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

Objectives. Preterm infants are frequently discharged from the hospital gro wth retarded and show reduced growth throughout childhood. In a large effic acy and safety trial, we tested the hypothesis that nutritional interventio n in the first 9 months postterm would reverse postdischarge growth deficit s and improve neurodevelopment without adverse safety outcomes. Participants and intervention. Two hundred eighty-four infants (mean gestat ion: 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' postmen strual 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 1 8 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 heavie r (difference 370 g; 95% confidence interval [CI]: 84-660) and longer (diff erence 1.1 cm; 95% CI: 0.3-1.9); the difference in length persisted at 18 m onths (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 month s (1.5cm [95% CI: 0.3-2.7]). There was no significant difference in develop mental 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, exclusi vely breastfed infants were already 513 g (95% CI: 310-715) lighter and 1.6 cm (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 int end to follow-up the children at older ages. The observed efficacy of PDF w as not associated with adverse safety outcomes. 2) We cannot reject the hyp othesis that postdischarge nutrition benefits motor development and this re quires additional study. 3) Our data raise the possibility that breastfed p ostdischarge preterm infants may require nutritional supplementation, curre ntly under investigation.