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Haemoconcentration risk at the end of pregnancy: effects on neonatal behaviour

  • Nuria Aranda (a1) (a2), Carmen Hernández-Martínez (a3) (a2), Victoria Arija (a1) (a4) (a2), Blanca Ribot (a1) (a2) and Josefa Canals (a3) (a2)...
Abstract Objective

To determine the associations between haemoconcentration at the end of pregnancy (third trimester and delivery) and neonatal behaviour in healthy pregnant women supplemented with moderate doses of Fe.


A prospective longitudinal study in which obstetric and clinical history, maternal toxic habits, maternal anxiety and Hb levels were recorded at the third trimester and delivery. Neonatal behaviour was assessed at 48–72 h of age using the Neonatal Behavioral Assessment Scale.


Unit of Obstetrics and Gynaecology of the Sant Joan University Hospital in Reus, Tarragona (Spain).


A total of 210 healthy and well-nourished pregnant women and their full-term, normal-weight newborns.


The results showed that, after adjusting for confounders, in the third trimester the risk of haemoconcentration (6·2 % of pregnant women) was related to decreased neonatal state regulation (B=−1·273, P=0·006) and alertness (B=−1·848, P=0·006) scores. In addition, the risk of haemoconcentration at delivery (12·0 % of pregnant women) was also related to decreased neonatal state regulation (B=−0·796, P=0·021) and poor robustness and endurance (B=−0·921, P=0·005) scores.


Our results show that the risk of haemoconcentration at the end of pregnancy is related to the neonate’s neurodevelopment (and self-regulation capabilities), suggesting that Fe supplementation patterns and maternal Fe status during pregnancy are important factors for neurodevelopment which may be carefully controlled.

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These authors contributed equally to this work.

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1. World Health Organization (2008) Worldwide Prevalence of Anaemia 1993–2005. WHO Global Database on Anaemia. Geneva: WHO.
2. Aranda N, Ribot B, Garcia E et al. (2011) Pre-pregnancy iron reserves, iron supplementation during pregnancy, and birth weight. Early Hum Dev 87, 791797.
3. Rasmussen K (2001) Is there a causal relationship between iron deficiency or iron-deficiency anemia and weight at birth, length of gestation and perinatal mortality? J Nutr 131, 2S-2, 590S601S.
4. Ribot B, Aranda N, Viteri F et al. (2012) Depleted iron stores without anaemia early in pregnancy carries increased risk of lower birthweight even when supplemented daily with moderate iron. Hum Reprod 27, 12601266.
5. Allen LH (1993) Iron deficiency anemia increases risk of preterm delivery. Nutr Rev 51, 4952.
6. Haider BA, Olofin I, Wang M et al. (2013) Anaemia, prenatal iron use, and risk of adverse pregnancy outcomes: systematic review and meta-analysis. BMJ 346, f3443.
7. Oyemade UJ, Cole OJ, Johnson AA et al. (1994) Prenatal predictors of performance on the Brazelton neonatal behavioural assessment scale. J Nutr 124, 6 Suppl, 1000S1005S.
8. Thompson RA & Nelson CA (2001) Developmental science and the media: early brain development. Am Psychol 56, 515.
9. Cucó G, Fernandez-Ballart J, Arija V et al. (2005) Effect of B1-, B6- and iron intake during pregnancy on neonatal behavior. Int J Vitam Nutr Res 75, 320326.
10. Hernández-Martínez C, Canals J, Aranda N et al. (2011) Effects of iron deficiency on neonatal behavior at different stages of pregnancy. Early Hum Dev 87, 165169.
11. Georgieff MK & Rao R (2001) The role of nutrition in cognitive development. In Handbook in Developmental Cognitive Neuroscience, pp. 491504 [CA Nelson and M Luciana, editors]. Cambridge, MA: MIT Press.
12. Casanueva E & Viteri FE (2003) Iron and oxidative stress in pregnancy. J Nutr 133, 5 Suppl. 2, 1700S1708S.
13. Aranda N, Ribot B, Viteri F et al. (2013) Predictors of haemoconcentration at delivery: association with low birth weight. Eur J Nutr 52, 16311639.
14. Arija V, Ribot B & Aranda N (2013) Prevalence of iron deficiency states and risk of haemoconcentration during pregnancy according to initial iron stores and iron supplementation. Public Health Nutr 16, 13711378.
15. Aisen P, Cohen G & Kang JO (1990) Iron toxicosis. Int Rev Exp Pathol 31, 146.
16. Casanueva E, Viteri F, Mares-Galindo M et al. (2006) Weekly iron as a safe alternative to daily supplementation for nonanemic pregnant women. Arch Med Res 37, 674–668.
17. Papadopoulou E, Stratakis N, Roumeliotaki T et al. (2013) The effect of high doses of folic acid and iron supplementation in early-to-mid pregnancy on prematurity and fetal growth retardation: the mother–child cohort study in Crete, Greece (Rhea study). Eur J Nutr 52, 326336.
18. Khambalia AZ, Aimone A, Nagubandi P et al. (2016) High maternal iron status, dietary iron intake and iron supplement use in pregnancy and risk of gestational diabetes mellitus: a prospective study and systematic review. Diabet Med 33, 12111221.
19. Sandstrom B (2001) Micronutrient interactions: effects on absorption and bioavailability. Br J Nutr 85, Suppl. 2, S181S185.
20. Ziaei S, Norrozi M, Faghihzadeh S et al. (2007) A randomised placebo-controlled trial to determine the effect of iron supplementation on pregnancy outcome in pregnant women with haemoglobin ≥13.2 g/dl. BJOG 114, 684688.
21. Gaillard R, Eilers PH, Yassine S et al. (2014) Risk factors and consequences of maternal anaemia and elevated haemoglobin levels during pregnancy: a population-based prospective cohort study. Paediatr Perinat Epidemiol 28, 213226.
22. Cordina M, Bhatti S, Fernandez M et al. (2015) Association between maternal haemoglobin at 27–29 weeks gestation and intrauterine growth restriction. Pregnancy Hypertens 5, 339345.
23. Steer P, Alam MA, Wadsworth J et al. (1995) Relation between maternal haemoglobin concentration and birth weight in different ethnic groups. BMJ 310, 489491.
24. Peña-Rosas J & Viteri F (2009) Effects and safety of preventive oral iron or iron + folic acid supplementation for women during pregnancy. Cochrane Database Syst Rev issue 4, CD004736.
25. Cung TG, Paus AS, Aghbar A et al. (2014) Stillbirths at a hospital in Nablus, 2010: a cohort study. Glob Health Action 7, 25222.
26. Ellison PT (2010) Fetal programming and fetal psychology. Infant Child Dev 19, 620.
27. Massaro AN, Rothbaum R & Aly H (2006) Fetal brain development: the role of maternal nutrition, exposures and behaviors. Eur J Paediatr Neurol 4, 19.
28. Tamura T, Goldenberg RL, Hou J et al. (2002) Cord serum ferritin concentrations and mental and psychomotor development of children at five years of age. J Pediatr 140, 165170.
29. Hanieh S, Ha TT, Simpson JA et al. (2013) The effect of intermittent antenatal iron supplementation on maternal and infant outcomes in rural Viet Nam: a cluster randomised trial. PLoS Med 10, e1001470.
30. Hernández-Martínez C, Arija V, Balaguer A et al. (2008) Do the emotional states of pregnant women affect neonatal behavior? Early Hum Dev 84, 745750.
31. Hernández-Martínez C, Arija V, Escribano J et al. (2010) Does maternal anxiety affect neonatal behaviour differently in boys and girls? Early Hum Dev 86, 209211.
32. Conroy S, Pariante CM, Marks MN et al. (2012) Maternal psychopathology and infant development at 18 months: the impact of maternal personality disorder and depression. J Am Acad Child Adolesc Psychiatry 51, 5161.
33. Koutra K, Chatzi L, Roumeliotaki T et al. (2012) Socio-demographic determinants of infant neurodevelopment at 18 months of age: Mother–Child Cohort (Rhea Study) in Crete, Greece. Infant Behav Dev 35, 4859.
34. Ding Y, Xu X, Wang Z et al. (2014) The relation of infant attachment to attachment and cognitive and behavioural outcomes in early childhood. Early Hum Dev 90, 459464.
35. Victora CG, Horta BL, de Mola CL et al. (2015) Association between breastfeeding and intelligence, educational attainment, and income at 30 years of age: a prospective birth cohort study from Brazil. Lancet Glob Health 3, e199e205.
36. Angulo-Barroso RM, Schapiro L, Liang W et al. (2011) Motor development in 9-month-old infants in relation to cultural differences and iron status. Dev Psychobiol 53, 196210.
37. Hernández-Martínez C, Arija V, Escribano J et al. (2012) A longitudinal study on the effects of maternal smoking and secondhand smoke exposure during pregnancy on neonatal neurobehavior. Early Hum Dev 88, 403408.
38. Georgieff MK (2007) Nutrition and the developing brain: nutrient priorities and measurement. Am J Clin Nutr 85, issue 2, 614S620S.
39. Dobbing JN & Sands J (1973) Quantitative growth and development of human brain. Arch Dis Child 48, 757767.
40. Rao R & Georgieff MK (2000) Early nutrition and brain development. In The Effects of Early Adversity on Neurobehavioral Development. Symposium on Child Psychology , pp. 130 [CA Nelson, editor]. Hillsdale, NJ: Erlbaum Associates.
41. Chen X, Scholl TO & Stein TP (2006) Association of elevated serum ferritin levels and the risk of gestational diabetes mellitus in pregnant women: the Camden study. Diabetes Care 29, 10771082.
42. Rambod M, Kovesdy CP & Kalantar-Zadeh K (2008) Combined high serum ferritin and low iron saturation in hemodialysis patients: the role of inflammation. Clin J Am Soc Nephrol 3, 16911701.
43. Ministerio de Sanidad y Consumo (2006) Guía para la Prevención de Defectos Congénitos. Madrid: Ministerio de Sanidad y Consumo; available at
44. Gomez F, Simo JM, Camps J et al. (2000) Evaluation of a particle-enhanced turbidimetric immunoassay for the measurement of ferritin: application to patients participating in an autologous blood transfusion program. Clin Biochem 33, 191196.
45. World Health Organization (2011) Haemoglobin Concentrations for the Diagnosis of Anaemia and Assessment of Severity. Vitamin and Mineral Nutrition Information System. Geneva: WHO.
46. World Health Organization, United Nations University & UNICEF (2001) Iron Deficiency Anaemia: Assessment, Prevention, and Control. A Guide for Programme Managers. WHO/NHD/01.3. Geneva: WHO.
47. Brazelton TB & Nugent JK (1997) Escala para la Evaluación del Comportamiento Neonatal. Barcelona: Paidós.
48. Spielberger CD, Gorsuch RL & Lushene RE (1994) STAI Cuestionario de Ansiedad Estado Rasgo [adaptación española: Nicolás Seisdedos Cubero]. Madrid: TEA Ediciones.
49. Hollingshead AB (2011) Four factor index of social status. Yale J Sociol 8, 2152.
50. World Health Organization (2006) Iron and Folate Supplementation. Standards for Maternal and Neonatal Care. Integrated Management of Pregnancy and Childbirth (IMPAC). Geneva: WHO.
51. Aranda N, Viteri FE, Montserrat C et al. (2010) Effects of C282Y, H63D, and S65C HFE gene mutations, diet, and life-style factors on iron status in a general Mediterranean population from Tarragona, Spain. Ann Hematol 89, 767773.
52. Aranda N, Viteri FE, Fernández-Ballart J et al. (2007) Frequency of the hemochromatosis gene (HFE) 282C→Y, 63H→D, and 65S→C mutations in a general Mediterranean population from Tarragona, Spain. Ann Hematol 86, 1721.
53. Walsh T, O’Broin SD, Cooley S et al. (2011) Laboratory assessment of iron status in pregnancy. Clin Chem Lab Med 49, 12251230.
54. Yip R (2000) Significance of an abnormally low or high hemoglobin concentration during pregnancy: special consideration of iron nutrition. Am J Clin Nutr 72, 1 Suppl., 272S279S.
55. Scholl TO (2005) Iron status during pregnancy: setting the stage for mother and infant. Am J Clin Nutr 81, issue 5, 1218S1222S.
56. Brazelton TB & Nugent JK (2011) The Neonatal Behavioral Assessment Scale, 4th ed. Cambridge: Mac Keith Press.
57. Debnath M, Venkatasubramanian G & Berk M (2015) Fetal programming of schizophrenia: select mechanisms. Neurosci Biobehav Rev 49, 90104.
58. Kingston D, McDonald S, Austin M et al. (2015) Association between prenatal and postnatal psychological distress and toddler cognitive development: a systematic review. PLoS One 10, e126929.
59. Glover V (2014) Maternal depression, anxiety and stress during pregnancy and child outcome; what needs to be done. Best Pract Res Clin Obstet Gynaecol 28, 2535.
60. O’Donnell KJ, Glover V, Barker ED et al. (2014) The persisting effect of maternal mood in pregnancy on childhood psychopathology. Dev Psychopathol 26, 393403.
61. Yang L, Ren AG, Liu JM et al. (2010) Influence of hemoglobin level during early gestation on the development of cognition of pre-school children. Zhonghua Liu Xing Bing Xue Za Zhi 31, 13531358.
62. Canals J, Hernández-Martínez C, Esparó 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.
63. Canals J, Esparó G & Fernández-Ballart JD (2006) Neonatal behaviour characteristics and psychological problems at 6 years. Acta Paediatr 95, 14121417.
64. Barker DJ (1998) In utero programming of chronic disease. Clin Sci (Lond) 95, 115128.
65. Iwamoto HS, Murray MA & Chernausek SD (1992) Effects of acute hypoxemia on insulin-like growth factors and their binding proteins in fetal sheep. Am J Physiol 263, 11511156.
66. Kim-Shapiro DB, Schechter AN & Gladwin MT (2006) Unraveling the reactions of nitric oxide, nitrite, and hemoglobin in physiology and therapeutics. Arterioscler Thromb Vasc Biol 26, 697705.
67. Sun L, Macgowan CK, Sled JG et al. (2015) Reduced fetal cerebral oxygen consumption is associated with smaller brain size in fetuses with congenital heart disease. Circulation 131, 13131323.
68. Walter PB, Knutson MD, Paler-Martinez A et al. (2002) Iron deficiency and iron excess damage mitochondria and mitochondrial DNA in rats. Proc Natl Acad Sci U S A 99, 22642269.
69. Viteri FE, Casanueva E, Tolentino MC et al. (2012) Antenatal iron supplements consumed daily produce oxidative stress in contrast to weekly supplementation in Mexican non-anemic women. Reprod Toxicol 34, 125132.
70. Peña-Rosas JP, De-Regil LM, Gomez Malave H et al. (2015) Intermittent oral iron supplementation during pregnancy. Cochrane Database Syst Rev issue 10, CD009997.
71. Shen Y, Yu HM, Yuan TM et al. (2007) Intrauterine infection induced oligodendrocyte injury and inducible nitric oxide synthase expression in the developing rat brain. J Perinat Med 35, 203209.
72. Ribot B, Aranda N, Giralt M et al. (2013) Effect of different doses of iron supplementation during pregnancy on maternal and infant health. Ann Hematol 92, 221229.
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