A systematic literature review of the relation between iron status/anemia in pregnancy and offspring neurodevelopment

Abstract

Background

The fetal brain starts developing early and animal studies have suggested that iron plays several roles for the development, but results from epidemiological studies investigating associations between gestational iron and offspring neurodevelopment are inconsistent.

Objective

To systematically examine results from observational studies and RCTs on gestational iron and offspring neurodevelopment, with focus on the importance of four domains: iron status indicators, exposure timing, neurodevelopmental outcomes, and offspring age.

Methods

PRISMA guidelines were followed. Embase, PsychInfo, Scopus, and The Cochrane library were searched in September 2017 and February 2018. Overall, 3307 articles were identified and 108 retrieved for full-text assessment. Pre-specified eligibility criteria were used to select studies and 27 articles were included;19 observational and 8 RCTs.

Results

Iron status in pregnancy was associated with offspring behavior, cognition, and academic achievement. The direction of associations with behavioral outcomes were unclear and the conclusions related to cognition and academic achievement were based on few studies, only. Little evidence was found for associations with motor development. Observed associations were shown to persist beyond infancy into adolescence, and results depended on iron status indicator type but not on the timing of exposure.

Conclusion

We conclude that there is some evidence that low pregnancy iron, possibly particularly in the 3rd trimester, may be associated with adverse offspring neurodevelopment. As most previous research used Hemoglobin, inferring results to iron deficiency should be done with caution. No conclusions could be reached regarding associations beyond early childhood, and supplementation with iron during pregnancy did not seem to influence offspring neurodevelopment.

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Acknowledgements

We acknowledge the contribution of the statistician Volkert Siersma from the University of Copenhagen to our work through providing statistical help and Gabriel Gulis from the University of Southern Denmark for supervising the writing process.

Funding

Twelve months of under-graduate research stipend was received from the Lundbeck Foundation.

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JJ, IOS, and BLH were responsible for project conception and developed the overall research plan. JJ and MS conducted the search. JJ analyzed data. JJ, IOS, and BLH wrote the paper. JJ had primary responsibility for final content. All authors read and approved the final manuscript.

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Correspondence to Berit L. Heitmann.

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Janbek, J., Sarki, M., Specht, I.O. et al. A systematic literature review of the relation between iron status/anemia in pregnancy and offspring neurodevelopment. Eur J Clin Nutr 73, 1561–1578 (2019). https://doi.org/10.1038/s41430-019-0400-6

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