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

Oro-facial clefts

id	Study   Auto Laspro - Venlafaxine, 2024Benevent - SNRI, 2023Ankarfeldt a - Duloxetine (Controls unexposed, NOS), 2021Ankarfeldt a - Duloxetine (Controls unexposed, sick), 2021Anderson - SNRI, 2020Huybrechts - Duloxetine (Controls unexposed, NOS), 2020Huybrechts - Duloxetine (Controls unexposed, sick), 2020	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.
S18325 R77197	Laspro - Venlafaxine, 2024	Oral clefts (ICD 10 codes Q35 or Q36 or Q37)	during pregnancy (anytime or not specified) excluded	nested case control	unexposed (general population or NOS)	Adjustment: No Monotherapy: no or not specified	1.53 [1.28;1.83] excluded (exposition period)	122/-   11,976/-	12,098	-		ref
S15171 R62284	Benevent - SNRI, 2023	Orofacial clefts	1st trimester	retrospective cohort (claims database)	unexposed (general population or NOS)	Adjustment: No Monotherapy: SNRI only	1.55 [0.10;25.03] C	0/314   150/146,855	150	314		ref
S11684 R42949	Ankarfeldt a - Duloxetine (Controls unexposed, NOS), 2021	Oro-facial clefts	1st trimester	population based cohort retrospective	unexposed (general population or NOS) excluded	Adjustment: Yes Monotherapy: no or not specified	1.33 [0.27;6.61] excluded (control group)	-/1,438   6/5,751	-	1,438		ref
S11685 R42965	Ankarfeldt a - Duloxetine (Controls unexposed, sick), 2021	Oro-facial clefts	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)	1.00 [0.14;7.10]	-/1,434   -/1,435	-	1,434		ref
S11771 R43266	Anderson - SNRI, 2020	Any oral cleft	1st trimester	case control	unexposed (general population or NOS)	Adjustment: Yes Monotherapy: SNRI only	2.35 [1.34;4.13]	-/-   0/-	-	-		ref
S11745 R43133	Huybrechts - Duloxetine (Controls unexposed, NOS), 2020	Oral cleft	1st trimester	retrospective cohort (claims database)	unexposed (general population or NOS) excluded	Adjustment: Yes Monotherapy: no or not specified	0.75 [0.24;2.33] excluded (control group)	-/2,532   -/-	-	2,532		ref
S11746 R43147	Huybrechts - Duloxetine (Controls unexposed, sick), 2020	Oral cleft	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 [0.22;7.64]	-/2,532   -/2,456	-	2,532		ref
					Total	4 studies	2.08 [1.25;3.47]		150	4,280
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