The results from the non-randomised 4XL study show significantly greater one-year weight loss and improvement in cardiometabolic risk factors after gastric bypass combined with lifestyle intervention than after lifestyle intervention alone. However, the non-randomised study design, the relatively small number of patients who underwent surgery, and the short follow-up time preclude us from evaluating whether the benefits of weight loss outweigh the risk of long-term complications. Nor can we exclude the possibility that systematic differences between the treatment groups in both selection and dropout may have affected the outcomes, reducing the internal validity and generalisability.
As of 9 October 2020, only a single randomised controlled study had been published comparing the effects of lifestyle intervention to those of bariatric surgery in adolescents, and even this study featured a type of surgery (gastric banding) that is rarely used (14). The effects on BMI of laparoscopic Roux-en-Y gastric bypass surgery versus caloric restriction (low calorie diet) are being compared in an ongoing randomised controlled trial of 13–16-year-olds with BMI > 35 kg/m2. The results from this study may strengthen the existing evidence base (https://clinicaltrials.gov/ct2/show/NCT02378259).
Our results are consistent with findings from two non-randomised studies that showed approximately 30 % weight loss one and two years after gastric bypass surgery, respectively (15, 16). The Swedish AMOS study compared gastric bypass surgery with conventional treatment and showed 31–32 % weight loss in the surgery group versus 3 % weight gain in the control group (16). A US study showed approximately 30 % weight loss one and two years after bypass surgery (15). The significant improvement in cardiometabolic risk factors in the surgery group confirms findings from previous observational studies (16, 17).
Two (5 %) postoperative complications were recorded, which is in accordance with international experience (16, 18). The risk of long-term complications following bariatric surgery in adolescents is poorly documented (9) and has not been examined in the current analysis either.
Anaemia and vitamin and mineral deficiencies are known adverse effects after gastric bypass (7, 16). In the current study, mean levels of haemoglobin, ferritin, calcium, vitamin D and vitamin B12 had not fallen significantly after one year. However, at the one-year follow-up, a number of patients had anaemia, iron deficiency or low vitamin B12 levels (Table 4), and about 2 out of 3 patients (61 %) had two-hour hypoglycaemia after an oral glucose tolerance test (blood sugar < 2.8 mmol/L). The incidence of two-hour hypoglycaemia was higher than shown previously in adults (19, 20), and lower age is known to be a risk factor (21). No fractures were recorded, and bone mineral measurements did not show a decrease in (mean) bone density to below that expected for age. It is nevertheless concerning that gastric bypass surgery is associated with an increased fracture risk (22) and postprandial hypoglycaemia. Lifelong follow-up with diagnostic testing and use of preventive measures would seem to be necessary.
The 4XL study is ongoing, and a ten-year follow-up is planned. A particular strength of the study is that the intervention group is being compared with an actively treated control group, with both groups of participants fulfilling the same inclusion criteria. In addition, the study is being run by a centre with specialist expertise in family-based lifestyle interventions in adolescents, bariatric surgery and clinical research. The complexity of the assessment and follow-up of this patient group requires a seamless and close collaboration between healthcare professionals specialising in the treatment of childhood obesity and surgeons with expertise in bariatric surgery.
Weaknesses of the study include the relatively small number of patients in the surgery group, the long recruitment period and differences between the groups in baseline age (17 years vs. 16 years) and BMI (45.6 kg/m2 vs. 43.3 kg/m2). The latter, however, had little effect on the between-group difference in the change in the primary outcome measure, which was adjusted for baseline weight in the primary analyses, and further adjustment for age did not affect the results. Although the sample size was lower than planned (n = 50 in the surgery group), the dropout rate (5 %) was lower than expected (30 %). The study therefore had sufficient power to answer the primary research question on weight loss as soon as 39 patients had attended the one-year follow-up.
A recently published meta-analysis showed that health-related quality of life improved significantly after surgery in adolescents, especially in the first few years, but that few data are available on the long-term incidence of psychosocial and mental health problems (23). Long-term results from the AMOS study show that mental health problems do not necessarily decrease after gastric bypass surgery in adolescents, and that individuals who undergo surgery may have a greater need for psychiatric help than those who do not undergo surgery (24). Health-related quality of life, psychological status, eating behaviour and long-term complications are all topics for future analyses and publications from the 4XL study.
Our results confirm that laparoscopic Roux-en-Y gastric bypass can be performed with satisfactory weight loss, improvement of cardiometabolic risk factors and a low incidence of early postoperative complications. The study also indicates that the incidence of adverse effects and complications is similar in the short-term to that observed in adults (7), but the study is too small at present to be able to draw definite conclusions about the incidence and severity of complications. Little is known about the long-term effects and complications of weight loss surgery in adolescents (9). It is therefore difficult to know whether bariatric surgery should be offered to more young people with morbid obesity, or whether it is better to recommend waiting until adulthood. Arguments for obesity surgery in adolescence are the possibility of significant weight loss, improved quality of life and a reduced risk of future obesity-related disease. Arguments against are the risk of serious complications, anaemia, hypoglycaemia, vitamin and mineral deficiencies, and mental health problems.