ArticlesEarly nutrition in preterm infants and later blood pressure: two cohorts after randomised trials
Introduction
The potential effect of early nutrition on cardiovascular disease is an issue of major public-health importance. Associations between low weight1 and thinness2 at birth and hypertension and coronary-artery disease in later life are thought to be consistent with the hypothesis that undernutrition in early life 'programmes' later cardiovascular outcomes such as blood pressure.3, 4, 5, 6, 7, 8 A greater risk of death from coronary heart disease in men who were light for age at 1 year9 also suggests that the critical period of sensitivity for nutrition in terms of its influence on cardiovascular disease extends into the first year of postnatal life.
Despite these strong epidemiological data relating size in early life to later outcome, an effect of fetal or infant nutrition on later risk factors for ischaemic heart disease is theoretical and has not been adequately established because of the lack of a randomised design in previous studies.
Breastfeeding has been associated with lower blood pressure in later life, 8, 10 but observational data cannot extricate any possible effects of diet from environmental influences associated with the maternal choice to breastfeed. An experimental study would be needed, but randomisation to breastfeeding or formula feeding would be difficult. We had an opportunity, however, to test the hypothesis that feeding of breastmilk to premature infants programmes later blood pressure in a formal experimental intervention trial. In the early 1980s, human-milk banks were in common use to provide preterm infants with breastmilk from unrelated donors. Random assignment of preterm infants to donated human milk or formula was ethical because at that time the optimum diet for babies born preterm was uncertain and the long-term outcomes of early feeding regimens unknown.11
Our study started in 1982. It consisted of two parallel randomised trials: one compared banked breastmilk with nutrient-enriched preterm formula; the other compared a standard term formula with the nutrient-enriched preterm formula. Our planned follow-up allowed us to test the generic hypothesis that early nutrition influences later blood pressure and the a-priori specific hypothesis that consumption of human milk in infancy leads to lower blood pressure in later life.
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Participants
The study participants were recruited from a cohort of 926 children born preterm who had participated in randomised controlled trials initially investigating the effects of early diet on later cognitive function.12 Planned later follow-up of this cohort was designed to test the hypothesis that early diet influences risk factors for cardiovascular disease.13
Between 1982 and 1985, babies with no major congenital anomalies and of birthweight less than 1850 g were recruited in five UK centres
Observations in cohorts after randomised trials
There were no significant differences in birthweight, duration of gestation, social class, SD scores for birthweight and discharge weight, and clinical variables between children who were or were not followed up at age 13–16 years (table 1).
As expected, early weight gain was significantly greater in infants assigned nutrient-enriched preterm formula than in those assigned banked breastmilk (table 2). Among the children followed up at age 13–16 years, there were no significant differences in
Discussion
We tested the hypothesis that diet in infancy influences or 'programmes' a key cardiovascular risk factor, namely blood pressure, in later life. Our study in preterm infants took two approaches: two parallel randomised trials that compared banked donated breastmilk with an infant formula or two formulas differing in nutrient content; and an observational study comparing human milk with other diets.
Our major finding related to the studies including use of breastmilk. We found lower blood
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