The Role of Umbilical Cord Blood Concentration of IGF-I, IGF-II, Leptin, Adiponectin, Ghrelin, Resistin, and Visfatin in Fetal Growth

Abstract

Objective Herein, we measured the concentration of insulinlike growth factor I (IGF-I), IGF-II, leptin, adiponectin, ghrelin, resistin, and visfatin in the umbilical cord blood of newborns categorized as “small for gestational age” (SGA), “appropriate for gestational age” (AGA), and “large for gestational age” (LGA). Our aim was to elucidate the link between the levels of these proteins and fetal growth.

Study Design A total of 96 term infants were included and categorized into three weight categories. Their venous cord blood samples were collected to measure the levels of IGF-I, IGF-II, leptin, adiponectin, ghrelin, resistin, and visfatin.

Results IGF-I, visfatin, and leptin levels showed significant differences among the groups. Pairwise comparisons showed that adiponectin (p = 0.023), resistin (p = 0.025), and ghrelin (p = 0.005) levels were significantly lower in the SGA group than in the LGA group. Correlation analyses showed a strong association of IGF-1, IGF-II, and leptin levels with birth weight (r = 0.644, p < 0.001; r = 0.441, p < 0.001; and r = 0.404, p < 0.001, respectively).

Conclusion SGA newborns showed a significantly higher visfatin concentration and lower ghrelin, leptin, resistin, and adiponectin levels than the AGA and LGA newborns did.

Keywords

fetal growth - visfatin - ghrelin - leptin - resistin

• References

• 1 Gicquel C, Le Bouc Y. Hormonal regulation of fetal growth. Horm Res 2006; 65 (Suppl. 03) 28-33
• 2 Dessì A, Ottonello G, Fanos V. Physiopathology of intrauterine growth retardation: from classic data to metabolomics. J Matern Fetal Neonatal Med 2012; 25 (Suppl. 05) 13-18
• 3 Meier U, Gressner AM. Endocrine regulation of energy metabolism: review of pathobiochemical and clinical chemical aspects of leptin, ghrelin, adiponectin, and resistin. Clin Chem 2004; 50 (09) 1511-1525
• 4 Briana DD, Malamitsi-Puchner A. The role of adipocytokines in fetal growth. Ann N Y Acad Sci 2010; 1205: 82-87
• 5 Baker J, Liu JP, Robertson EJ, Efstratiadis A. Role of insulin-like growth factors in embryonic and postnatal growth. Cell 1993; 75 (01) 73-82
• 6 DeChiara TM, Efstratiadis A, Robertson EJ. A growth-deficiency phenotype in heterozygous mice carrying an insulin-like growth factor II gene disrupted by targeting. Nature 1990; 345 (6270): 78-80
• 7 Powell-Braxton L, Hollingshead P, Warburton C. , et al. IGF-I is required for normal embryonic growth in mice. Genes Dev 1993; 7 (12B): 2609-2617
• 8 Ong K, Kratzsch J, Kiess W, Costello M, Scott C, Dunger D. ; The ALSPAC Study Team. Avon Longitudinal Study of Pregnancy and Childhood. Size at birth and cord blood levels of insulin, insulin-like growth factor I (IGF-I), IGF-II, IGF-binding protein-1 (IGFBP-1), IGFBP-3, and the soluble IGF-II/mannose-6-phosphate receptor in term human infants. J Clin Endocrinol Metab 2000; 85 (11) 4266-4269
• 9 Luo ZC, Nuyt AM, Delvin E. , et al. Maternal and fetal IGF-I and IGF-II levels, fetal growth, and gestational diabetes. J Clin Endocrinol Metab 2012; 97 (05) 1720-1728
• 10 Ostlund E, Bang P, Hagenäs L, Fried G. Insulin-like growth factor I in fetal serum obtained by cordocentesis is correlated with intrauterine growth retardation. Hum Reprod 1997; 12 (04) 840-844
• 11 Lubchenco LO, Hansman C, Boyd E. Intrauterine growth in length and head circumference as estimated from live births at gestational ages from 26 to 42 weeks. Pediatrics 1966; 37 (03) 403-408
• 12 Chauhan SP, Rice MM, Grobman WA. , et al; MSCE, for the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network. Neonatal morbidity of small- and large-for-gestational-age neonates born at term in uncomplicated pregnancies. Obstet Gynecol 2017; 130 (03) 511-519
• 13 Landmann E, Reiss I, Misselwitz B, Gortner L. Ponderal index for discrimination between symmetric and asymmetric growth restriction: percentiles for neonates from 30 weeks to 43 weeks of gestation. J Matern Fetal Neonatal Med 2006; 19 (03) 157-160
• 14 de Jong M, Cranendonk A, van Weissenbruch MM. Components of the metabolic syndrome in early childhood in very-low-birth-weight infants and term small and appropriate for gestational age infants. Pediatr Res 2015; 78 (04) 457-461
• 15 Yeung EH, McLain AC, Anderson N. , et al. Newborn adipokines and birth outcomes. Paediatr Perinat Epidemiol 2015; 29 (04) 317-325
• 16 Olsen IE, Groveman SA, Lawson ML, Clark RH, Zemel BS. New intrauterine growth curves based on United States data. Pediatrics 2010; 125 (02) e214-e224
• 17 Malamitsi-Puchner A, Briana DD, Boutsikou M, Kouskouni E, Hassiakos D, Gourgiotis D. Perinatal circulating visfatin levels in intrauterine growth restriction. Pediatrics 2007; 119 (06) e1314-e1318
• 18 Meral C, Cekmez F, Pirgon O. , et al. The relationship between serum visfatin, adiponectin, and insulin sensitivity markers in neonates after birth. J Matern Fetal Neonatal Med 2011; 24 (01) 166-170
• 19 Briana DD, Boutsikou M, Gourgiotis D. , et al. Role of visfatin, insulin-like growth factor-I and insulin in fetal growth. J Perinat Med 2007; 35 (04) 326-329
• 20 Tsai PJ, Yu CH, Hsu SP. , et al. Cord plasma concentrations of adiponectin and leptin in healthy term neonates: positive correlation with birthweight and neonatal adiposity. Clin Endocrinol (Oxf) 2004; 61 (01) 88-93
• 21 Cekmez F, Pirgon O, Tanju A, Ipcioglu OM. Cord plasma concentrations of visfatin, adiponectin and insulin in healthy term neonates: positive correlation with birthweight. Int J Biomed Sci 2009; 5 (03) 257-260
• 22 Kyriakakou M, Malamitsi-Puchner A, Militsi H. , et al. Leptin and adiponectin concentrations in intrauterine growth restricted and appropriate for gestational age fetuses, neonates, and their mothers. Eur J Endocrinol 2008; 158 (03) 343-348
• 23 Berg AH, Combs TP, Scherer PE. ACRP30/adiponectin: an adipokine regulating glucose and lipid metabolism. Trends Endocrinol Metab 2002; 13 (02) 84-89
• 24 Evagelidou EN, Giapros VI, Challa AS, Kiortsis DN, Tsatsoulis AA, Andronikou SK. Serum adiponectin levels, insulin resistance, and lipid profile in children born small for gestational age are affected by the severity of growth retardation at birth. Eur J Endocrinol 2007; 156 (02) 271-277
• 25 Martínez-Cordero C, Amador-Licona N, Guízar-Mendoza JM, Hernández-Méndez J, Ruelas-Orozco G. Body fat at birth and cord blood levels of insulin, adiponectin, leptin, and insulin-like growth factor-I in small-for-gestational-age infants. Arch Med Res 2006; 37 (04) 490-494
• 26 Karakosta P, Georgiou V, Fthenou E. , et al. Maternal weight status, cord blood leptin and fetal growth: a prospective mother-child cohort study (Rhea study). Paediatr Perinat Epidemiol 2013; 27 (05) 461-471
• 27 Mantzoros CS, Rifas-Shiman SL, Williams CJ, Fargnoli JL, Kelesidis T, Gillman MW. Cord blood leptin and adiponectin as predictors of adiposity in children at 3 years of age: a prospective cohort study. Pediatrics 2009; 123 (02) 682-689
• 28 Lepercq J, Taupin P, Dubois-Laforgue D. , et al. Heterogeneity of fetal growth in type 1 diabetic pregnancy. Diabetes Metab 2001; 27 (03) 339-344
• 29 Forhead AJ, Fowden AL. The hungry fetus? Role of leptin as a nutritional signal before birth. J Physiol 2009; 587 (Pt 6): 1145-1152
• 30 Harigaya A, Nagashima K, Nako Y, Morikawa A. Relationship between concentration of serum leptin and fetal growth. J Clin Endocrinol Metab 1997; 82 (10) 3281-3284
• 31 Harrington TA, Thomas EL, Frost G, Modi N, Bell JD. Distribution of adipose tissue in the newborn. Pediatr Res 2004; 55 (03) 437-441
• 32 Steppan CM, Bailey ST, Bhat S. , et al. The hormone resistin links obesity to diabetes. Nature 2001; 409 (6818): 307-312
• 33 Farid SD, Najati N, Gharebaghi MM, Haghjo AG, Ghojazadeh M. Resistin in cord blood of small for gestation age and appropriate for gestation age term neonates. Iran J Pediatr 2013; 23 (06) 659-663
• 34 Cho GJ, Yoo SW, Hong SC. , et al. Correlations between umbilical and maternal serum resistin levels and neonatal birth weight. Acta Obstet Gynecol Scand 2006; 85 (09) 1051-1056
• 35 Chanoine JP. Ghrelin in growth and development. Horm Res 2005; 63 (03) 129-138
• 36 Onal EE, Cinaz P, Atalay Y. , et al. Umbilical cord ghrelin concentrations in small- and appropriate-for-gestational age newborn infants: relationship to anthropometric markers. J Endocrinol 2004; 180 (02) 267-271
• 37 Chanoine JP, Yeung LP, Wong AC, Birmingham CL. Immunoreactive ghrelin in human cord blood: relation to anthropometry, leptin, and growth hormone. J Pediatr Gastroenterol Nutr 2002; 35 (03) 282-286
• 38 Otto B, Tschöp M, Heldwein W, Pfeiffer AF, Diederich S. Endogenous and exogenous glucocorticoids decrease plasma ghrelin in humans. Eur J Endocrinol 2004; 151 (01) 113-117
• 39 Espelund U, Hansen TK, Højlund K. , et al. Fasting unmasks a strong inverse association between ghrelin and cortisol in serum: studies in obese and normal-weight subjects. J Clin Endocrinol Metab 2005; 90 (02) 741-746
• 40 Agrogiannis GD, Sifakis S, Patsouris ES, Konstantinidou AE. Insulin-like growth factors in embryonic and fetal growth and skeletal development (Review). Mol Med Rep 2014; 10 (02) 579-584
• 41 Bhaumick B, Bala RM. Differential effects of insulin-like growth factors I and II on growth, differentiation and glucoregulation in differentiating chondrocyte cells in culture. Acta Endocrinol (Copenh) 1991; 125 (02) 201-211
• 42 Liu J-P, Baker J, Perkins AS, Robertson EJ, Efstratiadis A. Mice carrying null mutations of the genes encoding insulin-like growth factor I (Igf-1) and type 1 IGF receptor (Igf1r). Cell 1993; 75 (01) 59-72
• 43 Gluckman PD, Johnson-Barrett JJ, Butler JH, Edgar BW, Gunn TR. Studies of insulin-like growth factor -I and -II by specific radioligand assays in umbilical cord blood. Clin Endocrinol (Oxf) 1983; 19 (03) 405-413
• 44 Lassarre C, Hardouin S, Daffos F, Forestier F, Frankenne F, Binoux M. Serum insulin-like growth factors and insulin-like growth factor binding proteins in the human fetus. Relationships with growth in normal subjects and in subjects with intrauterine growth retardation. Pediatr Res 1991; 29 (03) 219-225
• 45 Christou H, Connors JM, Ziotopoulou M. , et al. Cord blood leptin and insulin-like growth factor levels are independent predictors of fetal growth. J Clin Endocrinol Metab 2001; 86 (02) 935-938
• 46 Randhawa R, Cohen P. The role of the insulin-like growth factor system in prenatal growth. Mol Genet Metab 2005; 86 (1-2): 84-90
• 47 Chiesa C, Osborn JF, Haass C. , et al. Ghrelin, leptin, IGF-1, IGFBP-3, and insulin concentrations at birth: is there a relationship with fetal growth and neonatal anthropometry?. Clin Chem 2008; 54 (03) 550-558
• 48 Bennet L, Oliver MH, Gunn AJ, Hennies M, Breier BH. Differential changes in insulin-like growth factors and their binding proteins following asphyxia in the preterm fetal sheep. J Physiol 2001; 531 (Pt 3): 835-841
• 49 Kitamura S, Yokota I, Hosoda H. , et al. Ghrelin concentration in cord and neonatal blood: relation to fetal growth and energy balance. J Clin Endocrinol Metab 2003; 88 (11) 5473-5477
• 50 Soriano-Guillén L, Barrios V, Chowen JA. , et al. Ghrelin levels from fetal life through early adulthood: relationship with endocrine and metabolic and anthropometric measures. J Pediatr 2004; 144 (01) 30-35