In the past, weight and weight gain have been the two parameters used frequently in neonatal units to monitor nutrition among high-risk infants. Our investigation sought to assess how several anthropometric measures (weight, length, head circumference, arm:head circumference ratio, and tricep skinfold) and serum albumin, transthyretin, and transferrin concentrations reflect protein and energy intake. After monitoring 42 preterm and 40 sick infants over 3 consecutive weeks, we found that transthyretin concentration proved the only serum protein which accurately measured energy and protein intakes in less than 1 week from dietary manipulation. Among preterm infants, as protein and energy intakes rose, transthyretin concentration increased significantly (p less than 0.001). Preterm infants ingested 79 +/- 39 kcal/kg/day and 2.04 +/- 1.02 g protein/kg/day at the first assessment point after birth and rose to 103 +/- 34 kcal/kg/day and 2.64 +/- 0.94 g protein/kg/day. Likewise, transthyretin measured 10.83 +/- 3.91 mg/dl at the initial measurement and rose to 14.80 +/- 4.44 at the second measurement time. Although protein intakes measured slightly lower in the sick group, their intakes correlated to transthyretin concentration (assessment time 1, r = 0.39; time 2, r = 0.33; time 3, r = 0.33). Thus, transthyretin concentration in neonatal infants offers a rapid, accurate, and moderately inexpensive way to monitor protein-energy adequacy.