Changes of leptin and metabolic hormones in preterm infants: a longitudinal study in early postnatal life

OBJECTIVES Very little is known concerning the physiological role of leptin and growth in the early postnatal period and the association of leptin with other metabolic hormones in preterm infants. This study aims to investigate these relationships, and to explore the longitudinal and dynamic profile of leptin and metabolic hormones including insulin, ACTH, cortisol and FT4 in this category of patient. We also postulate that a rapid increase in body weight and body mass index in the first few weeks of life may be associated with a corresponding increase in serum leptin if the 'adipoinsular axis' is active at this stage. DESIGN A longitudinal study in a cohort of preterm infants < 34 weeks gestation for the first five weeks of postnatal life. PATIENTS and METHODS Sixty-one preterm newborns < 34 weeks gestation were prospectively enrolled. Blood samples were collected in the morning when the newborns were 24 h of age (day 1), and on days 5, 14 and 35 of life. Serum leptin, insulin, cortisol, FT4, glucose and plasma ACTH concentrations were analysed using standard biochemical methods. Spearman's correlation coefficient was used to assess the inter-relationship of different metabolic hormones on the first day of life, and the relationship between metabolic hormones on day 1 and anthropometric or clinical parameters. The mixed-effects models were further used for analysing the multiple longitudinal measurements, and also for comparing the hormone concentrations between day 1 (baseline) and their corresponding levels on days 5, 14 and 35. RESULTS Serum leptin on day 1 (baseline) was significantly associated with serum insulin (r = 0.30, P < 0.05) and insulin:glucose ratio (r = 0.29, P < 0.05) in infants < 34 weeks gestation. Female preterm infants had significantly higher serum leptin (P < 0.05) and insulin (P < 0.05) levels than male infants. In addition, the duration between the last dose of antenatal dexamethasone and delivery significantly influenced the serum concentrations of leptin (r = - 0.27, P < 0.05), cortisol (r = 0.52, P < 0.001), plasma ACTH (r = 0.28, P < 0.05) and insulin:glucose ratio (r = - 0.27, P < 0.05) on the first day of life. Despite significant increase in body weight (P < 0.00001) and body mass index (P < 0.00001) by day 35 when compared to birth weight, no corresponding significant changes were observed for serum leptin, insulin and FT4. However, there was an increasing though statistically nonsignificant trend in serum leptin after day 14 of life. CONCLUSION This study characterized the longitudinal profile of leptin and metabolic hormones in preterm infants < 34 weeks gestation in the first 5 weeks of life. Serum leptin was significantly associated with serum insulin and insulin:glucose ratio supporting the hypothesis that an 'adipoinsular axis' exists and is likely to be functional before 34 weeks of gestation. Although a significant increase in body weight was demonstrated by day 35, no significant corresponding changes occurred with regard to serum leptin. We postulate that the limited quantity of adipose tissue at this stage of development might have contributed to this observation. Moreover, our results also showed that the duration between the last dose of antenatal corticosteroid and delivery could influence the postnatal concentrations of adipoinsular and pituitary-adrenal hormones. Thus, it is possible that antenatal dexamethasone might affect fetal growth and development via these neuroendocrine pathways in early intrauterine life.