Oxcarbazepine (Epilepsy)

Major congenital malformations

R analysis
id Study   Lib. in paper Exposition period    Study type 
 Control type 
 
Tags OR 95%CI x1/n1 x0/n0 no cases no exposed ROB Ref.
S15827
R65177		 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
R65179		 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
R65268		 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
R65270		 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
R48701		 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
R48704		 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
R48297		 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
R22591		 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
R48309		 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
R24145		 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
R24117		 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
S7784
R23002		 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
R23003		 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
R22649		 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
R37614		 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
R37613		 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
R37615		 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
R17155		 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
R17156		 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
R17157		 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
R15204		 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
R24013		 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
R18356		 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
R18346		 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
R18351		 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
R15798		 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
R15805		 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
R16235		 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
S6141
R16035		 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
R19481		 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
R19477		 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
R18989		 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 12 studies 1.51 [1.17;1.96] 148,254 1,999
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

StudyTE95% CIn casesn exposedweightROBABCDEF Cohen (Oxcarbazepine) (Epilepsy) (Controls unexposed, NOS), 2023Cohen, 2023 1 1.47[1.13; 1.92]147,9861,31368%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Hosny (Oxcarbazepine) (Controls unexposed, sick), 2021Hosny, 2021 2 2.60[0.08; 82.80]131%ROB confusion: criticalROB selection: moderateROB classification: unclearROB missing: lowROB mesure: unclearROB reporting: moderate Thomas (Oxcarbazepine) (Controls unexposed, sick), 2021Thomas, 2021 3 1.61[0.60; 4.20]21717%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Vajda (Oxcarbazepine) (Controls unexposed, sick), 2019Vajda, 2019 4 1.85[0.23; 15.04]6192%ROB confusion: seriousROB selection: moderateROB classification: lowROB missing: moderateROB mesure: moderateROB reporting: moderate Tomson (Oxcarbazepine) , 2018Tomson, 2018 5 1.02[0.52; 2.00]8433314%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Veiby (Oxcarbazepine) (Controls unexposed, sick), 2014Veiby, 2014 6 0.69[0.09; 5.06]107512%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: moderateROB reporting: moderate Hernández-Díaz (Oxcarbazepine) (Controls unexposed, disease free), 2012Hernández-Díaz, 2012 7 2.00[0.50; 7.40]91824%ROB confusion: moderateROB selection: lowROB classification: moderateROB missing: moderateROB mesure: moderateROB reporting: moderate Morrow (Oxcarbazepine) (Controls unexposed, sick), 2006Morrow, 2006 8 1.98[0.10; 38.04]871%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Viinikainen (Oxcarbazepine) (Controls unexposed, sick) a, 2006Viinikainen, 2006 9 34.33[0.49; 2389.88]020%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Kaaja (Oxcarbazepine), 2003Kaaja, 2003 10 10.80[1.10; 106.20]391%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Hvas (Oxcarbazepine) (Controls unexposed, sick), 2000Hvas, 2000 11 16.23[0.30; 885.49]070%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Samrén (Oxcarbazepine), 1999Samrén, 1999 12 22.27[0.89; 557.96]2921%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (12 studies) I2 = 2% 1.51[1.17; 1.96]148,2541,9990.2100.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Oxcarbazepine) (Epilepsy) (Controls unexposed, NOS; 2: Oxcarbazepine) (Controls unexposed, sick; 3: Oxcarbazepine) (Controls unexposed, sick; 4: Oxcarbazepine) (Controls unexposed, sick; 5: Oxcarbazepine; 6: Oxcarbazepine) (Controls unexposed, sick; 7: Oxcarbazepine) (Controls unexposed, disease free; 8: Oxcarbazepine) (Controls unexposed, sick; 9: Oxcarbazepine) (Controls unexposed, sick) ; 10: Oxcarbazepine; 11: Oxcarbazepine) (Controls unexposed, sick; 12: Oxcarbazepine;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.51[1.17; 1.96]148,2541,9992%NACohen (Oxcarbazepine) (Epilepsy) (Controls unexposed, NOS), 2023 Hosny (Oxcarbazepine) (Controls unexposed, sick), 2021 Thomas (Oxcarbazepine) (Controls unexposed, sick), 2021 Vajda (Oxcarbazepine) (Controls unexposed, sick), 2019 Tomson (Oxcarbazepine) , 2018 Veiby (Oxcarbazepine) (Controls unexposed, sick), 2014 Hernández-Díaz (Oxcarbazepine) (Controls unexposed, disease free), 2012 Morrow (Oxcarbazepine) (Controls unexposed, sick), 2006 Viinikainen (Oxcarbazepine) (Controls unexposed, sick) a, 2006 Kaaja (Oxcarbazepine), 2003 Hvas (Oxcarbazepine) (Controls unexposed, sick), 2000 Samrén (Oxcarbazepine), 1999 12 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.81[0.86; 3.83]148,0241,49731%NACohen (Oxcarbazepine) (Epilepsy) (Controls unexposed, NOS), 2023 Hernández-Díaz (Oxcarbazepine) (Controls unexposed, disease free), 2012 Samrén (Oxcarbazepine), 1999 3 unexposed, sickunexposed, sick 2.12[1.05; 4.26]1461690%NAHosny (Oxcarbazepine) (Controls unexposed, sick), 2021 Thomas (Oxcarbazepine) (Controls unexposed, sick), 2021 Vajda (Oxcarbazepine) (Controls unexposed, sick), 2019 Veiby (Oxcarbazepine) (Controls unexposed, sick), 2014 Morrow (Oxcarbazepine) (Controls unexposed, sick), 2006 Viinikainen (Oxcarbazepine) (Controls unexposed, sick) a, 2006 Kaaja (Oxcarbazepine), 2003 Hvas (Oxcarbazepine) (Controls unexposed, sick), 2000 8 exposed to other treatment, sickexposed to other treatment, sick 1.02[0.52; 2.00]84333 -NATomson (Oxcarbazepine) , 2018 1 Tags Adjustment   - No  - No 1.46[1.16; 1.85]148,2301,9190%NACohen (Oxcarbazepine) (Epilepsy) (Controls unexposed, NOS), 2023 Hosny (Oxcarbazepine) (Controls unexposed, sick), 2021 Vajda (Oxcarbazepine) (Controls unexposed, sick), 2019 Tomson (Oxcarbazepine) , 2018 Veiby (Oxcarbazepine) (Controls unexposed, sick), 2014 Hernández-Díaz (Oxcarbazepine) (Controls unexposed, disease free), 2012 Morrow (Oxcarbazepine) (Controls unexposed, sick), 2006 Viinikainen (Oxcarbazepine) (Controls unexposed, sick) a, 2006 Hvas (Oxcarbazepine) (Controls unexposed, sick), 2000 Samrén (Oxcarbazepine), 1999 10   - Yes  - Yes 3.11[0.53; 18.37]248056%NAThomas (Oxcarbazepine) (Controls unexposed, sick), 2021 Kaaja (Oxcarbazepine), 2003 2 MatchedMatched 22.27[0.89; 557.96]292 -NASamrén (Oxcarbazepine), 1999 1 Partial overlappingPartial overlapping 1.46[1.12; 1.89]148,0931,3640%NACohen (Oxcarbazepine) (Epilepsy) (Controls unexposed, NOS), 2023 Veiby (Oxcarbazepine) (Controls unexposed, sick), 2014 2 All studiesAll studies 1.51[1.17; 1.96]148,2541,9992%NACohen (Oxcarbazepine) (Epilepsy) (Controls unexposed, NOS), 2023 Hosny (Oxcarbazepine) (Controls unexposed, sick), 2021 Thomas (Oxcarbazepine) (Controls unexposed, sick), 2021 Vajda (Oxcarbazepine) (Controls unexposed, sick), 2019 Tomson (Oxcarbazepine) , 2018 Veiby (Oxcarbazepine) (Controls unexposed, sick), 2014 Hernández-Díaz (Oxcarbazepine) (Controls unexposed, disease free), 2012 Morrow (Oxcarbazepine) (Controls unexposed, sick), 2006 Viinikainen (Oxcarbazepine) (Controls unexposed, sick) a, 2006 Kaaja (Oxcarbazepine), 2003 Hvas (Oxcarbazepine) (Controls unexposed, sick), 2000 Samrén (Oxcarbazepine), 1999 120.2100.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-5.15.52.5980.000Cohen (Oxcarbazepine) (Epilepsy) (Controls unexposed, NOS), 2023Hosny (Oxcarbazepine) (Controls unexposed, sick), 2021Thomas (Oxcarbazepine) (Controls unexposed, sick), 2021Vajda (Oxcarbazepine) (Controls unexposed, sick), 2019Tomson (Oxcarbazepine) , 2018Veiby (Oxcarbazepine) (Controls unexposed, sick), 2014Hernández-Díaz (Oxcarbazepine) (Controls unexposed, disease free), 2012Morrow (Oxcarbazepine) (Controls unexposed, sick), 2006Viinikainen (Oxcarbazepine) (Controls unexposed, sick) a, 2006Kaaja (Oxcarbazepine), 2003Hvas (Oxcarbazepine) (Controls unexposed, sick), 2000Samrén (Oxcarbazepine), 1999

Asymetry test p-value = 0.0456 (by Egger's regression)

slope=0.2117 (0.1312); intercept=0.7454 (0.3266); t=2.2823; p=0.0456

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

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

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.54[1.20; 1.97]170,6901,5960%NACohen (Oxcarbazepine) (Epilepsy) (Controls unexposed, NOS), 2023 Thomas (Oxcarbazepine) (Controls unexposed, disease free), 2021 Veiby (Oxcarbazepine) (Controls unexposed, disease free), 2014 Hernández-Díaz (Oxcarbazepine) (Controls unexposed, disease free), 2012 Hvas (Oxcarbazepine) (Controls unexposed, disease free), 2000 Samrén (Oxcarbazepine), 1999 6 unexposed, sick controlsunexposed, sick controls 2.12[1.05; 4.26]1461690%NAHosny (Oxcarbazepine) (Controls unexposed, sick), 2021 Thomas (Oxcarbazepine) (Controls unexposed, sick), 2021 Vajda (Oxcarbazepine) (Controls unexposed, sick), 2019 Veiby (Oxcarbazepine) (Controls unexposed, sick), 2014 Morrow (Oxcarbazepine) (Controls unexposed, sick), 2006 Viinikainen (Oxcarbazepine) (Controls unexposed, sick) a, 2006 Kaaja (Oxcarbazepine), 2003 Hvas (Oxcarbazepine) (Controls unexposed, sick), 2000 8 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.10[0.87; 1.40]5281,7970%NACohen (Oxcarbazepine) (Epilepsy) (Controls exposed to LTG), 2023 Hosny (Oxcarbazepine) (Controls exposed to Lamotrigine, sick), 2021 Thomas (Oxcarbazepine) (Controls exposed to Lamotrigine, sick), 2021 Vajda (Oxcarbazepine) (Controls exposed to Lamotrigine, sick), 2019 Tomson (Oxcarbazepine) , 2018 Veiby (Oxcarbazepine) (Controls exposed to Lamotrigine, sick), 2014 Hernández-Díaz (Oxcarbazepine) (Controls exposed to Lamotrigine, sick), 2012 Morrow (Oxcarbazepine) (Controls exposed to Lamotrigine, sick), 2006 80.510.01.0