Carbamazepine (All indications)

Limb defects

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.
S12856
R48499		 Thomas (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2021 Skeletal malformations 1st trimester prospective cohort exposed to other treatment, sick excluded Adjustment: No 0.92 [0.05;17.29] C
excluded (control group) 		4/490   0/50 4 490
ref
S12858
R48511		 Thomas (Carbamazepine) (Controls unexposed, sick), 2021 Skeletal malformations 1st trimester prospective cohort unexposed, sick Adjustment: No 1.39 [0.25;7.64] C 4/490   2/340 6 490
ref
S9763
R34865		 Ban (Carbamazepine) (Mixed indications) (Controls exposed to Lamotrigine, sick), 2015 Limb anomaly 1st trimester prospective cohort exposed to other treatment, sick excluded Adjustment: No 0.79 [0.11;5.68] C
excluded (control group) 		2/343   2/273 4 343
ref
S9764
R34871		 Ban (Carbamazepine) (Mixed indications) (Controls unexposed NOS), 2015 Limb anomaly 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No 1.19 [0.30;4.78] C 2/343   1,263/257,153 1,265 343
ref
S9655
R34370		 Campbell (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2014 Skeletal defects 1st trimester prospective cohort exposed to other treatment, sick Adjustment: No 1.69 [0.38;7.56] C 4/1,657   3/2,098 7 1,657
ref
S9643
R34311		 Veiby (Carbamazepine) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014 Musculoskeletal throughout pregnancy population based cohort retrospective exposed to other treatment, sick Adjustment: No 1.14 [0.55;2.37] C 14/685   15/833 29 685
ref
S10290
R37676		 Vajda (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2013 Skeletal / Limb Malformations at least 1st trimester prospective cohort exposed to other treatment, sick excluded Adjustment: No 4.39 [0.21;91.71] C
excluded (control group) 		2/361   0/315 2 361
ref
S10291
R37682		 Vajda (Carbamazepine) (Controls unexposed, sick), 2013 Skeletal / Limb Malformations at least 1st trimester prospective cohort unexposed, sick Adjustment: No 0.81 [0.07;9.04] C 2/361   1/147 3 361
ref
S9628
R35309		 Mawer (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2010 Skeletal / Limb Malformations 1st trimester prospective cohort exposed to other treatment, sick excluded Adjustment: No 0.18 [0.01;4.55] C
excluded (control group) 		0/66   1/37 1 66
ref
S9629
R35313		 Mawer (Carbamazepine) (Controls unexposed, disease free), 2010 Skeletal / Limb Malformations 1st trimester prospective cohort unexposed, disease free excluded Adjustment: No Matched 4.34 [0.09;220.94] C
excluded (control group) 		0/66   0/285 0 66
ref
S9630
R35317		 Mawer (Carbamazepine) (Controls unexposed, sick), 2010 Skeletal / Limb Malformations 1st trimester prospective cohort unexposed, sick Adjustment: No 0.62 [0.01;31.78] C 0/66   0/41 0 66
ref
S9652
R35927		 Artama (Carbamazepine), 2005 Certain musculoskeletal deformities and Other anomalies of limbs 1st trimester retrospective cohort (registry) unexposed, sick Adjustment: No 1.51 [0.56;4.06] C 9/805   7/939 16 805
ref
Total 7 studies 1.26 [0.78;2.03] 1,326 4,407
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 Thomas (Carbamazepine) (Controls unexposed, sick), 2021Thomas, 2021 1 1.39[0.25; 7.64]64908%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Ban (Carbamazepine) (Mixed indications) (Controls unexposed NOS), 2015Ban, 2015 2 1.19[0.30; 4.78]1,26534312%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Campbell (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2014Campbell, 2014 3 1.69[0.38; 7.56]71,65710%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Veiby (Carbamazepine) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014Veiby, 2014 4 1.14[0.55; 2.37]2968542%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: moderateROB reporting: moderate Vajda (Carbamazepine) (Controls unexposed, sick), 2013Vajda, 2013 5 0.81[0.07; 9.04]33614%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Mawer (Carbamazepine) (Controls unexposed, sick), 2010Mawer, 2010 6 0.62[0.01; 31.78]0661%ROB confusion: criticalROB selection: moderateROB classification: lowROB missing: moderateROB mesure: moderateROB reporting: moderate Artama (Carbamazepine), 2005Artama, 2005 7 1.51[0.56; 4.06]1680523%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (7 studies) I2 = 0% 1.26[0.78; 2.03]1,3264,4070.25.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

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

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.26[0.78; 2.03]1,3264,4070%NAThomas (Carbamazepine) (Controls unexposed, sick), 2021 Ban (Carbamazepine) (Mixed indications) (Controls unexposed NOS), 2015 Campbell (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2014 Veiby (Carbamazepine) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014 Vajda (Carbamazepine) (Controls unexposed, sick), 2013 Mawer (Carbamazepine) (Controls unexposed, sick), 2010 Artama (Carbamazepine), 2005 7 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.19[0.30; 4.78]1,265343 -NABan (Carbamazepine) (Mixed indications) (Controls unexposed NOS), 2015 1 unexposed, sickunexposed, sick 1.34[0.61; 2.95]251,7220%NAThomas (Carbamazepine) (Controls unexposed, sick), 2021 Vajda (Carbamazepine) (Controls unexposed, sick), 2013 Mawer (Carbamazepine) (Controls unexposed, sick), 2010 Artama (Carbamazepine), 2005 4 exposed to other treatment, sickexposed to other treatment, sick 1.23[0.63; 2.38]362,3420%NACampbell (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2014 Veiby (Carbamazepine) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014 2 Tags Adjustment   - No  - No 1.26[0.78; 2.03]1,3264,4070%NAThomas (Carbamazepine) (Controls unexposed, sick), 2021 Ban (Carbamazepine) (Mixed indications) (Controls unexposed NOS), 2015 Campbell (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2014 Veiby (Carbamazepine) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014 Vajda (Carbamazepine) (Controls unexposed, sick), 2013 Mawer (Carbamazepine) (Controls unexposed, sick), 2010 Artama (Carbamazepine), 2005 7 All studiesAll studies 1.26[0.78; 2.03]1,3264,4070%NAThomas (Carbamazepine) (Controls unexposed, sick), 2021 Ban (Carbamazepine) (Mixed indications) (Controls unexposed NOS), 2015 Campbell (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2014 Veiby (Carbamazepine) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014 Vajda (Carbamazepine) (Controls unexposed, sick), 2013 Mawer (Carbamazepine) (Controls unexposed, sick), 2010 Artama (Carbamazepine), 2005 70.25.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-4.75.02.4120.000Thomas (Carbamazepine) (Controls unexposed, sick), 2021Ban (Carbamazepine) (Mixed indications) (Controls unexposed NOS), 2015Campbell (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2014Veiby (Carbamazepine) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014Vajda (Carbamazepine) (Controls unexposed, sick), 2013Mawer (Carbamazepine) (Controls unexposed, sick), 2010Artama (Carbamazepine), 2005

Asymetry test p-value = 0.5834 (by Egger's regression)

slope=0.3333 (0.1912); intercept=-0.1742 (0.2973); t=0.5858; p=0.5834

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 9628, 9629, 10290, 9763, 12856

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.37[0.37; 5.09]1,2654090%NABan (Carbamazepine) (Mixed indications) (Controls unexposed NOS), 2015 Mawer (Carbamazepine) (Controls unexposed, disease free), 2010 2 unexposed, sick controlsunexposed, sick controls 1.34[0.61; 2.95]251,7220%NAThomas (Carbamazepine) (Controls unexposed, sick), 2021 Vajda (Carbamazepine) (Controls unexposed, sick), 2013 Mawer (Carbamazepine) (Controls unexposed, sick), 2010 Artama (Carbamazepine), 2005 4 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.15[0.64; 2.07]473,6020%NAThomas (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2021 Ban (Carbamazepine) (Mixed indications) (Controls exposed to Lamotrigine, sick), 2015 Campbell (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2014 Veiby (Carbamazepine) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014 Vajda (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2013 Mawer (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2010 60.510.01.0