Carbamazepine (Epilepsy)

Spina bifida

id	Study   Auto Veiby (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2014Veiby (Carbamazepine) (Controls unexposed, sick), 2014Charlton (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2011Charlton (Carbamazepine) (Controls unexposed, sick), 2011Jentink (Carbamazepine), 2010Viinikainen (Carbamazepine) (Controls unexposed, sick) a, 2006Artama (Carbamazepine), 2005Källén (Carbamazepine), 1994Van der Pol (Carbamazepine) (Controls unexposed, disease free), 1991Van der Pol (Carbamazepine) (Controls unexposed, sick), 1991	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.
S6318 R26054	Veiby (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2014	Spina bifida	throughout pregnancy	population based cohort retrospective	exposed to other treatment, sick excluded	Adjustment: No	0.97 [0.02;48.83] C excluded (control group)	0/613   0/593	0	613		ref
S6320 R26059	Veiby (Carbamazepine) (Controls unexposed, sick), 2014	Spina bifida	throughout pregnancy	population based cohort retrospective	unexposed, sick	Adjustment: No	0.88 [0.05;17.04] C	0/613   3/3,773	3	613		ref
S8137 R24993	Charlton (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2011	Spina bifida	1st trimester	retrospective cohort (claims database)	exposed to other treatment, sick excluded	Adjustment: No	0.31 [0.01;15.93] C excluded (control group)	0/311   0/98	0	311		ref
S331 R24990	Charlton (Carbamazepine) (Controls unexposed, sick), 2011	Spina bifida	1st trimester	retrospective cohort (claims database)	unexposed, sick	Adjustment: No	0.58 [0.03;12.10] C	0/311   2/902	2	311		ref
S8411 R26708	Jentink (Carbamazepine), 2010	Spina bifida	1st trimester	case control	unexposed (general population or NOS)	Adjustment: Yes	2.60 [1.20;5.30]	8/-   -/-	-	-		ref
S5529 R16225	Viinikainen (Carbamazepine) (Controls unexposed, sick) a, 2006	Spina bifida	throughout pregnancy	prospective cohort	unexposed, sick	Adjustment: No	0.72 [0.01;36.90] C	0/72   0/52	0	72		ref
S302 R15848	Artama (Carbamazepine), 2005	Spina bifida	1st trimester	retrospective cohort (registry)	unexposed, sick	Adjustment: No	1.17 [0.02;58.86] C	0/805   0/939	0	805		ref
S8410 R26713	Källén (Carbamazepine), 1994	Spina bifida	during pregnancy (anytime or not specified) excluded	nested case control	unexposed, sick	Adjustment: No Matched	39.00 [0.53;2883.82] C excluded (exposition period)	2/3   0/6	2	3		ref
S6823 R19294	Van der Pol (Carbamazepine) (Controls unexposed, disease free), 1991	Spina bifida occulta	throughout pregnancy	prospective cohort	unexposed, disease free excluded	Adjustment: No Matched	5.19 [0.10;276.47] C excluded (control group)	0/11   0/55	0	11		ref
S6825 R19344	Van der Pol (Carbamazepine) (Controls unexposed, sick), 1991	Spina bifida occulta	throughout pregnancy	prospective cohort	unexposed, sick	Adjustment: No	0.65 [0.02;17.40] C	0/11   1/22	1	11		ref
					Total	6 studies	2.04 [1.05;3.97]		6	1,812
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 6823, 8137, 6318