The association between perinatal factors and cardiometabolic risk factors in children and adolescents with overweight or obesity: A retrospective two-cohort study.

BACKGROUND: Children with obesity have an increased risk of cardiometabolic risk factors, but not all children carry a similar risk. Perinatal factors, i.e., gestational age (GA) and birth weight for GA, may affect the risk for metabolic complications. However, there are conflicting data whether the association between birth size and cardiometabolic risk factors is independent among children with obesity. Moreover, differential effects of GA and birth weight for GA on cardiometabolic risk factors in pediatric obesity are still unexplored. We aimed to investigate the association between birth weight for GA and cardiometabolic risk factors in children and adolescents with overweight or obesity and to assess whether the association is modified by prematurity. METHODS AND FINDINGS: We conducted a retrospective study of 2 cohorts, using data from the world's 2 largest registers of pediatric obesity treatment-The Swedish childhood obesity treatment register (BORIS) and The Adiposity Patients Registry (APV) (1991 to 2020). Included were individuals with overweight or obesity between 2 to 18 years of age who had data of birth characteristics and cardiometabolic parameters. Birth data was collected as exposure variable and the first reported cardiometabolic parameters during pediatric obesity treatment as the main outcome. The median (Q1, Q3) age at the outcome measurement was 11.8 (9.4, 14.0) years. The main outcomes were hypertensive blood pressure (BP), impaired fasting glucose, elevated glycated hemoglobin (HbA1c), elevated total cholesterol, elevated low-density lipoprotein (LDL) cholesterol, elevated triglycerides, decreased high-density lipoprotein (HDL) cholesterol, and elevated transaminases. With logistic regression, we calculated the odds ratio (OR) and its 95% confidence interval (CI) for each cardiometabolic parameter. All the analyses were adjusted for sex, age, degree of obesity, migratory background, and register source. In total, 42,760 (51.9% females) individuals were included. Small for GA (SGA) was prevalent in 10.4%, appropriate for GA (AGA) in 72.4%, and large for GA (LGA) in 17.2%. Most individuals (92.5%) were born full-term, 7.5% were born preterm. Median (Q1, Q3) body mass index standard deviation score at follow-up was 2.74 (2.40, 3.11) units. Compared with AGA, children born SGA were more likely to have hypertensive BP (OR = 1.20 [95% CI 1.12 to 1.29], p < 0.001), elevated HbA1c (1.33 [1.06 to 1.66], p = 0.03), and elevated transaminases (1.21 [1.10 to 1.33], p < 0.001) as well as low HDL (1.19 [1.09 to 1.31], p < 0.001). On the contrary, individuals born LGA had lower odds for hypertensive BP (0.88 [0.83 to 0.94], p < 0.001), elevated HbA1c (0.81 [0.67 to 0.97], p < 0.001), and elevated transaminases (0.88 [0.81 to 0.94], p < 0.001). Preterm birth altered some of the associations between SGA and outcomes, e.g., by increasing the odds for hypertensive BP and by diminishing the odds for elevated transaminases. Potential selection bias due to occasionally missing data could not be excluded. CONCLUSIONS: Among children and adolescents with overweight/obesity, individuals born SGA are more likely to possess cardiometabolic risk factors compared to their counterparts born AGA. Targeted screening and treatment of obesity-related comorbidities should therefore be considered in this high-risk group of individuals.

Prevalence of increased transaminases and its association with sex, age, and metabolic parameters in children and adolescents with obesity - a nationwide cross-sectional cohort study.

BACKGROUND: Childhood obesity increases the risk of non-alcoholic fatty liver disease marked by elevated alanine aminotransferase (ALT). This study investigated the prevalence of increased ALT in children and adolescents with obesity, and its associations with sex, age, degree of obesity, and metabolic parameters. METHODS: Individuals between 5 and 17.99 years of age enrolled in the Swedish Childhood Obesity Treatment Register (BORIS) before March 2020 were included. Mildly increased ALT was defined by ALT 27-51 U/L (males) and 23-43 U/L (females), while markedly increased ALT by levels above. Multiple logistic regression models were used for statistical analysis. RESULTS: Among 11,776 individuals (age 11.0 ± 3.3 years, 53.5% males), the prevalence of mildly and markedly increased ALT were 37.9 and 10.6%, respectively. A sex-age interaction was found, where increasing age strengthened the odds of markedly increased ALT in males (OR, 99% CI: 1.34, 1.29-1.4 for each year) while the corresponding pattern in females with was minuscule (1.09, 1.02-1.10). Compared to class I obesity, class II and III obesity had greater odds ratios for mildly increased ALT (class II obesity OR, 99% CI: 1.51, 1.35-1.70; class III obesity OR, 99% CI: 2.17, 1.66-2.61) and for markedly increased ALT (class II obesity OR, 99% CI: 1.82, 1.51-2.20; class III obesity OR, 99% CI 3.38, 2.71-4.23). Dyslipidemia was associated with both mildly and markedly increased ALT, all p < 0.001. Prevalence of impaired fasting glucose was 19.1% in normal ALT group, 20.4% in mildly increased ALT group, and 29.0% in markedly increased ALT group. CONCLUSIONS: The risk of markedly increased ALT increased exponentially with age among boys, but not among girls. Higher degree of obesity was observed in individuals with mildly and markedly increased ALT. Further, metabolic derangements were more prevalent among individuals with mildly and markedly increased ALT.

Height and Growth Velocity in Children and Adolescents Undergoing Obesity Treatment: A Prospective Cohort Study.

CONTEXT: Pediatric obesity affects endocrine conditions, which may alter growth. OBJECTIVE: This work aimed to investigate the effect of obesity severity and obesity treatment outcome on growth. METHODS: This prospective cohort study included children (aged 3-18 years) enrolled in the Swedish Childhood Obesity Treatment Register (BORIS) (1998-2020). Obesity was categorized as class I and class II obesity. Obesity treatment outcome was measured as body mass index (BMI) z score changes and categorized into good (BMI z score reduction of ≥0.25), intermediate, and poor (increasing BMI z score). Height for age z score, final height, and growth velocity were compared between class I and class II obesity. Further, the effect of obesity treatment outcome on growth velocity during 2-year follow-up was assessed. RESULTS: A total of 27 997 individuals (mean age 10.2 ± 3.6 years) were included. Individuals with class II obesity were on average taller than those with class I obesity during childhood. Among males, reduced growth spurt was observed in class I obesity, and even absent in class II obesity. Females exhibited a similar but less pronounced pattern. Good obesity treatment outcome yielded lower growth velocity at ages 3 to 9 years but higher growth velocity at ages 10 to 13 years compared to poor treatment outcome. CONCLUSION: Obesity severity is positively associated with height and growth velocity in childhood. A hampered growth spurt during puberty should be anticipated, particularly in adolescents with severe obesity. Therefore no difference in final height between class I and class II obesity is expected. Successful obesity treatment does not harm, but rather normalizes, the growth velocity pattern.

Evaluating probiotic efficacy on weight loss in adults with overweight through a double-blind, placebo-controlled randomized trial.

The aim was to assess the weight-reducing effects of various doses of a probiotic dietary supplement and evaluate the tolerance and safety of increased dosage. A 3-month double-blinded, randomized, placebo-controlled trial, followed by a 3-month open phase, was conducted at Karolinska Institutet, Sweden. The probiotic compound AB001 was tested at two doses (single and double) and compared with placebo during the blinded phase, and at triple dose during the open phase. Eighty-one volunteers, 18-45 years old, with overweight were included. The primary outcome was change in weight. Secondary outcomes were changes in; BMI, waist circumference, blood pressure, blood lipids, glucose metabolism, liver enzymes, vitamin levels, and bowel habits. After 3 months (n = 81), no difference in weight, BMI, waist circumference, blood pressure, or biomarkers were observed between the groups. Forty-five individuals continued with triple dose. The group with initial single dose decreased 0.93 ± 4.73 kg (p = 0.34), and the group with double dose initially decreased 1.93 ± 3.70 kg (p = 0.027). Reported changes in bowel habits and gastro-intestinal problems were similar for all doses. The results indicate that a long-term use of at least double dose AB001 may be more beneficial for weight loss than lower doses. However, in the double blinded phase, no differences between groups were found. The probiotic compound AB001 was well tolerated and can safely be used up to double dose for 90 days followed by triple dose for 90 days.Trial registration: Clinicaltrial.gov NCT04897698, registered on 21 May 2021.

Associations between cardiorespiratory fitness and cardiometabolic risk factors in children and adolescents with obesity.

It is unclear if associations between cardiorespiratory fitness (CRF) and cardiometabolic risk factors are independent of degree of obesity, in children with obesity. The aim of this cross-sectional study on 151 children (36.4% girls), 9-17 years, from a Swedish obesity clinic, was to investigate associations between CRF and cardiometabolic risk factors, adjusted for body mass index standard deviation score (BMI SDS), in children with obesity. CRF was objectively assessed with the Åstrand-Rhyming submaximal cycle ergometer test, and blood samples (n = 96) and blood pressure (BP) (n = 84) according to clinical routine. Obesity specific reference values for CRF were used to create CRF levels. CRF was inversely associated with high-sensitivity C-reactive protein (hs-CRP), independent of BMI SDS, age, sex, and height. The inverse associations between CRF and diastolic BP did not remain significant when adjusted for BMI SDS. CRF and high-density lipoprotein cholesterol became inversely associated when adjusted for BMI SDS. Independent of degree of obesity, lower CRF is associated with higher levels of hs-CRP, as a biomarker of inflammation, in children with obesity and regular assessment of CRF should be encouraged. Future research in children with obesity should investigate if low-grade inflammation decreases when CRF is improved.

Risk and protective factors of non-alcoholic fatty liver disease in paediatric obesity: A nationwide nested case-control study.

Not all children with obesity carry a similar risk of non-alcoholic fatty liver disease (NAFLD). We investigated the effect of obesity severity, metabolic risk parameters, and obesity treatment outcome on later risk of NAFLD in paediatric obesity. We conducted a nested case-control study of children and adolescents enrolled in the Swedish Childhood Obesity Treatment Register (BORIS) (2001-2016). NAFLD was ascertained from the National Patient Register. Five controls per case were matched by sex and age at index date and at the obesity treatment initiation. Seventy-six pairs (n cases = 76, n controls = 241) were included in the analysis (29% females, mean age at obesity treatment initiation was 10.8 ± 3.07 years). Mean age of NAFLD diagnosis was 14.2 ± 3.07 years. The risk for NAFLD increased with severe obesity (odds ratio [OR]: 3.15, 95% confidence interval [CI]: 1.69-5.89), impaired fasting glucose (OR: 5.29, 95% CI: 1.40-20.06), high triglycerides (OR: 2.33, 95% CI: 1.22-4.43) and weight gain (OR: 4.67, 95% CI: 1.51-14.49 per body mass index standard deviation score [BMI SDS] unit). Relative weight loss of at least 0.25 BMI SDS units reduced NAFLD risk independently of other risk factors (OR: 0.09, 95% CI: 0.01-0.56). Severe obesity, impaired fasting glucose and high triglycerides are risk factors for future NAFLD in paediatric obesity. Successful obesity treatment almost eliminates the risk for NAFLD independently of obesity severity, IFG and high triglycerides.