Clonazepam (Epilepsy) updated on 02-10-2025

Major congenital malformations

id	Study   Auto Battino (Epilepsy), 2024Vajda (Epilepsy) (Controls exposed to Lamotrigine, sick), 2024Vajda (Epilepsy) (Controls unexposed, sick), 2024Thomas (Epilepsy) (Controls exposed to Lamotrigine, sick), 2021Thomas (Epilepsy) (Controls unexposed, sick), 2021Guveli (Epilepsy), 2017Veiby (Epilepsy) (Controls exposed to Lamotrigine, sick), 2014Veiby (Epilepsy) (Controls unexposed, disease free), 2014Veiby (Epilepsy) (Controls unexposed, sick), 2014Bànhidy (Epilepsy), 2011Morrow (Epilepsy) (Controls exposed to Lamotrigine, sick), 2006Morrow (Epilepsy) (Controls unexposed, sick), 2006Kaaja (Epilepsy), 2003Hvas (Epilepsy) (Controls unexposed, disease free), 2000Hvas (Epilepsy) (Controls unexposed, sick), 2000Canger (Epilepsy), 1999Samrén (Epilepsy), 1999Robert (Epilepsy), 1986	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 trimester	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.
S16578 R69637	Battino (Epilepsy), 2024	Major congenital malformations (MCMs)	early pregnancy	prospective cohort	exposed to other treatment, sick	Adjustment: No	0.31 [0.02;4.98] C	0/52   110/3,584	110	52		ref
S7777 R22986	Vajda (Epilepsy) (Controls exposed to Lamotrigine, sick), 2024	Fetal malformations	early pregnancy	prospective cohort	exposed to other treatment, sick excluded	Adjustment: No	0.98 [0.13;7.66] C excluded (control group)	1/24   20/473	21	24		ref
S7778 R22987	Vajda (Epilepsy) (Controls unexposed, sick), 2024	Fetal malformations	at least 1st trimester	prospective cohort	unexposed, sick	Adjustment: No	1.20 [0.15;9.31]	1/24   7/201	8	24		ref
S12876 R48643	Thomas (Epilepsy) (Controls exposed to Lamotrigine, sick), 2021	Major congenital malformations	1st trimester	prospective cohort	exposed to other treatment, sick excluded	Adjustment: No	4.62 [0.16;135.60] C excluded (control group)	0/4   1/50	1	4		ref
S12877 R48653	Thomas (Epilepsy) (Controls unexposed, sick), 2021	Major congenital malformations	1st trimester	prospective cohort	unexposed, sick	Adjustment: No	2.80 [0.14;56.50] C	0/4   16/340	16	4		ref
S16167 R67058	Guveli (Epilepsy), 2017	Major malformations	during pregnancy (anytime or not specified) excluded	retrospective cohort	unexposed, sick	Adjustment: No	5.44 [0.15;199.32] C excluded (exposition period)	0/2   1/26	1	2		ref
S6324 R17146	Veiby (Epilepsy) (Controls exposed to Lamotrigine, sick), 2014	Major malformations	throughout pregnancy	population based cohort retrospective	exposed to other treatment, sick excluded	Adjustment: No	0.64 [0.08;4.83] C excluded (control group)	1/40   23/593	24	40		ref
S6325 R17147	Veiby (Epilepsy) (Controls unexposed, disease free), 2014	Major malformations	throughout pregnancy	population based cohort retrospective	unexposed, disease free excluded	Adjustment: Yes	0.99 [0.14;7.22] excluded (control group)	1/40   22,371/771,412	22,372	40		ref
S6326 R17148	Veiby (Epilepsy) (Controls unexposed, sick), 2014	Major malformations	throughout pregnancy	population based cohort retrospective	unexposed, sick	Adjustment: No	0.89 [0.12;6.52] C	1/40   106/3,773	107	40		ref
S6494 R17804	Bànhidy (Epilepsy), 2011	Total congenital abnormalities	throughout pregnancy	case control	unexposed, sick	Adjustment: No Matched	0.28 [0.01;7.57] C	0/1   12/22	12	1		ref
S6067 R15782	Morrow (Epilepsy) (Controls exposed to Lamotrigine, sick), 2006	Major congenital malformation	1st trimester	prospective cohort	exposed to other treatment, sick excluded	Adjustment: No	1.71 [0.10;30.62] C excluded (control group)	0/9   21/647	21	9		ref
S6068 R15789	Morrow (Epilepsy) (Controls unexposed, sick), 2006	Major congenital malformation	1st trimester	prospective cohort	unexposed, sick	Adjustment: No	1.51 [0.08;28.41] C	0/9   8/227	8	9		ref
S6138 R16032	Kaaja (Epilepsy), 2003	Major malformation	1st trimester	prospective cohort	unexposed, sick	Adjustment: No	3.78 [0.17;83.10] C	0/13   2/239	2	13		ref
S6927 R19480	Hvas (Epilepsy) (Controls unexposed, disease free), 2000	Major congenital malformations	1st trimester	prospective cohort	unexposed, disease free excluded	Adjustment: No	2.89 [0.17;48.65] C excluded (control group)	0/15   280/23,827	280	15		ref
S6923 R19476	Hvas (Epilepsy) (Controls unexposed, sick), 2000	Major congenital malformations	1st trimester	prospective cohort	unexposed, sick	Adjustment: No	7.28 [0.14;381.01] C	0/15   0/106	0	15		ref
S328 R17701	Canger (Epilepsy), 1999	Severe malformations	1st trimester	prospective cohort	unexposed, sick	Adjustment: No	4.45 [0.08;250.02] C	0/6   0/25	0	6		ref
S7396 R21707	Samrén (Epilepsy), 1999	Major congential abnormalities	at least 1st trimester	retrospective cohort	unexposed, disease free	Adjustment: No Matched	3.93 [0.22;69.67] C	0/9   29/2,000	29	9		ref
S6165 R16218	Robert (Epilepsy), 1986	Major malformations	1st trimester	retrospective cohort	unexposed, sick	Adjustment: No	69.00 [0.56;8490.38] C	0/1   0/35	0	1		ref
					Total	11 studies	1.58 [0.67;3.77]		292	174
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 6927, 6067, 6324, 6325, 12876, 7777