Biological Trace Element Research

, Volume 136, Issue 2, pp 157–170 | Cite as

Depressed Antioxidant Status in Pregnant Women on Iron Supplements: Pathologic and Clinical Correlates

  • J. I. Anetor
  • O. A. Ajose
  • F. N. Adeleke
  • G. O. Olaniyan-Taylor
  • F. A. Fasola
Article

Abstract

Iron (Fe) remains a commonly prescribed supplement in pregnancy. Its possible pathologic potential is either uncommonly considered or ignored. We determined the antioxidant status in pregnant women with and without Fe supplements. Fifty-eight apparently healthy pregnant women on Fe supplements were selected for the study from the antenatal clinic of the University College Hospital, Ibadan, Nigeria. Fifty-five aged matched pregnant women who were not on Fe from various parishes of the Christ Apostolic Church, Ibadan (non-drug using Christian sect) were randomly selected as controls. Both groups were classified according to the trimesters of pregnancy. The gestational age in both pregnant women on Fe supplements and non-supplement pregnant women was similar. Fruit and vegetables consumption was higher in the supplement than in the non-supplement group (57.2% vs. 37.3%). Anthropometric indices, weight, height, and BMI, were also similar. But while the weight of the Fe supplement group decreased by nearly 3% in the third trimester, it increased by over 10% (p < 0.00) in the non-supplement group in the same period. Serum Fe level was significantly higher in the supplement than the non-supplement group (p < 0.001). In contrast, the levels of the antioxidants, ascorbic acid, copper (Cu), zinc (Zn), and bilirubin were all significantly decreased (p < 0.05, p < 0.001, p < 0.05, and p < 0.05, respectively). Uric acid level though also lower in the supplement group did not reach statistical significance (p > 0.05), while vitamin E was similar in both groups. There was relative stability of all antioxidants except uric acid, which declined from the first to the last trimester in the non-supplement group. The significantly higher Fe level in the second trimester was sustained in the third trimester though to a lesser degree (p < 0.05) and associated with significant decreases in the following antioxidant levels in the supplement group, ascorbic acid, bilirubin, Cu, and Zn (p < 0.02, p < 0.02, p < 0.02, and p < 0.001, respectively). Uric acid and vitamin E though lower in the supplement group were not significantly different. Remarkably, percentage changes between the first and third trimesters revealed that serum Fe increased by over 116% in the Fe supplement group, while it only increased by over 50% in the non-supplement group. This was associated with 23.50% decrease in ascorbate level (p < 0.003) in the supplement group, while it decreased by only 3.70% in the non-supplement group (p > 0.05). Again vitamin E decreased by 17.22% in the supplement group, while it decreased by only 7.30% in the non-supplement group during the period. Uric acid and bilirubin levels decreased by similar proportions during the period, while Zn decreased by 18.55% in the supplement group and by 14.86% in the non-supplement group. In contrast Cu increased by 7.20% in the supplement group, while it increased by only 2.96 in the non-supplement group. Additionally, all the antioxidants in the supplement group except vitamin E, viz, ascorbic acid, bilirubin, Cu, uric acid, and Zn, were significantly inversely correlated with serum Fe level (r − 0.299, p < 0.05, r − 0.278, p < 0.05, r − 0.383, p < 0.05, and r − 0.0369, p < 0.05). These data imply markedly depressed antioxidant status in the Fe supplement pregnant group with attendant oxidative stress (most probably pro-oxidant Fe-induced). This is associated with molecular and cellular damage as well as a number of pathologic and clinical correlates that underlie the exacerbation of morbidity and mortality in maternal and child populations, particularly in the developing countries. This appears to call for serious caution and prior evaluation of antioxidant and Fe status and during the use of Fe supplements in pregnancy for monitoring and prognostic purposes and to avert or ameliorate oxidative stress-induced pathologies in maternal and fetal systems.

Keywords

Antioxidant status Iron supplement Maternal morbidity and mortality Molecular damage Oxidative stress Pathologic correlate 

References

  1. 1.
    Whittaker PG, Lind T, Williams JG (1991) Iron absorption during normal pregnancy: a study using stable isotopes. Br J Nutr 65:457–463CrossRefPubMedGoogle Scholar
  2. 2.
    Ortega RM, Quitas ME, Andres P, Lopez-Sobaler AM (1998) Iron supplementation during pregnancy: standards and alternatives. Nutric Iron Hospitalaria 13:114–120Google Scholar
  3. 3.
    Halliwell B, Gutteridge JMC (1998) Free radicals in biology and medicine, 3rd edn. Oxford University Press, EnglandGoogle Scholar
  4. 4.
    Schofield C, Ashworth A (1997) Severe malnutrition in children: high case fatalities can be reduced. Afr Health 19:17–18PubMedGoogle Scholar
  5. 5.
    Simsek M, Naziroglu M, Simsek H, Cay M, Aksakal M, Kumru S (1998) Blood plasma levels of lipoperoxide, glutathione peroxidase, beta-carotene, vitamins A and E in women with habitual abortions. Cell Biochem Funct 16:227–231CrossRefPubMedGoogle Scholar
  6. 6.
    Hubel CA, Kozlov AV, Kagan VE, Evans RW, Davidge ST, Mclauglin MK, Roberts JM (1996) Decreased transferrin and increased transferrin saturation in sera of women with pre-eclampsia: implications for oxidative stress. Am J Obstet Gynecol 175:692–700CrossRefPubMedGoogle Scholar
  7. 7.
    Pietrangelo A (1998) Iron, oxidative stress, and liver fibrogenesis. J Hepatol 28:8–13CrossRefPubMedGoogle Scholar
  8. 8.
    Dizadgloflu M, Nackerdien Z, Chao BC, Gajewski E, Rao G (1991) Chemical nature of in vivo base damage in hydrogen peroxide treated mammalian cells. Arch Biochem Biophys 285:388–390CrossRefGoogle Scholar
  9. 9.
    Lachili B, Hininger I, Faure H, Arnaud J, Richard MJ, Favrer A, Rossel AM (2001) Increased lipid peroxidation in pregnant women after iron and vitamin C supplementation. Biol Trace Elem Res 83:103–110CrossRefPubMedGoogle Scholar
  10. 10.
    Kagan VE, Serbinova EA, Pacter L (1990) Antioxidant effects of ubiquinones in microsomes and mitochondria are mediated by tocopherol recycling. Biochem Biophys Res Commun 160:851–857CrossRefGoogle Scholar
  11. 11.
    Stookey LL (1970) A new spectrophotometric reagent for iron. Anal Chem 42:779CrossRefGoogle Scholar
  12. 12.
    Aye-Kway A (1977) A simple colorimetric method for ascorbic acid determination in blood or plasma. Clin Chem 86:153–157Google Scholar
  13. 13.
    Doumas BT, Wu TW (1991) The measurement of bilirubin fractions in serum. Crit Rev Clin Lab Sci 28:415–446CrossRefPubMedGoogle Scholar
  14. 14.
    Fossati P, Prencipi L, Berti G (1980) Use of 3, 5-dichloro 2-hydroxybenzene sulfonic acid-14-amino phenazone chromogenic system in direct enzymatic assay of uric acid in serum and urine. Clin Chem 26:227–231PubMedGoogle Scholar
  15. 15.
    Varley H, Gowenlock AH, Bell N (eds) (1980) Hormones, vitamins, drugs and poisons. In: Practical clinical biochemistry, vol 2. William Heinemann Medical Books Ltd, London, pp. 215–259Google Scholar
  16. 16.
    Barker H, Frank O (1968) Clinical vitaminology. Wiley, New York, p 172Google Scholar
  17. 17.
    Osheim DL (1983) Atomic absorption determination of serum copper; collaborative study. J Assoc Anal Chem 66:11140–1142Google Scholar
  18. 18.
    Smith JC Jr, Burttrimovitz GP, Purdy WC (1979) Direct measurement of zinc in plasma by atomic absorption spectroscopy. Clin Chem 25:1487–1491PubMedGoogle Scholar
  19. 19.
    Mario M, Jerry MR (1971) Plasma ascorbic levels in pregnancy. Am J Obstet Gynaecol 109:960Google Scholar
  20. 20.
    Schumann K (2001) Safety aspects of iron in food. Ann Nutr Metab 45:91–101CrossRefPubMedGoogle Scholar
  21. 21.
    Halliwell B (1989) Current status: free radicals, reactive oxygen species, and human diseases: a critical evaluation with special reference to atherosclerosis. Br J Exp Path 70:737–757Google Scholar
  22. 22.
    Ho E, Courtemanche C, Ames BN (2003) Zinc deficiency induces oxidative DNA damage and increases p53 expression in human lung fibroblasts. J Nutr 133:2543–2548PubMedGoogle Scholar
  23. 23.
    Chou PT, Khan AU (1983) L-ascorbic acid quenching of singlet delta molecular oxygen in aqueous media: generalized antioxidant property of vitamin C. Biochem Biophys Res Commun 115:932–937CrossRefPubMedGoogle Scholar
  24. 24.
    Buettner GR, Jurkiewicz BA (1996) Catalytic metals, ascorbate and free radicals: combinations to avoid. Radiat Res 145:532–541CrossRefPubMedGoogle Scholar
  25. 25.
    Frei B, England L, Ames BN (1989) Ascorbate is an outstanding anti-oxidant in human blood plasma. Proc Natl Acad Sci USA 86:6377–6381CrossRefPubMedGoogle Scholar
  26. 26.
    Cai L, Koropatnick J, Cherian MG (2001) Roles of vitamin C in radiation-induced DNA damage in presence and absence of copper. Chem Biol Interact 137:75–88CrossRefPubMedGoogle Scholar
  27. 27.
    Evans D, Cooke S (eds) (2007) Preface: oxidative damage to nucleic acids. Landes Bioscience, AustinGoogle Scholar
  28. 28.
    Barker DJP, Eriksson JG, Forsen T, Osmond C (2002) Fetal origins of adult disease: strength of effects and biological basis. Int J Epidemiol 31(6):1235–1239CrossRefPubMedGoogle Scholar
  29. 29.
    Garry PJ, Hunt WC, Baumgatner RN (2002) Effects of iron intake on stores in elderly men and women: longitudinal and cross-sectional results. J Am Coll Nutr 19:262–269Google Scholar
  30. 30.
    Berdanier CD (1998) Vitamin E. In: Advanced nutrition: micronutrients. CRC, Boca Raton, pp. 52–59Google Scholar
  31. 31.
    Scott KP, Shannon LL (1999) Analysis of cellular responses to free radicals: focus on exercise and skeletal muscle. Proc Nutr Soc 58:1025–1033CrossRefGoogle Scholar
  32. 32.
    Ward RJ, Peters TJ (1995) Free radicals. In: Marshall WJ, Bangert SK (eds) Clinical biochemistry: clinical and metabolic aspects. Churchill Livingstone, Edinburgh, pp 765–777Google Scholar
  33. 33.
    Ranthi SS, Srinivas M, Grover JK, Mitra D, Vats V, Sharma JD (1999) Zinc levels in women and newborns. Ind J Paed 66:681–684CrossRefGoogle Scholar
  34. 34.
    Martin-Lagos F, Nevarro-Alarcon M, Terres-Martos C, Lopez-Garcia de la Serrana H, Perez-Valero V, Lopez-Martinz MC (1998) Zinc and copper concentrations in serum from Spanish women during pregnancy. Biol Trace Elem Res 61:61–70CrossRefPubMedGoogle Scholar
  35. 35.
    Ajose AO, Fasubaa B, Anetor JI, Adelekan DA, Makinde NO (2001) Serum zinc and copper concentrations in Nigerian women with normal pregnancy. Nig Postgrad Med J 8:161–164Google Scholar
  36. 36.
    Arnaud J, Prual A, Preoziosi P, Cherouvener F, Favier A, Galan P, Hercberg S (1993) Effect of iron supplementation during pregnancy on trace elements (Cu, Se, Zn) concentrations in serum and breast milk from Nigerian women. Ann Nutr Metab 37:262–271CrossRefPubMedGoogle Scholar
  37. 37.
    Poskitt EME (1988) Nutrition in pregnancy and its effect on the fetus. In: Practical paediatric nutrition. Butterworths, London, pp 15–23Google Scholar
  38. 38.
    Anetor JI, Adelaja O, Adekunle AO (2003) Serum micronutrient levels, nucleic acid metabolism and antioxidant defences in pregnant Nigerians: implications for fetal and maternal health. Afr J Med Sci 32:257–262Google Scholar
  39. 39.
    Kimberly O, O’Brien O, Nelly Z, Laura EC, Jianping W, Steven AB (2002) Prenatal iron supplements impair zinc absorption in pregnant Peruvian Women. J Nutr 130:2251–2255Google Scholar
  40. 40.
    WHO (World Health Organization) (2002) The World Health Report 2002: reducing risks promoting healthy life. Geneva, SwitzerlandGoogle Scholar
  41. 41.
    Lee SH, Lancey R, Montaser A, Madani N, Linder MC (1993) Caeruloplasmin and copper transport during the latter part of gestation in the rat. Proc Soc Exp Biol Med 203:428–439PubMedGoogle Scholar
  42. 42.
    Goldstein IM, Charo IF (1982) Ceruloplasmin: an acute phase reactant and antioxidant. Lymphokines 8:373–411Google Scholar
  43. 43.
    Osaki S, Johnson DA, Frieden E (1971) The mobilization of iron from the perfused mammalian liver by a serum copper enzyme, ferroxidase 1. J Biol Chem 246:3018–3023PubMedGoogle Scholar
  44. 44.
    Slater TF, Cheeseman KH, Davies MJ, Proudfoot K, Xin W (1987) Free radical mechanisms in relation to tissue injury. Proc Nutr Soc 46:1–12CrossRefPubMedGoogle Scholar
  45. 45.
    Sevanian A, Davies KJA, Hochstein P (1991) Serum urate as an antioxidant for ascorbic acid. Am J Clin Nutr 54:1129s–1134sPubMedGoogle Scholar
  46. 46.
    Anetor JI, Yaqub SA, Anetor GO, Nsonwu AC, Adeniyi FAA, Fukushima S (2009) Mixed chemical-induced oxidative stress in occupational exposure in Nigerians. Afr J Biotech 8:821–826Google Scholar
  47. 47.
    Simic MG, Jovanic SV (1989) Antioxidant mechanisms of uric acid. J Am Chem Soc 111:5778–5782CrossRefGoogle Scholar
  48. 48.
    Paolo DM, Michael EM, Helmut S (1991) Antioxidant defense systems: the role of carotenoids, tocopherols and thiols. Am J Clin Nutr 53:194–200Google Scholar
  49. 49.
    Young IS, Woodside JV (2001) Antioxidants in health and disease. J Clin Path 54:176–186CrossRefPubMedGoogle Scholar
  50. 50.
    Smith FI (2000) Micronutrient intervention: option for Africa. In: JB Vincent (ed) Recent advances in Nutritional Science 130:715–718Google Scholar

Copyright information

© Humana Press Inc. 2009

Authors and Affiliations

  • J. I. Anetor
    • 1
    • 4
  • O. A. Ajose
    • 2
  • F. N. Adeleke
    • 1
  • G. O. Olaniyan-Taylor
    • 1
  • F. A. Fasola
    • 3
  1. 1.Department of Chemical Pathology, College of MedicineUniversity of IbadanIbadanNigeria
  2. 2.Department of Chemical Pathology, College of Health SciencesObafemi Awolowo UniversityIle-IfeNigeria
  3. 3.Department of Haematology, College of MedicineUniversity of IbadanIbadanNigeria
  4. 4.Department of Chemical Pathology, School of Clinical Medicine, College of Health SciencesIgbinedion UniversityOkadaNigeria

Personalised recommendations