Maternal early-pregnancy ferritin and offspring neurodevelopment: A prospective cohort study from gestation to school age

Sara Sammallahti*, Henning Tiemeier, Irwin K.M. Reiss, Martina U. Muckenthaler, Hanan El Marroun, Marijn Vermeulen

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Background: Iron plays a role in many key processes in the developing brain. During pregnancy, iron supplementation is widely recommended to prevent and treat iron deficiency; however, the prevalence of iron deficiency and the risk of iron overload vary greatly between populations. Evidence on the role of high levels of maternal ferritin, a storage iron marker during pregnancy in relation to offspring neurodevelopment is lacking. Objective: Our main objective was to examine if maternal ferritin levels during pregnancy are associated with child cognitive and motor abilities. Methods: We included Dutch mother-child dyads from the prospective population-based Generation R Study, born in 2002–2006. We compared children whose mothers had high (standard deviation score >+1) or low (standard deviation score <−1) early-pregnancy ferritin to children whose mothers had intermediate ferritin (reference group) using linear regression. Children underwent non-verbal intelligence and language tests at 4–9 years (cognitive abilities), finger-tapping and balancing tests at 8–12 years (motor abilities), and structural magnetic resonance imaging at 8–12 years (brain morphology). Covariates were child age, sex, maternal intelligence quotient estimate, age, body-mass-index, education, parity, smoking and alcohol use. Results: Of the 2479 mother-child dyads with data on maternal ferritin and at least one child neurodevelopmental outcome, 387 mothers had low (mean = 20.6 µg/L), 1700 intermediate (mean = 64.6 µg/L) and 392 high (mean = 170.3 µg/L) early-pregnancy ferritin. High maternal ferritin was associated with 2.54 points (95% confidence interval -4.16, -0.92) lower child intelligence quotient and 16.02 cm3 (95% confidence interval -30.57, -1.48) smaller brain volume. Results remained similar after excluding mothers with high C-reactive protein. Low maternal ferritin was not associated with child cognitive abilities. Maternal ferritin was unrelated to child motor outcomes. Conclusion: High maternal ferritin during pregnancy was associated with poorer child cognitive abilities and smaller brain volume. Maternal iron status during pregnancy may be associated with offspring neurodevelopment.

Original languageEnglish
Pages (from-to)425-434
Number of pages10
JournalPaediatric and Perinatal Epidemiology
Volume36
Issue number3
DOIs
Publication statusPublished - May 2022

Bibliographical note

Funding Information:
This study was supported by the Netherlands Organization for Scientific Research (NWO) and the Dutch Ministry of Health, Welfare and Sport (general design of the Generation R Study); LEaDing Fellows EU Marie Skłodowska‐Curie COFUND Programme (Dr Sammallahti); NWO Vici Grant 016.VICI.170.200 (Dr Tiemeier); and Stichting Volksbond Rotterdam, the Brain & Behavior Research Foundation NARSAD Young Investigator Grant 27853, and the European Union's Horizon 2020 Research and Innovation Program LifeCycle grant No. 733206 (Dr El Marroun). Funding sources had no role in study design, data collection, analysis or interpretation, reporting or submission for publication

Publisher Copyright: © 2021 The Authors. Paediatric and Perinatal Epidemiology published by John Wiley & Sons Ltd.

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