Carbamazepine (Epilepsy)

Minor 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.
S15365
R63214
Bromley (Carbamazepine) (Epilepsy) (Controls exposed to LTG), 2023 Minor congenital anomaly during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick excluded Adjustment: No 0.47 [0.06;3.94] C
excluded (control group)
1/27   8/106 9 27
ref
S15366
R63227
Bromley (Carbamazepine) (Epilepsy) (Controls unexposed, sick), 2023 Minor congenital anomaly during pregnancy (anytime or not specified) excluded prospective cohort unexposed, sick Adjustment: No 3.04 [0.18;50.32] C
excluded (exposition period)
1/27   1/80 2 27
ref
S12675
R47898
Mari (Carbamazepine), 2022 Minor congenital malformations throughout pregnancy retrospective cohort exposed to other treatment, sick Adjustment: No 2.88 [0.14;60.81] C 3/29   0/11 3 29
ref
S314
R18999
Barroso (Carbamazepine), 2015 Minor anomalies during pregnancy (anytime or not specified) excluded retrospective cohort unexposed, disease free Adjustment: No 12.44 [2.15;72.06] C
excluded (exposition period)
2/12   5/316 7 12
ref
S313
R18996
Barqawi (Carbamazepine), 2005 Minor congenital anomalies during pregnancy (anytime or not specified) excluded prospective cohort unexposed, sick Adjustment: No 13.70 [0.67;279.25] C
excluded (exposition period)
4/16   0/18 4 16
ref
S336
R18021
Dean (Carbamazepine), 2002 Minor congenital malformations at least 1st trimester retrospective cohort unexposed, sick Adjustment: No 3.67 [1.27;10.58] C 25/70   5/38 30 70
ref
S6298
R17070
Wide (Carbamazepine), 2000 Minor anomalies throughout pregnancy prospective cohort unexposed (general population or NOS) Adjustment: No Matched 11.00 [1.42;85.20] 15/39   5/37 20 39
ref
S7269
R21038
Battino (Carbamazepine), 1992 Minor anomalies 1st trimester prospective cohort unexposed, sick Adjustment: No 1.75 [0.09;34.55] C 5/59   0/9 5 59
ref
S6823
R19286
Van der Pol (Carbamazepine) (Controls unexposed, disease free), 1991 Waldrop score >2 throughout pregnancy prospective cohort unexposed, disease free excluded Adjustment: No Matched 1.69 [0.38;7.51] C
excluded (control group)
3/11   10/55 13 11
ref
S6825
R19336
Van der Pol (Carbamazepine) (Controls unexposed, sick), 1991 Waldrop score >2 throughout pregnancy prospective cohort unexposed, sick Adjustment: No 0.45 [0.09;2.16] C 3/11   10/22 13 11
ref
S6164
R16217
Robert (Carbamazepine), 1986 Minor malformations 1st trimester retrospective cohort unexposed, sick Adjustment: No 1.36 [0.06;33.05] C 0/3   4/35 4 3
ref
Total 6 studies 2.28 [0.84;6.14] 75 211
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 Mari (Carbamazepine), 2022Mari, 2022 1 2.88[0.14; 60.81]3299%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: unclear Dean (Carbamazepine), 2002Dean, 2002 2 3.67[1.27; 10.58]307034%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Wide (Carbamazepine), 2000Wide, 2000 3 11.00[1.42; 85.20]203917%ROB confusion: criticalROB selection: moderateROB classification: lowROB missing: lowROB mesure: moderateROB reporting: moderate Battino (Carbamazepine), 1992Battino, 1992 4 1.75[0.09; 34.55]5599%ROB confusion: criticalROB selection: moderateROB classification: lowROB missing: lowROB mesure: moderateROB reporting: moderate Van der Pol (Carbamazepine) (Controls unexposed, sick), 1991Van der Pol, 1991 5 0.45[0.09; 2.16]131123%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Robert (Carbamazepine), 1986Robert, 1986 6 1.36[0.06; 33.05]438%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (6 studies) I2 = 31% 2.28[0.84; 6.14]752110.250.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Carbamazepine; 2: Carbamazepine; 3: Carbamazepine; 4: Carbamazepine; 5: Carbamazepine) (Controls unexposed, sick; 6: Carbamazepine;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 2.28[0.84; 6.14]7521131%NAMari (Carbamazepine), 2022 Dean (Carbamazepine), 2002 Wide (Carbamazepine), 2000 Battino (Carbamazepine), 1992 Van der Pol (Carbamazepine) (Controls unexposed, sick), 1991 Robert (Carbamazepine), 1986 6 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 11.00[1.42; 85.21]2039 -NAWide (Carbamazepine), 2000 1 unexposed, sickunexposed, sick 1.54[0.47; 5.06]5214337%NADean (Carbamazepine), 2002 Battino (Carbamazepine), 1992 Van der Pol (Carbamazepine) (Controls unexposed, sick), 1991 Robert (Carbamazepine), 1986 4 exposed to other treatment, sickexposed to other treatment, sick 2.88[0.14; 60.81]329 -NAMari (Carbamazepine), 2022 1 Tags Adjustment   - No  - No 2.28[0.84; 6.14]7521131%NAMari (Carbamazepine), 2022 Dean (Carbamazepine), 2002 Wide (Carbamazepine), 2000 Battino (Carbamazepine), 1992 Van der Pol (Carbamazepine) (Controls unexposed, sick), 1991 Robert (Carbamazepine), 1986 6 MatchedMatched 11.00[1.42; 85.21]2039 -NAWide (Carbamazepine), 2000 1 All studiesAll studies 2.28[0.84; 6.14]7521131%NAMari (Carbamazepine), 2022 Dean (Carbamazepine), 2002 Wide (Carbamazepine), 2000 Battino (Carbamazepine), 1992 Van der Pol (Carbamazepine) (Controls unexposed, sick), 1991 Robert (Carbamazepine), 1986 60.250.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-3.84.71.9550.000Mari (Carbamazepine), 2022Dean (Carbamazepine), 2002Wide (Carbamazepine), 2000Battino (Carbamazepine), 1992Van der Pol (Carbamazepine) (Controls unexposed, sick), 1991Robert (Carbamazepine), 1986

Asymetry test p-value = 0.8580 (by Egger's regression)

slope=1.0854 (1.2375); intercept=-0.2571 (1.3476); t=0.1908; p=0.8580

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 6823, 15365

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 3.76[0.61; 23.15]335052%NAWide (Carbamazepine), 2000 Van der Pol (Carbamazepine) (Controls unexposed, disease free), 1991 2 unexposed, sick controlsunexposed, sick controls 1.54[0.47; 5.06]5214337%NADean (Carbamazepine), 2002 Battino (Carbamazepine), 1992 Van der Pol (Carbamazepine) (Controls unexposed, sick), 1991 Robert (Carbamazepine), 1986 4 exposed to other treatment, sick controlsexposed to other treatment, sick controls 2.88[0.14; 60.81]329 -NAMari (Carbamazepine), 2022 10.510.01.0