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DOI: 10.1055/s-0038-1669444
Cord Blood Erythropoietin and Hepcidin Reflect Lower Newborn Iron Stores due to Maternal Obesity during Pregnancy
Funding This work was supported by Meriter Foundation, National Institutes of Health (NIH 1 ULRR026011 UW CTSA Program and NIH T32 DK077586 Pediatric Endocrinology Scholar), UW Education & Research Committee-Wisconsin Partnership Program, and Thrasher Research Fund.Publikationsverlauf
13. Februar 2018
24. Juli 2018
Publikationsdatum:
07. September 2018 (online)
![](https://www.thieme-connect.de/media/ajp/201905/lookinside/thumbnails/10-1055-s-0038-1669444_180084-1.jpg)
Abstract
Objective Obesity during pregnancy impedes fetal iron endowment. In adults, both iron depletion and hypoxia stimulate erythropoietin (Epo) production, while hepcidin, the primary iron regulator, is inhibited by Epo and stimulated by obesity. To understand this relationship in fetuses, we investigated obesity, inflammation, and fetal iron status on fetal Epo and hepcidin levels.
Study Design Epo, hepcidin, C-reactive protein (CRP), and ferritin levels were measured in 201 newborns of 35 to 40 weeks' gestation with historical risk factors for a low fetal iron endowment, including half with maternal obesity.
Results Epo was unrelated to fetal size, but Epo was directly related to maternal body mass index (BMI; kg/m2) (p < 0.03) and CRP (p < 0.0005) at delivery. Epo levels were twice as likely to be elevated (≥50 IU/L) while comparing the lowest quartile of ferritin with the upper three quartiles (p < 0.01). Hepcidin was directly related to ferritin (p < 0.001) and indirectly related to maternal BMI (p < 0.015), but BMI became nonsignificant when undergoing multivariate analysis. Hepcidin was unrelated to Epo.
Conclusion Although some of the fetal responses involving Epo were similar to adults, we did not find a hepcidin–Epo relationship like that of adults, where fetal liver is the site of both hepcidin and Epo production.
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References
- 1 Schmatz M, Madan J, Marino T, Davis J. Maternal obesity: the interplay between inflammation, mother and fetus. J Perinatol 2010; 30 (07) 441-446
- 2 Dixit A, Girling JC. Obesity and pregnancy. J Obstet Gynaecol 2008; 28 (01) 14-23
- 3 Phillips AK, Roy SC, Lundberg R. , et al. Neonatal iron status is impaired by maternal obesity and excessive weight gain during pregnancy. J Perinatol 2014; 34 (07) 513-518
- 4 Jones AD, Zhao G, Jiang YP. , et al. Maternal obesity during pregnancy is negatively associated with maternal and neonatal iron status. Eur J Clin Nutr 2016; 70 (08) 918-924
- 5 O'Brien KO, Zavaleta N, Abrams SA, Caulfield LE. Maternal iron status influences iron transfer to the fetus during the third trimester of pregnancy. Am J Clin Nutr 2003; 77 (04) 924-930
- 6 Lesser KB, Schoel SB, Kling PJ. Elevated zinc protoporphyrin/heme ratios in umbilical cord blood after diabetic pregnancy. J Perinatol 2006; 26 (11) 671-676
- 7 Lozoff B, Georgieff MK. Iron deficiency and brain development. Semin Pediatr Neurol 2006; 13 (03) 158-165
- 8 Lott DG, Zimmerman MB, Labbé RF, Kling PJ, Widness JA. Erythrocyte zinc protoporphyrin is elevated with prematurity and fetal hypoxemia. Pediatrics 2005; 116 (02) 414-422
- 9 Dame C, Fahnenstich H, Freitag P. , et al. Erythropoietin mRNA expression in human fetal and neonatal tissue. Blood 1998; 92 (09) 3218-3225
- 10 Zhang Y, Wang L, Dey S. , et al. Erythropoietin action in stress response, tissue maintenance and metabolism. Int J Mol Sci 2014; 15 (06) 10296-10333
- 11 Kling PJ, Dragsten PR, Roberts RA. , et al. Iron deprivation increases erythropoietin production in vitro, in normal subjects and patients with malignancy. Br J Haematol 1996; 95 (02) 241-248
- 12 Sheffer-Mimouni G, Mimouni FB, Dollberg S, Mandel D, Deutsch V, Littner Y. Neonatal nucleated red blood cells in infants of overweight and obese mothers. J Am Coll Nutr 2007; 26 (03) 259-263
- 13 Milman N, Agger AO, Nielsen OJ. Iron status markers and serum erythropoietin in 120 mothers and newborn infants. Effect of iron supplementation in normal pregnancy. Acta Obstet Gynecol Scand 1994; 73 (03) 200-204
- 14 Ward DM, Kaplan J. Ferroportin-mediated iron transport: expression and regulation. Biochim Biophys Acta 2012; 1823 (09) 1426-1433
- 15 Rehu M, Punnonen K, Ostland V. , et al. Maternal serum hepcidin is low at term and independent of cord blood iron status. Eur J Haematol 2010; 85 (04) 345-352
- 16 Koenig MD, Tussing-Humphreys L, Day J, Cadwell B, Nemeth E. Hepcidin and iron homeostasis during pregnancy. Nutrients 2014; 6 (08) 3062-3083
- 17 Dao MC, Sen S, Iyer C, Klebenov D, Meydani SN. Obesity during pregnancy and fetal iron status: is Hepcidin the link?. J Perinatol 2013; 33 (03) 177-181
- 18 Ashby DR, Gale DP, Busbridge M. , et al. Erythropoietin administration in humans causes a marked and prolonged reduction in circulating hepcidin. Haematologica 2010; 95 (03) 505-508
- 19 Guo S, Frazer DM, Anderson GJ. Iron homeostasis: transport, metabolism, and regulation. Curr Opin Clin Nutr Metab Care 2016; 19 (04) 276-281
- 20 McLimore HM, Phillips AK, Blohowiak SE. , et al. Impact of multiple prenatal risk factors on newborn iron status at delivery. J Pediatr Hematol Oncol 2013; 35 (06) 473-477
- 21 Blohowiak SE, Chen ME, Repyak KS. , et al. Reticulocyte enrichment of zinc protoporphyrin/heme discriminates impaired iron supply during early development. Pediatr Res 2008; 64 (01) 63-67
- 22 Rasmussen KM, Yaktine AL. , eds; Institute of Medicine (US) and National Research Council (US) Committee to Reexamine IOM Pregnancy Weight Guidelines. Committee To Reexamine IOM Pregnancy Weight Guidelines. Weight Gain during Pregnancy: Reexamining the Guidelines. Washington, DC: National Academies Press; 2009
- 23 Teramo KA, Widness JA, Clemons GK, Voutilainen P, McKinlay S, Schwartz R. Amniotic fluid erythropoietin correlates with umbilical plasma erythropoietin in normal and abnormal pregnancy. Obstet Gynecol 1987; 69 (05) 710-716
- 24 Hay Jr WW, DiGiacomo JE, Meznarich HK, Hirst K, Zerbe G. Effects of glucose and insulin on fetal glucose oxidation and oxygen consumption. Am J Physiol 1989; 256 (6 Pt 1): E704-E713
- 25 Widness JA, Susa JB, Garcia JF. , et al. Increased erythropoiesis and elevated erythropoietin in infants born to diabetic mothers and in hyperinsulinemic rhesus fetuses. J Clin Invest 1981; 67 (03) 637-642
- 26 Widness JA, Clemons GK, Garcia JF, Oh W, Schwartz R. Increased immunoreactive erythropoietin in cord serum after labor. Am J Obstet Gynecol 1984; 148 (02) 194-197
- 27 Erdem A, Erdem M, Arslan M, Yazici G, Eskandari R, Himmetoglu O. The effect of maternal anemia and iron deficiency on fetal erythropoiesis: comparison between serum erythropoietin, hemoglobin and ferritin levels in mothers and newborns. J Matern Fetal Neonatal Med 2002; 11 (05) 329-332
- 28 McClung JP, Karl JP. Iron deficiency and obesity: the contribution of inflammation and diminished iron absorption. Nutr Rev 2009; 67 (02) 100-104
- 29 Petry CD, Wobken JD, McKay H. , et al. Placental transferrin receptor in diabetic pregnancies with increased fetal iron demand. Am J Physiol 1994; 267 (4 Pt 1): E507-E514
- 30 Trevisanuto D, Doglioni N, Altinier S, Zaninotto M, Plebani M, Zanardo V. High-sensitivity C-reactive protein in umbilical cord of small-for-gestational-age neonates. Neonatology 2007; 91 (03) 186-189
- 31 Kling PJ, Taing KM, Dvorak B, Woodward SS, Philipps AF. Insulin-like growth factor-I stimulates erythropoiesis when administered enterally. Growth Factors 2006; 24 (03) 218-223
- 32 Woo M, Hawkins M. Beyond erythropoiesis: emerging metabolic roles of erythropoietin. Diabetes 2014; 63 (07) 2229-2231
- 33 Wang L, Di L, Noguchi CT. Erythropoietin, a novel versatile player regulating energy metabolism beyond the erythroid system. Int J Biol Sci 2014; 10 (08) 921-939
- 34 Mei Z, Cogswell ME, Parvanta I. , et al. Hemoglobin and ferritin are currently the most efficient indicators of population response to iron interventions: an analysis of nine randomized controlled trials. J Nutr 2005; 135 (08) 1974-1980
- 35 Alnaeeli M, Raaka BM, Gavrilova O, Teng R, Chanturiya T, Noguchi CT. Erythropoietin signaling: a novel regulator of white adipose tissue inflammation during diet-induced obesity. Diabetes 2014; 63 (07) 2415-2431