Iron deficiency and neurodevelopment among low birth weight infants: a cross-sectional study in a tertiary center in Tanzania
Background: iron deficiency anaemia is known to cause delayed neurodevelopment. Likewise infants born with low birth weight are also prone to neurodevelopment. The impact of both presence of iron deficiency and low birth weight is therefore expected to augment this delayed or impaired neurodevelopment. This relationship has not been elucidated in any appreciable level. We therefore considered studying iron deficiency among low birth weight infants and assessing their neurodevelopment. In children, however its impact is not clearly known among low birth weight infants.
Broad objective: To assess neurodevelopment of low birth weight infants and its relation to their iron status and nutritional status.
Methods: A cross-sectional study of 270 low birth weight infants was assessed during follow-up at neonatal clinic at Muhimbili National Hospital at 12 weeks postnatal. . They underwent the Bayley Mental Developmental Scoring Tests, serum ferritin and complete blood counts. The BMDS test raw scores were converted into percentiles. Cognitive, language and motor development scores were considered normal with score of ≥85 percentile of raw scores and poor with if the score was <85. Iron deficiency were considered if serum ferritin was <12µ/dl.
Results: The prevalence of poor scores were 90% in cognitive, 60% in language (60%) and 88% in motor development. The prevalence of iron deficiency was 34.1%. Among those not receiving iron supplementation, Poor cognitive and language scores were associated with iron deficiency, while motor scores were not. Wasting was associated with poor language score.
Conclusion. Low birth weight, iron deficient and wasted infants had significant poorer neurodevelopmental outcomes confirming that Iron deficient, low birth weight infants are more prone to poor neurodevelopmental outcomes. Recommendations; Early iron supplementation program should be adhered to and a close follow-up of these vulnerable children be done to ensure that their iron and hemoglobin levels are normal. Further large scale studies on the temporal relationship of iron and neurodevelopment are required.
United Nations Children's Fund (UNICEF), Child statistics. Innocenti. Research Centre, Florence. 2001: Belgium.
Manji KP, Massawe AW, Mgone JM. Birthweight and neonatal outcome at the Muhimbili Medical Centre, Dar es Salaam, Tanzania. East Afr Med J. 1998;75(7):382-7
Prince M. No health without mental health; Global Mental Health. Lancet. 2007, 370: 857-77.
Stoltzfus RJ. Iron deficiency: Global prevalence and consequences. Food Nutr. Bull. 2003, 24(suppl. 4): S99-103.
Palti H, Meijer A, Adler B. Learning achievement and behaviour at school of anemic and non-anemic infants. Early Human Devel. 1985, 10: 217-33.
Soemantri AG, Husain MA, Pollit E. Effects of Iron deficiency on attention and learning processes in preschool children: Bandung, Indonesia. Am. J. Clin. Nutr. 1989, 50: 667-74.
Dobbing J.B. Under nutrition and the developing brain: the relevance of animal models to the human problems. Nutri. Diet.1972, 17: 35-46.
Black MM, Baqui AH, Zaman K, Ake Persson L, El Arifeen S, Le K, McNary SW, Parveen M, Hamadani JD, Black RE. Iron and zinc supplementation promote motor development and exploratory behavior among Bangladeshi infants. Am J Clin Nutr. 2004;80(4):903-10.
Beard JL, Connor JR, Jones BC. Iron in the brain. Nutri. Rev. 1993, 51(6): 157-70.
Hill JM 1988 The distribution of iron in the brain. In: Youdim MBH (ed) Brain Iron: Neurochemistry and Behavioural Aspects. Taylor and Francis, London, 1–24.
Lozoff BH. Behaviour of infants with iron deficiency Anemia. Child development. 1998, 1: 24-36.
Redding-Lallinger R, Kalokola FM, Tingy DY. The incidence of anaemia during the first year of life in infants in Tanzania. Tanz Med J. 1994;9:22-6.
Stoltzfus RJ, Mullany L, Black RE. Iron deficiency anaemia. Comparative quantification of health risks: global and regional burden of disease attributable to selected major risk factors. 2004;1:163-209.
McCann JC, Ames BN. An overview of evidence for a causal relation between iron deficiency during development and deficits in cognitive or behavioral function. The American journal of clinical nutrition. 2007, 1;85(4):931-45.
Armony-Sivan R, Eidelman AI, Lanir A, Sredni D and Yehuda S. Iron status and Neurobehavioural development of premature infants. Journal of Perinatology. 2004, 24: 757-762
WHO. Iron deficiency anemia; assessment, prevention, and control. a guide for program managers. Geneva, Switzerland: World Health Organization, (WHO/NHD/01.3), 2001.
Bayley N. Bayley Scales of Infant and Toddler Development third edition: Administration manual. Published by Harcourt Assessment, Inc, 19500 Bulverde road, San Antonio, TX, 78259, USA; 2006.
Abbot RL, O’Shea TM, Shankaran S and Bhaskar B. Adverse Neurodevelopmental outcomes among extremely low birth weight infants with a normal head ultrasound: Prevalence and antecedents. Pediatrics. 2005, 115(3); 673-680.
Davis NM, Ford GW, Anderson PJ, Doyle LW. Developmental coordination disorder at 8 years of age in a regional cohort of extremely-low birth weight or very preterm infants. Developmental Medicine & Child Neurology. 2007, 49: 325-330.
Goldenberg RL, DuBard MB, Cliver SP, Nelson KG, Blankson K, Ramey SL, Herman A. Pregnancy outcome and intelligence at age five years. Am J Obstet. Gynecol. 1996, 175(6): 1511-1515.
Caravale B, Tozzi C, Albino G, Vicari S. Cognitive development in low risk preterm infants at 3-4 years of life. Arch Dis Child Fetal Neonatal Ed. 2005, 90: F474-F479.
Marlow N, Hennessy EM, Bracewell MA, Wolke D. Motor and Executive Function at 6 Years of Age after Extremely Preterm Birth. Pediatrics. 2007, 120(4): 793-804.
Harvey D, Prince J, Bunton J, Parkinson C, Campbell S. Abilities of children who were small-for-gestational-age babies. Pediatrics. 1982 Mar 1;69(3):296-300.
Georgieff MK. Nutrition and the developing brain: nutrient priorities and measurement. The American journal of clinical nutrition. 2007 Feb 1;85(2):614S-20S.
Wiggins RC, Fuller G, Enna SJ. Undernutrition and the development of brain neurotransmitter systems. Life Sci. 1984, 19;35(21):2085-94.
Black MM .Micronutrient deficiencies and cognitive functioning. J Nutr. 2003 ;133(11 Suppl 2):3927S-3931S.
Georgieff MK, The role of iron in neurodevelopment: fetal iron deficiency and the developing hippocampus, Biochem Soc Trans. 2008 Dec;36(Pt 6):1267-71
Hintz SR, Kendrick DE, Vohr BR, Poole WK, Higgins RD, Gender differences in neurodevelopmental outcomes among extremely preterm, extremely-low-birthweight infants. Acta Pædiatrica. 2006, 95: 1239-1248.
O'Keeffe M.J. Non-anemic iron deficiency identified by ZPP test in extremely premature infants: prevalence, dietary risk factors, and association with neurodevelopmental problems Early Human Development. 2002, 70: 73–83.
Tamura T, Goldenberg R, Hou J, Johnston KE, Cliver SP, Ramey SL and Nelson KG. Cord ferritin concentrations and mental and psychomotor development of children at five years of age. J. Pediatr. 2002, 186: 458-6322.
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 Apr 1;105(4):e51
Durá TT, Díaz VL. Prevalence of iron deficiency in healthy 12-month-old infants. Anales espanoles de pediatria. 2002 Sep;57(3):209-14.
Georgieff MK, Intrauterine growth retardation and subsequent somatic growth and neurodevelopment. J. Pediatr. 1998, 133: 3-5.
Grantham-Mc, Gregor S, Ani C. A review of studies on the effect of iron deficiency on cognitive development in children. J Nutr. 2001;131(2S-2):649S-666S; discussion 666S-668S.
Akman M, The effects of iron deficiency on infants’ developmental test performance, Acta Pediatr. 2004, 93: 1391-1396.
Walker S. Child development: risk factors for adverse outcomes in developing countries .Lancet. 2007, 369:145-157.
Collard KJ. Iron homeostasis in the neonate. Pediatrics. 2009, 123(4): 1208-16.
Stoltzfus RJ, Kvalsvig JD, Chwaya HM, Montresor A, Albonico M, Tielsch JM, Savioli L, Pollit E. Effects of iron supplementation and anthelmintic treatment on motor and language development of preschool children in Zanzibar: double blind, placebo controlled study. BMJ. 2001, 323: 1-8.
Steinmacher J, Pohlandt F, Bode H, Sander S, Kron M, and Frary AR, Randomised trial of early verses late enteral iron supplementation in infants with a birth weight of less than 1301grams: neurocognitive development at 5.3 years corrected age. Pediatrics. 2007, 120(3): 538-546.
Rice D and Barone S. Critical period of vulnerability for the developing nervous system: evidence from humans and animal models. Environ Health Perspect. 2000, 108 (suppl 3): 511-533.
Siddappa AJ. Iron deficiency alters iron regulatory protein and iron transport protein expression in the perinatal brain. Pediatrics Res. 2003, 53(3): 800-807.
Beard JL, Unger EL, Bianco LE, Paul T, Rundle SE, Jones BC. Early postnatal iron repletion overcomes lasting effects of gestational iron deficiency in rats. J. Nutri. 2007, 137(5): 1176-1182.
Allen CM. Neurodevelopmental outcomes of preterm infants. Current Opinion in Neurology. 2008, 21: 123–128.
Siegel LS, Correction for prematurity and its consequences for the assessment of the very low birth weight infant. Child development. 1983, 54: 1176-1188
Connor JR and Menzies SL, Relationship of iron to oligodendrocytes and myelination. Glia. 1996, 17: 83-93.