Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2012 Oct;120(10):1353-61.
doi: 10.1289/ehp.1204934. Epub 2012 Jun 6.

Predicting later-life outcomes of early-life exposures

Kim Boekelheide  1 , Bruce Blumberg, Robert E Chapin, Ila Cote, Joseph H Graziano, Amanda Janesick, Robert Lane, Karen Lillycrop, Leslie Myatt, J Christopher States, Kristina A Thayer, Michael P Waalkes, John M Rogers
Affiliations
Review

Predicting later-life outcomes of early-life exposures

Kim Boekelheide et al. Environ Health Perspect. 2012 Oct.

Abstract

Background: In utero exposure of the fetus to a stressor can lead to disease in later life. Epigenetic mechanisms are likely mediators of later-life expression of early-life events.

Objectives: We examined the current state of understanding of later-life diseases resulting from early-life exposures in order to identify in utero and postnatal indicators of later-life diseases, develop an agenda for future research, and consider the risk assessment implications of this emerging knowledge.

Methods: This review was developed based on our participation in a National Research Council workshop titled "Use of in Utero and Postnatal Indicators to Predict Health Outcomes Later in Life: State of the Science and Research Recommendations." We used a case study approach to highlight the later-life consequences of early-life malnutrition and arsenic exposure.

Discussion: The environmental sensitivity of the epigenome is viewed as an adaptive mechanism by which the developing organism adjusts its metabolic and homeostatic systems to suit the anticipated extrauterine environment. Inappropriate adaptation may produce a mismatch resulting in subsequent increased susceptibility to disease. A nutritional mismatch between the prenatal and postnatal environments, or early-life obesogen exposure, may explain at least some of the recent rapid increases in the rates of obesity, type 2 diabetes, and cardiovascular diseases. Early-life arsenic exposure is also associated with later-life diseases, including cardiovascular disease and cancer.

Conclusions: With mounting evidence connecting early-life exposures and later-life disease, new strategies are needed to incorporate this emerging knowledge into health protective practices.

PubMed Disclaimer

Conflict of interest statement

This document has been reviewed by the National Health and Environmental Effects Research Laboratory, U.S. EPA, and approved for publication. Approval does not signify that the contents reflect the views of the agency, nor does mention of trade names or commercial products constitute endorsement or recommendation for use.

R.E.C. is employed by Pfizer Global Research and Development, Groton, CT. B.B. holds several patents related to nuclear receptor sequence and function that have been licensed to for-profìt entities and generate annual royalty payments. K.B. occasionally acts as an expert consultant for chemical and pharmaceutical companies. The other authors declare they have no actual or potential competing financial interests.

Figures

Figure 1
Figure 1
The combination of maternal nutrition (i.e., in utero nutrition) and postnatal nutrition can be adaptive or maladaptive, leading to increased or decreased disease risk later in life. During development, an organism responds to an environmental stimulus by shifting its developmental path to a phenotype that confers a survival or reproductive advantage in postnatal life; this process of programmed adaptation is called predictive adaptive response (PAR).
Figure 2
Figure 2
Studies of the Dutch famine birth cohort underscore the importance of timing in developmental processes. The timing of in utero nutritional deprivation is associated with different later-life disease outcomes (Roseboom et al. 2001, 2006).
Figure 3
Figure 3
Developmental exposures are focused through the lens of epigenetic mechanisms to influence later-life disease outcomes and susceptibilities.
See this image and copyright information in PMC

Comment in

References

    1. Adami HO, Lagiou P, Trichopoulos D. Breast cancer following diethylstilbestrol exposure in utero: insights from a tragedy. Eur J Epidemiol. 2012;27:1–3. - PubMed
    1. Almond D. Is the 1918 Influenza pandemic over? Long-term effects of in utero influenza exposure in the post-1940 U.S. population. J Polit Econ. 2006;114:672–712.
    1. Anway MD, Leathers C, Skinner MK. Endocrine disruptor vinclozolin induced epigenetic transgenerational adult-onset disease. Endocrinology. 2006;147(12):5515–5523. - PMC - PubMed
    1. Armitage JA, Khan IY, Taylor PD, Nathanielsz PW, Poston L. Developmental programming of the metabolic syndrome by maternal nutritional imbalance: how strong is the evidence from experimental models in mammals? J Physiol. 2004;561(pt 2):355–377. - PMC - PubMed
    1. Atzori L, Antonucci R, Barberini L, Locci E, Marincola FC, Scano P, et al. 1H NMR-based metabolomic analysis of urine from preterm and term neonates. Front Biosci. 2011;3:1005–1012. (Elite Ed) - PubMed

Publication types

MeSH terms