Does Antidepressant Use in Pregnancy Harm Child Neurodevelopment?

(Adds slug, and dropped word "reuptake" in para 2.)

April 29, 2020

NEW YORK (Reuters Health) - A new study suggests that in utero exposure to antidepressants may harm child neurodevelopment, although the authors caution against drawing firm conclusions based on their study.

The study shows that children of mothers with mood or anxiety disorders who took selective serotonin-reuptake inhibitors (SSRIs) or selective serotonin-norepinephrine reuptake inhibitors (SNRIs) had increased risk for "developmental vulnerability" and for deficits in language and/or cognitive abilities in kindergarten.

"Our results add to an emerging body of literature that reveals an association of negative academic outcomes in early childhood and language difficulties for children whose mothers have a clinical indication of a mood or anxiety disorder during pregnancy who have been treated with antidepressants," Dr. Deepa Singal of the University of Manitoba, in Winnipeg, Canada, and colleagues write in Pediatrics.

Their findings are based 528 children with and 2,522 without in utero exposure to SSRI or SNRI antidepressants. The sample was restricted to mothers diagnosed with a mood or anxiety disorder within three months of conception. Exposed mothers had two or more SSRI or SNRI prescriptions dispensed during pregnancy; unexposed mothers had no prescription for these medications.

Developmental health in kindergarten children was assessed using the Early Development Instrument (EDI), a 104-component teacher-administered questionnaire made up of five developmental domains: physical health/well-being, language/cognitive development, social competence, emotional maturity, and communication skills/general knowledge. Children are considered developmentally vulnerable in a domain if they score in the bottom 10th percentile based on national norms.

About 21% of exposed children were assessed as developmentally vulnerable on two or more EDI domains, compared to 16% of unexposed children (adjusted odds ratio, 1.43; 95% confidence interval, 1.08 to 1.90).

"This means for every 19 women who took an antidepressant during pregnancy in our study, one more child was at risk for vulnerability in two or more domains on the EDI," the authors note in their article.

They also found that 12.94% of children in the exposed group were vulnerable in the language and cognitive domain compared to 12.4% of unexposed children (aOR, 1.40; 95% CI, 1.03 to 1.91).

"This means, on average, 185 women would have to take an SSRI or SNRI during pregnancy for one more child to be vulnerable in language and cognition," they say.

"This is an extremely complex topic, as many women benefit from their medications and untreated depression can also pose harms to mothers and the developing child," Dr. Singal commented in email to Reuters Health.

He noted that pregnant women who are depressed are less likely to seek proper medical care, may not get adequate nutrition or enough sleep and are at increased risk for postpartum depression. "Women must weigh the risks and benefits of antidepressant use with their physicians before making a decision to stop and start taking antidepressants during pregnancy," said Dr. Singal.

"Our findings raise a concern that these medications are not benign to the developing fetus. This study highlights the importance of presenting a broader approach to managing maternal mental health, especially the consideration of non-pharmacologic approaches," Dr. Singal added. "Additionally, the study points to the need for early intervention and supports for children of mothers who have depression/anxiety during pregnancy."

The researchers caution that the findings need to be replicated in other large population-based samples before definitive conclusions or clinical recommendations can be made.

The authors of an editorial in Pediatrics agree that more research is needed.

Dr. Megan Galbally of Murdoch University, in Perth, Australia, and co-authors say while the findings are "concerning," it's important to recognize that the main outcome measure is school readiness which is different from a direct neuropsychological assessment of cognitive or language neurodevelopment.

While the EDI is "widely used and well-studied measure of school readiness, other studies have found that it has only modest specificity for developmental vulnerability and is not strongly correlated with language development," they point out. Other potential confounding factors, such as parental cognitive ability, exposure to parental smoking, child health and parent involvement, were not included in the analysis.

"Critical new research is needed to inform how to help women with significant depression during pregnancy while avoiding risk to their developing fetuses," Dr. Galbally and colleagues say.

The challenge now, they say, is to broaden the evidence with more studies. "Only then will women be able to understand the implications of agent, dose, and timing of exposure to antidepressant medication in pregnancy and be able to weigh both the risks and benefits of treatment for both their health and their children," they conclude.

SOURCE: Pediatrics, online April 27, 2020.