Leptin is involved in the regulation of body weight through a feedback signal between adipose tissue and the satiety center, to decrease food intake and increase energy expenditure. Newborn infants experience physiological weight loss during the first week of life. The leptin level may be decreased to enhance food intake and to decrease energy expenditure for physiological adaptation during early postnatal days. Insulin-like growth factor-I (IGF-I) and insulin are involved in the regulation of perinatal growth. Leptin might be interrelated with IGF-I or insulin, since both of these have adipogenic and somatotropic effects. We therefore hypothesized that leptin, IGF-I and insulin would be decreased during the first week of life, concurrently with physiological weight loss. Thirty preterm AGA infants (birth weight 1.574+/-313 g; GA 31.9+/-2.2 wk) were studied. All infants received parenteral nutrition from the third day after birth. Leptin was significantly decreased during the first week of life, and insulin was significantly increased at day 7 vs. day 1 and day 3. IGF-I did not change during the first week of life. Leptin was positively correlated with body weight (r = 0.368, p<0.01), body mass index (r = 0.267, p<0.05), and serum IGF-I (r = 0.330, p <0.01), but not with serum insulin. The percent of weight reduction during the first week of life was not correlated with the percent of leptin reduction during the first week of life. In conclusion, leptin was significantly decreased and positively correlated with body weight and IGF-I during the first week of life. Changes of leptin and insulin might be related to postnatal adaptation in metabolism, but the exact role of leptin, IGF-I and insulin in postnatal physiological weight loss is not clear.