University of Oulu

Polina Girchenko, Marius Lahti-Pulkkinen, Kati Heinonen, Rebecca M. Reynolds, Hannele Laivuori, Jari Lipsanen, Pia M. Villa, Esa Hämäläinen, Eero Kajantie, Jari Lahti, Katri Räikkönen, Persistently High Levels of Maternal Antenatal Inflammation Are Associated With and Mediate the Effect of Prenatal Environmental Adversities on Neurodevelopmental Delay in the Offspring, Biological Psychiatry, Volume 87, Issue 10, 2020, Pages 898-907, ISSN 0006-3223, https://doi.org/10.1016/j.biopsych.2019.12.004

Persistently high levels of maternal antenatal inflammation are associated with and mediate the effect of prenatal environmental adversities on neurodevelopmental delay in the offspring

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Author: Girchenko, Polina1; Lahti-Pulkkinen, Marius1,2,3; Heinonen, Kati1;
Organizations: 1Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland
2Public Health Promotion Unit, National Institute for Health and Welfare, Helsinki, Finland
3Centre for Cardiovascular Science, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom
4Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland
5Department of Medical and Clinical Genetics, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
6Department of Obstetrics and Gynecology, Tampere University Hospital and Faculty of Medicine and Health Technology, University of Tampere, Tampere, Finland
7Department of Clinical Chemistry, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
8Children’s Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
9PEDEGO Research Unit, MRC Oulu, Oulu University Hospital, University of Oulu, Oulu, Finland
10Department of Clinical and Molecular Medicine, Norwegian University for Science and Technology, Trondheim, Norway
11Turku Institute for Advanced Studies, University of Turku, Turku, Finland
Format: article
Version: accepted version
Access: embargoed
Persistent link: http://urn.fi/urn:nbn:fi-fe2020092275531
Language: English
Published: Elsevier, 2020
Publish Date: 2020-12-13
Description:

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 < 0.02) 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.

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Series: Biological psychiatry
ISSN: 0006-3223
ISSN-E: 1873-2402
ISSN-L: 0006-3223
Volume: 87
Issue: 10
Pages: 898 - 907
DOI: 10.1016/j.biopsych.2019.12.004
OADOI: https://oadoi.org/10.1016/j.biopsych.2019.12.004
Type of Publication: A1 Journal article – refereed
Field of Science: 3123 Gynaecology and paediatrics
Subjects:
Funding: The PREDO study is funded by Academy of Finland Grant Nos. 285324, 12848591, 1284859, 1312670, and 269925; European Union's Horizon 2020 Award SC1-2016-RTD-733280 for RECAP; European Commission Dynamics of Inequality Across the Life-course: structures and processes Grant No. 724363 for PremLife, EVO (a special state subsidy for health science research); University of Helsinki Research Funds; the Signe and Ane Gyllenberg Foundation; the Emil Aaltonen Foundation; the Finnish Diabetes Research Foundation; the Foundation for Cardiovascular Research; the Foundation for Pediatric Research; the Jane and Aatos Erkko Foundation; the Novo Nordisk Foundation; the Päivikki and Sakari Sohlberg Foundation; the Sigrid Juselius Foundation; and the Finnish Medical Foundation.
Copyright information: © 2019 Society of Biological Psychiatry. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/.
  https://creativecommons.org/licenses/by-nc-nd/4.0/