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The association between maternal immune activation and brain structure and function in human offspring: a systematic review

Molecular Psychiatry volume 30, pages 722–735 (2025)Cite this article

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Abstract

Maternal immune activation (MIA) during pregnancy, as a result of infectious or inflammatory stimuli, has gained increasing attention for its potential role in adverse child neurodevelopment, with studies focusing on associations in children born preterm. This systematic review summarizes research on the link between several types of prenatal MIA and subsequent child structural and/or functional brain development outcomes. We identified 111 neuroimaging studies in five MIA areas: inflammatory biomarkers (n = 13), chorioamnionitis (n = 18), other types of infections (n = 18), human immunodeficiency virus (HIV) (n = 42), and Zika virus (n = 20). Overall, there was large heterogeneity in the type of MIA exposure examined and in study methodology. Most studies had a prospective single cohort design and mainly focused on potential effects on the brain up to one year after birth. The median sample size was 53 participants. Severe infections, i.e., HIV and Zika virus, were associated with various types of cerebral lesions (e.g., microcephaly, atrophy, or periventricular leukomalacia) that were consistently identified across studies. For less severe infections and chronic inflammation, findings were generally inconsistent and mostly included deviations in white matter structure/function. Current findings have been mainly observed in the infants’ brain, presenting an opportunity for future studies to investigate whether these associations persist throughout development. Additionally, the inconsistent findings, encompassing both regions of interest and null results, call into question whether prenatal exposure to less severe infections and chronic inflammation exerts a small effect or no effect on child brain development.

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Fig. 1: Prisma Flow Diagram.
Fig. 2: Distribution of included cohort/case-control studies.
Fig. 3: Neuroimaging findings within a modality type observed in the same direction in at least two studies for the exposure ‘inflammatory biomarkers’.
Fig. 4: Neuroimaging findings within a modality type observed in the same direction in at least two studies for the exposure ‘chorioamnionitis’.
Fig. 5: Neuroimaging findings within a modality type observed in the same direction in at least two studies for the exposure ‘infections’ other than HIV and Zika virus.

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Acknowledgements

The authors would like to thank the medical library of the Erasmus MC for their help during the search strategy process and for performing the systematic search. Moreover, this project was funded by NIH grant: 1R01MH124776.

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Authors and Affiliations

  1. Department of Child and Adolescent Psychiatry/Psychology, Erasmus University Medical Center, Rotterdam, The Netherlands

    Anna Suleri, Olga Dmitrichenko, Ryan L. Muetzel & Charlotte A. M. Cecil

  2. The Generation R Study Group, Erasmus University Medical Center, Rotterdam, the Netherlands

    Anna Suleri

  3. Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Anna-Sophie Rommel, Olga Dmitrichenko, Lot de Witte & Veerle Bergink

  4. Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands

    Ryan L. Muetzel

  5. Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands

    Charlotte A. M. Cecil

  6. Department of Biomedical Data Sciences, Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands

    Charlotte A. M. Cecil

  7. Department of Psychiatry, Radboud UMC, Nijmegen, The Netherlands

    Lot de Witte

  8. Department of Psychiatry, Erasmus University Medical Center, Rotterdam, The Netherlands

    Veerle Bergink

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  1. Anna Suleri
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  2. Anna-Sophie Rommel
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  3. Olga Dmitrichenko
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  4. Ryan L. Muetzel
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  6. Lot de Witte
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  7. Veerle Bergink
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Contributions

Anna Suleri: conceptualization, data curation, investigation, visualization, writing – original draft, project administration. Anna-Sophie Rommel: conceptualization, validation, writing – review & editing. Olga Dmitrichenko: conceptualization, investigation, validation, writing – review & editing. Ryan Muetzel: conceptualization, writing – review & editing. Charlotte Cecil: writing – review & editing. Lot de Witte: conceptualization, writing – review & editing, funding acquisition. Veerle Bergink: conceptualization, supervision, validation, writing – review & editing, project administration, funding acquisition.

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Correspondence to Veerle Bergink.

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Suleri, A., Rommel, AS., Dmitrichenko, O. et al. The association between maternal immune activation and brain structure and function in human offspring: a systematic review. Mol Psychiatry 30, 722–735 (2025). https://doi.org/10.1038/s41380-024-02760-w

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