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Outcome of Childhood Obesity
CHAPTER 27
Outcome of Childhood Obesity DORTHE C. PEDERSEN, MSC • THORKILD I.A. SØRENSEN, MD • JENNIFER L. BAKER, PHD
INTRODUCTION Alongside with the increasing prevalence of obesity in childhood, the degree of obesity is also increasing, and health effects that used to be limited to adults in middle age are now appearing in children at progressively younger ages. In recognition of the serious concurrent and future health consequences of obesity in childhood, several international organizations have declared it a disease.1 The declaration is controversial, but it serves to highlight that obesity in childhood is a serious risk to health and that it requires professional and effective treatment. In this era where 18% of children worldwide have overweight or obesity,2 the impact on global public health is potentially enormous.
Immediate Consequences of Childhood Obesity Cardiovascular and metabolic complications Excess childhood body mass index (BMI; kg/m2) is linked to numerous cardiovascular disease (CVD) risk factors, such as adverse levels of lipids, lipoproteins, inflammatory cytokines, blood pressure, increased arterial stiffness, and endothelial dysfunction.3 Although direct comparisons across studies are challenging because of the various classification systems used for defining overweight and obesity in childhood, the totality of the evidence supports that the higher the level of excess adiposity, the more likely a child is to have elevated CVD risk factors. These associations are especially evident at the extremes of BMI, such that comparisons of children with BMI values from the 95th to 99th and greater than the 99th percentiles for age and sex show that their risks of having three elevated CVD risk factors increase from 18% to 33%.4 Although studies have yet to pinpoint the youngest ages at which elevated CVD risk factors emerge, adverse levels of lipids, lipoproteins, and blood pressure can be detected in children with excess BMI at ages as young as 6 years.5 Children with obesity are also at increased risks of developing hyperinsulinemia, insulin resistance, and
impaired glucose tolerance. The risks of these keep rising with higher levels of BMI. One study showed that 12% of children with moderate obesity (standard deviation score of 2–2.5) had impaired glucose tolerance, whereas 18% of children with severe obesity (standard deviation score above 2.5) had this condition.6 There are also indications that the risk of having lower glucose tolerance and higher insulin resistance increases with childhood age. Although there can be progression to type 2 diabetes mellitus (T2D), this only manifests in adolescents with severe obesity. Nonetheless, these complications of the hyperglycemic state do not occur in isolation—they tend to cluster with other components of the metabolic syndrome such as high blood pressure and adverse levels of lipids and lipoproteins.6
Hepatic complications The severity of obesity in children is strongly associated with the risk of nonalcoholic fatty liver disease (NAFLD), which ranges from steatosis to steatohepatitis to fibrosis and results in cirrhosis.3 NAFLD has been reported in young children but is more prevalent among children above age 10 years.7 Although the prevalence of NAFLD is up to 80% in children with obesity, compared with 3%–10% in the general pediatric population,7 the more severe cases of the disease can be difficult to estimate as a liver biopsy is needed to make the diagnosis.
Pulmonary complications A child with obesity is at increased risk of suffering from obstructive sleep apnea syndrome (OSAS). Both the prevalence and the severity of the disease increase with BMI, but the association between obesity and OSAS occurs mainly in adolescents.8 Associations with asthma and childhood obesity have been reported as well. A metaanalysis of prospective studies found that the risk of physiciandiagnosed asthma increased by 50% in children with obesity.9
Eating Disorders and Obesity in Children and Adolescents. https://doi.org/10.1016/B978-0-323-54852-6.00027-6 Copyright © 2019 Elsevier Inc. All rights reserved.
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Musculoskeletal complications Children with obesity are more likely to suffer from knee pain and increased rates of fractures.3 Furthermore, Blount disease, a growth disorder where the shin bone bows outward, is more prevalent in children with obesity and the risk increases with the severity of obesity.3 Additionally, children with obesity also have decreased mobility. In turn, this may be related to musculoskeletal fitness as it has been shown to be reduced in children and adolescents with obesity when compared with normal-weight peers. Reduced musculoskeletal fitness may further affect the level of physical activity negatively and thus exacerbate itself.10
Psychologic and psychosocial complications Stigmatization of children with obesity is one of the most well-documented psychosocial aspects of childhood obesity, covered in Chapter 19, but associations with several other psychosocial comorbidities also exist. Age is an important factor for psychosocial complications, as many of these become especially apparent around pubertal ages. Several studies demonstrate that children with obesity are more likely to have a lower health-related quality of life than normal-weight children3 and that the impact is stronger in older than younger children.11 Children with obesity have a four to eight times greater risk of being teased or bullied than their normal-weight peers.11 Studies have also shown that children and adolescents with obesity are more likely to be involved in bullying behavior. The issue is complex as children and adolescents with obesity, especially boys, may be both perpetrators and victims of bullying.12 Childhood obesity is also consistently associated with lower self-esteem, and children with obesity are more likely to have lower perceived self-worth than children with normal weight. Also, older children with obesity have lower self-esteem about their physical appearance than younger children with obesity.11 Obesity in childhood may be associated with depression, but findings are conflicting. Some studies show no increased risk of depression among children with obesity, whereas other studies find increased risks.11 Adolescents with obesity are also more likely to have anxiety than children with normal weight. For both depression and anxiety, there are some indications that girls with obesity are more likely to develop these conditions than boys with obesity.11 A higher prevalence of loss-of-control eating and binge eating symptoms may be found among children and adolescents with obesity than in children with normal weight.3 Nonetheless, it remains unclear
which comes first—the binge eating or the obesity. Worryingly, 24% of girls with overweight or obesity use extreme weight-control behaviors, which include the abuse of laxatives and diet pills as well as vomiting.13 Furthermore, the lifetime prevalence of bulimia is higher in individuals who have an onset of obesity in childhood.11
SUMMARY Risks for concurrent health consequences of obesity in childhood strongly depend on the severity of the obesity, with some indications that risks sharply increase among children with the highest BMI values. Furthermore, there are important effects of age; all health complications are more prevalent in older children. Nonetheless, obesity at young ages is harmful as CVD risk factors and NAFLD are identifiable in young children. In concordance with the physical consequences, age is also important for the risks of psychosocial comorbidities, as older children with obesity were more likely to have lower self-esteem and healthrelated quality of life and engage in extreme weight loss behaviors than younger children. As many of these complications and eating disorders become apparent at adolescent ages, this may be an especially vulnerable life stage for adolescents with obesity.
Long-term Consequences of Childhood Obesity Obesity One of the biggest risks of childhood obesity is the risk that the child will also be obese as an adult and thus suffer from all of its associated comorbidities. Although, as described in Chapter 10, not all obese children become obese adults, the risk increases with increasing childhood BMI. Furthermore, the risk increases with childhood age; an adolescent with obesity is more likely to be an obese adult than a young child with obesity.
All-cause mortality Excess BMI in children and adolescents is associated with an increased risk of all-cause mortality,14 and these risks appear at levels of BMI that are below current definitions of overweight and obesity.15 For example, compared with lean men in the Harvard Growth Study with more than 50 years of follow-up, men with a BMI above the 75th percentile in any 2 years at adolescent ages had a relative risk of all-cause mortality of 1.8. When examining long-term health consequences and searching for the underlying mechanisms, considering whether the associations operate through adult BMI is important.
CHAPTER 27 Outcome of Childhood Obesity In this study, the association remained statistically significant in the subgroup of men for whom adjustment for adult BMI was possible.16 This study did not detect an association in women, but other studies did show similar risk estimates as in men, however, without taking adult body size into account.
Cardiovascular disease Excess child BMI increases risks of coronary heart disease (CHD), and these risks are not limited only to children with overweight or obesity. Using data from a population-based cohort of Danish schoolchildren, we showed that the higher the child’s BMI, the higher the risk of CHD morbidity and mortality. Furthermore, these associations strengthened with childhood age from 7 to 13 years.17 For ischemic stroke, we found that there was a threshold effect of childhood BMI, as below-average BMI values were not associated with the risk, but above-average BMI values were. Compared with children with a BMI in the 25th to 75th percentiles, those with a BMI above the 95th percentile had a 77% increased risk of ischemic stroke at young ages (25–55 years).18
Type 2 diabetes mellitus Obesity in childhood, even among children younger than 6 years of age, increases risks of T2D. A recent metaanalysis found that one standard deviation increase in BMI was associated with an odds ratio of 1.8 and 1.7 among children ages 7–11 years and 12–18 years, respectively.19 A study in the population-based cohort of Danish schoolchildren showed that, again, there was a threshold effect for the association between child BMI and T2D in adulthood. Below-average BMI values did not have associations with T2D. However, at BMI values above average the association between BMI and T2D increased linearly. For example, a child BMI at one standard deviation above average is associated with a more than doubling of the risk of type 2 diabetes during the ages 30 through 46 years, slightly more so in women than in men (hazard ratios of 2.3 for women and 2.1 for men compared with a hazard ratio of 1.0 at average BMI).20
Cancer Excess BMI in childhood is also linked to increased risks of several forms of cancer. Cancer is a heterogeneous disease, and the strength and directions of the associations depend on the type of cancer. Higher childhood BMI is associated with a decreased risk of premenopausal breast cancer, and this is in accord with the known adult associations.21 Few studies in this area
167
on other cancers than breast cancer exist. In our work based on a cohort of Danish schoolchildren, it has been shown that higher childhood BMI values, yet at levels far below internationally accepted definitions of overweight and obesity, are associated with cancer of the liver,22 thyroid,23 pancreas (until the age of 70 years),24 colon,25 and esophagus.26 Associations were also found between BMI and endometrial cancer, but there was a threshold effect; substantially increased risks were only observed at high BMI values (>90th percentile).27
SUMMARY Higher childhood BMI values are associated with both adult morbidity and mortality, and obesity, especially in older children, confers the greatest risk for a wide range of chronic diseases. This series of studies gives insights into how early the origins of many diseases may lie, but they do not demonstrate whether child BMI exerts effects on adult disease independently of adult BMI. Nonetheless, they highlight that obesity in childhood is indicative of risks to adult health.
Weight Patterns from Childhood to Adult Ages and Mortality and Morbidity Relatively, few studies have investigated the association between weight patterns across the life course and risks of morbidity and mortality. A study in Swedish men showed that increases in age-adjusted BMI from age 8 to 20 years increased risks of all-cause and cardiovascular mortality. Men who had overweight at age 8 years, but not at age 20, had similar risk for cardiovascular mortality as men who had normal weight at both ages.15 A study in the cohort of Danish school children examined weight patterns in boys (ages 7–13 years) to early adulthood (around ages 19 years) and the risk of T2D and found that boys who gained in BMI had increased risks of adult T2D. Encouragingly, the study found that boys with overweight at age 7 years but who remitted by age 13 and maintained normal weight as young men reduced their risks of T2D to levels observed among men who were normal weight at all ages.28 Taken together, the results from these studies suggest that the consequences of childhood obesity are reversible if a child normalizes his weight before adolescence, whereas the consequences of obesity in adolescence are not fully reversible. Furthermore, the studies highlight that a substantial weight gain confers a great risk in itself independent of attained body weight and of age for different diseases.
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SUMMARY Overweight and obesity in childhood and adolescence increase risks of current and future health and well-being. Furthermore, the risk of obesity-related consequences increases with age; childhood and adolescence are two very different developmental phases in life. Because physicians are not exempt from stigmatizing children and adolescents with obesity and their families, special care should be taken to establish a good relationship with both the child and the parents to prevent the avoidance of the medical system, which is of obvious importance for this young patient group. Although the risk of negative outcomes increases dramatically at overweight and obese BMI values, for many diseases the risks increase across the entire range of BMI, whereas for other diseases there appears to be a threshold effect with increases in risk only for BMI values exceeding the average levels. Although it is intriguing that the adverse effects of childhood obesity seem to be reversible if the weight normalizes before adolescence, interpretations should be made carefully as there is limited evidence in this area. To improve our knowledge and to allow us to disentangle the effects of the severity of obesity and age, future research should focus on BMI across the range and the timing of when excess BMI emerges across the life course. Future studies should undertake careful examinations of the temporality of these associations, especially for the psychologic and psychosocial complications but others as well, as it is unclear whether overweight and obesity precede or follow the conditions. Furthermore, additional study designs are needed to elucidate the causality of these associations. These considerations are important because we need insight into whether the consequences of excess BMI in childhood can be reversed and whether there is an age, where this is no longer possible, as this would call for different approaches for treatment and prevention.
REFERENCES 1. Farpour-Lambert NJ, Baker JL, Hassapidou M, et al. Childhood obesity is a chronic disease demanding specific health care–a position statement from the Childhood Obesity Task Force (COTF) of the European Association for the Study of Obesity (EASO). Obes Facts. 2015;8(5):342–349. 2. NCD Risk Factor Collaboration (NCD-RisC). Data Visualisations, Child & Adolescent Body-Mass Index. http:// www.ncdrisc.org/overweight-prevalence-distributionado.html. Accessed January 31, 2018.
3. Kelly AS, Barlow SE, Rao G, et al. Severe obesity in children and adolescents: identification, associated health risks, and treatment approaches: a scientific statement from the American Heart Association. Circulation. 2013;128(15): 1689–1712. 4. Freedman DS, Mei Z, Srinivasan SR, Berenson GS, Dietz WH. Cardiovascular risk factors and excess adiposity among overweight children and adolescents: the Bogalusa Heart Study. J Pediatr. 2007;150(1):12–17.e12. 5. Skinner AC, Perrin EM, Moss LA, Skelton JA. Cardiometabolic risks and severity of obesity in children and young adults. N Engl J Med. 2015;373(14):1307–1317. 6. Calcaterra V, Klersy C, Muratori T, et al. Prevalence of metabolic syndrome (MS) in children and adolescents with varying degrees of obesity. Clin Endocrinol. 2008; 68(6):868–872. 7. Alisi A, Feldstein AE, Villani A, Raponi M, Nobili V. Pediatric nonalcoholic fatty liver disease: a multidisciplinary approach. Nat Rev Gastroenterol Hepatol. 2012;9(3):152–161. 8. Kohler MJ, Thormaehlen S, Kennedy JD, et al. Differences in the association between obesity and obstructive sleep apnea among children and adolescents. J Clin Sleep Med. 2009;5(6):506–511. 9. Egan KB, Ettinger AS, Bracken MB. Childhood body mass index and subsequent physician-diagnosed asthma: a systematic review and meta-analysis of prospective cohort studies. BMC Pediatr. 2013;13:121. 10. Thivel D, Ring-Dimitriou S, Weghuber D, Frelut ML, O’Malley G. Muscle strength and fitness in pediatric obesity: a systematic review from the European Childhood Obesity Group. Obes Facts. 2016;9(1):52–63. 11. Rankin J, Matthews L, Cobley S, et al. Psychological consequences of childhood obesity: psychiatric comorbidity and prevention. Adolesc Health Med Therapeut. 2016; 7:125–146. 12. Bacchini D, Licenziati MR, Garrasi A, et al. Bullying and victimization in overweight and obese outpatient children and adolescents: an Italian multicentric study. PLoS One. 2015;10(11):e0142715. 13. Neumark-Sztainer DR, Wall MM, Haines JI, Story MT, Sherwood NE, van den Berg PA. Shared risk and protective factors for overweight and disordered eating in adolescents. Am J Prev Med. 2007;33(5):359–369. 14. Mossberg HO. 40-year follow-up of overweight children. Lancet. 1989;2(8661):491–493. 15. Ohlsson C, Bygdell M, Sonden A, Rosengren A, Kindblom JM. Association between excessive BMI increase during puberty and risk of cardiovascular mortality in adult men: a population-based cohort study. Lancet Diabetes Endocrinol. 2016;4(12):1017–1024. 16. Must A, Jacques PF, Dallal GE, Bajema CJ, Dietz WH. Long-term morbidity and mortality of overweight adolescents. A follow-up of the Harvard Growth Study of 1922 to 1935. N Engl J Med. 1992;327(19):1350–1355. 17. Baker JL, Olsen LW, Sørensen TIA. Childhood body-mass index and the risk of coronary heart disease in adulthood. N Engl J Med. 2007;357(23):2329–2337.
CHAPTER 27 Outcome of Childhood Obesity 18. Gjærde LK, Gamborg M, Angquist L, Truelsen TC, Sørensen TIA, Baker JL. Association of childhood body mass index and change in body mass index with first adult ischemic stroke. JAMA Neurol. 2017;74(11):1312–1318. 19. Llewellyn A, Simmonds M, Owen CG, Woolacott N. Childhood obesity as a predictor of morbidity in adulthood: a systematic review and meta-analysis. Obes Rev. 2016;17(1):56–67. 20. Zimmermann E, Bjerregaard LG, Gamborg M, Vaag AA, Sørensen TIA, Baker JL. Childhood body mass index and development of type 2 diabetes throughout adult life-A largescale Danish cohort study. Obesity. 2017;25(5):965–971. 21. Ahlgren M, Melbye M, Wohlfahrt J, Sørensen TIA. Growth patterns and the risk of breast cancer in women. N Engl J Med. 2004;351(16):1619–1626. 22. Berentzen TL, Gamborg M, Holst C, Sørensen TIA, Baker JL. Body mass index in childhood and adult risk of primary liver cancer. J Hepatol. 2014;60(2):325–330. 23. Kitahara CM, Gamborg M, Berrington de Gonzalez A, Sørensen TIA, Baker JL. Childhood height and body mass index were associated with risk of adult thyroid cancer in a large cohort study. Cancer Res. 2014;74(1):235–242.
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24. Nogueira L, Stolzenberg-Solomon R, Gamborg M, Sørensen TIA, Baker JL. Childhood body mass index and risk of adult pancreatic cancer. Curr Dev Nutr. 2017;1(10). 25. Jensen BW, Gamborg M, Gogenur I, Renehan AG, Sørensen TIA, Baker JL. Childhood body mass index and height in relation to site-specific risks of colorectal cancers in adult life. Eur J Epidemiol. 2017;32(12):1097–1106. 26. Cook MB, Freedman ND, Gamborg M, Sørensen TIA, Baker JL. Childhood body mass index in relation to future risk of oesophageal adenocarcinoma. Br J Cancer. 2015;112(3):601–607. 27. Aarestrup J, Gamborg M, Ulrich LG, Sørensen TIA, Baker JL. Childhood body mass index and height and risk of histologic subtypes of endometrial cancer. Int J Obes. 2016;40(7):1096–1102. 28. Bjerregaard LG, Jensen BW, Angquist L, Osler M, Sørensen TIA, Baker JL. Change in overweight from childhood to early adulthood and risk of type 2 diabetes. N Engl J Med. 2018;378(14):1302–1312.
Outcome of Childhood Obesity DORTHE C. PEDERSEN, MSC • THORKILD I.A. SØRENSEN, MD • JENNIFER L. BAKER, PHD
INTRODUCTION Alongside with the increasing prevalence of obesity in childhood, the degree of obesity is also increasing, and health effects that used to be limited to adults in middle age are now appearing in children at progressively younger ages. In recognition of the serious concurrent and future health consequences of obesity in childhood, several international organizations have declared it a disease.1 The declaration is controversial, but it serves to highlight that obesity in childhood is a serious risk to health and that it requires professional and effective treatment. In this era where 18% of children worldwide have overweight or obesity,2 the impact on global public health is potentially enormous.
Immediate Consequences of Childhood Obesity Cardiovascular and metabolic complications Excess childhood body mass index (BMI; kg/m2) is linked to numerous cardiovascular disease (CVD) risk factors, such as adverse levels of lipids, lipoproteins, inflammatory cytokines, blood pressure, increased arterial stiffness, and endothelial dysfunction.3 Although direct comparisons across studies are challenging because of the various classification systems used for defining overweight and obesity in childhood, the totality of the evidence supports that the higher the level of excess adiposity, the more likely a child is to have elevated CVD risk factors. These associations are especially evident at the extremes of BMI, such that comparisons of children with BMI values from the 95th to 99th and greater than the 99th percentiles for age and sex show that their risks of having three elevated CVD risk factors increase from 18% to 33%.4 Although studies have yet to pinpoint the youngest ages at which elevated CVD risk factors emerge, adverse levels of lipids, lipoproteins, and blood pressure can be detected in children with excess BMI at ages as young as 6 years.5 Children with obesity are also at increased risks of developing hyperinsulinemia, insulin resistance, and
impaired glucose tolerance. The risks of these keep rising with higher levels of BMI. One study showed that 12% of children with moderate obesity (standard deviation score of 2–2.5) had impaired glucose tolerance, whereas 18% of children with severe obesity (standard deviation score above 2.5) had this condition.6 There are also indications that the risk of having lower glucose tolerance and higher insulin resistance increases with childhood age. Although there can be progression to type 2 diabetes mellitus (T2D), this only manifests in adolescents with severe obesity. Nonetheless, these complications of the hyperglycemic state do not occur in isolation—they tend to cluster with other components of the metabolic syndrome such as high blood pressure and adverse levels of lipids and lipoproteins.6
Hepatic complications The severity of obesity in children is strongly associated with the risk of nonalcoholic fatty liver disease (NAFLD), which ranges from steatosis to steatohepatitis to fibrosis and results in cirrhosis.3 NAFLD has been reported in young children but is more prevalent among children above age 10 years.7 Although the prevalence of NAFLD is up to 80% in children with obesity, compared with 3%–10% in the general pediatric population,7 the more severe cases of the disease can be difficult to estimate as a liver biopsy is needed to make the diagnosis.
Pulmonary complications A child with obesity is at increased risk of suffering from obstructive sleep apnea syndrome (OSAS). Both the prevalence and the severity of the disease increase with BMI, but the association between obesity and OSAS occurs mainly in adolescents.8 Associations with asthma and childhood obesity have been reported as well. A metaanalysis of prospective studies found that the risk of physiciandiagnosed asthma increased by 50% in children with obesity.9
Eating Disorders and Obesity in Children and Adolescents. https://doi.org/10.1016/B978-0-323-54852-6.00027-6 Copyright © 2019 Elsevier Inc. All rights reserved.
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Musculoskeletal complications Children with obesity are more likely to suffer from knee pain and increased rates of fractures.3 Furthermore, Blount disease, a growth disorder where the shin bone bows outward, is more prevalent in children with obesity and the risk increases with the severity of obesity.3 Additionally, children with obesity also have decreased mobility. In turn, this may be related to musculoskeletal fitness as it has been shown to be reduced in children and adolescents with obesity when compared with normal-weight peers. Reduced musculoskeletal fitness may further affect the level of physical activity negatively and thus exacerbate itself.10
Psychologic and psychosocial complications Stigmatization of children with obesity is one of the most well-documented psychosocial aspects of childhood obesity, covered in Chapter 19, but associations with several other psychosocial comorbidities also exist. Age is an important factor for psychosocial complications, as many of these become especially apparent around pubertal ages. Several studies demonstrate that children with obesity are more likely to have a lower health-related quality of life than normal-weight children3 and that the impact is stronger in older than younger children.11 Children with obesity have a four to eight times greater risk of being teased or bullied than their normal-weight peers.11 Studies have also shown that children and adolescents with obesity are more likely to be involved in bullying behavior. The issue is complex as children and adolescents with obesity, especially boys, may be both perpetrators and victims of bullying.12 Childhood obesity is also consistently associated with lower self-esteem, and children with obesity are more likely to have lower perceived self-worth than children with normal weight. Also, older children with obesity have lower self-esteem about their physical appearance than younger children with obesity.11 Obesity in childhood may be associated with depression, but findings are conflicting. Some studies show no increased risk of depression among children with obesity, whereas other studies find increased risks.11 Adolescents with obesity are also more likely to have anxiety than children with normal weight. For both depression and anxiety, there are some indications that girls with obesity are more likely to develop these conditions than boys with obesity.11 A higher prevalence of loss-of-control eating and binge eating symptoms may be found among children and adolescents with obesity than in children with normal weight.3 Nonetheless, it remains unclear
which comes first—the binge eating or the obesity. Worryingly, 24% of girls with overweight or obesity use extreme weight-control behaviors, which include the abuse of laxatives and diet pills as well as vomiting.13 Furthermore, the lifetime prevalence of bulimia is higher in individuals who have an onset of obesity in childhood.11
SUMMARY Risks for concurrent health consequences of obesity in childhood strongly depend on the severity of the obesity, with some indications that risks sharply increase among children with the highest BMI values. Furthermore, there are important effects of age; all health complications are more prevalent in older children. Nonetheless, obesity at young ages is harmful as CVD risk factors and NAFLD are identifiable in young children. In concordance with the physical consequences, age is also important for the risks of psychosocial comorbidities, as older children with obesity were more likely to have lower self-esteem and healthrelated quality of life and engage in extreme weight loss behaviors than younger children. As many of these complications and eating disorders become apparent at adolescent ages, this may be an especially vulnerable life stage for adolescents with obesity.
Long-term Consequences of Childhood Obesity Obesity One of the biggest risks of childhood obesity is the risk that the child will also be obese as an adult and thus suffer from all of its associated comorbidities. Although, as described in Chapter 10, not all obese children become obese adults, the risk increases with increasing childhood BMI. Furthermore, the risk increases with childhood age; an adolescent with obesity is more likely to be an obese adult than a young child with obesity.
All-cause mortality Excess BMI in children and adolescents is associated with an increased risk of all-cause mortality,14 and these risks appear at levels of BMI that are below current definitions of overweight and obesity.15 For example, compared with lean men in the Harvard Growth Study with more than 50 years of follow-up, men with a BMI above the 75th percentile in any 2 years at adolescent ages had a relative risk of all-cause mortality of 1.8. When examining long-term health consequences and searching for the underlying mechanisms, considering whether the associations operate through adult BMI is important.
CHAPTER 27 Outcome of Childhood Obesity In this study, the association remained statistically significant in the subgroup of men for whom adjustment for adult BMI was possible.16 This study did not detect an association in women, but other studies did show similar risk estimates as in men, however, without taking adult body size into account.
Cardiovascular disease Excess child BMI increases risks of coronary heart disease (CHD), and these risks are not limited only to children with overweight or obesity. Using data from a population-based cohort of Danish schoolchildren, we showed that the higher the child’s BMI, the higher the risk of CHD morbidity and mortality. Furthermore, these associations strengthened with childhood age from 7 to 13 years.17 For ischemic stroke, we found that there was a threshold effect of childhood BMI, as below-average BMI values were not associated with the risk, but above-average BMI values were. Compared with children with a BMI in the 25th to 75th percentiles, those with a BMI above the 95th percentile had a 77% increased risk of ischemic stroke at young ages (25–55 years).18
Type 2 diabetes mellitus Obesity in childhood, even among children younger than 6 years of age, increases risks of T2D. A recent metaanalysis found that one standard deviation increase in BMI was associated with an odds ratio of 1.8 and 1.7 among children ages 7–11 years and 12–18 years, respectively.19 A study in the population-based cohort of Danish schoolchildren showed that, again, there was a threshold effect for the association between child BMI and T2D in adulthood. Below-average BMI values did not have associations with T2D. However, at BMI values above average the association between BMI and T2D increased linearly. For example, a child BMI at one standard deviation above average is associated with a more than doubling of the risk of type 2 diabetes during the ages 30 through 46 years, slightly more so in women than in men (hazard ratios of 2.3 for women and 2.1 for men compared with a hazard ratio of 1.0 at average BMI).20
Cancer Excess BMI in childhood is also linked to increased risks of several forms of cancer. Cancer is a heterogeneous disease, and the strength and directions of the associations depend on the type of cancer. Higher childhood BMI is associated with a decreased risk of premenopausal breast cancer, and this is in accord with the known adult associations.21 Few studies in this area
167
on other cancers than breast cancer exist. In our work based on a cohort of Danish schoolchildren, it has been shown that higher childhood BMI values, yet at levels far below internationally accepted definitions of overweight and obesity, are associated with cancer of the liver,22 thyroid,23 pancreas (until the age of 70 years),24 colon,25 and esophagus.26 Associations were also found between BMI and endometrial cancer, but there was a threshold effect; substantially increased risks were only observed at high BMI values (>90th percentile).27
SUMMARY Higher childhood BMI values are associated with both adult morbidity and mortality, and obesity, especially in older children, confers the greatest risk for a wide range of chronic diseases. This series of studies gives insights into how early the origins of many diseases may lie, but they do not demonstrate whether child BMI exerts effects on adult disease independently of adult BMI. Nonetheless, they highlight that obesity in childhood is indicative of risks to adult health.
Weight Patterns from Childhood to Adult Ages and Mortality and Morbidity Relatively, few studies have investigated the association between weight patterns across the life course and risks of morbidity and mortality. A study in Swedish men showed that increases in age-adjusted BMI from age 8 to 20 years increased risks of all-cause and cardiovascular mortality. Men who had overweight at age 8 years, but not at age 20, had similar risk for cardiovascular mortality as men who had normal weight at both ages.15 A study in the cohort of Danish school children examined weight patterns in boys (ages 7–13 years) to early adulthood (around ages 19 years) and the risk of T2D and found that boys who gained in BMI had increased risks of adult T2D. Encouragingly, the study found that boys with overweight at age 7 years but who remitted by age 13 and maintained normal weight as young men reduced their risks of T2D to levels observed among men who were normal weight at all ages.28 Taken together, the results from these studies suggest that the consequences of childhood obesity are reversible if a child normalizes his weight before adolescence, whereas the consequences of obesity in adolescence are not fully reversible. Furthermore, the studies highlight that a substantial weight gain confers a great risk in itself independent of attained body weight and of age for different diseases.
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SECTION VIII Course and Outcome
SUMMARY Overweight and obesity in childhood and adolescence increase risks of current and future health and well-being. Furthermore, the risk of obesity-related consequences increases with age; childhood and adolescence are two very different developmental phases in life. Because physicians are not exempt from stigmatizing children and adolescents with obesity and their families, special care should be taken to establish a good relationship with both the child and the parents to prevent the avoidance of the medical system, which is of obvious importance for this young patient group. Although the risk of negative outcomes increases dramatically at overweight and obese BMI values, for many diseases the risks increase across the entire range of BMI, whereas for other diseases there appears to be a threshold effect with increases in risk only for BMI values exceeding the average levels. Although it is intriguing that the adverse effects of childhood obesity seem to be reversible if the weight normalizes before adolescence, interpretations should be made carefully as there is limited evidence in this area. To improve our knowledge and to allow us to disentangle the effects of the severity of obesity and age, future research should focus on BMI across the range and the timing of when excess BMI emerges across the life course. Future studies should undertake careful examinations of the temporality of these associations, especially for the psychologic and psychosocial complications but others as well, as it is unclear whether overweight and obesity precede or follow the conditions. Furthermore, additional study designs are needed to elucidate the causality of these associations. These considerations are important because we need insight into whether the consequences of excess BMI in childhood can be reversed and whether there is an age, where this is no longer possible, as this would call for different approaches for treatment and prevention.
REFERENCES 1. Farpour-Lambert NJ, Baker JL, Hassapidou M, et al. Childhood obesity is a chronic disease demanding specific health care–a position statement from the Childhood Obesity Task Force (COTF) of the European Association for the Study of Obesity (EASO). Obes Facts. 2015;8(5):342–349. 2. NCD Risk Factor Collaboration (NCD-RisC). Data Visualisations, Child & Adolescent Body-Mass Index. http:// www.ncdrisc.org/overweight-prevalence-distributionado.html. Accessed January 31, 2018.
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