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Updated: Oct 17, 2025

Using a Murine Model of Psychosocial Stress in Pregnancy as a Translationally Relevant Paradigm for Psychiatric Disorders in Mothers and Infants
Published on: June 13, 2021
Associations Between Maternal Depression, Antidepressant Use During Pregnancy, and Adverse Pregnancy Outcomes: An
Richelle Vlenterie1, Marleen M H J van Gelder, H Ross Anderson
1Department for Health Evidence, Radboud Institute for Health Sciences, and the Radboud REshape Innovation Center, Radboud University Medical Center, Nijmegen, the Netherlands; the Environmental Research Group, King's College, London, United Kingdom; the Department of Clinical Science, Obstetrics and Gynecology, Umeå University, Umeå, Sweden; the Singapore Institute for Clinical Sciences, Singapore; the Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Israel; the Department of Child and Adolescent Psychiatry, the Department of Psychology, Education and Child Studies, Erasmus School of Social and Behavioral Sciences, and the Department of Pediatrics, Erasmus University Rotterdam, Rotterdam, the Netherlands; the Department of Pharmacy (Centre IMAGe), Centre Hospitalier Universitaire Sainte-Justine and Faculté de Pharmacie, Université de Montréal, Montréal, Québec, Canada; the Division of Reproductive and Perinatal Health, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden; the Department of Health Science, Medical Faculty, Lund University, Lund, Sweden; the Vincent van Gogh Institute for Psychiatry, Venlo, the Netherlands; the Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, Michigan; the Department of Obstetrics & Gynecology, NorthShore University HealthSystem, and the University of Chicago Pritzker School of Medicine, Chicago, Illinois; the School of Public Health and the Irish Centre for Fetal and Neonatal Translational Research (INFANT), University College Cork, Cork, Ireland; the London School of Hygiene and Tropical Medicine, London, United Kingdom; the Elisabeth TweeSteden Hospital (ETZ), Tilburg, the Netherlands; the Department of Psychology and Logopedics, University of Helsinki, Helsinki, Finland; the Bradford Teaching Hospitals NHS Foundation Trust, Bradford, United Kingdom; Wayne State University, Detroit, Michigan; the Department of Public Health Science, Karolinska Institutet, Stockholm, Sweden; the PharmacoEpidemiology & Drug Safety Research Group, School of Pharmacy, University of Oslo, and the Department of Child Health and Development, Norwegian Institute of Public Health, Oslo, Norway; the Department of Epidemiology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire; the University of York, York, United Kingdom; the Faculty of Health, School of Nursing, York University, Toronto, Ontario, Canada; the Department of Psychiatry, University of Necmettin Erbakan, Meram Faculty of Medicine, Konya, Turkey; the School of Nursing and Midwifery, Aga Khan University, Karachi, Pakistan; the Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota; the Department of Psychiatry and Mental Health, University of Cape Town, and the South African Medical Research Council, Unit on Risk and Resilience in Mental Disorders, Cape Town, South Africa; the Charles Perrens Hospital and the Bordeaux Population Health Center, INSERM 1219, Bordeaux University, Bordeaux, France; the Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; the "Alexandra" General Hospital of Athens, Athens, Greece; the Department of Public and Occupational Health, Amsterdam Public Health Research Institute, Academic Medical Center - University of Amsterdam, Amsterdam, the Netherlands; the STIS and Clinical Pharmacology Service, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; the Department of Medical Psychology, Radboud Institute for Health Sciences, and the Department of Psychiatry, Radboud University Medical Center, Nijmegen, the Netherlands.
Objective:
To evaluate the associations of depressive symptoms and antidepressant use during pregnancy with the risks of preterm birth, low birth weight, small for gestational age (SGA), and low Apgar scores.
Data Sources:
MEDLINE, EMBASE, ClinicalTrials.gov, and PsycINFO up to June 2016.
Methods Of Study Selection:
Data were sought from studies examining associations of depression, depressive symptoms, or use of antidepressants during pregnancy with gestational age, birth weight, SGA, or Apgar scores. Authors shared the raw data of their studies for incorporation into this individual participant data meta-analysis.
Tabulation, Integration, And Results:
We performed one-stage random-effects meta-analyses to estimate odds ratios (ORs) with 95% CIs. The 215 eligible articles resulted in 402,375 women derived from 27 study databases. Increased risks were observed for preterm birth among women with a clinical diagnosis of depression during pregnancy irrespective of antidepressant use (OR 1.6, 95% CI 1.2-2.1) and among women with depression who did not use antidepressants (OR 2.2, 95% CI 1.7-3.0), as well as for low Apgar scores in the former (OR 1.5, 95% CI 1.3-1.7), but not the latter group. Selective serotonin reuptake inhibitor (SSRI) use was associated with preterm birth among women who used antidepressants with or without restriction to women with depressive symptoms or a diagnosis of depression (OR 1.6, 95% CI 1.0-2.5 and OR 1.9, 95% CI 1.2-2.8, respectively), as well as with low Apgar scores among women in the latter group (OR 1.7, 95% CI 1.1-2.8).
Conclusion:
Depressive symptoms or a clinical diagnosis of depression during pregnancy are associated with preterm birth and low Apgar scores, even without exposure to antidepressants. However, SSRIs may be independently associated with preterm birth and low Apgar scores.
Systematic Review Registration:
PROSPERO, CRD42016035711.
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