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



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.


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.


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.


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.

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The authors gratefully acknowledge the families enrolled in Generation XXI for their kindness, all members of the research team for their enthusiasm and perseverance and the participating hospitals and their staff for their help and support. They also acknowledge the project DOCnet (NORTE-01-0145-FEDER-000003), supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF).


This work was supported by Programa Operacional de Saúde – Saúde XXI, Quadro Comunitário de Apoio III and Administração Regional de Saúde Norte (Regional Department of Ministry of Health); FEDER through the Operational Programme Competitiveness and Internationalization and national funding from the Foundation for Science and Technology – FCT (Portuguese Ministry of Science, Technology and Higher Education) [POCI-01- 0145-FEDER-016837], under the project “PathMOB.: Risco cardiometabólico na infância: desde o início da vida ao fim da infância” [Ref. FCT PTDC/DTP-EPI/3306/2014], and FCT Investigator contract [IF/01060/2015] to ACS; Unidade de Investigação em Epidemiologia - Instituto de Saúde Pública da Universidade do Porto (EPIUnit) [POCI-01-0145-FEDER-006862; Ref. UID/DTP/04750/2013]; European Commission [project reference FP7-ENV-2013-603946]; and UK Medical Research Council [MC_UU_12013/5] and UK National Institute of Health Research Senior Investigator [NF-SI-0611-10196] to DAL.

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Correspondence to Maria João Fonseca.

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