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Neonatal iron status is impaired by maternal obesity and excessive weight gain during pregnancy

Abstract

Objective:

Maternal iron needs increase sixfold during pregnancy, but obesity interferes with iron absorption. We hypothesized that maternal obesity impairs fetal iron status.

Study Design:

Three hundred and sixteen newborns with risk factors for infantile iron deficiency anemia (IDA) were studied to examine obesity during pregnancy and neonatal iron status. Erythrocyte iron was assessed by cord blood hemoglobin (Hb), zinc protoporphyrin/heme (ZnPP/H) and reticulocyte-ZnPP/H, and storage iron by serum ferritin.

Result:

Women with body mass index (BMI) 30 kg m2, as compared with non-obese women, delivered larger offspring with higher reticulocyte-ZnPP/H and lower serum ferritin concentrations (P<0.05 for both). With increasing BMI, the estimated body iron was relatively lower (mg kg1) and the ratio of total Hb-bound iron (mg) per total body iron (mg) increased. Maternal diabetes compromised infant iron status, but multivariate analysis demonstrated that obesity was an independent predictor.

Conclusion:

Obesity during pregnancy and excessive weight gain are independent risk factors for iron deficiency in the newborn.

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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 (7): 441–446.

    Article  CAS  Google Scholar 

  2. 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 (4): 924–930.

    Article  CAS  Google Scholar 

  3. Saito I, Yonemasu K, Inami F . Association of body mass index, body fat, and weight gain with inflammation markers among rural residents in Japan. Circ J 2003; 67 (4): 323–329.

    Article  Google Scholar 

  4. McClung JP, Karl JP . Iron deficiency and obesity: the contribution of inflammation and diminished iron absorption. Nutr Rev 2009; 67 (2): 100–104.

    Article  Google Scholar 

  5. Zimmermann MB, Zeder C, Muthayya S, Winichagoon P, Chaouki N, Aeberli I et al Adiposity in women and children from transition countries predicts decreased iron absorption, iron deficiency and a reduced response to iron fortification. Int J Obes (Lond) 2008; 32 (7): 1098–1104.

    Article  CAS  Google Scholar 

  6. Yanoff LB, Menzie CM, Denkinger B, Sebring NG, McHugh T, Remaley AT et al Inflammation and iron deficiency in the hypoferremia of obesity. Int J Obes (Lond) 2007; 31 (9): 1412–1419.

    Article  CAS  Google Scholar 

  7. Bradley J, Leibold EA, Harris ZL, Wobken JD, Clarke S, Zumbrennen KB et al Influence of gestational age and fetal iron status on IRP activity and iron transporter protein expression in third-trimester human placenta. Am J Physiol Regul Integr Comp Physiol 2004; 287 (4): R894–R901.

    Article  CAS  Google Scholar 

  8. 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 (3): 177–181.

    Article  CAS  Google Scholar 

  9. Clark SF . Iron deficiency anemia. Nutr Clin Pract 2008; 23 (2): 128–141.

    Article  Google Scholar 

  10. Lozoff B, Beard J, Connor J, Barbara F, Georgieff M, Schallert T . Long-lasting neural and behavioral effects of iron deficiency in infancy. Nutr Rev 2006; 64 (5 Pt 2): S34–S43; discussion S72–S91.

    Article  Google Scholar 

  11. Fomon S . Iron. Nutrition of normal infants. Mosby, St Louis. 1993, pp 239–260.

  12. Lozoff B, Kaciroti N, Walter T . Iron deficiency in infancy: applying a physiologic framework for prediction. Am J Clin Nutr 2006; 84 (6): 1412–1421.

    Article  CAS  Google Scholar 

  13. Blohowiak SE, Chen ME, Repyak KS, Baumann-Blackmore NL, Carlton DP, Georgieff MK et al Reticulocyte enrichment of zinc protoporphyrin/heme discriminates impaired iron supply during early development. Pediatr Res 2008; 64: 63–67.

    Article  CAS  Google Scholar 

  14. Ullrich C, Wu A, Armsby C, Rieber S, Wingerter S, Brugnara C et al Screening healthy infants for iron deficiency using reticulocyte hemoglobin content. JAMA 2005; 294 (8): 924–930.

    Article  CAS  Google Scholar 

  15. Kasper DC, Widness JA, Haiden N, Berger A, Hayde M, Pollak A et al Characterization and differentiation of iron status in anemic very low birth weight infants using a diagnostic nomogram. Neonatology 2009; 95 (2): 164–171.

    Article  CAS  Google Scholar 

  16. Saarinen UM, Siimes MA . Developmental changes in serum iron, total iron binding capacity, and transferrin saturation in infancy. J Pediatr 1977; 91: 875–880.

    Article  CAS  Google Scholar 

  17. Siddappa AM, Rao R, Long JD, Widness JA, Georgieff M . The assessment of newborn iron stores at birth: a review of the literature and standards for ferritin concentrations. Neonatology 2007; 92: 73–82.

    Article  CAS  Google Scholar 

  18. Nold JL, Georgieff MK . Infants of diabetic mothers. Pediatr Clin N Am 2004; 51: 619–637.

    Article  Google Scholar 

  19. McLimore HM, Phillips AK, Blohowiak SE, Pham DQ, Coe CL, Fischer BA et al Impact of multiple prenatal risk factors on newborn iron status at delivery. J Pediatr Hematol Oncol 2013; 35 (6): 473–477.

    Article  CAS  Google Scholar 

  20. Alexander GR, Kogan MD, Himes JH . 1994–1996 US singleton birth weight percentiles for gestational age by race, Hispanic origin, and gender. Matern Child Health J 1999; 3 (4): 225–231.

    Article  CAS  Google Scholar 

  21. Rebouche CJ, Wilcox CL, Widness JA . Microanalysis of non-heme iron in animal tissues. J Biochem Biophys Methods 2004; 58 (3): 239–251.

    Article  CAS  Google Scholar 

  22. Committee to Reexamine IOM Pregnancy Weight Guidelines. Weight Gain during Pregnancy: Reexamining the Guidelines. Institute of Medicine, National Research Council, 2009.

  23. Committee on Obstetric Practice. Obesity in pregnancy. Obstet Gynecol 2013; 549: 213–217.

    Google Scholar 

  24. 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.

    Article  CAS  Google Scholar 

  25. Arbuckle TE, Wilkins R, Sherman GJ . Birth weight percentiles by gestational age in Canada. Obstet Gynecol 1993; 81: 39–48.

    CAS  PubMed  Google Scholar 

  26. Siimes MA, Saarinen UM, Dallman PR . Relationship between hemoglobin concentration and transferrin saturation in iron-sufficient infants. Am J Clin Nutr 1979; 32: 2295–2300.

    Article  CAS  Google Scholar 

  27. Siddappa AM, Georgieff MK, Wewerka SW, Worwa C, Nelson CA, deRegnier R-A . Iron deficiency alters auditory recognition memory in newborn infants of diabetic mothers. Pediatr Res 2004; 55: 1034–1041.

    Article  CAS  Google Scholar 

  28. Wisconsin Association for Perinatal Care Prenatal Testing Committee. Laboratory Testing During Pregnancy. Wisconsin Association for Perinatal Care Prenatal Testing Committee: Madison, WI, 2011.

  29. Widness JA, Susa JB, Garcia JF, Singer DB, Sehgal P, Oh W et al Increased erythropoiesis and elevated erythropoietin in infants born to diabetic mothers and in hyperinsulinemic rhesus fetuses. J Clin Invest 1981; 67: 637–642.

    Article  CAS  Google Scholar 

  30. Kleven KJ, Blohowiak SE, Kling PJ . Zinc protoporphyrin/heme in large-for-gestation newborns. Neonatology 2007; 92 (2): 91–95.

    Article  CAS  Google Scholar 

  31. Georgieff MK, Landon MB, Mills MM, Hedlund BE, Faassen AE, Schmidt RL et al Abnormal iron distribution in infants of diabetic mothers: spectrum and maternal antecedents. J Pediatr 1990; 117: 455–461.

    Article  CAS  Google Scholar 

  32. Lott DG, Zimmerman MB, Labbe' RF, Kling PJ, Widness JA . Erythrocyte zinc protoporphyrinratios are elevated with prematurity and with fetal hypoxia. Pediatrics 2005; 116: 414–422.

    Article  Google Scholar 

  33. Cogswell ME, Kettel-Khan L, Ramakrishnan U . Iron supplement use among women in the United States: science, policy and practice. J Nutr 2003; 133 (6): 1974S–1977S.

    Article  Google Scholar 

  34. Beard JL . Iron deficiency: assessment during pregnancy and its importance in pregnant adolescents. Am J Clin Nutr 1994; 59 (Suppl 2): 502S–508S; discussion 508S–510S.

    Article  CAS  Google Scholar 

  35. Georgieff MJ, Wewerka SW, Nelson CA, deRegnier R-A . Iron status at 9 months of infants with low iron stores at birth. J Pediatr 2002; 141: 405–409.

    Article  CAS  Google Scholar 

  36. Thorsdottir I, Gunnarsson BS, Atladottir H, Michaelsen KF, Palsson G . Iron status at 12 months of age—effects of body size, growth and diet in a population with high birth weight. Eur J Clin Nutr 2003; 57: 505–513.

    Article  CAS  Google Scholar 

  37. Gentile M, Panico S, Rubba F, Mattiello A, Chiodini P, Jossa F et al Obesity, overweight, and weight gain over adult life are main determinants of elevated hs-CRP in a cohort of Mediterranean women. Eur J Clin Nutr 2010; 64 (8): 873–878.

    Article  CAS  Google Scholar 

  38. Lozoff B, Georgieff MK . Iron deficiency and brain development. Sem Pediatr Neurol 2006; 13: 158–165.

    Article  Google Scholar 

  39. Muller KF, Lorenz L, Poets CF, Westerman M, Franz AR . Hepcidin concentrations in serum and urine correlated with iron homeostasis in preterm infants. J Pediatr 2012; 160: 949–953.

    Article  Google Scholar 

  40. Gambling L, Czopek A, Andersen HS, Holtrop G, SKS Srai, Krejpcio Z et al Fetal iron status regulates maternal iron metabolism during pregnancy in the rat. Am J Physiol Regul Integr Comp Physiol 2009; 296: R1063–R1070.

    Article  CAS  Google Scholar 

  41. Rao R, Georgieff MK . Iron in fetal and neonatal nutrition. Sem Fetal Neonat Med 2007; 12 (1): 54–63.

    Article  Google Scholar 

  42. Baker RD, Greer FR . Diagnosis and prevention of iron deficiency and iron-deficiency anemia in infants and young children (0–3 years of age). Pediatrics 2010; 126 (5): 1040–1050.

    Article  Google Scholar 

  43. Georgieff MK, Schmidt RL, Mills MM, Radmer WJ, Widness JA . Fetal iron and cytochrome c status after intrauterine hypoxemia and erythropoietin administration. Am J Physiol 1992; 262: R485–R491.

    CAS  PubMed  Google Scholar 

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Acknowledgements

We thank the participating families, Meriter Hospital Birthing Center Staff, Meriter Hospital Blood Bank, Deb Krumpos (RN), Sue Shafranski (RN), Patricia Green-Sotos (RN), Melinda E Chen (BS), Beth A Fischer (PhD), Jens Eichman (PhD), Chong Zhang, Vidya Sridhar (MBBS), Brian R Pisula (BS), Murray L Katcher (MD, PhD), Daphne Pham (PhD) and members of the Kling Laboratory Research Team. This work was supported by University of Wisconsin Shapiro Research Program (SCR), University of Wisconsin Cardiovascular Research Center (SCR), Meriter Foundation (PJK), Wisconsin Partnership Collaborative Health Sciences Program Grant (PJK), NIH 1 ULRR026011 UW CTSA, Thrasher Research Fund (PJK), UW Graduate School Competition (PJK).

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Correspondence to P J Kling.

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Phillips, A., Roy, S., Lundberg, R. et al. Neonatal iron status is impaired by maternal obesity and excessive weight gain during pregnancy. J Perinatol 34, 513–518 (2014). https://doi.org/10.1038/jp.2014.42

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