To examine the impact of pharmacologic treatment for depression on obstetric outcomes in women treated for depression during the 2 years prior to pregnancy.
Observational cohort study among 2859 women treated for depression during the 2 years prior to pregnancy. The primary exposure was any antidepressant treatment during pregnancy. Secondary analyses examined the impact of treatment by period of antidepressant exposure. Multivariable logistic regression models as well as propensity score analysis was utilized.
Among 2859 women, 1648 (58%) were treated with antidepressant medication during pregnancy. Women who received antidepressants had no difference in preterm and early-term deliveries, Apgar scores, and small for gestational age (SGA); they had a lower likelihood of breastfeeding (adjusted odds ratio (AOR) 0.69, (95% confidence interval (CI): 0.51 to 0.94)). In secondary analysis, women who used antidepressants all three trimesters who delivered at term were more likely to deliver early term (AOR 1.36, (95% CI: 1.09 to 1.72)). Women who were treated with antidepressants only during the first and second trimesters had a reduced likelihood of SGA (AOR: 0.51 (95% CI: 0.32 to 0.83)). Generally similar results were observed with propensity score analysis.
Antidepressant exposure during pregnancy does not confer an increased risk of preterm birth nor growth restriction in women recently treated for depression, but also does not appear to markedly improve these outcomes.
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Bennett HA EA, Taddio A, Koren G, Einarson TR . Prevalence of depression during pregnancy: systematic review. Obstet Gynecol 2004; 103 (4): 798–709.
Judd LL AH, Maser JD, Zeller PJ, Endicott J, Coryell W, Paulus MP et al. A prospective 12-year study of subsyndromal and syndromal depressive symptoms in unipolar major depressive disorders. Arch Gen Psychiatry 1998; 55 (8): 694–700.
Andersson L, Sundström-Poromaa I, Bixo M, Wulff M, Bondestam K, åStröm M . Point prevalence of psychiatric disorders during the second trimester of pregnancy: a population-based study. Am J Obstet Gynecol 2003; 189 (1): 148–154.
Lee A, Lam SK, Sze Mun Lau SM, Chong CS, Chui HW, Fong DY . Prevalence, course, and risk factors for antenatal anxiety and depression. Obst Gynecol 2007; 110 (5): 1102–1112.
Grigoriadis S, VonderPorten EH, Mamisashvili L, Tomlinson G, Dennis CL, Koren G et al. The impact of maternal depression during pregnancy on perinatal outcomes: a systematic review and meta-analysis. J Clin Psychiatry 2013; 74 (4): e321–e341.
Yonkers K, Wisner KL, Stewart DE, Oberlander TF, Dell DL, Stotland N et al. The management of depression during pregnancy: a report from the American Psychiatric Association and the American College of Obstetricians and Gynecologists. Obstet Gynecol 2009; 114 (3): 703–713.
Grote NK BJ, Gavin AR, Melville JL, Iyengar S, Katon WJ . A meta-analysis of depression during pregnancy and the risk of preterm birth, low birth weight, and intrauterine growth restriction. Arch Gen Psychiatry 2010; 67 (10): 1012–1024.
Hu R, Li Y, Zhang Z, Yan W . Antenatal depressive symptoms and the risk of preeclampsia or operative deliveries: a meta-analysis. PLos ONE 2015; 10 (3): e0119018.
Davalos D, Yadon CA, Tregellas HC . Untreated prenatal maternal depression and the potential risks to offspring: a review. Arch Womens Mental Health 2012; 15 (1): 1–14.
Szegda K, Markenson G, Bertone-Johnson ER, Chasan-Taber L . Depression during pregnancy: a risk factor for adverse neonatal outcomes? A critical review of the literature. J Matern Fetal Neonatal Med 2014; 27 (9): 960–967.
Dietz P, Williams SB, Callaghan WM, Bachman DJ, Whitlock EP, Hornbrook MC . Clinically identified maternal depression before, during, and after pregnancies ending in live births. Am J Psychiatry 2007; 164 (10): 1515–1520.
Hayes R, Wu P, Shelton RC, Cooper WO, Dupont WD, Mitchel E et al. Maternal antidepressant use and adverse outcomes: a cohort study of 228,876 pregnancies. Am J Obstet Gynecol 2012; 207 (1): 49.
Ramosn E OD, Rey E, Blais L, Bérard A . Prevalence and predictors of antidepressant use in a cohort of pregnant women. BJOG 2007; 114 (9): 1055–1064.
Oberlander T, Warburton W, Misri S, Aghajanian J, Hertzman C . Neonatal outcomes after prenatal exposure to selective serotonin reuptake inhibitor antidepressants and maternal depression using population-based linked health data. Arch Gen Psychiatry 2006; 63 (8): 898–906.
Wen S, Yang Q, Garner P, Fraser W, Olatunbosun O, Nimrod C et al. Selective serotonin reuptake inhibitors and adverse pregnancy outcomes. Am J Obstet Gynecol 2006; 194 (4): 961–966.
Steiner M . Prenatal exposure to antidepressants: how safe are they? Am J Psychiatry 2012; 169 (11): 1130–1132.
Ross LE GS, Mamisashvili L, Vonderporten EH, Roerecke M, Rehm J, Dennis CL et al. Selected pregnancy and delivery outcomes after exposure to antidepressant medication: a systematic review and meta-analysis. JAMA Psychiatry 2013; 70 (4): 436–443.
Maschi S, Clavenna A, Campi R, Schiavetti B, Bernat M, Bonati M . Neonatal outcome following pregnancy exposure to antidepressants: a prospective controlled cohort study. BJOG 2008; 115 (2): 283–289.
Huang H, Coleman S, Bridge JA, Yonkers K, Katon W . A meta-analysis of the relationship between antidepressant use in pregnancy and the risk of preterm birth and low birth weight. Gen Hosp Psychiatry 2014; 36 (1): 13–18.
Huybrechts K, Sanghani RS, Avorn J, Urato AC . Preterm birth and antidepressant medication use during pregnancy: a systematic review and meta-analysis. PLos ONE 2014; 9 (3): e92778.
Eke A, Saccone G, Berghella V . Selective serotonin reuptake inhibitor (SSRI) use during pregnancy and risk of preterm birth: a systematic review and meta-analysis. BJOG 2016; 123 (12): 1900–1907.
Chun-Fai-Chan B, Koren G, Fayez I, Kalra S, Voyer-Lavigne S, Boshier A et al. Pregnancy outcome of women exposed to bupropion during pregnancy: a prospective comparative study. Am J Obstet Gynecol 2005; 192 (3): 932–936.
Simon G, Cunningham ML, Davis RL . Outcomes of prenatal antidepressant exposure. Am J Psychiatry 2002; 159 (12): 2055–2061.
Suri R, Altshuler L, Hellemann G, Burt VK, Aquino A, Mintz J . Effects of antenatal depression and antidepressant treatment on gestational age at birth and risk of preterm birth. Am J Psychiatry 2007; 164 (8): 1206–1213.
Orr S, James SA, Blackmore Prince C . Maternal prenatal depressive symptoms and spontaneous preterm births among African-American women in Baltimore, Maryland. Am J Epidemiol 2002; 156 (9): 797–802.
Palmsten K, Hernández-Díaz S . Can nonrandomized studies on the safety of antidepressants during pregnancy convincingly beat confounding, chance, and prior beliefs? Epidemiology 2012; 23 (5): 686–688.
Accortt E, Schetter CD . Pregnant women screening positive for depressive symptoms at 24-28 weeks may have increased risk of preterm birth but more precise research is needed. Evid Based Nurs 2014; 17 (1): 11–12.
Wisner K, Sit DK, Hanusa BH, Moses-Kolko EL, Bogen DL, Hunker DF et al. Major depression and antidepressant treatment: impact on pregnancy and neonatal outcomes. Am J Psychiatry 2009; 166 (5): 557–566.
Oberlander T, Warburton W, Misri S, Aghajanian J, Hertzman C . Effects of timing and duration of gestational exposure to serotonin reuptake inhibitor antidepressants: population-based study. Br J Psychiatry 2008; 192 (5): 338–343.
Chambers C, Johnson KA, Dick LM, Felix RJ, Jones KL . Birth outcomes in pregnant women taking fluoxetine. N Engl J Med 1996; 335 (14): 1010–1015.
Uchida M, Spencer AE, Biederman J, Castro VM, Kenworthy T, Chan J et al. A systematic evaluation of the qtc interval and antidepressants in youth: An Electronic Health Record Study. J Dev Behav Pediatr 2015; 36 (6): 434–439.
Blumenthal S, Castro VM, Clements CC, Rosenfield HR, Murphy SN, Fava M et al. An electronic health records study of long-term weight gain following antidepressant use. JAMA Psychiatry 2014; 71 (8): 889–896.
Bureau UC . Household Income: 2013. American Community Survvey Briefs, United States Dept of Commerce, US Census Bureau 2014 Website: https://www.census.gov/content/dam/Census/library/publications/2014/acs/acsbr13-02.pdf. Access date 11/1/2016.
Clements C, Castro VM, Blumenthal SR, Rosenfield HR, Murphy SN, Fava M et al. Prenatal antidepressant exposure is associated with risk for attention-deficit hyperactivity disorder but not autism spectrum disorder in a large health system. Mol Psychiatry 2015; 20 (6): 727–734.
Oken E, Kleinman KP, Rich-Edwards J, Gillman MW . A nearly continuous measure of birth weight for gestational age using a United States national reference. BMC Pediatr 2003; 3: 6.
Yonkers K, Norwitz ER, Smith MV, Lockwood CJ, Gotman N, Luchansky E et al. Depression and serotonin reuptake inhibitor treatment as risk factors for preterm birth. Epidemiology 2012; 23 (5): 677–685.
Fong A, Simon-Freeman R, Westermann M, Pan D, Ogunyemi DA . Maternal Depression in Pregnancy and its Association with Adverse Pregnancy Outcomes. Society of Maternal Fetal Medicine 37th Annual Meeting; 2017 American Journal of Obstetrics and Gynecology: Las Vegas, NV, USA, 2017.
Cheng Y, Hubbard A, Caughey AB, Tager IB . The association between persistent fetal occiput posterior position and perinatal outcomes: an example of propensity score and covariate distance matching. Am J Epidemiol 2010; 171 (6): 656–663.
Abadie A, Imbens GW . Large sample properties of matching estimators for average treatment effects. Econometrica 2006; 74: 235–267.
Garrido M, Kelley AS, Paris J, Roza K, Meier DE, Morrison RS et al. Methods for constructing and assessing propensity scores. Health Serv Res 2014; 49 (5): 1701–1720.
Brooks J, Ohsfeldt RL . Squeezing the balloon: propensity scores and unmeasured covariate balance. Health Serv Res 2013; 48 (4): 1487–1507.
Imbens G . Nonparametric estimation of average treatment effects under exogeneity: a review. Rev Econ Stat 2004; 86 (1): 4–29.
Austin P . Optimal caliper widths for propensity-score matching when estimating differences in means and differences in proportions in observational studies. Pharm Stat 2011; 10 (2): 150–161.
Pearson K, Nonacs RM, Viguera AC, Heller VL, Petrillo LF, Brandes M et al. Birth outcomes following prenatal exposure to antidepressants. J Clin Psychiatry 2007; 68 (8): 1284–1289.
Malm H, Klaukka T, Neuvonen PJ . Risks associated with selective serotonin reuptake inhibitors in pregnancy. Obstet Gynecol 2005; 106 (6): 1289–1296.
El Marroun H, Jaddoe VW, Hudziak JJ, Roza SJ, Steegers EA, Hofman A et al. Maternal use of selective serotonin reuptake inhibitors, fetal growth, and risk of adverse birth outcomes. Arch Gen Psychiatry 2011; 69 (7): 706–714.
Freeman M . Breastfeeding and antidepressants: clinical dilemmas and expert perspectives. J Clin Psychiatry 2009; 70 (2): 291–292.
ACPS Jefferies Fetus and Newborn Committee. Selective serotonin reuptake inhibitors in pregnancy and infant outcomes. Paediatr Child Health 2011; 16 (9): 562–563.
Oberlander T, Misri S, Fitzgerald CE, Kostaras X, Rurak D, Riggs W . Pharmacologic factors associated with transient neonatal symptoms following prenatal psychotropic medication exposure. J Clin Psychiatry 2004; 65 (2): 230–237.
Lattimore K, Donn SM, Kaciroti N, Kemper AR, Neal CR Jr, Vazquez DM . Selective serotonin reuptake inhibitor (SSRI) use during pregnancy and effects on the fetus and newborn: a meta-analysis. J Perinatol 2005; 25 (9): 595–604.
Koren G, Nordeng H . Antidepressant use during pregnancy: the benefit-risk ratio. Am J Obstet Gynecol 2012; 207 (3): 157–163.
This work was supported through funding from the National Institute of Mental Health (5R01MH100286–02). This paper was presented as a poster at the Society for Maternal-Fetal Medicine 37th Annual Meeting, Las Vegas, NV, USA, 26 January 2017.
PRH has received consultant fees or served on scientific advisory boards for Proteus Biomedical, Genomind, Healthrageous, Perfect Health, and Psy Therapeutics. The remaining authors declare no conflict of interest.
Supplementary Information accompanies the paper on the Journal of Perinatology website
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Venkatesh, K., Castro, V., Perlis, R. et al. Impact of antidepressant treatment during pregnancy on obstetric outcomes among women previously treated for depression: an observational cohort study. J Perinatol 37, 1003–1009 (2017). https://doi.org/10.1038/jp.2017.92
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