The prevalence of obesity in childhood and adolescence has increased dramatically in the United States and in all developed countries since the early 1970s. Throughout childhood, obesity is defined as a body mass index (BMI) at or above the 95th percentile for age and sex using standard Centers for Disease Control and Prevention (CDC) growth curves; overweight is defined as BMI greater than the 85th to the 94th percentile. From National Health and Nutrition Examination Surveys (NHANES) data, the prevalence of obesity in 12- to 19-year-olds was 6.1% in 1971–1974 and increased serially at each evaluation to 20.5% in 2011–2012 (Figure 4-1).¹ Overall, 23.9 million American children (32% of boys and 31.6% of girls) have a BMI at or above the 85th percentile and are classified as overweight or obese.²

There are major discrepancies in obesity prevalence by sex, by racial and ethnic group, and by socioeconomic status (SES). From NHANES 2011–2012, 18.3% of non-Hispanic white male adolescents and 20.9% of non-Hispanic white female adolescents were obese compared with 21.4% of non-Hispanic black males and 22.7% of non-Hispanic black females, 23.9% of Hispanic males and 21.3% of Hispanic females, and 14.8% of Asian males and 7.3% of Asian females.¹ Using parental education as an SES standard, data from NHANES and from the National Survey of Children’s Health show that, since 2002, obesity rates have declined to less than 10% in adolescents whose parents have at least a 4-year college degree, close to the prevalence in 1970; this compares with a prevalence of 20%–25% in adolescents whose parents have at most a high school education.³

The severity of obesity has also been increasing exponentially over time. Severe obesity is defined as BMI greater than 120% of the 95th percentile for age/sex or an absolute BMI greater than 35 kg/m². From NHANES data, the prevalence of severe obesity is 5%–7% in males and 4%–6% in females.⁴ This is the fastest-growing subcategory of obesity in children and adolescents, in males and females, and in all racial/ethnic groups.⁵

Taken together, these statistics provide overwhelming evidence that obesity is an important problem for those who provide health care to adolescent females. In addition, obesity tracks strongly from childhood into adulthood, with an overall predicted prevalence of about 70%.⁴ In the Bogalusa Heart Study, of those with severe obesity at 12 years of age, 100% were obese as adults; 65% were morbidly obese, with BMI above 40 kg/m².⁶ Obesity is directly associated with risk factors for cardiovascular disease (CVD), including adverse levels of lipids and blood pressure (BP); metabolic risks, including severe insulin resistance and glucose intolerance; plus inflammation.^7,8,9,10 Severe obesity is even more strongly linked to increased cardiovascular risk. Investigators from the Bogalusa Heart Study quantified cardiovascular and metabolic risk factors, including dyslipidemia, hypertension, and hyperinsulinemia, in children 5 to 17 years of age. Among children with a BMI greater than the 95th percentile, 70%, 39%, and 18% had 1, 2, or 3 or more CVD risk factors, respectively. Contrast this with children with a BMI above the 99th percentile, with 84%, 59%, and 33% having 1, 2, or 3 or more identified CVD risk factors, respectively.⁶ Obese adolescents are clearly at high risk for CVD.

Evidence for the impact of obesity and its associated constellation of risk factors on the heart and coronary vasculature of obese adolescents comes from many sources. Noninvasive imaging demonstrates that obesity in adolescence predicts abnormalities of left ventricular (LV) hypertrophy and function, plus increased carotid thickness and stiffness in adult life.^11,12,13 These are known precursors of clinical CVD. Pathologic studies link obesity and CVD risk factors associated with obesity directly to the presence of early atherosclerosis in the coronary arteries and aorta in adolescents and young adults who died suddenly and unexpectedly.^14,15 There are now longitudinal studies linking adolescent obesity to coronary heart disease events in adult life. In the Princeton Lipid Research Follow-Up Study, obese adolescents with insulin resistance and dyslipidemia developed clinical CVD events at 28-year follow-up when compared with subjects without this risk constellation in adolescence.¹⁶

Identification and management of obesity are important issues for all those who provide care to adolescent females. Adolescence is a time when health habits are formed and risk behaviors like poor diet, physical inactivity, and cigarette smoking are often initiated. Primary care physicians are well positioned to provide important health guidance in this critical time period. The US Preventive Services Task Force provides evidence-based guidelines for adolescent health care in which screening for obesity is specifically recommended.¹⁷ Guidance for identification and management of obesity in adolescents is provided in the 2011 National Heart, Lung, and Blood Institute (NHLBI) Expert Panel Guidelines for Cardiovascular Health (Table 4-1).¹⁸ The first step is calculation and recording of BMI, with defined steps for specific management of elevated BMI and for identification of associated cardiovascular risks. All of this information is of special importance to those providing gynecologic and obstetric care to adolescents because the initial reproductive health visit is recommended to take place between 13 and 17 years of age.¹⁹ An analysis of adolescent health care visits revealed that the gynecologist is identified as the primary physician for 36% of older female adolescents, so screening for obesity, dyslipidemia, hypertension, insulin resistance, and type 2 diabetes will often need to occur in this setting.²⁰

Puberty is the complex process by which children develop secondary sexual characteristics and reproductive competence. The series of biologic changes that characterize the process involves complex neural and endocrinologic interactions that are described in terms of sequence and timing. Beginning in 1962, Tanner defined 5 specific stages of breast and pubic hair development in girls; these remain the cornerstone for describing pubertal development.^21,22 The Tanner stages are shown in Table 4-2, Table 4-3, and Figure 4-2.

There has been a well-documented decrease in the age of puberty (defined as the onset of menarche), from 16 to 17 years in the late 19th century to approximately 13 years of age by the middle of the 20th century, attributed to improved health and nutrition.²³ In the United States, by 1970 there was a further decline to just under 13 years of age.²⁴ Over the last 40 years, a gradual decrease has continued, so that white girls in the United States experience their first menstrual periods at 12.6 years, African American girls at 12.1 years, and Latinas at 12.2 years.²⁵ Earlier age at menarche has been strongly linked to obesity in multiple epidemiologic studies.²⁶ For example, in a longitudinal, multisite cohort study, white and black girls recruited at 9 years of age were divided into 3 groups based on age at menarche. The girls with earliest menarche had significantly higher mean BMI than the midonset girls, who had higher mean BMI than the late-onset group.²⁷ In the Bogalusa Heart Study, serial cross-sectional studies performed in 6- to 17-year-old girls showed that earlier age at menarche correlated significantly with increasing BMI.²⁸

In addition to the decrease in the age of menarche, there has been an even greater decline in the age at initiation of breast development. A longitudinal multisite study of more than a thousand girls followed from 6 to 8 years of age showed that at 7 years of age, 10.4% of white girls, 23.4% of black girls, and 14.9% of Hispanic girls had attained Tanner stage 2 or greater breast development.^29,30 Adiposity in early childhood has been shown to precede early breast development, with elevated age-normalized BMI at 3 years of age and increased velocity of BMI change from 3 to 7 years of age each significantly correlated with earlier breast development.³¹ Ascertainment of the Tanner stage of breast development can be complicated by the presence of obesity because fat tissue can be mistaken for breast tissue. This has been specifically addressed in longitudinal studies by use of palpation for glandular tissue rather than inspection alone or by use of the Tanner-described characteristics of areolar development.^26,30 These methods should be used by clinicians in assessing pubertal stage in obese girls.

Puberty is known to be associated with a reduction in insulin sensitivity in all adolescents. The fall in insulin sensitivity during puberty is associated with a compensatory increase in insulin secretion.^32,33 This hyperinsulinemic pattern is exaggerated in obese adolescents. In adults, the combination of insulin resistance with obesity is characteristic of the metabolic syndrome and frequently presages development of overt type 2 diabetes. In the Bogalusa Heart Study, serial cross-sectional surveys showed that early menarche was associated with higher BMI and fasting insulin levels in childhood and adolescence and with higher fasting glucose (FG) levels in young adulthood.³⁴

The mechanisms that underlie the association between childhood obesity and earlier pubarche are unclear. One potential explanation is related to leptin, a hormone produced by adipocytes that regulates appetite. Leptin levels are elevated in obese children, and there is a high correlation between leptin levels and BMI.³⁵ Both cross-sectional and longitudinal studies indicated a marked rise in serum leptin concentrations preceding changes in luteinizing hormone (LH) and estradiol, the hormones that initiate puberty.³⁶ Higher leptin levels are significantly associated with lower age at menarche.³⁷ A threshold level of leptin is thought to be necessary for puberty to progress, so elevated levels of leptin associated with obesity may function as a permissive factor allowing early initiation of puberty.³⁸

New research suggests that a combination of obesity-related hormonal disturbances together with inflammation, known to be increased in obese individuals, could explain the observed relationship between obesity and the declining age of puberty in girls. Sex hormone–binding globulin (SHBG) binds to the sex hormones androgen and estrogen. SHBG levels are initially high in childhood but decline significantly before puberty; this is thought to potentially be a critical factor in pubertal initiation. In a recently released longitudinal study, SHBG levels correlated inversely with BMI and insulin and positively with the inflammatory marker C-reactive protein. Obese girls had lower SHBG levels at 5 years of age, reached Tanner stage 2 earlier, and had earlier LH secretion and earlier menarche.³⁹

Other studies suggest that environmental chemicals are important in the etiology of early puberty. We are exposed to many estrogenically active chemicals, so-called xenoestrogens, in the course of everyday life. These include phthalates, parabens, and phenols, which are components in consumer products such as plastics, detergents, pharmaceuticals, and cosmetics. Findings from NHANES showed that the most common phthalates, parabens and phenols, are detectable in the urine of more than 90% of Americans.⁴⁰ A small study identified phthalate esters in the serum of Puerto Rican girls with premature breast development; this study was not controlled for BMI.⁴¹ Postmenopausal women with high serum levels of phthalates and phenols were found to have elevated breast density, a marker for risk of breast cancer, on mammography.⁴² Further research is warranted to evaluate the relative roles of obesity and estrogenically active chemicals in endocrine disruption, including premature thelarche.

Regardless of the specific etiology, obesity-related early puberty has important health implications. Several large studies have shown an increased incidence of psychosocial problems, including depression, anxiety, and risk-taking behaviors.⁴³ Early development of breast tissue and early puberty are also known to be risk factors for breast cancer, presumably because of the prolonged exposure to estrogen. A meta-analysis showed that breast cancer risk increases by 5% for each year younger at menarche.⁴⁴ Younger age at breast development was shown to independently increase the risk of breast cancer in a recent cohort study.⁴⁵ Finally, obesity-related early puberty predicts adult obesity and all of its important comorbidities: hypertension, dyslipidemia, diabetes, and premature atherosclerotic disease.^43,46

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women. Originally described in adult females with infertility and hyperandrogenism, the diagnosis has now broadened to include a heterogeneous group of disorders. There is a strong familial basis, but no single underlying genetic abnormality has been defined, suggesting that PCOS develops from a combination of heritable and environmental factors, among which obesity is prominent. Adult females with PCOS present with varying phenotypes in different clinical settings based on their symptoms (acne, hirsutism, or hair loss to dermatology; infertility to obstetrics; and irregular periods to gynecology), so there needs to be a high index of suspicion to correctly identify all cases. The most recent evidence-based guideline, published in 2013, recommends using the presence of 2 of these 3 criteria as diagnostic:

1. 
   

   Androgen excess, diagnosed clinically or biochemically;

   
   
2. 
   

   Ovulatory dysfunction, either oligo- or anovulation;

   
   
3. 
   

   Polycystic ovaries on ultrasound using defined criteria.

These factors are described in detail in Table 4-4. The expert panel who developed these guidelines also recommended a change in name because the presence of polycystic ovaries is not a requirement for diagnosis.⁴⁷

Polycystic ovary syndrome is commonly associated with obesity (present in 50% of patients) and with insulin resistance; impaired glucose tolerance and overt type 2 diabetes are also well described, reported in up to 38% of women with PCOS. Evidence is inconclusive that this constellation of risk factors, when associated with hyperandrogenism in PCOS, increases risk for premature atherosclerotic disease beyond the risk associated with the baseline constellation.

The diagnosis of PCOS in adolescence is challenging because the normal physiology of adolescence mimics many PCOS features. Oligomenorrhea is common after menarche during normal puberty, as is acne, considered a sign of hyperandrogenism in adults. Multifollicular ovarian morphology, a normal pubertal appearance, can be interpreted as polycystic ovaries on ultrasound evaluation.⁴⁸ Insulin resistance is also a normal feature of the pubertal transition. The diagnosis of PCOS can be especially challenging in obese adolescents because girls with BMI greater than the 95th percentile for age have been consistently shown to have significantly higher levels of insulin and testosterone than normal-weight girls at the same pubertal stage.⁴⁹ Finally, adolescent girls with PCOS have an increased risk of the metabolic syndrome associated with increasing androgen levels, independent of obesity and insulin resistance.⁴⁸

Current guidelines suggest consideration of PCOS in adolescent girls with persistent oligomenorrhea, particularly when there is a positive family history of PCOS. In this setting, the presence of clinical signs of androgen excess or biochemical evidence of hyperandrogenism can be used to make the diagnosis in the absence of other causes for androgen excess.⁴⁷ Demonstration of androgen excess can be difficult because of variability in testosterone levels by assay and by lab norms and because there are asymptomatic women with mild androgen excess. A plasma-free testosterone level above the normal adult range is the best single indicator of androgen excess. Anovulatory symptoms plus polycystic ovary morphology on ultrasound are not sufficient to make a diagnosis of PCOS in adolescents as multifollicular ovarian morphology is a normal feature in adolescence. Other causes to be excluded include thyroid dysfunction, hyperprolactinemia, nonclassical congenital adrenal hyperplasia, and Cushing’s syndrome.⁴⁷ Some have proposed that the heterogeneity of clinical and biochemical factors in women with PCOS can be explained by the action of early-onset obesity in genetically susceptible individuals.⁵⁰ Further research is needed to clarify a potential early role for obesity-mediated hyperandrogenism in the genesis of PCOS in susceptible peripubertal girls.

Once the diagnosis of PCOS is made, current guidelines recommend an oral glucose tolerance test (OGTT) to screen for impaired glucose tolerance, with rescreening every 3–5 years.⁴⁷ Comprehensive cardiovascular and metabolic risk screening would also include a fasting lipid profile, BP evaluation and measurement of hepatic function. As treatment, hormonal contraceptives are recommended as the first-line approach for menstrual abnormalities, hirsutism, and acne. Lifestyle therapy is recommended as the primary approach to obesity and insulin resistance, with addition of metformin if there is impaired glucose tolerance or type 2 diabetes mellitus (T2DM).⁴⁷ Recent research suggests that severe insulin resistance is characteristic of PCOS in obese adolescent females and that metformin should always be considered in this setting.⁵¹

Childbearing in the teenage years has been declining steadily since 1960. In the most recent report from the National Division of Vital Statistics, published in 2014, the birth rate of 26.6 births per 1000 teenagers aged 15 to 19 years is less than half the 1991 rate.⁵² The birth rate has also declined for 15- to 17-year-olds and for all racial and ethnic groups (Figure 4-3). There have been similar steady declines in the rates of pregnancies and abortions in teenaged females across all racial and ethnic groups.⁵³

Unfortunately, when babies are born to teenaged mothers, they have a significantly increased risk for a variety of poor pregnancy outcomes, with highest risks in the youngest mothers. From 2012 data, 9.6% of babies born to 15- to 17-year-old mothers had low birth weight compared with 9.2% of babies born to 18- to 19-year-old mothers and 7.9% to mothers over 20 years of age.⁵³ Preterm birth rates are significantly higher for young teenaged mothers: In this instance, 14.7% of babies are born prematurely to 15- to 17-year-olds compared with 12.6% to 18- to 19-year-olds and 11.4% to mothers over 20. Low birth weight and premature birth are associated with greater risk for illness, developmental delays, and death in the first year of life. In 2010, the infant mortality rate averaged 9 per 1000 live births for mothers 15–19 years of age compared with 5.87 per 1000 for women aged 20 and over.

Pregnancy in the obese adolescent occurs in this high-risk context with significant additional obesity-related risk to maternal and fetal health. In adults, maternal obesity is associated with significantly increased risk for pregnancy complications, including preeclampsia, hypertension, gestational diabetes, miscarriage, preterm delivery, cesarean delivery, and stillbirth.^54,55 Obesity during pregnancy is also associated with increased use of health care and physician services and longer hospital stays for delivery. Studies in pregnant obese adolescents confirmed these same risks, with a higher prevalence of maternal hypertension, gestational diabetes, preeclampsia, cesarean delivery, and early stillbirth.⁵⁶

Obesity has important health consequences for mothers after delivery. Adolescent females with high prepregnancy BMI and with excessive gestational weight gain are at known risk for postpartum weight retention and subsequent sustained obesity. From NHANES data, teen birth is a significant independent predictor of overweight and obesity later in life.⁵⁷ Gestational diabetes mellitus (GDM), strongly linked to prepartum BMI and excessive weight gain in pregnancy, also predicts development of type 2 diabetes: Approximately 50% of obese women with GDM will develop type 2 diabetes in the first decade postpregnancy.⁵⁸ In epidemiologic studies, history of GDM is also associated with increased risk of developing the metabolic syndrome and excess heart disease risk.⁵⁹ In the longitudinal Coronary Artery Risk Development in Young Adults (CARDIA) study, women were followed prospectively from a baseline age of 18–30 years and underwent carotid artery imaging 20 years later as a noninvasive measure of atherosclerosis. Women with GDM history had significantly greater carotid intima media thickness compared with women without GDM. The difference was attenuated but still significant when prepregnancy BMI was included in the analysis.⁶⁰ These increased risks for type 2 diabetes, metabolic syndrome, and CVD are even more serious when pregnancy occurs in an obese teenager because the metabolic insults occur earlier in life and the duration of risk exposure is extended.

Obesity in pregnancy is also associated with increased risks for offspring, independent of pregnancy complications. As noted, there is a higher incidence of premature birth and low birth weight, and these are associated with significantly greater risk for illness, developmental delay, and death in the first year of life.^52,53,54,55 Infants born to obese mothers have an increased risk for obesity developing in childhood and persisting into adult life. This relationship was even stronger when GDM was present.^61,62

Maternal obesity is significantly linked to congenital anomalies in offspring, including congenital heart disease and neural tube defects, with increasing risk with increasing adiposity.⁶³ Overweight and obese women who lose weight before pregnancy have been shown to have healthier pregnancies. The American Congress of Obstetricians and Gynecologists has developed specific recommendations for management of pregnancy in obese women.⁶⁴ These include preconception assessment and counseling about the maternal and fetal risks associated with obesity in pregnancy and referral to a weight reduction program. At the initial prenatal visit, measurement of height, weight, and BMI is recommended to inform appropriate gestational weight gain for the obstetrician and the patient. Nutritional counseling should be made available and regular exercise recommended. Anesthesia consultation is recommended before labor because of the increased problems with pain management during labor and anesthesia should cesarean section be necessary. There are specific recommendations to reduce the risk for wound breakdown, infections and venous thromboembolism after cesarean section. Finally, weight reduction counseling should be continued postpartum and before any attempt at another pregnancy. All of these recommendations apply equally to the pregnant, obese adolescent. In addition, the America Academy of Pediatrics (AAP) has developed recommendations for a teen-friendly clinic setting to provide comprehensive reproductive health care while addressing the unique biologic, cognitive, and psychosocial needs of adolescents.⁶⁵

Obesity in adolescence is strongly associated with a range of serious comorbidities, including hypertension, dyslipidemia, insulin resistance/prediabetes, nonalcoholic fatty liver disease (NAFLD), bone and joint problems, sleep apnea, and social/psychological problems. Looking at just the risk factors for CVD, 70% of obese youth aged 5 to 17 years have at least 1 risk factor.⁶ Obesity has important long-term health effects, including CVD and stroke, type 2 diabetes, and cancer. In fact, current adolescent overweight is forecast to increase future adult obesity by 5% to 15% by 2035, resulting in more than 100,000 excess prevalent cases of CVD.⁶⁶ In this section, the most important comorbidities associated with obesity in adolescence are reviewed, and diagnosis and topic-specific management strategies are outlined. An overall approach to management of obesity in adolescents ends the section.

Hypertension

Prevalence and Significance

Blood pressure levels that define hypertension in adults are clear, derived from outcome data demonstrating increased risk for CVD when systolic BP exceeds 140 mm Hg and diastolic BP exceeds 90 mm Hg. Hypertension in children and adolescents is more difficult to define because outcome data are largely unavailable and BP is strongly correlated with age, gender, and body size. This has resulted in tables of normative BP values based on age, sex, and height.⁶⁷ Using these tables, hypertension in adolescents is defined as systolic or diastolic BP greater than the 95th percentile for age, sex, and height on at least 3 separate occasions. Prehypertension is defined as BP readings greater than 120/80 mm Hg but less than the 95th percentile on 3 separate occasions.

Using this definition, the overall prevalence of hypertension in adolescence averages 3.5%, but it is substantially higher in obese adolescents. In a study of high school students, the prevalence of hypertension and prehypertension combined was 30% in adolescent boys and 23% to 30% in adolescent girls, depending on ethnicity.⁶⁸ From a long-term follow-up study, individuals who were obese at a mean age of 12 years had quadruple the risk of hypertension as adults at a mean age of 33 years.⁶⁹ Obesity is the largest single risk factor for hypertension in childhood and is a strong predictor of hypertension in adulthood.

Pathophysiology of Obesity-Related Hypertension

The mechanisms by which obesity contributes to the development of hypertension are multiple, complex, and, as yet, incompletely understood. Sodium retention is believed by many to be the common pathway leading to obesity-related hypertension.⁷⁰

1. 
   

   Hyperinsulinemia: Hyperinsulinemia, often seen with abdominal obesity, can result in chronic sodium retention by direct effects on the renal tubules and indirectly through stimulation of the sympathetic nervous system (SNS) and augmentation of aldosterone secretion. Insulin is also believed to be the signal that links dietary intake and nutritional status to SNS activity; multiple studies have reported increased SNS activity in obese individuals. Increased vascular resistance has been shown to correlate directly with fasting insulin levels and to improve with weight loss.

   
   
2. 
   

   Hyperuricemia: Hypertension is commonly seen in association with hyperuricemia, and this may be primary or related to hyperinsulinemia. In adolescents with essential hypertension, almost 90% were reported to have increased uric acid levels compared with only 30% of adolescents with secondary hypertension and no normotensive controls. In a randomized, double-blind, placebo-controlled, crossover trial of allopurinol in children with newly diagnosed essential hypertension, there was a significant reduction in BP associated with reduction of uric acid levels.⁷⁰

   
   
3. 
   

   Vascular stiffness: Increased measures of vascular stiffness are reported in obese adolescents; these may be primary and therefore contributory to pressure increase or may be secondary to established hypertension. Findings include increased carotid intima media thickness (cIMT) and reduced forearm blood flow response to ischemia with increased minimum vascular resistance. Increased cIMT has been shown to occur with obesity alone and to a greater extent with obesity and hypertension. Increased vascular resistance has been shown to correlate directly with fasting insulin levels and to improve with weight loss.

   
   
4. 
   

   Renin-angiotensin-aldosterone system: Stimulation of the renin-angiotensin-aldosterone system (RAAS) is also believed to contribute to the development of hypertension in obese individuals. The RAAS is an important modulator of efferent glomerular arteriolar tone and of tubular reabsorption of sodium. Obese adolescents have been shown to have significantly higher supine and upright aldosterone levels with no difference in plasma renin levels. In obese adolescents, a given increment in plasma renin activity produced a greater change in aldosterone levels than in nonobese patients, and weight loss resulted in a significant decrease in plasma aldosterone.