Abstract
Previous data suggested that small for gestational age newborns have increased levels of IGF binding protein 1 (IGFBP1) in amniotic fluid (AF) at 15-16 wk of pregnancy. In this study, we developed an RIA for IGFBP1 and measured IGFBP1 concentrations in 209 AF samples with normal fetal karyotype between 14 and 20 wk; we measured IGF-I, IGF-II, and C-peptide in the same samples. Concentrations of these growth-modulating factors were all positively correlated with gestational age at sampling (p < 0.0001). After correcting for gestational age, AF IGFBP1 remained strongly correlated with IGF-I and IGF-II (both p < 0.0001); their concentrations were many times higher in AF than in cord serum during the third trimester. None of the growth-modulating factors in AF correlated with birth weight, after correction for gestational age; birth weight percentile distribution was comparable in two groups of newborns who had AF values of IGF-I, IGF-II, IGFBP1, or C-peptide that were either less than or equal to the 50th percentile or more than the 50th percentile at sampling. However, placenta weight and the placenta weight to birth weight percentage were negatively correlated with AF IGF-I, IGF-II, and IGFBP1; placenta weight to birth weight percentage was lower in pregnancies with IGFBP1 values more than the 50th percentile compared with those less than or equal to the 50th percentile at sampling. In conclusion, AF concentrations of IGFBP1 increase gradually between 14 and 20 wk gestational age and correlate with IGF-I and IGF-II levels; high IGFBP1 levels do not predict small for gestational age newborns, but are associated with lower placenta weight.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
Abbreviations
- AF:
-
amniotic fluid
- AFP:
-
α-fetoprotein
- GA:
-
gestational age
- IGFBP1:
-
IGF binding protein 1
- IUGR:
-
intrauterine growth retardation
- SGA:
-
small for gestational age
References
Rastogi GK, Letarte J, Fraser TR 1970 Immunoreactive insulin content of 203 pancreases from foetuses of healthy mothers. Diabetologia 6: 445–446
Verhaeghe J, Loos R, Vlietinck R, Van Herck E, van Bree R, De Schutter A-M 1996 C-peptide, insulin-like growth factors I and II, and insulin-like growth factor binding protein-1 in cord serum of twins: genetic versus environmental regulation. Am J Obstet Gynecol 175: 1180–1188
Verhaeghe J, Van Bree R, Van Herck E, Laureys J, Bouillon R, Van Assche FA 1993 C-peptide, insulin-like growth factors I and II, and insulin-like growth factor binding protein-1 in umbilical cord serum: correlations with birth weight. Am J Obstet Gynecol 169: 89–97
Kruger C, Dorr HG, von Muhlendahl KE, Herkenhoff H 1997 Neonatal diabetes and intra-uterine growth retardation. Eur J Pediatr 156: 1–2
Fowden AL 1993 Insulin deficiency: effects on fetal growth and development. J Paediatr Child Health 29: 6–11
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 Metab 66: 422–429
Birnbacher R, Amann G, Breitschopf H, Lassmann H, Suchanek G, Heinz-Erian H 1998 Cellular localization of insulin-like growth factor II mRNA in the human fetus and the placenta: detection with a digoxigenin-labeled cRNA probe and immunocytochemistry. Pediatr Res 43: 614–620
Liu J-P, Baker J, Perkins AS, Robertson EJ, Efstratiadis A 1993 Mice carrying null mutations of the genes encoding insulin-like growth factor I (Igf-1) and type 1 IGF receptor (Igflr). Cell 75: 59–72
Baker J, Liu J-P, Robertson EJ, Efstratiadis A 1993 Role of insulin-like growth factors in embryonic and postnatal growth. Cell 75: 73–82
Woods KA, Camacho-Hübner C, Savage MO, Clark AJL 1996 Intrauterine growth retardation and postnatal growth failure associated with deletion of the insulin-like growth factor I gene. N Engl J Med 335: 1363–1367
Han VKM, Matsell DG, Delhanty PJD, Hill DJ, Shimasaki S, Nygard K 1996 IGF-binding protein mRNAs in the human fetus: tissue and cellular distribution of developmental expression. Horm Res 45: 160–166
Wang HS, Lim J, English J, Irvine L, Chard T 1991 The concentrations of insulin-like growth factor-I and insulin-like growth factor-binding protein-1 in human umbilical cord serum at delivery: relation to fetal weight. J Endocrinol 129: 459–464
Giudice LC, de Zegher F, Gargosky SE, Dsupin BA, de las Fuentes L, 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
Unterman T, Lascon R, Gotway MB, Oehler D, Gounis A, Simmons RA, Ogata ES 1990 Circulating levels of insulin-like growth factor binding protein-1 (IGFBP-1) and hepatic mRNA are increased in the small for gestational age (SGA) fetal rat. Endocrinology 127: 2035–2037
Rajkumar K, Barron D, Lewitt MS, Murphy LJ 1995 Growth retardation and hyperglycemia in insulin-like growth factor binding protein-1 transgenic mice. Endocrinology 136: 4029–4034
Han VKM, Bassett N, Walton J, Challis JRG 1996 The expression of insulin-like growth factor (IGF) and IGF-binding protein (IGFBP) genes in the human placenta and membranes: evidence for IGF-IGFBP interactions at the fetomaternal interface. J Clin Endocrinol Metab 81: 2680–2693
Thomsen BM, Clausen HV, Larsen LG, Nürnberg L, Ottesen B, Thomsen HK 1997 Patterns in expression of insulin-like growth factor-II and of proliferative activity in the normal human first and third trimester placenta demonstrated by non-isotopic in situ hybridization and immunohistochemical staining for MIB-1. Placenta 18: 145–154
Baxter RC, Martin JL, Wood MH 1987 Two immunoreactive binding proteins for insulin-like growth factors in human amniotic fluid: relationship to fetal maturity. J Clin Endocrinol Metab 65: 423–431
Hakala-Ala-Pietilä TH, Hakala-Ala-Pietila TH, Koistinen RA, Salonen RK, Seppälä MT 1993 Elevated second-trimester amniotic fluid concentration of insulin-like growth factor binding protein-1 in fetal growth retardation. Am J Obstet Gynecol 169: 35–39
Fallucca F, Sciullo E, Napoli A, Cardellini G, Maldonato A 1995 Amniotic fluid insulin and C peptide levels in diabetic and nondiabetic women during early pregnancy. J Clin Endocrinol Metab 80: 137–139
Carpenter MW, Canick JA, Star J, Carr SR, Burke ME, Shahinian K 1996 Fetal hyperinsulinism at 14-20 weeks and subsequent gestational diabetes. Obstet Gynecol 87: 89–93
Devlieger H, Martens G, Bekaert A, Eeckels R, Vlietinck R 2 . Standaarden van geboortegewicht-voor-zwangerschapsduur voor de Vlaamse boreling. In: Bekaert A, Martens G, Devlieger H (eds) Perinatale Activiteiten in Vlaanderen 1996 (Studiecentrum voor Perinatale Epidemiologie), Brussel, pp 94–116
Davey DA, MacGillivray I 1988 The classification and definition of hypertensive disorders of pregnancy. Am J Obstet Gynecol 158: 892–898
Verhaeghe J, Suiker AMH, Visser WJ, Van Herck E, Van Bree R, Bouillon R 1992 The effects of systemic insulin, insulin-like growth factor I and growth hormone on bone growth and turnover in spontaneously diabetic BB rats. J Endocrinol 134: 485–492
Suikkari AM, Koivisto VA, Koistinen R, Seppälä M, Yki-Järvinen H 1989 Dose-response characteristics for suppression of low molecular weight plasma insulin-like growth factor-binding protein by insulin. J Clin Endocrinol Metab 68: 135–140
Chard T, Blum WF, Brunjes J, Campbell DJ, Wathen NC 1994 Levels of insulin-like growth factor-binding protein-2 and insulin-like growth factor-II in maternal serum, amniotic fluid and extraembryonic coelomic fluid at 9-20 wk of pregnancy. J Endocrinol 142: 379–383
Wathen NC, Egembah S, Campbell DJ, Farkas A, Chard T 1993 Levels of insulin-like growth factor-binding protein-I increase rapidly in amniotic fluid from 11 to 16 weeks of pregnancy. J Endocrinol 137:R1–R4
Weiss PAM, Kainer F, Haeusler M, Pürstner P, Haas J 1998 Amniotic fluid insulin levels in nondiabetic women: an update. Arch Gynecol Obstet 262: 81–86
Weiss PAM, Pürstner P, Lichtenegger W, Winter R 1978 Alpha-fetoprotein content of amniotic fluid in normal and abnormal pregnancies. Obstet Gynecol 51: 582–585
Camper SA, Godbout R, Tilghman SM 1989 The developmental regulation of albumin and α-fetoprotein gene expression. Prog Nucleic Acid Res Mol Biol 36: 131–143
Straus DS, Ooi GT, Orlowski CC, Rechler MM 1991 Expression of the genes for insulin-like growth factor-I (IGF-I), IGF-II, and IGF-binding proteins-1 and -2 in fetal rat under conditions of intrauterine growth retardation caused by maternal fasting. Endocrinology 128: 518–525
Martina NA, Kim E, Chitkara U, Wathen NC, Chard T, Giudice LC 1997 Gestational age-dependent expression of insulin-like growth factor-binding protein-1 (IGFBP-1) phosphoisoforms in human extraembryonic cavities, maternal serum, and decidua suggests decidua as the primary source of IGFBP-1 in these fluids during early pregnancy. J Clin Endocrinol Metab 82: 1894–1898
Giudice LC, Martina NA, Crystal RA, Tazuke S, Druzin M 1997 Insulin-like growth factor binding protein-1 at the maternal-fetal interface and insulin-like growth factor-I, insulin-like growth factor-II, and insulin-like growth factor binding protein-1 in the circulation of women with severe preeclampsia. Am J Obstet Gynecol 176: 751–758
de Groot CJM, O'Brien TJ, Taylor RN 1996 Biochemical evidence of impaired trophoblastic invasion of decidual stroma in women destined to have preeclampsia. Am J Obstet Gynecol 175: 24–29
Phipps K, Barker DJP, Hales CN, Fall CHD, Osmond C, Clark PMS 1993 Fetal growth and impaired glucose tolerance in men and women. Diabetologia 36: 225–228
Barker DJP, Osmond C, Simmonds SJ, Wield GA 1993 The relation of small head circumference and thinness at birth to death from cardiovascular disease in adult life. BMJ 306: 422–426
Liu K-S, Wang C-Y, Mills N, Gyves M, Ilan J 1985 Insulin-related genes expressed in human placenta from normal and diabetic pregnancies. Proc Natl Acad Sci USA 82: 3868–3870
de Vries JIP, Visser GHA, Prechtl HFR 1982 The emergence of fetal behaviour. I. Qualitative aspects. Early Hum Dev 7: 301–322
Acknowledgements
The authors thank Prof. W. Heyns for his advice and help with the IGFBP1 purification, Prof. F.A. Van Assche for supervising this project, and Prof. R. Bouillon for supervising the amniotic fluid measurements. We also thank Drs. K. Devriendt and J. Billen for their help with the data collection. The ultrasound nursing staff kindly assisted with the sample collection.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Verhaeghe, J., Coopmans, W., van Herck, E. et al. IGF-I, IGF-II, IGF Binding Protein 1, and C-Peptide in Second Trimester Amniotic Fluid Are Dependent on Gestational Age but Do Not Predict Weight at Birth. Pediatr Res 46, 101–108 (1999). https://doi.org/10.1203/00006450-199907000-00017
Received:
Accepted:
Issue date:
DOI: https://doi.org/10.1203/00006450-199907000-00017
This article is cited by
-
Markers for cardiovascular disease in monozygotic twins discordant for the use of third-generation oral contraceptives
Journal of Human Hypertension (2003)
-
Tolerance of a Sterile Isotonic Electrolyte Solution Containing Select Recombinant Growth Factors in Neonates Recovering From Necrotizing Enterocolitis
Journal of Perinatology (2003)
