Prenatal exposure to selective serotonin reuptake inhibitors (SSRIs) appears to be associated with increased chances of developing an autism spectrum disorder (ASD), although such an exposure is unlikely to explain many cases of autism, a case-control study showed.
Children born to mothers who received a prescription for any antidepressant in the year before delivery were twice as likely to have an ASD (6.7% versus 3.3%; OR 2.0, 95% CI 1.2 to 3.6), according to Lisa Croen, PhD, of Kaiser Permanente Northern California in Oakland, and colleagues.
But the relationship was significant only when an SSRI was one of the antidepressants taken, the researchers reported online in Archives of General Psychiatry.
Adjusting for maternal history of depression and other mental health disorders did not affect the finding.
"Although these findings indicate that maternal treatment with SSRIs during pregnancy may confer some risk to the fetus with regard to neurodevelopment, this potential risk must be balanced with the risk to the mother or fetus of untreated mental health disorders," Croen and her colleagues wrote.
In addition, they noted, "the fraction of cases of ASD that may be attributed to use of antidepressants by the mother during pregnancy is less than 3% in our population, and it is reasonable to conclude that prenatal SSRI exposure is very unlikely to be a major risk factor for ASD."
Both the prevalence of ASDs and the use of antidepressants during pregnancy have increased in recent years, which has spurred some concerns that prenatal exposure to the drugs -- which can cross the placenta and are secreted in breast milk -- could increase the risk of ASDs.
To explore the issue, Croen and her colleagues performed a case-control study of mothers and children who were participating in the Childhood Autism Perinatal Study, which included members of the Kaiser Permanente Medical Care Program in Northern California.
The researchers used medical records to assess autism status in the children and use of antidepressants and other characteristics in the mothers.
Overall, they included 298 children with an ASD and 1,507 randomly selected controls matched by sex, birth year, and hospital of birth.
After adjusting for maternal age, race/ethnicity, and education and the child's birth weight, sex, birth year, and facility of birth, prenatal exposure to antidepressants -- and to SSRIs in particular -- was significantly associated with increased odds of having an ASD.
The strongest effect was associated with SSRI treatment during the first trimester after adjusting for maternal history of depression and other mental health disorders in the year before delivery (OR 3.5, 95% CI 1.5 to 7.9).
There was no association between the odds of having an ASD and prenatal exposure to non-SSRI antidepressants.
Although a case-control study cannot prove causality in the observed associations, there are some biologically plausible mechanisms that can explain the link between SSRIs and ASDs, according to the researchers.
Previous studies, they noted, have suggested that abnormalities in serotonin levels and serotoninergic pathways may play a role in autism.
In addition, transient inhibition of the serotonin transporter by fluoxetine (Prozac) during early brain development affected the emotional behaviors of adult rodents.
"Collectively, these studies suggest the possibility that prenatal exposure to SSRIs may operate directly on the developing brain, perhaps selectively in fetuses with abnormalities in serotonin-related genes," Croen and her colleagues wrote.
They acknowledged some limitations of the study, including the inability to validate case and control status through clinical evaluations, the inability to determine the actual use of antidepressants from medical records, and the potential for confounding by unmeasured factors.
Detection bias -- in which women prescribed SSRIs for anxiety may be more concerned about their child's development and more likely to get them checked for an ASD -- could also have influenced the results.
"We recommend that our findings be considered as preliminary and treated with caution, pending results from further studies designed to address the very complex question of whether prenatal exposure to SSRIs may be etiologically linked to later diagnoses of ASDs in offspring," the authors wrote.
This study was supported in part by a Kaiser Permanente Community Benefit Clinician Research Fund and Cooperative Agreement from the CDC.
The authors reported that they had no conflicts of interest.
- Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner
Archives of General PsychiatrySource Reference: Croen L, et al "Antidepressant use during pregnancy and childhood autism spectrum disorders" Arch Gen Psych 2011; DOI: 10.1001/archgenpsychiatry.2011.73.