A new study from researchers at Drexel University adds evidence that using common antidepressant medications during pregnancy may contribute to a higher risk of autism spectrum disorders (ASD) in children, although this risk is still very small.
Results from past studies of prenatal use of selective serotonin reuptake inhibitors (SSRIs) and ASD risk have not been consistent. An ongoing challenge in this line of research is trying to tease apart potential effects of the medication on risk from the effects associated with the condition for which the medication was prescribed (most commonly depression). Based on past studies, both SSRIs and genetic factors associated with depression are likely associated with greater risk of ASD.
This new study, published online ahead of print last month in the Journal of Autism and Developmental Disorders, suggests that under-reporting of maternal depression, if not properly considered in analyses, may influence results of studies trying to address this question.
In the study, the Drexel team analyzed large population based registers of nearly 750,000 births in Denmark from 1997 through 2006. They found that about 1.5 percent of children born to women who had taken an SSRI during pregnancy were diagnosed with ASD, compared to about 0.7 percent of children born to an otherwise similar group of women not taking the medication.
“We found a two-fold increased risk for ASD associated with in utero exposure to SSRIs compared to the unexposed reference group” said lead author Nicole Gidaya, PhD. “More importantly, in our analysis we accounted for under-reporting of maternal depression in the register. This suggests that under-reporting of the confounder, maternal depression, may be a limitation in approaches previously used in the other studies.”
Gidaya, who performed this study while a doctoral student in the Drexel University School of Public Health, noted that “if the increased ASD risk we saw here is real, it is important to realize that the number of ASD cases that could be prevented by reducing SSRI exposure in pregnancy still represents only a small fraction of overall cases of ASD.”
Antidepressant Use in Pregnancy Tied to Autism Risk
Boys with autism were three times more likely to have been exposed to antidepressants known as SSRIs in the womb than typically developing children, according to new research.
The new study also found that boys whose mothers took SSRIs—drugs including Celexa, Lexapro, Paxil, Prozac and Zoloft—during pregnancy were also more likely to have developmental delays.
Results of the study were published online April 14 and in the May print issue of Pediatrics.
“We found prenatal SSRI exposure was almost three times as likely in boys with autism spectrum disorders relative to typical development, with the greatest risk when exposure is during the first trimester,” said study co-author Li-Ching Lee, an associate scientist in the department of epidemiology at Johns Hopkins Bloomberg School of Public Health, in Baltimore.
While the study found an association between prenatal use of SSRI antidepressants and autism risk in boys, it did not prove cause-and-effect.
The study authors were quick to point out that there are risks to both the mother and fetus from untreated depression.
“It’s a complex decision whether to treat or not treat depression with medications during pregnancy,” Lee said. “There are so many factors to consider. We didn’t intend for our study to be used as a basis for clinical treatment decisions. Women should talk with their doctors about SSRI treatments.”
Other experts said the overall risk of having a child with autism remains very low.
SSRIs used during pregnancy cross the placenta and increase levels of the hormone serotonin in the fetus, as they do in the mother, the researchers said. Higher serotonin levels decrease depression, and these antidepressants are used in about 4 percent of all pregnancies, according to background information with the study.
The researchers further advised caution in interpreting the results in practice. Because of the challenges of distinguishing effects of medications from those of the condition indicating their use, more research in larger study populations will be needed to confirm the findings. In addition, the decision whether or not to use an SSRI in pregnancy is a complex one; pregnant women and their doctors need to consider women’s physical and mental health needs as well as other pregnancy-associated risks, including risks associated with untreated depression both during and after pregnancy.
However, the research team believes that the greater value of this finding is to direct further attention on understanding the mechanisms by which in utero SSRI exposure might influence the developing brain. Serotonin is a neurotransmitter whose use by the brain is altered during depression and modified by SSRI use, and has been shown to play an important role in brain development.
The authors of the current study point out that there is still a need for more population studies of possible associations between maternal SSRI use and autism, in light of the limitations of the present study and the conflicting results within the field’s previous studies of the question. They say future studies should use a large population sample where there is good quality data about exposure to medication, mental health diagnoses as well as ASD diagnoses.
“As we complete research in our attempts to understand autism’s causes we continue to realize that there are likely many genetic and non-genetic contributors,” said Craig Newschaffer, PhD, director of the A.J. Drexel Autism Institute and professor in Drexel’s School of Public Health, and the study’s senior author. “We must begin trying to map these multiple risk factors on to common pathways, so that these pathways can be a focus in our effort to prevent the impairment associated with ASD. Pathways involving the brain’s serotonin system are still one viable candidate.”
Antidepressant use in pregnancy may raise autism risk
Children whose mothers take Zoloft, Prozac, or similar antidepressants during pregnancy are twice as likely as other children to have a diagnosis of autism or a related disorder, according to a small new study, the first to examine the relationship between antidepressants and autism risk.
This class of antidepressants, known as selective serotonin reuptake inhibitors (SSRIs), may be especially risky early on in a pregnancy, the study suggests. Children who were exposed to the drugs during the first trimester were nearly four times as likely to develop an autism spectrum disorder (ASD) compared with unexposed children, according to the study, which appears in the Archives of General Psychiatry.
The study included fewer than 300 children with a diagnosed ASD and does not prove that taking SSRIs during pregnancy directly causes ASDs, which affect approximately 1 percent of children in the U.S. The findings will need to be confirmed in larger studies, and should not dissuade women from starting or continuing to take SSRIs, experts on prenatal drug exposure and mental health say.
Gidaya performed this research with the support of funding from Drexel’s Office of International Programs which allowed her to travel to Denmark.
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