Carbamazepine (Epilepsy)

Limb defects

id	Study   Auto Thomas (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2021Thomas (Carbamazepine) (Controls unexposed, sick), 2021Campbell (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2014Vajda (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2013Vajda (Carbamazepine) (Controls unexposed, sick), 2013Mawer (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2010Mawer (Carbamazepine) (Controls unexposed, disease free), 2010Mawer (Carbamazepine) (Controls unexposed, sick), 2010Artama (Carbamazepine), 2005	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 specifiedwhatever (meta-analysis)	Tags	OR 95%CI	x1/n1 x0/n0	no cases	no exposed	ROB	Ref.
S12854 R48479	Thomas (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2021	Skeletal malformations	1st trimester	prospective cohort	exposed to other treatment, sick excluded	Adjustment: No	0.92 [0.05;17.29] C excluded (control group)	4/490   0/50	4	490		ref
S12855 R48489	Thomas (Carbamazepine) (Controls unexposed, sick), 2021	Skeletal malformations	1st trimester	prospective cohort	unexposed, sick	Adjustment: No	1.39 [0.25;7.64] C	4/490   2/340	6	490		ref
S6290 R16965	Campbell (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2014	Skeletal defects	1st trimester	prospective cohort	exposed to other treatment, sick	Adjustment: No	1.69 [0.38;7.56] C	4/1,657   3/2,098	7	1,657		ref
S10289 R37672	Vajda (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2013	Skeletal / Limb Malformations	at least 1st trimester	prospective cohort	exposed to other treatment, sick excluded	Adjustment: No	4.39 [0.21;91.71] C excluded (control group)	2/361   0/315	2	361		ref
S9830 R37667	Vajda (Carbamazepine) (Controls unexposed, sick), 2013	Skeletal / Limb Malformations	at least 1st trimester	prospective cohort	unexposed, sick	Adjustment: No	0.81 [0.07;9.04] C	2/361   1/147	3	361		ref
S9845 R35323	Mawer (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2010	Skeletal / Limb Malformations	1st trimester	prospective cohort	exposed to other treatment, sick excluded	Adjustment: No	0.18 [0.01;4.55] C excluded (control group)	0/66   1/37	1	66		ref
S9846 R35329	Mawer (Carbamazepine) (Controls unexposed, disease free), 2010	Skeletal / Limb Malformations	1st trimester	prospective cohort	unexposed, disease free excluded	Adjustment: No Matched	4.34 [0.09;220.94] C excluded (control group)	0/66   0/285	0	66		ref
S9847 R35335	Mawer (Carbamazepine) (Controls unexposed, sick), 2010	Skeletal / Limb Malformations	1st trimester	prospective cohort	unexposed, sick	Adjustment: No	0.62 [0.01;31.78] C	0/66   0/41	0	66		ref
S302 R35920	Artama (Carbamazepine), 2005	Certain musculoskeletal deformities and Other anomalies of limbs	1st trimester	retrospective cohort (registry)	unexposed, sick	Adjustment: No	1.51 [0.56;4.06] C	9/805   7/939	16	805		ref
					Total	5 studies	1.41 [0.70;2.83]		32	3,379
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 9845, 9846, 10289, 12854