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

Educational Objective
To understand the benefits and risks of antidepressant use during pregnancy.
1 Credit CME
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.


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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Article Information

Corresponding Author: Jakob Christensen, DrMedSci, PhD, Department of Neurology, Aarhus University Hospital, Palle Juul-Jensens Blvd 165, DK-8200 Aarhus N, Denmark (jakob@farm.au.dk).

Accepted for Publication: September 15, 2021.

Author Contributions: Drs Trabjerg and Dreier had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Christensen, Dreier.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Christensen, Dreier.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Christensen, Trabjerg.

Obtained funding: Christensen.

Administrative, technical, or material support: Christensen.

Supervision: Christensen, Dreier.

Conflict of Interest Disclosures: Dr Christensen reported receiving personal fees from UCB Nordic and Eisai AB during the conduct of the study. No other disclosures were reported.

Funding/Support: The study was funded in part by the Central Denmark Region and the Novo Nordisk Foundation (NNF16OC0019126).

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Data Sharing Statement: Data were based on Danish national registers, and individual-level data cannot be shared. However, summary statistics, in addition to the results provided in the Results section and Supplement, may be provided on request.

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