At birth, elevated IGF-I levels have been linked to birth weight extremes; high birth weight and low birth weight are risk factors for adult-onset chronic diseases including obesity, cardiovascular disease, and type 2 diabetes. We examined associations between plasma IGF-I levels and birth weight among infants born to African American and White obese and nonobese women. Prepregnancy weight and height were assessed among 251 pregnant women and anthropometric measurements of full term infants (≥37 weeks of gestation) were taken at birth. Circulating IGF-I was measured by ELISA in umbilical cord blood plasma. Linear regression models were utilized to examine associations between birth weight and high IGF-I, using the bottom two tertiles as referents. Compared with infants with lower IGF-I levels (≤3rd tertile), those with higher IGF-I levels (>3rd tertile) were 130？g heavier at birth, ( , , ), after adjusting for gender, race/ethnicity, gestational age, delivery route, maternal BMI and smoking. Stratified analyses suggested that these associations are more pronounced in infants born to African American women and women with BMI ≥30？kg/m2; the cross product term for IGF-I and maternal BMI was statistically significant ( ). Our findings suggest that the association between IGF-I levels and birth weight depends more on maternal obesity than African American race/ethnicity. 1. Introduction Low birth weight (LBW) and high birth weight (HBW) are both important indicators of suboptimal intrauterine development and have been linked to risk of several chronic diseases later in life. HBW has been associated with childhood and adult obesity [1] and some cancers, including breast [2] and prostate cancer [3], whereas LBW is a consistently identified risk factor for cardiovascular disease (CVD) [4, 5] and type 2 diabetes (T2D) [6, 7]. IGF-I is a mitogenic and antiapoptotic paracrine growth factor expressed in all fetal organs [8, 9], and is essential in fetal and neonatal growth, differentiation and development [10–14]. Several lines of evidence suggest that IGF-I levels are associated with birth weight [15–26]; furthermore higher IGF-I levels are associated with higher BW, but not with lower birth weight [16, 17, 26]. In adulthood, elevated concentrations of IGF-I are associated with an increased risk of obesity and many cancers, including breast, lung, head and neck, colorectal, pancreas, synovial sarcoma, and prostate cancer [26–31]. Although concentrations of circulating IGF-I levels vary considerably by race/ethnicity and maternal prepregnancy obesity, few studies
References
[1]
Z. B. Yu, S. P. Han, G. Z. Zhu et al., “Birth weight and subsequent risk of obesity: a systematic review and meta-analysis,” Obesity Reviews, vol. 12, no. 7, pp. 525–542, 2011.
[2]
A. H. Wu, R. McKean-Cowdin, and C. C. Tseng, “Birth weight and other factors and risk of breast cancer in Asian-Americans,” Breast Cancer Research and Treatment, vol. 130, pp. 917–925, 2011.
[3]
T. I. L. Nilsen, P. R. Romundstad, R. Troisi, and L. J. Vatten, “Birth size and subsequent risk for prostate cancer: a prospective population-based study in Norway,” International Journal of Cancer, vol. 113, no. 6, pp. 1002–1004, 2005.
[4]
A. J. Drake and B. R. Walker, “The intergenerational effects of fetal programming: non-genomic mechanisms for the inheritance of low birth weight and cardiovascular risk,” Journal of Endocrinology, vol. 180, no. 1, pp. 1–16, 2004.
[5]
D. J. P. Barker, C. Osmond, J. Golding, D. Kuh, and M. E. J. Wadsworth, “Growth in utero, blood pressure in childhood and adult life, and mortality from cardiovascular disease,” British Medical Journal, vol. 298, no. 6673, pp. 564–567, 1989.
[6]
C. N. Hales and D. J. P. Barker, “Type 2 (non-insulin-dependent) diabetes mellitus: the thrifty phenotype hypothesis,” Diabetologia, vol. 35, no. 7, pp. 595–601, 1992.
[7]
P. H. Whincup, S. J. Kaye, C. G. Owen et al., “Birth weight and risk of type 2 diabetes a systematic review,” Journal of the American Medical Association, vol. 300, no. 24, pp. 2886–2897, 2008.
[8]
G. J. Allan, D. J. Flint, and K. Patel, “Insulin-like growth factor axis during embryonic development,” Reproduction, vol. 122, no. 1, pp. 31–39, 2001.
[9]
M. E. Fant and D. Weisoly, “Insulin and insulin-like growth factors in human development: implications for the perinatal period,” Seminars in Perinatology, vol. 25, no. 6, pp. 426–435, 2001.
[10]
J. Baker, J. P. Liu, E. J. Robertson, and A. Efstratiadis, “Role of insulin-like growth factors in embryonic and postnatal growth,” Cell, vol. 75, no. 1, pp. 73–82, 1993.
[11]
R. Baserga, F. Peruzzi, and K. Reiss, “The IGF-1 receptor in cancer biology,” International Journal of Cancer, vol. 107, no. 6, pp. 873–877, 2003.
[12]
L. C. Giudice, “Maternal-fetal conflict—lessons from a transgene,” Journal of Clinical Investigation, vol. 110, no. 3, pp. 307–309, 2002.
[13]
J. Nakae, Y. Kido, and D. Accili, “Distinct and overlapping functions of insulin and IGF-I receptors,” Endocrine Reviews, vol. 22, no. 6, pp. 818–835, 2001.
[14]
M. N. Pollak, E. S. Schernhammer, and S. E. Hankinson, “Insulin-like growth factors and neoplasia,” Nature Reviews Cancer, vol. 4, no. 7, pp. 505–518, 2004.
[15]
K. Langford, W. Blum, K. Nicolaides, J. Jones, A. McGregor, and J. Miell, “The pathophysiology of the insulin-like growth factor axis in fetal growth failure: a basis for programming by undernutrition?” European Journal of Clinical Investigation, vol. 24, no. 12, pp. 851–856, 1994.
[16]
C. Lassarre, S. Hardouin, F. Daffos, F. Forestier, F. Frankenne, and M. Binoux, “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,” Pediatric Research, vol. 29, no. 3, pp. 219–225, 1991.
[17]
I. K. Ashton, J. Zapf, I. Einschenk, and I. Z. MacKenzie, “Insulin-like growth factors (IGF) 1 and 2 in human foetal plasma and relationship to gestational age and foetal size during midpregnancy,” Acta Endocrinologica, vol. 110, no. 4, pp. 558–563, 1985.
[18]
K. Ong, J. Kratzsch, W. Kiess, M. Costello, C. Scott, and D. Dunger, “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,” Journal of Clinical Endocrinology and Metabolism, vol. 85, no. 11, pp. 4266–4269, 2000.
[19]
G. á. Martos-Moreno, V. Barrios, M. S. De Pipaón et al., “Influence of prematurity and growth restriction on the adipokine profile, IGF1, and ghrelin levels in cord blood: relationship with glucose metabolism,” European Journal of Endocrinology, vol. 161, no. 3, pp. 381–389, 2009.
[20]
P. Zhao, X. L. Zhang, C. Yu, X. Y. Lu, and Y. M. Wang, “Umbilical cord serum levels of insulin-like growth factor-1, insulin and growth hormone in neonates with intrauterine growth retardation,” Zhongguo Dang Dai Er Ke Za Zhi, vol. 12, no. 10, pp. 771–773, 2010.
[21]
M. P. P. Geary, P. J. Pringle, C. H. Rodeck, J. C. P. Kingdom, and P. C. Hindmarsh, “Sexual dimorphism in the growth hormone and insulin-like growth factor axis at birth,” Journal of Clinical Endocrinology and Metabolism, vol. 88, no. 8, pp. 3708–3714, 2003.
[22]
P. D. Gluckman, J. J. J. Barrett, and J. H. Butler, “Studies of insulin-like growth factor -I and -II by specific radioligand assays in umbilical cord blood,” Clinical Endocrinology, vol. 19, no. 3, pp. 405–413, 1983.
[23]
L. J. Vatten, S. T. Nilsen, R. A. ？deg？rd, P. R. Romundstad, and R. Austgulen, “Insulin-like growth factor I and leptin in umbilical cord plasma and infant birth size at term,” Pediatrics, vol. 109, no. 6, pp. 1131–1135, 2002.
[24]
M. S. Boyne, M. Thame, F. I. Bennett, C. Osmond, J. P. Miell, and T. E. Forrester, “The relationship among circulating insulin-like growth factor (IGF)-I, IGF-binding proteins-1 and -2, and birth anthropometry: a prospective study,” Journal of Clinical Endocrinology and Metabolism, vol. 88, no. 4, pp. 1687–1691, 2003.
[25]
S. Rohrmann, C. G. Sutcliffe, J. L. Bienstock et al., “Racial variation in sex steroid hormones and the insulin-like growth factor axis in umbilical cord blood of male neonates,” Cancer Epidemiology Biomarkers and Prevention, vol. 18, no. 5, pp. 1484–1491, 2009.
[26]
T. Agurs-Collins, S. Rohrmann, C. Sutcliffe et al., “Racial variation in umbilical cord blood sex steroid hormones and the insulin-like growth factor axis in African-American and white female neonates,” Cancer Causes Control, vol. 23, pp. 445–454, 2012.
[27]
M. H. Wu, Y. C. Chou, W. Y. Chou et al., “Relationships between critical period of estrogen exposure and circulating levels of insulin-like growth factor-I (IGF-I) in breast cancer: evidence from a case-control study,” International Journal of Cancer, vol. 126, no. 2, pp. 508–514, 2010.
[28]
M. M. Rajski, R. Zanetti-D？llenbach, B. Vogel, R. Herrmann, C. Rochlitz, and M. Buess, “IGF-I induced genes in stromal fibroblasts predict the clinical outcome of breast and lung cancer patients,” BMC Medicine, vol. 8, article 1, 2010.
[29]
J. B. Douglas, D. T. Silverman, M. N. Pollak, Y. Tao, A. S. Soliman, and R. Z. Stolzenberg-Solomon, “Serum IGF-I, IGF-II, IGFBP-3, and IGF-I/IGFBP-3 molar ratio and risk of pancreatic cancer in the prostate, lung, colorectal, and ovarian cancer screening trial,” Cancer Epidemiology Biomarkers and Prevention, vol. 19, no. 9, pp. 2298–2306, 2010.
[30]
P. Stattin, A. Bylund, S. Rinaldi et al., “Plasma insulin-like growth factor-I, insulin-like growth factor-binding proteins, and prostate cancer risk: a prospective study,” Journal of the National Cancer Institute, vol. 92, no. 23, pp. 1910–1917, 2000.
[31]
J. M. Chan, M. J. Stampfer, E. Giovannucci et al., “Plasma insulin-like growth factor-I and prostate cancer risk: a prospective study,” Science, vol. 279, no. 5350, pp. 563–566, 1998.
[32]
M. D. Holmes, M. J. Stampfer, A. M. Wolf et al., “Can behavioral risk factors explain the difference in body mass index between African-American and European-American women?” Ethnicity and Disease, vol. 8, no. 3, pp. 331–339, 1998.
[33]
H. Olausson, M. L？f, K. Brismar, E. Forsum, and A. Sohlstr？m, “Maternal serum concentrations of insulin-like growth factor (IGF)-I and IGF binding protein-1 before and during pregnancy in relation to maternal body weight and composition and infant birth weight,” British Journal of Nutrition, vol. 104, no. 6, pp. 842–848, 2010.
[34]
K. D. Henderson, M. I. Goran, L. N. Kolonel, B. E. Henderson, and L. Le Marchand, “Ethnic disparity in the relationship between obesity and plasma insulin-like growth factors: the multiethnic cohort,” Cancer Epidemiology Biomarkers and Prevention, vol. 15, no. 11, pp. 2298–2302, 2006.
[35]
S. M. Nelson, P. Matthews, and L. Poston, “Maternal metabolism and obesity: modifiable determinants of pregnancy outcome,” Human Reproduction Update, vol. 16, no. 3, Article ID dmp050, pp. 255–275, 2009.
[36]
C. Hoyo, A. P. Murtha, J. M. Schildkraut et al., “Methylation variation at IGF2 differentially methylated regions and maternal folic acid use before and during pregnancy,” Epigenetics, vol. 6, pp. 928–936, 2011.
[37]
E. Perkins, S. K. Murphy, A. P. Murtha et al., “Insulin-like growth factor 2/H19 methylation at birth and risk of overweight and obesity in children,” Journal of Pediatrics, vol. 161, pp. 31–39, 2012.
[38]
K. Ong, J. Kratzsch, W. Kiess, and D. Dunger, “Circulating IGF-I levels in childhood are related to both current body composition and early postnatal growth rate,” Journal of Clinical Endocrinology and Metabolism, vol. 87, no. 3, pp. 1041–1044, 2002.
[39]
C. H. D. Fall, A. N. Pandit, C. M. Law et al., “Size at birth and plasma insulin-like growth factor-1 concentrations,” Archives of Disease in Childhood, vol. 73, no. 4, pp. 287–293, 1995.
[40]
S. K. Akram, C. Carlsson-Skwirut, Z. A. Bhutta, and O. Soder, “Placental IGF-I, IGFBP-1, zinc, and iron, and maternal and infant anthropometry at birth,” Acta Paediatrica, vol. 100, pp. 1504–1509, 2011.
[41]
V. L. Clifton, N. A. Hodyl, V. E. Murphy, W. B. Giles, R. C. Baxter, and R. Smith, “Effect of maternal asthma, inhaled glucocorticoids and cigarette use during pregnancy on the newborn insulin-like growth factor axis,” Growth Hormone and IGF Research, vol. 20, no. 1, pp. 39–48, 2010.
[42]
P. Zhao, X. L. Zhang, C. Yu, X. Y. Lu, and Y. M. Wang, “Umbilical cord serum levels of insulin-like growth factor-1, insulin and growth hormone in neonates with intrauterine growth retardation,” Zhongguo Dang Dai Er Ke Za Zhi, vol. 12, no. 10, pp. 771–773, 2010.
[43]
N. Ohkawa, H. Shoji, T. Kitamura et al., “IGF-I, leptin and active ghrelin levels in very low birth weight infants during the first 8 weeks of life,” Acta Paediatrica, vol. 99, no. 1, pp. 37–41, 2010.
[44]
C. Chiesa, J. F. Osborn, C. Haass et al., “Ghrelin, leptin, IGF-1, IGFBP-3, and insulin concentrations at birth: is there a relationship with fetal growth and neonatal anthropometry?” Clinical Chemistry, vol. 54, no. 3, pp. 550–558, 2008.
[45]
H. S. Wang, J. Lim, J. English, L. Irvine, and T. Chard, “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,” Journal of Endocrinology, vol. 129, no. 3, pp. 459–464, 1991.
[46]
M. Deiber, P. Chatelain, D. Naville, G. Putet, and B. Salle, “Functional hypersomatotropism in small for gestational age (SGA) newborn infants,” Journal of Clinical Endocrinology and Metabolism, vol. 68, no. 1, pp. 232–233, 1989.
[47]
W. Ricart, J. Lopez, J. Mozas et al., “Maternal glucose tolerance status influences the risk of macrosomia in male but not in female fetuses,” Journal of Epidemiology & Community Health, vol. 63, pp. 64–68, 2009.
[48]
D. Simmons, “Interrelation between umbilical cord serum sex hormones, sex hormone- binding globulin, insulin-like growth factor I, and insulin in neonates from normal pregnancies and pregnancies complicated by diabetes,” Journal of Clinical Endocrinology and Metabolism, vol. 80, no. 7, pp. 2217–2221, 1995.
[49]
F. A. Hills, J. English, and T. Chard, “Circulating levels of IGF-I and IGF-binding protein-1 throughout pregnancy: relation to birthweight and maternal weight,” Journal of Endocrinology, vol. 148, no. 2, pp. 303–309, 1996.
[50]
P. M. Catalano, J. P. Kirwan, S. Haugel-De Mouzon, and J. King, “Gestational diabetes and insulin resistance: role in short- and long-term implications for mother and fetus,” Journal of Nutrition, vol. 133, no. 5, pp. 1674S–1683S, 2003.
[51]
B. Hoegsberg, P. A. Gruppuso, and D. R. Coustan, “Hyperinsulinemia in macrosomic infants of nondiabetic mothers,” Diabetes Care, vol. 16, no. 1, pp. 32–36, 1993.
[52]
W. Y. Sei and S. Y. Jee, “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,” Pediatrics International, vol. 42, no. 1, pp. 31–36, 2000.
