Oxcarbazepine (All indications)

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.
S15202
R62356		 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
S15203
R62357		 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
S15261
R62746		 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
S15262
R62747		 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
S9046
R30883		 The NAAED (Controls exposed to Lamotrigine, sick) (Indications NOS), 2022 Major congenital malformations 1st trimester prospective cohort exposed to other treatment, sick excluded Adjustment: No 0.87 [0.34;2.21] C
excluded (control group) 		5/304   44/2,333 49 304
ref
S9047
R30885		 The NAAED (Controls unexposed, disease free) (Indications NOS), 2022 Major congenital malformations 1st trimester prospective cohort unexposed, disease free Adjustment: No 1.66 [0.58;4.74] C 5/304   12/1,201 17 304
ref
S12890
R48707		 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
S12891
R48710		 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
S12831
R48319		 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
S12832
R48327		 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
S12833
R48331		 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
S9034
R30796		 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
S9035
R30799		 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
S9075
R31070		 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
S9076
R31071		 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
S9074
R31060		 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
S9042
R30870		 Bank (Oxcarbazepine) (Mixed indications), 2017 Major Malformation during pregnancy (anytime or not specified) excluded prospective cohort exposed to other treatment, sick Adjustment: No 10.14 [0.17;594.47] C
excluded (exposition period) 		0/4   0/36 0 4
ref
S9052
R30897		 Veiby (Oxcarbazepine) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014 Major congenital malformation throughout pregnancy population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No Partial overlapping 0.51 [0.07;3.84] C
excluded (control group) 		1/57   28/833 29 57
ref
S9053
R30899		 Veiby (Oxcarbazepine) (Controls unexposed, disease free) (Mixed indications), 2014 Major malformations throughout pregnancy population based cohort retrospective unexposed, disease free excluded Adjustment: Yes Partial overlapping 0.64 [0.10;4.61]
excluded (control group) 		1/57   22,371/771,412 22,372 57
ref
S9054
R30901		 Veiby (Oxcarbazepine) (Controls unexposed, sick) (Mixed indications), 2014 Major malformations throughout pregnancy population based cohort retrospective unexposed, sick Adjustment: No Controls: epilepsy indication Partial overlapping 0.62 [0.08;4.50] C 1/57   106/3,773 107 57
ref
S9050
R30891		 Källén (Oxcarbazepine) (Controls exposed to Lamotrigine, sick) (Indications NOS), 2013 Relatively severe malformations early pregnancy population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No Partial overlapping 3.14 [1.06;9.29] C
excluded (control group) 		4/40   37/1,084 41 40
ref
S9051
R30893		 Källén (Oxcarbazepine) (Controls unexposed, NOS) (Indications NOS), 2013 Relatively severe malformations early pregnancy population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Partial overlapping 2.27 [0.62;5.82] 4/40   49,499/1,575,847 49,503 40
ref
S9059
R30927		 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
S9060
R30929		 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
S9061
R30931		 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
S9062
R30933		 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
S9063
R30941		 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
S9065
R30944		 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
S9058
R30925		 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
S9048
R30887		 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
S9049
R30889		 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
S9070
R31052		 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 13 studies 1.52 [1.22;1.89] 197,765 2,167
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]147,9861,31370%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate The NAAED (Controls unexposed, disease free) (Indications NOS), 2022The NAAED, 2022 2 1.66[0.58; 4.74]173044%ROB confusion: criticalROB selection: unclearROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: low Hosny (Oxcarbazepine) (Controls unexposed, sick), 2021Hosny, 2021 3 2.60[0.08; 82.80]130%ROB confusion: criticalROB selection: moderateROB classification: unclearROB missing: lowROB mesure: unclearROB reporting: moderate Thomas (Oxcarbazepine) (Controls unexposed, sick), 2021Thomas, 2021 4 1.61[0.60; 4.20]21715%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Vajda (Oxcarbazepine) (Controls unexposed, sick), 2019Vajda, 2019 5 1.85[0.23; 15.04]6191%ROB confusion: criticalROB selection: moderateROB classification: lowROB missing: moderateROB mesure: moderateROB reporting: moderate Tomson (Oxcarbazepine), 2018Tomson, 2018 6 1.02[0.52; 2.00]8433311%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Veiby (Oxcarbazepine) (Controls unexposed, sick) (Mixed indications), 2014Veiby, 2014 7 0.62[0.08; 4.50]107571%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: moderateROB reporting: moderate Källén (Oxcarbazepine) (Controls unexposed, NOS) (Indications NOS), 2013Källén, 2013 8 2.27[0.62; 5.82]49,503404%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Morrow (Oxcarbazepine) (Controls unexposed, sick), 2006Morrow, 2006 9 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 10 34.33[0.49; 2389.88]020%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Kaaja (Oxcarbazepine), 2003Kaaja, 2003 11 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 12 16.23[0.30; 885.49]070%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Samrén (Oxcarbazepine), 1999Samrén, 1999 13 22.27[0.89; 557.96]2920%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (13 studies) I2 = 0% 1.52[1.22; 1.89]197,7652,1670.2100.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Oxcarbazepine) (Epilepsy) (Controls unexposed, NOS; 2: Controls unexposed, disease free) (Indications NOS; 3: Oxcarbazepine) (Controls unexposed, sick; 4: Oxcarbazepine) (Controls unexposed, sick; 5: Oxcarbazepine) (Controls unexposed, sick; 6: Oxcarbazepine; 7: Oxcarbazepine) (Controls unexposed, sick) (Mixed indications; 8: Oxcarbazepine) (Controls unexposed, NOS) (Indications NOS; 9: Oxcarbazepine) (Controls unexposed, sick; 10: Oxcarbazepine) (Controls unexposed, sick) ; 11: Oxcarbazepine; 12: Oxcarbazepine) (Controls unexposed, sick; 13: Oxcarbazepine;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.52[1.22; 1.89]197,7652,1670%NACohen (Oxcarbazepine) (Epilepsy) (Controls unexposed, NOS), 2023 The NAAED (Controls unexposed, disease free) (Indications NOS), 2022 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) (Mixed indications), 2014 Källén (Oxcarbazepine) (Controls unexposed, NOS) (Indications NOS), 2013 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 13 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.59[1.14; 2.22]197,5351,6597%NACohen (Oxcarbazepine) (Epilepsy) (Controls unexposed, NOS), 2023 The NAAED (Controls unexposed, disease free) (Indications NOS), 2022 Källén (Oxcarbazepine) (Controls unexposed, NOS) (Indications NOS), 2013 Samrén (Oxcarbazepine), 1999 4 unexposed, sickunexposed, sick 2.09[1.04; 4.20]1461750%NAHosny (Oxcarbazepine) (Controls unexposed, sick), 2021 Thomas (Oxcarbazepine) (Controls unexposed, sick), 2021 Vajda (Oxcarbazepine) (Controls unexposed, sick), 2019 Veiby (Oxcarbazepine) (Controls unexposed, sick) (Mixed indications), 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[1.15; 1.84]148,2382,0470%NACohen (Oxcarbazepine) (Epilepsy) (Controls unexposed, NOS), 2023 The NAAED (Controls unexposed, disease free) (Indications NOS), 2022 Hosny (Oxcarbazepine) (Controls unexposed, sick), 2021 Vajda (Oxcarbazepine) (Controls unexposed, sick), 2019 Tomson (Oxcarbazepine), 2018 Veiby (Oxcarbazepine) (Controls unexposed, sick) (Mixed indications), 2014 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 2.26[1.05; 4.85]49,52712012%NAThomas (Oxcarbazepine) (Controls unexposed, sick), 2021 Källén (Oxcarbazepine) (Controls unexposed, NOS) (Indications NOS), 2013 Kaaja (Oxcarbazepine), 2003 3 Controls   - epilepsy indication  - epilepsy indication 0.62[0.08; 4.50]10757 -NAVeiby (Oxcarbazepine) (Controls unexposed, sick) (Mixed indications), 2014 1 MatchedMatched 22.27[0.89; 557.96]292 -NASamrén (Oxcarbazepine), 1999 1 Partial overlappingPartial overlapping 1.49[1.15; 1.92]197,5961,4100%NACohen (Oxcarbazepine) (Epilepsy) (Controls unexposed, NOS), 2023 Veiby (Oxcarbazepine) (Controls unexposed, sick) (Mixed indications), 2014 Källén (Oxcarbazepine) (Controls unexposed, NOS) (Indications NOS), 2013 3 All studiesAll studies 1.52[1.22; 1.89]197,7652,1670%NACohen (Oxcarbazepine) (Epilepsy) (Controls unexposed, NOS), 2023 The NAAED (Controls unexposed, disease free) (Indications NOS), 2022 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) (Mixed indications), 2014 Källén (Oxcarbazepine) (Controls unexposed, NOS) (Indications NOS), 2013 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 130.2100.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-5.15.52.5980.000Cohen (Oxcarbazepine) (Epilepsy) (Controls unexposed, NOS), 2023The NAAED (Controls unexposed, disease free) (Indications NOS), 2022Hosny (Oxcarbazepine) (Controls unexposed, sick), 2021Thomas (Oxcarbazepine) (Controls unexposed, sick), 2021Vajda (Oxcarbazepine) (Controls unexposed, sick), 2019Tomson (Oxcarbazepine), 2018Veiby (Oxcarbazepine) (Controls unexposed, sick) (Mixed indications), 2014Källén (Oxcarbazepine) (Controls unexposed, NOS) (Indications NOS), 2013Morrow (Oxcarbazepine) (Controls unexposed, sick), 2006Viinikainen (Oxcarbazepine) (Controls unexposed, sick) a, 2006Kaaja (Oxcarbazepine), 2003Hvas (Oxcarbazepine) (Controls unexposed, sick), 2000Samrén (Oxcarbazepine), 1999

Asymetry test p-value = 0.0380 (by Egger's regression)

slope=0.2129 (0.1288); intercept=0.7474 (0.3170); t=2.3575; p=0.0380

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 9048, 9062, 9059, 9060, 9050, 9052, 9053, 9075, 9034, 12890, 12831, 12832, 9046, 15202, 15261

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.55[1.22; 1.98]220,2011,7640%NACohen (Oxcarbazepine) (Epilepsy) (Controls unexposed, NOS), 2023 The NAAED (Controls unexposed, disease free) (Indications NOS), 2022 Thomas (Oxcarbazepine) (Controls unexposed, disease free), 2021 Veiby (Oxcarbazepine) (Controls unexposed, disease free) (Mixed indications), 2014 Källén (Oxcarbazepine) (Controls unexposed, NOS) (Indications NOS), 2013 Hvas (Oxcarbazepine) (Controls unexposed, disease free), 2000 Samrén (Oxcarbazepine), 1999 7 unexposed, sick controlsunexposed, sick controls 2.09[1.04; 4.20]1461750%NAHosny (Oxcarbazepine) (Controls unexposed, sick), 2021 Thomas (Oxcarbazepine) (Controls unexposed, sick), 2021 Vajda (Oxcarbazepine) (Controls unexposed, sick), 2019 Veiby (Oxcarbazepine) (Controls unexposed, sick) (Mixed indications), 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 1.13[0.89; 1.42]6232,1470%NACohen (Oxcarbazepine) (Epilepsy) (Controls exposed to LTG), 2023 The NAAED (Controls exposed to Lamotrigine, sick) (Indications NOS), 2022 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) (Mixed indications), 2014 Källén (Oxcarbazepine) (Controls exposed to Lamotrigine, sick) (Indications NOS), 2013 Morrow (Oxcarbazepine) (Controls exposed to Lamotrigine, sick), 2006 90.510.01.0