Promotion of faster weight gain in infants born small for gestational age: is there an adverse effect on later blood pressure?

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.