The Relationship among Intrauterine Growth, Insulinlike Growth Factor I (IGF-I), IGF-Binding Protein-3, and Bone Mineral Status in Newborn Infants

Mustafa Akcakus; Esad Koklu; Selim Kurtoglu; Mustafa Kula; Selmin Suner Koklu

doi:10.1055/s-2006-954822

American Journal of Perinatology, Inhaltsverzeichnis

Am J Perinatol 2006; 23(8): 473-480
DOI: 10.1055/s-2006-954822

The Relationship among Intrauterine Growth, Insulinlike Growth Factor I (IGF-I), IGF-Binding Protein-3, and Bone Mineral Status in Newborn Infants

Mustafa Akcakus¹ , Esad Koklu¹ , Selim Kurtoglu¹ , Mustafa Kula² , Selmin Suner Koklu¹

¹Department of Pediatrics, Division of Neonatology, Erciyes University, School of Medicine, Kayser, Turkey
²Department of Nuclear Medicine, Erciyes University, School of Medicine, Kayser, Turkey

Abstract

ABSTRACT

Insulinlike growth factors (IGFs) exert profound effects on somatic growth and cellular proliferation of many tissues and play an essential role in bone metabolism. The aim of this study was to investigate how fetal growth and bone mineralization correlate with IGF-I and IGF-binding protein-3 (IGFBP-3) levels of newborn infants and their mothers. In addition, we aimed to determine the predictive value of anthropometric measurements on variability in bone mineral status. Umbilical cord venous blood samples were obtained at delivery from 100 term newborn infants. Forty of the newborn infants had birthweights appropriate for gestational age (AGA), 30 were small for gestational age (SGA), and 30 were large for gestational age (LGA). Data were acquired using whole-body dual-energy X-ray absorptiometry scanner with a pediatric platform. Umbilical cord serum IGF-I concentrations were higher in LGA newborns (p < 0.01), but lower in SGA newborns (p < 0.01) than in AGA newborns. Umbilical cord serum IGFBP-3 concentrations in LGA newborns were significantly greater than in SGA and AGA newborns (p < 0.01 and p < 0.01, respectively). Whole-body bone mineral density (WB BMD) was higher in LGA babies (0.442 ± 0.025 g/cm² [SD]; p < 0.01) but lower in SGA (0.381 ± 0.027 g/cm²; p < 0.0001) than in AGA babies (0.426 ± 0.022 g/cm²). WB BMD and content (WB BMC) were correlated significantly with birthweight, birth height, head circumference, body mass index (BMI) of the infants; ponderal index and triceps skinfold thickness (reflecting fat stores) of the infants; cord serum IGF-I concentration, serum IGF-I concentration of the mothers; and fat mass, proportionate fat mass, weight, and BMI of the mothers. In contrast, WB BMC was also correlated positively with cord serum IGFBP-3 concentration and gestational age, and WB BMD was positively correlated with serum IGFBP-3 levels of the mothers. Umbilical cord serum IGF-I concentration of the infants was correlated significantly with the concentration of the mothers (r = 0.232; p = 0.020). Umbilical cord serum IGF-I and IGFBP-3 concentrations were correlated significantly with the fat mass, gestational age, birthweight, birth height, head circumference, and BMI of the infants. Umbilical cord IGF-I concentration was also correlated with ponderal index and triceps skinfold thickness of the infants, maternal weight, BMI, and proportionate fat mass of the infants. Stepwise multiple regression analyses showed no significant relation between bone indices (WB BMD, WB BMC) and the infant's or mother's variations including serum IGF-I and IGFBP-3 concentrations. Birthweight and gestational age are related to bone indices. However, the present study does not provide support for the hypothesis that serum IGF-I and IGFBP-3 levels of infants and their mothers may play a major role in the regulation of bone metabolism in the developing skeleton.

KEYWORDS

Intrauterine growth - IGF-I - IGFBP-3 - bone mineral status

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REFERENCES

1 Christou H, Connors J M, Ziotopoulou M et al.. Cord blood leptin and insulin-like growth factor levels are independent predictors of fetal growth. J Clin Endocrinol Metab. 2001; 86 935-938
2 Johansson A G, Forslund A, Hambraeus L, Blum W F, Ljunghall S. Growth hormone-dependent insulin-like growth factor binding protein is a major determinant of bone mineral density in healthy men. J Bone Miner Res. 1994; 9 915-921
3 Andress D L, Birnbaum R S. Human osteoblast-derived insulin like growth factor (IGF) binding protein-5 stimulates osteoblast mitogenesis and potentiates IGF action. J Biol Chem. 1992; 267 22467-22472
4 Zhang M, Xuan S, Bouxsein M L et al.. Osteoblast-specific knockout of the insulin-like growth factor (IGF) receptor gene reveals an essential role of IGF signaling in bone matrix mineralization. J Biol Chem. 2002; 277 44005-44012
5 Mohan S, Baylink D J. IGF system components and their role in bone metabolism. In: Rosenfeld RG, Roberts CT Jr The IGF System: Molecular Biology, Physiology, and Clinical Applications. Totowa, NJ; Humana Press 1999: 457-496
6 Hill P A, Tumber A, Meikle M C. Multiple extracellular signals promote osteoblast survival and apoptosis. Endocrinology. 1997; 138 3849-3858
7 Hill P A, Reynolds J J, Meikle M C. Osteoblasts mediate insulin-like growth factor-I and -II stimulation of osteoclast formation and function. Endocrinology. 1995; 136 124-131
8 Lochmuller E M, Muller R, Kuhn V, Lill C A, Eckstein F. Can novel clinical densitometric techniques replace or improve DXA in predicting bone strength in osteoporosis at the hip and other skeletal sites?. J Bone Miner Res. 2003; 18 906-912
9 Venkataraman P S, Ahluwalia B W. Total bone mineral content and body composition by x-ray densitometry in newborns. Pediatrics. 1992; 90 767-770
10 Brunton J A, Weiler H A, Atkinson S A. Improvement in the accuracy of dual energy x-ray absorptiometry for whole body and regional analysis of body composition: validation using piglets and methodologic considerations in infants. Pediatr Res. 1997; 41 590-596
11 Ballard J L, Khoury J C, Wedig K, Wang L, Eilers-Walsman B L, Lipp R. New Ballard Score expanded to include extremely premature infants. J Pediatr. 1991; 119 417-423
12 Lubchenco L O, 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; 37 403-408
13 Koo W W, Walters J, Bush A J. Technical considerations of dual-energy X-ray absorptiometry-based bone mineral measurements for pediatric studies. J Bone Miner Res. 1995; 10 1998-2004
14 Harrast S D, Kalkwarf H J. Effects of gestational age, maternal diabetes, and intrauterine growth retardation on markers of fetal bone turnover in amniotic fluid. Calcif Tissue Int. 1998; 62 205-208
15 Namgung R, Tsang R C. Factors affecting newborn bone mineral content: in utero effects on newborn bone mineralization. Proc Nutr Soc. 2000; 59 55-63
16 Namgung R, Tsang R C, Specker B L, Sierra R I, Ho M L. Reduced serum osteocalcin and 1,25-dihydroxyvitamin D concentrations and low bone mineral content in small for gestational age infants: evidence of decreased bone formation rates. J Pediatr. 1993; 122 269-275
17 Weiler H, Fitzpatrick-Wong S, Veitch R et al.. Vitamin D deficiency and whole-body and femur bone mass relative to weight in healthy newborns. Can Med Assoc J. 2005; 172 757-761
18 Chen J Y, Ling U P, Chiang W L, Liu C B, Chanlai S P. Total body bone mineral content in small-for-gestational-age, appropriate-for-gestational-age, large-for-gestational-age term infants and appropriate-for-gestational-age preterm infants. Zhonghua Yi Xue Za Zhi (Taipei). 1995; 56 109-114
19 Chunga Vega F, Gomez de Tejada M J, Gonzalez Hachero J, Perez Cano R, Coronel Rodriguez C. Low bone mineral density in small for gestational age infants: correlation with cord blood zinc concentrations. Arch Dis Child Fetal Neonatal Ed. 1996; 75 F126-F129
20 Karlberg J. A biological-oriented mathematical model (ICP) for human growth. Acta Paediatr Scand Suppl. 1989; 350 70-94
21 Namgung R, Tsang R. Bone in the pregnant mother and newborn at birth. Clin Chim Acta. 2003; 333 1-11
22 Wan G, Leng J, Yu S. Localization and quantitative analysis of insulin-like growth factor-I in placenta of extreme fetus. Zhonghua Fu Chan Ke Za Zhi. 1998; 33 670-672
23 Yang S W, Yu J S. Relationship of insulin-like growth factor-I, insulin-like growth factor binding protein-3, insulin, growth hormone in cord blood and maternal factors with birth height and birthweight. Pediatr Int. 2000; 42 31-36
24 Ogilvy-Stuart A L, Hands S J, Adcock C J et al.. Insulin, insulin-like growth factor I (IGF-I), IGF-binding protein-1, growth hormone, and feeding in the newborn. J Clin Endocrinol Metab. 1998; 83 3550-3557
25 Pirazzoli P, Cacciari E, De Iasio R et al.. Developmental pattern of fetal growth hormone, insulin-like growth factor I, growth hormone binding protein and insulin-like growth factor binding protein-3. Arch Dis Child Fetal Neonatal Ed. 1997; 77 F100-F104
26 Wang H S, Lim J, English J, Irvine L, Chard T. The concentration 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. 1991; 129 459-464
27 Davidson S, Shtaif B, Gil-Ad I. Insulin, insulin-like growth factors-I and -II and insulin-like growth factor binding protein-3 in newborn serum: association with normal fetal head growth and head circumference. J Pediatr Endocrinol Metab. 2001; 14 151-158
28 Caufriez A, Frankenne F, Hennen G, Copinschi G. Regulation of maternal insulin-like growth factor I by placental growth hormone in pregnancy. Possible action of maternal IGF-I on fetal growth. Horm Res. 1994; 42 62-65
29 Mirlesse V, Frankenne F, Alsat E, Poncelet M, Hennen G, Evain-Brion D. Placental growth hormone levels in normal pregnancy and in pregnancies with intrauterine growth retardation. Pediatr Res. 1993; 34 439-442
30 Gallaher B W, Breier B H, Keven C L, Harding J E, Gluckman P D. Fetal programming of insulin-like growth factor (IGF)-I and IGF-binding protein-3: Evidence for an altered response to undernutrition in late gestation following exposure to periconceptual undernutrition in the sheep. J Endocrinol. 1998; 159 501-508
31 Zhu M, Xia Y, Zhang Z. The relation between human fetal growth and the blood levels of insulin-like growth factor-I. Zhonghua Fu Chan Ke Za Zhi. 1998; 33 667-669
32 Slattery M L, Baumgartner K B, Byers T et al.. Genetic, anthropometric, and lifestyle factors associated with IGF-I and IGFBP-3 levels in Hispanic and non-Hispanic white women. Cancer Causes Control. 2005; 16 1147-1157
33 Rosen C J, Kurland E S, Vereault D et al.. Association between serum insulin growth factor-I (IGF-I) and a simple sequence repeat in IGF-I gene: implications for genetic studies of bone mineral density. J Clin Endocrinol Metab. 1998; 83 2286-2290
34 Javaid M K, Godfrey K M, Taylor P et al.. Umbilical venous IGF-I concentration, neonatal bone mass, and body composition. J Bone Miner Res. 2004; 19 56-63
35 Godfrey K, Walker-Bone K, Robinson S et al.. Neonatal bone mass: Influence of parental birthweight, maternal smoking, body composition, and activity during pregnancy. J Bone Miner Res. 2001; 16 1694-1703
36 Godfrey K M, Breier B H, Cooper C. Constraint of the materno-placental supply of nutrients: causes and consequences. In: O'Brien PM, Wheeler T, Barker DJ Fetal Programming: Influences on Development and Disease in Later Life. London; RCOG Press 1999: 283-298
37 Breier B H, Vickers M H, Ikenasio B A, Chan K Y, Wong W P. Fetal programming of appetite and obesity. Mol Cell Endocrinol. 2001; 185 73-79

Mustafa AkcakusM.D.

Erciyes University, School of Medicine, Department of Pediatrics, Division of Neonatology

38039, Kayser, Turkey