Pregabalin (All indications) updated on 04-22-2025

Major congenital malformations

id	Study   Auto Moore (Pregabalin) (Mixed indications) (Controls exposed to LTG), 2025Moore (Pregabalin) (Mixed indications) (Controls unexposed, general pop), 2025The NAAED (Controls exposed to LTG) (Indications NOS), 2025The NAAED (Controls unexposed, disease free) (Indications NOS), 2025Battino (Epilepsy), 2024Dudukina (Controls exposed to LTG) (Mixed indications), 2023Dudukina (Controls unexposed, NOS) (Mixed indications), 2023Vajda (Controls exposed to Lamotrigine, sick), 2019Vajda (Controls unexposed, sick), 2019Patorno_MAX and MaketScan (Other indications), 2017Winterfeld (Other indications), 2016Veiby (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014Veiby (Controls unexposed, disease free) (Mixed indications), 2014Veiby (Controls unexposed, sick) (Mixed indications), 2014Källén (Controls exposed to Lamotrigine, sick) (Indications NOS), 2013Källén (Controls unexposed, NOS) (Indications NOS), 2013	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.
S18758 R79779	Moore (Pregabalin) (Mixed indications) (Controls exposed to LTG), 2025	Congenital conditions (any major structural congenital condition with no known associated/underlying genetic condition, as defined by EUROCAT)	during pregnancy (anytime or not specified)	population based cohort retrospective	exposed to other treatment, sick excluded	Adjustment: No	0.88 [0.56;1.39] C excluded (control group)	38/1,618   39/1,470	77	1,618		ref
S18759 R79783	Moore (Pregabalin) (Mixed indications) (Controls unexposed, general pop), 2025	Congenital conditions (any major structural congenital condition with no known associated/underlying genetic condition, as defined by EUROCAT)	during pregnancy (anytime or not specified) excluded	population based cohort retrospective	unexposed (general population or NOS)	Adjustment: Yes Matched	1.04 [0.73;1.49] excluded (exposition period)	38/1,618   302/15,857	340	1,618		ref
S16194 R67087	The NAAED (Controls exposed to LTG) (Indications NOS), 2025	Major congenital malformations	1st trimester	prospective cohort	exposed to other treatment, sick excluded	Adjustment: No	1.37 [0.33;5.75] C excluded (control group)	2/73   52/2,587	54	73		ref
S16184 R67076	The NAAED (Controls unexposed, disease free) (Indications NOS), 2025	Major congenital malformations	1st trimester	prospective cohort	unexposed, disease free	Adjustment: No	2.50 [0.56;11.14] C	2/73   15/1,346	17	73		ref
S16585 R69651	Battino (Epilepsy), 2024	Major congenital malformations (MCMs)	early pregnancy	prospective cohort	exposed to other treatment, sick	Adjustment: No	2.42 [0.14;43.19] C	0/7   110/3,584	110	7		ref
S15251 R62700	Dudukina (Controls exposed to LTG) (Mixed indications), 2023	Major congenital malformations	3 months or more before pregnancy or1st trimester	population based cohort retrospective	exposed to other treatment, sick excluded	Adjustment: Yes	1.25 [0.98;1.59] excluded (control group)	138/2,332   351/7,005	489	2,332		ref
S15252 R62721	Dudukina (Controls unexposed, NOS) (Mixed indications), 2023	Major congenital malformations	3 months or more before pregnancy or1st trimester excluded	population based cohort retrospective	unexposed (general population or NOS)	Adjustment: Yes	1.14 [0.96;1.35] excluded (exposition period)	138/2,332   126,437/3,063,173	126,575	2,332		ref
S8530 R28291	Vajda (Controls exposed to Lamotrigine, sick), 2019	Fetal malformations	at least 1st trimester	prospective cohort	exposed to other treatment, sick excluded	Adjustment: No	18.80 [0.36;971.86] C excluded (control group)	0/1   20/406	20	1		ref
S8531 R28292	Vajda (Controls unexposed, sick), 2019	Fetal malformations	at least 1st trimester	prospective cohort	unexposed, sick	Adjustment: No	31.00 [0.56;1711.11] C	0/1   5/176	5	1		ref
S8528 R28286	Patorno_MAX and MaketScan (Other indications), 2017	Major congenital malformations (MAX and Marketscan data)	1st trimester	retrospective cohort (claims database)	unexposed (general population or NOS)	Adjustment: Yes	0.99 [0.66;1.47]	24/471   38,116/1,750,259	38,140	471		ref
S8525 R28236	Winterfeld (Other indications), 2016	Overall major birth defects	1st trimester	prospective cohort	unexposed (general population or NOS)	Adjustment: No Matched	6.50 [1.70;24.70]	3/19   16/573	19	19		ref
S8534 R28299	Veiby (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014	Major congenital malformation	throughout pregnancy	population based cohort retrospective	exposed to other treatment, sick excluded	Adjustment: No	0.99 [0.13;7.54] C excluded (control group)	1/30   28/833	29	30		ref
S8535 R28301	Veiby (Controls unexposed, disease free) (Mixed indications), 2014	Major malformations	throughout pregnancy	population based cohort retrospective	unexposed, disease free excluded	Adjustment: No	1.15 [0.16;8.48] C excluded (control group)	1/30   22,371/771,412	22,372	30		ref
S8536 R28304	Veiby (Controls unexposed, sick) (Mixed indications), 2014	Major malformations	throughout pregnancy	population based cohort retrospective	unexposed, sick	Adjustment: No Controls: epilepsy indication	1.19 [0.16;8.84] C	1/30   106/3,773	107	30		ref
S8532 R28293	Källén (Controls exposed to Lamotrigine, sick) (Indications NOS), 2013	Relatively severe malformations	early pregnancy	population based cohort retrospective	exposed to other treatment, sick excluded	Adjustment: No	0.52 [0.12;2.18] C excluded (control group)	2/111   37/1,084	39	111		ref
S8533 R28295	Källén (Controls unexposed, NOS) (Indications NOS), 2013	Relatively severe malformations	early pregnancy	population based cohort retrospective	unexposed (general population or NOS)	Adjustment: No	0.57 [0.14;2.29] C	2/111   49,499/1,575,847	49,501	111		ref
					Total	7 studies	1.73 [0.80;3.76]		87,899	712
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 8532, 8534, 8535, 8530, 15251, 18758, 16194

Umbrella review (other published meta-analyses)