Randomized trial of nutrient-enriched formula versus standard formula for postdischarge preterm infants.

Objectives: Preterm infants are frequently discharged from the hospital growth retarded and show reduced growth throughout childhood. In a large efficacy and safety trial, we tested the hypothesis that nutritional intervention in the first 9 months postterm would reverse postdischarge growth deficits and improve neurodevelopment without adverse safety outcomes.

Participants And Intervention: Two hundred eighty-four infants (mean gestation: 30.9 weeks) were studied; 229 were randomly assigned a protein, energy, mineral, and micronutrient-enriched postdischarge formula (PDF; N = 113) or standard term formula (TF; N = 116) from discharge (mean 36.5 weeks' postmenstrual age). A reference group (N = 65) was breastfed until at least 6 weeks' postterm. Outcome measures. Anthropometry was performed at 6 weeks and 3, 6, 9, and 18 months. Development was measured at 9 months (Knobloch, Passamanick, and Sherrard's developmental screening inventory) and 18 months (Bayley Scales of Infant Development II; primary outcome) postterm.

Results: At 9 months, compared with the TF group, those fed PDF were heavier (difference 370 g; 95% confidence interval [CI]: 84-660) and longer (difference 1.1 cm; 95% CI: 0.3-1.9); the difference in length persisted at 18 months (difference 0.82 cm; 95% CI: -0.04-1.7). There was no effect on head circumference. The effect of diet was greatest in males; at 9 months length deficit with TF was 1.5cm (95% CI: 0.3-2.7), and this remained at 18 months (1.5cm [95% CI: 0.3-2.7]). There was no significant difference in developmental scores at 9 or 18 months, although PDF infants had a 2.8 (-1.3-6.8) point advantage in Bayley motor score scales. At 6 weeks' postterm, exclusively breastfed infants were already 513 g (95% CI: 310-715) lighter and 1.6cm (95% CI: 0.8-2.3) shorter than the PDF group, and they remained smaller up to 9 months' postterm.

Conclusions: 1) Improving postdischarge nutrition in the first 9 months may "reset" subsequent growth-at least until 18 months for body length. We intend to follow-up the children at older ages. The observed efficacy of PDF was not associated with adverse safety outcomes. 2) We cannot reject the hypothesis that postdischarge nutrition benefits motor development and this requires additional study. 3) Our data raise the possibility that breastfed postdischarge preterm infants may require nutritional supplementation, currently under investigation.