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May 11, 2022Research ArticleOpen Access

Maternal Serotonergic Antidepressant Use in Pregnancy and Risk of Seizures in Children

View ORCID ProfileKelsey Kathleen Wiggs, Ayehsa C Sujan, Martin E Rickert, Patrick D Quinn, Henrik Larsson, Paul Lichtenstein, Brian M D'Onofrio, View ORCID ProfileA Sara Oberg
First published May 11, 2022, DOI: https://doi.org/10.1212/WNL.0000000000200516
Kelsey Kathleen Wiggs
1Department of Psychological & Brain Sciences, Indiana University – Bloomington, Bloomington, IN, USA
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  • ORCID record for Kelsey Kathleen Wiggs
Ayehsa C Sujan
2Kaiser Permanente Northern California Division of Research, Oakland, CA
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  • For correspondence: ayesha.c.sujan@kp.org
Martin E Rickert
1Department of Psychological & Brain Sciences, Indiana University – Bloomington, Bloomington, IN, USA
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  • For correspondence: rickertm@indiana.edu
Patrick D Quinn
3Department of Applied Health Science, School of Public Health, Indiana University – Bloomington, Bloomington, IN, USA
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  • For correspondence: quinnp@iu.edu
Henrik Larsson
4Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
5School of Medical Sciences, Örebro University, Örebro, Sweden
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  • For correspondence: henrik.larsson@ki.se
Paul Lichtenstein
4Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
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  • For correspondence: paul.lichtenstein@ki.se
Brian M D'Onofrio
1Department of Psychological & Brain Sciences, Indiana University – Bloomington, Bloomington, IN, USA
4Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
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A Sara Oberg
4Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
6Department of Epidemiology, T.H. Chan School of Public Health, Harvard, Boston, USA
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  • ORCID record for A Sara Oberg
  • For correspondence: oberg@hsph.harvard.edu
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Citation
Maternal Serotonergic Antidepressant Use in Pregnancy and Risk of Seizures in Children
Kelsey Kathleen Wiggs, Ayehsa C Sujan, Martin E Rickert, Patrick D Quinn, Henrik Larsson, Paul Lichtenstein, Brian M D'Onofrio, A Sara Oberg
Neurology May 2022, 10.1212/WNL.0000000000200516; DOI: 10.1212/WNL.0000000000200516

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Abstract

Objective: To evaluate whether children born to women who use serotonergic antidepressants during pregnancy have higher risk of neonatal seizures and epilepsy.

Methods: We used Swedish register-based data to examine associations between maternal-reported use of selective-serotonin reuptake inhibitor (SSRI) and selective serotonin-norepinephrine reuptake inhibitors (SNRI) in pregnancy and diagnosis of neonatal seizures and/or epilepsy in over 1.2 million children. To account for systematic differences between exposed and unexposed children we adjusted for a wide range of measured confounders. After first evaluating the role of maternal indication for SSRI/SNRI use (i.e., depression and anxiety) and parental epilepsy, we adjusted for remaining parental background factors (e.g., age, co-morbidities, education, and family socioeconomic indices) and pregnancy-specific characteristics (e.g., maternal use of other psychotropic medications and tobacco smoking in early pregnancy).

Results: Compared with all other children, children of women that reported use of SSRI/SNRI in pregnancy had an elevated risk of neonatal seizures and epilepsy (risk ratio [RR]=1.41, 95% confidence interval [CI]=1.03-1.94; hazard ratio [HR]=1.21, 95% CI=1.03-1.43 respectively). The estimates of association were attenuated by adjustment for maternal indications for SSRI/SNRI use (RR=1.30, 95% CI=0.94-1.79; HR = 1.13, 95% CI = 0.95-1.33), but not by additional adjustment for parental history of epilepsy. Full adjustment for all measured parental and pregnancy-specific factors resulted in substantial attenuation of the remaining associations (RR = 1.10, 95% CI = 0.79-1.53; HR = 0.96, 95% CI = 0.81-1.14).

Conclusions: The present study found no support for the concern that maternal SSRI/SNRI use in pregnancy increases children’s risk for neonatal seizures or epilepsy.

Classification of Evidence: This study provides Class II evidence that exposure to SSRI/SNRI's in the first trimester of pregnancy is not associated with an increased incidence of neo-natal seizures/epilepsy.

  • Received August 24, 2021.
  • Accepted in final form February 28, 2022.
  • Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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