Carbamazepine (All indications)

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.
S15367
R63240		 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
S15368
R63253		 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
S12674
R47888		 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
S9605
R34052		 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
S9604
R34048		 Barqawi (Carbamazepine), 2005 Minor congenital anomalies during pregnancy (anytime or not specified) excluded retrospective cohort unexposed, sick Adjustment: No 13.70 [0.67;279.25] C
excluded (exposition period) 		4/16   0/18 4 16
ref
S9614
R34144		 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
S9651
R34340		 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
S9768
R34929		 Nulman (Carbamazepine) (Controls unexposed, NOS) (Mixed indications), 1997 Minor anomalies at least 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No Matched 3.71 [1.27;10.85] C 26/33   17/34 43 33
ref
S9654
R34364		 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
S9740
R34705		 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
S9741
R34730		 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
S9670
R34432		 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 7 studies 2.63 [1.25;5.54] 118 244
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]3295%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: unclear Dean (Carbamazepine), 2002Dean, 2002 2 3.67[1.27; 10.58]307028%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Wide (Carbamazepine), 2000Wide, 2000 3 11.00[1.42; 85.20]203911%ROB confusion: criticalROB selection: moderateROB classification: lowROB missing: lowROB mesure: moderateROB reporting: moderate Nulman (Carbamazepine) (Controls unexposed, NOS) (Mixed indications), 1997Nulman, 1997 4 3.71[1.27; 10.85]433328%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Battino (Carbamazepine), 1992Battino, 1992 5 1.75[0.09; 34.55]5596%ROB confusion: criticalROB selection: moderateROB classification: lowROB missing: lowROB mesure: moderateROB reporting: moderate Van der Pol (Carbamazepine) (Controls unexposed, sick), 1991Van der Pol, 1991 6 0.45[0.09; 2.16]131117%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Robert (Carbamazepine), 1986Robert, 1986 7 1.36[0.06; 33.05]435%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (7 studies) I2 = 22% 2.63[1.25; 5.54]1182440.250.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Carbamazepine; 2: Carbamazepine; 3: Carbamazepine; 4: Carbamazepine) (Controls unexposed, NOS) (Mixed indications; 5: Carbamazepine; 6: Carbamazepine) (Controls unexposed, sick; 7: Carbamazepine;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 2.63[1.25; 5.54]11824422%NAMari (Carbamazepine), 2022 Dean (Carbamazepine), 2002 Wide (Carbamazepine), 2000 Nulman (Carbamazepine) (Controls unexposed, NOS) (Mixed indications), 1997 Battino (Carbamazepine), 1992 Van der Pol (Carbamazepine) (Controls unexposed, sick), 1991 Robert (Carbamazepine), 1986 7 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 4.69[1.82; 12.12]63720%NAWide (Carbamazepine), 2000 Nulman (Carbamazepine) (Controls unexposed, NOS) (Mixed indications), 1997 2 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 2.63[1.25; 5.54]11824422%NAMari (Carbamazepine), 2022 Dean (Carbamazepine), 2002 Wide (Carbamazepine), 2000 Nulman (Carbamazepine) (Controls unexposed, NOS) (Mixed indications), 1997 Battino (Carbamazepine), 1992 Van der Pol (Carbamazepine) (Controls unexposed, sick), 1991 Robert (Carbamazepine), 1986 7 MatchedMatched 4.69[1.82; 12.12]63720%NAWide (Carbamazepine), 2000 Nulman (Carbamazepine) (Controls unexposed, NOS) (Mixed indications), 1997 2 All studiesAll studies 2.63[1.25; 5.54]11824422%NAMari (Carbamazepine), 2022 Dean (Carbamazepine), 2002 Wide (Carbamazepine), 2000 Nulman (Carbamazepine) (Controls unexposed, NOS) (Mixed indications), 1997 Battino (Carbamazepine), 1992 Van der Pol (Carbamazepine) (Controls unexposed, sick), 1991 Robert (Carbamazepine), 1986 70.250.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-3.84.81.9550.000Mari (Carbamazepine), 2022Dean (Carbamazepine), 2002Wide (Carbamazepine), 2000Nulman (Carbamazepine) (Controls unexposed, NOS) (Mixed indications), 1997Battino (Carbamazepine), 1992Van der Pol (Carbamazepine) (Controls unexposed, sick), 1991Robert (Carbamazepine), 1986

Asymetry test p-value = 0.6972 (by Egger's regression)

slope=1.3561 (0.9178); intercept=-0.4626 (1.1219); t=0.4123; p=0.6972

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 9740, 15367

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 3.51[1.52; 8.10]76836%NAWide (Carbamazepine), 2000 Nulman (Carbamazepine) (Controls unexposed, NOS) (Mixed indications), 1997 Van der Pol (Carbamazepine) (Controls unexposed, disease free), 1991 3 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