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. Design. 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. Setting. Subjects were recruited in 5 maternity hospitals in Cambridge, Nottingham, and Leicester, all in the United Kingdom. Participants. Healthy, term infants (gestation: greater than or equal to37 weeks) with birth weight <10th centile. Outcome Measures. 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 ∼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.