The developmental origins of health and disease (DOHaD) hypothesis posits that fetal and infant life are critical periods for cardiovascular disease and obesity risk later in life. Low birth weight, often indicating fetal growth restriction, is linked to increased adult cardiovascular disease risk. Conversely, high birth weight is associated with a higher risk of later-life obesity. Physical inactivity is a major cardiovascular disease risk factor, with a recent meta-analysis demonstrating a nonlinear association between physical activity and all-cause mortality. While low physical activity (PA) is linked to higher cardiometabolic risk in children and adolescents, and higher intensity PA is associated with lower risk, the interaction between birth weight and PA on cardiometabolic risk factors remains unclear. This study aimed to investigate whether device-measured MVPA modifies the relationship between birth weight and cardiometabolic risk factors in a large, diverse sample of children and adolescents, hypothesizing that higher MVPA might mitigate the negative effects of both low and high birth weight.

Extensive research supports the DOHaD concept, demonstrating a strong link between low birth weight and increased cardiovascular disease risk in adulthood. Similarly, high birth weight consistently predicts a heightened risk of obesity later in life. Physical inactivity is a well-established risk factor for cardiovascular diseases. Studies have shown a nonlinear relationship between physical activity and mortality. Previous research has investigated the potential interaction between birth weight and physical activity on cardiometabolic risk in children and adolescents, but with limited cardiometabolic outcomes and conflicting results. This study aims to address these gaps by using a large sample size and a broader range of cardiometabolic outcomes.

This study used pooled individual data from 12 cohort or cross-sectional studies, including 9100 children and adolescents. Birth weight was obtained from birth records or retrospective maternal report. Physical activity was measured using accelerometers (Actigraph), with MVPA and VPA calculated. Cardiometabolic risk factors included systolic and diastolic blood pressure, LDL-cholesterol, HDL-cholesterol, triglycerides, fasting glucose, insulin, HOMA-IR, and waist circumference. Multilevel linear regression was used to examine associations between birth weight, MVPA, and cardiometabolic risk factors, adjusting for age, sex, and parental education. Interaction effects between birth weight and MVPA were tested. Participants were divided into children (≤11.6 years) and adolescents (>11.6 years) based on age.

The study found that MVPA did not consistently modify the associations between birth weight and most cardiometabolic risk factors. However, a significant interaction was observed between birth weight and MVPA for waist circumference in children (p = 0.005) and HDL cholesterol in adolescents (p = 0.040). Sensitivity analyses using VPA indicated additional modification effects for diastolic blood pressure in children (p = 0.009), and LDL-cholesterol and triglycerides in adolescents (p = 0.009 and p = 0.028 respectively). Regardless of birth weight, MVPA was consistently associated with lower cardiometabolic risk factors.

The findings suggest that while MVPA may have a mitigating effect on the association between high birth weight and some cardiometabolic risks (waist circumference in children and HDL cholesterol in adolescents), it doesn't consistently modify the detrimental effects of low birth weight. This highlights the importance of optimal prenatal growth. The consistent association between MVPA and lower cardiometabolic risk across all birth weight categories emphasizes the significance of physical activity throughout childhood and adolescence. These findings support the promotion of both healthy prenatal growth and sufficient physical activity as crucial strategies for improving cardiometabolic health in young people.

This large-scale study demonstrates that, while MVPA shows promise in mitigating some cardiometabolic risks associated with higher birth weight, it does not consistently influence the effects of low birth weight. Maintaining optimal prenatal growth and promoting sufficient physical activity are essential for cardiometabolic health during childhood and adolescence. Future research should explore the specific mechanisms through which MVPA might interact with birth weight to influence different cardiometabolic risk factors and investigate potential age and sex specificities of these interactions.

The retrospective nature of birth weight data in some studies might introduce recall bias. The cross-sectional design of some studies limits the ability to establish causality. The use of accelerometers for PA assessment may not fully capture all types of physical activity. The diverse study populations might introduce heterogeneity in findings.