • Insulin resistance • Small increase (0.007) • Increased hunger due in zBMI over a 14 to low glucose levels month period of • No direct effect on treatment as compared lipids to no medication • F>M • No direct effect on lipids

Incidence and Risk Factors for Weight Special Consideration Special Consideration Associations Gain

• SEARCH for Diabetes in • There are few pediatric data • Metformin: effectiveness • GLP-1 receptor agonists: Youth study (2002-12): rate on the insulin regimens proven for adolescents. liraglutide, exenatide, of new diagnosed cases of used, but they all seem to • Metformin decreases hepatic lixisenatide, dulaglutide): few type 2 diabetes ↑ at 4.8% have equal efficacy. glucose output/ enhances studies have been carried each year. • Insulin and insulin analogues primarily hepatic and muscle out in the pediatric • Since T2D in youth only (insulin Glargine) cause insulin sensitivity without a population but several trials recognized recently, natural weight gain in adolescents. direct effect on β-cell are currently underway. history is lacking. There are • Sulfonylureas: not commonly function. • The TODAY study preferred only few studies examining used in pediatric patients • Metformin has the advantage early combination therapy in treatments beyond metformin and cause weight gain. of weight reduction, pediatric patients with type 2 and insulin. decrease in lipids without the diabetes, rather than wait for • Although only metformin and risk of hypoglycaemia. the failure of metformin insulin are currently licensed • Thiazolidinediones (TZD): monotherapy . for use for under age 18 Rosiglitazone and endocrinologists use oral pioglitazone are the only agents for children with type remaining drugs from TZD 2 diabetes mellitus. family in clinical use, and rosiglitazone was used in the TODAY study.

116 Reference/s: [327] [328] [329] [330] [331] [332] [333] Pediatric Obesity Algorithm®. ©2018-2020 Obesity Medicine Association. [334] [335] [336] [337] [338] Appendices -Added as reference for American Board of Obesity Medicine review

First Steps Second Steps Staged Treatment

• Initial identification of • If child not losing weight, • Recommendations for overweight or obese children child is usually referred to staged management were done in primary care office weight management clinic or, first published in 2007 in • First approach is counseling if no clinic available, to see a Pediatrics: AAP Expert on consuming 5 or more dietitian Committee fruits and vegetables/day, < 2 Recommendations hours screen time, 1 hour of play or exercise, and no SSBs • Family based counseling • Motivational Interviewing

Comprehensive Structured Weight Tertiary Care Prevention Plus Multidisciplinary Management Intervention Intervention • BMI <85th percentile or • BMI > 95th percentile • Structured intervention • Tertiary care center < 95th percentile with or > 85th percentile with at more frequent with designed protocol no health risk factors health risk factors intervals (weekly for 8- • May include meal • Basic Healthy • Monthly visits working 12 weeks) by team replacements, weight Behaviors on behavior change experienced with care loss medications and MI of children affected by • May include weight • Dietician evaluation obesity loss surgery • Family involvement, supervised activity • Negative energy balance through diet and exercise • May include medication management, meal replacements

• Metabolic: No metabolic abnormalities • Mechanical: No functional limitations Stage • Mental: No psychopathology 0 • Milieu: No parental, familial, or social environment concerns

• Metabolic: Mild metabolic abnormalities (i.e. IGT, pre-hypertension, mild lipid abnormalities, mild fatty infiltration of liver/elevation in transaminases • Mechanical: Mild bio-mechanical complications (i.e. OSA not requiring PAP therapy, mild MSK pain not interfering with ADL, GERD) Stage • Mental: Mild psychopathology, ADHD, LD, mild body image pre-occupation, occasional emotional/binge eating, bullying, mild developments delay 1 • Milieu: Minor problems in relationships, minor limitations in caregivers ability to support child’s needs

• Metabolic: Moderate metabolic complications requiring pharmacotherapy (i.e. Type 2 Diabetes Hypertension, lipid abnormalities, PCOS, moderate to severe fatty infiltration of liver) • Mechanical: Moderate bio-mechanical complications (i.e. OSA requiring PAP therapy, GERD, MSK pain limiting activity, moderate limitations in ADLs) Stage • Mental: Moderate mental health issues (i.e. major depression, anxiety, frequent binging, significant body image disturbance, moderate developmental delay) 2 • Milieu: Moderate problems in relationships, significant bullying at home or at school, significant limitations in caregivers ability to support child’s needs

• Metabolic: Uncontrolled metabolic complications (i.e. T2DM (+ complications/not meeting glycemic targets), uncontrolled hypertension, FSGS, markedly elevated liver enzymes and/or liver dysfunction, symptomatic gall stones, marked lipid abnormalities) • Mechanical: OSA requiring PAP therapy and suppl. oxygen, limited mobility, shortness of breath sitting/sleeping • Mental: Uncontrolled psychopathology, school refusal, daily binge eating, severe body image disturbance Stage • Milieu: Severe problems in relationships, caregivers unable to support child’s needs (may include exposure to family violence), dangerous environment (home, 3 neighborhood or school)

122obesitymedicine.org Pediatric Obesity Algorithm®. ©2018-2020 Obesity Medicine Association. Resources • Food Insecurity – American Academy of Pediatrics (AAP) and the Food Research & Action Center (FRAC). Addressing Food Insecurity: A Toolkit for Pediatricians. http://frac.org/aaptoolkit (accessed January 2018WIC: www.fns.usda.gov/wic/women-infants-and-children-wic – SNAP: www.fns.usda.gov/snap/supplemental-nutrition- assistanceprogram-snap – National School Lunch Program: www.fns.usda.gov/nslp/national- schoollunch-program-nslp – National School Breakfast Program: http://www.fns.usda.gov/sbp/schoolbreakfast-program-sbp – Child & Adult Care Food Program: http://www.fns.usda.gov/cacfp/childand-adult-care-food-program – Summer Food Service Program: http://www.fns.usda.gov/sfsp/summerfood-service-program

Sleep Disorders – https://emedicine.medscape.com/article/870192-overview – http://www.pennstatehershey.org/c/document_library/get_file?uuid=0c0ceca4-5963-4d8c-b297- 6189d1a92ae2&groupId=307082 – https://emedicine.medscape.com/article/304381-medication#2

BED Screening Tools – https://psychology-tools.com/binge-eating-scale/ – https://www1.bingeeatingdisorder.com/en/binge-eating-disorder-symptoms#binge-eating-disorder-checklist

Sleep Related Eating Disorder – https://sleepfoundation.org/sleep-disorders-problems

Centers for Disease Control and Prevention, Violence Prevention Program, ACEs Study - http://www.cdc.gov/violenceprevention/acestudy/about.html

Robert Wood Johnson Foundation, The Truth about ACEs - http://www.rwjf.org/en/library/infographics/the-truth-about-aces.html

ACEs Connection - http://www.acesconnection.com/blog/aces-101-faqs

• Bullying – Stop Bullying Now • www.stopbullyingnow.hrsa.gov/adults/default.aspx – Centers for Disease Control • www.cdc.gov/ncipc/dvp/electronic_aggression.htm

• Weight Stigma and Victimization – Rudd Center for Food Policy & Obesity: www.uconnruddcenter.org • Resources regarding weight stigma, how to incorporate into a practice, media, literature – AAP Institute for Healthy Childhood Weight: Change Talk • www.go.kognito.com/changetalk – Obesity Action Coalition • www.obesityaction.org

1. Rhee KE, Phelan S, McCaffery J. Early determinates of obesity: Genetic, epigenetic, and in utero influences. Int J Pediatrics. 2012. doi:10.1155/2012/463850 2. Archer E. The childhood obesity epidemic as a result of nongenetic evolution: The maternal resources hypothesis. Mayo Clin Proc. 2015;90(1):77- 92. 3. Pettersen-Dahl A, Murzakanova G, Sandvik L, Laine K. Maternal body mass index as a predictor for delivery method. Acta Obstet Gynecol Scand. 2018;97(2):212-218. 4. Yuan C, Gaskins AJ, Blaine AI, et al. Association between cesarean birth and risk of obesity in offspring in childhood, adolescence, and early adulthood. JAMA Pediatr. 2016;170(11):e162385. doi: 10.1001/jamapediatrics.2016.2385 5. Mulligan CM, Friedman JE. Maternal modifiers of the infant gut microbiota: metabolic consequences. J Endocrinol. 2017;235: R1-R12. 6. Principi N, Esposito S. Antibiotic administration and the development of obesity in children. Int J of Antimicrob Agents. 2016;47:171-177. 7. Nash MJ, Frank DN, Friedman JE. Early microbes modify immune system development and metabolic homeostasis---The “restaurant” hypothesis revisited. Front Endocrinol. 2017;8:349. doi:10.3389/fendo.2017.00349 8. Andrade MJ, Jayaprakash C, Bhat S, Evangelatos N, Brand A, Satyamoorthy K. Antibiotics-induced obesity: a mitochondrial perspective. Public Health Genomics. 2017;20:257-273. DOI:10.1159/000485095. 9. Shao X, Ding X, Wang B, et al. Antibiotic exposure in early life increases risk of childhood obesity: A systematic review and meta-analysis. Front. Endocrinol. 2017;8:170. doi:10.3389/fendo.2017.00170 10. Plagemann A, Harder T, Franke K, Kohlhoff R. Long term impact of neonatal breast feeding on body weight and glucose tolerance in children of diabetic mothers. Diabetes Care. 2002;25:16-22. 11. Shearrer GE, Whaley SE, Miller SJ, House BT, Held T, Davis JN. Association of gestational diabetes and breast feeding on obesity prevalence in predominately Hispanic low income youth. Pediatr Obes. 2015;10:165-171. 12. Dugas C, Perron J, Kearney M, et al. Postnatal prevention of childhood obesity in offspring prenatally exposed to gestational diabetes mellitus: Where are we now? Obes Facts. 2017;10:396-406.

13. http://www.cdc.gov/growthcharts/who_charts.htm 14. http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5909a1.htm?s_cid=rr5 909a1_w 15. Ogden CL, Kuczmarski RJ, Flegal KM et al. Centers for Disease Control and Prevention 2000 growth charts for the United States: improvements to the 1977 National Center for Health Statistics version. Pediatrics. 2002;109:45-60. 16. http://www.health.ny.gov/publications/4949.pdf 17. Freedman DS, Berenson GS. Tracking of BMI z scores for severe obesity. Pediatrics. 2017;140(3):e20171072. DOI: 10.1542/peds.2017-1072. 18. Freedman DS, Butte NF, Taveras EM, Goodman AB, Ogden CL, Blanck HM. Limitations of transforming very high body mass indexes into z-scores among 8.7 million 2-to 4 to year old children. J Pediatr. 2017;188:50-56. 19. Gulati AK, Kaplan DW, Daniels SR. Clinical tracking of severely obese children: A new growth chart. Pediatrics. 2012;130: 1136- 40. 20. Dietz WH. Time to adopt new measures of severe obesity in children and adolescents. Pediatrics. 2017;140(3):e20172148. 21. Katzmarzyk PT, Barlow S, Bouchard C, et al. An evolving scientific basis for the prevention and treatment of pediatric obesity. Int J Obes. 2014;38:887-905. 22. Bays HE, González-Campoy JM, Henry RR, et al. Is adiposopathy (sick fat) an endocrine disease? Int J Clin Pract. 2008;62:1474- 1483. 23. Bays HE. “Sick fat,” metabolic disease, and atherosclerosis. Am J Med. 2009;122:S26-37. 24. Barlow SE, Expert Committee. Expert committee recommendations regarding the prevention, assessment, and treatment of child and adolescent overweight and obesity: a summary report. Pediatrics. 2007;120 Suppl 4:S164-S192.

25. Davis MM, Gance-Cleveland B, Hassink S, et al. Recommendations for prevention of childhood obesity. Pediatrics. 2007;120 Suppl 4:S229-S253. 26. Krebs NF, Himes JH, Jacobson D, Nicklas TA, Guilday P, Styne D. Assessment of child and adolescent overweight and obesity. Pediatrics. 2007;120 Suppl 4: S193-S228. 27. Spear BA, Barlow SE, Ervin C, et al. Recommendations for treatment of child and adolescent overweight and obesity. Pediatrics. 2007;120 Suppl 4: S254-S288. 28. Agirbasli M, Tanrikulu A, Acar Sevim B, Azizy M, Bekiroglu N. Total cholesterol-to-high-density lipoprotein cholesterol ratio predicts high sensitivity C-reactive protein levels in Turkish children. J of Clin Lipidol. 2015; 9: 195-200. 29. Sakuno T, Tomita, LM, Tomita CM. Sonographic evaluation of visceral and subcutaneous fat in obese children. Radiol Bras. 2014;47(3):149-153. 30. American Academy of Pediatrics. Promoting food security for all children. Pediatrics. 2015;136:e1431-1438. 31. Barnidge E, LaBarge G, Grupsky K, & Arthur J. Screening for food insecurity in pediatric clinical settings: Opportunities and barriers. J Community Health. 2017;42:51-57. 32. Browne NT. (2017). Food insecurity: Assessment and intervention. J Pediatr Surg Nurs. 2017;6:7-10. 33. Coleman-Jensen A, Rabbitt MP, Gregory CA, Singh A. 2017. Household Food Security in the United States in 2016, ERR-237, U.S. Department of Agriculture, Economic Research Service. 34. Cook JT, Black M, Chilton M. Are food insecurity's health impacts underestimated in the U.S. population? Marginal food security also predicts adverse health outcomes in young U.S. children and mothers. 2013;Adv Nutr, 4:51-61. doi:10.3945/an.112.003228 35. Eicher-Miller HA, Mason AC, Weaver CM, McCabe GP, & Boushey CJ. Food insecurity is associated with iron deficiency anemia in US adolescents. Am J Clin Nutr. 2009;90(5):1358-1371. doi:10.3945/ajcn.2009.27886 36. Eisenmann JC, Gundersen C, Lohman BJ, Garasky S, Stewart SD. Is food insecurity related to overweight and obesity in children and adolescents? A summary of studies, 1995-2009. Obes Rev. 2011;12:e73-83. doi:10.1111/j.1467-789X.2010.00820.x

37. Fox CK, Cairns N, Sunni M, Turnberg GL, Gross AC. Addressing Food Insecurity in a Pediatric Weight Management Clinic: A Pilot Intervention. J Pediatr Health Care. 2016;30:e11-15. doi:10.1016/j.pedhc.2016.05.003 38. Gundersen C. (2013). Food insecurity is an ongoing national concern. Adv Nutr. 2013;4(1):36-41. doi:10.3945/an.112.003244 39. Gundersen C, Kreider B. Bounding the effects of food insecurity on children's health outcomes. J Health Econ. 2009;28(5):971-983. doi:10.1016/j.jhealeco.2009.06.012 40. Gundersen C, Ziliak JP. (2014). Childhood food insecurity in the U.S.: Trends, Causes, and Policy Options. Retrieved from http://www.futureofchildren.org/publications/docs/ResearchReport-July 2018.pdf 41. Hager ER, Quigg AM, Black MM, et al. Development and validity of a 2-item screen to identify families at risk for food insecurity. Pediatrics. 2010;126(1): e26-32. doi:10.1542/peds.2009-3146 42. Howard LL. Transitions between food insecurity and food security predict children's social skill development during elementary school. Br J Nutr. 2011;105(12):1852-1860. doi:10.1017/s0007114510005623 43. Kirkpatrick SI, McIntyre L, Potestio ML. Child hunger and long-term adverse consequences for health. Arch Pediatr Adolesc Med. 2010;164(8):754-762. doi:10.1001/archpediatrics.2010.117 44. Laraia BA. Food insecurity and chronic disease. Adv Nutr. 2013;4(2): 203-212. doi:10.3945/an.112.0032 45. Abbasi J. Interest in the ketogenic diet grows for weight loss and type 2 diabetes. JAMA. 2018;319(3):215-217. 46. Ramon-Krauel M, Salsberg SL, Ebbeling CB, et al. A low-glycemic-load versus low-fat diet in the treatment of fatty liver in obese children. Child Obes. 2013;9:252-60. doi: 10.1089/chi.2013.0022. 47. Gow ML, Ho M, Burrows TL. Impact of dietary macronutrient distribution on BMI and cardiometabolic outcomes in overweight and obese children and adolescents: a systematic review. Nutr Rev. 2014;72:453-70. 48. Epstein LH, Paluch RA, Beecher MD, Roemmich JN. Increasing healthy eating vs. reducing high energy-dense foods to treat pediatric obesity. Obesity. 2008;16:318-326. 49. Krebs NF, Gao D, Gralla J, Collin JS, Johnson SL. Efficacy and safety of a high protein, low carbohydrate diet for weight loss in severely obese adolescents. J Pediatr. 2010;157:252-258. 50. Fisher JO, Goran MI, Rowe S, Hetherington MM. Forefronts in portion size. An overview and synthesis of a roundtable discussion. Appetite. 2015;88:1-4.

51. Kirk S, Woo JG, Brehm B, Daniels SR, Saelens BE. Changes in eating behaviors of children with obesity in response to carbohydrate-modified and portion-controlled diets. Child Obes. 2017;13:377-383. 52. Kral TV, Hetherington MM. Variability in children's eating response to portion size. A biobehavioral perspective. Appetite. 2015;88:5-10. 53. Watowicz RP, Tindall RD, Hummel JC. The protein-sparing modified fast for adolescents with severe obesity. Infant Child Adolesc Nutr. 2015;7:233-241. 54. Visuthranukul C, Sirimongkol P, Prachansuwan A, Pruksananonda C, Chomtho S. Low-glycemic index diet may improve insulin sensitivity in obese children. Pediatr Res. 2015;78:567–73. 55. Schwingshackl L, Hobl LP, Hoffmann G Effects of low glycaemic index/low glycaemic load vs. high glycaemic index/ high glycaemic load diets on overweight/obesity and associated risk factors in children and adolescents: a systematic review and meta-analysis. Nutr J. 2015;14:87. 56. Jenkins DJ, Kendall CW, Augustin LS, et al. Glycemic index: overview of implications in health and disease. Am J Clin Nutr. 2002;76:266S–73S. 57. Dodds P, Wolfenden L, Chapman K, Wellard L, Hughes C, Wiggers J. The effect of energy and traffic light labelling on parent and child fast food selection: a randomized controlled trial. Appetite. 2014;73:23-30. 58. SHAPE America. Active Start: A Statement of Physical Activity Guidelines for Children from Birth to Age 5, 2nd Ed. Champaign, IL: Human Kinetics Publishing; 2009. 59. American Academy of Pediatrics. Active Healthy Living: Prevention of childhood obesity through increased physical activity. Pediatrics. 2006; 117:1834-1842. 60. Ahern D, Dixon E. Pediatric hypertension: A growing problem. Prim Care. 2015;42:143-150. 61. Falkner B. Recent clinical and translational advances in pediatric hypertension. Hypertension. 2015; 65:926-931. 62. Estrada E, Eneli I, Hampl S, et al. Children’s Hospital Association consensus statements for comorbidities of childhood obesity. Child Obes. 2014;10:304-317.

63. Falkner B. Monitoring and management of hypertension with obesity in adolescents. Integ Blood Pressure Control. 2017;10:33-39. 64. Flynn JT, Kaelber DC, Baker-Smith CM et al. Clinical practice guideline for screening and management of high blood pressure in children and adolescents. Pediatrics. 2017;140(3):e20171904 65. Andrews LE, Liu GT, Ko MW. Idiopathic intracranial hypertension and obesity. Horm Res Paediatr. 2014;81(4):217-225. 66. Brara SM, Koebnick C, Porter AH, Langer-Gould A. Pediatric idiopathic intracranial hypertension and extreme childhood obesity. J Pediatr. 2012;161(4):602-607. 67. Chandra V, Dutta S, Albanese CT, Shepard E, Farrales-Nguyen S, Morton J. Clinical resolution of severely symptomatic pseudotumor cerebri after gastric bypass in an adolescent. Surg Obes Relat Dis. 2007;3(2):198-200. 68. Friedman DI, Liu GT, Digre KB. Revised diagnostic criteria for the pseudotumor cerebri syndrome in adults and children. Neurology. 2013;81(13):1159-1165. 69. Graber JJ, Racela R, Henry K. Cerebellar tonsillar herniation after weight loss in a patient with idiopathic intracranial hypertension. Headache. 2010;50(1):146-148. 70. Krispel CM, Keltner JL, Smith W, Chu DG, Ali MR. Undiagnosed papilledema in a morbidly obese patient population: a prospective study. J Neuro-ophthalmol. 2011;31(4):310-315. 71. Leslie DB, Kellogg TA, Boutelle KN, et al. Preserved vision without growth retardation after laparoscopic Roux-en-Y gastric bypass in a morbidly obese child with pseudotumor cerebri: 36-month follow-up. J Pediatr Surg. 2008;43(7):e27-30. 72. Marton E, Feletti A, Mazzucco GM, Longatti P. Pseudotumor cerebri in pediatric age: role of obesity in the management of neurological impairments. Nutr Neurosci. 2008;11(1):25-31. 73. National Sleep Foundation: https://sleepfoundation.org/sleep-topics/sleep-hygiene. Updated 2018. Accessed July 1, 2018. 74. Hirshkowitz M, Whiton K, Albert SM, et al. National Sleep Foundation’s updated sleep duration recommendations: final report. Sleep Health. 2015;1(4):233-24. 75. Kotagal S, Pianosi P. 2006. Sleep disorders in children and adolescents: Clinical review. BMJ. 2006;332:828-832.

76. Wang Y, Carreras A, Lee S, et al. Chronic sleep fragmentation promotes obesity in young adult mice. Obesity. 2014;22(3):758-762. 77. Gozal D, Kheirandish-Gozal L. Childhood obesity and sleep: relatives, partners, or both?--a critical perspective on the evidence. Trans NY Acad Sci. 2012;1264:135-141. 78. Kennedy JD, Blunden S, Hirte C, et al. Reduced neurocognition in children who snore. Pediatr Pulmonol. 2004;37(4):330-337. 79. Sateia MJ. International classification of sleep disorders-3rd edition: Highlights and Modifications. Chest. 2014;146:1387-94. 80. Isacco L, Roch J, Quinart S, et al. Cardiometabolic risk is associated with the severity of sleep-disordered breathing in children with obesity. Physiol Behav. 2017;170:62-67. 81. Fatima Y, Doi SA, Mamun AA. Sleep quality and obesity in young subjects: a meta-analysis. Obes Rev. 2016;17:1154-1166. 82. Koren D, Taveras EM. Association of sleep disturbances with obesity, insulin resistance and the metabolic syndrome. Metabolism. 2018;84:67- 75. 83. Owens JA, Weiss MR. Insufficient sleep in adolescents: causes and consequences. Minerva Pediatr. 2017;69:326-336. 84. Gileles-Hillel A, Kheirandish-Gozal L, Gozal D. Biological plausibility linking sleep apnoea and metabolic dysfunction. Nat Rev Endocrinol. 2016;12:290-298. 85. Hakim F, Kheirandish-Gozal L, Gozal D. Obesity and altered sleep: A pathway to metabolic derangements in children? Semin Pediatr Neurol. 2015;22:77-85. 86. Combs D, Goodwin JL, Quan SF, Morgan WJ, & Parthasarathy S. Modified STOP-Bang Tool for stratifying obstructive sleep apnea risk in adolescent children. PLoS One. 2015;10:e0142242. 87. Janssen KC, Phillipson S, O’Connor J, Johns MW. Validation of the Epworth Sleepiness Scale for Children and Adolescents using Rasch analysis. Sleep Med. 2017;33:30-35. 88. Patinkin ZW, Feinn R, Santos M. Metabolic consequences of obstructive sleep apnea in adolescents with obesity: A systematic literature review and meta-analysis. Child Obes. 2017;13:102-110.

89. Capdevila OS, Kheirandish-Gozal L, Dayyat D, Gozal D. Pediatric obstructive sleep apnea: complications, management, and long-term outcomes. Proc Am Thorac Soc. 2008; 5(2);274-282. 90. Andersen IG, Holm JC, Homøe P. Obstructive sleep apnea in obese children and adolescents, treatment methods and outcome of treatment - A systematic review. Int J Pediatr Otorhinolaryngol. 2016;87:190-197. 91. Friedman M, Wilson M, Pulver T, et al. Screening for obstructive sleep apnea/hypopnea syndrome: subjective and objective factors. Otolaryngol Head Neck Surg. 2010;142:531-535. 92. Koren D, Dumin M, Gozal D. Role of sleep quality in the metabolic syndrome. Diabetes Metab Syndr Obes. 2016;9:281-310. 93. Marcus CL, Brooks LJ, Draper KA, et al. Diagnosis and management of childhood obstructive sleep apnea syndrome. Pediatrics. 2012;130(3):e714-755. 94. Narang I, Mathew JL. Childhood obesity and obstructive sleep apnea. J Nutr Metab. 2012;2012:134202 95. Weiss R, Taksali SE, Tamborlane WV, Burgert TS, Savoye M, Caprio S. Predictors of changes in glucose tolerance status in obese youth. Diabetes Care. 2005 Apr;28(4):902-9. 96. Steffen LM, Jacobs DR, Jr., Murtaugh MA, et al. Whole grain intake is associated with lower body mass and greater insulin sensitivity among adolescents. Am J Epidemiol. 2003;158:243–250. 97. Ebbeling CB, Leidig MM, Sinclair KB, Hangen JP, Ludwig JS. A reduced-glycemic load diet in the treatment of adolescent obesity. Arch Pediatr Adolesc Med. 2003;157:773–779. 98. Haemer MA, Grow MA, Fernandez C, et al. Addressing prediabetes in childhood obesity treatment programs: Support from research and current practice. Child Obes. 2014;10:292–303. 99. Brook CGD, Brown RS. Handbook of clinical pediatric endocrinology,1st ed. Malden, MA: Blackwell Pub;2008. 100. Elder, DA., Hornung LN, Herbers PM, Prigeon R, Woo JG, D’Allessio DA. Rapid deterioration of insulin secretion in obese adolescents preceding the onset of type 2 diabetes. J Pediatr. 2015;166:672-8. 101. American Diabetes Association. Standards of medical care in diabetes-2014. Diabetes Care. 2014;37(Suppl. 1):S14-S80. 102. Cook S, Kavey RE. Dyslipidemia and pediatric obesity. Pediatr Clin North Am. 2011;58:1363-73.

103. National Heart, Lung, and Blood Institute, US Department of Health and Human Service, National Institutes of Health. Expert Panel on Integrated Guidelines for Cardiovascular health and Risk Reduction in Children and Adolescents, Summary Report. October 2012. https://www.nhlbi.nih.gov/files/docs/peds_guidelines_sum.pdf 104. Koskinen J; Magnussen CG, Sinaiko A, et al. Childhood age and associations between childhood metabolic syndrome and adult risk for metabolic syndrome, Type 2 diabetes mellitus and carotid intima media thickness: the international childhood cardiovascular cohort consortium. J Am Heart Assoc. 2017;6:3005632.DOI:10.1161/JAHA.117.005632 105. Fernández-Friera, L; Fuster, V, López-Melgar B, et al. Normal LDL-cholesterol levels are associated with subclinical atherosclerosis in the absence of risk factors. J Am Coll Cardiol. 2017;70:24:2979-2991. 106. Fraporti MI, Scherer Adami F, Dutra Rosolen D. Cardiovascular risk factors in children. Rev Port Cardiol. 2017;36(10):699-705. 107. Zabarsky G; Beek C; Hagman E, Pierpont B, Caprio S, Weiss R. Impact of severe obesity on cardiovascular risk factors in youth. J Pediatr. 2018;192:105-14. 108. Reinehr T; Wunsch R, Pütter C; Scherag A. Relationship between carotid intima-media thickness and metabolic syndrome in adolescents. J Pediatr. 2013;163:327-32. 109. Cote AT, Harris KC, Panagiotopoulos C, Sandor GG, Devlin AM. Childhood obesity and cardiovascular dysfunction. J Am Coll Cardiol. 2013;62:1309-19. 110. Ortega FB, Lavie CJ, Blair SN. Obesity and cardiovascular disease. Circ Res. 2016;118:1752-1770. 111. Meyer AA, Kundt G, Lenschow U, Schuff-Werner P, Kienast W. Improvement of early vascular changes and cardiovascular risk factors in obese children after a six-month exercise program. J Am Coll Card. 2006;48:1865-70. 112. Zimmet P, Alberti KG, Kaufmann F, et al. The metabolic syndrome in children and adolescents; an IDF consensus report. Pediatr Diabetes. 2007; 299-386. 113. Grundy SM, Cleeman JI, Daniels SR, et al. Diagnosis and management of the metabolic syndrome: an American Heart Association/ National Heart, Lung and Blood Institute Scientific Statement. Circulation. 2005; 112, 2735–2752. 114. Reinehr T, Kleber M, Toschke AM. Lifestyle intervention in obese children is associated with a decrease of the metabolic syndrome prevalence. Atherosclerosis. 2009;207:174–180. 115. Cook S, Weitzman M, Auinger P, Nguyen M, Dietz W. Prevalence of a metabolic syndrome phenotype in adolescents: findings from the third National Health and Nutrition Examination Survey, 1988 –1994. Arch Pediatr Adolesc Med. 2003;157:821– 827.

116. Boney CM, Verma A, Tucker R, Vohr BR. Metabolic syndrome in childhood: association with birth weight, maternal obesity, and gestational diabetes mellitus. Pediatrics. 2005;115:e290–6. 117. Ibáñez L, Oberfield SE, Witchel S, et al. An International Consortium update: Pathophysiology, diagnosis, and treatment of polycystic ovarian syndrome in adolescence. Horm Res Paediatr. 2017;88:371-395. 118. Rosenfield RL. The diagnosis of polycystic ovary syndrome in adolescents. Pediatrics. 2015;136:1154-1165. 119. Novais EN, Millis MB. Slipped capital femoral epiphysis: prevalence, pathogenesis, and natural history. Clin Orthop Relat Res. 2012; 470 (12): 3432–3438. 120. Gilbert SR, Savage AJ, Whitesell R, Conklin MJ, Fineberg NS. BMI and magnitude of scoliosis at presentation to a specialty clinic. Pediatrics. 2015:135(6)e1417-24. 121. Peck DM, Voss LM, Voss TT. Slipped capital femoral epiphysis: Diagnosis and management. Am Fam Physician. 2017;95:779-784. 122. Perry DC, Metcalfe D, Costa ML, Van Staa T. A nationwide cohort study of slipped capital femoral epiphysis. Arch Dis Child. 2017;102:1132-1136. 123. Sabharwal S. Blount disease: an update. Orthop Clin North Am. 2015;46:37-47. 124. Sabharwal S. Blount disease. J Bone Joint Surg Am. 2009;91:1758-76. 125. Africa JA, Newton KP, Schwimmer JB. Lifestyle interventions including nutrition, exercise, and supplements for nonalcoholic fatty liver disease in children. Dig Dis Sci. 2016;61(5):1375-1386. 126. Anderson EL, Howe LD, Jones HE, Higgins JP, Lawlor DA, Fraser A. The prevalence of non-alcoholic fatty liver disease in children and adolescents: A systematic review and meta-analysis. PloS One. 2015;10:e0140908. 127. Clemente MG, Mandato C, Poeta M, Vajro P. Pediatric non-alcoholic fatty liver disease: Recent solutions, unresolved issues, and future research directions. World J Gastroenterol. 2016;22(36):8078-8093. 128. Goyal NP, Schwimmer JB. The genetics of pediatric nonalcoholic fatty liver disease. Clin Liver Dis. 2018;22:59-71. 129. Hannah WN Jr, Harrison SA. Lifestyle and dietary Interventions in the management of nonalcoholic fatty liver disease. Dig Dis Sci. 2016;61:1365-1374.

130. Lin SC, Heba E, Wolfson T, et al. Noninvasive diagnosis of nonalcoholic fatty liver disease and quantification of liver fat using a new quantitative ultrasound technique. Clin Gastroenterol Hepatol. 2015;13:1337-1345. 131. Middleton JP, Wiener RC, Barnes BH, Gurka MJ, DeBoer MD. Clinical features of pediatric nonalcoholic fatty liver disease: a need for increased awareness and a consensus for screening. Clin Pediatr. 2014;53:1318-1325. 132. Papandreou D, Karavetian M, Karabouta Z, Andreou E. Obese children with metabolic syndrome have 3 times higher risk to have nonalcoholic fatty liver disease compared with those without metabolic syndrome. Int J Endocrinol. 2017;2017:2671692. 133. Parrinello CM, Rudolph BJ, Lazo M, et al. Associations of insulin resistance and glycemia with liver enzymes in Hispanic/Latino youths: Results from the Hispanic Community Children's Health Study/Study of Latino Youth (SOL Youth). J Clin Gastroenterol. 2017; doi: 10.1097/MCG.0000000000000946. 134. Schwimmer JB, Dunn W, Norman GJ, et al. SAFETY study: alanine aminotransferase cutoff values are set too high for reliable detection of pediatric chronic liver disease. Gastroenterology. 2010;138:1357-1364. 135. Vos MB, Abrams SH, Barlow SE, et al. NASPGHAN Clinical Practice Guideline for the Diagnosis and Treatment of Nonalcoholic Fatty Liver Disease in Children: Recommendations from the Expert Committee on NAFLD (ECON) and the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN). J Pediatr Gastroenterol Nutr. 2017;64:319-334. 136. Yang M, Gong S, Ye SQ, et al. Non-alcoholic fatty liver disease in children: focus on nutritional interventions. Nutrients. 2014;6:4691-4705. 137. Nobili V, Alkhouri N, Alisi A, Della Corte C, Fitzpatrick E, Raponi M, et al. Nonalcoholic fatty liver disease: a challenge for pediatricians. JAMA Pediatrics. 2015;169(2):170-6 138. Yoneda M, Imajo K, Takahashi H, et al. Clinical strategy of diagnosing and following patients with nonalcoholic fatty liver disease based on invasive and noninvasive methods. Journal of gastroenterology. 2018;53:181-196. 139. Younossi ZM, Loomba R, Rinella ME, et al. Current and future therapeutic regimens for non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Hepatology. 2017. doi: 10.1002/hep.29724. 140. Younossi ZM, Loomba R, Anstee QM, et al. Diagnostic modalities for non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH) and associated fibrosis. Hepatology. 2017. doi: 10.1002/hep.29721 141. Khalife N, Kantomaa M, Glover V, et al. Childhood attention-deficit/hyperactivity disorder symptoms are risk factors for obesity and physical inactivity in adolescence. J Am Acad Child Adolesc Psychiatry. 2014;53: 425-436. 142. Nigg JT, Johnstone JM, Musser ED, Long HD, Willoughby MT, Shannon J. Attention-deficit/hyperactivity disorder (ADHD) and being overweight/obesity: New data and meta-analysis. Clin Psychol Rev. 2016;43:67-79.

143. Cortese S., Moreira-Maia CR, St. Fleur D, Morcillo-Peñalver C, Rohde LA, Faraone SV. Association Between ADHD and Obesity: A Systematic Review and Meta-Analysis. Am J Psychiatry. 2016;173:34-43. 144. Kooij JJS. Adult ADHD. Diagnostic Assessment and Treatment, 3rd ed. London, Springer-Verlag, 2013. 145. Van Veen MM, Kooij JJ, Boonstra AM, Gordijn MC, Van Someren EJ. Delayed circadian rhythm in adults with attention-deficit/hyperactivity disorder and chronic sleep-onset insomnia. Biol Psychiatry. 2010;67:1091–1096. 146. Kooij JJ, Bijlenga D. The circadian rhythm in adult attention-deficit/hyperactivity disorder: current state of affairs. Expert Rev Neurother. 2013; 13:1107–1116. 147. Schwartz BS, Bailey-Davis L, Bandeen-Roche K, et al. Attention deficit disorder, stimulant use, and childhood body mass index trajectory. Pediatrics. 2014;133:668-676. 148. Quek YH, Tam WWS, Zhang MWB, Ho RCM. Exploring the association between childhood and adolescent obesity and depression: a meta-analysis. Obes Rev. 2017;18:742-754. 149. Sanders RH, Han A, Baker JS, Cobley S. Childhood obesity and its physical and psychological co-morbidities: a systematic review of Australian children and adolescents. Eur J Pedatr. 2015;174:715-746. 150. Schwartz BS, Glass TA, Pollak J, et al. Depression, its co-morbidities and treatment, and childhood body mass index trajectories. Obesity. 2016;24:2585-2592. 151. Goldstein BI, Carnethon MR, Matthews KA, et al. Major depressive disorder and bipolar disorder predispose youth to accelerated atherosclerosis and early cardiovascular disease: A scientific statement from the American Heart Association. Circulation. 2015;132:965-986. 152. Mihalopaulos NL, Spigarelli MG. Comanagement of pediatric depression and obesity: A clear need for evidence. Clin Ther. 2013;37:1933-1937. 153. Fox CK, Gross AC, Rudser KD, Foy AM, Kelley AS. Depression, anxiety, and severity of obesity in adolescents: Is emotional eating the link? Clin Pediatr. 2016;55:1120-5. 154. Wehry AM, Beesdo-Baum K, Hennelly MM, Connolly SD, Strawn JR. Assessment and treatment of anxiety disorders in children and adolescents. Curr Psychiatry Rep. 2015;17:591. doi:10.1007/s11920-015-0591-z 155. Taylor VH, Forhan M, Vigod SN, McIntyre RS, Morrison KM. The impact of obesity on quality of life. Best Pract Res Clin Endocrinol Metab. 2013;27:139-146.

156. Rankin J, Matthews L, Cobley S, et al. Psychological consequences of childhood obesity: psychiatric comorbidity and prevention. Adolesc Health Med Ther. 2016;7:125-46. 157. Thompson JE, Phillips BA, McCracken A, Thomas K, Ward WL. Social anxiety in obese youth in treatment setting. Child Adolesc Social Work J. 2013;30:37-47. 158. Esposito M, Gallai B, Roccella M, et al. Anxiety and depression levels in prepubertal obese children: a case-control study. Neuropsychiatr Dis Treat. 2014;10:1897-1902. 159. Halfon N, Larson K, & Slusser W. Associations between obesity and comorbid mental health, developmental, and physical health conditions in a nationally representative sample of US children aged 10-17. Acad Pediatr. 2013;13:7-13. 160. van Strien T. Causes of emotional eating and matched treatment of obesity. Curr Diab Rep. 2018;18:35. 161. McElroy SL, Hudson JI, Mitchell JE, et al. Efficacy and safety of lisdexamfetamine for treatment of adults with moderate to severe binge-eating disorder: a randomized clinical trial. JAMA Psychiatry. 2015;72:234-46. 162. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders: 5th ed. Washington, D.C, American Psychiatric Association; 2013. 163. McElroy SL, Guerdjikova AI, Mori N., O’Melia AM. Pharmacological management of binge eating disorder: current and emerging treatment options. Ther Clin Risk Manag. 2012:8:219-241. 164. Kessler RC, Berglund PA, Chiu WT, et al. The prevalence and correlates of binge eating disorder in the World Health Organization World Mental Health Surveys. Biol Psychiatry. 2013;73:904-914. 165. Wilfley DE, Wilson GT, Agras WS. The clinical significance of binge eating disorder. Int J Eat Disord. 2003;34 Suppl:S96-S106. 166. Wilson GT, Wilfley DE, Agras WS, Bryson SW. Psychological treatments of binge eating disorder. Arch Gen Psychiatry. 2010;67:94-101. 167. Wang GJ, Geliebter A, Volkow ND, et al. Enhanced striatal dopamine release during food stimulation in binge eating disorder. Obesity. 2011;19: 1601- 1608. 168. Hail L, Le Grange D. Bulimia nervosa in adolescents: prevalence and treatment challenges. Adolesc Health Med Ther. 2018;9:11-16.

169. le Grange D, Crosby RD, Rathouz PJ, Leventhal B. A randomized controlled comparison of family-based treatment and supportive psychotherapy for adolescent bulimia nervosa. Arch Gen Psychiatry. 2007;64:1049-1056. 170. Schmidt U, Lee S, Beecham J, et al. A randomized controlled trial of family therapy and cognitive behavior therapy guided self –care for adolescents with bulimia nervosa and related disorders. Am J Psychiatry. 2007;164:591-598. 171. Mindell JA & Owens JA. A Clinical Guide to Pediatric Sleep: Diagnosis and Management of Sleep Problems; 3rdEd. Wolters Kluwer: Philadelphia; 2015. 172. Allison KC, Lundgren JD, O'Reardon JP, et al. Proposed diagnostic criteria for night eating syndrome. Int J Eat Disord. 2010;43:241-247. 173. Allison KC, Tarves EP. Treatment of night eating syndrome. Psych Clin North Am. 2011;34:785-796. 174. Birketvedt GS, Florholmen J, Sundsfjord J, et al. Behavioral and neuroendocrine characteristics of the night-eating syndrome. JAMA. 1999;282:657- 663. 175. Howell MJ, Schenck CH, Crow SJ. A review of nighttime eating disorders. Sleep Med Rev. 2009;13:23-34. 176. Hymowitz G, Salwen J, Salis KL. A mediational model of obesity related disordered eating: The roles of childhood emotional abuse and self-perception. Eat Behav. 2017;26:27-32. 177. McCuen-Wurst C, Ruggieri M, Allison KC. Disordered eating and obesity: associations between binge-eating disorder, night-eating syndrome, and weight-related comorbidities. Ann N Y Acad Sci. 2018;1411:96-105. 178. Nolan LJ, Geliebter A. Validation of the Night Eating Diagnostic Questionnaire (NEDQ) and its relationship with depression, sleep quality, "food addiction", and body mass index. Appetite. 2017;111:86-95. 179. Pawlow LA, O'Neil PM, Malcolm RJ. Night eating syndrome: effects of brief relaxation training on stress, mood, hunger, and eating patterns. Int J Obes Relat Metab Disord. 2003;27(8):970-978. 180. Winkelman JW, Johnson EA, Richards LM. Sleep-related eating disorder. Handb Clin Neurol. 2011;98:577-585. 181. Auger RR. Sleep related eating disorders. Psychiatry. 2006;3:64-70. 182. Brion A, Flamand M, Oudiette D, Voillery D, Golmard JL, Arnulf I. Sleep-related eating disorder versus sleepwalking: a controlled study. Sleep Med. 2012;13:1094-1101.

183. Farooqi S, O’Rahilly S. Genetics of obesity in humans. Endocr Rev. 2006;27:710–18. 184. Irizarry KA, Miller M, Freemark M, Haqq AM. Prader Willi syndrome: Genetics, Metabolomics, Hormonal Function, and New Approaches to Therapy. Adv Pediatr. 2016;63:47-77. 185. Chung WK. An overview of monogenic and syndromic obesity in humans. Pediatr Blood Cancer. 2012;58:122-8. 186. Jones KL, Jones MC, & Campo M. Smith’s Recognizable Patterns of Human Malformation, 7th ed. Saunders: Philadelphia; 2014. 187. Miller JL, Lynn CH, Driscoll DC, et al. Nutritional phases in Prader-Willi syndrome. Am J Med Genet A. 2011;155A:1040-1049. 188. Holick MF. Vitamin D deficiency. New Engl J Med. 2007;357:266-281. 189. Society for Adolescent Health and Medicine. Recommended vitamin D intake and management of low vitamin D status in adolescents: A position statement of the society for adolescent health and medicine. J Adolesc Health. 2013;52:801-803. 190. Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96:1911-1930. 191. IOM (Institute of Medicine). Dietary intake references for calcium and D. Washington DC: The National Academies Press; 2010. 192. Golden NH, Abrams SA, Committee on Nutrition. Optimizing bone health in children and adolescents. Pediatrics. 2014;134:e1229-e1243. 193. Misra M, Pacaud D, Petryk A, Collett-Solberg PF, Kappy M, Drug and Therapeutics Committee of the Lawson Wilkins Pediatric Endocrine Society. Vitamin D deficiency in children and its management: review of current knowledge and recommendations. Pediatrics. 2008;122:398-417. 194. Smotkin-Tangorra M, Purushothaman R, Gupta A, Nejati G, Anhalt H, Ten S. Prevalence of vitamin D insufficiency in obese children and adolescents. J Pediatr Endocrinol Metab. 2007;20:817-823. 195. Alemzadeh R, Kichler J, Babar G, Calhoun M. Hypovitaminosis D in obese children and adolescents: relationship with adiposity, insulin sensitivity, ethnicity, and season. Metabolism. 2008;57:183-191.

196. Pratt J, Browne A, Browne N, et al. ASMBS Pediatric Metabolic and Bariatric Surgery Guidelines, 2018. SOARD. 2018; 14:882-91. 197. Black JA, White B, Viner RM, Simmons RK. Bariatric surgery for obese children and adolescents: a systematic review and meta-analysis. Obes Rev. 2013;14:634-644. 198. Inge TH, Jenkins TM, Xanthakos SA, et al. Long-term outcomes of bariatric surgery in adolescents with severe obesity (FABS-5+): a prospective follow- up analysis. Lancet Diabetes Endocrinol. 2017;5:165-173. 199. Paulus GF, de Vaan LE, Verdam FJ, Bouvy ND, Ambergen TA, van Heurn LW. Bariatric surgery in morbidly obese adolescents: a systematic review and meta-analysis. Obes Surg. 2015;25:860-878. 200. Vilallonga R, Himpens J, van de Vrande S. Long-Term (7 Years) Follow-Up of Roux-en-Y Gastric Bypass on Obese Adolescent Patients (<18 Years). Obesity Facts. 2016;9:91-100. 201. White B, Doyle J, Colville S, Nicholls D, Viner RM, Christie D. Systematic review of psychological and social outcomes of adolescents undergoing bariatric surgery, and predictors of success. Clin Obes. 2015;5:312-324. 202. Inge TH, Courcoulas, AP, Jenkins TM, et al. Weight loss and health status 3 years after bariatric surgery in adolescents. New Engl J Med. 2016;374:113-23. 203. Theodorous AN, Schwartzberg DM, Burjonrappa, SC. The hunger games: A systematic review of pediatric bariatric surgery. J Pharm Nut Sci. 2015;5 (2): 1-15. 204. Anda RF, Felitti VJ, Bremner JD, et al. The enduring effects of abuse and related adverse experiences in childhood. A convergence of evidence from neurobiology and epidemiology. Eur Arch Psychiatry Clin Neurosci. 2006;256:174-186. 205. Bethell CD, Carle A, Hudziak J, et al. Methods to assess adverse childhood experiences of children and families: Toward approaches to promote child well-being in policy and practice. Acad Pediatr. 2017;17:S51-S69. 206. Center for Disease and Prevention. (2003). ACE Reporter: Origins and Essence of the Study. San Diego. Centers for Disease Control and Prevention. Adverse Childhood Experiences. Retrieved from: https://www.cdc.gov/violenceprevention/acestudy/index.html 207. Dong M, Anda, R.., Felitti, V.J., et al. The interrelatedness of multiple forms of childhood abuse, neglect, and household dysfunction. Child Abuse Negl. 2004;28:771–784. 208. Felitti VJ, Anda RF, Nordenberg D, et al. Relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults. The Adverse Childhood Experiences (ACE) Study. Am J Prev Med. 1998;14:245-258.

209. Fuemmeler BF, Dedert E, McClernon FJ, Beckham JC. Adverse childhood events are associated with obesity and disordered eating: results from a U.S. population-based survey of young adults. J Trauma Stress. 2009;22:329-333. 210. Injury Prevention and Control: Division of Violence Prevention. (2014, May 13). Retrieved from http://www.cdc.gov/violenceprevention/acestudy. 211. Isohookana R, Marttunen M, Hakko H, Riipinen P, Riala K. The impact of adverse childhood experiences on obesity and unhealthy weight control behaviors among adolescents. Compr Psychiatry. 2016;71:17-24. 212. Lynch BA, Agunwamba A, Wilson PM, et al. Adverse family experiences and obesity in children and adolescents in the United States. Prev Med. 2016;90:148- 154. 213. McDonnell CJ, Garbers SV. Adverse Childhood Experiences and Obesity: Systematic Review of Behavioral Interventions for Women. Psychol Trauma. 2017; doi: 10.1037/tra0000313. 214. Rehkopf DH, Headen I, Hubbard A, et al. Adverse childhood experiences and later life adult obesity and smoking in the United States. Ann Epidemiol. 2016;26:488-492.e485. 215. Sacks V., Murphey, D., & Moore, K. (2014). Adverse Childhood Experiences: national and state-level prevalence. Child Trends, July, Publication #2014-28. 216. Schofield TJ, Lee RD, Merrick MT. Safe, stable, nurturing relationships as a moderator of intergenerational continuity of child maltreatment: a meta-analysis. J Adolesc Health. 2013;53(4 Suppl):S32-38. 217. Storrs CT. (2009, October 7). Is Life Expectancy Reduced by a Traumatic Childhood? Retrieved from http://www.scientificamerican.com/article/childhood- adverse-event-life-expectancy-abuse-mortality. 218. Wade R Jr., Shea JA, Rubin D, Wood J. Adverse childhood experiences of low-income urban youth. Pediatrics. 2014;134(1):e13-20. 219. Griffiths LJ, Wolke D, Page AS, Horwood JP, ALSPAC Study Team. Obesity and bullying: different effects for boys and girls. Arch Dis Child. 2006;91:121–125. 220. Janssen I, Craig WM, Boyce WF, Pickett W. Associations between overweight and obesity with bullying behaviors in school-aged children. Pediatrics. 2004;113:1187–1194. 221. Lumeng JC, Forrest P, Appugliese DP, Kaciroti N, Corwyn RF, Bradley RH. Weight status as a predictor of being bullied in third through sixth grades. Pediatric. 2010;125:e1301–e1307.

222. Eisenberg ME, Neumark-Sztainer D, Story M. Associations of weight-based teasing and emotional well-being among adolescents. Arch Pediatr Adolesc Med. 2003;157:733–738. 223. Puhl RM, Luedicke J. Weight-based victimization among adolescents in the school setting: Emotional reactions and coping behaviors. J Youth Adolesc. 2012; 41: 27–40. 224. Hayden-Wade HA, Stein RI, Ghaderi A, Saelens BE, Zabinski MF, Wilfley DE. Prevalence, characteristics, and correlates of teasing experiences among overweight children vs. non-overweight peers. Obes Res. 2005;13:1381–1392. 225. Puhl RM, Peterson JL, Luedicke J. Weight-based victimization: bullying experiences of weight loss treatment-seeking youth. Pediatrics. 2013;131: e1– e9. 226. Himmelstein MS, Puhl RM, Quinn DM. Intersectionality: An understudied framework for addressing weight stigma. Amer J Prev Med. 2017;53:421-431. 227. Himmelstein MS, Puhl RM, Quinn DM. Weight stigma and health: The mediating role of coping responses. Health Psychol. 2018;37:139-147. 228. Kahan S, Puhl RM. The damaging effects of weight bias internalization. Obesity. 2017;25:280-281. 229. Phelan SM, Puhl RM, Burke SE, et al. The mixed impact of medical school on medical students' implicit and explicit weight bias. Med Educ. 2015;49:983-992. 230. Pont SJ, Puhl R, Cook SR, Slusser W., Section on Obesity, Obesity Society. Stigma experienced by children and adolescents with obesity. Pediatrics. 2017;140(6): e20173034. 231. Puhl RM, Heuer CA. The stigma of obesity: a review and update. Obesity. 2009;17:941-964. 232. Puhl RM, Luedicke J, Grilo CM. Obesity bias in training: attitudes, beliefs, and observations among advanced trainees in professional health disciplines. Obesity. 2014;22:1008-1015. 233. Puhl RM, Neumark-Sztainer D, Bryn Austin S, Suh Y, Wakefield DB. Policy actions to address weight-based bullying and eating disorders in schools: Views of teachers and school administrators. J Sch Health. 2016;86:507-515. 234. Puhl RM, Phelan SM, Nadglowski J, Kyle TK. Overcoming weight bias in the management of patients with diabetes and obesity. Clin Diabetes. 2016;34:44-50.

235. Pediatric Quality of Life Inventory: www.pedsql.org. Impact of Weight Quality of Life-Kids: www.qualityoflifeconsulting.com/iwqol-kids.html. 236. Anderson YC, Wynter LE, Treves KF, et al. Assessment of health-related quality of life and psychological well-being of children and adolescents with obesity enrolled in a New Zealand community-based intervention programme: an observational study. BMJ Open. 2017;7:e015770. 237. Buttitta M, Iliescu C, Rousseau A, Guerrien A. Quality of life in overweight and obese children and adolescents: a literature review. Qual Life Res. 2014;23(4):1117-1139. 238. Fonvig CE, Hamann SA, Nielsen TRH, et al. Subjective evaluation of psychosocial well-being in children and youths with overweight or obesity: the impact of multidisciplinary obesity treatment. Qual Life Res. 2017;26:3279-3288. 239. Griffiths LJ, Parsons TJ, Hill AJ. Self-esteem and quality of life in obese children and adolescents: a systematic review. Inter J Pediatr Obes. 2010;5:282-304. 240. Levers-Landis CE, Olayinka O, Burant C, Moore S. Predictors of weight-related quality of life in adolescents who are overweight or obese. J Dev Behav Pediatr. 2018;39:126-135. 241. Lee CT, Lin CY, Strong C, Lin YF, Chou YY, Tsai MC. Metabolic correlates of health-related quality of life among overweight and obese adolescents. BMC Pediatr. 2018;18:25. 242. Modi AC, Loux TJ, Bell SK, Harmon CM, Inge TH, Zeller MH. Weight-specific health-related quality of life in adolescents with extreme obesity. Obesity. 2008;16:2266 – 2271. 243. Mollerup PM, Nielsen TRH, Bøjsøe C, Kloppenborg JT, Baker JL, Holm JC. Quality of life improves in children and adolescents during a community-based overweight and obesity treatment. Qual Life Res. 2017;26:1597-1608. 244. Morrison KM, Shin S, Tarnopolsky M, Taylor VH. Association of depression & health related quality of life with body composition in children and youth with obesity. J Affect Disord. 2015;172:18-23. 245. Pratt KJ, Lamson AL, Swanson MS, Lazorick S, Collier DN. The importance of assessing for depression with HRQOL in treatment seeking obese youth and their caregivers. Qual Life Res. 2012;21:1367-1377. 246. Tsiros MD, Olds T, Buckley JD, et al. Health-related quality of life in obese children and adolescents. Inter J Obes. 2009;33:387-400. 247. Wille N, Bullinger M, Holl R, et al. Health-related quality of life in overweight and obese youths: results of a multicenter study. Health Qual Life Outcomes. 2010;8:36.

248. Zeller MH, Inge TH, Modi AC, et al. Severe obesity and comorbid condition impact on the weight-related quality of life of the adolescent patient. J Pediatr. 2015;166(3):651-659 e654. 249. Boland CL, Harris JB, Harris KB. Pharmacological management of obesity in pediatric patients. Ann Pharmacother. 2015;49:220-232. 250. Kaplowitz P. Is there a role for metformin in the treatment of childhood obesity? Pediatrics. 2017;140: e20171205. 251. Khokhar A, Umpaichitra V, Chin VL, Perez-Colon S. Metformin use in children and adolescents with prediabetes. Pediatr Clin North Amer. 2017;64:1341-1353. 252. McDonagh MS, Selph S, Ozpinar A, Foley C. Systematic review of the benefits and risks of metformin in treating obesity in children aged 18 years and younger. JAMA Pediat. 2014;168:178-184. 253. van der Aa MP, Hoving V, van de Garde EM, de Boer A, Knibbe CA, van der Vorst MM. The effect of eighteen-month metformin treatment in obese adolescents: comparison of results obtained in daily practice with results from a clinical trial. J Obes. 2016;doi: 10.1155/2016/7852648. 254. Apovian C. Naltrexone/bupropion for the treatment of obesity and obesity with Type 2 diabetes. Future Cardiol. 2016;12:129-38. 255. Srivastava G & Apovian C. Current pharmacotherapy for obesity. Nat Rev Endocrinol. 2018;14:12-24. 256. Srivastava G & Apovian C. Future pharmacotherapy for obesity: New anti-obesity drugs on the horizon. Curr Obes Rep. 2018;7:147-181. 257. Khera R, Murad MH, Chandar AK, et al. Association of pharmacological treatments for obesity with weight loss and adverse events: a systematic review and meta-analysis. JAMA. 2016;315:2424-2434. 258. Sherafat-Kazemzadeh R, Yanovski SZ, & Yanovski JA. Pharmacotherapy for childhood obesity: present and future prospects. Int J Obes. 2013;37:1-15. 259. Yanovski SZ & Yanovski JA. Long-term drug treatment for obesity: A systematic and clinical review. JAMA. 2014;311:74-86. 260. Greenway FL, Fujioka K, Plodkowski RA, et al. Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR-I): a multicenter, randomized, double-blind, placebo-controlled phase 3 trial. Lancet. 2010;376:595-605.

261. Guerdjikova AI, Mori N, Casuto LS, McElroy SL. Novel pharmacologic treatment in acute binge eating disorder---role of lisdexamfetamine. Neuropsychiatr Dis Treat. 2016;12:833-841. 262. Coghill DR, Caballero B, Sorooshian S, & Civil R. A systematic review of the safety of lisdexamfetamine dimesylate. CNS Drugs. 2014;28:497- 511. 263. Kelly AS, Rudser KD, Nathan BM, et al. The effect of glucagon-like peptide-1 receptor agonist therapy on body mass index in adolescents with severe obesity: A randomized, placebo-controlled, clinical trial. JAMA Pediatr. 2013;167:355-360. 264. Danne T, Biester T, Kapitzke K, et al. Liraglutide in an adolescent population with obesity: A randomized, double-blind, placebo-controlled 5- week trial to assess safety, tolerability, and pharmacokinetics of liraglutide in adolescents aged 12-17 years. J Pediatr. 2017;181:146-53. 265. Narayanaswami V, Dwoskin LP. Obesity: Current and potential pharmacotherapeutics and targets. Pharmacol Ther. 2017;170:116-147. 266. Fox CK, Marlatt KL, Rudser KD, Kelly AS. Topiramate for weight reduction in adolescents with severe obesity. Clin Pediatr. 2015;54(1):19-24. 267. Domecq JP, Prutsky G, Wang Z, et al. Drugs commonly associated with weight change: A systematic review and meta-analysis. J Clin Endocrinol Metab. 2015;100:363–370. 268. Yilmaz U, Yilmaz TS, Dizdarer G, Akinci G, Güzel O, Tekgül H. Efficacy and tolerability of the first antiepileptic drug in children with newly diagnosed idiopathic epilepsy. Seizure. 2014; 23:252-9. 269. Chen B, Choi H, Hirsch LJ, et al. Cosmetic side effects of antiepileptic drugs in adults with epilepsy. Epilepsy Behav. 2015;42:129–137. 270. Xiao Y, Gan L, Wang J, Luo M, Luo H. Vigabatrin versus carbamazepine monotherapy for epilepsy. Cochrane Database Syst Rev. 2012;18:1:CD008781. 271. Oswald I, Adam K. Benzodiazepines cause small loss of bodyweight. Br Med J. 1980;281:1039-40. 272. Antel J, Hebebrand J. Weight-reducing side effects of the antiepileptic agents topiramate and zonisamide. Handb Exp Pharmacol. 2012;209:433-66. 273. Lyseng-Williamson KA. Levetiracetam: a review of its use in epilepsy. Drugs. 2011;71:489-514.

274. Newcomer JW. Second-generation (atypical) antipsychotics and metabolic effects: a comprehensive literature review. CNS Drugs. 2005;19 Suppl 1:1-93. 275. Berthon B, MacDonald-Wicks LK, Wood LG. A systematic review of the effect of oral glucocorticoids on energy intake, appetite, and body weight in humans. Nutr Res. 2014;34:179–190. 276. Ben-Menachem E. Weight issues for people with epilepsy—A review. Epilepsia. 2007;48 Suppl 9:42-5. 277. McDonagh MS, Peterson K, Thakurta S, Low A. Drug class review: pharmacologic treatments for attention deficit hyperactivity disorder: final update 4 report. Drug Class Reviews. Portland (OR): Oregon Health & Science University; 2011. 278. Ruggiero S, Rafaniello, C, Bravaccio C, et al. Safety of attention-deficit/hyperactivity disorder medications in children: an intensive pharmacosurveillance monitoring study. J Child Adolesc Psychopharmacol. 2012;22:415-22. 279. Shamliyan T, Kane R, Ramakrishnan R, Taylor FR. Episodic migraines in children: limited evidence on preventive pharmacological treatments. J Child Neurol. 2013;28:1320-41. 280. Taylor FR. Weight change associated with the use of migraine-preventive medications. Clin Ther. 2008;30:1069-80. 281. Asconapé J. Some common issues in the use of antiepileptic drugs. Semin Neurol. 2002;22:27-39. 282. Messerli FH, Bell DS, Fonseca V, et al. Body weight changes with beta-blocker use: results from GEMINI. Am J Med. 2007;120:610-5. 283. Curtis JR, Westfall AO, Allison J, et al. Population based assessment of adverse events associated with long-term glucocorticoid use. Arthritis Rheum. 2006;55:420-6. 284. Gallo MF, Lopez LM, Grimes DA, Carayon F, Schulz KF, Helmerholst FM. Combination contraceptives: effects on weight. Cochrane Database Syst Rev. 2014;1:CD003987. 285. Lopez L, Edelman A, Chen M, Otterness C, Trussell J, Helmerholst FM. Progestin-only contraceptives: effects on weight. Cochrane Database Syst Rev. 2013;7:CD008815. 286. Stein SA, Lamos EM, and Davis SN. A review of the efficacy and safety of oral antidiabetic drugs. Expert Opin Drug Saf. 2013;12:153–175.

287. Leucht S, Cipriani A, Spineli L, et al. Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. Lancet. 2013;382:951–962. 288. Dent R, Blackmore A, Peterson A, et al. Changes in body weight and psychotropic drugs: A systematic synthesis of the literature. PLoS One. 2012;7: e36889. 289. Leslie WS, Hankey CR, Lean ME. Weight gain as an adverse effect of some commonly prescribed drugs a systematic review. QJM. 2007;100:395–404. 290. Bray GA, Ryan DH. Medical therapy for the patient with obesity. Circulation. 2012;125:1695-703. 291. Bak M, Fransen A, Janssen J, van Os J, Drukker M. Almost all antipsychotics result in weight gain: a meta-analysis. PLoS One. 2014;9: e94112. 292. Serretti A, Mandelli L. Antidepressants and bodyweight: A comprehensive review and meta-analysis. J Clin Psychiatry. 2010;71:1259-1272. 293 .Uguz F, Sahingoz M, Gunger B, Aksoy F, Askin R. Weight gain and associated factors in patients using newer antidepressant drugs. Gen Hosp Psychiatry. 2015;37:46-8. 294. Uher R, Mors O, Hauser J, et al. Changes in body weight during pharmacological treatment of depression. Int J Neuropsychopharmacol. 2011;14(3):367-75. 295. Ratzoni G, Gothelf D, Brand-Gothelf A, et al. Weight gain associated with olanzapine and risperidone in adolescent patients: a comparative prospective study. J Am Acad Child Adolesc Psychiatry. 2002;41(3):337–343. 296. De Hert M, Dobbelaere M, Sheridan EM, Cohen D, Correll CU. Metabolic and endocrine adverse effects of second-generation antipsychotics in children and adolescents: a systematic review of randomized, placebo controlled trials and guidelines for clinical practice. Eur Psychiatry. 2011;26:144–158. 297. Aman MG, Arnold LE, McDougle CJ, et al. Acute and long-term safety and tolerability of risperidone in children with autism. J Child Adolesc Psychopharmacol. 2005;15:869-884. 298. Bobo WV, Cooper WO, Stein CM, et al. Antipsychotics and the risk of type 2 diabetes mellitus in children and youth. JAMA Psychiatry. 2013;70(10):1067- 1075. 299. Galling B, Roldán A, Nielsen RE, et al. Type 2 diabetes mellitus in youth exposed to antipsychotics: a systematic review and meta-analysis. JAMA Psychiatry. 2016;73(3):247-259.

300. Anagnostou E, Aman MG, Handen BL, et al. Metformin for treatment of overweight induced by atypical antipsychotic medication in young people with autism spectrum disorder. JAMA Psychiatry. 2016;73:928-937. 301. Ilies D, Huet AS, Roy G, Stip E, Amor LB. Clinical factors associated with weight gain in French-Canadian children and adolescents treated with second generation antipsychotics: A 24-month retrospective study. Curr Res Diabetes Obes J. 2017;4(3): CRDOJ.MS.ID.555636. 302. Correll CU, Manu, P, Olshanskiy, V, Napolitano B, Kane JM, Malhotra AK. Cardiometabolic risk of second-generation antipsychotic medications during first-time use in children and adolescents. JAMA. 2009;302:1765–1773. 303. Rehman T, Sachan D, Chitkara A. Serum insulin and leptin levels in children with epilepsy on valproate-associated obesity. J Pediatr Neurosci. 2017;12:135– 137. 304. Verrotti A, Scardapane A, Franzoni E, Manco R, Chiarelli F. Increased oxidative stress in epileptic children treated with valproic acid. Epilepsy Res. 2008;78:171-177. 305. Biton V, Mirza W, Montouris G, Vuong A, Hammer AE, Barrett PS. Weight change associated with valproate and lamotrigine monotherapy in patients with epilepsy. Neurology. 2001;56:172-177. 306. Faught E, Limdi NA. Adverse and beneficial side effects of antiepileptic drugs. In: Ettinger AB, Devinsky O, eds Managing Epilepsy and Co-existing Disorders. Woburn MA:Butterworth-Heinemann;2002:447-464. 307. Hamed SA, Fida NM, Hamed EA. States of serum leptin and insulin in children with epilepsy: risk predictors of weight gain. Eur J Paediatr Neurol. 2009;13:261- 8. 308. Li HF, Zou Y, Xia ZZ, Gao F, Feng JH, Yang CW. Effects of topiramate on weight and metabolism in children with epilepsy. Acta Paediatr. 2009;98(9):1521-5. 309. Shapiro M, Reid A, Olsen B, Taasan M, McNamara J, Nguyen M. Topiramate, zonisamide and weight loss in children and adolescents prescribed psychiatric medications: A medical record review. Int J Psychiatry Med. 2016;51:56-68. 310. Verrotti A, Manco R, Agostinelli S, Coppola J, Chiarelli F. The metabolic syndrome in overweight epileptic patients treated with valproic acid. Epilepsia. 2010;51:268-273. 311. Peterlin BL, Rosso AL, Williams MA, et al. Episodic migraine and obesity and the influence of age, race, and sex. Neurology. 2013;81:1314–21. 312. Hershey AD, Powers SW, Nelson TD, et al. Obesity in the pediatric headache population: a multicenter study. Headache. 2009;49:170–7.

313. Ravid S, Shahar E, Schiff A, Gordon S. Obesity in children with headaches: association with headache type, frequency, and disability. Headache. 2013;53:954–61. 314. Peterlin BL, Rapoport AM, Kurth T. Migraine and obesity: epidemiology, mechanisms, and implications. Headache. 2010;50:631-48. 315. Kinik ST, Alehan F, Erol I, Kanra AR. Obesity and pediatric migraine. Cephalalgia. 2010;30:105–9. 316. Peterlin BL, Calhoun AH, Siegel S, Mathew NT. Rational combination therapy in refractory migraine. Headache. 2008;48:805–19. 317. Oakley CB, Scher AI, Recober A, Peterlin BL. Headache and obesity in the pediatric population. Curr Pain Headache Rep. 2014;18:416. 318. Winner P, Pearlman EM, Linder SL, et al. Topiramate for migraine prevention in children: a randomized, double-blind, placebo-controlled trial. Headache. 2005;45:1304-12. 319. Duffy A, Grof P. Lithium treatment in children and adolescents. Pharmacopsychiatry. 2018;doi:10.1055/a-0575-4179. 320. Weisler RH, Cutler AJ, Ballenger JC, Post RM, Ketter TA. The use of antiepileptic drugs in bipolar disorders: a review based on evidence from controlled trials. CNS Spectr. 2006;11:788–799. 321. Correll C U. Weight gain and metabolic effects of mood stabilizers and antipsychotics in pediatric bipolar disorder: a systematic review and pooled analysis of short-term trials. J Am Acad Child Adolesc Psychiatry. 2007;46:687-700. 322. Patel A, Chan W, Aparasu RR., et al. Effect of psychopharmacotherapy on body mass index among children and adolescents with bipolar disorders. J Child Adolesc Psychopharmacol. 2017;27:349-358. 323. Cates ME, Feldman JM, Boggs AA, Woolley TW, Whaley NP. Efficacy of add-on topiramate therapy in psychiatric patients with weight gain. Ann Pharmacother. 2008;42:505-10. 324. Gracious BL, Krysiak TE, Youngstrom EA. Amantadine treatment of psychotropic-induced weight gain in children and adolescents: case series. J Child Adolesc Psychopharmacol. 2002;12:249-57. 325. Cockerill RG, Biggs BK, Oesterle TS, Croarkin PE. Antidepressant use and body mass index change in overweight adolescents: A historical cohort study. Innov Clin Neurosci. 2014;11:14-21.

326. Jerrell JM, McIntyre RS. Metabolic, digestive, and reproductive adverse effects associated with antimanic treatment in children and adolescents: A retrospective cohort study. Prim Care Companion J Clin Psychiatry. 2010;12: PCC.09m00891.doi:10.4088/PCC.09m00891ora. 327. Rosenbloom AL, Silverstein JH, Amemiya S, Zeitler P, Kingensmith GL, International Society for Pediatric and Adolescent Diabetes. ISPAD clinical practice consensus guidelines 2006-2007. Type 2 diabetes mellitus in the child and adolescent. Pediatr Diabetes. 2008;9:512-526. 328. Mayer-Davis EJ, Lawrence JM, Dabelea D, et al. Incidence Trends of Type 1 and Type 2 Diabetes among Youths, 2002-2012. N Engl J Med. 2017;376:1419- 1429. 329. Urakami T. New insights into the pharmacological treatment of pediatric patients with type 2 diabetes. Clin Pediatr Endocrinol. 2018;27: 1–8. 330. Jones KL, Arslanian S, Peterokova VA, Park JS, Tomlinson MJ. Effect of metformin in pediatric patients with type 2 diabetes: a randomized controlled trial. Diabetes Care. 2002;25:89-94. 331. TODAY Study Group, Zeitler P, Hirst K, Pyle L, et al. A clinical trial to maintain glycemic control in youth with type 2 diabetes. New Engl J Med. 2012;366:2247–2256. 332. Tamborlane WV, Haymond MW, Dunger D, et al. Expanding treatment options for youth with type 2 diabetes: Current problems and proposed solutions: A white paper from the NICHD Diabetes Working Group. Diabetes Care. 2016;39:323–9. 333. Laffel L, Chang N, Grey M, et al. Metformin monotherapy in youth with recent onset type 2 diabetes: experience from the prerandomization run-in phase of the TODAY study. Pediatr Diabetes. 2012;13:369–75. 334. Arslanian S., TODAY study. Treatment effects on insulin sensitivity and b-cell function in TODAY. Pediatr Diabetes. 2012;13(Suppl 17):1–14. 335. Raman VS, Heptulla RA. New potential adjuncts to treatment of children with type 1 diabetes mellitus. Pediatr Res. 2009;65:370–374. 336. Sellers EA, Dean HJ. Short-term insulin therapy in adolescents with type 2 diabetes mellitus. J Pediatr Endocrinol Metab. 2004;17,:1561–1564. 337. Bretzel RG, Nuber U, Landgraf W, Owens DR, Bradley C, & Linn T. Once-daily basal insulin glargine versus thrice-daily prandial insulin lispro in people with type 2 diabetes on oral hypoglycaemic agents (APOLLO): an open randomised controlled trial. Lancet. 2008;371:1073–1084. 338. Gottschalk M, Danne T, Vlajnic A, Cara JF. Glimepiride versus metformin as monotherapy in pediatric patients with type 2 diabetes: a randomized, single-blind comparative study. Diabetes Care. 2007;30:790–794. 339. Hadjiyannakis S, Buchholz A, Chanoine JP, et al. The Edmonton Obesity Staging System for Pediatrics: A proposed clinical staging system for pediatric obesity. Paediatr Child Health. 2016;21:21-26.

Nothing to Disclose: Nancy T. Browne, MS, PPCNP-BC, CBN, FAANP; Marisa Censani, MD; Suzanne E. Cuda, MD, FAAP, FOMA; Madeline Joseph, MD, FAAP, FACEP; Valerie O’Hara, DO, FAAP; Lauren Rieck