Archival Report| Volume 87, ISSUE 10, P898-907, May 15, 2020

Persistently High Levels of Maternal Antenatal Inflammation Are Associated With and Mediate the Effect of Prenatal Environmental Adversities on Neurodevelopmental Delay in the Offspring

  • Polina Girchenko
    Address correspondence to Polina Girchenko, Ph.D., Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland. Haartmaninkatu 3, P.O. Box 9, FI-00014 University of Helsinki, Helsinki, Finland.
    Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland
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  • Marius Lahti-Pulkkinen
    Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland

    Public Health Promotion Unit, National Institute for Health and Welfare, Helsinki, Finland

    Centre for Cardiovascular Science, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom
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  • Kati Heinonen
    Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland
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  • Rebecca M. Reynolds
    Centre for Cardiovascular Science, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom
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  • Hannele Laivuori
    Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland

    Department of Medical and Clinical Genetics, University of Helsinki and Helsinki University Hospital, Helsinki, Finland

    Department of Obstetrics and Gynecology, Tampere University Hospital and Faculty of Medicine and Health Technology, University of Tampere, Tampere, Finland
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  • Jari Lipsanen
    Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland
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  • Pia M. Villa
    Department of Medical and Clinical Genetics, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
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  • Esa Hämäläinen
    Department of Clinical Chemistry, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
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  • Eero Kajantie
    Public Health Promotion Unit, National Institute for Health and Welfare, Helsinki, Finland

    Children’s Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland

    PEDEGO Research Unit, MRC Oulu, Oulu University Hospital, University of Oulu, Oulu, Finland

    Department of Clinical and Molecular Medicine, Norwegian University for Science and Technology, Trondheim, Norway
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  • Jari Lahti
    Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland

    Turku Institute for Advanced Studies, University of Turku, Turku, Finland
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  • Katri Räikkönen
    Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland
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Published:December 13, 2019DOI:



      Prenatal exposure to environmental adversities, including maternal overweight/obesity, diabetes/hypertensive disorders, or mood/anxiety disorders, increases the risk for adverse neurodevelopmental outcomes in children. However, the underlying biological mechanisms remain elusive. We tested whether maternal antenatal inflammation was associated with the number of neurodevelopmental delay areas in children and whether it mediated the association between exposure to any prenatal environmental adversity and child neurodevelopmental delay.


      Mother-child dyads (N = 418) from the PREDO (Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction) study were followed up to 10.8 years. We analyzed maternal plasma high-sensitivity C-reactive protein and glycoprotein acetyls at 3 consecutive antenatal time points, measured maternal body mass index in early pregnancy, extracted data on diabetes/hypertensive disorders in pregnancy from medical records, and extracted data on mood/anxiety disorders until childbirth from the Care Register for Health Care. To estimate the number of neurodevelopmental delay areas in children across cognitive, motor, and social functioning, we pooled data from the Care Register for Health Care on psychological development disorders with mother-reported Ages and Stages Questionnaire data on developmental milestones.


      Higher levels of maternal high-sensitivity C-reactive protein and glycoprotein acetyls at and across all 3 antenatal time points were associated with 1.30- to 2.36-fold (p values < .02) increased relative risk for higher number of areas of child neurodevelopmental delay. Higher maternal inflammation across the 3 time points also mediated the effect of any prenatal environmental adversity on child neurodevelopmental delay.


      Higher levels of maternal inflammation, especially when persisting throughout pregnancy, increase a child’s risk of neurodevelopmental delay and mediate the effect of prenatal environmental adversity on child neurodevelopmental delay.


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      Linked Article

      • The Maternal Immunome as a Potential Biomarker for the Child’s Neurodevelopmental Trajectory
        Biological PsychiatryVol. 87Issue 10
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          Environmental influences in pregnancy shape the neurodevelopmental trajectory of the child. This process is known as fetal programming and was first introduced by Barker (1), who posed the hypothesis that any stimulus during the critical period of embryonic and fetal development, such as insufficient nutrition, can lead to permanent structural, physiological, or metabolic changes in the offspring and thus might predispose the fetus for postnatal disease (2).
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