Serotonin and Noradrenaline Reuptake Inhibitors (SNRI) updated on 10-20-2025

Table   Graphic     exposition period:

Congenital malformations
Adverse outcome OR 95%CII2k No. casesNo. exposedpublication biasROBE-value
All congenital malformations (majors, minors, majors and minors, or unspecified)1.08 [0.95, 1.23]15%14 studies147,80210,695low ROB-
Major congenital malformations1.09 [0.97, 1.22]6%14 studies147,77110,695low ROB-
Congenital heart defects1.30 [1.07, 1.58]31%10 studies41,70415,457low ROB1.92 [1.34; .]
Limb defects0.87 [0.49, 1.57]58%5 studies6225,084not evaluable ROB-
Nervous system anomalies1.11 [0.62, 1.99]0%5 studies2985,084not evaluable ROB-
Respiratory system anomalies1.77 [1.03, 3.05]0%5 studies525,084not evaluable ROB2.94 [1.19; .]
Urinary malformations1.25 [0.82, 1.91]0%5 studies8345,084not evaluable ROB-
Cardiac septal defects1.30 [0.88, 1.93]49%5 studies23,8884,918not evaluable ROB-
Oro-facial clefts2.08 [1.25, 3.47]0%4 studies1504,280not evaluable ROB3.59 [1.82; .]
Digestive system anomalies1.08 [0.66, 1.78]29%4 studies1975,018not evaluable ROB-
Genital anomalies0.91 [0.54, 1.55]0%4 studies3855,018not evaluable ROB-
Ventricular septal defect1.32 [0.93, 1.86]0%3 studies8186,059not evaluable ROB-
Abdominal wall defects0.99 [0.11, 8.89]61%2 studies482,846not evaluable ROB-
Eye defects0.79 [0.30, 2.10]0%3 studies1084,280not evaluable ROB-
Atrial septal defect2.49 [1.33, 4.66]0%2 studies5866not evaluable ROB4.41 [1.99; .]
Hypospadias1.39 [0.86, 2.25]0%3 studies7,7374,114not evaluable ROB-
Ear, face and neck anomalies4.32 [0.80, 23.30]0%2 studies951,748not evaluable ROB-
Minor congenital malformations1.02 [0.52, 2.01]39%2 studies1881,714not evaluable ROB-
Cleft lip with or without cleft palate1.97 [1.01, 3.86]-1 studynot evaluable ROB3.35 [1.09; .]
Cleft palate3.12 [1.53, 6.37]-1 studynot evaluable ROB5.69 [2.43; .]
Craniosynostosis1.48 [0.78, 2.81]0%2 studies738not evaluable ROB-
Ear malformations--0 study-
Hypoplastic left heart (HLH/HLHS)8.08 [1.81, 35.98]78%2 studiesnot evaluable ROB15.64 [3.03; .]
Other anomalies/syndromes (non chromosomal)1.75 [0.73, 4.18]-1 study221,434not evaluable ROB-
Other congenital malformations (Q80 to Q99)1.33 [0.41, 4.30]-1 study2,532not evaluable ROB-
Severe congenital heart defect1.78 [0.67, 4.71]-1 study26847not evaluable ROB-
Chromosomal abnormalities1.02 [0.06, 16.45]-1 study228314not evaluable ROB-
Coarctation of aorta3.88 [1.85, 8.14]-1 studynot evaluable ROB7.22 [3.10; .]
Eye, ear, face and neck malformations0.70 [0.22, 2.21]-1 study738not evaluable ROB-
Gastroschisis4.30 [1.83, 10.11]-1 studynot evaluable ROB8.07 [3.06; .]
Neural Tube Defects2.48 [1.18, 5.20]-1 studynot evaluable ROB4.40 [1.65; .]
Pulmonary valve stenosis2.64 [1.22, 5.70]-1 studynot evaluable ROB4.72 [1.75; .]
Spina bifida1.95 [0.74, 5.14]-1 studynot evaluable ROB-
Tetralogy of Fallot1.59 [0.55, 4.59]-1 studynot evaluable ROB-
Transposition of the great vessels2.28 [0.79, 6.59]-1 studynot evaluable ROB-

Growth parameters and prematurity
Adverse outcome OR 95%CII2k No. casesNo. exposedpublication biasROBE-value
Preterm (< 37 weeks)1.64 [1.43, 1.89]65%14 studies364,28010,116low ROB2.67 [2.21; .]
Small for gestational age (weight)1.09 [0.85, 1.38]56%7 studies291,3767,837not evaluable ROB-
Low birth weight (< 2500g)1.67 [1.29, 2.16]0%4 studies76,278833not evaluable ROB2.72 [1.90; .]
Large for gestational age (weight)1.23 [0.89, 1.70]0%2 studies78,598609not evaluable ROB-
Macrosomia (> 4000g)0.80 [0.50, 1.29]-1 study46,068538not evaluable ROB-
Extremely preterm (< 28 weeks)1.93 [0.27, 13.77]-1 study246310not evaluable ROB-
Very preterm (28 to 32 weeks)0.85 [0.21, 3.43]-1 study1,104310not evaluable ROB-

Maternal consequences
Adverse outcome OR 95%CII2k No. casesNo. exposedpublication biasROBE-value
Preeclampsia1.58 [1.22, 2.06]65%12 studies62,8175,652low ROB2.54 [1.73; .]
Postpartum hemorrhage1.67 [1.46, 1.92]0%5 studies142,7433,263not evaluable ROB2.73 [2.28; .]
Assisted deliveries (forceps, vacuum, ...)0.48 [0.18, 1.30]-1 study46,04071not evaluable ROB-
Caesarean1.37 [0.85, 2.20]-1 study111,66971not evaluable ROB-
Maternal consequences (as a whole)1.39 [0.75, 2.59]-1 study311,15271not evaluable ROB-
Gestational diabetes1.27 [1.08, 1.49]-1 study20,9051,894not evaluable ROB1.86 [1.39; .]

Neonatal disorders
Adverse outcome OR 95%CII2k No. casesNo. exposedpublication biasROBE-value
Neonatal medical care1.72 [1.37, 2.15]0%5 studies66,240757not evaluable ROB2.83 [2.09; .]
Low Apgar score (< 7) (at 5 min)1.93 [1.30, 2.88]48%4 studies32,9995,988not evaluable ROB3.28 [1.92; .]
Jaundice / Icterus1.26 [0.85, 1.85]38%2 studies52,125677not evaluable ROB-
Low Apgar score (< 7) (at 1 min)1.04 [0.38, 2.85]-1 study14,88771not evaluable ROB-
Low Apgar score (< 7) (NOS)1.90 [1.08, 3.33]-1 study15,555538not evaluable ROB3.21 [1.39; .]
Neonatal death (< 28 days of life)5.23 [0.32, 84.55]-1 study62771not evaluable ROB-
Neonatal disorders (as a whole)2.21 [1.36, 3.60]-1 study161,45171not evaluable ROB3.85 [2.05; .]
Neonatal hypoglycemia1.72 [1.22, 2.43]-1 study34,830538not evaluable ROB2.83 [1.74; .]
Neonatal intracranial hemorrhage0.60 [0.04, 9.66]-1 study1,635538not evaluable ROB-
Persistent pulmonary hypertension1.79 [0.13, 24.26]45%2 studies1558not evaluable ROB-
Withdrawal syndrome / Neonatal abstinence syndrome / Poor neonatal adaptation4.76 [2.28, 9.95]-1 study59not evaluable ROB8.99 [3.98; .]
Neonatal tachypnea1.89 [1.06, 3.37]-1 study56139not evaluable ROB3.18 [1.30; .]

Long term consequences
Adverse outcome OR 95%CII2k No. casesNo. exposedpublication biasROBE-value
Child/Infant death (> 28 days of life)25.18 [1.55, 408.70]-1 study13071not evaluable ROB49.85 [2.48; .]

Intrauterine deaths
Adverse outcome OR 95%CII2k No. casesNo. exposedpublication biasROBE-value
Early intrauterine deaths (< 22 weeks) / Spontaneous abortions1.53 [1.18, 1.98]53%8 studies5,8002,320not evaluable ROB2.42 [1.63; .]
Elective/induced termination of pregnancy1.86 [1.21, 2.86]81%5 studies9412,223not evaluable ROB3.13 [1.72; .]
Late intrauterine deaths (> 22 weeks) / Stillbirths1.16 [0.53, 2.56]0%3 studies342,505not evaluable ROB-
Therapeutic terminations of pregnancy1.68 [0.62, 4.57]31%2 studies9150not evaluable ROB-
Ectopic pregnancy0.96 [0.81, 1.14]-1 study2,2896,620not evaluable ROB-

Neuro-developmental disorders
Adverse outcome OR 95%CII2k No. casesNo. exposedpublication biasROBE-value
ASD (Autism spectrum disorder): Diagnosis1.36 [0.96, 1.94]36%6 studies7,03211,937not evaluable ROB-
ASD (Autism spectrum disorder): Diagnosis/Risk1.36 [0.96, 1.94]36%6 studies7,03211,937not evaluable ROB-
ADHD (Attention deficit hyperactivity disorder): Diagnosis1.18 [0.77, 1.81]63%5 studies4,87510,622not evaluable ROB-
ADHD (Attention deficit hyperactivity disorder): Diagnosis/Risk1.18 [0.77, 1.81]63%5 studies4,87510,622not evaluable ROB-
Cognitive developmental disorders/delay (3-6 years old)1.38 [0.80, 2.37]0%2 studies5,152not evaluable ROB-
Language disorders/delay1.23 [0.98, 1.55]0%2 studies5038,602not evaluable ROB-
Childhood autism (F84.0)0.47 [0.07, 3.36]-1 study2,031673not evaluable ROB-
Learning disorders 1.10 [0.54, 2.24]-1 study438,540not evaluable ROB-
Neuro-developmental disorders (as a whole)1.03 [0.86, 1.23]-1 study1,0128,540not evaluable ROB-
Psychomotor developmental disorders/delay0.95 [0.52, 1.74]-1 study698,540not evaluable ROB-
Severe cognitive developmental delay (Mental retardation) (3-6 years old)1.21 [0.47, 3.11]-1 study5,090not evaluable ROB-
Cognitive developmental disorders/delay (> 6 years old)0.99 [0.33, 2.95]-1 study818not evaluable ROB-
Severe cognitive developmental delay (Mental retardation) (> 6 years old)0.99 [0.33, 2.95]-1 study818not evaluable ROB-

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