Area of Interest: This proposal looks for environmental risk factors for autism during the critical period of susceptibility, in the womb.
What We Know about Exposures in the Womb: Three generations are directly exposed during every woman's pregnancy: mother, first generation; fetus, second generation; reproductive cells, third generation. Because cells and tissues are rapidly growing and changing in the womb, they are more vulnerable to errors caused by exposures at that time. These errors may not be apparent at birth, or in every generation. New errors that occur in reproductive cells are different from errors that occur in the body of the fetus and are also different from genetic inheritance established long before. For this reason, children with autism may not have parents with autism or grandparents with autism. But these new changes in reproductive cells might carry risk forward for many subsequent generations.
What Led Us to Propose This Study: Children diagnosed with autism in the 1990s to early 2000s were formed from reproductive cells that existed when their grandmother was pregnant. The epidemic of autism beginning in the 1990s matches the rise of new environmental exposures during 1960s pregnancies. These exposures include more smoking, coffee drinking, and alcohol use by pregnant women, but also frequent use of new prescription drugs in pregnancy, and new and heavy exposure to environmental chemicals like pesticides.
Innovative Research Question: In this study, we ask whether specific exposures during the 1960s to grandfathers and grandmothers during conception and pregnancy are linked to autism in their grandchildren. No study has been able to ask this question before now.
How We Propose to Answer This Research Question. A 50+ year follow-up of 20,000 pregnancies that occurred in the 1960s, The Child Health and Development Studies (CHDS), offers this novel research opportunity. We will study whether CHDS pregnancy exposures in grandparents are linked to autism in their grandchildren. In this study we will investigate smoking, alcohol, coffee, and prescription drugs. These data on grandparents have already been recorded. But to do this study we have to find cases of autism in CHDS grandchildren (Aim 1) and then use statistical methods to see if grandparent exposures are related to grandchildren's risk (Aim 2). The proposed study will accomplish a 50+ year study in three generations at low cost. An advantage of our study is that risk factors were recorded when they happened, so women do not need to try to remember them. This will be a prospective study that is less prone to error.
Our Qualifications for This Research: Researchers at the CHDS have 50+ years of experience in finding cancer cases for our study population. Similar methods are required to find autism cases and we are confident this can be done. In addition we are working as a team with researchers at the California Department of Public Health who have experience in finding autism cases using California databases and in doing research on autism. Together, we have decades of experience required to complete this project successfully.
Impact: If we find new grandparent risk factors, this will lead to experimental studies to learn how they cause autism. If the risk factors we study are not linked to autism, the work we will have done to find grandchildren cases in the CHDS can be used for new studies of other risk factors. The next logical study would be to see whether environmental chemicals in our stored grandparent's blood samples are linked to grandchildren's autism. Thus, funding the proposed study will advance the search for causes of autism no matter what we find. Identifying causes holds the key to preventing autism in future generations.