Iron, anemia and erythrocytosis in pregnant women at highlands: risks in mothers and newborns
DOI:
https://doi.org/10.31403/rpgo.v58i50Abstract
Iron is essential for health but in excess may be harmful. The living organism has ability to store and re-use the iron body and as such its requirement is small (1-2 mg absorbed/day). Hepcidin, a hormone produced in the liver, has an important role in iron homeostasis by blocking the iron transport protein and inhibiting iron absorption. Maternal anemia due to iron deficiency is a public health problem when it is moderate (7-<9 g/dL) and severe (Hb<7 g/dL) since it increases the risk of maternal and neonatal morbi-mortality. Similarly, high levels of hemoglobin during pregnancy affect the mother and newborn. In Peru, there is a National Program to supplement with iron to all pregnant women anemic or not. Scientific evidence shows that hemoglobin values between 9-10.5 g/dL are optimal for best fetal growth and that treatment with iron supplementation to non anemic women increases levels of hemoglobin, oxidative stress, and has adverse effects on the newborn. Since many populations at highlands have increased hemoglobin levels, it has been suggested to correct hemoglobin cutoff to define anemia. Several studies have demonstrated that it would not be necessary to change this cut-off as defined for population at sea level. In conclusion, studies results do not support the need for generalized iron supplementation to all pregnant women. Iron supplementation to pregnant women at high altitude should be avoided if diagnosis of anemia is not clearly demonstrated. It is recommended for each altitudinal population determining the level of anemia and body iron status before deciding to treat with iron supplements.
Key words: Maternal anemia, maternal erythrocytosis, hepcidin, altitude, iron.
Downloads
References
Ayoya MA, Bendech MA, Zagré NM, Tchibindat F. Maternal anaemia in West and Central Africa: time for urgent action. Public Health Nutr. 2012;15:916-27.
Ugwuja EI, Akubugwo EI, Ibiam UA, Obidoa O. Maternal sociodemographic parameters: impact on trace element status and pregnancy outcomes in Nigerian women. J Health Popul Nutr. 2011;29:156-62.
Lang E, Qadri SM, Lang F. Killing me softly – Suicidal erythrocyte death. Int J Biochem Cell Biol. 2012 Apr 27. [Epub ahead of print]
World Health Organization. 11 Prevalence of anaemia in women. En: Reproductive Health Indicators. Guidelines for their generation, interpretation and analysis for global monitoring. WHO: France. 2006:41-3.
Gonzales GF, Tapia V, Gasco M, Carrillo CE. Hemoglobina materna en el Perú: Diferencias Regionales y Efectos perinatales. Rev Per Med Exp Salud Publica 2011;28:484-91.
Brabin BJ, Hakimi M, Pelletier D. An analysis of anemia and pregnancy-related maternal mortality. J Nutr. 2001;131(2S-2):604S-14S; discussion 614S-5S.
Mamun AA, Padmadas SS, Khatun M. Maternal health during pregnancy and perinatal mortality in Bangladesh: evidence from a large-scale community-based clinical trial. Paediatr Perinat Epidemiol. 2006;20:482-90.
Gonzales GF, Tapia V, Gasco M, Carrillo CE, Fort A. Association of hemoglobin values at first booking with
adverse maternal outcomes, in populations living at different altitudes (0-4500 m). Int J Obstet Gynecol. 2012;117:134-9.
Huma N, Salim UR, Anjum FM, Murtaza MA, Sheik MA. Food fortification strategy-preventing iron deficiency
anemia: a review. Crit Rev Food Sci Nutr. 2007;47:259- 65.
Reveiz L, Gyte GM, Cuervo LG, Casasbuenas A. Treatments for iron-deficiency anaemia in pregnancy.Cochrane Database Syst Rev. 2011;(10):CD003094.
Picciano MF. Pregnancy and lactation: physiological adjustments, nutritional requeriments and the role of dietary supplements. J Nutr. 2003;133:1997S-2002S.
Chelchowska M, Laskowska-Klita T, Leibschang J. Concentration of ferritin, transferrin and iron as a markers of iron deficiency in healthy women in reproductive age. Pol Merkur Lekarski. 2007;22:25-7.
Kubik P, Leibschang J, Kowalska B, Laskowska-Klita T, Stanisławska A, Chełchowska M, Maciejewski T. [Evaluation of iron balance in healthy pregnant women and their newborns].[Article in Polish] Ginekol Pol. 2010;81:358-63.
Gautam CS, Saha L, Sekhri K, Saha PK. Iron deficiency in pregnancy and the rationality of iron supplements prescribed during pregnancy. Medscape J Med. 2008;10:283.
Mukherji J. Iron deficiency anemia in pregnancy. Rational Drug Bull. 2002;12:2–5.
Wiegerinck MM, Mol BW. [Insufficient evidence supporting iron supplementation in anaemia during pregnancy][Article in Dutch]. Ned Tijdschr Geneeskd. 2012;156:A4293.
Gernand AD, Christian P, Schulze KJ, Shaikh S, Labrique AB, Shamim AA, West KP Jr. Maternal nutritional status in early pregnancy is associated with body water and plasma volume changes in a pregnancy cohort in rural bangladesh. J Nutr. 2012;142:1109-15.
Beentjes M, Jans S. [Revised practice guideline 'Anaemia in midwifery practice']. [Article in Dutch]. Ned Tijdschr Geneeskd. 2012;156:A3711.
Pavord S, Myers B, Robinson S, Allard S, Strong J, Oppenheimer C; British Committee for Standards in Haematology. UK guidelines on the management of iron deficiency in pregnancy. Br J Haematol. 2012;156:588-600.
Toxqui L, De Piero A, Courtois V, Bastida S, Sanchez-Muñiz FJ, Vaquero MP. Deficiencia y Sobrecarga de hierro; implicaciones en el estado oxidativo y la salud cardiovascular. Nutr Hosp. 2010;25:350-65.
Zaccone V, Gasbarrini G. [From iron accumulation to organ damage.][Article in Italian]. Minerva Med. 2012;103:123-40.
Reeves JT, Leon-Velarde F. Chronic mountain sickness: recent studies of the relationship between hemoglobin concentration and oxygen transport. High Alt Med Biol. 2004;5:147-55.
Xing Y, Yan H, Dang S, Zhuoma B, Zhou X, Wang D. Hemoglobin levels and anemia evaluation during pregnancy in the highlands of Tibet: a hospital-based study. BMC Public Health. 2009;9:336.
Muñoz M, Villar I, García-erce JA. An update on iron physiology. World J Gastroenterol. 2009;15:4617-26.
Salinas W, Valenzuela R, Valdivia SS, Blitchtein D, Flores ME, Lino J, Cuevas C, Munayco C, Sachún M, Campos J. Lineamientos de gestión de la estrategia sanitaria de alimentación y nutrición saludable. Lima: Ministerio de Salud, Instituto Nacional de Salud. 2011:54 p.
Anderson GJ, Wang F. Essential but toxic: Controlling the flux of iron in the body. Clin Exp Pharmacol Physiol. 2011;doi: 10.1111/j.1440-1681.2011.05661.x. [Epub ahead of print]
Ganz T, Nemeth E. Iron metabolism: interactions with normal and disordered erythropoiesis. Cold Spring Harb Perspect Med. 2012;2:a011668.
Chifman J, Kniss A, Neupane P, Williams I, Leung B, Deng Z, Mendes P, Hower V, Torti FM, Akman SA, Torti SV, Laubenbacher R. The core control system of intracellular iron homeostasis: a mathematical model. J
Theor Biol. 2012;300:91-9.
Fleming RE, Ponka P. Iron overload in human disease. New Eng J Med. 2012;366:348-59.
Ganz T, Nemeth E. Interactions with normal and disordered erythropoiesis. Cold Spring Harb Perspect Med. 2012;2:a011668
Pasricha SR. Is it time for hepcidin to join the diagnostic toolkit for iron deficiency? Expert Rev Hematol. 2012;5:153-5.
Ganz T, Nemeth E. Hepcidin and iron homeostasis. Biochem Biophys Acta. 2012a [Epub ahead of print]
Nemeth E, Ganz T. The role of hepcidin in iron metabolism. Acta Haematol. 2009;122:78-86.
Young MF, Griffin I, Pressman E, McIntyre AW, Cooper E, McNanley T, Harris ZL, Westerman M, O'Brien KO. Maternal hepcidin is associated with placental transfer of iron derived from dietary heme and nonheme sources. J Nutr. 2012;142:33-9.
Rehu M, Punnonen K, Ostland V, Heinonen S, Westerman M, Pulkki K, Sankilampi U. Maternal serum hepcidin is low at term and independent of cord blood iron status. Eur J Haematol. 2010;85:345-52.
Berglund S, Lönnerdal B, Westrup B, Domellöf M. Effects of iron supplementation on serum hepcidin and
serum erythropoietin in low-birth-weight infants. Am J Clin Nutr. 2011;94:1553-61.
Coyne DW. Hepcidin: clinical utility as a diagnostic tool and therapeutic target. Kidney Int. 2011;80:240-4.
Zhang DL, Senecal T, Ghosh MC, Ollivierre-Wilson H, Tu T, Rouault TA. Hepcidin regulates ferroportin expression and intracellular iron homeostasis of erythroblasts. Blood. 2011;118:2868-77
Piperno A, Galimberti S, Mariani R, Pelucchi S, Ravasi G, Lombardi C, Bilo G, Revera M, Giuliano A, Faini A, Mainini V, Westerman M, Ganz T, Valsecchi MG, Mancia G, Parati G; HIGHCARE investigators Modulation of hepcidin production during hypoxia-induced erythropoiesis in humans in vivo: data from the HIGHCARE project. Blood. 2011;117:2953-9.
Talbot NP, Lakhal S, Smith TG, Privat C, Nickol AH, Rivera-Ch M, León-Velarde F, Dorrington KL, Mole DR, Robbins PA. Regulation of hepcidin expression at high altitude. Blood. 2012;119:857-60.
Hintze KJ, McClung JP. Hepcidin: a critical regulator of iron metabolism during hypoxia. Adv Hematol. 2011;2011:510304.
Gonzales GF. [Hemoglobin and testosterone: importance on high altitude acclimatization and adaptation].
Rev Peru Med Exp Salud Publica. 2011;28:92-100.
Bachman E, Feng R, Travison T, Li M, Olbina G, Ostland V, Ulloor J, Zhang A, Basaria S, Ganz T, Westerman M, Bhasin S. Testosterone suppresses hepcidin in men: a potential mechanism for testosterone-induced erythrocytosis. J Clin Endocrinol Metab. 2010;95:4743-7.
Yamamoto H, Tsubakihara Y. Limiting iron supplementation for anemia in dialysis patients-the basis for Japan's conservative guidelines. Semin Dial. 2011;24:269-71.
de Pee S, Spiegel P, Kraemer K, Wilkinson C, Bilukha O, Seal A, Macias K, Oman A, Fall AB, Yip R, West K, Zlotkin S, Bloem MW. Assessing the impact of micronutrient intervention programs implemented under special circumstances--meeting report. Food Nutr Bull. 2011;32:256-63.
Palacios S. The management of iron deficiency in menometrorrhagia. Gynecol Endocrinol. 2011;27 Suppl
:1126-30.
Senga EL, Harper G, Koshy G, Kazembe PN, Brabin BJ. Reduced risk for placental malaria in iron deficient women. Malar J. 2011;10:47.
Chełchowska M, Lewandowski L, Ambroszkiewicz J, Swiatek E, Gajewska J, Ołtarzewski M, Laskowska-Klita T. [The effect of tobacco smoking during pregnancy on concentration of pro-hepcidin and some parameters of iron metabolism in matched-maternal cord pairs].[Article in Polish]. Przegl Lek. 2008;65:474-8.
Walsh T, O'Broin SD, Cooley S, Donnelly J, Kennedy J, Harrison RF, McMahon C, Geary M. Laboratory assessment of iron status in pregnancy. Clin Chem Lab Med. 2011;49:1225-30.
Yang Z, Dewey KG, Lönnerdal B, Hernell O, Chaparro C, Adu-Afarwuah S, McLean ED, Cohen RJ, Domellöf M, Allen LH, Brown KH. Comparison of plasma ferritin concentration with the ratio of plasma transferrin receptor to ferritin in estimating body iron stores: results of 4 intervention trials. Am J Clin Nutr. 2008;87:1892-8.
Moore LG. Human genetic adaptation to high altitude. High Alt Med Biol. 2001;2:257-9.
WHO/NHD. Iron Deficiency Anaemia: Assessment, Prevention and Control. A Guide for Programme Managers. 2001:99.
Hurtado A, Merino C, Delgado E. Influence of anoxemia on the hemopoietic activity. Arch Int Med. 1945;75:284–323.
Yepez R, Estevez E, Galan P, Chauliac M, Davila M, Calle A, Estrella R, Masse-Raimbault AM, Hercberg S. [High altitude anemia: validity of definition criteria] Sante.1994;4:9-13. [Article in French]
Berger J, Aguayo VM, San Miguel JL, Lujan C, Tellez W, Traissac P. Definition and prevalence of anemia in Bolivian women of childbearing age living at high altitudes: the effect of iron-folate supplementation. Nutr Rev. 1997;55:247–56.
U.S. Centers for Disease Control and Prevention. Recommendations to prevent and control iron deficiency in the United States. MMWR. 1998;47(RR-3):1–36.
Dirren H, Logman MHGM, Barclay DV, Freire WB. Altitude correction for hemoglobin. Eur J Clin Nutr. 1994;48:625–32.
Dallman PR, Siimes MA, Steckel A. Iron deficiency in infancy and childhood. Am J Clin Nutr. 1980;33:86–118.
CDC: Altitude hemoglobin curve and CDC anemia criteria which uses the altitude adjustment. Atlanta: Centers for Disease Control and Prevention; 1995.
Cohen JH, Haas JD. Hemoglobin correction factors for estimating the prevalence of iron deficiency anemia in pregnant women residing at high altitudes in Bolivia. Rev Panam Salud Pública. 1999;6:392-9.
Cook JD, Boy E, Flowers C, Droca M del C. The influence of high-altitude living on body iron. Blood. 2005;106:1441-6.
Reynafarje Hurtado C. Iron metabolism during pregnancy at high altitudes. Arch Biol Med Exp. 1987;20:31-7.
Wu T, Kayser B. High altitude adaptation in Tibetans. High Alt Med Biol. 2006;7:193-208.
Wu T, Wang X, Wei C, Cheng H, Wang X, Li Y, Dong G, Zhao H, Young P, Li G, Wang Z. Hemoglobin levels in Qinghai-Tibet: different effects of gender for Tibetans vs Han. J Appl Physiol. 2005;98:598-604.
Kolsteren P, van der Stuyft P. Diagnosis of anemia at high altitude: problems encountered in Tibet. Ann Soc Belg Med Trop. 1994;74:317-22.
Dang SN, Yan H, Wang XL. Study on the hemoglobin levels of children under the age of three years and the prevalence of anemia at high altitude. Zhonghua Liu Xing Bing Xue Za Zhi. 2003;24:1108-11.
Casanueva E, Viteri FE, Mares-Galindo M, Meza-Camacho C, Loría A, Schnaas L, Valdés-Ramos R. Weekly iron as a safe alternative to daily supplementation for nonanemic pregnant women. Arch Med Res. 2006;37:674-82.
Scanlon KS, Yip R, Schieve LA, Cogswell ME. High and low hemoglobin levels during pregnancy: differential risks for preterm birth and small for gestational age. Obstet Gynecol. 2000;96:741-8.
Gonzales GF. Diferencias en la detección de anemia en la altura según la Organización Mundial de la Salud. Rev Per Med Exp Salud Publica. 2012b;29:158 (Carta al Editor).
Facchini FS, Carantoni M, Jeppesen J, Reaven GM. Hematocrit and hemoglobin are independently related to insulin resistance and compensatory hyperinsulinemia in healthy, non-obese men and women. Metabolism.
;47:831-5.
Barbieri M, Ragno E, Benvenuti E, Zito GA, Corssi A, Ferrucci L, Paolisso G. New aspects of the insulin resistance syndrome: impact on haematological parameters. Diabetologia. 2001; 44:1232-37.
Choi KM, Lee J, Kim YH, Kim KB, Kim DL, Kim SG, Shin DH, Kim NH, Park IB, Choi DS, Baik SH. Koreans-Southwest Seoul (SWS) Study. Relation between insulin resistance and hematological parameters in elderly. Diabetes Res Clin Pract. 2003;60:205-12.
Yilmaz MI, Sonmez A, Saglam M, Gulec M, Kilic S, Eyileten T, Caglar K, Oguz Y, Vural A. Yenicesu M, Zoccali C. Hemoglobin is inversely related to flow-mediated dilatation in chronic kidney disease. Kidney Int. 2009;75:1316-21.
Julian CG, Wilson MJ, Lopez M, Yamashiro H, Tellez W, Rodriguez A, Bigham AW, Shriver MD, Rodriguez C, Vargas E, Moore LG. Augmented uterine artery blood flow and oxygen delivery protect Andeans from altitude-associated reductions in fetal growth. Am J Physiol Regul Integr Comp Physiol. 2009;296:R1564-75.
Meyer C, Heiss C, Drexhage C, Kehmeier ES, Balzer J, Mühlfeld A, Merx MW, Lauer T, Kühl H, Floege J, Kelm M, Rassaf T. Hemodialysis-induced release of hemoglobin limits nitric oxide bioavailability and impairs vascular function. J Am Coll Cardiol. 2010;55:454-9
Clement FM, Klarenbach S, Tonelli M, Johnson JA, Manns BJ. The impact of selecting a high hemoglobin
target level on health-related quality of life for patients with chronic kidney disease: a systematic review and
meta-analysis. Arch Intern Med. 2009;169:1104-12.
Bilgi M, Güllü H, Kozanoğlu I, Ozdoğu H, Sezgin N, Sezgin AT, Altay H, Erol T, Müderrisoğlu H. Evaluation of blood rheology in patients with coronary slow flow or non-obstructive coronary artery disease. Clin Hemorheol Microcirc. 2012 Apr 13. [Epub ahead of print]
Beall CM, Laskowski D, Erzurum SC. Nitric oxide in adaptation to altitude. Free Radic Biol Med. 2012;52:1123-34.
Okumiya K, Sakamoto R, Kimura Y, Ishine M, Kosaka Y, Wada T, Wada C, Nakatsuka M, Ishimoto Y, Hirosaki M, Kasahara Y, Konno A, Chen W, Fujisawa M, Otsuka K, Nakashima M, Wang H, Dai Q, Yang A, Qiao H, Gao J, Li Z, Zhang Y, Ge RL, Matsubayashi K. Comprehensive geriatric assessment of elderly highlanders in Qinghai, China II: the association of polycythemia with lifestylerelated diseases among the three ethnicities. Geriatr Gerontol Int. 2009;9:342-51.
Gonzales GF, Tapia V. Asociación de los diferentes niveles de hipoxemia en la altura con el perfil lipídico
y la glicemia en varones y mujeres a 4,100 m en los Andes centrales del Perú. Endocrinología & Nutrición. 2012.
Huisman A, Aarnoudse JG. Increased 2nd trimester hemoglobin concentration in pregnancies later complicated by hypertension and growth retardation. Early evidence of a reduced plasma volume. Acta Obstet Gynecol Scand. 1986;65:605-8.
Murphy JF, O’Riordan J, Newcombe RG, Coles EC, Pearson JF. Relation of haemoglobin levels in first and
second trimesters to outcome of pregnancy. Lancet. 1986;i:992-5
Stephansson O, Dickman PW, Johansson A, Cnattingius S. Maternal hemoglobin concentration during pregnancy and risk of stillbirth. JAMA. 2000;284:2611-7.
Tomashek KM, Ananth CV, Cogswell ME. Risk of stillbirth in relation to maternal hemoglobin concentration
during pregnancy. Matern Child Nutr. 2006;2:19-28.
Gonzales GF, Tapia V, Gasco M, Carrillo CE. Maternal hemoglobin concentration and adverse pregnancy outcomes at low and moderate altitudes in Peru. J Matern Fetal Neon Med. 2012b;
Gonzales GF, Steenland K, Tapia V. Maternal hemoglobin level and fetal outcome at low and high altitudes. Am J Physiol Regul Integr Comp Physiol. 2009;297(5):R1477-85
Phaloprakarn C, Tangjitgamol S. Impact of high maternal hemoglobin at first antenatal visit on pregnancy outcomes: a cohort study. J Perinat Med. 2008;36:115-9.
Anim-Nyame N, Sooranna SR, Johnson MR, Gamble J, Sterr PJ. Resting peripheral blood flow in normal pregnancy and in pre-eclampsia. Clin Sci (Lond). 2000;99:505-10.
Steer PJ. Maternal hemoglobin concentration and birth weight. Am J Clin Nutr. 2000;71(5Suppl):1285S-7S.
Gonzales GF, Tapia V, Fort AL. Maternal and perinatal outcomes in second hemoglobin measurement in nonanemic women at first booking: Effect of altitude of residence in Peru. ISRN Obstet Gynecol. 2012d;2012:368571.
Kozuki N, Lee AC, Katz J. Moderate to severe, but not mild, maternal anemia is associated with increased
risk of small-for-gestational-age outcomes. J Nutr. 2012;142:358-62.
Viteri FE, Casanueva E, Tolentino MC, Díaz-Francés J, Erazo AB. Antenatal iron supplements consumed daily produce oxidative stress in contrast to weekly supplementation in Mexican non-anemic women. Reprod Toxicol. 2012;34:125-32.
Ziaei S, Norrozi M, Faghihzadeh S, Jafarbegloo E. A randomized placebo-controlled trial to determine the effect of iron supplementation on pregnancy outcome in pregnant women with haemoglobin > or = 13.2 g/dl. BJOG. 2007;114:684-8
Downloads
Published
How to Cite
Issue
Section
License
Esta revista provee acceso libre inmediato a su contenido bajo el principio de que hacer disponible gratuitamente la investigación al publico, lo cual fomenta un mayor intercambio de conocimiento global.
