Associations of growth trajectories from birth to two years of age with adolescent blood pressure: the mediating role of current BMI in the follow-up of an antenatal micronutrient supplementation trial

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Abstract
While early-life growth patterns are thought to be pivotal for long-term cardiovascular health, their specific links to adolescent blood pressure (BP) and potential mediators remain unclear. We aimed to examine the associations of growth trajectories from birth to age two with systolic and diastolic BP in adolescence, and to quantify the proportion mediated by concurrent adolescent BMI. In a prospective birth cohort in rural China, we repeatedly measured infant weight and length at birth and at 1, 3, 6, 9, 12, 18, and 24 months of age. Adolescent BP was measured and converted into percentiles. We used group-based trajectory modeling to identify early-life weight-, length-, BMI- and weight-for-length z-score trajectories and examined their associations with adolescent BP. A general causal mediation estimated the natural indirect effects and corresponding proportions mediated through adolescent BMI. Among the 1388 infants enrolled, 741 (60.9% male; mean age, 11.26 (SD, 0.57) years old) were followed at adolescence. Greater and rapid BMI and weight-for-length growth trajectories were statistically associated with elevated adolescent BP and BP percentiles, with adjusted mean differences ranging from 2.32 to 5.29 mmHg. Adolescent BMI mediated a substantial portion (up to 85%) of the association with systolic BP, but it showed no significant mediating effect for diastolic BP. Conclusion: Rapid adiposity growth in infancy predicts elevated adolescent BP. Since adolescent BMI did not fully explain this association, especially for diastolic BP, preventive interventions within the first 1000 days may be critical for lifelong cardiovascular health beyond managing later childhood weight. Trial registration: ISRCTN08850194, retrospectively registered December 14, 2006. https://www.isrctn.com/ISRCTN08850194?q=ISRCTN08850194&filters=&sort=&offset=1&totalResults=1&page=1&pageSize=10. What is Known • Childhood body mass index (BMI) is positively associated with blood pressure at later life. What is New • This study identifies distinct weight, length, BMI, and weight-for-length growth trajectories from birth to two years of age and links rapid weight-related growth trajectories to elevated blood pressure in early adolescence. • Using causal mediation analysis, it shows adolescent BMI largely mediates the association for systolic, but not diastolic, blood pressure, highlighting interventions within the first 1000 day for lifelong cardiovascular health beyond managing later childhood weight.

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