Direct and BMI-mediated effect of birthweight on childhood cardio-metabolic health—a birth cohort study

Background Different directions of the association of birthweight with cardio-metabolic health have been found, especially in children, which may be explained by the mediating effect of attained adiposity. We aimed to untangle direct and BMI-mediated associations of birthweight with childhood cardio-metabolic indicators. Methods Children from Generation XXI birth cohort were included ( n = 4881). Birthweight was abstracted from clinical files. At age 4 and 7, children were re-evaluated. Glucose, triglycerides, LDL-cholesterol, systolic (SBP) and diastolic blood pressure (DBP) z-scores were the cardio-metabolic traits analyzed. Regression coefficients and respective 95% confidence intervals [β (95%CI)] were computed using path analysis. Results Birthweight had inverse total effect on SBP at age 4 [−0.005 (−0.010; −0.001)] and 7 [−0.011 (−0.017; −0.006)] and DBP at 7 [−0.008 (−0.012; −0.004)]. Direct effects were found for SBP at 4 [−0.013 (−0.018; −0.009)] and 7 [−0.014 (−0.019; −0.009)], and DBP at 7 [−0.010 (−0.015; −0.006)], explaining the inverse total effects. Positive BMI-mediated indirect effects were found for all cardio-metabolic traits: higher birthweight was associated with higher childhood BMI, which in turn was associated with higher levels of cardio-metabolic traits. Conclusions Positive BMI-mediated effect of birthweight on all cardio-metabolic traits was found. However, direct effects were in the opposite direction, significant for blood pressure, which may explain the diversity of results observed in the literature. Combining the direct and BMI-mediated effects, higher birthweight was associated with lower blood pressure at age 7 and have no effect on other cardio-metabolic traits.