Oxcarbazepine (Epilepsy)

All congenital malformations (majors, minors, majors and minors, or unspecified)

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.
S15827 R65178	Cohen (Oxcarbazepine) (Epilepsy) (Controls exposed to LTG), 2023	Major congenital malformations (excluding genetic/chromosomal)	1st trimester	population based cohort retrospective	exposed to other treatment, sick excluded	Adjustment: Yes Partial overlapping	1.09 [0.83;1.44] excluded (control group)	58/1,313 314/8,339	372	1,313		ref
S15828 R65180	Cohen (Oxcarbazepine) (Epilepsy) (Controls unexposed, NOS), 2023	Major congenital malformations (excluding genetic/chromosomal)	1st trimester	population based cohort retrospective	unexposed (general population or NOS)	Adjustment: No Partial overlapping	1.47 [1.13;1.92] ^C	58/1,313 147,928/4,866,362	147,986	1,313		ref
S15856 R65269	Li (Oxcarbazepine) (Controls exposed to LTG), 2023	Major congenital malformation	during pregnancy (anytime or not specified)	prospective cohort	exposed to other treatment, sick excluded	Adjustment: No	4.52 [0.21;97.17] ^C excluded (control group)	2/44 0/38	2	44		ref
S15857 R65271	Li (Oxcarbazepine) (Controls unexposed, sick), 2023	Major congenital malformation	during pregnancy (anytime or not specified) excluded	prospective cohort	unexposed, sick	Adjustment: No	1.67 [0.34;8.33] ^C excluded (exposition period)	2/44 7/253	9	44		ref
S12888 R48703	Hosny (Oxcarbazepine) (Controls exposed to Lamotrigine, sick), 2021	Major birth defects	1st trimester	prospective cohort	exposed to other treatment, sick excluded	Adjustment: No	0.20 [0.00;28.47] ^C excluded (control group)	0/3 0/1	0	3		ref
S12889 R48706	Hosny (Oxcarbazepine) (Controls unexposed, sick), 2021	Major birth defects	1st trimester	prospective cohort	unexposed, sick	Adjustment: No	2.60 [0.08;82.80] ^C	0/3 1/21	1	3		ref
S12828 R48298	Thomas (Oxcarbazepine) (Controls exposed to Lamotrigine, sick), 2021	Major congenital malformations	1st trimester	prospective cohort	exposed to other treatment, sick excluded	Adjustment: No	3.71 [0.42;32.79] ^C excluded (control group)	5/71 1/50	6	71		ref
S7548 R26663	Thomas (Oxcarbazepine) (Controls unexposed, disease free), 2021	Major congenital malformations	1st trimester	prospective cohort	unexposed, disease free excluded	Adjustment: No	2.12 [0.62;7.29] excluded (control group)	3/41 11/319	14	41		ref
S12830 R48310	Thomas (Oxcarbazepine) (Controls unexposed, sick), 2021	Major congenital malformations	1st trimester	prospective cohort	unexposed, sick	Adjustment: Yes	1.61 [0.60;4.20]	5/71 16/340	21	71		ref
S7959 R26670	AlSheikh (Oxcarbazepine) (Controls exposed to Lamotrigine, sick), 2020	Fetal/neonatal malformation	during pregnancy (anytime or not specified)	prospective cohort	exposed to other treatment, sick excluded	Adjustment: No	7.80 [0.12;487.53] ^C excluded (control group)	0/3 0/20	0	3		ref
S7957 R26669	AlSheikh (Oxcarbazepine) (Controls unexposed, sick), 2020	Fetal/neonatal malformation	during pregnancy (anytime or not specified) excluded	prospective cohort	unexposed, sick	Adjustment: No	0.87 [0.03;29.20] ^C excluded (exposition period)	0/3 1/8	1	3		ref
S8084 R24705	Aydin (Oxcarbazepine) (Controls exposed to Lamotrigine, sick), 2020	Congenital chromosomal/structural anomalies	throughout pregnancy	retrospective cohort	exposed to other treatment, sick excluded	Adjustment: No	1.86 [0.03;115.45] ^C excluded (control group)	0/4 0/7	0	4		ref
S8075 R24645	Aydin (Oxcarbazepine) (Controls unexposed, sick), 2020	Congenital chromosomal/structural anomalies	throughout pregnancy	retrospective cohort	unexposed, sick	Adjustment: No	6.14 [0.10;363.16] ^C	0/4 0/22	0	4		ref
S7784 R35155	Vajda (Oxcarbazepine) (Controls exposed to Lamotrigine, sick), 2019	Fetal malformations	at least 1st trimester	prospective cohort	exposed to other treatment, sick excluded	Adjustment: No	1.07 [0.14;8.44] ^C excluded (control group)	1/19 20/406	21	19		ref
S7785 R35156	Vajda (Oxcarbazepine) (Controls unexposed, sick), 2019	Fetal malformations	at least 1st trimester	prospective cohort	unexposed, sick	Adjustment: No	1.85 [0.23;15.04]	1/19 5/176	6	19		ref
S7659 R26665	Tomson (Oxcarbazepine) , 2018	Major congenital malformation	at least 1st trimester	prospective cohort	exposed to other treatment, sick	Adjustment: No	1.02 [0.52;2.00] ^C	10/333 74/2,514	84	333		ref
S10271 R37640	Razaz (Oxcarbazepine) (Controls exposed to Lamotrigine, sick), 2017	Major malformations	during pregnancy (anytime or not specified)	population based cohort retrospective	exposed to other treatment, sick excluded	Adjustment: No	0.99 [0.13;7.71] ^C excluded (control group)	1/23 22/503	23	23		ref
S10270 R37641	Razaz (Oxcarbazepine) (Controls unexposed, disease free), 2017	Major malformations	during pregnancy (anytime or not specified)	population based cohort retrospective	unexposed, disease free excluded	Adjustment: No	1.34 [0.18;9.96] ^C excluded (control group)	1/23 46,632/1,424,279	46,633	23		ref
S10272 R37642	Razaz (Oxcarbazepine) (Controls unexposed, sick), 2017	Major malformations	during pregnancy (anytime or not specified) excluded	population based cohort retrospective	unexposed, sick	Adjustment: No	0.93 [0.12;6.98] ^C excluded (exposition period)	1/23 87/1,868	88	23		ref
S6333 R26666	Veiby (Oxcarbazepine) (Controls exposed to Lamotrigine, sick), 2014	Major malformations	throughout pregnancy	population based cohort retrospective	exposed to other treatment, sick excluded	Adjustment: No Partial overlapping	0.50 [0.07;3.75] ^C excluded (control group)	1/51 23/593	24	51		ref
S6334 R26667	Veiby (Oxcarbazepine) (Controls unexposed, disease free), 2014	Major malformations	throughout pregnancy	population based cohort retrospective	unexposed, disease free excluded	Adjustment: Yes Partial overlapping	0.72 [0.10;5.18] excluded (control group)	1/51 22,371/771,412	22,372	51		ref
S6335 R26668	Veiby (Oxcarbazepine) (Controls unexposed, sick), 2014	Major malformations	throughout pregnancy	population based cohort retrospective	unexposed, sick	Adjustment: No Partial overlapping	0.69 [0.09;5.06] ^C	1/51 106/3,773	107	51		ref
S5942 R26649	Hernández-Díaz (Oxcarbazepine) (Controls exposed to Lamotrigine, sick), 2012	Major congenital malformations	1st trimester	prospective cohort	exposed to other treatment, sick excluded	Adjustment: No Controls: mixed indications	1.50 [0.50;4.60] excluded (control group)	-/- -/-	-	-		ref
S7937 R26650	Hernández-Díaz (Oxcarbazepine) (Controls unexposed, disease free), 2012	Major congenital malformations	1st trimester	prospective cohort	unexposed, disease free	Adjustment: No	2.00 [0.50;7.40]	4/182 5/442	9	182		ref
S6650 R26656	Kini (Oxcarbazepine) (Controls exposed to Lamotrigine, sick), 2007	Major malformations	during pregnancy (anytime or not specified)	prospective cohort	exposed to other treatment, sick excluded	Adjustment: No	29.00 [0.23;3625.72] ^C excluded (control group)	0/1 0/15	0	1		ref
S6640 R26657	Kini (Oxcarbazepine) (Controls unexposed, disease free), 2007	Major malformations	during pregnancy (anytime or not specified)	prospective cohort	unexposed, disease free excluded	Adjustment: No Matched	41.91 [0.76;2311.57] ^C excluded (control group)	0/1 5/236	5	1		ref
S6645 R26658	Kini (Oxcarbazepine) (Controls unexposed, sick), 2007	Major malformations	during pregnancy (anytime or not specified) excluded	prospective cohort	unexposed, sick	Adjustment: No	67.00 [0.54;8247.13] ^C excluded (exposition period)	0/1 0/34	0	1		ref
S6071 R26659	Morrow (Oxcarbazepine) (Controls exposed to Lamotrigine, sick), 2006	Major congenital malformation	1st trimester	prospective cohort	exposed to other treatment, sick excluded	Adjustment: No	2.24 [0.12;41.02] ^C excluded (control group)	0/7 21/647	21	7		ref
S6072 R26660	Morrow (Oxcarbazepine) (Controls unexposed, sick), 2006	Major congenital malformation	1st trimester	prospective cohort	unexposed, sick	Adjustment: No	1.98 [0.10;38.04] ^C	0/7 8/227	8	7		ref
S6170 R26673	Viinikainen (Oxcarbazepine) (Controls unexposed, sick) a, 2006	Major malformations	throughout pregnancy	prospective cohort	unexposed, sick	Adjustment: No	34.33 [0.49;2389.88] ^C	0/2 0/52	0	2		ref
S6096 R15863	Artama (Oxcarbazepine), 2005	Malformations	1st trimester	retrospective cohort (registry)	unexposed, sick	Adjustment: No	0.36 [0.01;2.23]	1/99 26/939	27	99		ref
S6141 R26653	Kaaja (Oxcarbazepine), 2003	Major malformation	1st trimester	prospective cohort	unexposed, sick	Adjustment: Yes	10.80 [1.10;106.20]	1/9 2/239	3	9		ref
S6928 R26651	Hvas (Oxcarbazepine) (Controls unexposed, disease free), 2000	Major congenital malformations	1st trimester	retrospective cohort	unexposed, disease free excluded	Adjustment: No	6.46 [0.36;114.91] ^C excluded (control group)	0/7 280/23,827	280	7		ref
S6924 R26652	Hvas (Oxcarbazepine) (Controls unexposed, sick), 2000	Major congenital malformations	1st trimester	retrospective cohort	unexposed, sick	Adjustment: No	16.23 [0.30;885.49] ^C	0/7 0/106	0	7		ref
S6716 R26661	Samrén (Oxcarbazepine), 1999	Major congential abnormalities	at least 1st trimester	retrospective cohort	unexposed, disease free	Adjustment: No Matched	22.27 [0.89;557.96] ^C	0/2 29/2,000	29	2		ref
					Total	14 studies	1.49 [1.19;1.87]		148,281	2,102
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: Oxcarbazepine) (Epilepsy) (Controls unexposed, NOS; 2: Oxcarbazepine) (Controls unexposed, sick; 3: Oxcarbazepine) (Controls unexposed, sick; 4: Oxcarbazepine) (Controls unexposed, sick; 5: Oxcarbazepine) (Controls unexposed, sick; 6: Oxcarbazepine; 7: Oxcarbazepine) (Controls unexposed, sick; 8: Oxcarbazepine) (Controls unexposed, disease free; 9: Oxcarbazepine) (Controls unexposed, sick; 10: Oxcarbazepine) (Controls unexposed, sick) ; 11: Oxcarbazepine; 12: Oxcarbazepine; 13: Oxcarbazepine) (Controls unexposed, sick; 14: Oxcarbazepine;

Sensitivity analysis

Publication bias and p-hacking diagnosis

funnel plot

Asymetry test p-value = 0.0844 (by Egger's regression)

slope=0.2385 (0.1356); intercept=0.5905 (0.3139); t=1.8811; p=0.0844

p values plot

Sub-groups analysis using all included studies

excluded 6928, 6071, 6650, 6640, 5942, 6333, 6334, 10271, 10270, 7784, 7959, 8084, 12888, 12828, 7548, 15827, 15856

S15827 R65178	Cohen (Oxcarbazepine) (Epilepsy) (Controls exposed to LTG), 2023	Major congenital malformations (excluding genetic/chromosomal) (67)	1st trimester	exposed to other treatment, sick	1.09 [0.83;1.44]	58/1313 314/8339
S15828 R65180	Cohen (Oxcarbazepine) (Epilepsy) (Controls unexposed, NOS), 2023	Major congenital malformations (excluding genetic/chromosomal) (67)	1st trimester	unexposed (general population or NOS)	1.47 [1.13;1.92]	58/1313 147928/4866362
S15856 R65269	Li (Oxcarbazepine) (Controls exposed to LTG), 2023	Major congenital malformation (67)	during pregnancy (anytime or not specified)	exposed to other treatment, sick	4.52 [0.21;97.17]	2/44 0/38
S15857 R65271	Li (Oxcarbazepine) (Controls unexposed, sick), 2023	Major congenital malformation (67)	during pregnancy (anytime or not specified)	unexposed, sick	1.67 [0.34;8.33]	2/44 7/253
S12888 R48703	Hosny (Oxcarbazepine) (Controls exposed to Lamotrigine, sick), 2021	Major birth defects (67)	1st trimester	exposed to other treatment, sick	0.20 [0.00;28.47]	0/3 0/1
S12889 R48706	Hosny (Oxcarbazepine) (Controls unexposed, sick), 2021	Major birth defects (67)	1st trimester	unexposed, sick	2.60 [0.08;82.80]	0/3 1/21
S12828 R48298	Thomas (Oxcarbazepine) (Controls exposed to Lamotrigine, sick), 2021	Major congenital malformations (67)	1st trimester	exposed to other treatment, sick	3.71 [0.42;32.79]	5/71 1/50
S7548 R26663	Thomas (Oxcarbazepine) (Controls unexposed, disease free), 2021	Major congenital malformations (67)	1st trimester	unexposed, disease free	2.12 [0.62;7.29]	3/41 11/319
S12830 R48310	Thomas (Oxcarbazepine) (Controls unexposed, sick), 2021	Major congenital malformations (67)	1st trimester	unexposed, sick	1.61 [0.60;4.20]	5/71 16/340
S7959 R26670	AlSheikh (Oxcarbazepine) (Controls exposed to Lamotrigine, sick), 2020	Fetal/neonatal malformation (67)	during pregnancy (anytime or not specified)	exposed to other treatment, sick	7.80 [0.12;487.53]	0/3 0/20
S7957 R26669	AlSheikh (Oxcarbazepine) (Controls unexposed, sick), 2020	Fetal/neonatal malformation (67)	during pregnancy (anytime or not specified)	unexposed, sick	0.87 [0.03;29.20]	0/3 1/8
S8084 R24705	Aydin (Oxcarbazepine) (Controls exposed to Lamotrigine, sick), 2020	Congenital chromosomal/structural anomalies (67)	throughout pregnancy	exposed to other treatment, sick	1.86 [0.03;115.45]	0/4 0/7
S8075 R24645	Aydin (Oxcarbazepine) (Controls unexposed, sick), 2020	Congenital chromosomal/structural anomalies (67)	throughout pregnancy	unexposed, sick	6.14 [0.10;363.16]	0/4 0/22
S7784 R35155	Vajda (Oxcarbazepine) (Controls exposed to Lamotrigine, sick), 2019	Fetal malformations (67)	at least 1st trimester	exposed to other treatment, sick	1.07 [0.14;8.44]	1/19 20/406
S7785 R35156	Vajda (Oxcarbazepine) (Controls unexposed, sick), 2019	Fetal malformations (67)	at least 1st trimester	unexposed, sick	1.85 [0.23;15.04]	1/19 5/176
S7659 R26665	Tomson (Oxcarbazepine) , 2018	Major congenital malformation (67)	at least 1st trimester	exposed to other treatment, sick	1.02 [0.52;2.00]	10/333 74/2514
S10271 R37640	Razaz (Oxcarbazepine) (Controls exposed to Lamotrigine, sick), 2017	Major malformations (67)	during pregnancy (anytime or not specified)	exposed to other treatment, sick	0.99 [0.13;7.71]	1/23 22/503
S10270 R37641	Razaz (Oxcarbazepine) (Controls unexposed, disease free), 2017	Major malformations (67)	during pregnancy (anytime or not specified)	unexposed, disease free	1.34 [0.18;9.96]	1/23 46632/1424279
S10272 R37642	Razaz (Oxcarbazepine) (Controls unexposed, sick), 2017	Major malformations (67)	during pregnancy (anytime or not specified)	unexposed, sick	0.93 [0.12;6.98]	1/23 87/1868
S6333 R26666	Veiby (Oxcarbazepine) (Controls exposed to Lamotrigine, sick), 2014	Major malformations (67)	throughout pregnancy	exposed to other treatment, sick	0.50 [0.07;3.75]	1/51 23/593
S6334 R26667	Veiby (Oxcarbazepine) (Controls unexposed, disease free), 2014	Major malformations (67)	throughout pregnancy	unexposed, disease free	0.72 [0.10;5.18]	1/51 22371/771412
S6335 R26668	Veiby (Oxcarbazepine) (Controls unexposed, sick), 2014	Major malformations (67)	throughout pregnancy	unexposed, sick	0.69 [0.09;5.06]	1/51 106/3773
S5942 R26649	Hernández-Díaz (Oxcarbazepine) (Controls exposed to Lamotrigine, sick), 2012	Major congenital malformations (67)	1st trimester	exposed to other treatment, sick	1.50 [0.50;4.60]	-9/-9 -9/-9
S7937 R26650	Hernández-Díaz (Oxcarbazepine) (Controls unexposed, disease free), 2012	Major congenital malformations (67)	1st trimester	unexposed, disease free	2.00 [0.50;7.40]	4/182 5/442
S6650 R26656	Kini (Oxcarbazepine) (Controls exposed to Lamotrigine, sick), 2007	Major malformations (67)	during pregnancy (anytime or not specified)	exposed to other treatment, sick	29.00 [0.23;3625.72]	0/1 0/15
S6640 R26657	Kini (Oxcarbazepine) (Controls unexposed, disease free), 2007	Major malformations (67)	during pregnancy (anytime or not specified)	unexposed, disease free	41.91 [0.76;2311.57]	0/1 5/236
S6645 R26658	Kini (Oxcarbazepine) (Controls unexposed, sick), 2007	Major malformations (67)	during pregnancy (anytime or not specified)	unexposed, sick	67.00 [0.54;8247.13]	0/1 0/34
S6071 R26659	Morrow (Oxcarbazepine) (Controls exposed to Lamotrigine, sick), 2006	Major congenital malformation (67)	1st trimester	exposed to other treatment, sick	2.24 [0.12;41.02]	0/7 21/647
S6072 R26660	Morrow (Oxcarbazepine) (Controls unexposed, sick), 2006	Major congenital malformation (67)	1st trimester	unexposed, sick	1.98 [0.10;38.04]	0/7 8/227
S6170 R26673	Viinikainen (Oxcarbazepine) (Controls unexposed, sick) a, 2006	Major malformations (67)	throughout pregnancy	unexposed, sick	34.33 [0.49;2389.88]	0/2 0/52
S6096 R15863	Artama (Oxcarbazepine), 2005	Malformations (67)	1st trimester	unexposed, sick	0.36 [0.01;2.23]	1/99 26/939
S6141 R26653	Kaaja (Oxcarbazepine), 2003	Major malformation (67)	1st trimester	unexposed, sick	10.80 [1.10;106.20]	1/9 2/239
S6928 R26651	Hvas (Oxcarbazepine) (Controls unexposed, disease free), 2000	Major congenital malformations (67)	1st trimester	unexposed, disease free	6.46 [0.36;114.91]	0/7 280/23827
S6924 R26652	Hvas (Oxcarbazepine) (Controls unexposed, sick), 2000	Major congenital malformations (67)	1st trimester	unexposed, sick	16.23 [0.30;885.49]	0/7 0/106
S6716 R26661	Samrén (Oxcarbazepine), 1999	Major congential abnormalities (67)	at least 1st trimester	unexposed, disease free	22.27 [0.89;557.96]	0/2 29/2000