Exposure to sugar rationing in first 1000 days after conception and long term cardiovascular outcomes: natural experiment study

Abstract Objective To examine whether exposure to sugar rationing during early life is associated with a reduction in the risk of cardiovascular outcomes in adulthood. Design Natural experiment study. Setting UK population based cohort. Participants 63 433 UK Biobank participants born between October 1951 and March 1956 without prevalent cardiovascular disease, multiple births, adoption, or birth outside the UK. Exposure was quasi-experimentally assigned on the basis of birth date relative to the end of sugar rationing in 1953. External validation cohorts from the Health and Retirement Study and the English Longitudinal Study of Ageing were used. Main outcome measures Primary outcomes were incident cardiovascular disease, myocardial infarction, heart failure, atrial fibrillation, stroke, and cardiovascular disease mortality, ascertained through linked health records. Hazard ratios were estimated using Cox and parametric hazard models adjusted for demographic, socioeconomic, lifestyle, parental health, and genetic factors and geographical controls. Multiple cardiac parameters were measured in a subset undergoing cardiac magnetic resonance imaging. Results Longer exposure to sugar rationing was associated with progressively lower cardiovascular risks in adulthood. Compared with people never exposed to rationing, those exposed in utero plus 1-2 years had hazard ratios of 0.80 (95% confidence interval (CI) 0.73 to 0.90) for cardiovascular disease, 0.75 (0.63 to 0.90) for myocardial infarction, 0.74 (0.59 to 0.95) for heart failure, 0.76 (0.66 to 0.92) for atrial fibrillation, 0.69 (0.53 to 0.89) for stroke, and 0.73 (0.54 to 0.98) for cardiovascular disease mortality. Incident diabetes and hypertension jointly mediated 31.1% of the sugar rationing-cardiovascular disease association, whereas birth weight contributed only 2.2%. Sugar rationing was also associated with a modest increase in left ventricular stroke volume index (0.73 (95% CI 0.05 to 1.41) mL/m 2 ) and ejection fraction (0.84%, 95% CI 0.40% to 1.28%). Conclusion Exposure to sugar rationing during the first 1000 days of life was associated with lower cardiovascular risks in adulthood and slightly more favourable cardiac indices, suggesting long term cardiovascular benefits of early life sugar restriction.