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

BMJ 1998;317:1481-1487 ( 28 November )

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

A Lucas, MRC clinical research professor, ^a R Morley, head of clinical trials group, ^a T J Cole, statistician. ^b

^a Medical Research Council Childhood Nutrition Research Centre, Institute of Child Health, London WC1N 1EH, ^b Medical Research Council Dunn Nutrition Unit, Cambridge, CB4 1XJ

Correspondence to: Professor Lucas A.Lucas{at}ich.ucl.ac.uk

Objectives: To determine whether perinatal nutrition influencescognitive function at 7 1/2 - 8 years in children born preterm.
Design: Randomised, blinded nutritional interventiontrial. Blinded follow up at 7 1/2 - 8years.
Setting: Intervention phase in two neonatal units;follow up in a clinic or schoolsetting.
Subjects: 424 preterm infants who weighed under 1850 gat birth; 360 of those who survived were tested at 7 1/2 - 8years.
Interventions: Standard infant formula versus nutrient enrichedpreterm formula randomly assigned as sole diet (trial A) or supplementsto maternal milk (trial B) fed for a mean of 1month.
Main outcome measures: Intelligence quotient (IQ) at 7 1/2 - 8 years withabbreviated Weschler intelligence scale for children(revised).
Results: There was a major sex difference in the impactof diet. At 7 1/2 - 8 years boys previously fed standard versus pretermformula as sole diet had a 12.2 point disadvantage (95% confidenceinterval 3.7 to 20.6; P<0.01) in verbal IQ. In those with highestintakes of trial diets corresponding figures were 9.5 point disadvantageand 14.4 point disadvantage in overall IQ (1.2 to 17.7; P<0.05)and verbal IQ (5.7 to 23.2; P<0.01). Consequently, more infantsfed term formula had low verbal IQ (<85): 31% versus 14% for bothsexes (P=0.02) and 47% versus 13% in boys P=0.009). There wasa higher incidence of cerebral palsy in those fed term formula;exclusion of such children did not alter thefindings.
Conclusions: Preterm infants are vulnerable to suboptimalearly nutrition in terms of their cognitive performance $---$ notably,language based skills $---$ at 7 1/2 - 8 years, when cognitive scores arehighly predictive of adult ones. Our data on cerebral palsy generatea new hypothesis that suboptimal nutritional management duringa critical or plastic early period of rapid brain growth couldimpair functional compensation in those sustaining an earlierbrain insult. Cognitive function, notably in males, may be permanentlyimpaired by suboptimal neonatalnutrition.

Key messages

Suboptimal nutrition during sensitive stages in early brain development may have long term effects on cognitive function
In a randomised trial of early nutrition in preterm infants those fed standard rather than nutrient enriched preterm formula had reduced verbal IQ scores at 7 1/2 to 8 years, at least in boys
In exploratory analyses on children of both sexes verbal IQ below 85 and cerebral palsy were more prevalent in the standard formula group
Our data show the potential vulnerability of the human brain to early suboptimal nutrition
Avoidance of undernutrition in sick preterm infants seems important in optimising later neurodevelopmental outcomes

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