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Original Investigation
November 2, 2021

Association of Maternal Antidepressant Prescription During Pregnancy With Standardized Test Scores of Danish School-aged Children

Author Affiliations
  • 1National Centre for Register-Based Research, Department of Economics and Business Economics, Aarhus University, Aarhus, Denmark
  • 2Department of Neurology, Aarhus University Hospital, Aarhus, Denmark
  • 3Centre for Integrated Register-based Research (CIRRAU), Aarhus University, Aarhus, Denmark
JAMA. 2021;326(17):1725-1735. doi:10.1001/jama.2021.17380
Key Points

Question  Is there an association between maternal antidepressant prescription during pregnancy and standardized test scores of Danish school-aged children?

Findings  In this population-based retrospective cohort study that included 575 369 public schoolchildren in Denmark, maternal antidepressant prescription during pregnancy was associated with significantly lower standardized test scores (range, 1-100) in mathematics (adjusted test score difference, −2.2) but no significant difference in language test scores (adjusted test score difference, −0.1) compared with children whose mothers did not fill prescriptions for antidepressants during pregnancy.

Meaning  Among Danish public schoolchildren, maternal antidepressant prescription during pregnancy was associated with statistically significantly lower standardized test scores in mathematics that were small in magnitude and no significant difference in language test scores.

Abstract

Importance  Concerns exist about long-term neurodevelopmental consequences of prenatal exposure to antidepressants.

Objective  To evaluate whether maternal prescription fill for antidepressants in pregnancy was associated with performance in standardized tests among Danish schoolchildren.

Design, Setting, and Participants  Population-based retrospective cohort study of children born in Denmark between January 1, 1997, and December 31, 2009, attending public primary and lower secondary school. The children included had completed a language or mathematics test as part of the Danish National Test Program between January 1, 2010, and December 31, 2018. The age range of the eligible schoolchildren was 7 to 17 years.

Exposures  Maternal prescription fill for antidepressants during pregnancy, obtained from the Danish Prescription Register.

Main Outcomes and Measures  The difference in standardized scores between children with and without maternal prescription fill for antidepressants in mathematics and language tests (scale, 1-100; higher scores indicate better test results) was estimated using linear regression models, adjusted for relevant confounders. Ten sensitivity analyses were performed, including a sibling-controlled analysis.

Results  Among the 575 369 children included (51.1% males), 10 198 (1.8%) were born to mothers filling an antidepressant prescription during pregnancy. The mean (SD) age of children at the time of testing spanned from 8.9 (0.4) years in grade 2 to 14.9 (0.4) years in grade 8. Maternal prescription fill for antidepressants was significantly associated with a poorer performance in mathematics (mean test scores for the group exposed to maternal antidepressant fill: 52.1 [95% CI, 51.7-52.6] and for the group not exposed to maternal antidepressant fill: 57.4 [95% CI, 57.3-57.4]; adjusted difference, −2.2 [95% CI, −2.7 to −1.6]), but not in language (mean test scores for the exposed group: 53.4 [95% CI, 53.1-53.7] and for the not exposed group: 56.6 [95% CI, 56.5-56.6]; adjusted difference, −0.1 [95% CI, −0.6 to 0.3]). In the sibling-controlled analysis, the adjusted difference in mathematics (mean scores for the exposed group: 53.5 [95% CI, 52.7-54.3] and for the not exposed group: 59.0 [95% CI, 58.9-59.1]) was −2.8 (95% CI, −4.5 to −1.2) and in language (mean test scores for the exposed group: 53.9 [95% CI, 53.2-54.6] and for the not exposed group: 56.6 [95% CI, 56.5-56.7]) was −0.3 (95% CI, −1.9 to 1.2).

Conclusions and Relevance  In this study of public schoolchildren in Denmark, children whose mothers had filled prescriptions for antidepressants during pregnancy, compared with children whose mothers did not fill prescriptions for antidepressants during pregnancy, had a 2-point lower standardized test score in mathematics, a difference that was statistically significant, but had no significant difference in language test scores. 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.

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