Predicting later-life outcomes of early-life exposures.
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.


OBJECTIVE
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.


CONCLUSIONS
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.
Department of Pathology and Laboratory Medicine, Division of Biology and Medicine, Brown University, Providence, Rhode Island 02912, USA. kim_boekelheide@brown.edu
Kim
K
Boekelheide
Bruce
B
Blumberg
Robert E
RE
Chapin
Ila
I
Cote
Joseph H
JH
Graziano
Amanda
A
Janesick
Robert
R
Lane
Karen
K
Lillycrop
Leslie
L
Myatt
J Christopher
JC
States
Kristina A
KA
Thayer
Michael P
MP
Waalkes
John M
JM
Rogers
D000818:Animals; D001151:Arsenic / Q000633:toxicity*; D002318:Cardiovascular Diseases / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D004198:Disease Susceptibility / Q000453:epidemiology / Q000209:etiology*; D004784:Environmental Monitoring; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D044342:Malnutrition / Q000453:epidemiology / Q000209:etiology / Q000503:physiopathology*; D018811:Maternal Exposure; D051379:Mice; D009765:Obesity / Q000235:genetics; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000453:epidemiology / Q000235:genetics*; D051381:Rats; D018570:Risk Assessment
D001151:Arsenic