Benefits of Iron supplementation for low birth weight infants: A systematic review

BMC Pediatrics

Sing Zhu¹  Fang Wang¹  Wei-Ya Qiu¹  Zhi-Bin Li¹  Pei-Li Hu¹  Jing-Mei Yi¹  Hui Long¹ 

[1]Department of Pediatrics, General Hospital of Chinese People’s Liberation Army, #28 Fuxing Road, Haidian District, Beijing, 100853, China

关键词: Low birth weight;    Iron supplementation;    Iron deficiency;    Infant;    Anemia;   

Others  :  1170734
DOI  :  10.1186/1471-2431-12-99

 received in 2012-01-16, accepted in 2012-07-02,  发布年份 2012

【 摘 要 】

Background

A number of studies have reported on the effects of iron supplementation in low birth weight infants; however, no systematic review of the available evidence has been conducted to date. Hence, we performed a systematic review of the literature to examine the effects of iron supplementation on hematologic iron status, growth, neurodevelopment, and adverse effects in low birth weight/premature infants.

Methods

We searched the Cochrane Library, Medline, and PubMed for articles reporting on the effects of iron supplementation in low weight infants. The following search terms were used: “preterm born infant(s)/children”; “preterm infants”; “prematurely born children” “weight less than 1500 g at birth”; “born prematurely”; “low birth weight infant(s)”; “infants born preterm”; “prematurity”; “small-for-gestational age”; “very small gestational age infants”; “iron supplementation”; “iron intake”; “iron supplements”; “ferric and/or ferrous compounds”; and “ferrous sulphate/fumarate/sulfate”.

Results

A total of 15 studies were identified and included in the systematic review. Supplemental iron was given orally or as an iron-fortified formula in 14/15 studies. The duration of treatment ranged from 1 week to 18 months. Iron supplementation significantly increased hematologic measures of iron status (including hemoglobin, hematocrit, serum ferritin) relative to placebo or over time in most studies. All controlled studies that examined iron-deficiency anemia (IDA)/ID reported a decreased prevalence of IDA/ID with iron supplementation. Dose dependent decreases in the prevalence of IDA/ID were reported in several studies. Of the 5 studies reporting on growth, none found any significant effect on growth-related parameters (length, height, weight, and head circumference). Only 2 studies reported on neurodevelopment; no marked effects were reported. There were no consistently reported adverse effects, including oxidative stress, inhibited nutrient absorption, morbidity, or the requirement for blood transfusion.

Conclusion

The available data suggest that iron supplementation increases the levels of hematologic indicators of iron status and reduces the prevalence of IDA/ID in low birth weight/premature infants. There is insufficient evidence to make a definitive statement regarding the effects of iron supplementation on growth, neurodevelopment, or the occurrence of adverse effects in low birth weight/premature infants.

【 授权许可】

   
2012 LONG et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Collard KJ: Iron homeostasis in the neonate. Pediatrics 2009, 123:1208-1216.
• [2]Lundstrom U, Siimes MA, Dallman PR: At what age does iron supplementation become necessary in low-birth-weight infants? J Pediatr 1977, 91:878-883.
• [3]Rao R, Georgieff MK: Iron therapy for preterm infants. Clin Perinatol 2009, 36:27-42.
• [4]Gorten MK, Cross ER: Iron Metabolism in Premature Infants. Ii. Prevention of Iron Deficiency. J Pediatr 1964, 64:509-520.
• [5]Faldella G, Alessandroni R, Salvioli GP, Capelli M, Paolini M, Minak G: Tiraferri S: Lack of correlation between free erythrocyte porphyrin and serum ferritin values at birth and at 2 months of life in low birthweight infants. Arch Dis Child 1983, 58:216-219.
• [6]Kon N, Tanaka K, Sekigawa M, Negishi Y, Yoshikawa N, Hisata K, Shoji H, Shimizu T: Association between iron status and neurodevelopmental outcomes among VLBW infants. Brain Dev 2010, 32:849-854.
• [7]Roncagliolo M, Garrido M, Walter T, Peirano P, Lozoff B: Evidence of altered central nervous system development in infants with iron deficiency anemia at 6 mo: delayed maturation of auditory brainstem responses. Am J Clin Nutr 1998, 68:683-690.
• [8]Lozoff B, Brittenham GM, Viteri FE, Wolf AW, Urrutia JJ: Developmental deficits in iron-deficient infants: effects of age and severity of iron lack. J Pediatr 1982, 101:948-952.
• [9]Lozoff B, Georgieff MK: Iron deficiency and brain development. Semin Pediatr Neurol 2006, 13:158-165.
• [10]Shafir T, Angulo-Barroso R, Jing Y, Angelilli ML, Jacobson SW, Lozoff B: Iron deficiency and infant motor development. Early Hum Dev 2008, 84:479-485.
• [11]Beard JL: Why iron deficiency is important in infant development. J Nutr 2008, 138:2534-2536.
• [12]Lozoff B, Jimenez E, Hagen J, Mollen E, Wolf AW: Poorer behavioral and developmental outcome more than 10 years after treatment for iron deficiency in infancy. Pediatrics 2000, 105:E51.
• [13]Angulo-Kinzler RM, Peirano P, Lin E, Garrido M, Lozoff B: Spontaneous motor activity in human infants with iron-deficiency anemia. Early Hum Dev 2002, 66:67-79.
• [14]Grantham-McGregor S, Ani C: A review of studies on the effect of iron deficiency on cognitive development in children. J Nutr 2001, 131:649S-666S. discussion 666S-668S
• [15]Kleinman RE: Pediatric nutrition handbook. 6th edition. Elk Grove Village, IL: American Academy of Pediatrics; 2009.
• [16]Gera T, Sachdev HP, Nestel P, Sachdev SS: Effect of iron supplementation on haemoglobin response in children: systematic review of randomised controlled trials. J Pediatr Gastroenterol Nutr 2007, 44:468-486.
• [17]Iannotti LL, Tielsch JM, Black MM, Black RE: Iron supplementation in early childhood: health benefits and risks. Am J Clin Nutr 2006, 84:1261-1276.
• [18]Ramakrishnan U, Aburto N, McCabe G, Martorell R: Multimicronutrient interventions but not vitamin a or iron interventions alone improve child growth: results of 3 meta-analyses. J Nutr 2004, 134:2592-2602.
• [19]Sachdev H, Gera T, Nestel P: Effect of iron supplementation on physical growth in children: systematic review of randomised controlled trials. Public Health Nutr 2006, 9:904-920.
• [20]Sachdev H, Gera T, Nestel P: Effect of iron supplementation on mental and motor development in children: systematic review of randomised controlled trials. Public Health Nutr 2005, 8:117-132.
• [21]Verhagen AP, de Vet HC, de Bie RA, Kessels AG, Boers M, Bouter LM, Knipschild PG: The Delphi list: a criteria list for quality assessment of randomized clinical trials for conducting systematic reviews developed by Delphi consensus. J Clin Epidemiol 1998, 51:1235-1241.
• [22]Hammond D, Murphy A: The influence of exogenous iron on formation of hemoglobin in the premature infant. Pediatrics 1960, 25:362-374.
• [23]Brozovic B, Burland WL, Simpson K, Lord J: Iron status of preterm low birthweight infants and their response to oral iron. Arch Dis Child 1974, 49:386-389.
• [24]Iwai Y, Takanashi T, Nakao Y, Mikawa H: Iron status in low birth weight infants on breast and formula feeding. Eur J Pediatr 1986, 145:63-65.
• [25]Hall RT, Wheeler RE, Benson J, Harris G, Rippetoe L: Feeding iron-fortified premature formula during initial hospitalization to infants less than 1800 grams birth weight. Pediatrics 1993, 92:409-414.
• [26]Griffin IJ, Cooke RJ, Reid MM, McCormick KP, Smith JS: Iron nutritional status in preterm infants fed formulas fortified with iron. Arch Dis Child Fetal Neonatal Ed 1999, 81:F45-F49.
• [27]Franz AR, Mihatsch WA, Sander S, Kron M, Pohlandt F: Prospective randomized trial of early versus late enteral iron supplementation in infants with a birth weight of less than 1301 grams. Pediatrics 2000, 106:700-706.
• [28]Friel JK, Andrews WL, Aziz K, Kwa PG, Lepage G, L'Abbe MR: A randomized trial of two levels of iron supplementation and developmental outcome in low birth weight infants. J Pediatr 2001, 139:254-260.
• [29]Aggarwal D, Sachdev HP, Nagpal J, Singh T, Mallika V: Haematological effect of iron supplementation in breast fed term low birth weight infants. Arch Dis Child 2005, 90:26-29.
• [30]Miller SM, McPherson RJ, Juul SE: Iron sulfate supplementation decreases zinc protoporphyrin to heme ratio in premature infants. J Pediatr 2006, 148:44-48.
• [31]Arnon S, Shiff Y, Litmanovitz I, Regev RH, Bauer S, Shainkin-Kestenbaum R, Bental Y, Dolfin T: The efficacy and safety of early supplementation of iron polymaltose complex in preterm infants. Am J Perinatol 2007, 24:95-100.
• [32]Steinmacher J, Pohlandt F, Bode H, Sander S, Kron M, Franz AR: 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. Pediatric 2007, 120:538-546.
• [33]Braekke K, Bechensteen AG, Halvorsen BL, Blomhoff R, Haaland K, Staff AC: Oxidative stress markers and antioxidant status after oral iron supplementation to very low birth weight infants. J Pediatr 2007, 151:23-28.
• [34]Sankar MJ, Saxena R, Mani K, Agarwal R, Deorari AK, Paul VK: Early iron supplementation in very low birth weight infants–a randomized controlled trial. Acta Paediatr 2009, 98:953-958.
• [35]Berglund S, Westrup B, Domellof M: Iron supplements reduce the risk of iron deficiency anemia in marginally low birth weight infants. Pediatrics 2010, 126:e874-e883.
• [36]Thibeault DW: The precarious antioxidant defenses of the preterm infant. Am J Perinatol 2000, 17:167-181.