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Factors affecting newborn bone mineral content: in utero effects on newborn bone mineralization

Published online by Cambridge University Press:  28 February 2007

Ran Namgung
Affiliation:
Yonsei University College of Medicine, Department of Pediatrics, 134 Shinochon-Dong, Sudaemoon-Ku, Seoul 120-752, Korea
Reginald C. Tsang*
Affiliation:
University of Cincinnati Children's Hospital Medical Centre, Division of Neonatology, 231 Bethesda Avenue, Cincinnati, OH 45267-0541, USA
*
*Corresponding author: Professor R. C. Tsang, fax +1 513 558 7770, email [email protected]
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Abstract

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Several factors have been found recently to have a significant impact on newborn bone mineral content (BMC) and developing fetal bone. Recently we showed that maternal vitamin D deficiency may affect fetal bone mineralization. Korean winter-born newborn infants had extremely low serum 25-hydroxyvitamin D (25-OHD), high serum cross-linked carboxy-terminal telopeptide of type I collagen (ICTP; a bone resorption marker), and markedly lower (8 %) total body BMC than summer-born newborn infants. Infant total body BMC was positively correlated with cord serum 25-OHD and inversely correlated with ICTP, which was also negatively correlated with vitamin D status. In three separate studies on North American neonates we found markedly lower (8–12 %) BMC in summer newborn infants compared with winter newborn infants, the opposite of the findings for Korean neonates. The major reason for the conflicting BMC results might be the markedly different maternal vitamin D status of the North American and Korean subjects. Recently, we found evidence of decreased bone formation rates in infants who were small-for-gestational age (SGA) compared with infants who were appropriate-for-gestational age; we reported reduced BMC, cord serum osteocalcin (a marker of bone formation) and 1,25-dihydroxyvitamin D (the active metabolite of vitamin D), but no alterations in indices of fetal bone collagen metabolism. In theory, reduced utero-placental blood flow in SGA infants may result in reduced transplacental mineral supply and reduced fetal bone formation. Infants of diabetic mothers (IDM) have low BMC at birth, and infant BMC correlated inversely with poor control of diabetes in the mother, specifically first trimester maternal mean capillary blood glucose concentration, implying that factors early in pregnancy might have an effect on fetal BMC. The low BMC in IDM may be related to the decreased transplacental mineral transfer. Cord serum ICTP concentrations were higher in IDM than in control subjects, implying increased intrauterine bone resorption. BMC is consistently increased with increasing body weight and length in infants. Race and gender differences in BMC appear in early life, but not at birth. Ethanol consumption and smoking by the mother during pregnancy affect fetal skeletal development.

Type
Plenary Lecture
Copyright
Copyright © The Nutrition Society 2000

References

Abrams, SA, O'Brien, KO, Liang, LK & Stuff, JE (1995) Differences in calcium absorption and kinetics between black and white girls. Journal of Bone Mineral Research 10, 829833.CrossRefGoogle ScholarPubMed
Aitken, JM, Anderson, JB & Horton, PW (1973) Seasonal variations in bone mineral content after menopause. Nature 241, 5960.CrossRefGoogle Scholar
Bergstralh, EJ, Sinaki, M, Offord, KP, Wahner, HW & Melton, LJ (1990) Effect of season on physical activity score, back extensor muscle strength, and lumbar bone mineral density. Journal of Bone Mineral Research 5, 371377.CrossRefGoogle ScholarPubMed
Bernstein, IM, DeSouza, M & Copeland, KC (1991) Insulin-like growth factor I in substrate-deprived, growth-retarded fetal rats. Pediatric Research 30, 154157.CrossRefGoogle ScholarPubMed
Bouillon, RA, Auwerx, JD, Lissens, WD & Pelemans, WK (1987) Vitamin D status in the elderly: seasonal substrate deficiency causes 1,25-dihydroxycholecalciferol deficiency. American Journal of Clinical Nutrition 45, 755763.CrossRefGoogle ScholarPubMed
Brooke, OG, Brown, IRF, Bone, CDM, Carter, ND, Cleeve, HJW, Maxwell, JD, Robinson, VP & Winder, SM (1980) Vitamin D supplements in pregnant Asian women: effects on calcium status and fetal growth. British Medical Journal 280, 751754.CrossRefGoogle ScholarPubMed
Burgeson, RE (1988) New collagen, new concepts. Annual Review of Cell Biology 4, 551557.CrossRefGoogle ScholarPubMed
Chunga Vega, F, Gomez de Tejada, MJ, Gonzalez Hachero, J, Perez Cano, R & Coronel Rodriquez, C (1996) Low bone mineral density in small for gestational age infants: correlation with cord blood zinc concentrations. Archives of Disease in Childhood 75, F126F129.CrossRefGoogle ScholarPubMed
Comar, CL (1956) Radiocalcium studies in pregnancy. Annals of the New York Academy of Sciences 64, 281298.CrossRefGoogle Scholar
Cornish, J, Callon, KE & Reid, IR (1996) Insulin increases histomorphometric indices of bone formation in vivo. Calcified Tissue International 59, 492495.CrossRefGoogle ScholarPubMed
Dawson-Hughes, B, Dallal, Ge, Krall, EA, Harris, S, Sokoll, LJ & Falconer, G (1991) Effect of vitamin D supplementation on wintertime and overall bone loss in healthy postmenopausal women. Annals of Internal Medicine 115, 505512.CrossRefGoogle ScholarPubMed
Demarini, S, Specker, BL, Sierra, RI, Miodovnik, M & Tsang, RC (1995) Evidence of increased intrauterine bone resorption in term infants of mothers with insulin-dependent diabetes. Journal of Pediatrics 126, 796798.CrossRefGoogle ScholarPubMed
Demignon, J & Robut-Bonneton, C (1988) Effects of experimental diabetes on the vitamin D metabolism of pregnant rats and their fetuses. Calcified Tissue International 42, 127135.CrossRefGoogle ScholarPubMed
Durand, D, Barlet, JP & Braithwaite, GD (1983a) The influence of 1,25-dihydroxycholecalciferol on the mineral content of foetal guinea-pigs. Reproduction Nutrition Development 23, 235244.CrossRefGoogle ScholarPubMed
Durand, D, Braithwaite, GD & Barlet, JP (1983b) The effect of 1-a-hydroxycholecalciferol on the placental transfer of calcium and phosphate in sheep. British Journal of Nutrition 49, 475480.CrossRefGoogle ScholarPubMed
Eriksen, EF, Charles, P, Melsen, F, Mosekilde, L, Risteli, L & Risteli, J (1993) Serum markers of type I collagen formation and degradation in metabolic bone disease: correlation with bone histomorphometry. Journal of Bone Mineral Research 8, 127132.CrossRefGoogle ScholarPubMed
Fonsca, V, Agnew, JE, Nag, D & Dandona, P (1988) Bone density and cortical thickness in nutritional vitamin D deficiency: effect of secondary hyperparathyroidism. Annals of Clinical Biochemistry 25, 271274.CrossRefGoogle Scholar
Habek, D (1998) Effect of smoking on the feto-placental unit. Lijec Vjesn 120, 215219.Google ScholarPubMed
Harrast, SD & Kalkwarf, HJ (1998) Effects of gestational age, maternal diabetes, and intrauterine growth retardation on markers of fetal bone turnover in amniotic fluid. Calcified Tissue International 62, 205208.CrossRefGoogle ScholarPubMed
Husain, SM, Birdsey, TJ, Glazier, JD, Mughal, MZ, Garland, HO & Sibley, CP (1994) Effect of diabetes mellitus on maternofetal flux of calcium and magnesium and calbindin9K mRNA expression in rat placenta. Pediatric Research 35, 376381.CrossRefGoogle ScholarPubMed
Jones, G, Riley, M & Dwyer, T (1999) Maternal smoking during pregnancy, growth, and bone mass in prepubertal children. Journal of Bone Mineral Research 14, 146151.CrossRefGoogle ScholarPubMed
Keiver, K, Ellis, L, Anzarut, A & Weinberg, J (1997) Effect of prenatal ethanol exposure on fetal calcium metabolism. Alcoholism Clinical and Experimental Research 21, 16121618.CrossRefGoogle ScholarPubMed
Keiver, K, Herbert, L & Weinberg, J (1996) Effect of maternal ethanol consumption on maternal and fetal calcium metabolism. Alcoholism Clinical and Experimental Research 20, 13051312.CrossRefGoogle ScholarPubMed
Kollee, L, Mannens, L, Trijbels, J, Veerkamp, J, Jassen, A & Haard-Hustings, H (1979) Experimental intrauterine growth retardation in the rat; evaluation of the Wigglesworth model. Early Human Development 3, 295300.CrossRefGoogle ScholarPubMed
Krølner, B (1983) Seasonal variation of lumbar spine bone mineral content in normal women. Calcified Tissue International 35, 145147.CrossRefGoogle ScholarPubMed
Kuroda, E, Okano, T & Mizuno, N (1981) Plasma levels of 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3 in maternal, cord and neonatal blood. Journal of Nutritional Science and Vitaminology 27, 5565.CrossRefGoogle Scholar
Lapillonne, A, Brillon, P, Claris, O, Chatelain, PG, Delmas, PD & Salle, BL (1997a) Body composition in appropriate and in small for gestational age infants. Acta Paediatrica 86, 196200.CrossRefGoogle ScholarPubMed
Lapillonne, A, Guerion, S, Braillon, P, Claris, O, Delmas, PD & Salle, BL (1997b) Diabetes during pregnancy does not alter whole body bone mineral content in infants. Journal of Clinical Endocrinology and Metabolism 82, 39933997.CrossRefGoogle Scholar
Lassarre, C, Hardouin, S, Daffos, F, Forestier, F, Frankenne, F & Binoux, M (1991) 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 29, 219225.CrossRefGoogle ScholarPubMed
Levine, ME, Boisseau, VC & Aviolo, LV (1976) Effects of diabetes mellitus on bone mass in juvenile and adult onset diabetes. New England Journal of Medicine 294, 241245.CrossRefGoogle Scholar
Li, JY, Specker, BL, Ho, ML & Tsang, RC (1989) Bone mineral content in black and white children 1 to 6 years of age. American Journal of Diseases in Children 143, 13461349.CrossRefGoogle ScholarPubMed
Luciano, A, Bolognani, M, Biondani, P, Ghizzi, C, Zoppi, G & Signori, E (1998) The influence of maternal passive and light active smoking on intrauterine growth and body composition of the newborn. European Journal of Clinical Nutrition 52, 760763.CrossRefGoogle ScholarPubMed
Lukert, BP, Carey, M, McCarty, B, Tiemann, S, Goodnight, L, Helm, M, Hassanein, R, Stevenson, C, Stoskopf, M & Doolan, L (1987) Influence of nutritional factors on calcium regulating hormones and bone loss. Calcified Tissue International 40, 119125.CrossRefGoogle ScholarPubMed
Mehta, KC, Kalkwarf, HJ, Mimouni, F, Khoury, J & Tsang, RC (1998) Randomized trial of magnesium administration to prevent hypocalcemia in infants of diabetic mothers. Journal of Perinatology 18, 352356.Google ScholarPubMed
Melhus, H, Michalsson, K, Holmberg, L, Wolk, A & Ljunghall, S (1999) Smoking, antioxidant vitamins, and the risk of hip fracture. Journal of Bone Mineral Research 14, 129135.CrossRefGoogle ScholarPubMed
Mimouni, F, Steichen, JJ, Tsang, RC, Hertzberg, V & Miodovnik, M (1988) Decreased bone mineral content in infants of diabetic mothers. American Journal of Perinatology 5, 339343.CrossRefGoogle ScholarPubMed
Minton, SD, Steichen, JJ & Tsang, RC (1983) Decreased bone mineral content in small for gestational age infants compared with appropriate for gestational age infants: normal serum 25-hydroxyvitamin D and decreasing parathyroid hormone. Pediatrics 71, 383388.CrossRefGoogle ScholarPubMed
Moncrieff, M & Fadahunsi, TO (1974) Congenital rickets due to maternal vitamin D deficiency. Archives of Disease in Childhood 49, 810811.CrossRefGoogle ScholarPubMed
Mora, S, Prinster, C, Bellini, A, Weber, G, Proverbio, MC, Puzzovio, M, Bianchi, C & Chiumello, G (1997) Bone turnover in neonates: Changes of urinary excretion rate of collagen type I cross-linked peptides during the first days of life and influence of gestational age. Bone 20, 563566.CrossRefGoogle ScholarPubMed
Mughal, MZ, Ross, R & Tsang, RC (1989) Clearance of calcium across in situ perfused placentas in intrauterine growth-retarded rat fetuses. Pediatric Research 24, 420422.CrossRefGoogle Scholar
Namgung, R, Mimouni, F, Campaigne, BN, Ho, ML & Tsang, RC (1992) Low bone mineral content in summer-born compared with winter-born infants. Journal of Pediatric Gastroenterology and Nutrition 15, 285288.Google ScholarPubMed
Namgung, R, Tsang, RC, Lee, C, Han, DG, Ho, ML & Sierra, RI (1998) Low total body bone mineral content and high bone resorption in Korean winter-born versus summer-born newborn infants. Journal of Pediatrics 132, 421425.CrossRefGoogle ScholarPubMed
Namgung, R, Tsang, RC, Sierra, RI & Ho, ML (1996) Normal serum indices of bone collagen biosynthesis and degradation in small for gestational age infants. Journal of Pediatric Gastroenterology and Nutrition 23, 224228.Google ScholarPubMed
Namgung, R, Tsang, RC, Specker, BL, Sierra, RI & Ho, ML (1993) 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. Journal of Pediatrics 122, 269275.CrossRefGoogle Scholar
Namgung, R, Tsang, RC, Specker, BL, Sierra, RI & Ho, ML (1994) Low bone mineral content and high serum osteocalcin and 1,25(OH)2 vitamin D in summer- versus winter-born newborn infants: An early fetal effect? Journal of Pediatric Gastroenterology and Nutrition 19, 220227.Google Scholar
Ogeuh, O, Khastgir, G, Studd, J, Jones, J, Alaghband-Zadeh, J & Johnson, MR (1998) The relationship of fetal serum markers of bone metabolism to gestational age. Early Human Development 29, 109112.CrossRefGoogle Scholar
Okonofua, F, Menon, RK, Houlder, S, Thomas, M, Robinson, D, O'Brien, S & Dandona, P (1987) Calcium, vitamin D and parathyroid hormone relationships in pregnant Caucasian and Asian women and their neonates. Annals of Clinical Biochemistry 24, 2228.CrossRefGoogle ScholarPubMed
Ooms, ME, Lips, P, Roos, JC, van der Vijgh, WJF, Popp-Snijders, C, Bezemer, PD & Bouter, LM (1995) Vitamin D status and sex hormone binding globulin: determinants of bone turnover and bone mineral density in elderly women. Journal of Bone Mineral Research 10, 11771184.CrossRefGoogle ScholarPubMed
Orwoll, ES & Meier, DE (1986) Alterations in calcium, vitamin D, and parathyroid hormone physiology in normal men with aging: relationship to the development of senile osteopenia. Journal of Clinical Endocrinology and Metabolism 63, 12621269.CrossRefGoogle Scholar
Parfitt, AM, Simon, LS, Villanueva, AR & Krane, SM (1987) Procollagen type I carboxyterminal extension peptide in serum as a marker of collagen biosynthesis in bone. Correlation with iliac bone formation rates and comparison with total alkaline phosphatase. Journal of Bone Mineral Research 2, 427436.CrossRefGoogle ScholarPubMed
Peacock, M, Liu, G, Carey, M, Ambrosius, W, Turner, CH, Hui, S & Johnston, CC Jr (1998) Bone mass and structure at the hip in men and women over the age of 60 years. Osteoporosis International 8, 231239.CrossRefGoogle ScholarPubMed
Petersen, F, Gotfredsen, A & Knudsen, FU (1989) Total body bone mineral in light-for-gestational-age infants and appropriate-for-gestational-age infants. Acta Paediatrica Scandinavica 78, 347350.CrossRefGoogle ScholarPubMed
Pohlandt, F & Mathers, N (1989) Bone mineral content of appropriate and light for gestational age preterm and term newborn infants. Acta Paediatrica Scandinavica 78, 835839.CrossRefGoogle ScholarPubMed
Rupich, RC, Specker, BL, Lieuw-A-Fam, N & Ho, M (1996) Gender and race differences in bone mass during infancy. Calcified Tissue International 58, 395397.CrossRefGoogle ScholarPubMed
Sampson, HW (1998) Effect of alcohol consumption on adult and aged bone: a histomorphometric study of the rat animal model. Alcoholism Clinical and Experimental Research 22, 20292034.Google Scholar
Sampson, HW, Hebert, VA, Booe, HL & Champney, TH (1998) Effect of alcohol consumption on adult and aged bone: composition, morphology, and hormone levels of a rat animal model. Alcoholism Clinical and Experimental Research 22, 17461753.Google ScholarPubMed
Sampson, HW, Perks, N, Champney, TH & DeFee, B II (1996) Alcohol consumption inhibits bone growth and development in young actively growing rats. Alcoholism Clinical and Experimental Research 20, 13751384.CrossRefGoogle ScholarPubMed
Scharla, SH, Scheidt-Nave, C, Leidig, G, Woitge, H, Wuster, C, Seibel, MJ & Ziegler, R (1996) Lower serum 25-hydroxyvitamin D is associated with increased bone resorption markers and lower bone density at the proximal femur in normal females: a population-based study. Experimental and Clinical Endocrinology and Diabetes 104, 289292.CrossRefGoogle ScholarPubMed
Seller, MJ & Bnait, KS (1995) Effects of tobacco smoke inhalation on the developing mouse embryo and fetus. Reproductive Toxicology 9, 449459.CrossRefGoogle ScholarPubMed
Sherman, SS, Tobin, JD, Hollis, BW, Gundberg, CM, Roy, TA & Plato, CC (1992) Biochemical parameters associated with low bone density in healthy men and women. Journal of Bone Mineral Research 7, 11231130.CrossRefGoogle ScholarPubMed
Specker, BL, Ho, ML, Oestreich, A, Yin, TA, Shui, QM, Chen, XC & Tsang, RC (1992) Prospective study of vitamin D supplementation and rickets in China. Journal of Pediatrics 120, 733739.CrossRefGoogle ScholarPubMed
Steichen, JJ, Kaplan, B, Edwards, N & Tsang, RC (1976) Bone mineral content in full-term infants measured by direct photon absorptiometry. American Journal of Roentgenology 126, 12831285.CrossRefGoogle ScholarPubMed
Steichen, JJ, Tsang, RC & Ho, ML (1981) Perinatal magnesium, calcium and 1,25-dihydroxyvitamin D in relation to prospective randomized management of maternal diabetes. Pediatric Research 15, 683A.Google Scholar
Thieriot-Prevost, G, Boccara, JF, Francoual, C, Badoual, J & Job, JC (1988) Serum insulin-like growth factor I and serum growth-promoting activity during the first postnatal year in infants with intrauterine growth retardation. Pediatric Research 24, 380382.CrossRefGoogle ScholarPubMed
Tsang, RC, Kleinman, L, Sutherland, JM & Light, IJ (1972) Hypocalcemia in infants of diabetic mothers: studies in Ca, P and Mg metabolism and in parathormone responsiveness. Journal of Pediatrics 80, 384395.CrossRefGoogle Scholar
Unterman, TG, Simmons, RC, Glick, RP & Ogata, ES (1993) Circulating levels of insulin, insulin-like growth factor-I (IGF-I), IGF-II, and IGF-binding proteins in the small for gestational age fetal rat. Endocrinology 132, 327336.CrossRefGoogle ScholarPubMed
Verhaeghe, J, Bouillon, R, Lissens, W, Visser, WJ & Van Assche, FA (1988) Diabetes and low Ca-P diets have opposite effects on adult and fetal bone and mineral metabolism. American Journal of Physiology 254, E496E504.Google Scholar
Verhaeghe, J, Bouillon, R, Nyomba, BL, Lissens, W & Van Assche, FA (1986) Vitamin D and bone mineral homeostasis during pregnancy in the diabetic BB rat. Endocrinology 118, 10191025.CrossRefGoogle ScholarPubMed
Verhaeghe, J, Van Bree, R, Van Herck, E, Rummens, K, Vercruysse, L, Bouillon, R & Pijnenborg, R (1999) Pathogenesis of fetal hypomineralization in diabetic rats: evidence for delayed bone maturation. Pediatric Research 45, 209217.CrossRefGoogle ScholarPubMed
Verity, CM, Burman, D, Beadle, PC, Holton, JB & Morris, A (1981) Seasonal changes in perinatal vitamin D metabolism: maternal and cord blood biochemistry in normal pregnancies. Archives of Disease in Childhood 56, 943948.CrossRefGoogle ScholarPubMed
Weinberg, J, D'Alquen, G & Bezio, S (1990) Interactive effects of ethanol intake and maternal nutritional status on skeletal development of fetal rats. Alcohol 7, 383388.CrossRefGoogle ScholarPubMed
Wigglesworth, J (1964) Experimental growth retardation in the foetal rat. Journal of Pathology and Bacteriology 88, 113.CrossRefGoogle ScholarPubMed
Woitge, HW, Scheidt-Nave, C, Kissling, C, Leidig-Bruckner, G, Meyer, K, Grauer, A, Scharla, SH, Ziegler, R & Seibel, MJ (1998) Seasonal variation of biochemical indexes of bone turnover: results of a population-based study. Journal of Clinical Endocrinology and Metabolism 83, 6875.Google ScholarPubMed
Zaren, B, Lindmark, G & Gebre-Medhin, M (1996) Maternal smoking and body composition of the newborn. Acta Paediatrica 85, 213219.CrossRefGoogle ScholarPubMed
Zittermann, A, Scheld, K & Stehle, P (1998) Seasonal variations in vitamin D status and calcium absorption do not influence bone turnover in young women. European Journal of Clinical Nutrition 52, 501506.CrossRefGoogle Scholar