Serotonin and Noradrenaline Reuptake Inhibitors (SNRI) updated on 07-01-2025

Genital anomalies

id	Study   Auto Benevent - SNRI, 2023Ankarfeldt a - Duloxetine (Controls unexposed, NOS), 2021Ankarfeldt a - Duloxetine (Controls unexposed, sick), 2021Huybrechts - Duloxetine (Controls unexposed, NOS), 2020Huybrechts - Duloxetine (Controls unexposed, sick), 2020Bérard b - SNRI=Venlafaxine (Controls unexposed, sick), 2017	Lib. in paper	Exposition period  Auto during pregnancy (anytime or not specified)1st trimester2nd trimester3rd trimester2nd and/or 3rd trimesterthroughout pregnancyearly pregnancydays before deliverylate pregnancypreconception-onlypericonceptionalpreconceptional for kinetic reasonat least 1st trimester3 months (or more) before pregnancy or during pregnancy1st and 2nd trimester3 months or more before pregnancy or1st trimesterPaternal exp. genotoxic window only (0–3 months preconception)Paternal exposure: epigenetic window only (3–xxx months preconception)Paternal exposure: genotoxic/epigenetic window (0–xxx months preconception)Paternal exposure: other window	Study type  All studies Case control excluded Only case control	Control type    Auto unexposed (general population or NOS)unexposed, sickunexposed, disease freeexposed to other treatment, sicknot specifiedsiblingwhatever (meta-analysis)	Tags	OR 95%CI	x1/n1 x0/n0	no cases	no exposed	ROB	Ref.
S15171 R62288	Benevent - SNRI, 2023	Genital anomalies	1st trimester	retrospective cohort (claims database)	unexposed (general population or NOS)	Adjustment: No Monotherapy: SNRI only	0.63 [0.04;10.07] C	0/314   372/146,855	372	314		ref
S11684 R42945	Ankarfeldt a - Duloxetine (Controls unexposed, NOS), 2021	Genital malformations	1st trimester	population based cohort retrospective	unexposed (general population or NOS) excluded	Adjustment: Yes Monotherapy: no or not specified	0.75 [0.31;1.80] excluded (control group)	6/1,438   32/5,751	38	1,438		ref
S11685 R42961	Ankarfeldt a - Duloxetine (Controls unexposed, sick), 2021	Genital malformations	1st trimester	population based cohort retrospective	unexposed, sick	Adjustment: Yes Monotherapy: no or not specified Unexposed sick: intermediate history of illness/treatment (3-12 months before pregnancy)	0.86 [0.29;2.55]	6/1,434   7/1,435	13	1,434		ref
S11745 R43135	Huybrechts - Duloxetine (Controls unexposed, NOS), 2020	Genital (male and female) malformations	1st trimester	retrospective cohort (claims database)	unexposed (general population or NOS) excluded	Adjustment: Yes Monotherapy: no or not specified	1.08 [0.61;1.90] excluded (control group)	-/2,532   -/-	-	2,532		ref
S11746 R43149	Huybrechts - Duloxetine (Controls unexposed, sick), 2020	Genital (male and female) malformations	1st trimester	retrospective cohort (claims database)	unexposed, sick	Adjustment: Yes Monotherapy: no or not specified Unexposed sick: intermediate history of illness/treatment (3-12 months before pregnancy)	1.30 [0.54;3.16]	-/2,532   -/2,456	-	2,532		ref
S11696 R43029	Bérard b - SNRI=Venlafaxine (Controls unexposed, sick), 2017	Genital organs malformations	1st trimester	retrospective cohort (claims database)	unexposed, sick	Adjustment: Yes Monotherapy: SNRI only Unexposed sick: intermediate history of illness/treatment (3-12 months before pregnancy)	0.69 [0.29;1.67]	-/738   -/14,847	-	738		ref
					Total	4 studies	0.91 [0.54;1.55]		385	5,018
x1: number of endpoints among exposed, n1: number of exposed; x0: number of endpoints among non exposed, n0: number of non exposed; C: calculated odds ratio from numbers of events and effectives

Forest plot

Sensitivity analysis

Publication bias and p-hacking diagnosis

Sub-groups analysis using all included studies

excluded 11745, 11684

Umbrella review (other published meta-analyses)