Carbamazepine (Epilepsy)

Congenital heart defects

R analysis

id	Study	Lib. in paper	Exposition period	Study type All studies Case control excluded Only case control	Control type	Tags	OR 95%CI	x1/n1 x0/n0	no cases	no exposed	ROB	Ref.
S12854 R48476	Thomas (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2021	Cardiac malformations	1st trimester	prospective cohort	exposed to other treatment, sick excluded	Adjustment: No	0.71 [0.09;5.89] ^C excluded (control group)	7/490 1/50	8	490		ref
S12855 R48486	Thomas (Carbamazepine) (Controls unexposed, sick), 2021	Cardiac malformations	1st trimester	prospective cohort	unexposed, sick	Adjustment: No	0.53 [0.20;1.45] ^C	7/490 9/340	16	490		ref
S382 R16393	Tomson (Carbamazepine), 2018	Cardiac malformations	at least 1st trimester	prospective cohort	exposed to other treatment, sick	Adjustment: No	2.42 [1.29;4.54] ^C	28/1,957 15/2,514	43	1,957		ref
S6290 R16963	Campbell (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2014	Cardiac defects	1st trimester	prospective cohort	exposed to other treatment, sick	Adjustment: No	1.98 [0.85;4.58] ^C	14/1,657 9/2,098	23	1,657		ref
S10289 R37670	Vajda (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2013	Cardiac Malformations	at least 1st trimester	prospective cohort	exposed to other treatment, sick excluded	Adjustment: No	0.87 [0.17;4.35] ^C excluded (control group)	3/361 3/315	6	361		ref
S9830 R37665	Vajda (Carbamazepine) (Controls unexposed, sick), 2013	Cardiac Malformations	at least 1st trimester	prospective cohort	unexposed, sick	Adjustment: No	1.22 [0.13;11.86] ^C	3/361 1/147	4	361		ref
S5937 R23780	Hernández-Díaz (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2012	Cardiovascular anomalies	1st trimester	prospective cohort	exposed to other treatment, sick	Adjustment: No Controls: mixed indications	1.51 [0.30;7.51] ^C	3/1,033 3/1,562	6	1,033		ref
S5483 R15645	Bànhidy (Carbamazepine), 2011	Cardiovascular congenital abnormalities	throughout pregnancy	case control	unexposed, sick	Adjustment: No Matched	0.80 [0.16;3.88] ^C	4/14 5/15	9	14		ref
S9845 R35321	Mawer (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2010	Cardiac Malformations	1st trimester	prospective cohort	exposed to other treatment, sick excluded	Adjustment: No	0.56 [0.01;28.68] ^C excluded (control group)	0/66 0/37	0	66		ref
S9846 R35327	Mawer (Carbamazepine) (Controls unexposed, disease free), 2010	Cardiac Malformations	1st trimester	prospective cohort	unexposed, disease free excluded	Adjustment: No Matched	1.44 [0.06;35.82] ^C excluded (control group)	0/66 1/285	1	66		ref
S9847 R35333	Mawer (Carbamazepine) (Controls unexposed, sick), 2010	Cardiac Malformations	1st trimester	prospective cohort	unexposed, sick	Adjustment: No	0.62 [0.01;31.78] ^C	0/66 0/41	0	66		ref
S302 R15853	Artama (Carbamazepine), 2005	Cardiovascular	1st trimester	retrospective cohort (registry)	unexposed, sick	Adjustment: No	0.50 [0.13;1.93] ^C	3/805 7/939	10	805		ref
S6509 R17928	Canger (Carbamazepine), 1999	Cardiac malformations	1st trimester	prospective cohort	unexposed, sick	Adjustment: No	0.22 [0.00;11.25] ^C	0/113 0/25	0	113		ref
S6685 R18583	D'Souza (Carbamazepine) (Controls unexposed, disease free), 1991	Heart disease	throughout pregnancy	prospective cohort	unexposed, disease free excluded	Adjustment: No Matched	24.60 [0.40;1512.72] ^C excluded (control group)	0/3 0/62	0	3		ref
S6689 R18700	D'Souza (Carbamazepine) (Controls unexposed, sick), 1991	Heart disease	throughout pregnancy	prospective cohort	unexposed, sick	Adjustment: No	0.87 [0.03;29.20] ^C	0/3 1/8	1	3		ref
S6823 R19299	Van der Pol (Carbamazepine) (Controls unexposed, disease free), 1991	Cardiac anomaly	throughout pregnancy	prospective cohort	unexposed, disease free excluded	Adjustment: No Matched	5.40 [0.31;93.62] ^C excluded (control group)	1/11 1/55	2	11		ref
S6825 R19349	Van der Pol (Carbamazepine) (Controls unexposed, sick), 1991	Cardiac anomaly	throughout pregnancy	prospective cohort	unexposed, sick	Adjustment: No	6.79 [0.25;182.34] ^C	1/11 0/22	1	11		ref
					Total	11 studies	1.29 [0.81;2.05]		113	6,510
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

1: Carbamazepine) (Controls unexposed, sick; 2: Carbamazepine; 3: Carbamazepine) (Controls exposed to Lamotrigine, sick; 4: Carbamazepine) (Controls unexposed, sick; 5: Carbamazepine) (Controls exposed to Lamotrigine, sick; 6: Carbamazepine; 7: Carbamazepine) (Controls unexposed, sick; 8: Carbamazepine; 9: Carbamazepine; 10: Carbamazepine) (Controls unexposed, sick; 11: Carbamazepine) (Controls unexposed, sick;

Sensitivity analysis

Publication bias and p-hacking diagnosis

funnel plot

Asymetry test p-value = 0.2368 (by Egger's regression)

slope=0.7625 (0.3899); intercept=-0.7601 (0.5997); t=1.2676; p=0.2368

p values plot

Sub-groups analysis using all included studies

excluded 6685, 6823, 9845, 9846, 10289, 12854

S12854 R48476	Thomas (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2021	Cardiac malformations (73)	1st trimester	exposed to other treatment, sick	0.71 [0.09;5.89]	7/490 1/50
S12855 R48486	Thomas (Carbamazepine) (Controls unexposed, sick), 2021	Cardiac malformations (73)	1st trimester	unexposed, sick	0.53 [0.20;1.45]	7/490 9/340
S382 R16393	Tomson (Carbamazepine), 2018	Cardiac malformations (73)	at least 1st trimester	exposed to other treatment, sick	2.42 [1.29;4.54]	28/1957 15/2514
S6290 R16963	Campbell (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2014	Cardiac defects (73)	1st trimester	exposed to other treatment, sick	1.98 [0.85;4.58]	14/1657 9/2098
S10289 R37670	Vajda (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2013	Cardiac Malformations (73)	at least 1st trimester	exposed to other treatment, sick	0.87 [0.17;4.35]	3/361 3/315
S9830 R37665	Vajda (Carbamazepine) (Controls unexposed, sick), 2013	Cardiac Malformations (73)	at least 1st trimester	unexposed, sick	1.22 [0.13;11.86]	3/361 1/147
S5937 R23780	Hernández-Díaz (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2012	Cardiovascular anomalies (73)	1st trimester	exposed to other treatment, sick	1.51 [0.30;7.51]	3/1033 3/1562
S5483 R15645	Bànhidy (Carbamazepine), 2011	Cardiovascular congenital abnormalities (73)	throughout pregnancy	unexposed, sick	0.80 [0.16;3.88]	4/14 5/15
S9845 R35321	Mawer (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2010	Cardiac Malformations (73)	1st trimester	exposed to other treatment, sick	0.56 [0.01;28.68]	0/66 0/37
S9846 R35327	Mawer (Carbamazepine) (Controls unexposed, disease free), 2010	Cardiac Malformations (73)	1st trimester	unexposed, disease free	1.44 [0.06;35.82]	0/66 1/285
S9847 R35333	Mawer (Carbamazepine) (Controls unexposed, sick), 2010	Cardiac Malformations (73)	1st trimester	unexposed, sick	0.62 [0.01;31.78]	0/66 0/41
S302 R15853	Artama (Carbamazepine), 2005	Cardiovascular (73)	1st trimester	unexposed, sick	0.50 [0.13;1.93]	3/805 7/939
S6509 R17928	Canger (Carbamazepine), 1999	Cardiac malformations (73)	1st trimester	unexposed, sick	0.22 [0.00;11.25]	0/113 0/25
S6685 R18583	D'Souza (Carbamazepine) (Controls unexposed, disease free), 1991	Heart disease (73)	throughout pregnancy	unexposed, disease free	24.60 [0.40;1512.72]	0/3 0/62
S6689 R18700	D'Souza (Carbamazepine) (Controls unexposed, sick), 1991	Heart disease (73)	throughout pregnancy	unexposed, sick	0.87 [0.03;29.20]	0/3 1/8
S6823 R19299	Van der Pol (Carbamazepine) (Controls unexposed, disease free), 1991	Cardiac anomaly (73)	throughout pregnancy	unexposed, disease free	5.40 [0.31;93.62]	1/11 1/55
S6825 R19349	Van der Pol (Carbamazepine) (Controls unexposed, sick), 1991	Cardiac anomaly (73)	throughout pregnancy	unexposed, sick	6.79 [0.25;182.34]	1/11 0/22