Autism is largely genetic, but evidence also points to "triggers" in the prenatal environment.
Worry has always been a side effect of pregnancy. But one anxiety--will my baby be normal?--has recently come to include a new concern: autism. First identified in 1943, the disorder is commanding unprecedented interest, mostly because of the reported rise in its incidence, but also because its origins lie in the fascinating crux between genes and the environment. "Autism is primarily genetic, but something beyond genes is also involved," says pediatric neurologist Andrew Zimmerman, M.D., an associate professor of neurology at Johns Hopkins University School of Medicine and a research scientist at the Kennedy Krieger Institute in Baltimore. That something may be found in the womb.
Among the most intriguing areas of investigation is how environmental influences might "hijack" fetal genes and alter their effect on brain development. But tracking cause and effect in such a complex syndrome is difficult, and scientists expect that results will come slowly. "If you think of autism research as a game of Monopoly, we just passed Go," says toxicologist Isaac Pessah, Ph.D., director of the Children's Center for Environmental Health and Disease Prevention at the University of California, Davis.
The who, what and when of autism Neither a disease nor a mental illness, autism is a behavioral syndrome that originates early in life, possibly well before birth. It's the most severe of a range of developmental problems known as autism spectrum disorders (ASD), and it affects far more boys than girls. Whether its incidence is increasing remains controversial (see "Autism's Rise: Real or an Illusion?" at left), but everyone agrees that the syndrome has a powerful impact on affected children and their families.
Because their brains are "wired" differently, autistic children may react intensely to sensations such as sound and touch. Most have limited interests and trouble with language, social skills, communication and attention. Only recently have scientists understood that autism is actually several different disorders, the causes of which may involve many different genes and environmental exposures.
Some experts suspect that the stage is set for autism early in the first trimester, a suspicion rooted in the birth-defect epidemic caused by the morning-sickness remedy thalidomide in the 1960s. Of the babies born with severe limb abnormalities after their mothers took the drug, 5 percent also had autism, about 30 times the expected rate. This points to brain injury between 20 and 36 days after conception, when arms and legs are being formed. In contrast, an Ohio State University study found that women who'd suffered major stress, such as the death of a spouse, between the 24th and 28th weeks of pregnancy had a higher risk of delivering an autistic child.
Evidence also points to prenatal hormone levels: The more testosterone is present in the womb, the more likely a child is to have ASD. And researchers at the Centers for Disease Control and Prevention have noted possible associations with obstetrical complications, including preterm delivery, low birth weight and breech presentation of the baby.
Whenever it begins, the cascade of events that leads to autism probably starts with a genetic vulnerability, most likely with dysfunction in five to 15 genes. "With multiple dysfunctional genes, the child's system becomes susceptible to environmental insult," Pessah says.
Many questions about moms One focus of current investigation is whether a maternal immune system gone awry could raise the risk of autism. "We've found increased numbers of persons with autoimmune diseases, such as rheumatoid arthritis and lupus, in the families we've studied," says Zimmerman. One study showed double the risk in children whose mothers suffered from psoriasis during pregnancy.
Zimmerman has also found an association with a mother's low levels of serotonin, a brain chemical known as a mood regulator and closely linked to depression. His study showed the mothers of autistic children having low levels of serotonin in the fluid that carries the chemical to the fetus, even though the women were not depressed. "A mother's levels are important to fetal brain growth," he says. "Mom's serotonin might be important to jump-start the fetus's production of its own."
Some scientists suspect that a mother's age could also be a risk factor. "We don't see teenage mothers or women in their early 20s bringing young autistic children to the clinic," says Zimmerman. "It's mostly mothers in their 30s and 40s." Advanced maternal age means more exposure to all kinds of toxins, viruses and chemicals, he adds, "and the older they are, the more likely people are to develop autoimmune diseases; this is especially true for women."
The role of toxins Blood tests show that most Americans' bodies carry a significant burden of pollution, including plastic softeners, flame retardants, pesticides and heavy metals. While acknowledging that chemical exposure probably won't cause autism unless there is genetic susceptibility, Pessah is testing hair, blood, tissue and urine samples from 700 families with autism, looking for toxic triggers. "Heavy metals, including cadmium, manganese, arsenic, lead and mercury, are prominent targets of investigation," he says.
In fact, mercury is the 800-pound gorilla of autism research. Large studies have determined that thimerosol, the mercury-based preservative once used in childhood vaccines, is not connected with autism. The focus is now on a mother's intake of methylmercury, the organic form that's found in fish. Also, a couple of recent studies have linked higher mercury levels in outdoor air to a rise in autism.
Though research on the origins of autism isn't yet conclusive, enough is known about the effect of environmental factors on the fetal brain to offer moms-to-be some practical guidance:
Limit intake of contaminated fish Large, predatory fish, such as tuna or swordfish, contain high levels of mercury; farmed seafood such as salmon may have higher levels of industrial chemicals, such as PCBs. "It's best to eat wild-caught and smaller fish lower on the food chain," says Pessah.
Minimize chemical exposures "There are chemicals around the house, such as sprays or air fresheners, that haven't been fully tested," Pessah says. Especially early on in pregnancy, don't use products you know little about, such as cleansers with complicated ingredients.
Give up cigarettes Mothers who smoke regularly during early pregnancy have a 40 percent increased risk of bearing an autistic child, according to Swedish researchers.
Avoid exposure to illnesses Make sure your immunizations are up-to-date; rubella (German measles) is particularly important, as prenatal exposure has been linked to autism.
Monitor autoimmune problems If you have autoimmunity issues, Zimmerman says, "consult with your obstetrician to make sure your condition is under control."
Stay as stress-free as possible "Major life stressors are more common during pregnancies with children later diagnosed as autistic," says Zimmerman. "However, even with stress and other risk factors, most mothers will have healthy pregnancies and their children will not develop autism."