University of Oulu

Anna Suarez, Jari Lahti, Marius Lahti-Pulkkinen, Polina Girchenko, Darina Czamara, Janine Arloth, Anni LK. Malmberg, Esa Hämäläinen, Eero Kajantie, Hannele Laivuori, Pia M. Villa, Rebecca M. Reynolds, Nadine Provençal, Elisabeth B. Binder, Katri Räikkönen, A polyepigenetic glucocorticoid exposure score at birth and childhood mental and behavioral disorders, Neurobiology of Stress, Volume 13, 2020, 100275, ISSN 2352-2895,

A polyepigenetic glucocorticoid exposure score at birth and childhood mental and behavioral disorders

Saved in:
Author: Suarez, Anna1; Lahti, Jari1,2; Lahti-Pulkkinen, Marius1,3,4;
Organizations: 1Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Finland
2Turku Institute for Advanced Studies, University of Turku, Turku, Finland
3National Institute for Health and Welfare, Helsinki, Finland
4Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom
5Department of Translational Research in Psychiatry, Max-Planck Institute of Psychiatry, Munich, Germany
6Institute of Computational Biology, Helmholtz Zentrum München, Germany
7Department of Clinical Chemistry, University of Eastern Finland, Kuopio, Finland
8PEDEGO Research Unit, MRC Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
9Department of Clinical and Molecular Medicine, Norwegian University for Science and Technology, Trondheim, Norway
10Children's Hospital, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
11Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland
12Department of Obstetrics and Gynecology, Tampere University Hospital and Faculty of Medicine and Health Technology, University of Tampere, Tampere, Finland
13Medical and Clinical Genetics, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
14Faculty of Health Sciences, Simon Fraser University, Burnaby, BC, Canada
15BC Children's Hospital Research Institute, Vancouver, BC, Canada
16Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, USA
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.1 MB)
Persistent link:
Language: English
Published: Elsevier, 2020
Publish Date: 2021-03-11


Background: Maternal depression and anxiety during pregnancy may enhance fetal exposure to glucocorticoids (GCs) and harm neurodevelopment. We tested whether a novel cross-tissue polyepigenetic biomarker indicative of in utero exposure to GC is associated with mental and behavioral disorders and their severity in children, possibly mediating the associations between maternal prenatal depressive and anxiety symptoms and these child outcomes.

Methods: Children (n = 814) from the Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction (PREDO) study were followed-up from birth to age 7.1–10.7 years. A weighted polyepigenetic GC exposure score was calculated based on the methylation profile of 24 CpGs from umbilical cord blood. Child diagnosis of mental and behavioral disorder (n = 99) and its severity, defined as the number of days the child had received treatment (all 99 had received outpatient treatment and 8 had been additionally in inpatient treatment) for mental or behavioral disorder as the primary diagnosis, came from the Care Register for Health Care. Mothers (n = 408) reported on child total behavior problems at child’s age of 2.3–5.8 years and their own depressive and anxiety symptoms during pregnancy (n = 583).

Results: The fetal polyepigenetic GC exposure score at birth was not associated with child hazard of mental and behavioral disorder (HR = 0.82, 95% CI 0.54; 1.24, p = 0.35) or total behavior problems (unstandardized beta = −0.10, 95% CI -0.31; 0.10, p = 0.33). However, for one standard deviation decrease in the polyepigenetic score, the child had spent 2.94 (95%CI 1.59; 5.45, p < 0.001) more days in inpatient or outpatient treatment with any mental and behavioral disorder as the primary diagnosis. Criteria for mediation tests were not met.

Conclusions: These findings suggest that fetal polyepigenetic GC exposure score at birth was not associated with any mental or behavioral disorder diagnosis or mother-rated total behavior problems, but it may contribute to identifying children at birth who are at risk for more severe mental or behavioral disorders.

see all

Series: Neurobiology of stress
ISSN: 2352-2895
ISSN-E: 2352-2895
ISSN-L: 2352-2895
Volume: 13
Article number: 100275
DOI: 10.1016/j.ynstr.2020.100275
Type of Publication: A1 Journal article – refereed
Field of Science: 3124 Neurology and psychiatry
3123 Gynaecology and paediatrics
Funding: This work was supported by the Academy of Finland, European Union's Horizon 2020 Award (grant number SC1-2016-RTD-733280) for RECAP, European Commission Dynamics of Inequality Across the Life-course: structures and processes (DIAL) (grant number 724363) for PremLife, EVO (special state subsidy for research), Signe and Ane Gyllenberg Foundation, Orion Research Foundation, Emil Aaltonen Foundation, Finnish Medical Foundation, Jane and Aatos Erkko Foundation, Novo Nordisk Foundation, Päivikki and Sakari Sohlberg Foundation, Sigrid Juselius Foundation, Sir Jules Thorn Charitable Trust, Doctoral School of Psychology, Learning and Education, and University of Helsinki Research Funds.
Copyright information: © 2020 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license.