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(Circulation. 2004;109:1108-1113.)
© 2004 American Heart Association, Inc.

Clinical Investigation and Reports

Is Slower Early Growth Beneficial for Long-Term Cardiovascular Health?

Atul Singhal, MD, MRCP; Tim J. Cole, ScD; Mary Fewtrell, MD, MRCP; John Deanfield, FRCP; Alan Lucas, MD, FRCP, FMed Sci

From MRC Childhood Nutrition Research Center (A.S., M.F., A.L.), Department of Pediatric Epidemiology and Biostatistics (T.J.C.), and Department of Vascular Physiology (J.D.), Institute of Child Health, London, UK.

Correspondence to Dr A Singhal, MRC Childhood Nutrition Research Center, Institute of Child Health, 30 Guilford St, London, UK, WC1N 1EH. E-mail a.singhal{at}ich.ucl.ac.uk

Received June 25, 2003; revision received November 4, 2003; accepted November 17, 2003.

Background— Accelerated neonatal growth increases the later propensity to cardiovascular disease (CVD) in animals, whereas slower growth is thought to have a beneficial effect. To test this hypothesis in humans, we measured flow-mediated endothelium-dependent dilation (FMD) in a population subject to slower early growth and in healthy controls.

Methods and Results— High-resolution vascular ultrasound was used to measure the change in brachial artery diameter in response to reactive hyperemia in adolescents age 13 to 16 years who were either part of a cohort born preterm and followed up prospectively (n=216) or controls born at term (n=61). Greater weight gain or linear growth in the first 2 weeks postnatally was associated with lower FMD at adolescence (regression coefficient, -0.026-mm change in mean arterial diameter per 100-g increase in weight; 95% CI, -0.040 to -0.012 mm; P=0.0003) independent of birthweight and potential confounding factors. Mean FMD in the half of the preterm population with the lowest rates of early growth was higher than in both the half with the greatest growth (P=0.001) and subjects born at term (P=0.03).

Conclusions— FMD was 4% lower in adolescents with the highest compared with the lowest rate of weight gain in the first 2 weeks after birth, a substantial negative effect similar to that for insulin-dependent diabetes mellitus or smoking in adults. Our findings are consistent with the adverse effects of accelerated neonatal growth on long-term cardiovascular health and suggest that postnatal growth patterns could explain the previously reported association between birthweight and later CVD.

Key Words: infants • vasodilation • atherosclerosis • cardiovascular diseases

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