Increased risk of severe congenital heart defects in offspring exposed to selective serotonin-reuptake inhibitors in early pregnancy – an epidemiological study using validated EUROCAT data

BMC Pregnancy and Childbirth

Anne-Marie Nybo Andersen²  Ester Garne¹  Anne Vinkel Hansen¹  Tanja Majbrit Knudsen² 

[1] Paediatric Department, Hospital Lillebaelt, Skovvangen 2-6, 6000 Kolding, Denmark;Department of Public Health, University of Copenhagen, Oester Farimagsgade 5, 1014 Copenhagen K, Denmark

关键词: Cohort study;    EUROCAT;    Socioeconomic status;    Congenital heart defects;    Antidepressant;    SSRI drugs;   

Others  :  1125449
DOI  :  10.1186/1471-2393-14-333

 received in 2014-03-15, accepted in 2014-09-17,  发布年份 2014

【 摘 要 】

Background

Previous studies suggest a possible association between maternal use of selective serotonin-reuptake inhibitors (SSRIs) during early pregnancy and congenital heart defects (CHD). The purpose of this study was to verify this association by using validated data from the Danish EUROCAT Register, and secondary, to investigate whether the risk differs between various socioeconomic groups.

Methods

We conducted a cohort study based on Danish administrative register data linked with the Danish EUROCAT Register, which includes all CHD diagnosed in live births, fetal deaths and in pregnancies terminated due to congenital anomalies. The study population consisted of all registered pregnancies (n = 72,280) in Funen, Denmark in the period 1995–2008. SSRI-use was assessed using The Danish National Prescription Registry, information on marital status, maternal educational level, income, and country of origin from Statistics Denmark was used as indicators of socioeconomic situation, and the CHD were studied in subgroups defined by EUROCAT. Logistic Regression was used to investigate the association between redeemed prescriptions for SSRIs and CHD.

Results

The risk of severe CHD in the offspring of the 845 pregnant women who used SSRIs during first trimester increased four times (AOR 4.03 (95% CI 1.75-9.26)). We found no increased risk of septal defects. Socioeconomic position did not modify the association between maternal SSRI-use during pregnancy and severe CHD.

Conclusion

This study, which is based on data with high case ascertainment, suggests that maternal use of SSRIs during first trimester increases the risk of severe CHD, but does not support findings from previous studies, based on administrative register data, regarding an increased risk of septal defects. The study was unable to document an interaction between socioeconomic status and maternal SSRI-use on the risk of severe CHD.

【 授权许可】

   
2014 Knudsen et al.; licensee BioMed Central Ltd.

【 参考文献 】

• [1]Grigoriadis S, Robinson GE: Gender issues in depression. Ann Clin Psychiatry 2007, 19(4):247-255.
• [2]de Las Cuevas C, Sanz EJ: Safety of selective serotonin reuptake inhibitors in pregnancy. Curr Drug Saf 2006, 1(1):17-24.
• [3]Vlaminck JJ, van Vliet IM, Zitman FG: Withdrawal symptoms of antidepressants. Ned Tijdschr Geneeskd 2005, 149(13):698-701.
• [4]Cooper WO, Willy ME, Pont SJ, Ray WA: Increasing use of antidepressants in pregnancy. Am J Obstet Gynecol 2007, 196(6):544. e541-545
• [5]Nye tal fra Sundhedsstyrelsen: Forbrug af antidepressive midler i forbindelse med graviditet og fødsel 1997–2006. Sundhedsstyrelsen København 2007, 20:1-8. [New data from Danish Health and Medicines Authority: Use of antidepressants during pregnancy and childbirth 1997-2006. Danish Health and Medicines Authority Copenhagen 2007, 20:1-8]
• [6]Bakker MK, Kolling P, vanden 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):600-606.
• [7]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(2):194. e191-195
• [8]Hansen DG, Sondergaard J, Vach W, Gram LF, Rosholm JU, Mortensen PB, Kragstrup J: Socio-economic inequalities in first-time use of antidepressants: a population-based study. Eur J Clin Pharmacol 2004, 60(1):51-55.
• [9]Lewis AJ, Bailey C, Galbally M: Anti-depressant use during pregnancy in Australia: findings from the Longitudinal Study of Australian Children. Aust N Z J Public Health 2012, 36(5):487-488.
• [10]von Soest T, Bramness JG, Pedersen W, Wichstrom L: The relationship between socio-economic status and antidepressant prescription: a longitudinal survey and register study of young adults. Epidemiol Psychiatr Sci 2012, 21(1):87-95.
• [11]Sadler TW: Selective serotonin reuptake inhibitors (SSRIs) and heart defects: potential mechanisms for the observed associations. Reprod Toxicol 2011, 32(4):484-489.
• [12]Alwan S, Reefhuis J, Rasmussen SA, Olney RS, Friedman JM: Use of selective serotonin-reuptake inhibitors in pregnancy and the risk of birth defects. N Engl J Med 2007, 356(26):2684-2692.
• [13]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(2):94-100.
• [14]Berard A, Ramos E, Rey E, Blais L, St-Andre M, Oraichi D: First trimester exposure to paroxetine and risk of cardiac malformations in infants: the importance of dosage. Birth Defects Res B Dev Reprod Toxicol 2007, 80(1):18-27.
• [15]Diav-Citrin O, Shechtman S, Weinbaum D, Wajnberg R, Avgil M, Di Gianantonio E, Clementi M, Weber-Schoendorfer C, Schaefer C, Ornoy A: Paroxetine and fluoxetine in pregnancy: a prospective, multicentre, controlled, observational study. Br J Clin Pharmacol 2008, 66(5):695-705.
• [16]Jimenez-Solem E, Andersen JT, Petersen M, Broedbaek K, Jensen JK, Afzal S, Gislason GH, Torp-Pedersen C, Poulsen HE: Exposure to selective serotonin reuptake inhibitors and the risk of congenital malformations: a nationwide cohort study. BMJ open 2012, 2(3):1-9.
• [17]Kallen BA, Otterblad Olausson P: Maternal use of selective serotonin re-uptake inhibitors in early pregnancy and infant congenital malformations. Birth Defects Res A Clin Mol Teratol 2007, 79(4):301-308.
• [18]Kornum JB, Nielsen RB, Pedersen L, Mortensen PB, Norgaard M: Use of selective serotonin-reuptake inhibitors during early pregnancy and risk of congenital malformations: updated analysis. Clin Epidemiol 2010, 2:29-36.
• [19]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(26):2675-2683.
• [20]Malm H, Artama M, Gissler M, Ritvanen A: Selective serotonin reuptake inhibitors and risk for major congenital anomalies. Obstet Gynecol 2011, 118(1):111-120.
• [21]Oberlander TF, Warburton W, Misri S, Riggs W, Aghajanian J, Hertzman C: Major congenital malformations following prenatal exposure to serotonin reuptake inhibitors and benzodiazepines using population-based health data. Birth Defects Res B Dev Reprod Toxicol 2008, 83(1):68-76.
• [22]Pedersen LH, Henriksen TB, Vestergaard M, Olsen J, Bech BH: Selective serotonin reuptake inhibitors in pregnancy and congenital malformations: population based cohort study. BMJ 2009, 339:b3569.
• [23]Reis M, Kallen B: Delivery outcome after maternal use of antidepressant drugs in pregnancy: an update using Swedish data. Psychol Med 2010, 40(10):1723-1733.
• [24]Margulis AV, Abou-Ali A, Strazzeri MM, Ding Y, Kuyateh F, Frimpong EY, Levenson MS, Hammad TA: Use of selective serotonin reuptake inhibitors in pregnancy and cardiac malformations: a propensity-score matched cohort in CPRD. Pharmacoepidemiol Drug Saf 2013, 22(9):942-951.
• [25]Cole JA, Ephross SA, Cosmatos IS, Walker AM: Paroxetine in the first trimester and the prevalence of congenital malformations. Pharmacoepidemiol Drug Saf 2007, 16(10):1075-1085.
• [26]Davis RL, Rubanowice D, McPhillips H, Raebel MA, Andrade SE, Smith D, Yood MU, Platt R: Risks of congenital malformations and perinatal events among infants exposed to antidepressant medications during pregnancy. Pharmacoepidemiol Drug Saf 2007, 16(10):1086-1094.
• [27]Einarson A, Pistelli A, DeSantis M, Malm H, Paulus WD, Panchaud A, Kennedy D, Einarson TR, Koren G: Evaluation of the risk of congenital cardiovascular defects associated with use of paroxetine during pregnancy. Am J Psychiatry 2008, 165(6):749-752.
• [28]Nordeng H, van Gelder MM, Spigset O, Koren G, Einarson A, Eberhard-Gran M: Pregnancy outcome after exposure to antidepressants and the role of maternal depression: results from the Norwegian Mother and Child Cohort Study. J Clin Psychopharmacol 2012, 32(2):186-194.
• [29]Simon GE, Cunningham ML, Davis RL: Outcomes of prenatal antidepressant exposure. Am J Psychiatry 2002, 159(12):2055-2061.
• [30]Wichman CL, Moore KM, Lang TR, St Sauver JL, Heise RH Jr, Watson WJ: Congenital heart disease associated with selective serotonin reuptake inhibitor use during pregnancy. Mayo Clin Proc 2009, 84(1):23-27.
• [31]Einarson TR, Kennedy D, Einarson A: Do findings differ across research design? The case of antidepressant use in pregnancy and malformations. J Popul Ther Clin Pharmacol 2012, 19(2):e334-e348.
• [32]Boyd PA, Haeusler M, Barisic I, Loane M, Garne E, Dolk H: Paper 1: The EUROCAT network–organization and processes. Birth Defects Res A Clin Mol Teratol 2011, 91(Suppl 1):S2-S15.
• [33]Garne E: Congenital heart defects – occurrence, surgery and prognosis in a Danish County. Scand Cardiovasc J 2004, 38(6):357-362.
• [34]Agha MM, Glazier RH, Moineddin R, Moore AM, Guttmann A: Socioeconomic status and prevalence of congenital heart defects: does universal access to health care system eliminate the gap? Birth Defects Res A Clin Mol Teratol 2011, 91(12):1011-1018.
• [35]Varela MM, Nohr EA, Llopis-Gonzalez A, Andersen AM, Olsen J: Socio-occupational status and congenital anomalies. Eur J Pub Health 2009, 19(2):161-167.
• [36]Kuciene R, Dulskiene V: Maternal socioeconomic and lifestyle factors during pregnancy and the risk of congenital heart defects. Medicina (Kaunas, Lithuania) 2009, 45(11):904-909.
• [37]Vlismas K, Stavrinos V, Panagiotakos DB: Socio-economic status, dietary habits and health-related outcomes in various parts of the world: a review. Cent Eur J Public Health 2009, 17(2):55-63.
• [38]Knudsen LB, Olsen J: The Danish Medical Birth Registry. Dan Med Bull 1998, 45(3):320-323.
• [39]Lynge E, Sandegaard JL, Rebolj M: The Danish National Patient Register. Scand J Public Health 2011, 39(7 Suppl):30-33.
• [40]Kildemoes HW, Sorensen HT, Hallas J: The Danish National Prescription Registry. Scand J Public Health 2011, 39(7 Suppl):38-41.
• [41]Baadsgaard M, Quitzau J: Danish registers on personal income and transfer payments. Scand J Public Health 2011, 39(7 Suppl):103-105.
• [42]Pedersen CB: The Danish Civil Registration System. Scand J Public Health 2011, 39(7 Suppl):22-25.
• [43]von Elm E, Altman DG, Egger M, Pocock SJ, Gotzsche PC, Vandenbroucke JP: The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: Guidelines for reporting observational studies. J Clin Epidemiol 2008, 61(4):344-349.
• [44]Mors O, Perto GP, Mortensen PB: The Danish Psychiatric Central Research Register. Scand J Public Health 2011, 39(7 Suppl):54-57.
• [45]Garne E, Olsen MS, Johnsen SP, Hjortdal V, Andersen HO, Nissen H, Sondergaard L, Videbaek J: How do we define congenital heart defects for scientific studies? Congenit Heart Dis 2012, 7(1):46-49.
• [46]Garne E: Atrial and ventricular septal defects - epidemiology and spontaneous closure. J Matern Fetal Neonatal Med 2006, 19(5):271-276.
• [47]Sorensen HT, Hansen I, Ejlersen E, Sabroe S, Hamburger H: Identification of patients treated with strong analgesics: an assessment of two Danish information systems with respect to epidemiological research. J Med Syst 1996, 20(1):57-65.
• [48]Thygesen LC, Daasnes C, Thaulow I, Bronnum-Hansen H: Introduction to Danish (nationwide) registers on health and social issues: structure, access, legislation, and archiving. Scand J Public Health 2011, 39(7 Suppl):12-16.
• [49]Garne E, Hansen AV, Birkelund SB, Andersen A-MN: Major congenital anomalies in a Danish region – prevalence, fetal and infant mortality and chronic maternal diseases. Dan Med J 2014, 61(6):A4825.
• [50]Olesen C, Thrane N, Ronholt AM, Olsen J, Henriksen TB: Association between social position and congenital anomalies: a population-based study among 19,874 Danish women. Scand J Public Health 2009, 37(3):246-251.
• [51]Puho EH, Vogt G, Csaky-Szunyogh M, Metneki J, Czeizel AE: Maternal demographic and socioeconomic characteristics of live-born infants with isolated ocular congenital abnormalities. Ophthalmic Epidemiol 2008, 15(4):257-263.
• [52]Wasserman CR, Shaw GM, Selvin S, Gould JB, Syme SL: Socioeconomic status, neighborhood social conditions, and neural tube defects. Am J Public Health 1998, 88(11):1674-1680.
• [53]Klieger-Grossmann C, Weitzner B, Panchaud A, Pistelli A, Einarson T, Koren G, Einarson A: Pregnancy outcomes following use of escitalopram: a prospective comparative cohort study. J Clin Pharmacol 2012, 52(5):766-770.
• [54]Nikfar S, Rahimi R, Hendoiee N, Abdollahi M: Increasing the risk of spontaneous abortion and major malformations in newborns following use of serotonin reuptake inhibitors during pregnancy: A systematic review and updated meta-analysis. Daru: journal of Faculty of Pharmacy, Tehran University of Medical Sciences 2012, 20(1):75. BioMed Central Full Text
• [55]Udechuku A, Nguyen T, Hill R, Szego K: Antidepressants in pregnancy: a systematic review. Aust N Z J Psychiatry 2010, 44(11):978-996.