Venlafaxine updated on 07-01-2025

Major congenital malformations

id	Study   Auto Chan (Controls exposed to TCA), 2024Chan (Controls unexposed, general pop), 2024Anderson, 2020Richardson, 2019Bérard b (Controls exposed to TCA), 2017Bérard b (Controls unexposed, sick), 2017Ozturk, 2016Te Winkel, 2016Furu, 2015Einarson, 2009Oberlander, 2008	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.
S18320 R77164	Chan (Controls exposed to TCA), 2024	Any major malformations	1st trimester	retrospective cohort (claims database)	exposed to other treatment, sick excluded	Adjustment: No Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...)	1.11 [0.37;3.33] C excluded (control group)	4/47   25/322	29	47		ref
S18321 R77167	Chan (Controls unexposed, general pop), 2024	Any major malformations	1st trimester	retrospective cohort (claims database)	unexposed (general population or NOS)	Adjustment: Yes Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...)	1.71 [0.61;4.77]	4/47   22,628/462,377	22,632	47		ref
S11773 R43305	Anderson, 2020	Major birth defects	1st trimester	case control	unexposed (general population or NOS)	Adjustment: No Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...)	2.00 [1.26;3.19] C	112/133   30,518/41,975	30,630	133		ref
S11775 R43327	Richardson, 2019	Major congenital malformation (genetic conditions excluded)	1st trimester	prospective cohort	unexposed (general population or NOS)	Adjustment: Yes Matched Monotherapy: no or not specified	1.10 [0.32;2.97]	4/270   19/1,400	23	270		ref
S11697 R43035	Bérard b (Controls exposed to TCA), 2017	Major congenital malformations overall	1st trimester	retrospective cohort (claims database)	exposed to other treatment, sick excluded	Adjustment: No Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...)	0.91 [0.63;1.32] C excluded (control group)	91/738   51/382	142	738		ref
S11698 R43037	Bérard b (Controls unexposed, sick), 2017	Major congenital malformations overall	1st trimester	retrospective cohort (claims database)	unexposed, sick	Adjustment: Yes Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...) Unexposed sick: intermediate history of illness/treatment (3-12 months before pregnancy)	1.10 [0.87;1.38]	91/738   1,650/14,847	1,741	738		ref
S11792 R43389	Ozturk, 2016	Major congenital defects	at least 1st trimester	prospective cohort	unexposed (general population or NOS)	Adjustment: No Monotherapy: no or not specified	3.30 [0.16;68.08] C	0/11   3/246	3	11		ref
S11777 R43338	Te Winkel, 2016	Major congenital malformation (excluding chromosomal and genetic disorders)	1st trimester	prospective cohort	unexposed (general population or NOS)	Adjustment: No Monotherapy: no or not specified	1.34 [0.67;2.69]	17/523   16/656	33	523		ref
S11689 R42979	Furu, 2015	Major birth defects	1st trimester	population based cohort retrospective	unexposed (general population or NOS)	Adjustment: Yes Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...)	1.06 [0.86;1.32]	95/2,763   71,374/2,266,875	71,469	2,763		ref
S11754 R43200	Einarson, 2009	Major malformations	1st trimester	prospective cohort	unexposed (general population or NOS)	Adjustment: No Monotherapy: no or not specified	0.48 [0.11;2.03] C	2/154   25/928	27	154		ref
S11797 R43400	Oberlander, 2008	Major congenital anomalies	1st trimester	retrospective cohort (claims database)	unexposed (general population or NOS)	Adjustment: No Monotherapy: substance alone among the specific class of antidep (SSRI, SNRI, ...)	0.76 [0.34;1.71] C	6/250   3,369/107,320	3,375	250		ref
					Total	9 studies	1.17 [0.97;1.41]		129,933	4,889
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 11697, 18320

Umbrella review (other published meta-analyses)