Published Online
on December 18, 2006

A more recent version of this article appeared on January 16, 2007

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Submitted on February 8, 2006
Accepted on October 20, 2006

Promotion of Faster Weight Gain in Infants Born Small for Gestational Age. Is There an Adverse Effect on Later Blood Pressure?

Atul Singhal MD, MRCP^*, Tim J. Cole PhD, ScD, Mary Fewtrell MD, MRCP, Kathy Kennedy MSc, Terence Stephenson DM, FRCP, FRPCH, Alun Elias-Jones FRCP, FRCPCH, and Alan Lucas MD, FRCP, FMed Sci

From the Medical Research Council Childhood Nutrition Research Centre (A.S., M.F., K.K., A.L.) and Centre for Pediatric Epidemiology and Biostatistics (T.J.C.), Institute of Child Health, London; Academic Division of Child Health, University Hospital, Nottingham (T.S.); and Leicester General Hospital National Health Service Trust, Gwendolen Road, Leicester (A.E.-J.), UK.

^* To whom correspondence should be addressed. E-mail: a.singhal{at}ich.ucl.ac.uk.

Background--Being born small for gestational age is associated with later risk factors for cardiovascular disease, such as high blood pressure. Promotion of postnatal growth has been proposed to ameliorate these effects. There is evidence in animals and infants born prematurely, however, that promotion of growth by increased postnatal nutrition increases rather than decreases later cardiovascular risk. We report the long-term impact of growth promotion in term infants born small for gestational age (birth weight <10th percentile).

Methods and Results--Blood pressure was measured at 6 to 8 years in 153 of 299 (51%) of a cohort of children born small for gestational age and randomly assigned at birth to receive either a standard or a nutrient-enriched formula. The enriched formula contained 28% more protein than standard formula and promoted weight gain. Diastolic and mean (but not systolic) blood pressure was significantly lower in children assigned to standard compared with nutrient-enriched formula (unadjusted mean difference for diastolic blood pressure, -3.2 mm Hg; 95% CI, -5.8 to -0.5; P=0.02) independent of potential confounding factors (adjusted difference, -3.5 mm Hg; P=0.01). In observational analyses, faster weight gain in infancy was associated with higher later blood pressure.

Conclusions--In the present randomized study targeted to investigate the effect of early nutrition on long-term cardiovascular health, we found that a nutrient-enriched diet increased later blood pressure. These findings support an adverse effect of relative "overnutrition" in infancy on long-term cardiovascular disease risk, have implications for the early origins of cardiovascular disease hypothesis, and do not support the promotion of faster weight gain in infants born small for gestational age.

Key words: blood pressure • follow-up studies • gestational age • nutrition

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