Tricyclic antidepressants updated on 07-01-2025

Preterm (< 37 weeks)

id	Study   Auto Lee (Controls exposed to SSRI), 2025Lee (Controls unexposed, general pop), 2025Martin - Amitriptyline, 2024Song, 2023Chen, 2021Bahat, 2020Ozturk - Amitriptyline, 2016Reis (Controls exposed to SSRIs), 2010Reis (Controls unexposed, NOS), 2010Davis, 2007Pearson (Controls exposed to SSRIs), 2007Pearson (Controls unexposed, NOS), 2007Simon (Controls exposed to SSRIs), 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.
S18445 R78337	Lee (Controls exposed to SSRI), 2025	Preterm birth (infant born at gestational age <37 weeks)	during pregnancy (anytime or not specified)	retrospective cohort (claims database)	exposed to other treatment, sick excluded	Adjustment: No Monotherapy: TCA only	1.06 [0.77;1.47] C excluded (control group)	58/613   131/1,465	189	613		ref
S18410 R77738	Lee (Controls unexposed, general pop), 2025	Preterm birth (infant born at gestational age <37 weeks)	during pregnancy (anytime or not specified)	retrospective cohort (claims database)	unexposed (general population or NOS)	Adjustment: Yes Monotherapy: TCA only	0.99 [0.75;1.30]	58/613   28,543/463,440	28,601	613		ref
S18222 R76450	Martin - Amitriptyline, 2024	Preterm delivery (delivery at <259 days (37 weeks’))	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, ...)	1.36 [1.23;1.52]	405/4,773   119,950/2,408,707	120,355	4,773		ref
S15168 R62250	Song, 2023	Preterm labour or birth (birth before 37 weeks of gestation)	3 months (or more) before pregnancy or during pregnancy excluded	nested case control	unexposed (general population or NOS)	Adjustment: No Monotherapy: no or not specified	1.14 [1.06;1.23] C excluded (exposition period)	787/12,041   6,498/112,565	7,285	12,041		ref
S11180 R41169	Chen, 2021	Preterm birth (<37 completed weeks of gestation)	during pregnancy (anytime or not specified)	population based cohort retrospective	unexposed, sick	Adjustment: Yes Monotherapy: no or not specified Unexposed sick: recent illness/treatment (during or juste before pregnancy or treatment stopped in view of pregnancy)	1.49 [1.21;1.85]	20/380   55/1,789	75	380		ref
S11453 R42094	Bahat, 2020	Preterm birth (NOS)	1st trimester	prospective cohort	unexposed (general population or NOS)	Adjustment: Yes Monotherapy: no or not specified	0.88 [0.25;3.11]	-/-   -/-	-	-		ref
S11594 R42483	Ozturk - Amitriptyline, 2016	Preterm Births (<37 weeks)	at least 1st trimester	prospective cohort	unexposed (general population or NOS)	Adjustment: No Monotherapy: no or not specified	3.99 [0.19;83.55] C	0/4   8/246	8	4		ref
S10933 R41671	Reis (Controls exposed to SSRIs), 2010	Preterm birth (<37 weeks)	2nd and/or 3rd trimester	population based cohort retrospective	exposed to other treatment, sick excluded	Adjustment: No Monotherapy: TCA only	1.56 [1.22;2.00] C excluded (control group)	87/784   356/4,809	443	784		ref
S10934 R41664	Reis (Controls unexposed, NOS), 2010	Preterm birth (<37 weeks)	2nd and/or 3rd trimester	population based cohort retrospective	unexposed (general population or NOS)	Adjustment: Yes Monotherapy: TCA only	2.36 [1.89;2.94]	87/784   57,946/1,062,190	58,033	784		ref
S10930 R40593	Davis, 2007	Preterm delivery	during pregnancy (anytime or not specified)	retrospective cohort (claims database)	unexposed (general population or NOS)	Adjustment: No Monotherapy: no or not specified	1.67 [1.25;2.22]	42/381   5,392/81,146	5,434	381		ref
S11218 R41281	Pearson (Controls exposed to SSRIs), 2007	Prematurity (NOS)	during pregnancy (anytime or not specified)	retrospective cohort	exposed to other treatment, sick excluded	Adjustment: No Monotherapy: TCA only	2.52 [0.58;10.88] C excluded (control group)	6/37   3/42	9	37		ref
S11217 R41278	Pearson (Controls unexposed, NOS), 2007	Prematurity (NOS)	during pregnancy (anytime or not specified)	retrospective cohort	unexposed (general population or NOS)	Adjustment: No Monotherapy: TCA only	1.72 [0.63;4.71] C	6/37   17/168	23	37		ref
S10935 R40670	Simon (Controls exposed to SSRIs), 2002	Estimated gestational age ≤36 weeks	during pregnancy (anytime or not specified)	retrospective cohort (claims database)	exposed to other treatment, sick excluded	Adjustment: No Monotherapy: TCA only	0.98 [0.51;1.88] C excluded (control group)	21/209   19/185	40	209		ref
S10936 R40686	Simon (Controls unexposed, NOS), 2002	Estimated gestational age ≤36 weeks	during pregnancy (anytime or not specified)	retrospective cohort (claims database)	unexposed (general population or NOS)	Adjustment: Yes Matched Monotherapy: TCA only	1.86 [0.83;4.17]	21/209   11/209	32	209		ref
					Total	9 studies	1.53 [1.23;1.89]		212,561	7,181
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 10935, 11218, 10933, 18445

Umbrella review (other published meta-analyses)