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

Abstract

Objectives: To determine whether perinatal nutrition influences cognitive function at 7 1/2 - 8 years in children born preterm.

Design: Randomised, blinded nutritional intervention trial. Blinded follow up at 7 1/2 - 8 years.

Setting: Intervention phase in two neonatal units; follow up in a clinic or school setting.

Subjects: 424 preterm infants who weighed under 1850 g at birth; 360 of those who survived were tested at 7 1/2 - 8 years.

Interventions: Standard infant formula versus nutrient enriched preterm formula randomly assigned as sole diet (trial A) or supplements to maternal milk (trial B) fed for a mean of 1 month.

Main outcome measures: Intelligence quotient (IQ) at 7 1/2 - 8 years with abbreviated Weschler intelligence scale for children (revised).

Results: There was a major sex difference in the impact of diet. At 7 1/2 - 8 years boys previously fed standard versus preterm formula as sole diet had a 12.2 point disadvantage (95% confidence interval 3.7 to 20.6; P<0.01) in verbal IQ. In those with highest intakes of trial diets corresponding figures were 9.5 point disadvantage and 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 infants fed term formula had low verbal IQ (<85): 31% versus 14% for both sexes (P=0.02) and 47% versus 13% in boys P=0.009). There was a higher incidence of cerebral palsy in those fed term formula; exclusion of such children did not alter the findings.

Conclusions: Preterm infants are vulnerable to suboptimal early nutrition in terms of their cognitive performance--notably, language based skills--at 7 1/2 - 8 years, when cognitive scores are highly predictive of adult ones. Our data on cerebral palsy generate a new hypothesis that suboptimal nutritional management during a critical or plastic early period of rapid brain growth could impair functional compensation in those sustaining an earlier brain insult. Cognitive function, notably in males, may be permanently impaired by suboptimal neonatal nutrition.

Figures

Figure 1

Design of longitudinal study of early diet and later developmental status. Comparison of standard term versus preterm formula for 424 infants weighing under 1850 g at birth

Figure 2

Mean (SE) verbal intelligence quotient (IQ) and overall IQ in boys and girls fed standard versus preterm formula as their sole diet. Dietary comparison is made for all boys and also for those receiving highest intakes of trial diets (see text).*P