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Maternal iron levels early in pregnancy are not associated with offspring IQ score at age 8, findings from a Mendelian randomization study.

ABSTRACT: 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.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.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.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.

SUBMITTER: Lewis SJ

PROVIDER: S-EPMC3975809 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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Maternal iron levels early in pregnancy are not associated with offspring IQ score at age 8, findings from a Mendelian randomization study.

Lewis S J SJ Bonilla C C Brion M-J MJ Lawlor D A DA Gunnell D D Ben-Shlomo Y Y Ness A A Smith G D GD

European journal of clinical nutrition 20140108 4

<h4>Background/objectives</h4>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.<h4>Subjects/methods</h4>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 ass ...[more]

PMID: 24398642

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Project description:ObjectivesBreast feeding is associated with health benefits for both mother and child, but many studies focusing on neurodevelopment have lacked information on important confounders and few randomised trials exist. Our objective was to examine the influence of breast feeding on child IQ at 5 years of age while taking maternal IQ and other relevant factors into account.DesignProspective observational study.SettingPopulation-based birth cohort in Denmark.ParticipantsWe used data from The Lifestyle During Pregnancy Study 1782 mother-child pairs sampled from the Danish National Birth Cohort (n=101 042).Outcome measuresChild IQ was assessed at age 5 years by the Wechsler Primary and Preschool Scales of Intelligence-Revised. On the same occasion maternal intelligence was assessed by Wechsler Adult Intelligence Scale and Raven's Standard Progressive Matrices. Exposure data on duration of breast feeding (n=1385) were extracted from telephone interviews conducted when the child was 6 and 18 months, and analyses were weighted by relevant sampling fractions.ResultsIn multivariable linear regression analyses adjusted for potential confounders breast feeding was associated with child IQ at 5 years (categorical χ2 test for overall association p=0.03). Compared with children who were breast fed ≤1 month, children breast fed for 2-3, 4-6, 7-9 and 10 or more months had 3.06 (95% CI 0.39 to 5.72), 2.03 (95% CI -0.38 to 4.44), 3.53 (95% CI 1.18 to 5.87) and 3.28 (95% CI 0.88 to 5.67) points higher IQ after adjustment for core confounders, respectively. There was no dose-response relation and further analyses indicated that the main difference in IQ was between breast feeding ≤1 month versus >1 month.ConclusionsBreastfeeding duration of 1 month or shorter compared with longer periods was associated with approximately three points lower IQ, but there was no evidence of a dose-response relation in this prospective birth cohort, where we were able to adjust for some of the most critical confounders, including maternal intelligence.

Project description:ImportanceThe potential neurotoxicity associated with exposure to fluoride, which has generated controversy about community water fluoridation, remains unclear.ObjectiveTo examine the association between fluoride exposure during pregnancy and IQ scores in a prospective birth cohort.Design, setting, and participantsThis prospective, multicenter birth cohort study used information from the Maternal-Infant Research on Environmental Chemicals cohort. Children were born between 2008 and 2012; 41% lived in communities supplied with fluoridated municipal water. The study sample included 601 mother-child pairs recruited from 6 major cities in Canada; children were between ages 3 and 4 years at testing. Data were analyzed between March 2017 and January 2019.ExposuresMaternal urinary fluoride (MUFSG), adjusted for specific gravity and averaged across 3 trimesters available for 512 pregnant women, as well as self-reported maternal daily fluoride intake from water and beverage consumption available for 400 pregnant women.Main outcomes and measuresChildren's IQ was assessed at ages 3 to 4 years using the Wechsler Primary and Preschool Scale of Intelligence-III. Multiple linear regression analyses were used to examine covariate-adjusted associations between each fluoride exposure measure and IQ score.ResultsOf 512 mother-child pairs, the mean (SD) age for enrollment for mothers was 32.3 (5.1) years, 463 (90%) were white, and 264 children (52%) were female. Data on MUFSG concentrations, IQ scores, and complete covariates were available for 512 mother-child pairs; data on maternal fluoride intake and children's IQ were available for 400 of 601 mother-child pairs. Women living in areas with fluoridated tap water (n = 141) compared with nonfluoridated water (n = 228) had significantly higher mean (SD) MUFSG concentrations (0.69 [0.42] mg/L vs 0.40 [0.27] mg/L; P = .001; to convert to millimoles per liter, multiply by 0.05263) and fluoride intake levels (0.93 [0.43] vs 0.30 [0.26] mg of fluoride per day; P = .001). Children had mean (SD) Full Scale IQ scores of 107.16 (13.26), range 52-143, with girls showing significantly higher mean (SD) scores than boys: 109.56 (11.96) vs 104.61 (14.09); P = .001. There was a significant interaction (P = .02) between child sex and MUFSG (6.89; 95% CI, 0.96-12.82) indicating a differential association between boys and girls. A 1-mg/L increase in MUFSG was associated with a 4.49-point lower IQ score (95% CI, -8.38 to -0.60) in boys, but there was no statistically significant association with IQ scores in girls (B = 2.40; 95% CI, -2.53 to 7.33). A 1-mg higher daily intake of fluoride among pregnant women was associated with a 3.66 lower IQ score (95% CI, -7.16 to -0.14) in boys and girls.Conclusions and relevanceIn this study, maternal exposure to higher levels of fluoride during pregnancy was associated with lower IQ scores in children aged 3 to 4 years. These findings indicate the possible need to reduce fluoride intake during pregnancy.

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Dataset Information

Maternal iron levels early in pregnancy are not associated with offspring IQ score at age 8, findings from a Mendelian randomization study.

Publications

Maternal iron levels early in pregnancy are not associated with offspring IQ score at age 8, findings from a Mendelian randomization study.

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