CLINICAL STUDY Elevated ghrelin levels in preterm born children during prepubertal ages and relationship with catch-up growth Feyza Darendeliler 1 , Firdevs Bas 1 , Ruveyde Bundak 1 , Asuman Coban 2 , Rian Disci 3 , Ozlem Sancakli 4 , Gulbin Gokcay 5 , Zeynep Ince 2 and Gulay Can 2 1 Pediatric Endocrinology Unit, Department of Pediatrics, 2 Neonatalogy Unit, Department of Pediatrics, 3 Department of Biostatistics, 4 Department of Pediatrics and 5 Social Pediatrics Unit, Department of Pediatrics, Istanbul Faculty of Medicine, Istanbul University, 34390 Istanbul, Turkey (Correspondence should be addressed to F Darendeliler who is now at I ˙ stanbul Tıp Faku ¨ltesi, C ¸ ocuk Klinig ˘i, C ¸ apa, 34390 Istanbul, Turkey; Email: feyzad@istanbul.edu.tr) Abstract Background: Ghrelin, the natural ligand of the GH secretagogue receptor, has potent orexigenic effect. Ghrelin levels are negatively associated with insulin secretion, increased in anorexia, and reduced in obesity. Increased ghrelin levels may be associated with early postnatal growth in preterm born children. Objective: Aim of this study was to evaluate ghrelin and insulin levels at prepubertal ages in preterm born children born appropriate for gestational age (AGA) or small for gestational age (SGA) and relationships with catch-up growth (CUG) in a prospective cross-sectional study. Methods: Eighty-four preterm born children grouped as preterm SGA (nZ28) and preterm AGA (nZ56) were evaluated at age 4.7G0.2 and 4.7G0.1 years with respect to their ghrelin and insulin levels. Their data were compared with that of body mass index matched term SGA (nZ35) and term AGA (nZ44) children of age 4.6G0.2 and 3.8G0.1 years. All children had height appropriate for their target height. CUG was defined as the difference between birth size and recent size and expressed as D height and D weight SDS. Results: Preterm SGA and preterm AGA children had similar ghrelin levels (1717.0G166.9 and 1656.5G103.8 pg/ml), although D height and D weight SDS in preterm SGA were significantly higher than in preterm AGA children (P!0.001). Ghrelin levels in both preterm groups were higher than term SGA (469.2G132.5 pg/ml) and term AGA children (659.6G143.3 pg/ml; P!0.001 for all). D Height and D weight SDS of the term SGA children were similar to that of preterm SGA children. Ghrelin did not have correlation with CUG but had inverse correlation with recent anthropometric indices. Insulin was significantly higher in term SGA children than other groups (P!0.001). Conclusions: Preterm children have higher ghrelin levels at prepubertal ages regardless of the magnitude of their CUG. Term SGA children, on the other hand, behave differently and have lower ghrelin levels than preterm children at prepubertal ages, which may be related to elevated insulin levels in this group. European Journal of Endocrinology 159 555–560 Introduction Ghrelin, a 28-amino-acid peptide, is predominantly produced in the stomach but its expression has been demonstrated in several other organs including hypo- thalamus and pituitary gland (1, 2). It has been shown to be a natural ligand of growth hormone (GH) secretago- gue receptor and plays a major role in the control of somatotrop function (2). It has also been considered as a major orexigenic factor and controls energy balance, enhancing fat mass deposition, and food intake (3). Circulating ghrelin levels are negatively associated with body mass index (BMI); ghrelin secretion is increased in anorexia and cachexia and reduced in obesity (2, 4). There is a strong negative association between insulin and ghrelin levels (5). In humans, circulating ghrelin levels are increased by energy restriction and decreased by food intake (6). It has been shown that early in the neonatal period ghrelin levels increase in preterm infants (7, 8). Interestingly, this increase is not inhibited by food intake (7). The absence of inhibition of ghrelin by food intake has been shown in prepubertal children as well, in contrast to adults (9, 10). This ghrelin refractoriness to food intake from birth to childhood may suggest that this hormone may play an anabolic drive in the growth and development. In fact, it has been shown that small for gestational age (SGA) and very low birth weight infants show higher increase in ghrelin levels at birth and after birth, which may indicate increased European Journal of Endocrinology (2008) 159 555–560 ISSN 0804-4643 q 2008 European Society of Endocrinology DOI: 10.1530/EJE-08-0357 Online version via www.eje-online.org