Children whose mothers took fertility drugs were almost twice as likely to have autism as other children, new research finds. Being conceived by in vitro fertilization (IVF) or born prematurely also seemed to up the risk of autism, according to another study.
In the first study, researchers asked 111 women taking part in the Nurses' Health Study II who had a child with an autism spectrum disorder about their history of fertility problems and use of ovulation-inducing drugs, such as Clomid or gonadotropins.
About 34 percent of moms with an autistic child had used fertility drugs compared to about 24 percent of some 3,900 mothers without an autistic child, the researchers found.
Clomid and gonadotropins are often used as a first-line treatment for infertility, defined as trying for a year or longer to get pregnant without success, said lead study author Kristen Lyall, a postdoctoral research fellow at the Harvard School of Public Health.
Nearly 47 percent of moms of autistic kids reported infertility, compared to about 33 percent of the other mothers, her team found.
One caveat to those statistics is that older women are both more likely to have fertility problems and to take ovulation-inducing drugs, and prior research has shown older moms are also more likely to have autistic children.
In the study, the median maternal age at the time the first child was born was 35, compared to about 25 for the general U.S. population, Lyall noted.
Even so, when the age of the mother and pregnancy complications were taken into account -- which can also heighten the risk of autism -- women with infertility and who used ovulation drugs still had a twofold greater chance of having a child with an autism spectrum disorder.
The absolute risk for any one mother to have a child with autism remained relatively low, the authors noted. In the study, about 4 percent of mothers who took fertility drugs had a child with an autism spectrum disorder, compared to about 2 percent of moms who didn't take fertility drugs.
Still, "we found that a history of infertility and use of ovulation-inducing drugs was significantly associated with an increased risk of having a children with an autism spectrum disorder," said Lyall, who noted that the findings are preliminary, involved a relatively small sample of women and needed to be confirmed by future research.
The autism risk was less pronounced among younger mothers who took fertility drugs, Lyall added. Among women aged 25 to 34, about 3.1 percent who had infertility and took fertility drugs had an autistic child, compared to 2.6 percent of women in that age group who didn't.
The study was to be presented last week at the International Meeting for Autism Research in Philadelphia.
Another study to be presented at the meeting, this time by Israeli researchers, found that in vitro fertilization and pre-term birth were both associated with an increased risk of autism in offspring.
About 10.2 percent of 461 children diagnosed with an autism spectrum disorder were conceived using IVF, while about 3.5 percent of children in the general Israeli population are conceived that way, according to the study.
Moms who had IVF tended to be older, with a median age of 32.6 years compared to just under 31 years of age for mothers who didn't get IVF, the study authors noted.
Nearly 4 percent of the kids with autism were born prematurely, while nearly 5 percent had a low birth weight, compared to about 1 percent in the general population.
"Prematurity and low birth weight also adversely affect the child's functioning in adaptive skills," noted study lead author Dr. Ditza Zachor, who is director of the Autism Center at Assaf Harofeh Medical Center at Tel Aviv University. "This means that these two risk factors act as 'second hits' that affect the child more than just having autism."
Zachor stressed that the findings are preliminary and more widespread research is needed. "This will give us the answer if these procedures carry any risk for the baby."
So what does all this mean for couples struggling to conceive? Dr. Andrew Zimmerman, director of medical research at Kennedy Krieger Institute's Center for Autism and Related Disorders in Baltimore, said that women taking fertility drugs or undergoing IVF should not be unnecessarily alarmed.
The vast majority of children conceived in this way will not end up with autism, and most children who have autism were not conceived using IVF or with the help of fertility drugs, he said.
However, many physicians who work with kids with autism have remarked that lots of their patients seem to have been conceived via IVF. Prior to these studies, the observation was largely anecdotal, he said.
"I don't think we are at a point yet where we can make recommendations, but we are getting to a point where we are beginning to understand there probably is a relationship," Zimmerman said.
The reasons for the connection are not known, but it may be something about the process of in vitro fertilization, in which a sperm and egg are joined outside the womb, an embryo is created and implanted, or sometimes frozen and stored, then thawed for later use. Taking fertility drugs in early pregnancy could also contribute, Zimmerman said.
Autism is a neurodevelopmental disorder that's characterized by problems with social interaction, verbal and nonverbal communication, and restricted interests and behaviors.