At least for a fetus in utero, timing matters when thinking about the impact of the absence or presence of substances.  Moreover, the presence or absence of the dose may have long-term effects through epigenetic effects such as methylation . A new example arises from further research on children in utero during the Dutch Hunger Winter, as reported in a May 14, 2015 article in ScienceDaily. The article explains the following basis for the findings:

“Researchers at Columbia University’s Mailman School of Public Health and Leiden University in the Netherlands found that children whose mothers were malnourished at famine levels during the first 10 weeks of pregnancy had changes in DNA methylation known to suppress genes involved in growth, development, and metabolism documented at age 59. This is the first study to look at prenatal nutrition and genome-wide DNA patterns in adults exposed to severe under-nutrition at different periods of gestation. Findings are published in the International Journal of Epidemiology.

The study evaluated how famine exposure — defined as 900 calories daily or less — during the Dutch Hunger Winter of 1944-1945 affected genome-wide DNA methylation levels. The researchers also studied the impact of short-term exposure, pre-conception and post-conception. The study used blood samples of 422 individuals exposed to the famine at any time during gestation and 463 controls without prenatal famine exposure.

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The findings show associations between famine exposure during weeks 1-10 of gestation and DNA changes, but not later in pregnancy. DNA methylation changes were also seen among individuals conceived at the height of the famine between March and May 1945 who were not exposed to all 10 weeks of early gestation. “The first ten weeks of gestation is a uniquely sensitive period when the blood methylome — or whole-genome DNA methylation — is especially sensitive to the prenatal environment,” said L.H. Lumey, MD, PhD, associate professor of Epidemiology at the Mailman School of Public Health, and last author. “This is the period when a woman may not even be aware that she is pregnant.”

The article is:   E. W. Tobi, R. C. Slieker, A. D. Stein, H. E. D. Suchiman, P. E. Slagboom, E. W. van Zwet, B. T. Heijmans, L. Lumey. Early gestation as the critical time-window for changes in the prenatal environment to affect the adult human blood methylome. International Journal of Epidemiology, 2015; DOI: 10.1093/ije/dyv043


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