Selective serotonin reuptake inhibitor antidepressant use in first trimester pregnancy and risk of specific congenital anomalies: A European register-based study

Anthony Wemakor, Karen Casson, Ester Garne, Marian Bakker, Marie-Claude Addor, Larraitz Arriola, Miriam Gatt, Babak Khoshnood, Kari Klungsoyr, Vera Nelen, Mary O'Mahony, Anna Pierini, Anke Rissmann, David Tucker, Breidge Boyle, Lolkje de Jong-van den Berg, Helen Dolk

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Abstract 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, fetaldeaths 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) andwith severe CHD (adjOR 1.56, 95 % CI 1.02–2.39), particularly Tetralogy of Fallot (adjOR 3.16, 95 % CI1.52–6.58) 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 % CI1.61–5.61), 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 byindication or associated factors.
LanguageEnglish
Pages1187-1198
JournalEuropean Journal of Epidemiology
Volume30
Issue number11
Early online date7 Jul 2015
DOIs
Publication statusPublished - Nov 2015

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Congenital Heart Defects
Serotonin Uptake Inhibitors
First Pregnancy Trimester
Antidepressive Agents
Pregnancy
Registries
Ebstein Anomaly
Gastroschisis
Clubfoot
Paroxetine
Tetralogy of Fallot
Fluoxetine
Case-Control Studies
Pathologic Constriction
Fetus
Parturition
Kidney
Population

Keywords

  • Congenital anomaly
  • SSRI Medication
  • Depression
  • Epidemiology
  • Registry

Cite this

Wemakor, Anthony ; Casson, Karen ; Garne, Ester ; Bakker, Marian ; Addor, Marie-Claude ; Arriola, Larraitz ; Gatt, Miriam ; Khoshnood, Babak ; Klungsoyr, Kari ; Nelen, Vera ; O'Mahony, Mary ; Pierini, Anna ; Rissmann, Anke ; Tucker, David ; Boyle, Breidge ; de Jong-van den Berg, Lolkje ; Dolk, Helen. / Selective serotonin reuptake inhibitor antidepressant use in first trimester pregnancy and risk of specific congenital anomalies: A European register-based study. In: European Journal of Epidemiology. 2015 ; Vol. 30, No. 11. pp. 1187-1198.
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Wemakor, A, Casson, K, Garne, E, Bakker, M, Addor, M-C, Arriola, L, Gatt, M, Khoshnood, B, Klungsoyr, K, Nelen, V, O'Mahony, M, Pierini, A, Rissmann, A, Tucker, D, Boyle, B, de Jong-van den Berg, L & Dolk, H 2015, 'Selective serotonin reuptake inhibitor antidepressant use in first trimester pregnancy and risk of specific congenital anomalies: A European register-based study', European Journal of Epidemiology, vol. 30, no. 11, pp. 1187-1198. https://doi.org/10.1007/s10654-015-0065-y

Selective serotonin reuptake inhibitor antidepressant use in first trimester pregnancy and risk of specific congenital anomalies: A European register-based study. / Wemakor, Anthony; Casson, Karen; Garne, Ester; Bakker, Marian; Addor, Marie-Claude; Arriola, Larraitz; Gatt, Miriam; Khoshnood, Babak; Klungsoyr, Kari; Nelen, Vera; O'Mahony, Mary; Pierini, Anna; Rissmann, Anke; Tucker, David; Boyle, Breidge; de Jong-van den Berg, Lolkje; Dolk, Helen.

In: European Journal of Epidemiology, Vol. 30, No. 11, 11.2015, p. 1187-1198.

Research output: Contribution to journalArticle

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AU - Wemakor, Anthony

AU - Casson, Karen

AU - Garne, Ester

AU - Bakker, Marian

AU - Addor, Marie-Claude

AU - Arriola, Larraitz

AU - Gatt, Miriam

AU - Khoshnood, Babak

AU - Klungsoyr, Kari

AU - Nelen, Vera

AU - O'Mahony, Mary

AU - Pierini, Anna

AU - Rissmann, Anke

AU - Tucker, David

AU - Boyle, Breidge

AU - de Jong-van den Berg, Lolkje

AU - Dolk, Helen

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N2 - Abstract 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, fetaldeaths 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) andwith severe CHD (adjOR 1.56, 95 % CI 1.02–2.39), particularly Tetralogy of Fallot (adjOR 3.16, 95 % CI1.52–6.58) 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 % CI1.61–5.61), 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 byindication or associated factors.

AB - Abstract 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, fetaldeaths 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) andwith severe CHD (adjOR 1.56, 95 % CI 1.02–2.39), particularly Tetralogy of Fallot (adjOR 3.16, 95 % CI1.52–6.58) 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 % CI1.61–5.61), 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 byindication or associated factors.

KW - Congenital anomaly

KW - SSRI Medication

KW - Depression

KW - Epidemiology

KW - Registry

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