The baby’s earliest environment—the womb—is critical: Because the fetal brain produces about 250,000 neurons every minute during pregnancy, experiences that interfere with that process can affect the developing brain in lasting ways. Studies have linked autism to a number of factors in pregnancy, among them the mother’s diet, the medicines she takes, and her mental, immune, and metabolic conditions, including preeclampsia (a form of high blood pressure) and gestational diabetes. Other preliminary work has implicated the quality of the air she breathes and the pesticides she is exposed to. And some research suggests that birth complications and birth timing may also play a role.
The relationship between many of these factors and autism is still speculative. “That question of causality, it’s a burden that is very difficult to fulfill,” says Brian Lee, an epidemiologist at Drexel University in Philadelphia. This is generally true of research into environmental exposures, and particularly so for studies of pregnant women: Researchers cannot ethically expose pregnant women to possible risks; observational studies can only identify correlations, not causes; and the results of animal studies do not always extrapolate to people.
But researchers are starting to uncover biological threads that tie some of these prenatal exposures together. Many affect common biochemical pathways previously implicated in autism, such as those involving inflammation and aberrant immunity in both mother and baby. Each may only “contribute a little bit of risk here and there,” Lee says, but it is crucial to try to understand how all the pieces add up.
Autism has been tied to events throughout pregnancy, including the first few days after conception. Even before a tiny human blastocyst attaches itself to the nutrient-rich lining of its mother’s uterus, factors that will shape its nervous system are already in play. In the days immediately following conception, genes that govern brain wiring are turned on and off in a process that requires folate, or vitamin B9. Folate may be important for the building of fundamental brain structures later on, too.
If a mother’s diet is deficient in folate, these processes can go awry, increasing the risk for neural defects, such as spina bifida and possibly autism. In a 2013 study, Norwegian researchers followed more than 85,000 women from 18 weeks into their pregnancies until an average of about six years after delivery, collecting information that included whether and when the women took supplements of folic acid, the synthetic form of folate, as well as the health of their children. Those who took supplements, especially between four weeks before and eight weeks after conception, were about 40 percent less likely to have children diagnosed with autism than those who did not take the supplements. Other studies have linked vitamin-D deficiency in pregnant women with autism in their children, but the implications are unclear.
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