1932

Abstract

Iron deficiency is the most common micronutrient deficiency in the world and disproportionately affects pregnant women and young children. Iron deficiency has negative effects on pregnancy outcomes in women and on immune function and neurodevelopment in children. Iron supplementation programs have been successful in reducing this health burden. However, iron supplementation of iron-sufficient individuals is likely not necessary and may carry health risks for iron-sufficient and potentially some iron-deficient populations. This review considers the physiology of iron as a nutrient and how this physiology informs decision-making about weighing the benefits and risks of iron supplementation in iron-deficient, iron-sufficient, and iron-overloaded pregnant women and children.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-nutr-082018-124213
2019-08-21
2024-04-18
Loading full text...

Full text loading...

/deliver/fulltext/nutr/39/1/annurev-nutr-082018-124213.html?itemId=/content/journals/10.1146/annurev-nutr-082018-124213&mimeType=html&fmt=ahah

Literature Cited

  1. 1.
    Akman M, Cebeci D, Okur V, Angin H, Abali O, Akman AC 2004. The effects of iron deficiency on infants’ developmental test performance. Acta Paediatr 93:1391–96
    [Google Scholar]
  2. 2.
    Am. Acad. Pediatr. 1999. Iron fortification of infant formulas. Pediatrics 104:119–23
    [Google Scholar]
  3. 3.
    Amin SB, Orlando M, Eddins A, MacDonald M, Monczynski C, Wang H 2010. In utero iron status and auditory neural maturation in premature infants as evaluated by auditory brainstem response. J. Pediatr. 156:377–81
    [Google Scholar]
  4. 4.
    Ashorn P, Hallamaa L, Allen LH, Ashorn U, Chandrasiri U et al. 2018. Co-causation of reduced newborn size by maternal undernutrition, infections, and inflammation. Matern. Child Nutr. 14:3e12585
    [Google Scholar]
  5. 5.
    Bah A, Pasricha SR, Jallow MW, Sise EA, Wegmuller R et al. 2017. Serum hepcidin concentrations decline during pregnancy and may identify iron deficiency: analysis of a longitudinal pregnancy cohort in the Gambia. J. Nutr. 147:1131–37
    [Google Scholar]
  6. 6.
    Baker RD, Greer FR Comm. Nutr. Am. Acad. Pediatr 2010. Diagnosis and prevention of iron deficiency and iron-deficiency anemia in infants and young children (0–3 years of age). 1261040–50
  7. 7.
    Bastian TW, von Hohenberg WC, Mickelson DJ, Lanier LM, Georgieff MK 2016. Iron deficiency impairs developing hippocampal neuron gene expression, energy metabolism and dendrite complexity. Dev. Neurosci. 38:264–76
    [Google Scholar]
  8. 8.
    Beard JL. 2001. Iron biology in immune function, muscle metabolism and neuronal functioning. J. Nutr. 131:568S–79S
    [Google Scholar]
  9. 9.
    Beard JL, Erikson KM, Jones BC 2003. Neonatal iron deficiency results in irreversible changes in dopamine function in rats. J. Nutr. 133:1174–79
    [Google Scholar]
  10. 10.
    Berglund SK, Chmielewska A, Starnberg J, Westrup B, Hägglöf B et al. 2018. Effects of iron supplementation of low-birth-weight infants on cognition and behavior at 7 years: a randomized controlled trial. Pediatr. Res. 83:111–18
    [Google Scholar]
  11. 11.
    Berglund SK, Westrup B, Hägglöf B, Hernell O, Domellöf M 2013. Effects of iron supplementation of LBW infants on cognition and behavior at 3 years. Pediatrics 131:47–55
    [Google Scholar]
  12. 12.
    Black MM, Baqui AH, Zaman K, Ake Persson L, El Arifeen S et al. 2004. Iron and zinc supplementation promote motor development and exploratory behavior among Bangladeshi infants. Am. J. Clin. Nutr. 80:903–10
    [Google Scholar]
  13. 13.
    Bradley CK, Hillman L, Sherman AR, Leedy D, Cordano A 1993. Evaluation of two iron-fortified, milk-based formulas during infancy. Pediatrics 91:908–14
    [Google Scholar]
  14. 14.
    Braekke K, Bechensteen AG, Halvorsen BL, Blomhoff R, Haaland K, Staff AC 2007. Oxidative stress markers and antioxidant status after oral iron supplementation to very low birth weight infants. J. Pediatr. 151:23–28
    [Google Scholar]
  15. 15.
    Brittenham GM, Andersson M, Egli I, Foman JT, Zeder C et al. 2014. Circulating non-transferrin-bound iron after oral administration of supplemental and fortification doses of iron to healthy women: a randomized study. Am. J. Clin. Nutr. 100:813–20
    [Google Scholar]
  16. 16.
    Brunette KE, Tran PV, Wobken JD, Carlson ES, Georgieff MK 2010. Gestational and neonatal iron deficiency alters apical dendrite structure of CA1 pyramidal neurons in adult rat hippocampus. Dev. Neurosci. 32:238–48
    [Google Scholar]
  17. 17.
    Cao C, O'Brien KO. 2013. Pregnancy and iron homeostasis: an update. Nutr. Rev. 71:35–51
    [Google Scholar]
  18. 18.
    Chang SC, O'Brien KO, Nathanson MS, Mancini J, Witter FR 2003. Hemoglobin concentrations influence birth outcomes in pregnant African-American adolescents. J. Nutr. 133:2348–55
    [Google Scholar]
  19. 19.
    Chockalingam UM, Murphy E, Ophoven JC, Weisdorf SA, Georgieff MK 1987. Cord transferrin and ferritin levels in newborn infants at risk for prenatal uteroplacental insufficiency and chronic hypoxia. J. Pediatr. 111:283–86
    [Google Scholar]
  20. 20.
    Christian P, Morgan ME, Murray-Kolb L, LeClerq SE, Khatry SK et al. 2011. Preschool iron–folic acid and zinc supplementation in children exposed to iron–folic acid in utero confers no added cognitive benefit in early school-age. J. Nutr. 141:2042–48
    [Google Scholar]
  21. 21.
    Christian P, Murray-Kob LE, Khatry SK, Katz J, Schaefer BA et al. 2010. Prenatal micronutrient supplementation and intellectual and motor function in early school-aged children in Nepal. JAMA 304:2716–23
    [Google Scholar]
  22. 22.
    Clark MA, Goheen MM, Fulford A, Prentice AM, Elnagheeb MA et al. 2014. Host iron status and iron supplementation mediate susceptibility to erythrocytic stage Plasmodium falciparum. Nat. Commun 5:4446
    [Google Scholar]
  23. 23.
    Clark KM, Li M, Zhu B, Liang F, Shao J et al. 2017. Breastfeeding, mixed, or formula feeding at 9 months of age and the prevalence of iron deficiency and iron deficiency anemia in two cohorts in China. J. Pediatr. 181:56–61
    [Google Scholar]
  24. 24.
    Combs GF, Trumbo PR, McKinley MC, Milner J, Studenski S et al. 2013. Biomarkers in nutrition: new frontiers in research and application. Ann. N. Y. Acad. Sci. 1278:1–10
    [Google Scholar]
  25. 25.
    Connor JR, Menzies SL. 1996. Relationship of iron to oligodendrocytes and myelination. Glia 17:83–93
    [Google Scholar]
  26. 26.
    Cusick SE, Georgieff MK. 2016. The role of nutrition in brain development: the golden opportunity of the “first 1000 days.”. J. Pediatr. 175:16–21
    [Google Scholar]
  27. 27.
    Cusick SE, Opoka RO, Abrams SA, John CC, Georgieff MK, Mupere E 2016. Delaying iron therapy until 28 days after antimalarial treatment is associated with greater iron incorporation and equivalent hematologic recovery after 56 days in children: a randomized controlled trial. J. Nutr. 146:1769–74
    [Google Scholar]
  28. 28.
    Delpisheh A, Brabin L, Drummond S, Brabin BJ 2008. Prenatal smoking exposure and asymmetric fetal growth restriction. Ann. Hum. Biol. 35:573–83
    [Google Scholar]
  29. 29.
    Dewey KG, Domellöf M, Cohen RJ, Landa Rivera L, Hernell O, Lönnerdal B 2002. Iron supplementation affects growth and morbidity of breast-fed infants: results of a randomized trial in Sweden and Honduras. J. Nutr. 132:3249–55
    [Google Scholar]
  30. 30.
    Dewey KG, Oaks BM. 2017. U-shaped curve for risk associated with maternal hemoglobin, iron status, or iron supplementation. Am. J. Clin. Nutr. 106:Suppl.1694S–702S
    [Google Scholar]
  31. 31.
    Domellöf M, Cohen RJ, Dewey KG, Hernell O, Landa Rivera L, Lönnerdal B 2001. Iron supplementation of breast-fed Honduran and Swedish infants from 4 to 9 months of age. J. Pediatr. 138:679–87
    [Google Scholar]
  32. 32.
    Domellöf M, Georgieff MK. 2015. Postdischarge iron requirements of the preterm infant. J. Pediatr. 167:Suppl.S31–35
    [Google Scholar]
  33. 33.
    Domellöf M, Hernell O, Abrams SA, Chen Z, Lönnerdal B 2009. Iron supplementation does not affect copper and zinc absorption in breastfed infants. Am. J. Clin. Nutr. 89:185–90
    [Google Scholar]
  34. 34.
    EFSA Panel Diet. Prod. Nutr. Allerg 2015. Scientific opinion on dietary reference values for iron. EFSA J. 13:4254
    [Google Scholar]
  35. 35.
    Ehrenkranz RA, Gettner PA, Nelli CM, Sherwonit EA, Williams JE et al. 1992. Iron absorption and incorporation into red blood cells by very low birth weight infants: studies with the stable isotope 58Fe. J. Pediatr. Gastroenterol. Nutr. 15:270–78
    [Google Scholar]
  36. 36.
    Esamai F, Liechty E, Ikemeri J, Westcott J, Kemp J et al. 2014. Zinc absorption from micronutrient powder is low but is not affected by iron in Kenyan infants. Nutrients 6:5636–51
    [Google Scholar]
  37. 37.
    Etheredge AJ, Premji Z, Gunaratna NS, Abioye AI, Aboud S et al. 2015. Iron supplementation in iron-replete and nonanemic pregnant women in Tanzania: a randomized clinical trial. JAMA Pediatr 169:947–55
    [Google Scholar]
  38. 38.
    Finkelstein JL, O'Brien KO, Abrams SA, Zavaleta N 2013. Infant iron status affects iron absorption in Peruvian breastfed infants at 2 and 5 months of age. Am. J. Clin. Nutr. 98:1475–84
    [Google Scholar]
  39. 39.
    Fisher A, Nemeth A. 2017. Iron homeostasis during pregnancy. Am. J. Clin. Nutr. 106:Suppl.1567S–74S
    [Google Scholar]
  40. 40.
    Franz AR, Mihatsch WA, Sander S, Kron M, Pohlandt F 2000. Prospective randomized trial of early versus late enteral iron supplementation in infants with a birth weight of less than 1301 grams. Pediatrics 106:700–6
    [Google Scholar]
  41. 41.
    Fretham SJB, Carlson ES, Wobken J, Tran PV, Petryk A, Georgieff MK 2012. Temporal manipulation of transferrin-receptor-1-dependent iron uptake identifies a sensitive period in mouse hippocampal neurodevelopment. Hippocampus 22:1691–1702
    [Google Scholar]
  42. 42.
    Friel JK, Aziz K, Andrews WL, Harding SV, Courage ML, Adams RJ 2003. A double-masked, randomized control trial of iron supplementation in early infancy in healthy term breast-fed infants. J. Pediatr. 143:582–86
    [Google Scholar]
  43. 43.
    Gahagan S, Yu S, Kaciroti N, Castillo M, Lozoff B 2009. Linear and ponderal growth trajectories in well-nourished, iron-sufficient infants are unimpaired by iron supplementation. J. Nutr. 139:2106–12
    [Google Scholar]
  44. 44.
    Ganz T, Nemeth E. 2012. Hepcidin and iron homeostasis. Biochim. Biophys. Acta 1823:1434–43
    [Google Scholar]
  45. 45.
    Geng F, Mai X, Zhan J, Xu L, Zhao Z et al. 2015. Impact of fetal–neonatal iron deficiency on recognition memory at 2 months of age. J. Pediatr. 167:1226–32
    [Google Scholar]
  46. 46.
    Georgieff MK. 2017. Iron assessment to protect the developing brain. Am. J. Clin. Nutr. 106:Suppl. 61588S–93S
    [Google Scholar]
  47. 47.
    Georgieff MK, Landon MB, Mills MM, Hedlund BE, Faassen AE et al. 1990. Abnormal iron distribution in infants of diabetic mothers: spectrum and maternal antecedents. J. Pediatr. 117:455–61
    [Google Scholar]
  48. 48.
    Georgieff MK, Schmidt RL, Mills MM, Radmer WJ, Widness JA 1992. Fetal iron and cytochrome c status after intrauterine hypoxemia and erythropoietin administration. Am. J. Physiol. 262:R485–91
    [Google Scholar]
  49. 49.
    Goheen MM, Bah A, Wegmüller R, Verhoef H, Darboe B et al. 2017. Host iron status and erythropoietic response to iron supplementation determines susceptibility to the RBC stage of falciparum malaria during pregnancy. Sci. Rep. 7:17674
    [Google Scholar]
  50. 50.
    Goldenberg RL, Tamura T, DuBard M, Johnston KE, Copper RL, Neggers Y 1996. Plasma ferritin and pregnancy outcome. Am. J. Obstet. Gynecol. 175:1356–59
    [Google Scholar]
  51. 51.
    Golub MS, Hogrefe CE, Malka R, Higgins JM 2014. Developmental plasticity of red blood cell homeostasis. Am. J. Hematol. 89:459–66
    [Google Scholar]
  52. 52.
    Gonzales GF, Steenland K, Tapia V 2009. Maternal hemoglobin level and fetal outcome at low and high altitudes. Am. J. Physiol. 297:R1477–85
    [Google Scholar]
  53. 53.
    Griffin I, Cooke RJ. 2010. Iron retention in preterm infants fed low iron intakes: a metabolic balance study. Early Hum. Dev. 86:Suppl. 149–53
    [Google Scholar]
  54. 54.
    Gupta PM, Hamner HC, Suchdev PS, Flores-Ayala R, Mei Z 2017. Iron status of toddlers, non-pregnant females and pregnant females in the United States. Am. J. Clin. Nutr. 106:Suppl. 61640S–46S
    [Google Scholar]
  55. 55.
    Gupta PM, Perrine CG, Mei Z, Scanlon KS 2016. Iron, anemia and iron deficiency anemia among young children in the United States. Nutrients 8:330
    [Google Scholar]
  56. 56.
    Hämäläinen H, Hakkarainen K, Heinonen S 2003. Anaemia in the first but not in the second or third trimester is a risk factor for low birth weight. Clin. Nutr. 22:271–75
    [Google Scholar]
  57. 57.
    Hasanbegović E, Sabanović S. 2004. [Effects of iron therapy on motor and mental development of infants and small children suffering from iron deficiency anaemia]. Med. Arh. 58:227–29 In Bosnian )
    [Google Scholar]
  58. 58.
    Haschke F, Ziegler EE, Edwards BB, Fomon SJ 1986. Effect of iron fortification of infant formula on trace mineral absorption. J. Pediatr. Gastroenterol. Nutr. 5:768–73
    [Google Scholar]
  59. 59.
    Hernell O, Fewtrell MS, Georgieff MK, Krebs NF, Lönnerdal B 2015. Summary of current recommendations on iron provision and monitoring of iron status for breastfed and formula-fed infants in resource-rich and resource-constrained countries. J. Pediatr. 167:Suppl.S40–47
    [Google Scholar]
  60. 60.
    Hernell O, Lönnerdal B. 2002. Iron status of infants fed low-iron formula: no effect of added bovine lactoferrin or nucleotides. Am. J. Clin. Nutr. 76:858–64
    [Google Scholar]
  61. 61.
    Hwang HS, Kim YH, Kwon JY, Park YW 2010. Uterine and umbilical artery Doppler velocimetry as a predictor for adverse pregnancy outcomes in pregnant women with anemia. J. Perinat. Med. 38:467–71
    [Google Scholar]
  62. 62.
    Idjradinata P, Pollitt E. 1993. Reversal of developmental delays in iron-deficient anaemic infants treated with iron. Lancet 341:1–4
    [Google Scholar]
  63. 63.
    Idjradinata P, Watkins WE, Pollitt E 1994. Adverse effect of iron supplementation on weight gain of iron-replete young children. Lancet 343:1252–54
    [Google Scholar]
  64. 64.
    Insel BJ, Schaefer CA, McKeague IW, Susser ES, Brown AS 2008. Maternal iron deficiency and the risk of schizophrenia in offspring. Arch. Gen. Psychiatry 65:1136–44
    [Google Scholar]
  65. 65.
    Jaramillo EG, Mupere E, Opoka RO, Hodges JS, Lund TC et al. 2017. Delaying the start of iron until 28 days after antimalarial treatment is associated with lower incidence of subsequent illness in children with malaria and iron deficiency. PLOS ONE 12:e0183977
    [Google Scholar]
  66. 66.
    Kabyemela ER, Fried M, Kurtis JD, Mutabingwa TK, Duffy PE 2008. Decreased susceptibility to Plasmodium falciparum infection in pregnant women with iron deficiency. J. Infect. Dis. 198:163–66
    [Google Scholar]
  67. 67.
    Kennedy BC, Dimova JG, Siddappa AJM, Tran PV, Gewirtz JC, Georgieff MK 2014. Prenatal choline supplementation ameliorates the long-term neurobehavioral effects of fetal–neonatal iron deficiency in rats. J. Nutr. 144:1858–65
    [Google Scholar]
  68. 68.
    Kleinman RE. 2015. Expert recommendations on iron fortification in infants. J. Pediatr. 167:Suppl.S48–49
    [Google Scholar]
  69. 69.
    Kortman GA, Raffatellu M, Swinkels DW, Tjalsma H 2014. Nutritional iron turned inside out: intestinal stress from a gut microbial perspective. FEMS Microbiol. Rev. 38:1202–1234
    [Google Scholar]
  70. 70.
    Krebs NF, Domellöf M, Ziegler E 2015. Balancing benefits and risks of iron supplementation in resource-rich countries. J. Pediatr. 167:Suppl.S20–25
    [Google Scholar]
  71. 71.
    Krebs NF, Westcott J, Butler N, Robinson C, Bell M, Hambidge KM 2006. Meat as a first complementary food for breastfed infants: feasibility and impact on zinc intake and status. J. Pediatr. Gastroenterol. Nutr. 42:207–14
    [Google Scholar]
  72. 72.
    Kuzawa CW. 1998. Adipose tissue in human infancy and childhood: an evolutionary perspective. Am. J. Phys. Anthropol. 107:Suppl. 27177–209
    [Google Scholar]
  73. 73.
    Lao TT, Tam KF, Chan LY 2000. Third trimester iron status and pregnancy outcome in non-anaemic women: pregnancy unfavourably affected by maternal iron excess. Hum. Reprod. 15:1843–48
    [Google Scholar]
  74. 74.
    Lind T, Lönnerdal B, Stenlund H, Gamayanti IL, Ismail D et al. 2004. A community-based randomized controlled trial of iron and zinc supplementation in Indonesian infants: effects on growth and development. Am. J. Clin. Nutr. 80:729–36
    [Google Scholar]
  75. 75.
    Lind T, Lönnerdal B, Stenlund H, Ismail D, Seswandhana R et al. 2003. A community-based randomized controlled trial of iron and zinc supplementation in Indonesian infants: interactions between iron and zinc. Am. J. Clin. Nutr. 77:883–90
    [Google Scholar]
  76. 76.
    Lind T, Seswandhana R, Persson LA, Lönnerdal B 2008. Iron supplementation of iron-replete Indonesian infants is associated with reduced weight-for-age. Acta Paediatr 97:770–75
    [Google Scholar]
  77. 77.
    Lönnerdal B. 2017. Excess iron intake as a factor in growth, infections, and development of infants and young children. Am. J. Clin. Nutr. 106:Suppl. 61681S–87S
    [Google Scholar]
  78. 78.
    Lönnerdal B, Hernell O. 1994. Iron, zinc, copper and selenium status of breast-fed infants and infants fed trace element fortified milk-based infant formula. Acta Paediatr 83:367–73
    [Google Scholar]
  79. 79.
    Lorenz L, Peter A, Poets CF, Franz AR 2013. A review of cord blood concentrations of iron status parameters to define reference ranges for preterm infants. Neonatology 104:194–202
    [Google Scholar]
  80. 80.
    Lozoff B, Beard J, Connor J, Felt B, Georgieff M, Schallert T 2006. Long-lasting neural and behavioral effects of early iron deficiency in infancy. Nutr. Rev. 64:Suppl. 2S34–43
    [Google Scholar]
  81. 81.
    Lozoff B, Brittenham GM, Wolf AW, McClish DK, Kuhnert PM et al. 1987. Iron deficiency anemia and iron therapy effects on infant developmental test performance. Pediatrics 79:981–95
    [Google Scholar]
  82. 82.
    Lozoff B, Castillo M, Clark KM, Smith JB 2012. Iron-fortified versus low-iron infant formula: developmental outcome at 10 years. Arch. Pediatr. Adolesc. Med. 166:208–15
    [Google Scholar]
  83. 83.
    Lozoff B, Clark KM, Jing Y, Armony-Sivan R, Angelilli ML, Jacobson SW 2008. Dose–response relationships between iron deficiency with or without anemia and infant social–emotional behavior. J. Pediatr. 152:696–702
    [Google Scholar]
  84. 84.
    Lozoff B, De Andraca I, Castillo M, Smith JB, Walter T, Pino P 2003. Behavioral and developmental effects of preventing iron-deficiency anemia in healthy full-term infants. Pediatrics 112:846–54
    [Google Scholar]
  85. 85.
    Lozoff B, Wolf A, Jimenez E 1996. Iron-deficiency anemia and infant development: effects of extended oral iron therapy. J. Pediatr. 129:382–89
    [Google Scholar]
  86. 86.
    Lukowski AF, Koss M, Burden MJ, Jonides J, Nelson CA et al. 2010. Iron deficiency in infancy and neurocognitive functioning at 19 years: evidence of long-term deficits in executive function and recognition memory. Nutr. Neurosci. 13:54–70
    [Google Scholar]
  87. 87.
    Lynch S, Pfeiffer CM, Georgieff MK, Brittenham G, Fairweather-Tait S et al. 2018. Biomarkers of Nutrition for Development (BOND)—iron review. J. Nutr. 48:Suppl. 11001S–67S
    [Google Scholar]
  88. 88.
    Majumdar I, Paul P, Talib VH, Ranga S 2003. The effect of iron therapy on the growth of iron-replete and iron-deplete children. J. Trop. Pediatr. 49:84–88
    [Google Scholar]
  89. 89.
    McDonald MC, Abrams SA, Schanler RJ 1998. Iron absorption and red blood cell incorporation in premature infants fed an iron-fortified infant formula. Pediatr. Res. 44:507–11
    [Google Scholar]
  90. 90.
    Mevissen-Verhage EAE, Marcelis JH, Harmsen-Van Amerongen WCM, de Vos NM, Verhoef J 1985. Effect of iron on neonatal gut flora during the first three months of life. Eur. J. Clin. Microbiol. 4:273–78
    [Google Scholar]
  91. 91.
    Mohamed MA, Ahmad T, Macri C, Aly H 2012. Racial disparities in maternal hemoglobin concentrations and pregnancy outcomes. J. Perinat. Med. 40:141–49
    [Google Scholar]
  92. 92.
    Monk C, Georgieff MK, Xu D, Hao X, Bansal R et al. 2015. Maternal prenatal iron status and tissue organization in the neonatal brain. Pediatr. Res. 79:482–88
    [Google Scholar]
  93. 93.
    Murray-Kolb LE, Khatry SK, Katz J, Schaefer BA, Cole PM, LeClerq SC 2012. Preschool micronutrient supplementation effects on intellectual and motor function in school-aged Nepalese children. Arch. Pediatr. Adolesc. Med. 166:404–10
    [Google Scholar]
  94. 94.
    Mwangi MN, Roth JM, Smit MR, Trijsburg L, Mwangi AM et al. 2015. Effect of daily antenatal iron supplementation on Plasmodium infection in Kenyan women: a randomized clinical trial. JAMA 314:1009–20
    [Google Scholar]
  95. 95.
    Neuberger A, Okebe J, Yahav D, Paul M 2016. Oral iron supplements for children in malaria-endemic areas. Cochrane Database Syst. Rev. 2:CD006589
    [Google Scholar]
  96. 96.
    Ojukwu JU, Okebe JU, Yahav D, Paul M 2009. Oral iron supplementation for preventing or treating anaemia among children in malaria-endemic areas. Cochrane Database Syst. Rev. 3:CD006589
    [Google Scholar]
  97. 97.
    Okebe JU, Yahav D, Shbita R, Paul M 2011. Oral iron supplements for children in malaria-endemic areas. Cochrane Database Syst. Rev. 10:CD006589
    [Google Scholar]
  98. 98.
    Paganini D, Uyoga MA, Cercamondi CI, Moretti D, Mwasi E et al. 2017. Consumption of galacto-oligosaccharides increases iron absorption from a micronutrient powder containing ferrous fumarate and sodium iron EDTA: a stable-isotope study in Kenyan infants. Am. J. Clin. Nutr. 106:1020–31
    [Google Scholar]
  99. 99.
    Paganini D, Zimmermann MB. 2017. The effects of iron fortification and supplementation on the gut microbiome and diarrhea in infants and children: a review. Am. J. Clin. Nutr. 106:Suppl.1688S–93S
    [Google Scholar]
  100. 100.
    Pasricha SR, Hayes E, Kaumba K, Biggs BA 2013. Effect of daily iron supplementation on health in children aged 4–23 months: a systematic review and meta-analysis of randomized controlled trials. Lancet Glob. Health 1:e77–86
    [Google Scholar]
  101. 101.
    Pena-Rosas JP, De-Regil LM, Dowswell T, Viteri FE 2012. Daily oral iron supplementation during pregnancy. Cochrane Database Syst. Rev. 12:CD004736
    [Google Scholar]
  102. 102.
    Pena-Rosas JP, De-Regil LM, Garcia-Casal MN, Dowswell T 2015. Daily oral iron supplementation during pregnancy. Cochrane Database Syst. Rev.CD004736
    [Google Scholar]
  103. 103.
    Petry CD, Eaton MA, Wobken JD, Mills MM, Johnson DE, Georgieff MK 1992. Iron deficiency of liver, heart, and brain in newborn infants of diabetic mothers. J. Pediatr. 121:109–14
    [Google Scholar]
  104. 104.
    Petry N, Olofin I, Hurrell RF, Boy E, Wirth JP et al. 2016. The proportion of anemia associated with iron deficiency in low, medium, and high human development index countries: a systematic analysis of national surveys. Nutrients 8:693
    [Google Scholar]
  105. 105.
    Pisansky MT, Wickham RJ, Su J, Fretham S, Yuan L-L et al. 2013. Iron deficiency with or without anemia impairs prepulse inhibition of the startle reflex. Hippocampus 23:952–62
    [Google Scholar]
  106. 106.
    Rao R, Ennis K, Lubach G, Lock E, Georgieff MK, Coe C 2016. Metabolomic analysis of CSF indicates brain metabolic impairment precedes hematological indices of anemia in the iron-deficient infant monkey. Nutr. Neurosci. 21:40–48
    [Google Scholar]
  107. 107.
    Ren A, Wang J, Ye RW, Li S, Liu JM, Li Z 2007. Low first-trimester hemoglobin and low birth weight, preterm birth and small for gestational age newborns. Int. J. Gynaecol. Obstet. 98:124–28
    [Google Scholar]
  108. 108.
    Rivera JA, Shamah T, Villalpando S, Monterrubio E 2010. Effectiveness of a large-scale iron-fortified milk distribution program on anemia and iron deficiency in low-income young children in Mexico. Am. J. Clin. Nutr. 91:431–39
    [Google Scholar]
  109. 109.
    Roncagliolo M, Garrido M, Walter T, Peirano P, Lozoff B 1998. Interaction of iron deficiency anemia and neurofunctions in cognitive development. Am. J. Clin. Nutr. 68:683–90
    [Google Scholar]
  110. 110.
    Santos DCC, Angulo-Barroso RM, Li M, Bian Y, Sturza J et al. 2018. Timing, duration and severity of iron deficiency in early development and motor outcomes at 9 months. Eur. J. Clin. Nutr. 72:332–41
    [Google Scholar]
  111. 111.
    Sazawal S, Black RE, Ramsan M, Chwaya HM, Stoltzfus RJ 2006. Effects of routine prophylactic supplementation with iron and folic acid on admission to hospital and mortality in preschool children in a high malaria transmission setting: community-based, randomised, placebo-controlled trial. Lancet 367:133–43
    [Google Scholar]
  112. 112.
    Sazawal S, Dhingra U, Dhingra P, Hiremath G, Sarkar A, Dutta A 2010. Micronutrient fortified milk improves iron status, anemia and growth among children 1–4 years: a double masked, randomized, controlled trial. PLOS ONE 5:e12167
    [Google Scholar]
  113. 113.
    Scanlon KS, Yip R, Schieve LA, Cogswell ME 2000. High and low hemoglobin levels during pregnancy: differential risks for preterm birth and small for gestational age. Obstet. Gynecol. 96:741–48
    [Google Scholar]
  114. 114.
    Schmidt AT, Waldow KJ, Grove WM, Salinas JA, Georgieff MK 2007. Dissociating the long-term effects of fetal/neonatal iron deficiency on three types of learning in the rat. Behav. Neurosci. 121:475–82
    [Google Scholar]
  115. 115.
    Schmidt RJ, Tancredi DJ, Krakowiak P, Hansen RL, Ozonoff S 2014. Maternal intake of supplemental iron and risk of autism spectrum disorder. Am. J. Epidemiol. 180:890–900
    [Google Scholar]
  116. 116.
    Scholl TO. 1998. High third-trimester ferritin concentration: associations with very preterm delivery, infection, and maternal nutritional status. Obstet. Gynecol. 92:161–66
    [Google Scholar]
  117. 117.
    Schuijt TJ, Lankelma JM, Scicluna BP, de Sousa e Melo F, Roelofs JJ et al. 2016. The gut microbiota plays a protective role in the host defence against pneumococcal pneumonia. Gut 65:575–83
    [Google Scholar]
  118. 118.
    Senga EL, Harper G, Koshy G, Kazembe PN, Brabin BJ 2011. Reduced risk for placental malaria in iron deficient women. Malar. J. 10:47
    [Google Scholar]
  119. 119.
    Shao J, Lou J, Rao R, Georgieff MK, Kaciroti N et al. 2012. Maternal serum ferritin concentration is positively associated with newborn iron stores in women with low ferritin status in late pregnancy. J. Nutr. 142:2004–9
    [Google Scholar]
  120. 120.
    Siddappa AM, Georgieff MK, Wewerka S, Worwa C, Nelson CA, deRegnier R-A 2004. Auditory recognition memory in iron-deficient infants of diabetic mothers. Pediatr. Res. 55:1034–41
    [Google Scholar]
  121. 121.
    Siddappa AM, Rao R, Long JD, Widness JA, Georgieff MK 2007. The assessment of newborn iron stores at birth: a review of the literature and standards for ferritin concentrations. Neonatology 92:73–82
    [Google Scholar]
  122. 122.
    Simonyté Sjodin K, Domellöf M, Lagerqvist C, Hernell O, Lönnerdal B et al. 2018. Administration of ferrous sulfate drops has significant effects on the gut microbiota of iron-sufficient infants: a randomized controlled study. Gut In press. https://dx.doi.org/10.1136/gutjnl-2018-316988
    [Crossref] [Google Scholar]
  123. 123.
    Soofi S, Cousens S, Iqbal SP, Akhund T, Khan J et al. 2013. Effect of provision of daily zinc and iron with several micronutrients on growth and morbidity among young children in Pakistan: a cluster-randomised trial. Lancet 382:29–40
    [Google Scholar]
  124. 124.
    Steinmacher J, Pohlandt F, Bode H, Sander S, Kron M, Franz AR 2007. Randomized trial of early versus late enteral iron supplementation in infants with a birth weight of less than 1301 grams: neurocognitive development at 5.3 years’ corrected age. Pediatrics 120:538–46
    [Google Scholar]
  125. 125.
    Stekel A, Olivares M, Pizarro F, Chadud P, Cayazzo M et al. 1986. [Prevention of iron deficiency in infants by fortified milk: field study of a low-fat milk]. Arch. Latinoam. Nutr. 36:654–61 In Spanish )
    [Google Scholar]
  126. 126.
    Stoltzfus RJ, Dreyfuss ML 1998. Guidelines for the Use of Iron Supplements to Prevent and Treat Iron Deficiency Anemia Washington, DC: ILSI Press
  127. 127.
    Stoltzfus RJ, Kvalsvig JD, Chwaya HM, Montresor A, Albonico M et al. 2001. Effects of iron supplementation and anthelmintic treatment on motor and language development of preschool children in Zanzibar: double blind, placebo controlled study. BMJ 323:1389–93
    [Google Scholar]
  128. 128.
    Suchdev PS, Williams AM, Mei Z, Flores-Ayala R, Pasricha S-R et al. 2017. Assessment of iron status in settings of inflammation: challenges and potential approaches. Am. J. Clin. Nutr. 106:Suppl. 61626S–33S
    [Google Scholar]
  129. 129.
    Sweet DG, Savage G, Tubman TR, Lappin TR, Halliday HL 2001. Study of maternal influences on fetal iron status at term using cord blood transferrin receptors. Arch. Dis. Child. 84:F40–43
    [Google Scholar]
  130. 130.
    Tamura T, Goldenberg RL, Hou J, Johnston KE, Cliver SP et al. 2002. Cord serum ferritin concentrations and mental and psychomotor development of children at five years of age. J. Pediatr. 140:165–70
    [Google Scholar]
  131. 131.
    Tamura T, Goldenberg RL, Johnston KE, Cliver SP, Hickey CA 1996. Serum ferritin: a predictor of early spontaneous preterm delivery. Obstet. Gynecol. 87:360–65
    [Google Scholar]
  132. 132.
    Tang M, Frank DN, Hendricks E, Ir D, Esamai F et al. 2017. Iron in micronutrient powder promotes an unfavorable gut microbiota in Kenyan infants. Nutrients 9:776
    [Google Scholar]
  133. 133.
    Tang M, Frank DN, Sherlock L, Ir D, Robertson CE, Krebs NF 2016. Effect of vitamin E with therapeutic iron supplementation on iron repletion and gut microbiome in US iron deficient infants and toddlers. J. Pediatr. Gastroenterol. Nutr. 63:379–85
    [Google Scholar]
  134. 134.
    Taylor CL, Brannon PM. 2017. Introduction to workshop on iron screening and supplementation in iron-replete pregnant women and young children. Am. J. Clin. Nutr. 106:Suppl. 61547S–54S
    [Google Scholar]
  135. 135.
    Tielsch JM, Khatry SK, Stoltzfus RJ, Katz J, LeClerq SC et al. 2007. Effect of daily zinc supplementation on child mortality in southern Nepal: a community-based, cluster randomised, placebo-controlled trial. Lancet 370:1230–39
    [Google Scholar]
  136. 136.
    Toldi G, Stenczer B, Molvarec A, Takats Z, Beko G et al. 2010. Hepcidin concentrations and iron homeostasis in preeclampsia. Clin. Chem. Lab. Med. 48:1423–26
    [Google Scholar]
  137. 137.
    Tran PV, Kennedy BC, Lien YC, Simmons RA, Georgieff MK 2015. Fetal iron deficiency induces chromatin remodeling at the Bdnf locus in adult rat hippocampus. Am. J. Physiol. 308:R276–82
    [Google Scholar]
  138. 138.
    Tran PV, Kennedy BC, Pisansky MT, Won KJ, Gewirtz JC et al. 2016. Prenatal choline supplementation diminishes early-life iron deficiency–induced preprogramming of networks associated with behavioral abnormalities in the adult rat hippocampus. J. Nutr. 146:484–93
    [Google Scholar]
  139. 139.
    Unger EL, Hurst AR, Georgieff MK, Schallert T, Rao R et al. 2012. Behavior and monoamine deficits in prenatal and perinatal iron deficiency are not corrected by early postnatal moderate-iron or high-iron diets in rats. J. Nutr. 142:2040–49
    [Google Scholar]
  140. 140.
    US Prevent. Serv. Task Force 2015. Iron deficiency anemia in pregnant women: screening and supplementation. US Prevent. Serv. Task Force https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/iron-deficiency-anemia-in-pregnant-women-screening-and-supplementation
    [Google Scholar]
  141. 141.
    van der Merwe LF, Eussun SR 2017. Iron status of young children in Europe. Am. J. Clin. Nutr. 106:Suppl. 6.1663S–71S
    [Google Scholar]
  142. 142.
    van Santen S, Kroot JJ, Zijderveld G, Wiegerinck ET, Spaanderman ME, Swinkels DW 2013. The iron regulatory hormone hepcidin is decreased in pregnancy: a prospective longitudinal study. Clin. Chem. Lab. Med. 51:1395–401
    [Google Scholar]
  143. 143.
    Veenemans J, Schouten LR, Ottenhof MJ, Mank TG, Uges DR et al. 2012. Effect of preventive supplementation with zinc and other micronutrients on non-malarial morbidity in Tanzanian pre-school children: a randomized trial. PLOS ONE 7:e41630
    [Google Scholar]
  144. 144.
    Verhoeff FH, Brabin BJ, van Buuren S, Chimsuku L, Kazembe P et al. 2001. An analysis of intra-uterine growth retardation in rural Malawi. Eur. J. Clin. Nutr. 55:682–89
    [Google Scholar]
  145. 145.
    Villalpando S, Shamah T, Rivera JA, Lara Y, Monterrubio E 2006. Fortifying milk with ferrous gluconate and zinc oxide in a public nutrition program reduced the prevalence of anemia in toddlers. J. Nutr. 136:2633–37
    [Google Scholar]
  146. 146.
    Vricella LK. 2017. Emerging understanding and measurement of plasma volume expansion in pregnancy. Am. J. Clin. Nutr. 106:Suppl. 61620S–25S
    [Google Scholar]
  147. 147.
    Walker S, Wachs T, Gardner J, Lozoff B, Wasserman G et al. 2007. Child development: risk factors for adverse outcomes in developing countries. Lancet 369:145–57
    [Google Scholar]
  148. 148.
    Walker S, Wachs T, Grantham-McGregor S, Black M, Nelson C et al. 2011. Inequality in early childhood: risk and protective factors for early child development. Lancet 378:1325–38
    [Google Scholar]
  149. 149.
    Wallace DF. 2016. The regulation of iron absorption and homeostasis. Clin. Biochem. Rev. 37:51–62
    [Google Scholar]
  150. 150.
    Wallin DJ, Tkac I, Stucker S, Ennis KM, Sola-Visner M et al. 2015. Phlebotomy-induced anemia alters hippocampal neurochemistry in neonatal mice. Pediatr. Res. 77:765–71
    [Google Scholar]
  151. 151.
    Walter T, De Andraca I, Chadud P, Perales CG 1989. Iron deficiency anemia: adverse effects on infant psychomotor development. Pediatrics 84:7–17
    [Google Scholar]
  152. 152.
    Walter T, Pino P, Pizarro F, Lozoff B 1998. Prevention of iron-deficiency anemia: comparison of high- and low-iron formulas in term healthy infants after six months of life. J. Pediatr. 132:635–40
    [Google Scholar]
  153. 153.
    WHO (World Health Organ.) 2007. Conclusions and recommendations of the WHO consultation on prevention and control of iron deficiency in infants and young children in malaria-endemic areas. Food Nutr. Bull. 28:Suppl. 4S621–27
    [Google Scholar]
  154. 154.
    WHO (World Health Organ.) 2014. World Malaria Report 2014 Geneva: WHO
  155. 155.
    WHO (World Health Organ.) 2016. Guideline: Daily Iron Supplementation in Infants and Children Geneva: WHO
  156. 156.
    WHO (World Health Organ.) 2016. WHO guideline development group—the use of ferritin concentrations to assess iron status in populations. WHO http://www.who.int/nutrition/events/2016_meeting_guidelinedevelopmentgroup_ferritin_2to4march/en/
    [Google Scholar]
  157. 157.
    WHO (World Health Organ.) 2019. Iron with or without folic acid supplementation in women in malaria-endemic areas: full set of recommendations. WHO http://www.who.int/elena/titles/full_recommendations/ifa_supplementation_malaria/en/
    [Google Scholar]
  158. 158.
    WHO (World Health Organ.), UNICEF 2006. Iron Supplementation of Young Children in Regions Where Malaria Transmission Is Intense and Infectious Disease Highly Prevalent Geneva: WHO, UNICEF
  159. 159.
    Xiong X, Buekens P, Alexander S, Demianczuk N, Wollast E 2000. Anemia during pregnancy and birth outcome: a meta-analysis. Am. J. Perinatol. 17:137–46
    [Google Scholar]
  160. 160.
    Youdim MB, Sills MA, Heydorn WE, Creed GJ, Jacobowitz DM 1986. Iron deficiency alters discrete proteins in rat caudate nucleus and nucleus accumbens. J. Neurochem. 47:794–99
    [Google Scholar]
  161. 161.
    Zamora TG, Guiang SF, Georgieff MK, Widness JA 2016. Iron is prioritized to red blood cells over the brain in phlebotomized anemic newborn lambs. Pediatr. Res. 79:922–28
    [Google Scholar]
  162. 162.
    Zhang C, Rawal S. 2017. Dietary iron intake, iron status and gestational diabetes. Am. J. Clin. Nutr. 106:Suppl. 6.1672S–80S
    [Google Scholar]
  163. 163.
    Zhang Q, Ananth CV, Li Z, Smulian JC 2009. Maternal anaemia and preterm birth: a prospective cohort study. Int. J. Epidemiol. 38:1380–89
    [Google Scholar]
  164. 164.
    Zhao G, Guobin X, Zhou M, Jiang Y, Richards B et al. 2015. Prenatal iron supplementation reduces maternal anemia, iron deficiency, iron deficiency anemia in a randomized clinical trial in rural China, but iron deficiency remains widespread in mothers and neonates. J. Nutr. 145:1916–23
    [Google Scholar]
  165. 165.
    Zhou LM, Yang WW, Hua JZ, Deng CQ, Tao X, Stoltzfus RJ 1998. Relation of hemoglobin measured at different times in pregnancy to preterm birth and low birth weight in Shanghai, China. Am. J. Epidemiol 148:998–1006
    [Google Scholar]
  166. 166.
    Ziaei S, Norrozi M, Faghihzadeh S, Jafarbegloo E 2007. A randomized placebo-controlled trial to determine the effect of iron supplementation on pregnancy outcome in pregnant women with haemoglobin ≥13.2 g/dl. BJOG 114:684–88 Corrigendum 2007. BJOG 114:1311
    [Google Scholar]
  167. 167.
    Ziegler EE, Nelson SE, Jeter JM 2009. Iron supplementation of breastfed infants from an early age. Am. J. Clin. Nutr. 89:525–32
    [Google Scholar]
  168. 168.
    Ziegler EE, Nelson SE, Jeter JM 2009. Iron status of breastfed infants is improved equally by medicinal iron and iron-fortified cereal. Am. J. Clin. Nutr. 90:76–87
    [Google Scholar]
  169. 169.
    Ziegler EE, O'Donnell AM, Nelson SE, Fomon SJ 1976. Body composition of the reference fetus. Growth 40:329–41
    [Google Scholar]
  170. 170.
    Zlotkin SH, Davidsson L, Lozoff B 2015. Balancing the benefits and risks of iron fortification in resource-constrained settings. J. Pediatr. 167:Suppl.S26–30
    [Google Scholar]
/content/journals/10.1146/annurev-nutr-082018-124213
Loading
/content/journals/10.1146/annurev-nutr-082018-124213
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error