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Hypotheses on the Fetal Origins of Adult Diseases: Contributions of Epidemiological Studies

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Abstract

Epidemiological studies have demonstrated associations between low birth weight and cardiovascular disease, type 2 diabetes and their risk factors in adult life. These findings have led to sharp debates in the literature concerning potential methodological study flaws and the effect size and causality of the associations. More recent studies seem to have overcome most methodological flaws and suggest a small effect size of low birth weight on adult diseases for the individual. However, the effect size may still be important on a population level. Various causal pathways have been hypothesized as mechanisms underlying these associations. These hypotheses have proposed central roles for (1) fetal undernutrition, (2) increased cortisol exposure, (3) genetic susceptibility and (4) accelerated post-natal growth. These hypotheses have been studied in various epidemiological study designs. Thus far, it is still not known which mechanisms underlie the associations between low birth weight and diseases in adult life. The causal pathways linking low birth weight to diseases in later life seem to be complex and may include combined environmental and genetic mechanisms in various periods of life. Well-designed epidemiological studies are necessary to estimate the population effect size and to identify the underlying mechanisms. This knowledge is needed to develop strategies for identifying groups at risk and prevention focused on early life.

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Abbreviations

11βHSD:

11beta-hydroxysteroid-dehydrogenase

BMI:

body mass index

IGF-1:

insulin like growth factor-1

IGF-2:

insulin like growth factor 2

INS VNTR:

insulin variable number tandem repeat gene

PPARγ2:

peroxisome proliferator-activated receptor gamma 2 gene

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Authors and Affiliations

  1. Department of Epidemiology and Biostatistics, Erasmus Medical Center, Rotterdam, The Netherlands

    Vincent W. V. Jaddoe & Jacqueline C. M. Witteman

  2. Department of Pediatrics, Erasmus Medical Center, Sophia Children’s Hospital, Rotterdam, The Netherlands

    Vincent W. V. Jaddoe

  3. Department of Epidemiology and Biostatistics, Erasmus Medical Center, PO Box 1738, 3000, DR Rotterdam, The Netherlands

    Vincent W. V. Jaddoe

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  1. Vincent W. V. Jaddoe
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Correspondence to Vincent W. V. Jaddoe.

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Jaddoe, V.W.V., Witteman, J.C.M. Hypotheses on the Fetal Origins of Adult Diseases: Contributions of Epidemiological Studies. Eur J Epidemiol 21, 91–102 (2006). https://doi.org/10.1007/s10654-005-5924-5

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