Background: Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed psychotropics for major depressive disorder during pregnancy and are used in up to 6.2% of pregnancies. Objective: To compare the perinatal outcomes of pregnancies complicated by maternal depression with or without SSRI therapy versus nondepressed pregnancies. Methods: International Classification of Diseases (ICD)-9 codes for depression were identified among women who delivered at the University of Iowa from April 2009 to March 2011. Data were extracted from linked maternal-neonatal records for all charts with an ICD-9 code for depression and an equal number of women without ICD-9 codes for depression. Results: Of the 3,695 women who delivered between 2009 and 2011, 238 had an ICD-9 code for depression. Sixteen women had depression listed in their records but did not have an ICD-9 code for depression. Their data were combined with those of the women with ICD-9 codes for depression, and it was found that 126 women (50%) in this combined depression cohort received an SSRI. Women with depression had increased alcohol and tobacco use, BMI and premature delivery rates (p < 0.01). Maternal depression was associated with an increased frequency of neonatal intensive care unit (NICU) admission (p < 0.001). In addition to depression, maternal SSRI use, obesity and smoking were univariate predictors of NICU admission. Conclusions: Among women with depression, the use of an SSRI was not associated with significant differences in any of the measured maternal or neonatal parameters, but further studies are needed to evaluate the specific effects of SSRI exposure in early or late gestation. Despite SSRI utilization, women with depression continue to have increased risks during pregnancy.

Keywords:
Maternal depression, Selective serotonin reuptake inhibitors, Perinatal outcomes, Pregnancy
1.
Stewart DE: Clinical practice. Depression during pregnancy. N Engl J Med 2011;365:1605-1611.
2.
Oberlander TF, 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;63:898-906.
3.
Grzeskowiak LE, Gilbert AL, Morrison JL: Investigating outcomes following the use of selective serotonin reuptake inhibitors for treating depression in pregnancy: a focus on methodological issues. Drug Saf 2011;34:1027-1048.
4.
Andrade SE, Raebel MA, Brown J, Lane K, Livingston J, Boudreau D, Rolnick SJ, Roblin D, Smith DH, Willy ME, Staffa JA, Platt R: Use of antidepressant medications during pregnancy: a multisite study. Am J Obstet Gynecol 2008;198:194.e1-194.e5.
5.
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.
6.
Davalos DB, Yadon CA, Tregellas HC: Untreated prenatal maternal depression and the potential risks to offspring: a review. Arch Womens Ment Health 2012;15:1-14.
7.
Suri R, Altshuler L, Hendrick V, Rasgon N, Lee E, Mintz J: The impact of depression and fluoxetine treatment on obstetrical outcome. Arch Womens Ment Health 2004;7:193-200.
8.
Wogelius P, Norgaard M, Gislum M, Pedersen L, Munk E, Mortensen PB, Lipworth L, Sorensen HT: Maternal use of selective serotonin reuptake inhibitors and risk of congenital malformations. Epidemiology 2006;17:701-704.
9.
Kallen B, Otterblad Olausson P: Antidepressant drugs during pregnancy and infant congenital heart defect. Reprod Toxicol 2006;21:221-222.
10.
Louik C, Lin AE, Werler MM, Hernandez-Diaz S, Mitchell AA: First-trimester use of selective serotonin-reuptake inhibitors and the risk of birth defects. N Engl J Med 2007;356:2675-2683.
11.
Greene MF: Teratogenicity of SSRIs - serious concern or much ado about little? N Engl J Med 2007;356:2732-2733.
12.
Bakker MK, Kerstjens-Frederikse WS, Buys CH, de Walle HE, de Jong-van den Berg LT: First-trimester use of paroxetine and congenital heart defects: a population-based case-control study. Birth Defects Res A Clin Mol Teratol 2010;88:94-100.
13.
Alwan S, Reefhuis J, Rasmussen SA, Olney RS, Friedman JM; National Birth Defects Prevention Study: Use of selective serotonin-reuptake inhibitors in pregnancy and the risk of birth defects. N Engl J Med 2007;356:2684-2692.
14.
Davis RL, Rubanowice D, McPhillips H, Raebel MA, Andrade SE, Smith D, Yood MU, Platt R; HMO Research Network Center for Education, Research in Therapeutics: Risks of congenital malformations and perinatal events among infants exposed to antidepressant medications during pregnancy. Pharmacoepidemiol Drug Saf 2007;16:1086-1094.
15.
Lund N, Pedersen LH, Henriksen TB: Selective serotonin reuptake inhibitor exposure in utero and pregnancy outcomes. Arch Pediatr Adolesc Med 2009;163:949-954.
16.
Kallen B: Neonate characteristics after maternal use of antidepressants in late pregnancy. Arch Pediatr Adolesc Med 2004;158:312-316.
17.
Rampono J, Simmer K, Ilett KF, Hackett LP, Doherty DA, Elliot R, Kok CH, Coenen A, Forman T: Placental transfer of SSRI and SNRI antidepressants and effects on the neonate. Pharmacopsychiatry 2009;42:95-100.
18.
Levinson-Castiel R, Merlob P, Linder N, Sirota L, Klinger G: Neonatal abstinence syndrome after in utero exposure to selective serotonin reuptake inhibitors in term infants. Arch Pediatr Adolesc Med 2006;160:173-176.
19.
Zeskind PS, Stephens LE: Maternal selective serotonin reuptake inhibitor use during pregnancy and newborn neurobehavior. Pediatrics 2004;113:368-375.
20.
Leibovitch L, Rymer-Haskel N, Schushan-Eisen I, Kuint J, Strauss T, Maayan-Metzger A: Short-term neonatal outcome among term infants after in utero exposure to serotonin reuptake inhibitors. Neonatology 2013;104:65-70.
21.
Chambers CD, Hernandez-Diaz S, Van Marter LJ, Werler MM, Louik C, Jones KL, Mitchell AA: Selective serotonin-reuptake inhibitors and risk of persistent pulmonary hypertension of the newborn. N Engl J Med 2006;354:579-587.
22.
Ericson A, Kallen B, Wiholm B: Delivery outcome after the use of antidepressants in early pregnancy. Eur J Clin Pharmacol 1999;55:503-508.
23.
Kulin NA, Pastuszak A, Sage SR, Schick-Boschetto B, Spivey G, Feldkamp M, Ormond K, Matsui D, Stein-Schechman AK, Cook L, Brochu J, Rieder M, Koren G: Pregnancy outcome following maternal use of the new selective serotonin reuptake inhibitors: a prospective controlled multicenter study. JAMA 1998;279:609-610.
24.
Kroenke K, Spitzer RL, Williams JB: The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med 2001;16:606-613.
25.
El Marroun H, Jaddoe VW, Hudziak JJ, Roza SJ, Steegers EA, Hofman A, Verhulst FC, White TJ, Stricker BH, Tiemeier H: Maternal use of selective serotonin reuptake inhibitors, fetal growth, and risk of adverse birth outcomes. Arch Gen Psychiatry 2012;69:706-714.
26.
Lau C, Rogers JM, Desai M, Ross MG: Fetal programming of adult disease: implications for prenatal care. Obstet Gynecol 2011;117:978-985.
27.
Moses-Kolko EL, Bogen D, Perel J, Bregar A, Uhl K, Levin B, Wisner KL: Neonatal signs after late in utero exposure to serotonin reuptake inhibitors: literature review and implications for clinical applications. JAMA 2005;293:2372-2383.
28.
Grigoriadis S, VonderPorten EH, Mamisashvili L, Eady A, Tomlinson G, Dennis CL, Koren G, Steiner M, Mousmanis P, Cheung A, Ross LE: The effect of prenatal antidepressant exposure on neonatal adaptation: a systematic review and meta-analysis. J Clin Psychiatry 2013;74:e309-e320.
© 2013 S. Karger AG, Basel
2013
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.