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Prenatal SSRI Use May Be Linked to Autism Spectrum Disorder
Medscape Medical News
April 14, 2014

Prenatal use of selective serotonin reuptake inhibitors (SSRIs) appears to be a risk factor for autism spectrum disorders (ASDs) and other developmental delays (DDs) in young children, but underlying maternal depression may be a confounder, according to findings of a population-based case-control study published online April 14 in Pediatrics.

"Serotonin is critical in early brain development, creating concerns regarding prenatal exposure to factors influencing serotonin levels, like [SSRIs]," write Rebecca A. Harrington, PhD, MPH, from the Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland, and colleagues. "Prenatal SSRI use was recently associated with autism; however, its association with other developmental delays is unclear."

Therefore, the investigators analyzed the possible associations between prenatal SSRI use and the likelihood of ASDs and other DDs in the offspring in a group of 966 mother?child pairs. The pairs were enrolled in the Childhood Autism Risks from Genetics and the Environment (CHARGE) Study. Of those, 492 children had ASD, 154 had DD, and 320 had typical development (TD), according to standardized measures. The investigators interviewed the biological mothers regarding prenatal SSRI use, maternal mental health history, and sociodemographic factors.

Boys With ASD More Likely to Have Prenatal SSRI Exposure

Although children with TD had the lowest prevalence of prenatal SSRI exposure (3.4%), it was not statistically significantly different from the prevalence seen in children with ASD (5.9%) or DD (5.2%).

However, when the team analyzed boys separately, they found that boys with ASD were nearly 3 times as likely to have prenatal SSRI exposure compared with boys with TD (adjusted odds ratio [OR], 2.91; 95% confidence interval [CI], 1.07 - 7.93). This finding in boys with ASD was even more pronounced with first-trimester SSRI exposure (OR, 3.22; 95% CI, 1.17 - 8.84).

Boys with DD also had increased prenatal SSRI exposure compared with boys with TD (OR, 3.39; 95% CI, 0.98 - 11.75), but this only reached statistical significance in the second and third trimester (second trimester: OR, 4.41; 95% CI, 1.01 - 19.17; third trimester: OR, 4.98; 95% CI, 1.20 - 20.62). Among mothers with a history of anxiety or mood disorder, findings were similar but not statistically significant.

The authors note that the relatively small number of girls in the study precluded them as a separate subgroup (eg, just 17.5% of the children with ASD).

"This population-based case-control study in young children provides evidence that prenatal SSRI use may be a risk factor for autism and other developmental delays," the study authors write. "However, underlying depression and its genetic underpinnings may be a confounder."

Limitations of this study include difficulty in isolating SSRIs' effects from those of their indications for use, reliance on self-report with potential recall bias, lack of data on SSRI dosage precluding dose-response analyses, and a relatively small sample of DD children.

"In boys, prenatal exposure to SSRIs may increase susceptibility to ASD or DD," the authors conclude. "Larger samples are needed to replicate DD results. Because maternal depression itself carries risks for the fetus, the benefits of prenatal SSRI use should be carefully weighed against potential harms."

This research was supported by US National Institute on Environmental Health Sciences, the MIND Institute, and Autism Speaks. Funded by the National Institutes of Health. The authors have disclosed no relevant financial relationships.

Pediatrics. Published online April 14, 2014.
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