Antidepressants during pregnancy associated with increased autism risk

The use of antidepressants, especially selective serotonin reuptake inhibitors, during the final two trimesters of pregnancy was associated with increased risk for autism spectrum disorder in children, according to an article published online by JAMA Pediatrics.

Antidepressants (ADs) are widely used during pregnancy to treat depression. Autism spectrum disorder (ASD) is a neurodevelopmental syndrome characterized by altered communication, language and social interaction and by particular patterns of interests and behaviors. Few studies have investigated the effect of AD use during pregnancy on the risk of ASD in children. A better understanding of the long-term neurodevelopmental effects of ADs on children when used during gestation is a public health priority.

Anick Bérard, Ph.D., of the University of Montreal, Canada, and coauthors used data on all pregnancies and children in Québec between January 1998 and December 2009. The authors identified 145,456 full-term singleton infants born alive. Of the infants, 1,054 (0.72 percent) had at least one ASD diagnosis; the average age at first ASD diagnosis was 4.6 years and the average age of children at the end of follow-up was 6.2 years. Boys with ASD outnumbered girls 4 to 1.

The authors identified 4,724 infants (3.2 percent) who were exposed to ADs in utero; 4,200 (88.9 percent) infants were exposed during the first trimester and 2,532 (53.6 percent) infants were exposed during the second and/or third trimester. There were 31 infants (1.2 percent) exposed to ADs during the second and/or third trimester diagnosed with ASD and 40 infants (1.0 percent) exposed during the first trimester diagnosed with ASD, according to the results.

The use of ADs during the second and/or third trimester was associated with an 87 percent increased of ASD (32 exposed infants), while no association was observed between the use of ADs during the first trimester or the year before pregnancy and the risk of ASD.

Results indicate the increased risk of ASD was observed with selective serotonin reuptake inhibitors (22 exposed infants) and with the use of more than one class of AD during the second and/or third trimester (five exposed infants). In children of mothers with a history of depression, the use of ADs during the second and/or third trimester was associated with an increased risk for ASD in the study (29 exposed infants).

The authors suggest several mechanisms may account for the increased risk of ASD associated with maternal use of ADs during pregnancy. Limitations to the study include its use of prescription filling data, which may not reflect actual use. The data also contained no information on maternal lifestyle.

"Further research is needed to specifically assess the risk of ASD associated with antidepressant types and dosages during pregnancy," the study concludes.

Using antidepressants during pregnancy greatly increases the risk of autism, Professor Anick Bérard of the University of Montreal and its affiliated CHU Sainte-Justine children's hospital revealed today. Prof. Bérard, an internationally renowned expert in the fields of pharmaceutical safety during pregnancy, came to her conclusions after reviewing data covering 145,456 pregnancies. "The variety of causes of autism remain unclear, but studies have shown that both genetics and environment can play a role," she explained. "Our study has established that taking antidepressants during the second or third trimester of pregnancy almost doubles the risk that the child will be diagnosed with autism by age 7, especially if the mother takes selective serotonin reuptake inhibitors, often known by its acronym SSRIs." Her findings were published today in JAMA Pediatrics.

Bérard and her colleagues worked with data from the Quebec Pregnancy Cohort and studied 145,456 children between the time of their conception up to age ten. In addition to information about the mother's use of antidepressants and the child's eventual diagnosis of autism, the data included a wealth of details that enabled the team to tease out the specific impact of the antidepressant drugs. For example, some people are genetically predisposed to autism (i.e., a family history of it.) Maternal age, and depression are known to be associated with the development of autism, as are certain socio-economic factors such as being exposed to poverty, and the team was able to take all of these into consideration. "We defined exposure to antidepressants as the mother having had one or more prescription for antidepressants filled during the second or third trimester of the pregnancy. This period was chosen as the infant's critical brain development occurs during this time," Prof. Bérard said. "Amongst all the children in the study, we then identified which children had been diagnosed with a form of autism by looking at hospital records indicating diagnosed childhood autism, atypical autism, Asperger's syndrome, or a pervasive developmental disorder. Finally, we looked for a statistical association between the two groups, and found a very significant one: an 87% increased risk." The results remained unchanged when only considering children who had been diagnosed by specialists such as psychiatrists and neurologists.

The findings are hugely important as six to ten percent of pregnant women are currently being treated for depression with antidepressants. In the current study, 1,054 children were diagnosed with autism (0.72% of the children in the study), on average at 4.5 years of age. Moreover, the prevalence of autism amongst children has increased from 4 in 10,000 children in 1966 to 100 in 10,000 today. While that increase can be attributed to both better detection and widening criteria for diagnosis, researchers believe that environmental factors are also playing a part. "It is biologically plausible that anti-depressants are causing autism if used at the time of brain development in the womb, as serotonin is involved in numerous pre- and postnatal developmental processes, including cell division, the migration of neuros, cell differentiation and synaptogenesis - the creation of links between brain cells," Prof. Bérard explained. "Some classes of anti-depressants work by inhibiting serotonin (SSRIs and some other antidepressant classes), which will have a negative impact on the ability of the brain to fully develop and adapt in-utero"

The World Health Organization indicates that depression will be the second leading cause of death by 2020, which leads the researchers to believe that antidepressants will likely to remain widely prescribed, including during pregnancy. "Our work contributes to a better understanding of the long-term neurodevelopmental effects of anti-depressants on children when they are used during gestation. Uncovering the outcomes of these drugs is a public health priority, given their widespread use," Prof. Bérard said.