Selective serotonin reuptake inhibitor antidepressant use in first trimester pregnancy and risk of specific congenital anomalies: a European register-based study
- 1.5k Downloads
Evidence of an association between early pregnancy exposure to selective serotonin reuptake inhibitors (SSRI) and congenital heart defects (CHD) has contributed to recommendations to weigh benefits and risks carefully. The objective of this study was to determine the specificity of association between first trimester exposure to SSRIs and specific CHD and other congenital anomalies (CA) associated with SSRI exposure in the literature (signals). A population-based case-malformed control study was conducted in 12 EUROCAT CA registries covering 2.1 million births 1995–2009 including livebirths, fetal deaths from 20 weeks gestation and terminations of pregnancy for fetal anomaly. Babies/fetuses with specific CHD (n = 12,876) and non-CHD signal CA (n = 13,024), were compared with malformed controls whose diagnosed CA have not been associated with SSRI in the literature (n = 17,083). SSRI exposure in first trimester pregnancy was associated with CHD overall (OR adjusted for registry 1.41, 95 % CI 1.07–1.86, fluoxetine adjOR 1.43 95 % CI 0.85–2.40, paroxetine adjOR 1.53, 95 % CI 0.91–2.58) and with severe CHD (adjOR 1.56, 95 % CI 1.02–2.39), particularly Tetralogy of Fallot (adjOR 3.16, 95 % CI 1.52–6.58) and Ebstein’s anomaly (adjOR 8.23, 95 % CI 2.92–23.16). Significant associations with SSRI exposure were also found for ano-rectal atresia/stenosis (adjOR 2.46, 95 % CI 1.06–5.68), gastroschisis (adjOR 2.42, 95 % CI 1.10–5.29), renal dysplasia (adjOR 3.01, 95 % CI 1.61–5.61), and clubfoot (adjOR 2.41, 95 % CI 1.59–3.65). These data support a teratogenic effect of SSRIs specific to certain anomalies, but cannot exclude confounding by indication or associated factors.
KeywordsCongenital anomaly SSRI Medication Depression Epidemiology Registry
We thank the many people throughout Europe involved in providing and processing information, including affected families, clinicians, health professionals, medical record clerks and registry staff.
Compliance with Ethical Standards
AW was funded by a Ulster University Vice Chancellor’s Research Studentship. EUROCAT is co-funded by the EC, under the framework of the EU Health Programme 2008–2013, Grant Agreement 2010 22 04 (Executive Agency for Health & Consumers). EUROCAT registries are funded as fully described in Paper 6 of EUROCAT Report 9—EUROCAT Member Registries: Organization and Activities.
Conflict of interest
The congenital anomaly registries and institutions where EG, MKB, DT, BK, VN, MoM, AP, MG, MCA, AR, LA, LdJvdB and HD are employed have previously received funding from Glaxo Smith Kline for a study of safety of antiepileptic lamotrigine use in pregnancy. No author has had any association with or interest in any antidepressant manufacturer in relation to the current study.
- 3.Alonso J, Angermeyer MC, Bernert S, Bruffaerts R, Brugha TS, Bryson H, et al. Prevalence of mental disorders in Europe: results from the European Study of the Epidemiology of Mental Disorders (ESEMeD) project. Acta Psychiatr Scand. 2004;420:21–7.Google Scholar
- 8.NICE. Antenatal and postnatal mental health: clinical management and service guidance. London: British Psychological Society and Gaskell; 2007.Google Scholar
- 9.Andrade SE, Gurwitz JH, Davis RL, Chan KA, et al. Prescription drug use in pregnancy. Obstet Gynecol. 2004;191(2):398–407.Google Scholar
- 14.Charlton R, Jordan S, Pierini A, Garne E, Neville A, Hansen A, Gini R, Thayer D, Tingay K, Puccini A, Bos H, Nybo Andersen A, Sinclair M, Dolk H, de Jong-van den Berg L. Selective serotonin reuptake inhibitor prescribing before, during and after pregnancy: a population-based study in six European regions. BJOG. 2014;. doi: 10.1111/1471-0528.13143.PubMedGoogle Scholar
- 15.Andrade SE, Raebel MA, Brown J, Lane K, Livingston J, Boudreau D, et al. Use of antidepressant medications during pregnancy: a multisite study. Obstet Gynecol. 2008;198(2):194.e1–5.Google Scholar
- 16.Bakker MK, Kolling P, van den Berg PB, de Walle HE, de Jong van den Berg LT. Increase in use of selective serotonin reuptake inhibitors in pregnancy during the last decade, a population-based cohort study from the Netherlands. Br J Clin Pharmacol. 2008;65(4):600–6.CrossRefPubMedCentralPubMedGoogle Scholar
- 22.GlaxoSmithKline. Preliminary report on bupropion in pregnancy and the occurrence of cardiovascular and major congenital malformation. 2005.Google Scholar
- 38.Sivojelezova A, Shuhaiber S, Sarkissian L, Einarson A, Koren G. Citalopram use in pregnancy: prospective comparative evaluation of pregnancy and fetal outcome. Obstet Gynecol. 2005;193(6):2004–9.Google Scholar
- 39.Wen SW, Yang Q, Garner P, Fraser W, Olatunbosun O, Nimrod C, et al. Selective serotonin reuptake inhibitors and adverse pregnancy outcomes. Obstet Gynecol. 2006;194(4):961–6.Google Scholar
- 50.Grigoriadis S, VonderPorten EH, Mamisashvili L, Roerecke M, Rehm J, Dennis C, et al. Antidepressant exposure during pregnancy and congenital malformations: Is there an association? A systematic review and meta-analysis of the best evidence. J Clin Psychiatry. 2013;74(4):e293–308.CrossRefPubMedGoogle Scholar
- 52.Olivier JDA, Akerud H, Kaihola H, Pawluski JL, Skalkidou A, Hogberg U, et al. The effects of maternal depression and maternal selective serotonin reuptake inhibitor exposure on the offspring. Front Clin Neurosci. 2013;7:73.Google Scholar
- 63.EUROCAT. EUROCAT Guide 1.3 and reference documents. Instructions for the registration and surveillance of congenital anomalies. http://www.eurocat-network.eu/aboutus/datacollection/guidelinesforregistration/guide1_3instructionmanual (2005). Accessed Nov 2014.
- 68.Bakker, M, De Jonge L. EUROCAT Special Report: Sources of information on medication use in pregnancy. http://www.eurocat-network.eu/content/Special-Report-Medication-Use-In-Pregnancy.pdf. Accessed Nov 2014.
- 69.WHO Collaborating Centre for Drug Statistics Methodology. ATC/DDD Index 2010. http://www.whocc.no/atc_ddd_index/ (2009) Accessed 24 April 2010.
- 79.Krauss MJ, Morrissey AE, Winn HN, Amon E, Leet TL. Microcephaly: an epidemiologic analysis. Obstet Gynecol. 2003;188(6):1484–90.Google Scholar