Randomized clinical trials in infancy: methodologic issues.

Randomized clinical trials of early nutritional interventions in infants are necessary to establish safety and efficacy of supplementation of infant formulas with LCPUFAS for term and preterm infants. Such trials pose significant methodologic difficulties when applied to infants because of the rapidly changing development of the infant's central nervous system and its interdependence with multiple environmental factors. Current assessments of infant cognitive development in the first year of life lack stability and predictive relationships to later outcomes. Thus, intervention trials need to extend beyond the first two years of life. Small sample sizes, high attrition rates, and lack of attention to confounding variables known to be related to child outcomes are additional problems in the majority of studies to date, especially for preterm populations. Attention to selection and attrition biases and the roles of mediating and moderating factors in affecting intervention effects are also necessary to determine the benefits vs risks of LCPUFA supplementation of infant formula.