University of Oulu

Sammallahti, S., Cortes Hidalgo, A.P., Tuominen, S. et al. Maternal anxiety during pregnancy and newborn epigenome-wide DNA methylation. Mol Psychiatry 26, 1832–1845 (2021).

Maternal anxiety during pregnancy and newborn epigenome-wide DNA methylation

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Author: Sammallahti, Sara1,2,3,4; Cortes Hidalgo, Andrea P.1,2; Tuominen, Samuli4;
Organizations: 1Erasmus MC, Univ Med Ctr Rotterdam, Dept Adolescent & Child Psychiat & Psychol, Rotterdam, Netherlands.
2Erasmus MC, Univ Med Ctr Rotterdam, Generat R Study Grp, Rotterdam, Netherlands.
3Harvard TH Chan Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA USA.
4Univ Helsinki, Dept Psychol & Logoped, Helsinki, Finland.
5Leiden Univ, Inst Educ & Child Studies, Leiden, Netherlands.
6Univ Cincinnati, Coll Med, Dept Environm Hlth, Cincinnati, OH 45267 USA.
7Barcelona Inst Global Hlth, ISGlobal, Barcelona, Spain.
8CIBER Epidemiol & Salud Publ CIBERESP, Barcelona, Spain.
9Univ Pompeu Fabra UPF, Barcelona, Spain.
10Univ Bristol, Bristol Med Sch, MRC Integrat Epidemiol Unit, Populat Hlth Sci, Bristol, Avon, England.
11Icahn Sch Med Mt Sinai, Dept Environm Med & Publ Hlth, New York, NY 10029 USA.
12Icahn Sch Med Mt Sinai, New York, NY 10029 USA.
13Norwegian Inst Publ Hlth, Ctr Fertil & Hlth, Oslo, Norway.
14Oslo Univ Hosp, Oslo Ctr Biostat & Epidemiol, Oslo, Norway.
15Westat Corp, Durham, NC USA.
16St Antoine Med Sch, INSERM, EPAR, UMR S 1136, Paris, France.
17Sorbonne Univ, Pierre Louis Inst Epidemiol & Publ Hlth IPLESP, Epidemiol Allerg & Resp Dis Dept EPAR, Paris, France.
18Harvard Med Sch, Dept Populat Med, Harvard Pilgrim Hlth Care Inst, Boston, MA 02115 USA.
19Univ Cape Town, Dept Psychiat & Mental Hlth, Cape Town, South Africa.
20South African Med Res Council SAMRC, Unit Risk & Resilience Mental Disorders, Cape Town, South Africa.
21Univ Cape Town, Neurosci Inst, Cape Town, South Africa.
22Beckman Res Inst City Hope, Dept Populat Sci, Duarte, CA USA.
23Columbia Univ, Dept Epidemiol, New York, NY USA.
24Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
25Max Planck Inst Psychiat, Dept Translat Res Psychiat, Munich, Germany.
26Columbia Univ, Mailman Sch Publ Hlth, Precis Environm Hlth, New York, NY USA.
27Univ Calif Berkeley, Sch Publ Hlth, Div Environm Hlth Sci, Berkeley, CA 94720 USA.
28Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.
29Harvard Med Sch, Boston, MA 02115 USA.
30Erasmus MC, Univ Med Ctr Rotterdam, Dept Pediat, Rotterdam, Netherlands.
31Erasmus Univ, Dept Psychol Educ & Child Studies, Rotterdam, Netherlands.
32Univ Cambridge, Sch Clin Med, Cambridge, England.
33Leiden Univ, Leiden Inst Brain & Cognit, Leiden, Netherlands.
34Vrije Univ Amsterdam, Clin Child & Family Studies, Amsterdam, Netherlands.
35Finnish Inst Hlth & Welf, Helsinki, Finland.
36Oulu Univ Hosp, Oulu, Finland.
37Univ Oulu, PEDEGO Res Unit, MRC Oulu, Oulu, Finland.
38Helsinki Univ Hosp, Childrens Hosp, Helsinki, Finland.
39Univ Helsinki, Helsinki, Finland.
40Norwegian Univ Sci & Technol, Dept Clin & Mol Med, Trondheim, Norway.
41IMIM Hosp del Mar Med Res Inst, Barcelona, Spain.
42Univ Southern Denmark, Inst Clin Res, Odense, Denmark.
43Dept Obstet & Gynaecol, Odense, Denmark.
44Univ Copenhagen, Fac Hlth & Med Sci, Dept Publ Hlth, Copenhagen, Denmark.
45Univ Copenhagen, Novo Nordisk Fdn, Fac Med & Hlth Sci, Ctr Basic Metab Res, Copenhagen, Denmark.
46Natl Inst Publ Hlth, Ctr Nutr & Hlth Res, Cuernavaca, Mor, Mexico.
47Bradford Teaching Hosp, Bradford Inst Hlth Res, NHS Fdn Trust, Bradford, W Yorkshire, England.
48Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA.
49Icahn Sch Med Mt Sinai, Environm Med & Publ Hlth, Inst Expos Res, New York, NY 10029 USA.
50Univ Cape Town, Dept Paediat & Child Hlth, Cape Town, South Africa.
51South African Med Res Council SAMRC, Unit Child & Adolescent Hlth, Cape Town, South Africa.
52NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
53Erasmus MC, Univ Med Ctr Rotterdam, Dept Epidemiol, Rotterdam, Netherlands.
54Leiden Univ, Dept Biomed Data Sci, Mol Epidemiol, Med Ctr, Leiden, Netherlands.
Format: article
Version: accepted version
Access: open
Online Access: PDF Full Text (PDF, 0.2 MB)
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Language: English
Published: Springer Nature, 2021
Publish Date: 2021-07-07


Maternal anxiety during pregnancy is associated with adverse foetal, neonatal, and child outcomes, but biological mechanisms remain unclear. Altered foetal DNA methylation (DNAm) has been proposed as a potential underlying mechanism. In the current study, we performed a meta-analysis to examine the associations between maternal anxiety, measured prospectively during pregnancy, and genome-wide DNAm from umbilical cord blood. Sixteen non-overlapping cohorts from 12 independent longitudinal studies of the Pregnancy And Childhood Epigenetics Consortium participated, resulting in a combined dataset of 7243 mother-child dyads. We examined prenatal anxiety in relation to genome-wide DNAm and differentially methylated regions. We observed no association between the general symptoms of anxiety during pregnancy or pregnancy-related anxiety, and DNAm at any of the CpG sites, after multiple-testing correction. Furthermore, we identify no differentially methylated regions associated with maternal anxiety. At the cohort-level, of the 21 associations observed in individual cohorts, none replicated consistently in the other cohorts. In conclusion, contrary to some previous studies proposing cord blood DNAm as a promising potential mechanism explaining the link between maternal anxiety during pregnancy and adverse outcomes in offspring, we found no consistent evidence for any robust associations between maternal anxiety and DNAm in cord blood. Larger studies and analysis of DNAm in other tissues may be needed to establish subtle or subgroup-specific associations between maternal anxiety and the foetal epigenome.

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Series: Molecular psychiatry
ISSN: 1359-4184
ISSN-E: 1476-5578
ISSN-L: 1359-4184
Volume: 26
Pages: 1832 - 1845
DOI: 10.1038/s41380-020-00976-0
Type of Publication: A1 Journal article – refereed
Field of Science: 3124 Neurology and psychiatry
Funding: Acknowledgements for each of the participating studies are listed in the Funding and Acknowledgements supplement.
EU Grant Number: (956454) RecaP - Capture, recycling and societal management of phosphorus in the environment
(733206) LIFECYCLE - Early-life stressors and LifeCycle health
Copyright information: © The Author(s), under exclusive licence to Springer Nature Limited 2021. This is a post-peer-review, pre-copyedit version of an article published in Mol Psychiatry. The final authenticated version is available online at