Abstract Iron deficiency (ID) is the most common micronutrient deficiency in children. Due to insufficient iron storage at birth and rapid catch-up growth after birth, preterm infants tend to have a high incidence rate of ID. During the critical period of brain development, ID alters iron-dependent neurometabolism, neurochemistry, neuroanatomy, and gene/protein profiles. This affects the central nervous system and causes the change in neurocognitive and behavioral development. Iron supplementation in infancy cannot reverse neurodevelopmental impairment caused by perinatal ID. The influence of ID on neurodevelopment is time-and region-specific, and in the high-risk population, early diagnosis and optimal iron treatment may help with the recovery of brain function and improve quality of life and long-term prognosis in preterm infants.
XU Lin,LI Ming-Yan,SHEN Yue-Liang. Research advances in the relationship between iron deficiency and neurodevelopment in preterm infants[J]. CJCP, 2018, 20(12): 1070-1074.
XU Lin,LI Ming-Yan,SHEN Yue-Liang. Research advances in the relationship between iron deficiency and neurodevelopment in preterm infants[J]. CJCP, 2018, 20(12): 1070-1074.
Zhao G, Xu G, Zhou M, et al. Prenatal iron supplementation reduces maternal anemia, iron deficiency, and iron deficiency anemia in a randomized clinical trial in rural China, but iron deficiency remains widespread in mothers and neonates[J]. J Nutr, 2015, 145(8):1916-1923.
[2]
McArdle HJ, Gambling L, Kennedy C. Iron deficiency during pregnancy:the consequences for placental function and fetal outcome[J]. Proc Nutr Soc, 2014, 73(1):9-15.
[3]
MacQueen BC, Christensen RD, Ward DM, et al. The iron status at birth of neonates with risk factors for developing iron deficiency:a pilot study[J]. J Perinatol, 2017, 37(4):436-440.
[4]
McCarthy PJ, Zundel HR, Johnson KR, et al. Impact of growth restriction and other prenatal risk factors on cord blood iron status in prematurity[J]. J Pediatr Hematol Oncol, 2016, 38(3):210-215.
[5]
Das B, Sundaram V, Kumar P, et al. Effect of placental transfusion on iron stores in moderately preterm neonates of 30-33 weeks gestation[J]. Indian J Pediatr, 2018, 85(3):172-178.
[6]
van de Lagemaat M, Amesz EM, Schaafsma A, et al. Iron deficiency and anemia in iron-fortified formula and human milk-fed preterm infants until 6 months post-term[J]. Eur J Nutr, 2014, 53(5):1263-1271.
[7]
Rao R, Georgieff MK. Iron in fetal and neonatal nutrition[J]. Semin Fetal Neonatal Med, 2007, 12(1):54-63.
[8]
Estrada JA, Contreras I, Pliego-Rivero FB, et al. Molecular mechanisms of cognitive impairment in iron deficiency:alterations in brain-derived neurotrophic factor and insulin-like growth factor expression and function in the central nervous system[J]. Nutr Neurosci, 2014, 17(5):193-206.
[9]
Bakoyiannis I, Gkioka E, Daskalopoulou A, et al. An explanation of the pathophysiology of adverse neurodevelopmental outcomes in iron deficiency[J]. Rev Neurosci, 2015, 26(4):479-488.
[10]
邵洁.早期缺铁与大脑发育[J]. 中国儿童保健杂志, 2014, 23(2):116-118.
[11]
Lee DL, Strathmann FG, Gelein R, et al. Iron deficiency disrupts axon maturation of the developing auditory nerve[J]. J Neurosci, 2012, 32(14):5010-5015.
[12]
Unger EL, Bianco LE, Jones BC, et al. Low brain iron effects and reversibility on striatal dopamine dynamics[J]. Exp Neurol, 2014, 261:462-468.
[13]
Jellen LC, Lu L, Wang X, et al. Iron deficiency alters expression of dopamine-related genes in the ventral midbrain in mice[J]. Neuroscience, 2013, 252:13-23.
[14]
Felt BT, Beard JL, Schallert T, et al. Persistent neurochemical and behavioral abnormalities in adulthood despite early iron supplementation for perinatal iron deficiency anemia in rats[J]. Behav Brain Res, 2006, 171(2):261-270.
[15]
Golub MS, Hogrefe CE. Fetal iron deficiency and genotype influence emotionality in infant rhesus monkeys[J]. J Nutr, 2015, 145(3):647-653.
[16]
Golub M, Hogrefe C.Prenatal iron deficiency and monoamine oxidase A (MAOA) polymorphisms:combined risk for later cognitive performance in rhesus monkeys[J]. Genes Nutr, 2014, 9(2):381.
[17]
Basu S, Kumar D, Anupurba S, et al. Effect of maternal iron deficiency anemia on fetal neural development[J]. J Perinatol, 2018, 38(3):233-239.
[18]
Mudd AT, Fil JE, Knight LC, et al. Early-life iron deficiency reduces brain iron content and alters brain tissue composition despite iron repletion:A neuroimaging assessment[J]. Nutrients, 2018, 10(2). pii:E135. doi:10.3390/nu10020135.
[19]
Mudd AT, Fil JE, Knight LC, et al. Dietary iron repletion following early-life dietary iron deficiency does not correct regional volumetric or diffusion tensor changes in the developing pig brain[J]. Front Neurol, 2017, 8:735.
[20]
Rao R, Tkac I, Unger E, et al. Iron supplementation dose for perinatal iron deficiency differentially alters the neurochemistry of the frontal cortex and hippocampus in adult rats[J]. Pediatr Res, 2013, 73(1):31-37.
[21]
de Deungria M, Rao R, Wobken JD, et al. Perinatal iron deficiency decreases cytochrome c oxidase (CytOx) activity in selected regions of neonatal rat brain[J]. Pediat Res, 2000, 48(2):169-176.
[22]
Iglesias L, Canals J, Arija V. Effects of prenatal iron status on child neurodevelopment and behavior:A systematic review[J]. Crit Rev Food Sci Nutr, 2018, 58(10):1604-1614.
[23]
Schachtschneider KM, Liu Y, Rund LA, et al. Impact of neonatal iron deficiency on hippocampal DNA methylation and gene transcription in a porcine biomedical model of cognitive development[J]. BMC Genomics, 2016, 17(1):856.
[24]
Brydges CR, Landes JK, Reid CL, et al. Cognitive outcomes in children and adolescents born very preterm:a meta-analysis[J]. Dev Med Child Neurol, 2018, 60(5):452-468.
[25]
Geng F, Mai X, Zhan J, et al. Impact of fetal-neonatal iron deficiency on recognition memory at 2 months of age[J]. J Pediatr, 2015, 167(6):1226-1232.
[26]
Lou J, Mai X, Lozoff B, et al.Prenatal iron deficiency and auditory brainstem responses at 3 and 10 months:A pilot study[J]. Hong Kong J Paediatr, 2016, 20(2):71-79.
[27]
Tran TD, Biggs BA, Tran T, et al. Impact on infants' cognitive development of antenatal exposure to iron deficiency disorder and common mental disorders[J]. PLoS One, 2013, 8(9):e74876.
[28]
Vaughn J, Brown J, Carter JP. The effects of maternal anemia on infant behavior[J]. J Natl Med Assoc, 1986, 78(10):963-968.
[29]
Therien JM, Worwa CT, Mattia FR, et al. Altered pathways for auditory discrimination and recognition memory in preterm infants[J]. Dev Med Child Neurol, 2004, 46(12):816-824.
[30]
Li M, Zhu L, Mai X, et al. Sex and gestational age effects on auditory brainstem responses in preterm and term infants[J].Early Hum Dev, 2013, 89(1):43-48.
[31]
Amin SB, Orlando M, Wang H. Latent iron deficiency in utero is associated with abnormal auditory neural myelination in ≥ 35 weeks gestational age infants[J]. J Pediatr, 2013, 163(5):1267-1271.
[32]
Choudhury V, Amin SB, Agarwal A, et al. Latent iron deficiency at birth influences auditory neural maturation in late preterm and term infants[J]. Am J Clin Nutr, 2015, 102(5):1030-1034.
[33]
Schmidt AT, Ladwig EK, Wobken JD, et al. Delayed alternation performance in rats following recovery from early iron deficiency[J]. Physiol Behav, 2010, 101(4):503-508.
[34]
Lozoff B, Smith JB, Kaciroti N, et al. Functional significance of early-life iron deficiency:outcomes at 25 years[J]. J Pediatr, 2013, 163(5):1260-1266.
[35]
Algarin C, Karunakaran KD, Reyes S, et al. Differences on brain connectivity in adulthood are present in subjects with iron deficiency anemia in infancy[J]. Front Aging Neurosci, 2017, 9:54. doi:10.3389/fnagi.
[36]
Moos T, Skjorringe T, Thomsen LL. Iron deficiency and iron treatment in the fetal developing brain-a pilot study introducing an experimental rat model[J]. Reprod Health, 2018, 15(Suppl 1):93.
[37]
Unger EL, Hurst AR, Georgieff MK, et al. 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]. J Nutr, 2012, 142(11):2040-2049.
[38]
Berglund SK, Westrup B, Hägglöf B, et al. Effects of iron supplementation of LBW infants on cognition and behavior at 3 years[J]. Pediatrics, 2013, 131(1):47-55.
[39]
Steinmacher J, Pohlandt F, Bode H, et al. 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[J]. Pediatrics, 2007, 120(3):538-546.
[40]
Berglund SK, Chmielewska A, Starnberg J, et al. Effects of iron supplementation of low-birth-weight infants on cognition and behavior at 7 years:a randomized controlled trial[J]. Pediatric Res, 2018, 83(1-1):111-118.
[41]
Berglund SK, Westrup B, Haraldsson E, et al. Effects of iron supplementation on auditory brainstem response in marginally LBW infants[J]. Pediatric Res, 2011, 70(6):601-606.
[42]
Friel JK, Andrews WL, Aziz K, et al. A randomized trial of two levels of iron supplementation and developmental outcome in low birth weight infants[J]. J Pediatr, 2001, 139(2):254-260.
[43]
Uijterschout L, Domellöf M, Abbink M, et al. Iron deficiency in the first 6 months of age in infants born between 32 and 37 weeks of gestational age[J]. Eur J Clin Nutr, 2015, 69(5):598-602.
[44]
Committee on Nutrition of the Preterm Infant, European Society of Paediatric Gastroenterology and Nutrition. Nutrition and feeding of preterm infants[J]. Acta Paediatr Scand, 1987, suppl 336:1-14.
[45]
Nutrition Committee, Canadian Pediatric Society. Nutrition needs and feeding of premature infants[J]. Can Med Assoc J, 1995, 152(11):1765-1785.
[46]
Baker RD, Greer FR. Diagnosis and prevention of iron deficiency and iron-deficiency anemia in infants and young children (0-3 years of age)[J]. Pediatrics, 2010, 126(5):1040-1050.
