Abstract
The aim of this study was to relate human fetal growth retardation to specific hormone alterations. Serum levels of GH, IGF-I, IGF-II, and IGF binding protein (BP) 3 were measured during the second half of gestation after cordocentesis in 230 fetuses who were classified into normally grown(n = 166) and growth-retarded (n = 64) groups according to ante- and neonatal measurements. The normally grown group showed a progressive decline in serum GH levels toward term (r = -0.42, p = 0.0001), whereas serum IGF-I was increased (r = 0.55, p = 0.0001), as were serum IGF-II (r = 0.21, p = 0.008) and IGFBP3 levels (r = 0.19, p = 0.02), although less markedly. For all hormone levels, wide individual differences were found at any given age of gestation. The incidental presence of fetal malformations in either the normally grown group (n = 107 cases) or the growth-retarded group (n = 50 cases) had no apparent effect on these hormone levels as compared with members of the groups showing no fetal malformations (n = 73 cases). Comparison of the normally grown group with the growth-retarded group showed that serum IGF-I levels were significantly lower in the growth-retarded group (p = 0.001). No differences were found between the groups in serum GH, IGF-II, and IGFBP3 levels, although if data for the third trimester were taken alone, serum IGF-II levels were found to be lower in the growth-retarded group (p= 0.05). In conclusion, during the second half of gestation, fetal serum IGF-I levels may be influenced by nutritional factors controlling fetal growth. However, the wide individual differences in measurements make it a very poor biologic marker of intrauterine growth retardation.
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Abbreviations
- IGFBP3:
-
IGF binding protein 3
- IUGR:
-
intrauterine growth retardation
- CV:
-
coefficient of variance
References
Gluckman PD, Brinsmead MW 1976 Somatomedin in cord blood: relationship to gestational age and birth. J Clin Endocrinol Metab 43: 1378–1381
Bennett A, Wilson DM, Liu F, Nagashima R, Rosenfeld RG, Hintz RL 1983 Levels of insulin-like growth factors I and II in human cord blood. J Clin Endocrinol Metab 57: 609–612
Ashton IK, Zapf J, Einschenk I, Mackenzie IZ 1985 Insulin-like growth factors (IGF) 1 and 2 in human foetal plasma and relationship to gestational age and foetal size during midpregnancy. Acta Endocrinol 110: 558–563
D'Ercole AJ, Hill DJ, Strain AJ, Underwood LE 1986 Tissue and plasma somatomedin C/insulin-like growth factor I concentrations in the human fetus during the first half of gestation. Pediatr Res 20: 253–255
Thieriot-Prevost G, Daffos F, Forestier F, Job JC 1986 Serum somatomedin C, bioassayable growth-promoting activity (thymidine activity) and transferrin in human fetuses: in utero study. Pediatr Res 20: 71–73
Lassarre C, Hardouin S, Daffos F, Forestier F, Frankenne F, Binoux M 1991 Serum insulin-like growth factor binding proteins in the human fetus. Pediatr Res 29: 219–225
Bang P, Westgren M, Schwander J, Blum WF, Rosenfeld RG, Stangenberg M 1994 Ontogeny of Insulin-like growth factor-binding protein-1, 2, and 3: quantitative measurements by radioimmunoassay in human fetal serum. Pediatr Res 36: 528–536
Liu JP, Baker J, Perkins AS, Robertson EK, Efstratiadis A 1993 Mice carrying null mutations of the genes encoding insulin-like growth factor I (IGF-I) and type 1 IGF receptor (IGF-lr). Cell 75: 59–72
Baker J, Liu JP, Robertson EJ, Efstratiadis A 1993 Role of insulin like growth factors in embryonic and postnatal growth. Cell 75: 73–82
Taboury J, Vuillard E 1991 Guide pratique d'échographie gynécologique et obstétricale. Ed Masson, Paris
Leroy B, Lefort F 1971 A propos du poids et de la taille des nouveaux-nés à la naissance. Rev Fr Gynecol 66: 391–396
Nicolaides KH, Soothill PW, Rodeck CH, Campbell S 1986 Ultrasound guided sampling of the umbilical cord and placental blood to assess fetal wellbeing. Lancet 1065: 7
Binoux M, Seurin D, Lassare C, Gourmelen M 1984 Preferential measurements of insulin-like growth factor (IGF-I) related peptides in serum with the aid of IGF binding proteins (IGFBP3) produced by rat liver in culture: estimation of serum IGFBP levels. J Clin Endocrinol Metab 59: 453–462
Binoux M, Lassare C, Gourmelen M 1986 Specific assay for insulin-like growth factor (IGF) 2 using the IGF binding proteins extracted from human cerebrospinal fluid. J Clin Endocrinol Metab 63: 1151–1155
Blum WF, Ranke MB, Kietzmann K, Gaugel HJ, Zeisel HJ, Bierich JR 1990 A specific radioimmunoassay for the growth hormone(GH)-dependent somatomedin-binding protein: its use for dignosis of GH deficiency. J Clin Endocrinol Metab 70: 1292–1298
Khoury MJ, Erckson JD, Cordero JF, Mc Carthy BJ 1988 Congenital malformations and intrauterine growth retardation: a population study. Pediatrics 82: 83–90
Salardi S, Orsini LF, Lacciari E, Righetti F, Donati S, Mandini M, Cilognani A, Bovicelli L 1991 Growth hormone, insulin-like growth factor I, insulin and C-peptide during human fetal life: in utero study. Clin Endocrinol 34: 187–190
Kaplan SL, Grumbach MM, Shepard TH 1972 The ontogenesis of human fetal hormones GH and insulin. J Clin Invest 51: 3080–3093
Silverman BL, Bettendorf M, Kaplan SL, Grumbach MM, Miller WL 1989 Regulation of growth hormone (GH) secretion by GH. Endocrinology 124: 84–89
De Zegher F, Bettendorf M, Kaplan SL, Grumbach MM 1988 Hormone ontogeny in the ovine fetus. XXI. The effect of insulin-like growth factor I on plasma fetal growth hormone, insulin and glucose concentrations. Endocrinology 123: 658–660
Blanchard MM, Goodyer CG, Charrier J, Barenton B 1988 In vitro regulation of growth hormone release from ovine pituitary cells during fetal and neonatal development: effects of GH-releasing factor, somatostatin and insulin-like growth factor I. Endocrinology 122: 2114–2120
Kim JD, Nanto-Salonen K, Szepankiewicz JR, Rosenfeld RG, Glasscock GF 1993 Evidence for pituitary regulation of somatic growth, insulin-like growth factors 1 and 2 and their binding proteins in the fetal rats. Pediatr Res 33: 144–151
Han VKM, Lund PK, Lee DC, D'Ercole AJ 1988 Expression of somatomedin/insulin-like growth factor messenger ribonucleic acids in the human fetus, identification, characterization and tissue distribution. J Clin Endocrinol Met 66: 422–429
Kao PC, Matheny AP, Lang CA 1994 Insulin-like growth factor I comparisons in healthy twin children. J Clin Endocrinol Metab 78: 310–312
Schuller AGP, Zwarhoff EC, Drop SLS 1993 Gene expression of the six insulin-like growth factor binding proteins in the mouse conceptus during mid and late gestation. Endocrinology 132: 2544–2550
Donovan SM, Oh Y, Pham H, Rosenfeld RG 1989 Ontogeny of serum IGF binding proteins in the rat. Endocrinology 125: 2621–2627
Leger J, Noel M, Limal JM, Czernichow P, on behalf of the Study Group of IUGR; 1995 Growth factors and intrauterine growth retardation. II. Serum growth hormone, insulin-like growth factor (IGF) I, and IGF-binding protein 3 levels in children with intrauterine growth retardation as compared with normal controls: prospective study from birth to two years of age. Pediatr Res 40: 101–107
Crystal RA, Giudice LC 1991 Insulin-like growth factor binding protein (IGFBP) profiles in human fetal cord sera: ontogeny during gestation and differences in newborns with intra-uterine growth retardation(IUGR) and large for gestation age (LGA) newborns. In Spencer EM (ed) Modern Concepts of Insulin-like Growth Factors. Elsevier, New York, pp 395–408
Foley TP, De Philip R, Pericelli A, Miller A 1980 Low somatomedin activity in cord serum from infants with intrauterine growth retardation. J Pediatr 96: 605–610
Theriot-Prevost G, Daffos F, Forestier F 1985 Serum somatomedin C, bioassayable growth-promoting activity (thymidine activity) in appropriate and small-forgestational-age human newborns. Acta Endocrinol 110: 32–35
Verhaeghe J, Van Bree R, Van Herck E, Laureys J, Bouillon R, Van Assch FA 1993 C-peptide, insulin-like growth factors I and II, and insulin-like growth factor binding protein I in umbilical cord serum: correlations with birth weight. Am J Obstet Gynecol 169: 89–97
Varvarigou A, Vagenakis AG, Makri M, Beratis NG 1994 Growth hormone, insulin-like growth factor 1 and prolactin in small for gestational age neonates. Biol Neonate 65: 94–102
Giudice LC, De Zegher F, Gargosky SE, Dsupin BA, Fuentes DL, Crystal RA, Hintz RL, Rosenfeld RG 1995 Insulin-like growth factors and their binding proteins in the term and preterm human fetus and neonate with normal and extremes of intrauterine growth. J Clin Endocrinol Metab 80: 1548–1555
De Prins FA, Hill DJ, Fekete M, Robsen DJ, Fieller NRJ, Van Assche FA, Milner RDG 1984 Reduced plasma somatomedin activity and costal cartilage sulfate incorporation activity during experimental growth retardation in the fetal rat. Pediatr Res 18: 1100–1104
Vileisis RA, D'Ercole AJ 1986 Tissue and serum concentrations of somatomedin C/insulin-like growth factor I in fetal rats made growth retarded by uterine artery ligation. Pediatr Res 20: 126–130
Unterman TG, Simmons RA, Glick RP, Ogata E 1993 Circulating levels of insulin, insulin-like growth factors (IGF-I), IGF-II and IGF-binding proteins in the small for gestational age fetal rat. Endocrinology 132: 327–336
Jones CT, Gu W, Harding JE, Prile DA, Parer JT 1988 Studies on the growth of fetal sheep. Effects of surgical reduction in placental size or experimental manipulation of uterine blood flow on plasma sulphation promoting activity and on the concentration of insulin-like growth factors I and II. J Dev Physiol 10: 179
Owens JA, Kind KL, Carbone F, Robinson JS, Owens PC 1994 Circulating insulin-like growth factors-I and II and substrates in fetal sheep following restriction of placental growth. J Endocrinol 140: 5–13
Davenport ML, D'Ercole AJ, Underwood LE 1990 Effect of maternal fasting on fetal growth, serum insulin-like growth factors (IGFs) and tissue IGF messenger ribonucleic acids. Endocrinology 126: 2062–2067
Bernstein IM, De Souza MM, Copeland KC 1991 Insulin-like growth factor I in substrate deprivated growth retarded fetal rats. Pediatr Res 30: 154–157
Wolstenholme J, Rooney DE, Davison EV 1994 Confined placental mosaicism, IUGR, and adverse pregnancy outcome: a controlled retrospective U.K. collaborative survey. Prenat Diagn 14: 345–361
Strauss DS, Ooi GT, Orlowski CC, Rechler MM 1991 Expression of the genes for insulin-like growth factor I (IGFI), IGFII and IGF binding protein 1 and 2 in fetal rat under conditions of intrauterine growth retardation caused by maternal fasting. Endocrinology 128: 518–525
Deiber M, Chatelain P, Naville D, Putet G, Salle B 1989 Functional hypersomatotropism in small for gestational age (SGA) newborn infants. J Clin Endocrinol Metab 68: 232–234
De Zegher F, Kimpen J, Raus J, Vanderschueren-Lodeweyckx M 1990 Hypersomatropism in the dysmature infant at term and preterm birth. Biol Neonate 58: 188–191
Gluckman PD, Breier BH, Oliver M, Harding J, Basset N 1990 Fetal growth in late gestation. A constrained pattern of growth. Acta Paediatr Scand Suppl 367: 105–110
Bassett NS, Oliver MH, Breier BH, Gluckman PD 1990 The effect of maternal starvation on plasma insulin-like growth factor I concentration in the late gestation ovine fetus. Pediatr Res 27: 401–404
Gluckman PD, Butler JH, Comline R, Fowden A 1987 The effects of pancreatectomy on the plasma concentration of insulin-like growth factor I and II in the sheep fetus. J Dev Physiol 9: 79–88
Owens JA . 1991 Endocrine and substrate control of fetal growth: placental and maternal influences and insulin-like growth factors. Reprod Fertil Dev 3: 501–517
Hill DJ, Freemark M, Strain AJ, Handwerger S, Milner RDG 1988 Placental lactogen and growth hormone receptors in human fetal tissue: relationship to fetal plasma human placental lactogen concentration and fetal growth. J Clin Endocrinol Metab 66: 1283–1290
Gluckman PD, Butler JH, Elliot T 1983 The ontogeny of somatotrophic binding sites in ovine hepatic membranes. Endocrinology 112: 1607–1612
Garcia aragon J, Lobie PE, Muscat GEO, Gobius KS, Norstedt G, Waters MJ 1992 Prenatal expression of the growth hormone (GH) receptor/binding protein in the rat: a role for GH in embryonic and fetal development. Development 114: 869–876
Daughaday WH, Trivedi B, Andrews BA 1987 The ontogeny of serum GH binding protein in man: a possible indicator of hepatic GH receptor development. J Clin Endocrinol Metab 65: 1072–1074
Massa G, De Zegher F, Vandershuren-Lodeweyckx M 1992 Serum growth hormone-binding proteins in the human fetus and infant. Pediatr Res 32: 69–72
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Supported by Grant 92CN41 from the Institut National de la Santé et de la Recherche Medicale.
Presented in part at the Fourth Joint Meeting of the Lawson Wilkins Pediatric Endocrine Society and the European Society for Paediatric Endocrinology, San Francisco, CA 1993 (Pediatr Res 1993;33(suppl):403(abstr).
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Leger, J., Oury, J., Noel, M. et al. Growth Factors and Intrauterine Growth Retardation. I. Serum Growth Hormone, Insulin-Like Growth Factor (IGF)-I, IGF-II, and IGF Binding Protein 3 Levels in Normally Grown and Gestation. Pediatr Res 40, 94–100 (1996). https://doi.org/10.1203/00006450-199607000-00017
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DOI: https://doi.org/10.1203/00006450-199607000-00017
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