Polina Girchenko1, Marius Lahti-Pulkkinen2, Kati Heinonen3, Rebecca M Reynolds4, Hannele Laivuori5, Jari Lipsanen3, Pia M Villa6, Esa Hämäläinen7, Eero Kajantie8, Jari Lahti9, Katri Räikkönen3. 1. Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland. Electronic address: polina.girchenko@helsinki.fi. 2. 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. 3. Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland. 4. Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom. 5. 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. 6. Department of Medical and Clinical Genetics, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. 7. Department of Clinical Chemistry, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. 8. 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. 9. Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Turku Institute for Advanced Studies, University of Turku, Turku, Finland.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Authors: Polina Girchenko; Marius Lahti-Pulkkinen; Jari Lipsanen; Kati Heinonen; Jari Lahti; Ville Rantalainen; Esa Hämäläinen; Hannele Laivuori; Pia M Villa; Eero Kajantie; Katri Räikkönen Journal: Mol Psychiatry Date: 2022-08-10 Impact factor: 13.437
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