Associations Between Maternal Depression, Antidepressant Use During Pregnancy, and Adverse Pregnancy Outcomes: An Individual Participant Data Meta-analysis : Obstetrics & Gynecology

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Contents: Systematic Review

Associations Between Maternal Depression, Antidepressant Use During Pregnancy, and Adverse Pregnancy Outcomes

An Individual Participant Data Meta-analysis

Vlenterie, Richelle PhD; van Gelder, Marleen M. H. J. PhD; Anderson, H. Ross MD; Andersson, Liselott PhD; Broekman, Birit F. P. PhD; Dubnov-Raz, Gal PhD; El Marroun, Hanan PhD; Ferreira, Ema MSc; Fransson, Emma PhD; van der Heijden, Frank M. M. A. PhD; Holzman, Claudia B. PhD; Kim, J. Jo PhD; Khashan, Ali S. PhD; Kirkwood, Betty R. PhD; Kuijpers, Harold J. H. MD; Lahti-Pulkkinen, Marius PhD; Mason, Dan PhD; Misra, Dawn PhD; Niemi, Maria PhD; Nordeng, Hedvig M. E. PhD; Peacock, Janet L. PhD; Pickett, Kate E. PhD; Prady, Stephanie L. PhD; Premji, Shahirose S. PhD; Räikkönen, Katri PhD; Rubertsson, Christine PhD; Sahingoz, Mine MD; Shaikh, Kiran PhD; Silver, Richard K. MD; Slaughter-Acey, Jaime PhD; Soremekun, Seyi PhD; Stein, Dan J. PhD; Sundström-Poromaa, Inger PhD; Sutter-Dallay, Anne-Laure PhD; Tiemeier, Henning PhD; Uguz, Faruk MD; Varela, Pinelopi MSc; Vrijkotte, Tanja G.M. PhD; Winterfeld, Ursula PhD; Zar, Heather J. PhD; Zervas, Iannis M. PhD; Prins, Judith B. PhD; Pop-Purceleanu, Monica PhD; Roeleveld, Nel PhD

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Obstetrics & Gynecology 138(4):p 633-646, October 2021. | DOI: 10.1097/AOG.0000000000004538


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.


MEDLINE, EMBASE,, and PsycINFO up to June 2016.


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.


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).


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.


PROSPERO, CRD42016035711.

© 2021 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.

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