title: Maternal iron levels early in pregnancy are not associated with offspring IQ score at age 8, findings from a Mendelian randomization study.
abstract: OBJECTIVE
  Iron is fundamental to many basic biological functions, and animal studies suggest that iron deficiency early in life can have a lasting impact on the developing brain.
  
  
  METHODS
  We used a population-based cohort of mothers and their children to assess the effect of iron status among pregnant women on the cognitive ability of their offspring. But to avoid the inherent confounding that occurs within observational epidemiology studies we examined the association of maternal genotype at single-nucleotide polymorphisms in the genes HFE (rs1799945) and (rs1800562), TF (rs3811647) and TMPRSS6 (rs1800562), which are related to iron, haemoglobin or transferrin levels, on their child's cognitive test scores at age 8.
  
  
  RESULTS
  We found strong associations between HFE and TMPRSS6 genotypes and mother's haemoglobin levels early in pregnancy (P-values are all ≤ 4.1 × 10(-5)) and a genetic score comprised of alleles at these loci was even more strongly associated with haemoglobin levels (P=3.0 × 10(-18)), suggesting that this was a good instrument to use to look at the effect of prenatal iron levels on offspring cognition. However, mother's genotype at the above loci was not associated with offspring IQ at age 8.
  
  
  CONCLUSIONS
  We therefore concluded that there is no evidence of an effect of exposure to low levels of iron (within the normal range) in pregnancy on offspring cognition at age 8. However, pregnant women in the UK with low haemoglobin levels are prescribed iron supplements and so we were unable to look at the effect of iron deficiency in our study.
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: S J
authors.initials: SJ
authors.lastname: Lewis
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: C
authors.initials: C
authors.lastname: Bonilla
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: M-J
authors.initials: MJ
authors.lastname: Brion
authors.affiliation: MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: D A
authors.initials: DA
authors.lastname: Lawlor
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: D
authors.initials: D
authors.lastname: Gunnell
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Y
authors.initials: Y
authors.lastname: Ben-Shlomo
authors.affiliation: School of Oral and Dental Sciences, University of Bristol, Bristol, UK.
authors.forename: A
authors.initials: A
authors.lastname: Ness
authors.affiliation: MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: G D
authors.initials: GD
authors.lastname: Smith
mesh_terms: D018798:Anemia, Iron-Deficiency / Q000188:drug therapy / Q000235:genetics; D002648:Child; D003071:Cognition / Q000187:drug effects*; D019587:Dietary Supplements; D005260:Female; D056426:Genetic Loci; D005838:Genotype; D000071020:Hemochromatosis Protein; D006454:Hemoglobins / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006801:Humans; D019266:Iron, Dietary / Q000008:administration & dosage / Q000097:blood*; D016015:Logistic Models; D008137:Longitudinal Studies; D039382:Maternal Nutritional Physiological Phenomena; D008565:Membrane Proteins / Q000235:genetics; D009752:Nutritional Status; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D012697:Serine Endopeptidases / Q000235:genetics; D012959:Socioeconomic Factors; D014168:Transferrin / Q000378:metabolism
chemical_list: C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D006454:Hemoglobins; D015395:Histocompatibility Antigens Class I; D019266:Iron, Dietary; D008565:Membrane Proteins; D014168:Transferrin; D012697:Serine Endopeptidases; C504318:TMPRSS6 protein, human