Neurodevelopment in children born small for gestational age: a randomized trial of nutrient-enriched versus standard formula and comparison with a reference breastfed group.
OBJECTIVE
Many studies have shown that children born small for gestational age (SGA) are at a neurodevelopmental disadvantage. We have shown that nutrient enrichment of formula fed to term SGA infants improves their growth and hypothesized that it also would improve their neurodevelopmental outcome.


METHODS
A randomized, controlled trial of standard term-infant (n = 147) or nutrient-enriched (n = 152) formula for the first 9 months. A reference group of 175 breastfed SGA infants was also recruited.


METHODS
Subjects were recruited in 5 maternity hospitals in Cambridge, Nottingham, and Leicester, all in the United Kingdom.


METHODS
Healthy, term infants (gestation: > or =37 weeks) with birth weight <10th centile.


METHODS
Bayley mental and psychomotor scores at 18 months (primary) and developmental scores from Knobloch, Pasamanick, and Sherrard's developmental screening inventory at 9 months (secondary).


RESULTS
There was no significant intergroup difference in Bayley Mental Development Index (MDI) or Psychomotor Development Index (PDI) scores at 18 months. However, at 9 months, children fed the enriched formula had a significantly lower developmental quotient (99.5 vs 102.0; 95% confidence interval [CI] for difference: -4.6, -0.4). A significant disadvantage was seen in girls (-5.1; 95% CI: -7.8, -2.4) but not in boys (0.9; 95% CI: -2.4, 4.2). Breastfed infants had significantly higher MDI and PDI scores at 18 months than formula-fed infants. Confounding factors accounted for approximately 34% of the observed association between breastfeeding and MDI score and none of the association between breastfeeding and PDI score.


CONCLUSIONS
The previously reported enhanced linear growth in SGA children fed enriched formula was not matched by a neurodevelopmental advantage. At 9 months, girls fed the enriched formula had a significant developmental disadvantage, although this was not seen at 18 months. Later follow-up will determine any long-term effects on health or development. Meanwhile, use of enriched formula for term SGA children should not be promoted. It seems that breastfeeding may be especially beneficial for neurodevelopment in children born SGA.
Morley
Ruth
R
Medical Research Council Childhood Nutrition Research Centre, Institute of Child Health, London, United Kingdom. morleyr@unimelb.edu.au
Fewtrell
Mary S
MS
Abbott
Rebecca A
RA
Stephenson
Terence
T
MacFadyen
Una
U
Lucas
Alan
A
D001942:Breast Feeding; D002657:Child Development; D002675:Child, Preschool; D019587:Dietary Supplements; D005260:Female; D006801:Humans; D007223:Infant; D041943:Infant Formula; D007227:Infant Nutritional Physiological Phenomena; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age; D008297:Male; D009483:Neuropsychological Tests