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.


The Swedish Childhood Obesity Treatment Register (BORIS)
The Swedish Childhood Obesity Treatment Register (BORIS) is a prospective register of children and adolescents undergoing obesity treatment [3]. Guidelines for obesity treatment in Sweden include that treatment should be initiated at an early age and before a severe obesity is manifested. Treatment focus on lifestyle modification to reduce the degree of obesity by improving dietary habits and increasing physical activity. No pharmacological treatment is currently available. All health care, including treatment of obesity, is free of charge for children and adolescents up to 18 years of age. Generally, treatment is aimed to be tailored towards the families' needs and abilities to adhere to specific programs. Treatment may therefore be delivered differently.
According to Swedish regulations, families were informed in writing and verbally about data collection in BORIS. Post an opt-out approval (possibility to choose not to participate) by parents/guardians, data of the children's weight and height were recorded by the local healthcare provider during treatment visits.
For individuals in BORIS, birth data was collected from the Swedish medical birth register. In Sweden all residents are assigned a unique personal identification number, which was used by the governmental agency the National Board of Health and Welfare to link the two registers on an individual level. The Swedish Medical Birth Register was founded in 1973 and includes data on almost all deliveries in Sweden, since it is compulsory for all health care providers to report to the register.
Supplementary material for "The association between perinatal factors and cardiometabolic risk factors in children and adolescents with overweight or obesity: A retrospective two-cohort study" by Prinz N, et al.  Figure 2 and Supplementary Figure 1. Obesity classification according to IOTF [11,12] Hypertensive blood pressure [6]: Supplementary material for "The association between perinatal factors and cardiometabolic risk factors in children and adolescents with overweight or obesity: A retrospective two-cohort study" by Prinz N, et al.

Systolic and diastolic blood pressure
Of 38 553 individuals with reported blood pressure, systolic and diastolic hypertensive blood pressure was present in 26.3% and 12.4% respectively. Any hypertensive blood pressure was present in 30.7%. Individuals born SGA were more likely to have both systolic and diastolic blood pressure, while individuals born LGA only had a decreased risk for systolic but not diastolic hypertensive blood pressure, see Supplementary Figure 2 below.
Supplementary Figure 2. Odds ratios (OR) and 95% confidence intervals (CI) for systolic and diastolic blood pressure from logistic regression. Grey markers are unadjusted OR and black markers are OR adjusted for sex, age group, degree of obesity [11,12], immigration, and obesity register (APV or BORIS). Dashed line indicates OR=1.00.

Any hypertensive blood pressure
Systolic hypertensive blood pressure Diastolic hypertensive blood pressure

Odds Ratios (log scale)
Supplementary material for "The association between perinatal factors and cardiometabolic risk factors in children and adolescents with overweight or obesity: A retrospective two-cohort study" by Prinz N, et al.