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

Abstract

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.

Longitudinal analysis of vitamin D levels considering sunshine duration and suggestion for a standardised approach for vitamin D supplementation in children and adolescents with obesity

“…The APV registry is a standardised multicentre database for the prospective documentation of anthropometric, demographic and metabolic parameters in overweight or obese children. Anonymised data are aggregated into a cumulative database for clinical research and quality assurance, as described previously [ 26 , 27 ]. The APV initiative is authorised by the Ethics Committee of the University of Ulm, Germany and approved by the local review board of Charité Universitätsmedizin Berlin.…”

Birth size, growth trajectory and later cardio-metabolic risk

“…Of note, while preterm birth has been described as a risk factor for type 1 diabetes ( 79 ), being born SGA seems to have a protective effect on this disease onset ( 81 ). These observations suggest different repercussions of SGA and preterm birth on glucose-insulin metabolism ( 82 ).…”

Associations of birth weight, plasma metabolome in adulthood and risk of type 2 diabetes

“…3,4 There is compelling evidence that individuals with low birth weight have long-term metabolic abnormalities through early life and adulthood, such as elevated glycated haemoglobin (HbA1c), higher triglycerides, and lower high-density lipoprotein (HDL). [5][6][7] However, the majority of these studies measured a limited set of metabolomic biomarkers and failed to distinguish subclasses and a series of constituents according to lipoprotein particles, which may have contrasting effects on T2D risk. To our knowledge, only one study explored the relationship between birth weight and metabolome, but that study did not test whether metabolome abnormalities mediated the relationship between birth weight and cardiometabolic disease.…”

“…There is compelling evidence that individuals with low birth weight have long‐term metabolic abnormalities through early life and adulthood, such as elevated glycated haemoglobin (HbA1c), higher triglycerides, and lower high‐density lipoprotein (HDL) 5–7 . However, the majority of these studies measured a limited set of metabolomic biomarkers and failed to distinguish subclasses and a series of constituents according to lipoprotein particles, which may have contrasting effects on T2D risk.…”