Exposure to selective serotonin reuptake inhibitors anti-depressants in early pregnancy may modestly increase risk of autism spectrum disorders, according to a Kaiser Permanente study published online in the current issue of Archives of General Psychiatry. However the researchers cautioned that the number of children exposed prenatally to SSRIs was low and that further studies are needed to validate these results
Funded by the Centers for Disease Control and Prevention, the population-based, case-control study of 1,805 children is the first to systematically address the association between prenatal SSRI exposure and ASD risk.
Researchers reported a two-fold increased risk of ASD associated with maternal treatment with SSRI anti-depressants during the year before delivery. The strongest effect was associated with first trimester treatment, said the study's lead author, Lisa Croen, PhD, director of the Autism Research Program at the Kaiser Permanente Division of Research in Oakland, Calif. She explained that in utero exposure to anti-depressant medications was reported in 6.7 percent of cases and 3.3 percent of controls.
"Our results suggest a possible, albeit small, risk to the unborn child associated with in utero exposure to SSRIs, but this possible risk must be balanced with risk to the mother of untreated mental health disorders," said Croen, who explained that further studies are needed to replicate and extend these findings.
Researchers conducted a population-based, case-control study among 298 children with ASD and 1,507 randomly selected control children drawn from the Kaiser Permanente Northern California membership. Information on maternal use of anti-depressant medications, maternal mental health history, autism and demographic characteristics was collected from medical records.
After adjusting for maternal age, race/ethnicity, education and child's birth weight, gender, birth year, and facility of birth, mothers of children subsequently diagnosed with ASD were twice as likely to have at least one anti-depressant prescription in the year prior to delivery of the study child, and over three times as likely to have a prescription in the first trimester of pregnancy.
To further evaluate whether the observed association between prenatal SSRI exposure and ASD risk could be attributed to SSRI treatment rather than to the women's depression or anxiety for which she was prescribed the medication, researchers conducted an analysis of the subgroup of women with a history of mental health disorders in the year before delivery. Risk of ASD associated with SSRI use anytime during this year remained somewhat elevated in this subgroup, but did not reach statistical significance.
To assess the possibility that women prescribed SSRIs during the year before delivery had a more severe underlying condition that accounts for the finding, researchers examined indicators of severity of psychiatric illness. Among these women, the proportion with previous psychiatric hospitalizations and the mean number of hospitalizations was not significantly different in cases compared to controls.
Prior studies have indicated that abnormalities in serotonin levels and serotonin pathways may play a role in autism. Collectively these studies suggest the possibility that prenatal SSRI exposure may operate directly on the developing brain, perhaps selectively in fetuses with abnormalities in serotonin-related genes, explained Croen. She adds that physiologic changes related to maternal stress or depression during pregnancy, in combination with SSRI exposure, may contribute to changes in fetal brain development leading to later-diagnosed ASD.
Co-authors on the study include Judith Grether, PhD, recently retired research scientist, with the California Department of Public Health; Cathleen Yoshida, MS, and Roxana Odouli, MSPH, both with the Kaiser Permanente Division of Research; and Victoria Hendrick, MD, with the UCLA Neuropsychiatric Institute and Hospital. The research was supported by a Kaiser Permanente Community Benefit Research Fund and by the Centers for Disease Control and Prevention.
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