Elsevier

The Lancet

Volume 357, Issue 9254, 10 February 2001, Pages 413-419
The Lancet

Articles
Early nutrition in preterm infants and later blood pressure: two cohorts after randomised trials

https://doi.org/10.1016/S0140-6736(00)04004-6Get rights and content

Summary

Background

Despite data relating body size in early life to later cardiovascular outcomes, the hypothesis that nutrition affects such outcomes has not been established. Breastfeeding has been associated with lower blood pressure in later life, but previous studies have not controlled for possible confounding factors by using a randomised design with prospective follow-up. We undertook such a study to test the hypothesis that early diet programmes blood pressure in later life in children randomly assigned different diets at birth.

Methods

Blood pressure was measured at age 13–16 years in 216 (23%) of a cohort of 926 children who were born prematurely and had participated at birth in two parallel randomised trials in five neonatal units in the UK. Dietary interventions were: donated banked breastmilk versus preterm formula and standard term formula versus preterm formula.

Findings

Children followed up at age 13–16 years were similar to those not followed up in terms of social class and anthropometry at birth. Mean arterial blood pressure at age 13–16 years was lower in the 66 children assigned banked breastmilk (alone or in addition to mother's milk) than in the 64 assigned preterm formula (mean 81·9 [SD 7·8] vs 86·1 [6·5] mm Hg; 95% CI for difference −6·6 to −1·6; p=0·001). In non-randomised analyses, the proportion of enteral intake as human milk in the neonatal period was inversely related to later mean arterial pressure (β=−0·3 mm Hg per 10% increase [95% CI −0·5 to −0·1]; p=0·006). No differences were found in the term formula (n=44) versus preterm formula (n=42) comparison.

Interpretation

Breastmilk consumption was associated with lower later blood pressure in children born prematurely. Our data provide experimental evidence of programming of a cardiovascular risk factor by early diet and further support the long-term beneficial effects of breastmilk.

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.

Section snippets

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

References (30)

  • DJP Barker et al.

    Weight in infancy and death from ischaemic heart disease

    Lancet

    (1989)
  • T Baranowski et al.

    Height, infant-feeding practices and cardiovascular functioning among 3 or 4 year old children in three ethnic groups

    J Clin Epidemiol

    (1992)
  • CM Law et al.

    Is blood pressure inversely related to birth weight? The strength of evidence from a systematic review of the literature

    J Hypertens

    (1996)
  • DJP Barker et al.

    The relation of small head circumference and thinness at birth to death from cardiovascular disease in adult life

    BMJ

    (1993)
  • DJP Barker et al.

    Growth in utero, blood pressure in childhood and adult life, and mortality from cardiovascular disease

    BMJ

    (1989)
  • PH Whincup et al.

    Early influences on blood pressure: a study of children aged 5–7 years

    BMJ

    (1989)
  • PH Whincup et al.

    Do maternal and intrauterine factors influence blood pressure in childhood?

    Arch Dis Child

    (1992)
  • CM Law et al.

    Initiation of hypertension in utero and its amplification throughout life

    BMJ

    (1993)
  • P Whincup et al.

    Birth weight and blood pressure: cross sectional and longitudinal relations in childhood

    BMJ

    (1995)
  • L Taittonen et al.

    Prenatal and postnatal factors in predicting later blood pressure among children: cardiovascular risk in young Finns

    Pediatr Res

    (1996)
  • AC Wilson et al.

    Relation of infant diet to childhood health: seven year follow up of cohort in Dundee infant feeding study

    BMJ

    (1998)
  • A Lucas et al.

    Multicentre trial on feeding of low birthweight infants: effects of diet on early growth

    Arch Dis Child

    (1984)
  • A Lucas et al.

    Randomised trial of early diet in preterm babies and later intelligence quotient

    BMJ

    (1998)
  • A Lucas et al.

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

    BMJ

    (1994)
  • JV Freeman et al.

    Cross-sectional stature and weight reference curves for the UK, 1990

    Arch Dis Child

    (1990)
  • Cited by (495)

    • Relationships between early flavor/texture exposure, and food acceptability and neophobia

      2022, Flavor: From Food to Behaviors, Wellbeing and Health, Second Edition
    View all citing articles on Scopus
    View full text