Zhou SJ, Gibson RA, Crowther CA, Baghurst P, Makrides M. Effect of iron supplementation during pregnancy on the intelligence quotient and behavior of children at 4 y of age: long-term follow-up of a randomized controlled trial. Am J Clin Nutr 83, 1112-1117

Child Nutrition Research Centre and the Department of Pediatrics, Women's & Children's Hospital, University of Adelaide, North Adelaide, Australia.
American Journal of Clinical Nutrition (Impact Factor: 6.77). 06/2006; 83(5):1112-7.
Source: PubMed


Iron supplements are often prescribed during pregnancy despite the lack of intervention trials that have assessed the effects of supplementation in pregnancy on childhood development.
The objective was to determine whether iron supplementation during pregnancy influences childhood intelligence quotient (IQ) in an industrialized country.
Pregnant women (n = 430) were randomly allocated to receive iron (20 mg/d) or placebo from 20 wk gestation until delivery, and the women and their children were followed up over the long term (4 y). Seventy percent of these families participated in the follow-up. The proportion of women with iron deficiency anemia at the end of pregnancy was 1% (2 of 146) in the iron group and 11% (15 of 141) in the placebo group. The primary outcome was the IQ of the children at 4 y of age, as assessed by the Stanford-Binet Intelligence Scale. Secondary outcomes included child behavior and the general health of the mothers.
The mean IQ was not significantly different (P = 0.980) between the children of the iron-supplemented mothers (109 +/- 11; n = 153) and the children of the mothers in the placebo group (109 +/- 11; n = 149). However, the percentage of children with an abnormal behavior score was higher in the iron group (24 of 151, or 16%) than in the placebo group (12 of 149, or 8%); the relative risk was 1.97 (95% CI: 1.03, 3.80; P = 0.037). There was no significant difference in the health of the mothers between groups, as assessed by the SF-36 Health Survey.
Prenatal iron supplementation that reduces the incidence of iron deficiency anemia from 11% to 1% has no effect on the IQ of the offspring at 4 y of age.

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Available from: Peter Baghurst, Oct 05, 2015
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    • "(ASN) [PREPRINTER stage] Similar to other nutritional deficiencies, ID occurs as a spectrum beginning with tissue iron store depletion and, if unsupplemented, progressing to impaired erythropoiesis or anemia (Connor et al., 2001; Collard, 2009; Ganz, 2013). All stages of maternal ID have been associated with adverse effects on the offspring, but only the most severe stage of ID can be reliably diagnosed via maternal blood or cord blood samples (Scholl and Reilly, 2000; Gambling et al., 2003; Lisle et al., 2003; Gambling et al., 2004; Andersen et al., 2006; Felt et al., 2006; Zhou et al., 2006; Zimmermann et al., 2007; Banhidy et al., 2010). Marginal maternal iron intake leads to low fetal Fe levels in CNS tissue but is below the threshold of generating anemia. "
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    ABSTRACT: The deleterious effects of anemia on auditory nerve (AN) development have been well investigated; however, we have previously reported that significant functional consequences in the auditory brainstem response (ABR) can also occur as a consequence of marginal iron deficiency (ID). As the ABR has widespread clinical use, we evaluated the ability of this electrophysiological method to characterize the threshold of tissue ID in rats by examining the relationship between markers of tissue ID and severity of ABR latency defects. To generate various levels of ID, female Long-Evans rats were exposed to diets containing sufficient, borderline, or deficient iron (Fe) concentrations throughout gestation and offspring lifetime. We measured hematological indices of whole body iron stores in dams and offspring to assess the degree of ID. Progression of AN ID in the offspring was measured as ferritin protein levels at different times during postnatal development to complement ABR functional measurements. The severity of ABR deficits correlated with the level of Fe restriction in each diet. The sufficient Fe diet did not induce AN ID and consequently did not show an impaired ABR latency response. The borderline Fe diet, which depleted AN Fe stores but did not cause systemic anemia resulted in significantly increased ABR latency isolated to Peak I.The low Fe diet, which induced anemia and growth retardation, significantly increased ABR latencies of Peaks I to IV. Our findings indicate that changes in the ABR could be related to various degrees of ID experienced throughout development.
    ASN Neuro 01/2015; 7(1). DOI:10.1177/1759091415569911 · 4.02 Impact Factor
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    • "On the other hand, Rioux et al. [12] in a study of 63 mother infant pairs in Canada found no significant relationship between maternal antenatal iron level and infant’s cognitive performance at 6 months. Several trials of universal antenatal iron supplementation have also concluded that it had no consistent effect on the intelligence quotient of children when they were four years old [13] and child behavior at early school age [14]. All of the human studies were conducted in well-nourished populations in high-income countries. "
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    ABSTRACT: The aim of this study was to examine the effects of antenatal exposure to iron deficiency anemia (IDA) and common mental disorders (CMD) on cognitive development of 6 months old infants in a developing country. A prospective population-based study in a rural province in Vietnam, which enrolled pregnant women at 12-20 weeks gestation and followed them up with their infants until six months postpartum. Criteria for IDA were Hb <11 g/dL and serum ferritin <15 ng/mL. CMD symptoms were assessed by the Edinburgh Postnatal Depression Scale-Vietnam validation. Infant cognitive development was assessed by Bayley Scales of Infant and Toddler Development, 3(rd) Ed. Path analyses were performed to determine the direct and indirect, partly or fully mediated, causal effects of the antenatal exposures. A total of 497 pregnant women were recruited, of those 378 women provided complete data which were included in the analyses. Statistically significant direct adverse effects of persistent antenatal IDA (estimated difference of -11.62 points; 95% CI -23.01 to -0.22) and antenatal CMD (-4.80 points; 95% CI: -9.40 to -0.20) on infant Bayley cognitive scores at six months were found. Higher birthweight, household wealth, and self-rated sufficient supply of breastmilk were associated with higher cognitive scores. Maternal age >30 years and primiparity had an indirect adverse effect on infants' Bayley cognitive scores. These findings suggest that antenatal IDA and CMD both have adverse effects on child cognitive development, which if unrecognized and unaddressed are likely to be lasting. It is crucial that both these risks are considered by policy makers, clinicians, and researchers seeking to improve child cognitive function in developing countries.
    PLoS ONE 09/2013; 8(9):e74876. DOI:10.1371/journal.pone.0074876 · 3.23 Impact Factor
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    • "This review includes two publications (both study quality A) from the same Australian RCT assessing the effects of iron supplementation during pregnancy on offspring cognitive/behavioral function (39, 40). These studies show that iron supplements (20 mg/day) during the last half of gestation did not have any effect on cognitive function at 4 years or on behavioral scores at 6–8 years in the offspring. "
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    ABSTRACT: The present literature review is part of the NNR5 project with the aim of reviewing and updating the scientific basis of the 4th edition of the Nordic Nutrition Recommendations (NNR) issued in 2004. The objective of this systematic literature review was to assess the health effects of different intakes of iron, at different life stages (infants, children, adolescents, adults, elderly, and during pregnancy and lactation), in order to estimate the requirement for adequate growth, development, and maintenance of health. The initial literature search resulted in 1,076 abstracts. Out of those, 276 papers were identified as potentially relevant. Of those, 49 were considered relevant and were quality assessed (A, B, or C). An additional search on iron and diabetes yielded six articles that were quality assessed. Thus, a total of 55 articles were evaluated. The grade of evidence was classified as convincing (grade 1), probable (grade 2), suggestive (grade 3), and inconclusive (grade 4). There is suggestive evidence that prevention or treatment of iron deficiency (ID) and iron deficiency anemia (IDA) improves cognitive, motoric, and behavioral development in young children, and that treatment of IDA improves attention and concentration in school children and adult women. There is insufficient evidence to show negative health effects of iron intakes in doses suggested by the NNR 4. There is insufficient evidence to suggest that normal birth weight, healthy, exclusively breast-fed infants need additional dietary iron before 6 months of life in the Nordic countries. An iron concentration of 4-8 mg/L in infant formulas seems to be safe and effective for normal birth weight infants. There is probable evidence that iron supplements (1-2 mg/kg/day) given up to 6 months of age to infants with low birth weight (<2,500 g) prevents IDA and possibly reduce the risk of behavioral problems later on. There is probable evidence that ID and IDA in pregnant women can be effectively prevented by iron supplementation at a dose of 40 mg/day from week 18-20 of gestation. There is probable evidence that a high intake of heme iron, but not total dietary, non-heme or supplemental iron, is associated with increased risk of type 2 diabetes (T2D) and gestational diabetes. Overall, the evidence does not support a change of the iron intakes recommended in the NNR 4. However, one could consider adding recommendations for infants below 6 months of age, low birth weight infants and pregnant women.
    Food & Nutrition Research 07/2013; 57. DOI:10.3402/fnr.v57i0.21667 · 1.79 Impact Factor
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