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Microcytosis is associated with low cognitive outcomes in healthy 2-year-olds in a high-resource setting

  • Elaine K. McCarthy (a1) (a2), Mairead E. Kiely (a1) (a2), Geraldine Hannon (a2), Caroline Ahearne (a2), Louise C. Kenny (a2) (a3), Jonathan O’B. Hourihane (a2) (a4), Alan D. Irvine (a5) (a6) (a7) and Deirdre M. Murray (a2) (a4)...

Abstract

Fe deficiency in early childhood is associated with long-term consequences for cognitive, motor and behavioural development; however explorations in healthy children from low risk, high-resource settings have been limited. We aimed to explore associations between Fe status and neurodevelopmental outcomes in low risk, healthy 2-year-olds. This study was a secondary analysis of a nested case–control subgroup from the prospective, maternal-infant Cork Babies after Screening for Pregnancy Endpoints: Evaluating the Longitudinal Impact using Neurological and Nutritional Endpoints (BASELINE) Birth Cohort Study. At 2 years, serum ferritin, Hb and mean corpuscular volume (MCV) were measured and neurodevelopment was assessed using the Bayley Scales of Infant and Toddler Development (n 87). Five children had Fe deficiency (ferritin <12 µg/l) and no child had Fe deficiency anaemia (Hb<110 g/l+ferritin<12 µg/l). Children with microcytosis (MCV<74 fl, n 13) had significantly lower mean cognitive composite scores (88·5 (sd 13·3) v. 97·0 (sd 7·8), P=0·04, Cohen’s d effect size=0·8) than those without microcytosis. The ferritin concentration which best predicted microcytosis was calculated as 18·4 µg/l (AUC=0·87 (95% CI 0·75, 0·98), P<0·0001, sensitivity 92 %, specificity 75 %). Using 18·5 µg/l as a threshold, children with concentrations <18·5 µg/l had significantly lower mean cognitive composite scores (92·3 (sd 10·5) v. 97·8 (sd 8·1), P=0·012, Cohen’s d effect size=0·6) compared with those with ferritin ≥18·5 µg/l. All associations were robust after adjustment for potential confounding factors. Despite a low prevalence of Fe deficiency using current diagnostic criteria in this healthy cohort, microcytosis was associated with lower cognitive outcomes at 2 years. This exploratory study emphasises the need for re-evaluation of the diagnostic criteria for Fe deficiency in young children, with further research in adequately powered studies warranted.

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Corresponding author

* Corresponding author: Dr D. M. Murray, email d.murray@ucc.ie

References

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1. Agostoni, C, Decsi, T, Fewtrell, M, et al. (2008) Complementary feeding: a commentary by the ESPGHAN Committee on Nutrition. J Pediatr Gastroenterol Nutr 46, 99110.
2. McCarthy, EK, Ní Chaoimh, C, Hourihane, JO, et al. (2017) Iron intakes and status of 2-year-old children in the Cork BASELINE Birth Cohort Study. Matern Child Nutr 13, e12320.
3. Gunnarsson, BS, Thorsdottir, I & Palsson, G (2004) Iron status in 2-year-old Icelandic children and associations with dietary intake and growth. Eur J Clin Nutr 58, 901906.
4. McLean, E, Cogswell, M, Egli, I, et al. (2009) Worldwide prevalence of anaemia, WHO Vitamin and Mineral Nutrition Information System, 1993–2005. Public Health Nutr 12, 444454.
5. Eussen, S, Alles, M, Uijterschout, L, et al. (2015) Iron intake and status of children aged 6-36 months in Europe: a systematic review. Ann Nutr Metab 66, 8092.
6. Lozoff, B & Georgieff, MK (2006) Iron deficiency and brain development. Semin Pediatr Neurol 13, 158165.
7. Lozoff, B (2007) Iron deficiency and child development. Food Nutr Bull 28, 4 Suppl., S560S571.
8. Lozoff, B, Beard, J, Connor, J, et al. (2006) Long-lasting neural and behavioral effects of iron deficiency in infancy. Nutr Rev 64, 5 Pt 2, S34S43; discussion S72–S91.
9. Grantham-McGregor, S & Ani, C (2001) A review of studies on the effect of iron deficiency on cognitive development in children. J Nutr 131, 2S-2, 649S666S; discussion 666S-668S.
10. Lozoff, B, Smith, JB, Kaciroti, N, et al. (2013) Functional significance of early-life iron deficiency: outcomes at 25 years. J Pediatr 163, 12601266.
11. Kenny, LC, Black, MA, Poston, L, et al. (2014) Early pregnancy prediction of preeclampsia in nulliparous women, combining clinical risk and biomarkers: the Screening for Pregnancy Endpoints (SCOPE) international cohort study. Hypertension 64, 644652.
12. O’Donovan, SM, Murray, DM, Hourihane, JO, et al. (2015) Cohort profile: The Cork BASELINE Birth Cohort Study: Babies after SCOPE: Evaluating the Longitudinal Impact on Neurological and Nutritional Endpoints. Int J Epidemiol 44, 764775.
13. O’Neill, SM, Hannon, G, Khashan, AS, et al. (2017) Thin-for-gestational age infants are at increased risk of neurodevelopmental delay at 2 years. Arch Dis Child Fetal Neonatal Ed 102, F197–F202.
14. McCowan, LM, Thompson, JM, Taylor, RS, et al. (2013) Clinical prediction in early pregnancy of infants small for gestational age by customised birthweight centiles: findings from a healthy nulliparous cohort. PLOS ONE 8, e70917.
15. Bayley, N (2006) The Bayley Scales of Infant and Toddler Development, 3rd ed. San Antonio, TX: The Psychological Corporation.
16. Savchev, S, Sanz-Cortes, M, Cruz-Martinez, R, et al. (2013) Neurodevelopmental outcome of full-term small-for-gestational-age infants with normal placental function. Ultrasound Obstet Gynecol 42, 201206.
17. Rao, R & Georgieff, MK (2007) Iron in fetal and neonatal nutrition. Semin Fetal Neonatal Med 12, 5463.
18. Thorisdottir, AV, Thorsdottir, I & Palsson, GI (2011) Nutrition and iron status of 1-year olds following a Revision in infant dietary recommendations. Anemia 2011, 986303.
19. Vendt, N, Grunberg, H, Leedo, S, et al. (2007) Prevalence and causes of iron deficiency anemias in infants aged 9 to 12 months in Estonia. Medicina (Kaunas) 43, 947952.
20. Lozoff, B, Brittenham, GM, Wolf, AW, et al. (1987) Iron deficiency anemia and iron therapy effects on infant developmental test performance. Pediatrics 79, 981995.
21. Brotanek, JM, Gosz, J, Weitzman, M, et al. (2007) Iron deficiency in early childhood in the United States: risk factors and racial/ethnic disparities. Pediatrics 120, 568575.
22. Freeman, VE, Mulder, J, van’t Hof, MA, et al. (1998) A longitudinal study of iron status in children at 12, 24 and 36 months. Public Health Nutr 1, 93100.
23. Shafir, T, Angulo-Barroso, R, Jing, Y, et al. (2008) Iron deficiency and infant motor development. Early Hum Dev 84, 479485.
24. Gunnarsson, BS, Thorsdottir, I, Palsson, G, et al. (2007) Iron status at 1 and 6 years versus developmental scores at 6 years in a well-nourished affluent population. Acta Paediatr 96, 391395.
25. Thorisdottir, AV, Gunnarsdottir, I, Palsson, GI, et al. (2013) Iron status and developmental scores in 6-year-olds highlights ongoing need to tackle iron deficiency in infants. Acta Paediatr 102, 914919.
26. Sherriff, A, Emond, A, Bell, JC, et al. (2001) Should infants be screened for anaemia? A prospective study investigating the relation between haemoglobin at 8, 12, and 18 months and development at 18 months. Arch Dis Child 84, 480485.
27. Johnson, SR, Winkleby, MA, Boyce, WT, et al. (1992) The association between hemoglobin and behavior problems in a sample of low-income Hispanic preschool children. J Dev Behav Pediatr 13, 209214.
28. Ruff, HA, Markowitz, ME, Bijur, PE, et al. (1996) Relationships among blood lead levels, iron deficiency, and cognitive development in two-year-old children. Environ Health Perspect 104, 180185.
29. DeLoughery, TG (2014) Microcytic anemia. N Engl J Med 371, 13241331.
30. Domellof, M, Braegger, C, Campoy, C, et al. (2014) Iron requirements of infants and toddlers. J Pediatr Gastroenterol Nutr 58, 119129.
31. Shafir, T, Angulo-Barroso, R, Calatroni, A, et al. (2006) Effects of iron deficiency in infancy on patterns of motor development over time. Hum Mov Sci 25, 821838.
32. Doom, JR & Georgieff, MK (2014) Striking while the iron is hot: understanding the biological and neurodevelopmental effects of iron deficiency to optimize intervention in early childhood. Curr Pediatr Rep 2, 291298.
33. Wainwright, PE & Colombo, J (2006) Nutrition and the development of cognitive functions: interpretation of behavioral studies in animals and human infants. Am J Clin Nutr 84, 961970.
34. Canals, J, Hernandez-Martinez, C, Esparo, G, et al. (2011) Neonatal Behavioral Assessment Scale as a predictor of cognitive development and IQ in full-term infants: a 6-year longitudinal study. Acta Paediatr 100, 13311337.

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Microcytosis is associated with low cognitive outcomes in healthy 2-year-olds in a high-resource setting

  • Elaine K. McCarthy (a1) (a2), Mairead E. Kiely (a1) (a2), Geraldine Hannon (a2), Caroline Ahearne (a2), Louise C. Kenny (a2) (a3), Jonathan O’B. Hourihane (a2) (a4), Alan D. Irvine (a5) (a6) (a7) and Deirdre M. Murray (a2) (a4)...

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