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

Small for gestational age (weight)

id	Study   Auto Lee (Controls exposed to TCAs), 2025Lee (Controls unexposed, general pop), 2025Martin - Venlafaxine, 2024Ankarfeldt - Duloxetine (Controls unexposed, NOS), 2023Ankarfeldt - Duloxetine (Controls unexposed, sick), 2023Benevent - SNRI, 2023Huybrechts - Duloxetine (Controls unexposed, NOS), 2020Richardson - Venlafaxine, 2019Reis - SNRI (Controls exposed to TCA), 2010Reis - SNRI (Controls unexposed, NOS), 2010	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.
S18440 R78234	Lee (Controls exposed to TCAs), 2025	Small for gestational age (birth weight <2 standard deviations below the mean for gestational age)	during pregnancy (anytime or not specified)	retrospective cohort (claims database)	exposed to other treatment, sick excluded	Adjustment: No Monotherapy: SNRI only	0.27 [0.02;4.62] C excluded (control group)	0/71   15/613	15	71		ref
S18441 R78255	Lee (Controls unexposed, general pop), 2025	Small for gestational age (birth weight <2 standard deviations below the mean for gestational age)	during pregnancy (anytime or not specified)	retrospective cohort (claims database)	unexposed (general population or NOS)	Adjustment: No Monotherapy: SNRI only	0.46 [0.03;7.48] C	0/71   6,986/463,440	6,986	71		ref
S18310 R77108	Martin - Venlafaxine, 2024	Small for gestational age (SGA, defined as those with a birth weight in the lowest 10 percentiles for gestational age (<10th percentile)	during pregnancy (anytime or not specified)	population based cohort retrospective	unexposed (general population or NOS)	Adjustment: Yes Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...)	0.91 [0.83;1.00]	564/5,495   229,066/2,408,707	229,630	5,495		ref
S15178 R62301	Ankarfeldt - Duloxetine (Controls unexposed, NOS), 2023	Small for gestational age (SGA, birth weight under the tenth percentiles stratified on pregnancy week and sex)	late pregnancy	population based cohort retrospective	unexposed (general population or NOS) excluded	Adjustment: Yes Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...)	0.75 [0.53;1.06] excluded (control group)	36/450   187,611/2,082,019	187,647	450		ref
S15179 R62305	Ankarfeldt - Duloxetine (Controls unexposed, sick), 2023	Small for gestational age (SGA, birth weight under the tenth percentiles stratified on pregnancy week and sex)	late pregnancy	population based cohort retrospective	unexposed, sick	Adjustment: Yes Monotherapy: substance alone among all Antidep (SSRI, SNRI, ...) Unexposed sick: intermediate history of illness/treatment (3-12 months before pregnancy)	0.81 [0.56;1.18]	36/450   343/3,772	379	450		ref
S15171 R62277	Benevent - SNRI, 2023	Small for gestational age	during pregnancy (anytime or not specified)	retrospective cohort (claims database)	unexposed (general population or NOS)	Adjustment: No Monotherapy: SNRI only	1.42 [0.59;3.46] C	5/270   1,682/128,692	1,687	270		ref
S11745 R43125	Huybrechts - Duloxetine (Controls unexposed, NOS), 2020	Small for gestational age (ICD-9 codes 656.5x, 764.0x, 764.1x, and 764.9x)	late pregnancy	retrospective cohort (claims database)	unexposed (general population or NOS)	Adjustment: Yes Monotherapy: no or not specified	1.20 [0.83;1.72]	29/880   27,762/1,364,101	27,791	880		ref
S11774 R43311	Richardson - Venlafaxine, 2019	Small for gestational age	at least 1st trimester	prospective cohort	unexposed (general population or NOS)	Adjustment: Yes Matched Monotherapy: no or not specified	1.03 [0.51;1.89]	12/133   65/722	77	133		ref
S11693 R43000	Reis - SNRI (Controls exposed to TCA), 2010	Small for gestational age (<2 S.D. from expected weight)	2nd and/or 3rd trimester	population based cohort retrospective	exposed to other treatment, sick excluded	Adjustment: No Monotherapy: SNRI only	2.57 [1.32;5.01] C excluded (control group)	24/538   14/784	38	538		ref
S11694 R43012	Reis - SNRI (Controls unexposed, NOS), 2010	Small for gestational age (<2 S.D. from expected weight)	2nd and/or 3rd trimester	population based cohort retrospective	unexposed (general population or NOS)	Adjustment: Yes Monotherapy: SNRI only	1.84 [1.20;2.81]	24/538   24,802/1,062,190	24,826	538		ref
					Total	7 studies	1.09 [0.85;1.38]		291,376	7,837
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 11693, 15178, 18440

Umbrella review (other published meta-analyses)