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Cesarean delivery and blood DNA methylation at birth and childhood: meta-analysis in the Pregnancy and Childhood Epigenetics Consortium

Cesarean delivery and blood DNA methylation at birth and childhood: meta-analysis in the Pregnancy and Childhood Epigenetics Consortium
Cesarean delivery and blood DNA methylation at birth and childhood: meta-analysis in the Pregnancy and Childhood Epigenetics Consortium

Children born via cesarean delivery have a higher risk of metabolic, immunological, and neurodevelopmental disorders compared to those born via vaginal delivery, although mechanisms remain unclear. We conducted a meta-analysis of epigenome-wide association studies to examine the associations between delivery mode and blood DNA methylation at birth and its persistence in early childhood. Participants were from 19 pregnancy cohorts (9833 term newborns) and 6 pediatric cohorts (2429 children aged 6 to 10 years). We identified six CpGs in cord blood associated with cesarean delivery (effect size range: 0.4 to 0.7%, P < 1.0 × 10 -7): MAP2K2 (cg19423175), LIM2 (cg01500140), CNP (cg13917614), BLM (cg18247172), RASA3 (cg22348356), and RUNX3 (cg20674490), independent of cell proportions and other confounders. In childhood, none of these CpGs were associated with cesarean delivery, and no additional CpGs were identified. Delivery mode was associated with cell proportions at birth but not in childhood. Further research is needed to elucidate cesarean delivery's molecular influence on offspring health.

Humans, DNA Methylation, Female, Pregnancy, Cesarean Section, Child, Epigenesis, Genetic, Infant, Newborn, CpG Islands, Genome-Wide Association Study, Fetal Blood/metabolism
2375-2548
Wang, Siwen
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Casey, Emma
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Sordillo, Joanne
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Aguilar-Lacasaña, Sofía
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Morales Berstein, Fernanda
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Biedrzycki, Richard J.
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Brescianini, Sonia
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Hough, Amy
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Isaevska, Elena
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Kim, Woo Jin
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Lecorguillé, Marion
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Li, Sebastian Shaobo
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Page, Christian M.
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Park, Jaehyun
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Röder, Stefan
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Salontaji, Kristina
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Santorelli, Gillian
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Sun, Yidan
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Won, Sungho
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Zillich, Eric
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Zillich, Lea
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Annesi-Maesano, Isabella
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Arshad, S. Hasan
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Bustamante, Mariona
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Cecil, Charlotte A.M.
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Elliott, Hannah R.
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Ewart, Susan
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Felix, Janine F.
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Gagliardi, Luigi
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Håberg, Siri E.
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Herberth, Gunda
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Heude, Barbara
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Holloway, John W.
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Huels, Anke
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Karmaus, Wilfried
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Koppelman, Gerard H.
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London, Stephanie J.
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Mumford, Sunni L.
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Nisticò, Lorenza
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Popovic, Maja
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Rusconi, Franca
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Schisterman, Enrique F.
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Stein, Dan J.
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Send, Tabea
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Tiemeier, Henning
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Vonk, Judith M.
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Vrijheid, Martine
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Wiemels, Joseph Leo
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Witt, Stephanie H.
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Wright, John
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et al.
Wang, Siwen
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Casey, Emma
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Sordillo, Joanne
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Aguilar-Lacasaña, Sofía
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Morales Berstein, Fernanda
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Biedrzycki, Richard J.
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Brescianini, Sonia
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Hough, Amy
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Isaevska, Elena
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Kim, Woo Jin
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Lecorguillé, Marion
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Li, Sebastian Shaobo
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Page, Christian M.
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Park, Jaehyun
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Röder, Stefan
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Salontaji, Kristina
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Santorelli, Gillian
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Sun, Yidan
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Won, Sungho
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Zillich, Eric
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Zillich, Lea
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Annesi-Maesano, Isabella
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Arshad, S. Hasan
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Bustamante, Mariona
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Cecil, Charlotte A.M.
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Elliott, Hannah R.
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Ewart, Susan
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Felix, Janine F.
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Gagliardi, Luigi
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Håberg, Siri E.
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Herberth, Gunda
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Heude, Barbara
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Holloway, John W.
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Huels, Anke
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Karmaus, Wilfried
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Koppelman, Gerard H.
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London, Stephanie J.
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Mumford, Sunni L.
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Nisticò, Lorenza
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Popovic, Maja
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Rusconi, Franca
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Schisterman, Enrique F.
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Stein, Dan J.
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Send, Tabea
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Tiemeier, Henning
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Vonk, Judith M.
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Vrijheid, Martine
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Wiemels, Joseph Leo
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Witt, Stephanie H.
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Wright, John
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Wang, Siwen, Casey, Emma and Sordillo, Joanne , et al. (2024) Cesarean delivery and blood DNA methylation at birth and childhood: meta-analysis in the Pregnancy and Childhood Epigenetics Consortium. Science Advances, 10 (48), [eadr2084]. (doi:10.1126/sciadv.adr2084).

Record type: Article

Abstract

Children born via cesarean delivery have a higher risk of metabolic, immunological, and neurodevelopmental disorders compared to those born via vaginal delivery, although mechanisms remain unclear. We conducted a meta-analysis of epigenome-wide association studies to examine the associations between delivery mode and blood DNA methylation at birth and its persistence in early childhood. Participants were from 19 pregnancy cohorts (9833 term newborns) and 6 pediatric cohorts (2429 children aged 6 to 10 years). We identified six CpGs in cord blood associated with cesarean delivery (effect size range: 0.4 to 0.7%, P < 1.0 × 10 -7): MAP2K2 (cg19423175), LIM2 (cg01500140), CNP (cg13917614), BLM (cg18247172), RASA3 (cg22348356), and RUNX3 (cg20674490), independent of cell proportions and other confounders. In childhood, none of these CpGs were associated with cesarean delivery, and no additional CpGs were identified. Delivery mode was associated with cell proportions at birth but not in childhood. Further research is needed to elucidate cesarean delivery's molecular influence on offspring health.

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Accepted/In Press date: 25 October 2024
Published date: 29 November 2024
Keywords: Humans, DNA Methylation, Female, Pregnancy, Cesarean Section, Child, Epigenesis, Genetic, Infant, Newborn, CpG Islands, Genome-Wide Association Study, Fetal Blood/metabolism

Identifiers

Local EPrints ID: 500555
URI: http://eprints.soton.ac.uk/id/eprint/500555
DOI: doi:10.1126/sciadv.adr2084
ISSN: 2375-2548
PURE UUID: f67aefe7-60d3-4976-a0b3-2794c69cd4de
ORCID for John W. Holloway: ORCID iD orcid.org/0000-0001-9998-0464

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Date deposited: 06 May 2025 16:38
Last modified: 22 Aug 2025 01:42

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Contributors

Author: Siwen Wang
Author: Emma Casey
Author: Joanne Sordillo
Author: Sofía Aguilar-Lacasaña
Author: Fernanda Morales Berstein
Author: Richard J. Biedrzycki
Author: Sonia Brescianini
Author: Amy Hough
Author: Elena Isaevska
Author: Woo Jin Kim
Author: Marion Lecorguillé
Author: Sebastian Shaobo Li
Author: Christian M. Page
Author: Jaehyun Park
Author: Stefan Röder
Author: Kristina Salontaji
Author: Gillian Santorelli
Author: Yidan Sun
Author: Sungho Won
Author: Eric Zillich
Author: Lea Zillich
Author: Isabella Annesi-Maesano
Author: S. Hasan Arshad
Author: Mariona Bustamante
Author: Charlotte A.M. Cecil
Author: Hannah R. Elliott
Author: Susan Ewart
Author: Janine F. Felix
Author: Luigi Gagliardi
Author: Siri E. Håberg
Author: Gunda Herberth
Author: Barbara Heude
Author: John W. Holloway ORCID iD
Author: Anke Huels
Author: Wilfried Karmaus
Author: Gerard H. Koppelman
Author: Stephanie J. London
Author: Sunni L. Mumford
Author: Lorenza Nisticò
Author: Maja Popovic
Author: Franca Rusconi
Author: Enrique F. Schisterman
Author: Dan J. Stein
Author: Tabea Send
Author: Henning Tiemeier
Author: Judith M. Vonk
Author: Martine Vrijheid
Author: Joseph Leo Wiemels
Author: Stephanie H. Witt
Author: John Wright
Corporate Author: et al.

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