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Serotonin is critical to early brain development. Anything that influences serotonin
levels can have a potential effect on developmental and birth outcomes.
So, the question arises whether the increased use of SSRIs in recent
years is contributing to the rise in ASD.
SSRIs in pregnancy associated with autism and developmental delay
The highest association for autism was found after fetal exposure to mother's medication for depression and anxiety during her first trimester and in children born with developmental delays — after exposure during her third trimester of pregnancy.
In a study of nearly 1,000 mother-child pairs, researchers from the Bloomberg School of Public health found that prenatal exposure to selective serotonin reuptake inhibitors (SSRIs), a frequently prescribed treatment for depression, anxiety and similar disorders, was associated with autism spectrum disorder (ASD) and developmental delays (DD) in boys.
The study, published in the online edition of Pediatrics, analyzed data from large samples of ASD and DD cases, and population-based controls, where a uniform protocol had confirmed ASD and DD diagnoses by trained clinicians using validated standardized instruments.
The study included 966 mother-child pairs from the Childhood Autism Risks from Genetics and the Environment (CHARGE) Study, a population-based case-control study based at the University of California at Davis’ MIND Institute.
Researchers broke the collected data, from children two to five years old, into three diagnoses:
(1) autism spectrum disorder (ASD) - 82.5% boys
(2) developmental delays (DD) - 65.6% boys
(3) those with typical development (TD) - 85.6% boys
While the study included girls, the substantially stronger effect in boys alone suggests possible gender difference in the effect of prenatal SSRI exposure.
“We found prenatal SSRI exposure was nearly 3 times as likely in boys with ASD relative to typical development, with the greatest risk when exposure took place during the first trimester,” said Li-Ching Lee, Ph.D., Sc.M., psychiatric epidemiologist in the Bloomberg School’s Department of Epidemiology. “SSRI was also elevated among boys with DD, with the strongest exposure effect in the third trimester.”
The data analysis was completed by Rebecca Harrington, Ph.D., M.P.H, in conjunction with her doctoral dissertation at the Bloomberg School. Dr. Lee was one of her advisors.
Serotonin is critical to early brain development; exposure during pregnancy to anything that influences serotonin levels can have a potential effect on developmental and birth outcomes.
And the prevalence of ASD continues to rise. According to the Centers for Disease Control and Prevention, an estimated 1 in 68 children in the U.S. identifies with ASD, which is almost five times more common in boys than girls. The question arises whether the increased use of SSRI in recent years is contributing to the rise in ASD.
"This study provides more evidence that in some children, prenatal exposure to SSRIs may influence their risk for developing an autism spectrum disorder,” said Irva Hertz-Picciotto, Ph.D., M.P.H., chief of the Division of Environmental and Occupational Health in the UC Davis Department of Public Health Sciences and a researcher at the UC Davis MIND Institute. “This research also highlights the challenge for women and their physicians to balance the risks versus the benefits of taking these medications, given that a mother’s underlying mental-health conditions also may pose a risk, both to herself and her child.”
The authors realize that maternal depression itself carries risks for the fetus, and the benefits of using SSRI during pregnancy should be considered carefully against any potential harm. Researchers also note that large sample studies are still needed to investigate the effects of maternal SSRI use on female infants who develop ASD.
Reseachers acknowledged limitations of the study include the difficulty in isolating SSRI effects from indications for use, lack of information on SSRI dosage precluded dose-response analyses, and the relatively small sample of developmentally delayed children resulted in imprecise estimates of association, all of these limitations should be viewed with caution.
OBJECTIVE: To examine associations between prenatal use of selective serotonin reuptake inhibitors (SSRIs) and the odds of autism spectrum disorders (ASDs) and other developmental delays (DDs).
METHODS: A total of 966 mother-child pairs were evaluated (492 ASD, 154 DD, 320 typical development [TD]) from the Childhood Autism Risks from Genetics and the Environment (CHARGE) Study, a population-based case-control study. Standardized measures confirmed developmental status. Interviews with biological mothers ascertained prenatal SSRI use, maternal mental health history, and sociodemographic information.
RESULTS: Overall, prevalence of prenatal SSRI exposure was lowest in TD children (3.4%) but did not differ significantly from ASD (5.9%) or DD (5.2%) children. Among boys, prenatal SSRI exposure was nearly 3 times as likely in children with ASD relative to TD (adjusted odds ratio [OR]: 2.91; 95% confidence interval [CI]: 1.07–7.93); the strongest association occurred with first-trimester exposure (OR: 3.22; 95% CI: 1.17–8.84). Exposure was also elevated among boys with DD (OR: 3.39; 95% CI: 0.98–11.75) and was strongest in the third trimester (OR: 4.98; 95% CI: 1.20–20.62). Findings were similar among mothers with an anxiety or mood disorder history.
CONCLUSIONS: In boys, prenatal exposure to SSRIs may increase susceptibility to ASD or DD. Findings from published studies on SSRIs and ASD continues to be inconsistent. Potential recall bias and residual confounding by indication are concerns. 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.
“Prenatal SSRI Use and Offspring With Autism Spectrum Disorder or Developmental Delay” was written by Rebecca A. Harrington, PhD, MPH; Li-Ching Lee, PhD, ScM; Rosa M. Crum, MD, MHS; Andrew W. Zimmerman, MD; and Irva Hertz-Picciotto, PhD, MPH.
Data collection of this research was supported by U.S. National Institute of Environmental Health Sciences (NIEHS (#P01-ES11269 and #R01-ES015359), UC Davis MIND Institute and Autism Speaks.
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