Children Are Not Just Small Adults

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By Izabela Korwel posted 03-25-2014 17:19

  

Identifying the effects of early life exposures, including their effects and consequences later in life, as well as remedies, was the subject of yesterday's session titled "Perinatal Exposures and Children's Health Outcomes."

Children are more susceptible to environmental factors. This susceptibility is due to their smaller body size, a still developing metabolism, lack of blood-brain barrier, and more. Radim Sram presented that the increase in air pollution—higher PM2.5 and benzo(a)pyrene levels in the Czech region of Silesia as a result from steel industry increased production—was followed quickly by an increase in many childhood respiratory diseases, with the most susceptible group being infants. The sensitivity decreased with age.

One of suggested solutions to fetal exposures was to limit them by educating pregnant woman on effects of smoking, diet, etc., but in many situations, exposure cannot be prevented. Christine Poirier discussed the use of AZT, a drug designed to prevent the HIV infection of the fetus. The drug has a major role in preventing the transfer of the virus; however, it is also genotoxic to the host cells. Particularly in babies, AZT affects the heart and brain mitochondria, causing loss and alteration in DNA. This adverse effect was shown to be persistent—not going away for years after the drug was withdrawn.

While the argument was made that it is environment which plays a major role in gene-environmental interaction, it was clearly not the case in the talk by Nina Holland. She works with a population of children exposed to high levels of organophosphate pesticides. Their levels top the national average reported in NHANES. The increase in neurodevelopmental problems, like lower IQ or increased odds of ADHD, in this population are not only dependent on higher organophosphate metabolite levels in blood, but also in genetic polymorphism of paraxonase (PON1) enzyme. One particular polymorphism resulting in low enzyme expression and activity was found to be culprit in shorter gestation, smaller heads, and more risk for autism. Also, children with low PON1 expression in that population have higher chance to be obese when exposed to the same high levels of pesticides.  

At the same time, the talk by Robert Wright was a cautionary tale in interpretation of epigenetic results. The focus of his research are changes in methylation in "junk" DNA, which is the remains of viral infection many millions of years ago. In particular, the decrease in methylation of LINE-1 is associated with inflammation which can it turn shorten the pregnancy. Increase in methylation of LINE-1 correlated with pregnancy duration shortening by two days. Since increase in methylation typically lessens the gene expression, there clearly is another cause of inflammation, affecting in turn the LINE-1 methylation observed in the study.

The research on fetal exposures, how they contribute to various diseases, and when the effects show up for the first time are currently a top priority for NIEHS, according Jerrold Heindel. His talk provided not only an overview of current state of knowledge, but also provided many tips in which directions the research should go. Letting animals mature after developmental exposures, looking at epigenetics for functional changes in gene expression, and identifying biomarkers are just a few of the ideas he presented. 

Ultimately, the session provided far more questions than answers.

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