Does early nutrition in infants born before term programme later blood pressure?

Objectives--To test whether nutrition early in infants' development programmes later blood pressure and whether the reported relation between low birth weight and later high blood pressure is due to poor nutrition or growth before full term.

Design--Prospective randomisation of preterm infants to early diets differing greatly in nutrient content in four parallel multicentre trials, with blinded follow up 7.5-8 years later.

Setting--Neonatal units at Cambridge, Ipswich, King's Lynn, Norwich, and Sheffield.

Subjects--758 children weighing under 1850 g at birth.

Main outcome measure--Blood pressure at age of 7.5-8 years.

Results--There were major differences in nutrient intake from randomised diets (preterm formula v standard formula and preterm formula v donor breast milk; in each case with or without mother's milk), but follow up showed no differences in later blood pressure. Individual subjects showed large variation in protein and energy intakes and in growth performance, including degrees of growth failure seldom seen in utero, but these factors were also unrelated to later blood pressure.

Conclusion--Extremes of nutritional intake and growth performance in preterm infants do not programme later blood pressure at 7.5-8 years of age. These findings do not support the hypothesis that high blood pressure has early nutritional origins. We suggest that the long term rise in blood pressure reported in individuals who had low birthweight (at full term) is not, as previously speculated, due to poor fetal nutrition or growth as such.

Introduction

The possibility that nutrition in early life could influence propensity to adult disease(1) is of great concern to public health. This idea originates from the more general concept in developmental biology recently redefined by Lucas as programming,(2) the process whereby a stimulus or insult when applied at a critical or sensitive period of development results in a long term or permanent effect on the structure or function of the organism. Animal evidence for programming during critical periods of development dates back over 100 years(3); that early nutrition could operate in this way(1) is supported by numerous experimental studies in animals.(2)(4)(5) Corresponding evidence in humans has been more difficult to obtain. Our approach is to conduct formal long term prospective outcome studies of individuals randomly assigned to their early diet.(6)(7) Recent retrospective epidemiological studies have linked possible markers of early nutrition, notably size at birth or in infancy, with cardiovascular disease or its risk factors in adult life.(8)(9) Several investigators have shown that babies born small have higher blood pressure in later life.(9)(10)

Barker et al suggested that small size at birth reflects suboptimal fetal nutrition and argued that nutritional intervention during pregnancy might favourably influence later blood pressure.(11) Since 1982 we have explored the hypothesis that early nutrition programmes later blood pressure in a large multicentre study of preterm infants born in the third or late second trimester. Their diets were strictly randomly assigned until they reached, on average, full term, and their blood pressure was measured at 7.5-8 years of age. This study allowed us to extricate the effects of nutrition before term from other factors that might have influenced later blood pressure had these infants remained in utero. Furthermore, when premature babies reach the equivalent of full term they have often developed severe growth failure,(6) commonly compounded by preexisting growth retardation at birth,(12) which would enable us to examine effects on later blood pressure of extremes of growth failure seldom seen in the fetus born at term.

Subjects and methods

We enrolled 926 infants with birth weights under 1850 g admitted to the neonatal units in Cambridge, Ipswich, King's Lynn, Norwich, and Sheffield between 1982 and 1985.(6) Ethical approval was obtained in …