What Is the Evidence for Paediatric/Adolescent Bariatric Surgery?

Obesity is a global epidemic. Childhood obesity in particular has become an increasing concern due to the rising prevalence of associated co-morbidities including metabolic syndrome and diabetes, obstructive sleep apnoea syndrome (OSAS) and psychosocial impairments, at ever-younger ages. These co-morbidities have a cumulative health impact, making the duration of obesity increasingly important and predisposing patients to a significant risk of premature morbidity and mortality [1]. As such, childhood obesity is fast becoming the most significant threat to the health of our younger generations.

Lifestyle interventions have been shown to have limited success in treatment of severe obesity in children. In adults, sustained BMI reduction and significant and definitive risk reductions for developing cardiovascular, cancer, endocrine, infectious and psychiatric disorders have been found in surgical cohorts as compared to controls [2]. With such life-changing results in the adult population, why not, then, apply the same intervention prior to the development of complications of co-morbidities in the paediatric population? This article aims to explain the rationale for paediatric bariatric surgery, review the growing evidence base of outcomes and explore the controversies that still exist in order to delineate the future of this growing problem.

Defining obesity in children presents slightly different challenges to that in adults. The body mass index (BMI) provides a relatively good gauge of body fat, whilst being easy to measure and subsequently calculate. As such, standard levels of BMI classify obesity in adults; if the BMI > 30 kg/m², this is considered obese. Children have varying proportions of body fat at varying ages which also differs depending on gender. As such, fixed levels of BMI provide inaccurate comparisons.

In children, gender and age-specific BMI growth charts of large reference populations consider the pattern of growth over time. BMI Z-scores/standard deviation score (BMI-SDS), a measure of how many standard deviations a child’s BMI is above the mean, are used to provide set definitions of obesity. The most widely used definition of ‘severe’ obesity is a BMI > 99th centile, broadly equivalent to a BMI Z-score of +2.5, an adult BMI equivalent 30 kg/m² [3]. Adolescent BMI > 99th centile has specifically been shown to have a strong positive correlation with adverse cardiovascular risk profile [1].

Prevalence of childhood obesity has risen by 47.1% between 1980 and 2013. Although the overall proportion of childhood obesity appears to have plateaued out over the last decade, there is no convincing evidence of a sustainable decline. The National Child Measurement Programme (NCMP) in the UK identified 21.9% children aged 4–5 were classified as overweight or obese, a figure, which rose to one third of 10–11-year-olds [4]. Based on a definition of a BMI > 99th centile, 2.9% of girls and 3.9% of boys in the UK have severe obesity [5]. This finding is paralleled in other developed countries with the prevalence of severe obesity affecting approximately 4% of US adolescents [6]. This is an effect now seen in developing countries with a 60% increase in prevalence in recent years [7]. Childhood obesity is, therefore, a truly global phenomenon of growing concern.

Community-based interventions have yet to demonstrate significant and sustainable results. A 2009 Cochrane review of combined behavioural and lifestyle management of paediatric obesity in 5230 patients as compared to controls demonstrated a − 0.06 overall reduction of BMI-SDS in the under 12-year-olds, with only a slight improvement of −0.47 BMI-SDS in a more recent systematic review in 2014 [8, 9]. A decrease in BMI-SDS of <−0.25 was found in <10% of the group. In addition, children with a lower BMI (30–35) achieved better results than those deemed to more extreme obesity (BMI 35+), indicating lifestyle intervention is more effective in those with lower BMI scores.

As discussed, lifestyle modification alone does not appear to achieve substantial and sustainable weight loss in obese adolescents. As far back as 1993, Must et al. studied the long term relationship between overweight and obese adolescents and cardiovascular morbidity and found increased mortality with coronary heart disease in men [10]. Similar increases in all-cause mortality have since been demonstrated in another study of 1.46 million white adults [11]. Failure of lifestyle management, increased mortality for untreated patients and early results of adolescent surgery have all indicated that adolescent bariatric surgery is a successful therapeutic option if lifestyle modifications fail.

There are multiple guidelines regarding criteria for surgery. Aikenhead et al. reviewed current guidelines worldwide and suggested that although they were all similar, they lacked uniformity regarding the age and severity of obesity at which intervention should be offered [12]. NICE (National Institute for Health and Clinical Excellence, UK) suggests that the surgery should only be carried out in this age group under exceptional circumstances, however, recommends following the same BMI criteria as adults [13]. The international paediatric endosurgery group (IPEG) recommends surgery in adolescents who have attained or almost attained adult stature with specific guidance (see Table 1) [14]. The unifying factor in all guidelines appears to be recommending the use of multi-disciplinary team (MDT) and the need for long-term follow-up.

There is no specific evidence for the use of a multidisciplinary team either for adults or adolescents undergoing bariatric surgery. Considering the complex nature of intervention, however, particularly at the vulnerable age of these patients, the MDT has become well established as the gold standard of care necessary to provide a safe and efficient service.

The team members recommended by the American Society of Metabolic and Obesity Surgeons (ASMBS) in 2012 [15] includes the following:

Further recommendations, although not essential, include a coordinator and an exercise physiologist or physical therapist to provide safe physical activity prescriptions to morbidly obese adolescents. Teams should follow up patients for at least for 2 years after surgery. Transition arrangements should be finalised with adult teams however as far as the authors are aware, there are no published guidelines about this.

Increased paediatric obesity has also seen rise in the prevalence of obesity-related co-morbidities at ever younger ages, affecting almost all organ systems. It has long been recognised that obese children are at a high risk of metabolic syndrome, a constellation of glucose resistance, hypertension and hypercholesterolemia. Regression modelling from the FABS-5+ study demonstrated that there is also a significant proportional relationship between BMI and cardiometabolic risk. For every 10 kg/m² increase in BMI, there was a 34% increase in dyslipidaemia risk, 46% higher risk of hypertension and 25% rise in insulin concentration. Because the cardiovascular complications of metabolic syndrome result from cumulative years of exposure and subsequent atherosclerosis, earlier onset of obesity equates to an increased risk of premature death from cardiovascular disease. A retrospective review of 2.3 million Israeli adolescents (mean age 17.3+/−0.4) by Twig et al. aimed to quantify the risk of cardiovascular death in adulthood over 43 years [25]. Hazard ratios for the obese adolescent group (BMI >95th centile) as compared to the 24th centile were 4.9 for death from coronary heart disease, 2.6 for stroke and 3.5 for death from total cardiovascular causes. Adult literature has clearly demonstrated improvement in individual cardiovascular risk factors after bariatric surgery, but also a clear overall reduction of the risk of stroke, myocardial infarction and death by approximately 50% [26]. Although there are no similar long-term studies in the adolescent population as yet, both the FABS-5+ and AMOS cohorts have demonstrated ongoing long-term regression of hypertension, dyslipidaemia and diabetes in the majority of patients. Ippisch et al. also quantified the reversibility of cardiac abnormalities in adolescents (mean age 16+/−1 years) pre and post-bariatric surgery. Echocardiography found that predictors of future cardiovascular morbidity including the left ventricular mass, hypertrophy, diastolic function and cardiac workload all significantly improved following surgically induced weight loss in 38 adolescents over 10 months [27]. It would therefore be logical to suggest that cardiovascular morbidity and mortality should decrease in severely obese adolescents undergoing bariatric surgery.

The prevalence of type 2 diabetes mellitus (T2DM) in young people has risen significantly over the last 25 years following the rise in childhood obesity. Whilst in 1992, it accounted for 3% of all new cases of diabetes in children [28]; it currently accounts for almost 50% [29]. The associated complications affect several organ systems with severity directly related to length of disease due to a cumulative effect. Other than a significantly increased cardiovascular risk, T2DM in adults is responsible for more cases of renal failure and peripheral vascular disease leading to amputation than any other disease [30]. Adolescent type 2 diabetes also appears to be a more aggressive form with renal complications developing much earlier compared with type 1 diabetes; 6% of adolescents develop renal failure by age 20 years, and by 29 years of age, 2.3% have developed end-stage renal disease [31]. There also appears to be a more rapid progression to insulin requirements in adolescent T2DM when compared to type 1 [32•].

RYGB has been shown to increase insulin sensitivity by four times in adolescents both with and without diabetes after surgery [33]. Five-year remission rates of diabetes post adolescent surgery in the AMOS and FABS-5+ cohorts are at 100 and 88%, respectively, although numbers were small (n = 9, n = 3). There appears to be a greater efficacy in remission of diabetes after bariatric surgery in adolescents compared to adults, possibly due to a shorter duration of obesity and reduced severity of disease at presentation. Panunzi et al. combined data from the Swedish Obesity Subjects (SOS) trial and two randomised controlled studies in adults and found shorter diabetes duration and lower fasting glucose prior to surgery independently predicted significantly higher rates of remission [34]. This may be a further contributory factor suggesting we should be operating on adolescents earlier.

Non-alcoholic fatty liver disease (NAFLD) is strongly associated with obesity and is considered a spectrum of pathology ranging from NAFLD to non-alcoholic steatohepatitis (NASH), with a 20% 10-year progression to cirrhosis and fibrosis. With the increasing prevalence of obesity, NASH is currently the primary cause of liver function abnormalities and chronic liver disease in children [35] and is predicted to be the most common indication for liver transplantation in the next 10 years [36]. Of 148 adolescents undergoing bariatric surgery in the Teen-LABS cohort, 59% had biopsy evidence of NAFLD with mild fibrosis seen in 18% [37]. An adult meta-analysis by Muhammadi et al. showed improvement or resolution of steatosis in over 90% of patients after bariatric surgery [38]. No such outcome data exists in children; however, the AMOS study did demonstrate a 92 and 100% resolution of alanine aminotransferase and aspartate aminotransferase to normal levels at 5-year follow-up post-bariatric surgery. This does raise the question whether earlier intervention in adolescents not only prevents progression from NAFLD to NASH but also leads to normalisation of inflammation and fibrosis in patients who already have NASH at the time of surgery [39].

Obesity-associated respiratory pathologies including obstructive sleep apnoea have both immediate consequences of poor school performance and irritability alongside long-term consequences such as sustained nocturnal hypertension, left ventricular hypertrophy and increased cardiovascular and cerebrovascular morbidity and mortality [40, 41]. Adult studies have demonstrated the usefulness of bariatric surgery in improving OSA outcomes with a systematic review of 1350 patients demonstrating greater than twice the reduction in apnoea-hypopnoea index in surgical patients vs non-surgical controls [42]. Of 19 adolescents undergoing RYGB with pre-operative obstructive sleep apnoea, Kalra et al. saw a marked decrease in severity of OSAS in all patients undergoing post-operative polysomnograms, although they were only able to follow up 53% [43]. Further work by Amin et al. in a small, prospective study of seven adolescents undergoing surgery demonstrated a 40% reduction in apnoea score at 5 weeks compared to controls [44].

The consequences of obesity on psychosocial well-being are also not to be underestimated. Multiple studies have demonstrated significant reductions in global self-esteem and quality of life in obese youth and adolescents seeking weight loss surgery have been shown to have higher levels of depressive symptoms [45‐47]. These children have also been found to have lower attainment in education and training and are more likely to not complete education, which may be partly attributable to the frequency of weight-based victimisation and stigma [48, 49]. The AMOS collaboration demonstrated a substantial improvement in psychosocial well-being in adolescents 2 years post-gastric bypass vs controls. Symptoms of anxiety, depression, anger and disruptive behaviour were significantly reduced (p = 0.001) and self-esteem, self-concept and overall mood significantly improved (p < 0.001) [50]. However, clinically depressive symptoms were found in 19% at 2 years, with two cases of attempted suicide. The Teen-LABS consortium has also demonstrated variable mental health outcomes with surgery. Of 11 patients presenting with ≥1 mental health symptom pre-surgery, remission was only found in 45% [51], although no new cases developed. These findings suggest that not all adolescents benefit psychologically from bariatric surgery, and the role of psychological screening prior to operation is essential. It may however also suggest the need to intervene earlier prior to the development of psychosocial consequences of obesity in formative adolescent years.

The Teen-LABS consortium has also shown the effects of adolescent bariatric surgery on other organ systems. A significant number of severely obese adolescents have evidence of early kidney dysfunction [52], which appears to improve after surgery in their cohort [53]. Further work by this group demonstrated significant improvements in musculoskeletal pain and mobility [54] which they previously correlated to quality of life [55]. In addition, a range of carcinomas has also been independently associated with obesity including breast, colorectal, endometrial, hepatic and pancreatic [56]. As obesity has become a phenomenon over the last 30 years, it is possible we are yet to reach the peak of this effect on cancer incidence. Although there are no current data on this from the adolescent population, adult literature shows a 30–80% reduction in cancer risk after bariatric surgery over 10 years.

Despite very encouraging results in both weight loss and resolution of co-morbidities comparable to adult series, surgical and nutritional complications need to be carefully considered when assessing the justification for adolescent bariatric surgery. A recent review of the literature by Beamish et al. compiled side effects from the four main registries of bariatric surgery in adolescents: Teen-LABS, AMOS, Saudi Arabia and the Germany Obesity Registry. Only one 30-day mortality has been reported in more than 750 cases compared to an incidence of 0.08–0.31 in adult studies. Reporting of ‘minor complications’ and additional operations appeared to be higher in adolescent studies compared to adult series with 13–17% requiring additional operations as compared to 6–7% in adult cohorts [57•].

Perioperative outcomes in 77 RYGB adolescent patients from one US centre (mean age 16.8 +/−2.1) reported 3% intraoperative complications and 22% perioperative complications (<30 days) [58]. These most commonly included gastro-jejunal anastomotic stricture (17%), reoperation (13%), anastomotic leak (7%) and dehydration (7%). The FABS-5+ and AMOS studies have contributed significantly to our understanding of long-term complications. Further procedures were common in both cohorts; 26% required endoscopy in the FABS-5+ group; however, the need for this was not reported in the AMOS cohort. Rates of intra-abdominal surgery were comparable between the FABS-5+ and AMOS groups at 24 and 25%, respectively. Whilst the FABS-5+ group had a higher need for cholecystectomy (21 vs 11%), only two patients (3%) required a diagnostic laparoscopy. The need for laparoscopy for small bowel obstruction was significantly higher in the AMOS group, required in 14%. This was comparable to a Swedish adult cohort, and they have since changed their practice to close the mesenteric window as a consequence of this finding.

The AMOS study showed that the cumulative hospital stay over 5 years was greater in the adolescent surgical patients than in their age-matched controls (16.1 vs. 2.8 days). Two patients did not survive at 9 and 24 months post-operatively in the FABS-5+ group; however, both cases were felt to be unrelated to the surgery. There was no mortality over 5 years in the AMOS group. This data indicates the risks of surgery need to be thoroughly considered and discussed with patients and their families when considering surgical weight-loss procedures.

In the absence of supplementation, inadequate absorption of calcium, vitamin D, iron, vitamin B1, B6, B12, A and folate can occur resulting in nutritional deficiencies [59, 60]. This can manifest clinically as peripheral neuropathy (inadequate B12), beriberi syndrome (B1 deficiency), iron deficiency anaemia and osteoporosis and osteopenia. Overall, 72% had a variation of nutritional deficiency in the AMOS study with ‘several’ vitamin deficiencies identified in the FABS-5+ study, which was not further quantified. In both groups, these were predominantly mild and manageable. Anaemia was found in 46% of patients in FABS 5+ with a higher transfusion rate (5 vs 2.5%) than that found in AMOS, where only 32% were affected. The AMOS 5-year study showed that although vitamin D insufficiency was 63% in surgical group 5 years post-operatively, it was 57% in adolescent controls; however, neither study had any growth velocity data. An early study published in 1994 demonstrated only 14% of adolescents undergoing RYGB took recommended supplements [61]. This emphasises the importance of the role of the nutritionists and psychologists post-operatively to encourage compliance in this group of patients.

Though bariatric surgery clearly incurs a substantial cost at delivery, in light of the potential resolution of long-term morbidity emerging from prospective studies, it appears this cost is justified. An analysis by Teen-LABS compared the cost of adolescents with no surgery with those undergoing surgery, including rates of perioperative mortality, complications and initial morbidity over time. After 3 years, surgery led to a gain of 0.199 quality-adjusted life years (QALY) compared with no surgery at a cost of $154,684 per QALY [62]. The trajectory showed cost decreased over time, and surgery was found to be cost effective at 5 years. Although not measured, the indirect cost must be much greater considering the improvements in psychosocial health and mobility beginning to emerge from the teen-LABS group.

Epidemiologic data has confirmed that paediatric obesity is increasing in prevalence and severity. Increasing studies have shown that obesity in the adolescent age group increases mortality due to a multitude of associated co-morbidities.

Multiple studies have now shown reproducible, safe and effective results of adolescent bariatric surgery with weight loss and resolution of co-morbidities equivalent to that seen in the adult population. Overall health and psychosocial well-being also appears to be improved. As long-term outcomes are still largely unknown and complications such as vitamin deficiency and re-operation appear to be slightly higher than that seen in the adult cohort, it is imperative that surgery should only be provided by multi-disciplinary specialist teams dedicated to the holistic care of paediatric patients to ensure safety and delivery of excellent clinical care.