Selective Serotonin Reuptake Inhibitor (SSRI) updated on 07-01-2025

Low birth weight (< 2500g)

id	Study   Auto Lee (Controls exposed to TCAs), 2025Lee (Controls unexposed, general pop), 2025Benevent, 2023Rommel, 2022Levy, 2020Gungor (Controls exposed to Mirtazapine), 2019Gungor (Controls unexposed, disease free), 2019Gungor (Controls unexposed, sick), 2019Giardinelli (Controls unexposed, disease free), 2018Giardinelli (Controls unexposed, sick), 2018Ogawa, 2018Cantarutti (Controls unexposed, NOS), 2016Cantarutti (Controls unexposed, sick), 2016Kivistö, 2016Norby, 2016Engelstad (Controls unexposed, sick), 2014Sahingöz (Controls unexposed, disease free), 2014Sahingöz (Controls unexposed, sick), 2014de Vries, 2013Colvin, 2012El Marroun (Controls unexposed, disease free), 2012Grzeskowiak a (Controls unexposed, disease free), 2012Grzeskowiak a (Controls unexposed, sick), 2012Klieger-Grossmann - Escitalopram, 2012Roca, 2011Reis (Controls exposed to TCA), 2010Reis (Controls unexposed, NOS), 2010Calderon-Margalit, 2009Lund (Controls unexposed, disease free), 2009Lund (Controls unexposed, sick), 2009Pearson (Controls exposed to TCA), 2007Wen, 2006Simon (Controls exposed to TCA), 2002Simon (Controls unexposed, NOS), 2002	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.
S18442 R78275	Lee (Controls exposed to TCAs), 2025	Low birth weight (birth weight <2500 g)	during pregnancy (anytime or not specified)	retrospective cohort (claims database)	exposed to other treatment, sick excluded	Adjustment: No Monotherapy: SSRI only	0.89 [0.66;1.21] C excluded (control group)	147/1,465   68/613	215	1,465		ref
S18408 R77697	Lee (Controls unexposed, general pop), 2025	Low birth weight (birth weight <2500 g)	during pregnancy (anytime or not specified)	retrospective cohort (claims database)	unexposed (general population or NOS)	Adjustment: Yes Monotherapy: SSRI only	1.17 [0.98;1.41]	147/1,465   31,347/463,440	31,494	1,465		ref
S12482 R47053	Benevent, 2023	Low birth weight	at least 1st trimester	retrospective cohort (claims database)	unexposed (general population or NOS)	Adjustment: No Monotherapy: SSRI only	1.58 [1.30;1.92] C	110/1,327   7,763/143,301	7,873	1,327		ref
S18233 R76473	Rommel, 2022	Low birthweight (1500–2499g)	during pregnancy (anytime or not specified)	population based cohort retrospective	unexposed, sick	Adjustment: Yes Monotherapy: SSRI only Unexposed sick: intermediate history of illness/treatment (3-12 months before pregnancy)	1.20 [1.08;1.32]	-/16,429   -/23,676	-	16,429		ref
S5461 R24124	Levy, 2020	Birthweight < 10th centile	throughout pregnancy	retrospective cohort	unexposed (general population or NOS)	Adjustment: No Matched Monotherapy: no or not specified	1.84 [0.68;4.93] C	12/82   7/82	19	82		ref
S12918 R49000	Gungor (Controls exposed to Mirtazapine), 2019	Low Birth Weight (birth weight lower than 2500 g)	during pregnancy (anytime or not specified)	prospective cohort	exposed to other treatment, sick excluded	Adjustment: No Monotherapy: SSRI only	1.67 [0.17;16.17] C excluded (control group)	4/40   1/16	5	40		ref
S8158 R25127	Gungor (Controls unexposed, disease free), 2019	Low Birth Weight (birth weight lower than 2500 g)	during pregnancy (anytime or not specified)	prospective cohort	unexposed, disease free excluded	Adjustment: No Monotherapy: SSRI only	1.17 [0.20;6.92] C excluded (control group)	4/40   2/23	6	40		ref
S8159 R25133	Gungor (Controls unexposed, sick), 2019	Low Birth Weight (birth weight lower than 2500 g)	during pregnancy (anytime or not specified)	prospective cohort	unexposed, sick	Adjustment: No Monotherapy: SSRI only Unexposed sick: old history of illness/treatment (> 12 months before pregnancy) or not specified	0.74 [0.15;3.65] C	4/40   3/23	7	40		ref
S7921 R23966	Giardinelli (Controls unexposed, disease free), 2018	Low birth weight (less than 2500 g)	during pregnancy (anytime or not specified)	prospective cohort	unexposed, disease free excluded	Adjustment: No Monotherapy: no or not specified	15.16 [0.79;291.53] C excluded (control group)	5/24   0/26	5	24		ref
S7916 R23957	Giardinelli (Controls unexposed, sick), 2018	Low birth weight (less than 2500 g)	during pregnancy (anytime or not specified)	prospective cohort	unexposed, sick	Adjustment: No Monotherapy: no or not specified Unexposed sick: recent illness/treatment (during or juste before pregnancy or treatment stopped in view of pregnancy)	0.95 [0.23;3.83] C	5/24   5/23	10	24		ref
S13263 R51074	Ogawa, 2018	Low birth weight	2nd and/or 3rd trimester	nested case control	unexposed (general population or NOS)	Adjustment: Yes Monotherapy: no or not specified	0.42 [0.06;3.05]	-/-   1,624/-	-	-		ref
S7574 R22622	Cantarutti (Controls unexposed, NOS), 2016	Low birth weight (< 2500 g)	during pregnancy (anytime or not specified)	retrospective cohort (claims database)	unexposed (general population or NOS) excluded	Adjustment: Yes Monotherapy: no or not specified	1.30 [1.10;1.50] excluded (control group)	-/-   -/374,830	-	-		ref
S7648 R22626	Cantarutti (Controls unexposed, sick), 2016	Low birth weight (< 2500 g)	during pregnancy (anytime or not specified)	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)	1.10 [0.90;1.30]	-/-   -/6,548	-	-		ref
S7570 R22771	Kivistö, 2016	Low birth weight (<2500 g)	during pregnancy (anytime or not specified)	retrospective cohort	unexposed (general population or NOS)	Adjustment: Yes Monotherapy: SSRI only	1.22 [0.81;1.82]	30/358   1,573/24,402	1,603	358		ref
S5430 R21317	Norby, 2016	Birth weight < 2500 g	during pregnancy (anytime or not specified)	population based cohort retrospective	unexposed (general population or NOS)	Adjustment: No Monotherapy: no or not specified	1.50 [1.40;1.60]	-/17,736   -/718,533	-	17,736		ref
S12948 R49136	Engelstad (Controls unexposed, sick), 2014	Birth Weight < 10th Percentile	during pregnancy (anytime or not specified)	retrospective cohort	unexposed, sick	Adjustment: No Monotherapy: SSRI only	0.75 [0.35;1.62] C	13/126   17/128	30	126		ref
S7769 R22977	Sahingöz (Controls unexposed, disease free), 2014	Low birth weight (< 2,500 g)	during pregnancy (anytime or not specified)	retrospective cohort	unexposed, disease free excluded	Adjustment: No Monotherapy: no or not specified	1.32 [0.08;22.26] C excluded (control group)	1/23   1/30	2	23		ref
S7576 R22975	Sahingöz (Controls unexposed, sick), 2014	Low birth weight (< 2,500 g)	during pregnancy (anytime or not specified)	retrospective cohort	unexposed, sick	Adjustment: No Monotherapy: no or not specified	0.28 [0.03;2.58] C	1/23   5/36	6	23		ref
S7980 R24318	de Vries, 2013	Birthweight (<2750g)	during pregnancy (anytime or not specified)	prospective cohort	unexposed (general population or NOS)	Adjustment: No Monotherapy: SSRI only	2.58 [0.67;9.98] C	10/63   3/44	13	63		ref
S5428 R20511	Colvin, 2012	Birth weight <2500 g	during pregnancy (anytime or not specified)	retrospective cohort (claims database)	unexposed (general population or NOS)	Adjustment: Yes Monotherapy: no or not specified	1.19 [0.99;1.43]	364/3,764   6,744/94,561	7,108	3,764		ref
S5411 R15321	El Marroun (Controls unexposed, disease free), 2012	Low birth weight (< 2,500 g)	during pregnancy (anytime or not specified)	prospective cohort	unexposed, disease free	Adjustment: Yes Monotherapy: no or not specified	1.65 [0.77;3.56]	-/99   -/7,027	-	99		ref
S5961 R15333	Grzeskowiak a (Controls unexposed, disease free), 2012	Low birth weight (<2500 g)	during pregnancy (anytime or not specified)	retrospective cohort	unexposed, disease free excluded	Adjustment: Yes Monotherapy: SSRI only	2.57 [1.57;4.21] excluded (control group)	42/221   2,734/32,004	2,776	221		ref
S5367 R15328	Grzeskowiak a (Controls unexposed, sick), 2012	Low birth weight (<2500 g)	during pregnancy (anytime or not specified)	retrospective cohort	unexposed, sick	Adjustment: Yes Monotherapy: SSRI only Unexposed sick: recent illness/treatment (during or juste before pregnancy or treatment stopped in view of pregnancy)	2.26 [1.31;3.91]	42/221   150/1,566	192	221		ref
S5395 R16290	Klieger-Grossmann - Escitalopram, 2012	Low birth weight (<2500 g)	during pregnancy (anytime or not specified)	prospective cohort	unexposed (general population or NOS)	Adjustment: No Matched Monotherapy: SSRI only	5.13 [1.69;15.56] C	17/172   4/191	21	172		ref
S5379 R17676	Roca, 2011	Low birth weight (<2500 g)	during pregnancy (anytime or not specified)	prospective cohort	unexposed, disease free	Adjustment: No Matched Monotherapy: no or not specified	1.37 [0.54;3.49] C	8/84   12/168	20	84		ref
S6999 R19852	Reis (Controls exposed to TCA), 2010	Low birthweight (<2500 g)	2nd and/or 3rd trimester	population based cohort retrospective	exposed to other treatment, sick excluded	Adjustment: No Monotherapy: SSRI only	0.83 [0.58;1.19] C excluded (control group)	190/4,809   37/784	227	4,809		ref
S5410 R17512	Reis (Controls unexposed, NOS), 2010	Low birthweight (<2500 g)	2nd and/or 3rd trimester	population based cohort retrospective	unexposed (general population or NOS)	Adjustment: Yes Monotherapy: SSRI only	1.13 [0.97;1.31]	190/4,809   37,105/1,062,190	37,295	4,809		ref
S5406 R15089	Calderon-Margalit, 2009	Low Birth-Weight (< 2500gr)	during pregnancy (anytime or not specified)	prospective cohort	unexposed (general population or NOS)	Adjustment: Yes Monotherapy: no or not specified	1.04 [0.45;2.39]	-/132   -/2,493	-	132		ref
S491 R16207	Lund (Controls unexposed, disease free), 2009	Birth weight < 2500 g	during pregnancy (anytime or not specified)	prospective cohort	unexposed, disease free excluded	Adjustment: Yes Monotherapy: no or not specified	0.63 [0.15;2.67] excluded (control group)	11/329   1,522/51,770	1,533	329		ref
S6162 R16211	Lund (Controls unexposed, sick), 2009	Birth weight < 2500 g	during pregnancy (anytime or not specified)	prospective cohort	unexposed, sick	Adjustment: No Monotherapy: no or not specified Unexposed sick: old history of illness/treatment (> 12 months before pregnancy) or not specified	1.07 [0.57;1.99] C	11/329   154/4,902	165	329		ref
S11220 R41288	Pearson (Controls exposed to TCA), 2007	Low birth weight (NOS)	during pregnancy (anytime or not specified)	retrospective cohort	exposed to other treatment, sick	Adjustment: No Monotherapy: SSRI only	0.43 [0.04;4.91] C	1/42   2/37	3	42		ref
S5405 R16045	Wen, 2006	Birth weight < 2500 g	3 months (or more) before pregnancy or during pregnancy excluded	retrospective cohort (claims database)	unexposed (general population or NOS)	Adjustment: Yes Matched Monotherapy: no or not specified	1.58 [1.19;2.11] excluded (exposition period)	87/972   206/3,878	293	972		ref
S6994 R19830	Simon (Controls exposed to TCA), 2002	Birth weight <2500 g	during pregnancy (anytime or not specified)	retrospective cohort (claims database)	exposed to other treatment, sick excluded	Adjustment: No Monotherapy: SSRI only	1.38 [0.58;3.27] C excluded (control group)	12/185   10/209	22	185		ref
S492 R17417	Simon (Controls unexposed, NOS), 2002	Birth weight <2500 g	during pregnancy (anytime or not specified)	retrospective cohort (claims database)	unexposed (general population or NOS)	Adjustment: Yes Matched Monotherapy: SSRI only	2.73 [0.92;8.09]	12/185   6/185	18	185		ref
					Total	23 studies	1.29 [1.16;1.43]		85,877	47,510
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 6994, 491, 6999, 5961, 7769, 7574, 7921, 12918, 8158, 18442

Umbrella review (other published meta-analyses)