Many women continue taking prescription medications while pregnant—to manage chronic conditions such as migraines, depression, or seizures—and a growing body of research suggests that some of these drugs could increase their unborn baby’s chances of developing autism.
A worrisome study published Tuesday in the Journal of the American Medical Association found that women who took the anti-seizure drug valproate during pregnancy had nearly triple the risk of giving birth to a child who later developed autism compared with those who didn’t take the drug.
Valproate, which has long been known to cause birth defects such as cleft palates and spine abnormalities, is one of the most powerful drugs to control seizures related to epilepsy. But nearly 80 percent of the 1 million women who are prescribed the drug every year take it to treat conditions other than epilepsy, such as migraines, chronic pain, or bipolar disorder.
“I’ve seen children born to mothers who were treated with this drug who have autism, usually a more severe form that involves cognitive problems along with social difficulties,” said Dr. Kimford Meador, a pediatric neurologist at Emory University who wrote an editorial that accompanied the study. “It looks like it’s one cause of autism, but it certainly doesn’t explain all of the autism we see.”
(Certain genes, for example, may play an even bigger role in determining autism risk: Babies who have an older sibling with autism are nine times more likely to develop autism compared to those who don’t.)
The rate of autism in the general population of Danish children studied was 1.5 percent. It was 4.4 percent in the Danish children born to mothers who took valproate during pregnancy. The researchers didn’t find any increased autism risk in children whose mothers took other anti-seizure drugs.
The research raises larger concerns about the effects of an ever growing array of drugs—designed to treat mental or neurological illnesses—on the brain of a growing fetus.
Another study published last week in the British Medical Journal found that antidepressant use to manage depression during pregnancy was also associated with a three times greater risk of autism, echoing results of a review study conducted by Boston researchers last year.
Note that these are all population studies that make statistical associations and can’t conclude definitively that the drugs led to the heightened autism risk; conducting controlled trials that compare a drug against a placebo in pregnant women would be unethical so researchers rely on making observations in women who chose to take the drugs during pregnancy.
“The system of proper brain development in a fetus relies on chemicals to work in a finely orchestrated system,” said Dr. Adam Urato, chair of obstetrics-gynecology at Metrowest Medical Center in Framingham, Mass, who co-authored the review study on antidepressant use in pregnancy. “There’s obvious concern that using drugs that change the adult brain chemistry will also change the brain chemistry of the fetus.”
While the American College of Obstetricians and Gynecologists warns against the use of antidepressants during pregnancy except in severe cases of depression, many women accidentally become pregnant while taking the drugs; they may remain on them until their first prenatal visit several weeks after conception. The same occurs with valproate and other medications.
Fetal medicine specialists consider the first 12 weeks of pregnancy to be the most vulnerable time for the fetus, when organs are forming. That’s why it’s a good idea for women to have a preconception visit with their doctor to determine which medications they should discontinue before trying to become pregnant.
Even beyond 12 weeks, drugs can interfere with the programming of certain fetal genes, which occurs throughout the entire pregnancy.
Complicating matters are all the drugs women take that haven’t been well studied for fetal health risks. These include Ritalin and Adderall, which more women are taking beyond their teens to help manage attention deficit disorder. “They’re coming under increasing scrutiny for their safety of use during pregnancy,” Urato said, “but right now they’re a huge unknown.”
He said he’s worried that these stimulant drugs could raise a baby’s autism risk or cause more subtle mental health effects such as developmental delays or learning disabilities later in life.
Meador recently led a study that found 6-year-old children who were exposed to valproate in the womb had IQs that were, on average, 7 to 10 points lower than in children who were exposed to other anti-seizure medications.
“It’s very concerning that we still see a great deal of valproate being prescribed to young women of childbearing age who can do just as well on other drugs,” Meador said. Topiramate and gabapentin, for example, can be used to treat both seizures and chronic migraines. (Topirmate has also been associated with birth defects, but the risks are smaller than with valproate.)
“Alternatives should certainly be considered first,” Meador added. And when doctors do have to prescribe valproate, they should ensure that women take the proper precautions to avoid getting pregnant.