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Background <p>Breastfeeding is associated with short- and long-term beneficial effects on child health, including greater cognitive development, and enhanced immune programming. However, the underlying biological mechanisms are only partially understood, with epigenetics emerging as a potential contributor. In this study, we aimed to investigate whether breastfeeding practices are associated with differential DNA methylation (DNAm) in childhood blood.</p> Results <p>We conducted meta-analyses of epigenome-wide association studies (meta-EWASs) in 3421 children from eleven international population-based birth cohorts from the Pregnancy And Childhood Epigenetics (PACE) Consortium. Breastfeeding was assessed as “ever” being breastfed vs. “never”, and duration of any and exclusive breastfeeding. DNAm was measured in childhood blood (ages 5–12 years) using the Illumina 450&#xa0;K or EPIC arrays, with cord blood at birth used as negative outcome control. At False Discovery Rate (FDR) &lt; 5%, positive associations at six cytosine-phosphate-guanine (CpG) sites were identified in childhood blood: four with duration of exclusive breastfeeding, and three with duration of exclusive breastfeeding of more than three months compared to never. The annotated genes (<i>ALAD</i>, <i>FNBP4</i>, and <i>CHFR</i>) are related to developmental and immune processes. None of these CpG sites were FDR-significant in cord blood prior to breastfeeding.</p> Conclusions <p>Breastfeeding was associated with differential DNAm in childhood blood at a limited number of CpG sites. Future studies in diverse populations are needed to examine the robustness of these associations, the sources of heterogeneity, and the generalizability of the findings.</p>

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Breastfeeding association with DNA methylation in the pregnancy and childhood epigenetics (PACE) consortium

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月28日

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  • Doretta Caramaschi,
  • Sílvia Fernández-Barrés,
  • Emma Casey,
  • Adrià Cruells,
  • Darina Czamara,
  • Mohammed El Sharkawy,
  • Hannah R. Elliott,
  • Ruby Fore,
  • Richa Gairola,
  • Olena Gruzieva,
  • Anke Huels,
  • Jari Lahti,
  • Hami Lee,
  • Roberta Magnano San Lio,
  • Anni Malmberg,
  • Toby Mansell,
  • Simon K. Merid,
  • Boris Novakovic,
  • Raffael Ott,
  • Dolors Pelegrí,
  • Faisal I Rezwan,
  • Sheryl L. Rifas-Shiman,
  • Andreas Weiss,
  • Blandine de Lauzon-Guillain,
  • Liesbeth Duijts,
  • Veit Grote,
  • John W. Holloway,
  • Nastassja Koen,
  • Caroline L. Relton,
  • Dan J. Stein,
  • Heather J. Zar,
  • Joseph M. Braun,
  • Kim M. Cecil,
  • Marie-France Hivert,
  • Sandra Hummel,
  • Vincent W. V. Jaddoe,
  • Μarianna Karachaliou,
  • Wilfried Karmaus,
  • Manolis Kogevinas,
  • Berthold Koletzko,
  • Inger Kull,
  • Erik Melén,
  • Emily Oken,
  • Katri Räikkönen,
  • Richard Saffery,
  • Martine Vrijheid,
  • John Wright,
  • Kimberly Yolton,
  • Barbara Heude,
  • Janine F. Felix,
  • Mariona Bustamante

摘要

Background

Breastfeeding is associated with short- and long-term beneficial effects on child health, including greater cognitive development, and enhanced immune programming. However, the underlying biological mechanisms are only partially understood, with epigenetics emerging as a potential contributor. In this study, we aimed to investigate whether breastfeeding practices are associated with differential DNA methylation (DNAm) in childhood blood.

Results

We conducted meta-analyses of epigenome-wide association studies (meta-EWASs) in 3421 children from eleven international population-based birth cohorts from the Pregnancy And Childhood Epigenetics (PACE) Consortium. Breastfeeding was assessed as “ever” being breastfed vs. “never”, and duration of any and exclusive breastfeeding. DNAm was measured in childhood blood (ages 5–12 years) using the Illumina 450 K or EPIC arrays, with cord blood at birth used as negative outcome control. At False Discovery Rate (FDR) < 5%, positive associations at six cytosine-phosphate-guanine (CpG) sites were identified in childhood blood: four with duration of exclusive breastfeeding, and three with duration of exclusive breastfeeding of more than three months compared to never. The annotated genes (ALAD, FNBP4, and CHFR) are related to developmental and immune processes. None of these CpG sites were FDR-significant in cord blood prior to breastfeeding.

Conclusions

Breastfeeding was associated with differential DNAm in childhood blood at a limited number of CpG sites. Future studies in diverse populations are needed to examine the robustness of these associations, the sources of heterogeneity, and the generalizability of the findings.