Cesarean Delivery and Blood DNA Methylation at Birth and Childhood: Meta-Analysis in the Pregnancy and Childhood Epigenetics Consortium

Siwen Wang; Emma Casey; Joanne Sordillo; Sofia Aguilar-Lacasaña; Fernanda Morales Berstein; Richard J Biedrzycki; Sonia Brescianini; Su Chen; Amy Hough; Elena Isaevska; Woo Jin Kim; Marion Lecorguillé; Sebastian Shaobo Li; Christian Page; Jaehyun Park; Stefan Roeder; Kristina Salontaji; Gillian Santorelli; Yidan Sun; Sungho Won; Eric Zillich; Lea Zillich; Isabella Annesi-Maesano; Syed Hasan Arshad; Mariona Bustamante; Charlotte A M Cecil; Hannah Elliott; Susan Ewart; Janine Felix; Luigi Gagliardi; Siri E Håberg; Gunda Herberth; Barbara Heude; John W. Holloway; Anke Hüls; Wilfried Karmaus; Gerard Koppelman; Stephanie London; Sunni Mumford; Lorenza Nisticò; Maja Popovic; Franca Rusconi; Enrique Schisterman; Dan J Stein; Tabea Sarah Send; Henning Tiemeier; Judith Vonk; Martine Vrijheid; Joseph L Wiemels; Stephanie H Witt; John Wright; Edwina Yeung; Heather Zar; Ana Claudia Zenclussen; Hongmei Zhang; Jorge Chavarro; Marie-France Hivert

doi:10.1126/sciadv.adr2084

Cesarean Delivery and Blood DNA Methylation at Birth and Childhood: Meta-Analysis in the Pregnancy and Childhood Epigenetics Consortium

Siwen Wang, Emma Casey, Joanne Sordillo, Sofia Aguilar-Lacasaña, Fernanda Morales Berstein, Richard J Biedrzycki, Sonia Brescianini, Su Chen, Amy Hough, Elena Isaevska, Woo Jin Kim, Marion Lecorguillé, Sebastian Shaobo Li, Christian Page, Jaehyun Park, Stefan Roeder, Kristina Salontaji, Gillian Santorelli, Yidan Sun, Sungho WonEric Zillich, Lea Zillich, Isabella Annesi-Maesano, Syed Hasan Arshad, Mariona Bustamante, Charlotte A M Cecil, Hannah Elliott, Susan Ewart, Janine Felix, Luigi Gagliardi, Siri E Håberg, Gunda Herberth, Barbara Heude, John W. Holloway, Anke Hüls, Wilfried Karmaus, Gerard Koppelman, Stephanie London, Sunni Mumford, Lorenza Nisticò, Maja Popovic, Franca Rusconi, Enrique Schisterman, Dan J Stein, Tabea Sarah Send, Henning Tiemeier, Judith Vonk, Martine Vrijheid, Joseph L Wiemels, Stephanie H Witt, John Wright, Edwina Yeung, Heather Zar, Ana Claudia Zenclussen, Hongmei Zhang, Jorge Chavarro, Marie-France Hivert

Research output: Contribution to journal › Article (Academic Journal) › peer-review

2 Citations (Scopus)

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.

Original language	English
Article number	eadr2084
Number of pages	13
Journal	Science Advances
Volume	10
Issue number	48
Early online date	27 Nov 2024
DOIs	https://doi.org/10.1126/sciadv.adr2084
Publication status	Published - 29 Nov 2024

Bibliographical note

Publisher Copyright:
© 2024 the Authors, some rights reserved.

Access to Document

10.1126/sciadv.adr2084Licence: CC BY-NC

Handle.net

Persistent link

Cite this

Wang, S., Casey, E., Sordillo, J., Aguilar-Lacasaña, S., Berstein, F. M., Biedrzycki, R. J., Brescianini, S., Chen, S., Hough, A., Isaevska, E., Kim, W. J., Lecorguillé, M., Shaobo Li, S., Page, C., Park, J., Roeder, S., Salontaji, K., Santorelli, G., Sun, Y., ... Hivert, M.-F. (2024). Cesarean Delivery and Blood DNA Methylation at Birth and Childhood: Meta-Analysis in the Pregnancy and Childhood Epigenetics Consortium. Science Advances, 10(48), Article eadr2084 . https://doi.org/10.1126/sciadv.adr2084

@article{40927a1075824819a28609ddac010dd3,

title = "Cesarean Delivery and Blood DNA Methylation at Birth and Childhood: Meta-Analysis in the Pregnancy and Childhood Epigenetics Consortium",

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{\textquoteright}s molecular influence on offspring health.",

author = "Siwen Wang and Emma Casey and Joanne Sordillo and Sofia Aguilar-Lacasa{\~n}a and Berstein, \{Fernanda Morales\} and Biedrzycki, \{Richard J\} and Sonia Brescianini and Su Chen and Amy Hough and Elena Isaevska and Kim, \{Woo Jin\} and Marion Lecorguill{\'e} and \{Shaobo Li\}, Sebastian and Christian Page and Jaehyun Park and Stefan Roeder and Kristina Salontaji and Gillian Santorelli and Yidan Sun and Sungho Won and Eric Zillich and Lea Zillich and Isabella Annesi-Maesano and Arshad, \{Syed Hasan\} and Mariona Bustamante and Cecil, \{Charlotte A M\} and Hannah Elliott and Susan Ewart and Janine Felix and Luigi Gagliardi and H{\aa}berg, \{Siri E\} and Gunda Herberth and Barbara Heude and Holloway, \{John W.\} and Anke H{\"u}ls and Wilfried Karmaus and Gerard Koppelman and Stephanie London and Sunni Mumford and Lorenza Nistic{\`o} and Maja Popovic and Franca Rusconi and Enrique Schisterman and Stein, \{Dan J\} and Send, \{Tabea Sarah\} and Henning Tiemeier and Judith Vonk and Martine Vrijheid and Wiemels, \{Joseph L\} and Witt, \{Stephanie H\} and John Wright and Edwina Yeung and Heather Zar and Zenclussen, \{Ana Claudia\} and Hongmei Zhang and Jorge Chavarro and Marie-France Hivert",

note = "Publisher Copyright: {\textcopyright} 2024 the Authors, some rights reserved.",

year = "2024",

month = nov,

day = "29",

doi = "10.1126/sciadv.adr2084",

language = "English",

volume = "10",

journal = "Science Advances",

issn = "2375-2548",

publisher = "American Association for the Advancement of Science",

number = "48",

}

Wang, S, Casey, E, Sordillo, J, Aguilar-Lacasaña, S, Berstein, FM, Biedrzycki, RJ, Brescianini, S, Chen, S, Hough, A, Isaevska, E, Kim, WJ, Lecorguillé, M, Shaobo Li, S, Page, C, Park, J, Roeder, S, Salontaji, K, Santorelli, G, Sun, Y, Won, S, Zillich, E, Zillich, L, Annesi-Maesano, I, Arshad, SH, Bustamante, M, Cecil, CAM, Elliott, H, Ewart, S, Felix, J, Gagliardi, L, Håberg, SE, Herberth, G, Heude, B, Holloway, JW, Hüls, A, Karmaus, W, Koppelman, G, London, S, Mumford, S, Nisticò, L, Popovic, M, Rusconi, F, Schisterman, E, Stein, DJ, Send, TS, Tiemeier, H, Vonk, J, Vrijheid, M, Wiemels, JL, Witt, SH, Wright, J, Yeung, E, Zar, H, Zenclussen, AC, Zhang, H, Chavarro, J & Hivert, M-F 2024, 'Cesarean Delivery and Blood DNA Methylation at Birth and Childhood: Meta-Analysis in the Pregnancy and Childhood Epigenetics Consortium', Science Advances, vol. 10, no. 48, eadr2084 . https://doi.org/10.1126/sciadv.adr2084

TY - JOUR

T1 - Cesarean Delivery and Blood DNA Methylation at Birth and Childhood

T2 - Meta-Analysis in the Pregnancy and Childhood Epigenetics Consortium

AU - Wang, Siwen

AU - Casey, Emma

AU - Sordillo, Joanne

AU - Aguilar-Lacasaña, Sofia

AU - Berstein, Fernanda Morales

AU - Biedrzycki, Richard J

AU - Brescianini, Sonia

AU - Chen, Su

AU - Hough, Amy

AU - Isaevska, Elena

AU - Kim, Woo Jin

AU - Lecorguillé, Marion

AU - Shaobo Li, Sebastian

AU - Page, Christian

AU - Park, Jaehyun

AU - Roeder, Stefan

AU - Salontaji, Kristina

AU - Santorelli, Gillian

AU - Sun, Yidan

AU - Won, Sungho

AU - Zillich, Eric

AU - Zillich, Lea

AU - Annesi-Maesano, Isabella

AU - Arshad, Syed Hasan

AU - Bustamante, Mariona

AU - Cecil, Charlotte A M

AU - Elliott, Hannah

AU - Ewart, Susan

AU - Felix, Janine

AU - Gagliardi, Luigi

AU - Håberg, Siri E

AU - Herberth, Gunda

AU - Heude, Barbara

AU - Holloway, John W.

AU - Hüls, Anke

AU - Karmaus, Wilfried

AU - Koppelman, Gerard

AU - London, Stephanie

AU - Mumford, Sunni

AU - Nisticò, Lorenza

AU - Popovic, Maja

AU - Rusconi, Franca

AU - Schisterman, Enrique

AU - Stein, Dan J

AU - Send, Tabea Sarah

AU - Tiemeier, Henning

AU - Vonk, Judith

AU - Vrijheid, Martine

AU - Wiemels, Joseph L

AU - Witt, Stephanie H

AU - Wright, John

AU - Yeung, Edwina

AU - Zar, Heather

AU - Zenclussen, Ana Claudia

AU - Zhang, Hongmei

AU - Chavarro, Jorge

AU - Hivert, Marie-France

PY - 2024/11/29

Y1 - 2024/11/29

N2 - 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.

AB - 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.

UR - https://www.science.org/doi/10.1126/sciadv.adr2084

U2 - 10.1126/sciadv.adr2084

DO - 10.1126/sciadv.adr2084

M3 - Article (Academic Journal)

C2 - 39602535

SN - 2375-2548

VL - 10

JO - Science Advances

JF - Science Advances

IS - 48

M1 - eadr2084

ER -

Cesarean Delivery and Blood DNA Methylation at Birth and Childhood: Meta-Analysis in the Pregnancy and Childhood Epigenetics Consortium

Abstract

Bibliographical note

Access to Document

Handle.net

Other files and links

Fingerprint

Cite this