TY - JOUR
T1 - Maternal anxiety during pregnancy and newborn epigenome-wide DNA methylation
AU - Sammallahti, Sara
AU - Cortes Hidalgo, Andrea P.
AU - Tuominen, Samuli
AU - Malmberg, Anni
AU - Mulder, Rosa H.
AU - Brunst, Kelly J.
AU - Alemany, Silvia
AU - McBride, Nancy S.
AU - Yousefi, Paul
AU - Heiss, Jonathan A.
AU - McRae, Nia
AU - Page, Christian M.
AU - Jin, Jianping
AU - Pesce, Giancarlo
AU - Caramaschi, Doretta
AU - Rifas-Shiman, Sheryl L.
AU - Koen, Nastassja
AU - Adams, Charleen D.
AU - Magnus, Maria C.
AU - Baïz, Nour
AU - Ratanatharathorn, Andrew
AU - Czamara, Darina
AU - Håberg, Siri E.
AU - Colicino, Elena
AU - Baccarelli, Andrea A.
AU - Cardenas, Andres
AU - DeMeo, Dawn L.
AU - Lawlor, Deborah A.
AU - Relton, Caroline L.
AU - Felix, Janine F.
AU - van IJzendoorn, Marinus H.
AU - Bakermans-Kranenburg, Marian J.
AU - Kajantie, Eero
AU - Räikkönen, Katri
AU - Sunyer, Jordi
AU - Sharp, Gemma C.
AU - Houtepen, Lotte C.
AU - Nohr, Ellen A.
AU - Sørensen, Thorkild I.A.
AU - Téllez-Rojo, Martha M.
AU - Wright, Robert O.
AU - Annesi-Maesano, Isabella
AU - Wright, John
AU - Hivert, Marie France
AU - Wright, Rosalind J.
AU - Zar, Heather J.
AU - Stein, Dan J.
AU - London, Stephanie J.
AU - Cecil, Charlotte A.M.
AU - Tiemeier, Henning
AU - Lahti, Jari
N1 - Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2021/6
Y1 - 2021/6
N2 - 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.
AB - 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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U2 - 10.1038/s41380-020-00976-0
DO - 10.1038/s41380-020-00976-0
M3 - Article
C2 - 33414500
AN - SCOPUS:85099079606
SN - 1359-4184
VL - 26
SP - 1832
EP - 1845
JO - Molecular Psychiatry
JF - Molecular Psychiatry
IS - 6
ER -