An analysis of medical records data from three Massachusetts health care systems finds no evidence that prenatal exposure to antidepressants increases the risk for autism and related disorders or for attention-deficit hyperactivity disorder (ADHD). In their report being published online in Translational Psychiatry, the Massachusetts General Hospital (MGH)-based research team finds evidence that any increased incidence of autism or ADHD found in previous studies was probably associated with the severity of the mother’s depression – a known risk factor for several neuropsychiatric disorders – and not from antidepressant exposure during pregnancy.
“The fact that we now have found, in two large case-control studies, no increase in the risk for autism with antidepressant use itself should be very reassuring,” says Roy Perlis, MD, MSc, MGH Department of Psychiatry, senior author of the current report and of an earlier study published in 2014. “Some of the studies that have suggested an association did not account for key differences between mothers who take antidepressants and those who don’t, in particular that those taking antidepressants are more likely to have more severe illness.”
The 2014 study, which was published in Molecular Psychiatry, analyzed electronic health record (EHR) data for children born at three Partners Healthcare System hospitals – MGH, Brigham and Women’s Hospital and Newton-Wellesley Hospital. The current study also included EHR data from Boston Children’s Hospital and from Beth Israel Deaconess Hospital, along with information from an additional group of children from the Partners EHR.
The researchers compared data on more than 1,200 children with an autism-related diagnostic code to that of more than 3,500 demographically matched control children with no neuropsychiatric diagnosis. As in the previous study, information regarding the children was paired with data from their mothers’ EHRs, with specific attention to factors related to the mother’s mental health. They also compared data on around 1,700 children with ADHD with that of a control group of nearly 3,800.
While the incidence of both autism and ADHD was increased in the children of women who had taken antidepressants prior to becoming pregnant, antidepressant exposure during pregnancy did not increase the incidence of either condition. Maternal psychotherapy, which like prepregnancy antidepressant use indicates more serious depression, did significantly increase the risk of either autism or ADHD, supporting the hypothesis that studies finding an increased incidence actually reflected the risk conferred by maternal depression itself.
“While taking any medicine during pregnancy can be a difficult decision, we hope the results of our two papers – which now cover more than 2,500 children with autism and almost 4,000 with ADHD – will provide some reassurance to women concerned about getting treatment for depression or anxiety during pregnancy,” says Perlis, an associate professor of Psychiatry at Harvard Medical School. “While there are depression treatments that don’t involve medication, for some patients they are not effective, available or preferred. We want women and the clinicians working with them to be as informed as possible when making this decision.”
About this autism research
The lead author of the Translational Psychiatry paper is Victor Castro from MGH Psychiatry and Partners Research Computing. Additional co-authors are Caitlin Clements and Alysa Doyle, PhD, MGH Psychiatry; Anjali Kaimal, MD, MAS, MGH Obstetrics and Gynecology; Elise Robinson, PhD, MGH Center for Human Genetic Research; Sek Won Kong, MD, Boston Children’s Hospital; Roscoe Brady, MD, PhD, Beth Israel Deaconess Medical Center; Isaac Kohane, MD, Brigham and Women’s Hospital, and Susanne Churchill, PhD, Harvard Medical School.
Funding: Support for the study includes National Institute of Mental Health grant R01MH086026.
Source: Noah Brown – Massachusetts General Hospital Image Source: The image is in the public domain Original Research: Full open access research for “Absence of evidence for increase in risk for autism or attention-deficit hyperactivity disorder following antidepressant exposure during pregnancy: a replication study” by V M Castro, S W Kong, C C Clements, R Brady, A J Kaimal, A E Doyle, E B Robinson, S E Churchill, I S Kohane and R H Perlis in Translational Psychiatry. Published online January 5 2016 doi:10.1038/tp.2015.190
Absence of evidence for increase in risk for autism or attention-deficit hyperactivity disorder following antidepressant exposure during pregnancy: a replication study
Multiple studies have examined the risk of prenatal antidepressant exposure and risk for autism spectrum disorder (ASD) or attention-deficit hyperactivity disorder (ADHD), with inconsistent results. Precisely estimating such risk, if any, is of great importance in light of the need to balance such risk with the benefit of depression and anxiety treatment. We developed a method to integrate data from multiple New England health systems, matching offspring and maternal health data in electronic health records to characterize diagnoses and medication exposure. Children with ASD or ADHD were matched 1:3 with children without neurodevelopmental disorders. Association between maternal antidepressant exposure and ASD or ADHD liability was examined using logistic regression, adjusting for potential sociodemographic and psychiatric confounding variables. In new cohorts of 1245 ASD cases and 1701 ADHD cases, along with age-, sex- and socioeconomic status matched controls, neither disorder was significantly associated with prenatal antidepressant exposure in crude or adjusted models (adjusted odds ratio 0.90, 95% confidence interval 0.50−1.54 for ASD; 0.97, 95% confidence interval 0.53−1.69 for ADHD). Pre-pregnancy antidepressant exposure significantly increased risk for both disorders. These results suggest that prior reports of association between prenatal antidepressant exposure and neurodevelopmental disease are likely to represent a false-positive finding, which may arise in part through confounding by indication. They further demonstrate the potential to integrate data across electronic health records studies spanning multiple health systems to enable efficient pharmacovigilance investigation.
“Absence of evidence for increase in risk for autism or attention-deficit hyperactivity disorder following antidepressant exposure during pregnancy: a replication study” by V M Castro, S W Kong, C C Clements, R Brady, A J Kaimal, A E Doyle, E B Robinson, S E Churchill, I S Kohane and R H Perlis in Translational Psychiatry. Published online January 5 2016 doi:10.1038/tp.2015.190