Antidepressant use in pregnancy not linked to child mental health problems after accounting for maternal depression

Children born to mothers who used antidepressants during pregnancy do not appear to face higher risks of developing depression or anxiety by adolescence, according to a large study published in the Journal of the American Academy of Child & Adolescent Psychiatry. After accounting for maternal mental health and other relevant factors, researchers found no significant difference in psychiatric outcomes between children exposed to selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors during pregnancy and those who were not.

Antidepressants known as selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors are commonly prescribed to treat depression and anxiety. These medications work by increasing levels of neurotransmitters, such as serotonin and norepinephrine, which play a role in mood regulation. They are widely used, especially among women of childbearing age. In the United States, up to 15% of reproductive-aged women and 6% to 8% of pregnant women are prescribed one of these medications.

The question of whether antidepressants taken during pregnancy might affect a child’s long-term mental health has been a topic of ongoing concern. Some earlier studies suggested that children exposed to these medications before birth may be at higher risk for conditions like depression or anxiety. However, distinguishing the effects of the medication from the effects of maternal depression itself has proven challenging. Depression during pregnancy is a known risk factor for a wide range of child developmental issues, so it has remained unclear whether observed risks were due to the medications or to the illness being treated.

“My training is in both epidemiology and neuroscience so I have been interested in studying long-term development from a brain and behavioral perspective,” said study author Ardesheer Talati, a professor of clinical neurobiology and co-director of the Columbia Psychiatry Grand Rounds at Columbia University and the New York State Psychiatric Institute. “I am also interested in translational research. Preclinical studies had suggested some risks associated with antidepressant exposure in mice, but it is critical to test whether such findings also apply to human populations, where depression does not occur randomly or in a vacuum.”

The researchers conducted a retrospective cohort study using health records from the Rochester Epidemiology Project, a population-based data resource in Olmsted County, Minnesota. They followed a group of children born between 1997 and 2010 and tracked their psychiatric diagnoses through 2021. The study included 837 children whose mothers used either selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors during pregnancy, along with comparison groups of 863 children whose mothers did not use antidepressants during pregnancy and 399 whose mothers had discontinued use before becoming pregnant.

The research team extracted data from the mothers’ and children’s medical records, including information about medication use, psychiatric diagnoses, delivery outcomes, and demographic characteristics. Two board-certified psychiatrists independently verified whether mothers had taken the medications during pregnancy and adjudicated whether children had been diagnosed with depression or anxiety. Children were followed from birth until either a mental health diagnosis was made or the study period ended.

Initial analyses showed that children exposed to antidepressants during pregnancy had higher rates of depression or anxiety diagnoses compared to children of nonusers. But once the researchers adjusted for whether the mother had experienced depression during pregnancy, the association disappeared. The adjusted hazard ratio for developing depression or anxiety was 1.00, meaning there was no increased risk. Children whose mothers had used antidepressants before but not during pregnancy showed a similar pattern. These results suggest that the increased rates of psychiatric diagnoses in exposed children may be explained by maternal depression itself rather than by any direct effect of the medications.

The researchers also looked at exposure to selective serotonin reuptake inhibitors specifically and found the same result: no increased risk after adjusting for maternal mental health. Additional analyses showed that these findings held true when limiting follow-up to the first 15 years of life, excluding early childhood diagnoses, or excluding mothers who experienced depression in the decade after childbirth.

Importantly, the researchers found no differences in psychiatric outcomes between children whose mothers used antidepressants during pregnancy and those whose mothers had only used them beforehand. This further supports the idea that maternal illness—not in utero medication exposure—is likely the driving factor behind the association between maternal antidepressant use and child mental health. Sensitivity analyses that examined differences by the child’s sex, timing of antidepressant exposure during pregnancy, and other factors yielded similar results.

“We show the complexity that studies testing the long-term effects of prenatal exposures such as depression have,” Talati told PsyPost. “Indeed if we just look overall, the children exposed to antidepressant medications in pregnancy do have higher rates of psychopathology themselves (so you would be tempted to say, antidepressants cause risk in the kids).”

“However, once you adjust for potential confounding factors, these findings whittle away. Moreover, the children of the women who used antidepressant medications before, but not during pregnancy had comparable rates, suggesting that it is either maternal depression or some underlying vulnerability that is driving the increased psychopathology (called “confounding by indication”), rather than the medication per se.”

These findings align with an earlier study published in 2023 that used data from over 1 million births in Denmark. That study also found a modest association between prenatal antidepressant exposure and emotional disorders in children, including depression and anxiety. However, it similarly showed that the association was greatly reduced or disappeared after adjusting for maternal mental health and other confounding factors. In fact, the Danish study found that maternal antidepressant use after pregnancy and paternal use during the mother’s pregnancy were also associated with increased child risk—further pointing to shared familial or genetic influences rather than a causal effect of medication use during pregnancy.

Both studies relied on large, population-based cohorts and advanced statistical techniques to minimize bias. The Minnesota study, in particular, included rigorous manual review and psychiatrist adjudication of medical records, which helped ensure that both medication exposure and psychiatric diagnoses were accurately captured. But the authors acknowledge some limitations. The study relied on prescription records rather than pharmacy fill data, so it’s possible that some mothers prescribed antidepressants did not take them.

Because the research is observational, it cannot definitively prove that antidepressants during pregnancy have no effect. “We cannot really randomize pregnant women to medications or not, so must rely on ‘real world’ use and data,” Talati noted. “While we do our best to account for all the confounders, there are always going to be differences that you cannot see or measure.”

Looking ahead, the researchers plan to continue exploring how antidepressant exposure during pregnancy might affect child development beyond emotional disorders, including gut health and disorders involving brain-gut interactions.

“We have been following in different cohorts using different approaches; moreover, because these antidepressant medications work by altering serotonin levels, and the vast majority of the serotonin resides in the gut, we also have an arm of the study showing the effects of prenatal SSRI use on offspring gut development and disorders of brain-gut interaction,” Talati said. “Finally, we want to get a better handle on timing of mechanisms—> e.g., are there particular periods in pregnancy that confer the greatest risk.”

The study, “Prenatal Antidepressant Exposure and Risk of Depression and Anxiety Disorders: An Electronic Health Records–Based Cohort Study,” was authored by Ardesheer Talati, Jennifer L. Vande Voort, Launia J. White, David Hodge, Cynthia J. Stoppel, Myrna M. Weissman, Jay A. Gingrich, and William V. Bobo.