Biological embedding of early-life exposures and disease risk in humans: A role for DNA methylation

Christiana A. Demetriou, Karin van Veldhoven, Caroline Relton, Silvia Stringhini, Kyriacos Kyriacou, Paolo Vineis

Research output: Contribution to journalReview articlepeer-review

50 Citations (Scopus)


Background: Following wider acceptance of 'the thrifty phenotype' hypothesis and the convincing evidence that early-life exposures can influence adult health even decades after the exposure, much interest has been placed on the mechanisms through which early-life exposures become biologically embedded. Materials and methods: In this review, we summarize the current literature regarding biological embedding of early-life experiences. To this end, we conducted a literature search to identify studies investigating early-life exposures in relation to DNA methylation changes. In addition, we summarize the challenges faced in investigations of epigenetic effects, stemming from the peculiarities of this emergent and complex field. A proper systematic review and meta-analyses were not feasible given the nature of the evidence. Results: We identified seven studies on early-life socio-economic circumstances, 10 studies on childhood obesity and six studies on early-life nutrition all relating to DNA methylation changes that met the stipulated inclusion criteria. The pool of evidence gathered, albeit small, favours a role of epigenetics and DNA methylation in biological embedding, but replication of findings, multiple comparison corrections, publication bias and causality are concerns remaining to be addressed in future investigations. Conclusions: Based on these results, we hypothesize that epigenetics, in particular DNA methylation, is a plausible mechanism through which early-life exposures are biologically embedded. This review describes the current status of the field and acts as a stepping stone for future, better designed investigations on how early-life exposures might become biologically embedded through epigenetic effects.

Original languageEnglish
Pages (from-to)303-332
Number of pages30
JournalEuropean Journal of Clinical Investigation
Issue number3
Publication statusPublished - 1 Mar 2015
Externally publishedYes


  • Biological embedding
  • Body mass index
  • DNA methylation, epigenetics
  • Early-life nutrition
  • Early-life socio-economic status


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