I. Multicentre clinical trial on the effects of diet on low birthweight infants

Optimal dietary management of preterm infants is uncertain partly because it has been based largely on short term studies rather than on clinical outcome data. We introduce as a possible model for further trials, the structure of a large five-centre study designed to investigate dietary influences on morbidity and long term neurodevelopment, growth and clinical outcome. Currently, >600 unselected preterm infants (<1850g), both ill and well, have been randomised into 4 parallel trials involving paired comparisons of banked milk (BBM), adapted formula, or preterm formula (PTF) fed as sole diets or in conjunction with maternal milk. Overall postrandomization incidence of NEC (3.6%), death (5.8%) and serious metabolic complications are used to illustrate the very large calculated sample sizes required to provide adequate reassurance on clinical safety of available diets. In the short term BBM fed infants, compared with those fed PTF, have reduced steady gains in weight (p<0.001), length and OFC (p<0.02), different body proportions (reduced ratio; length or OFC: weight2, (p<0.01), and marginally lower body water (by deuterium isotope dilution). Whereas at 2 kg, a PTF fed infant born at 1kg/28 weeks has maintained its birth centile, weight falls <3rd centile (Lubcenko) on breastmilk. These continuing trials will test the hypotheses that early growth influences neurodevelopment and programmes future growth.