Association Between Maternal Antidepressant Prescription Fills During Pregnancy and Standardized Test Scores in Children

April 2022

The decision of whether to use antidepressants during pregnancy is a complex one that requires consideration of both the risk of fetal harm and worsening maternal depression. Few long-term studies have explored the effects of fetal exposure to antidepressants on cognition. In this new report from Denmark, the investigators conducted a population-based retrospective cohort study to see whether there is an association between fetal antidepressant exposure and standardized test performance in children.

The investigators used national registers to establish a cohort of children born between 1997 and 2009 and their parents. They obtained records of maternal antidepressant prescriptions from the Danish National Prescription Registry. Standardized test scores in grades 3, 6, and 8 for mathematics and grades 2, 4, 6, and 8 for language came from the Danish National School Test Program. Children were assumed to be exposed to antidepressants if their mothers filled prescriptions for ≥1 antidepressants between 30 days before the estimated date of their last menstrual period and the day before giving birth. The primary outcomes were scores on standardized tests in language and mathematics.

The cohort included 565,171 children without maternal antidepressant prescription fills during pregnancy and 10,198 children—1.8% of the total—with maternal antidepressant prescription fills during pregnancy.

When the investigators adjusted for potential confounders, such as socioeconomic status, test performance in mathematics was significantly worse in children of mothers with antidepressant prescription fills than in children of mothers without antidepressant prescription fills. This difference was 2.2 points, a level the investigators reasoned was probably not clinically relevant. There was no statistically significant difference in language scores between groups.

The investigators performed interaction analyses for comparison between groups by grade level and sex, and found that the difference between groups in mathematics scores increased with grade level. In 8th grade, children of mothers with antidepressant prescription fills scored 5.2 points lower than children without antidepressant prescription fills. The investigators speculated that this could be because of the need to engage more widespread networks in the brain as mathematics becomes more complex.

There were no differences in language scores between groups at any grade level. However, maternal antidepressant prescription fill was associated with poorer language scores in boys but not girls.

In exploratory analyses, tricyclic antidepressants and bupropion, a norepinephrine–dopamine reuptake inhibitor, were not associated with lower mathematics test scores in children of mothers with antidepressant prescription fills. Because there were not enough prescriptions for some antidepressant classes, the investigators could not evaluate for an association between specific classes and mathematics test scores.

This study has implications for the treatment of depression during pregnancy. “The magnitude of the difference in the mathematics test score was small and of uncertain clinical importance, and the findings must be weighed against the benefits of treating maternal depression during pregnancy,” the investigators concluded.


Christensen J, Trabjerg BB, Sun Y, Dreier JW. Association of maternal antidepressant prescription during pregnancy with standardized test scores of Danish school-aged children. JAMA. 2021;326:1725-1735.

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