Serotonin and Noradrenaline Reuptake Inhibitors (SNRI)

Table   Graphic  
individual studies
OutcomeTE95% CIn casesn exposedkPub. bias Congenital malformations All congenital malformations (majors, minors, majors and minors, or unspecified) Oberlander - Venlafaxine, 2008 Einarson - Venlafaxine, 2009 Reis - SNRI (Controls unexposed, NOS), 2010 Furu - Venlafaxine, 2015 Te Winkel - Venlafaxine, 2016 Ozturk - Venlafaxine, 2016 Bérard b - SNRI=Venlafaxine (Controls unexposed, sick), 2017 Richardson - Venlafaxine, 2019 Bahat - Duloxetine, 2020 Huybrechts - Duloxetine (Controls unexposed, sick), 2020 Anderson - SNRI, 2020 Ankarfeldt a - Duloxetine (Controls unexposed, sick), 2021 Benevent - SNRI, 2023 Chan (Controls unexposed, sick), 2024 141.08[0.95; 1.23]147,80210,695low Major congenital malformations Oberlander - Venlafaxine, 2008 Einarson - Venlafaxine, 2009 Reis - SNRI (Controls unexposed, NOS), 2010 Furu - Venlafaxine, 2015 Te Winkel - Venlafaxine, 2016 Ozturk - Venlafaxine, 2016 Bérard b - SNRI=Venlafaxine (Controls unexposed, sick), 2017 Richardson - Venlafaxine, 2019 Bahat - Duloxetine, 2020 Huybrechts - Duloxetine (Controls unexposed, sick), 2020 Anderson - SNRI, 2020 Ankarfeldt a - Duloxetine (Controls unexposed, sick), 2021 Benevent - SNRI, 2023 Chan (Controls unexposed, sick), 2024 141.09[0.97; 1.22]147,77110,695low Congenital heart defects Oberlander - Venlafaxine, 2008 Reis - SNRI (Controls unexposed, NOS), 2010 Huybrechts - SNRI (Controls unexposed, sick), 2014 Furu - Venlafaxine, 2015 Bérard b - SNRI=Venlafaxine (Controls unexposed, sick), 2017 Huybrechts - Duloxetine (Controls unexposed, sick), 2020 Anderson - SNRI, 2020 Ankarfeldt a - Duloxetine (Controls unexposed, sick), 2021 Benevent - SNRI, 2023 Chan (Controls unexposed, sick), 2024 101.30[1.07; 1.58]41,70415,457low Limb defects Bérard b - SNRI=Venlafaxine (Controls unexposed, sick), 2017 Huybrechts - Duloxetine (Controls unexposed, sick), 2020 Ankarfeldt a - Duloxetine (Controls unexposed, sick), 2021 Benevent - SNRI, 2023 Chan (Controls unexposed, sick), 2024 50.87[0.49; 1.57]6225,084not evaluable Nervous system anomalies Bérard b - SNRI=Venlafaxine (Controls unexposed, sick), 2017 Huybrechts - Duloxetine (Controls unexposed, sick), 2020 Ankarfeldt a - Duloxetine (Controls unexposed, sick), 2021 Benevent - SNRI, 2023 Chan (Controls unexposed, sick), 2024 51.11[0.62; 1.99]2985,084not evaluable Respiratory system anomalies Bérard b - SNRI=Venlafaxine (Controls unexposed, sick), 2017 Huybrechts - Duloxetine (Controls unexposed, sick), 2020 Ankarfeldt a - Duloxetine (Controls unexposed, sick), 2021 Benevent - SNRI, 2023 Chan (Controls unexposed, sick), 2024 51.77[1.03; 3.05]525,084not evaluable Urinary malformations Bérard b - SNRI=Venlafaxine (Controls unexposed, sick), 2017 Huybrechts - Duloxetine (Controls unexposed, sick), 2020 Ankarfeldt a - Duloxetine (Controls unexposed, sick), 2021 Benevent - SNRI, 2023 Chan (Controls unexposed, sick), 2024 51.25[0.82; 1.91]8345,084not evaluable Cardiac septal defects Reis - SNRI (Controls unexposed, NOS), 2010 Furu - Venlafaxine, 2015 Bérard b - SNRI=Venlafaxine (Controls unexposed, sick), 2017 Anderson - SNRI, 2020 Chan (Controls unexposed, sick), 2024 51.30[0.88; 1.93]23,8884,918not evaluable Oro-facial clefts Huybrechts - Duloxetine (Controls unexposed, sick), 2020 Anderson - SNRI, 2020 Ankarfeldt a - Duloxetine (Controls unexposed, sick), 2021 Benevent - SNRI, 2023 42.08[1.25; 3.47]1504,280not evaluable Digestive system anomalies Bérard b - SNRI=Venlafaxine (Controls unexposed, sick), 2017 Huybrechts - Duloxetine (Controls unexposed, sick), 2020 Ankarfeldt a - Duloxetine (Controls unexposed, sick), 2021 Benevent - SNRI, 2023 41.08[0.66; 1.78]1975,018not evaluable Genital anomalies Bérard b - SNRI=Venlafaxine (Controls unexposed, sick), 2017 Huybrechts - Duloxetine (Controls unexposed, sick), 2020 Ankarfeldt a - Duloxetine (Controls unexposed, sick), 2021 Benevent - SNRI, 2023 40.91[0.54; 1.55]3855,018not evaluable Ventricular septal defect Huybrechts - SNRI (Controls unexposed, sick), 2014 Anderson - SNRI, 2020 Chan (Controls unexposed, sick), 2024 31.32[0.93; 1.86]8186,059not evaluable Abdominal wall defects Huybrechts - Duloxetine (Controls unexposed, sick), 2020 Benevent - SNRI, 2023 20.99[0.11; 8.89]482,846not evaluable Eye defects Huybrechts - Duloxetine (Controls unexposed, sick), 2020 Ankarfeldt a - Duloxetine (Controls unexposed, sick), 2021 Benevent - SNRI, 2023 30.79[0.30; 2.10]1084,280not evaluable Atrial septal defect Anderson - SNRI, 2020 Chan (Controls unexposed, sick), 2024 22.49[1.33; 4.66]5866not evaluable Hypospadias Reis - SNRI (Controls unexposed, NOS), 2010 Furu - Venlafaxine, 2015 Anderson - SNRI, 2020 31.39[0.86; 2.25]7,7374,114not evaluable Ear, face and neck anomalies Ankarfeldt a - Duloxetine (Controls unexposed, sick), 2021 Benevent - SNRI, 2023 24.32[0.80; 23.30]951,748not evaluable Minor congenital malformations Richardson - Venlafaxine, 2019 Ankarfeldt a - Duloxetine (Controls unexposed, sick), 2021 21.02[0.52; 2.01]1881,714not evaluable Cleft lip with or without cleft palate Anderson - SNRI, 2020 11.97[1.01; 3.86]--not evaluable Cleft palate Anderson - SNRI, 2020 13.12[1.53; 6.37]--not evaluable Craniosynostosis Bérard b - SNRI=Venlafaxine (Controls unexposed, sick), 2017 Anderson - SNRI, 2020 21.48[0.78; 2.81]-738not evaluable Ear malformations 0----- Hypoplastic left heart (HLH/HLHS) Anderson - SNRI, 2020 Kolding - Venlafaxine (Controls unexposed, disease free), 2021 28.08[1.81; 35.98]--not evaluable Other anomalies/syndromes (non chromosomal) Ankarfeldt a - Duloxetine (Controls unexposed, sick), 2021 11.75[0.73; 4.18]221,434not evaluable Other congenital malformations (Q80 to Q99) Huybrechts - Duloxetine (Controls unexposed, sick), 2020 11.33[0.41; 4.30]-2,532not evaluable Severe congenital heart defect Kolding - Venlafaxine (Controls unexposed, sick), 2021 11.78[0.67; 4.71]26847not evaluable Chromosomal abnormalities Benevent - SNRI, 2023 11.02[0.06; 16.45]228314not evaluable Coarctation of aorta Anderson - SNRI, 2020 13.88[1.85; 8.14]--not evaluable Eye, ear, face and neck malformations Bérard b - SNRI=Venlafaxine (Controls unexposed, sick), 2017 10.70[0.22; 2.21]-738not evaluable Gastroschisis Anderson - SNRI, 2020 14.30[1.83; 10.11]--not evaluable Neural Tube Defects Anderson - SNRI, 2020 12.48[1.18; 5.20]--not evaluable Pulmonary valve stenosis Anderson - SNRI, 2020 12.64[1.22; 5.70]--not evaluable Spina bifida Anderson - SNRI, 2020 11.95[0.74; 5.14]--not evaluable Tetralogy of Fallot Anderson - SNRI, 2020 11.59[0.55; 4.59]--not evaluable Transposition of the great vessels Anderson - SNRI, 2020 12.28[0.79; 6.59]--not evaluable Growth parameters and prematurity Preterm (< 37 weeks) Calderon-Margalit - Venlafaxine, 2009 Reis - SNRI (Controls unexposed, NOS), 2010 Te Winkel - Venlafaxine, 2016 Ozturk - Venlafaxine, 2016 Robinson-Wolrath - SNRI, 2016 Richardson - Venlafaxine, 2019 Huybrechts - Duloxetine (Controls unexposed, NOS), 2020 Bahat - Duloxetine, 2020 Marks - Duloxetine (Controls exposed to Bupropion), 2021 Chen - SNRI, 2021 Ankarfeldt - Duloxetine (Controls unexposed, sick), 2023 Benevent - SNRI, 2023 Martin - Venlafaxine, 2024 Lee (Controls unexposed, general pop), 2025 141.64[1.43; 1.89]364,28010,116low Small for gestational age (weight) Reis - SNRI (Controls unexposed, NOS), 2010 Richardson - Venlafaxine, 2019 Huybrechts - Duloxetine (Controls unexposed, NOS), 2020 Benevent - SNRI, 2023 Ankarfeldt - Duloxetine (Controls unexposed, sick), 2023 Martin - Venlafaxine, 2024 Lee (Controls unexposed, general pop), 2025 71.09[0.85; 1.38]291,3767,837not evaluable Low birth weight (< 2500g) Calderon-Margalit - Venlafaxine, 2009 Reis - SNRI (Controls unexposed, NOS), 2010 Benevent - SNRI, 2023 Lee (Controls unexposed, general pop), 2025 41.67[1.29; 2.16]76,278833not evaluable Large for gestational age (weight) Reis - SNRI (Controls unexposed, NOS), 2010 Lee (Controls unexposed, general pop), 2025 21.23[0.89; 1.70]78,598609not evaluable Macrosomia (> 4000g) Reis - SNRI (Controls unexposed, NOS), 2010 10.80[0.50; 1.29]46,068538not evaluable Extremely preterm (< 28 weeks) Benevent - SNRI, 2023 11.93[0.27; 13.77]246310not evaluable Very preterm (28 to 32 weeks) Benevent - SNRI, 2023 10.85[0.21; 3.43]1,104310not evaluable Maternal consequences Preeclampsia De Vera - SNRI, 2012 Palmsten - SNRI (Controls unexposed, sick), 2012 Palmsten a - SNRI (Controls unexposed, sick), 2013 Avalos - SNRI (Controls unexposed, sick), 2015 De Ocampo - SNRI, 2016 Lupattelli - SNRI (Controls unexposed, sick), 2017 Bernard - SNRI, 2019 Huybrechts - Duloxetine (Controls unexposed, NOS), 2020 Yang - SNRI, 2021 Frayne - SNRI, 2021 Tran - SNRI (Controls unexposed, NOS), 2022 Benevent - SNRI, 2023 121.58[1.22; 2.06]62,8175,652low Postpartum hemorrhage Palmsten b - SNRI, 2013 Hanley - SNRI, 2016 Huybrechts - Duloxetine (Controls unexposed, NOS), 2020 Jackson - SNRI, 2024 Lee (Controls unexposed, general pop), 2025 51.67[1.46; 1.92]142,7433,263not evaluable Assisted deliveries (forceps, vacuum, ...) Lee (Controls unexposed, general pop), 2025 10.48[0.18; 1.30]46,04071not evaluable Caesarean Lee (Controls unexposed, general pop), 2025 11.37[0.85; 2.20]111,66971not evaluable Maternal consequences (as a whole) Lee (Controls unexposed, general pop), 2025 11.39[0.75; 2.59]311,15271not evaluable Gestational diabetes Dandjinou - SNRI, 2019 11.27[1.08; 1.49]20,9051,894not evaluable Neonatal disorders Neonatal medical care Calderon-Margalit - Venlafaxine, 2009 Reis - SNRI (Controls unexposed, NOS), 2010 Robinson-Wolrath - SNRI, 2016 Marks - Duloxetine (Controls exposed to Bupropion), 2021 Lee (Controls unexposed, general pop), 2025 51.72[1.37; 2.15]66,240757not evaluable Low Apgar score (< 7) (at 5 min) Calderon-Margalit - Venlafaxine, 2009 Marks - Duloxetine (Controls exposed to Bupropion), 2021 Martin - Venlafaxine, 2024 Lee (Controls unexposed, general pop), 2025 41.93[1.30; 2.88]32,9995,988not evaluable Jaundice / Icterus Reis - SNRI (Controls unexposed, NOS), 2010 Marks - Duloxetine (Controls exposed to Bupropion), 2021 21.26[0.85; 1.85]52,125677not evaluable Low Apgar score (< 7) (at 1 min) Lee (Controls unexposed, general pop), 2025 11.04[0.38; 2.85]14,88771not evaluable Low Apgar score (< 7) (NOS) Reis - SNRI (Controls unexposed, NOS), 2010 11.90[1.08; 3.33]15,555538not evaluable Neonatal death (< 28 days of life) Lee (Controls unexposed, general pop), 2025 15.23[0.32; 84.55]62771not evaluable Neonatal disorders (as a whole) Lee (Controls unexposed, general pop), 2025 12.21[1.36; 3.60]161,45171not evaluable Neonatal hypoglycemia Reis - SNRI (Controls unexposed, NOS), 2010 11.72[1.22; 2.43]34,830538not evaluable Neonatal intracranial hemorrhage Reis - SNRI (Controls unexposed, NOS), 2010 10.60[0.04; 9.66]1,635538not evaluable Persistent pulmonary hypertension Bérard a - Venlafaxine, 2017 Marks - Duloxetine (Controls exposed to Bupropion), 2021 21.79[0.13; 24.26]250558not evaluable Withdrawal syndrome / Neonatal abstinence syndrome / Poor neonatal adaptation Marks - Duloxetine (Controls unexposed, sick), 2021 14.76[2.28; 9.95]-59not evaluable Neonatal tachypnea Marks - Duloxetine (Controls exposed to Bupropion), 2021 11.89[1.06; 3.37]56139not evaluable Long term consequences Child/Infant death (> 28 days of life) Lee (Controls unexposed, general pop), 2025 125.18[1.55; 408.70]13071not evaluable Intrauterine deaths Early intrauterine deaths (< 22 weeks) / Spontaneous abortions Einarson - Venlafaxine, 2001 Yaris - Venlafaxine, 2005 Nakhai-Pour - Venlafaxine, 2010 Kjaersgaard - Venlafaxine (Controls unexposed, sick), 2013 Te Winkel - Venlafaxine, 2016 Ozturk - Venlafaxine, 2016 Richardson - Venlafaxine, 2019 Ankarfeldt b - Duloxetine (Controls unexposed, sick), 2021 81.53[1.18; 1.98]5,8002,344not evaluable Elective/induced termination of pregnancy Kieler - Venlafaxine, 2015 Te Winkel - Venlafaxine, 2016 Ozturk - Venlafaxine, 2016 Richardson - Venlafaxine, 2019 Ankarfeldt b - Duloxetine (Controls unexposed, sick), 2021 51.86[1.21; 2.86]15,8432,223not evaluable Late intrauterine deaths (> 22 weeks) / Stillbirths Te Winkel - Venlafaxine, 2016 Richardson - Venlafaxine, 2019 Ankarfeldt a - Duloxetine (Controls unexposed, sick), 2021 31.16[0.53; 2.56]342,505not evaluable Therapeutic terminations of pregnancy Einarson - Venlafaxine, 2001 Kieler - Venlafaxine, 2015 21.68[0.62; 4.57]9150not evaluable Ectopic pregnancy Wall-Wieler - SNRI, 2020 10.96[0.81; 1.14]2,2896,620not evaluable Neuro-developmental disorders ASD (Autism spectrum disorder): Diagnosis Sørensen - SNRI (Controls unexposed, NOS), 2013 Boukhris - SNRI (Controls unexposed, NOS), 2016 Rai - Venlafaxine (Controls unexposed, sick), 2017 Hagberg - SNRI (Controls unexposed, sick), 2018 Suarez - SNRI (Controls unexposed, discontinuers), 2022 Heuvelman - Venlafaxine, 2023 61.36[0.96; 1.94]7,03211,937not evaluable ASD (Autism spectrum disorder): Diagnosis/Risk Sørensen - SNRI (Controls unexposed, NOS), 2013 Boukhris - SNRI (Controls unexposed, NOS), 2016 Rai - Venlafaxine (Controls unexposed, sick), 2017 Hagberg - SNRI (Controls unexposed, sick), 2018 Suarez - SNRI (Controls unexposed, discontinuers), 2022 Heuvelman - Venlafaxine, 2023 61.36[0.96; 1.94]7,03211,937not evaluable ADHD (Attention deficit hyperactivity disorder): Diagnosis Laugesen - SNRI, 2013 Boukhris - SNRI (Controls unexposed, NOS), 2017 Yeh - SNRI, 2021 Suarez - SNRI (Controls unexposed, discontinuers), 2022 Heuvelman - Venlafaxine, 2023 51.18[0.77; 1.81]4,87510,622not evaluable ADHD (Attention deficit hyperactivity disorder): Diagnosis/Risk Laugesen - SNRI, 2013 Boukhris - SNRI (Controls unexposed, NOS), 2017 Yeh - SNRI, 2021 Suarez - SNRI (Controls unexposed, discontinuers), 2022 Heuvelman - Venlafaxine, 2023 51.18[0.77; 1.81]4,87510,622not evaluable Cognitive developmental disorders/delay (3-6 years old) Nulman - Venlafaxine (Controls unexposed, sick), 2012 Suarez - SNRI (Controls unexposed, discontinuers), 2022 21.38[0.80; 2.37]25,152not evaluable Language disorders/delay Nulman - Venlafaxine (Controls unexposed, sick), 2012 Suarez - SNRI (Controls unexposed, discontinuers), 2022 21.23[0.98; 1.55]5038,602not evaluable Childhood autism (F84.0) Sørensen - SNRI (Controls unexposed, NOS), 2013 10.47[0.07; 3.36]2,031673not evaluable Learning disorders Suarez - SNRI (Controls unexposed, discontinuers), 2022 11.10[0.54; 2.24]438,540not evaluable Neuro-developmental disorders (as a whole) Suarez - SNRI (Controls unexposed, discontinuers), 2022 11.03[0.86; 1.23]1,0128,540not evaluable Psychomotor developmental disorders/delay Suarez - SNRI (Controls unexposed, discontinuers), 2022 10.95[0.52; 1.74]698,540not evaluable Severe cognitive developmental delay (Mental retardation) (3-6 years old) Suarez - SNRI (Controls unexposed, discontinuers), 2022 11.21[0.47; 3.11]25,090not evaluable Cognitive developmental disorders/delay (> 6 years old) Heuvelman - Venlafaxine, 2023 10.99[0.33; 2.95]-818not evaluable Severe cognitive developmental delay (Mental retardation) (> 6 years old) Heuvelman - Venlafaxine, 2023 10.99[0.33; 2.95]-818not evaluable0.0100.01.0

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