Carbamazepine (All indications)

Congenital heart 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.
S15198
R62336		 Cohen (Carbamazepine) (Mixed indications) (Controls unexposed, NOS), 2023 Cardiac system malformation 1st trimester population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Partial overlapping 0.76 [0.54;1.08] -/2,674   -/4,866,362 - 2,674
ref
S12856
R48496		 Thomas (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2021 Cardiac malformations 1st trimester prospective cohort exposed to other treatment, sick excluded Adjustment: No 0.71 [0.09;5.89] C
excluded (control group) 		7/490   1/50 8 490
ref
S12858
R48508		 Thomas (Carbamazepine) (Controls unexposed, sick), 2021 Cardiac malformations 1st trimester prospective cohort unexposed, sick Adjustment: No 0.53 [0.20;1.45] C 7/490   9/340 16 490
ref
S9678
R34450		 Tomson (Carbamazepine), 2018 Cardiac malformations at least 1st trimester prospective cohort exposed to other treatment, sick Adjustment: No 2.42 [1.29;4.54] C 28/1,957   15/2,514 43 1,957
ref
S9763
R34864		 Ban (Carbamazepine) (Mixed indications) (Controls exposed to Lamotrigine, sick), 2015 Heart anomaly 1st trimester prospective cohort exposed to other treatment, sick excluded Adjustment: No 0.68 [0.22;2.04] C
excluded (control group) 		6/343   7/273 13 343
ref
S9764
R34870		 Ban (Carbamazepine) (Mixed indications) (Controls unexposed NOS), 2015 Heart anomaly 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: Yes 2.21 [0.76;6.40] 6/343   2,041/257,153 2,047 343
ref
S9655
R34368		 Campbell (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2014 Cardiac defects 1st trimester prospective cohort exposed to other treatment, sick Adjustment: No 1.98 [0.85;4.58] C 14/1,657   9/2,098 23 1,657
ref
S9643
R34306		 Veiby (Carbamazepine) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014 Circulatory throughout pregnancy population based cohort retrospective exposed to other treatment, sick Adjustment: No 0.93 [0.41;2.14] C 10/685   13/833 23 685
ref
S9625
R34225		 Källén (Carbamazepine) (Controls exposed to Lamotrigine, sick) (Indications NOS), 2013 Any cardiac defect early pregnancy population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No Partial overlapping 0.93 [0.41;2.13] C
excluded (control group) 		13/1,511   10/1,084 23 1,511
ref
S9626
R34233		 Källén (Carbamazepine) (Controls unexposed, NOS) (Indications NOS), 2013 Any cardiac defect early pregnancy population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Partial overlapping 0.70 [0.41;1.21] 13/1,511   16,145/1,575,847 16,158 1,511
ref
S10290
R37674		 Vajda (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2013 Cardiac Malformations at least 1st trimester prospective cohort exposed to other treatment, sick excluded Adjustment: No 0.87 [0.17;4.35] C
excluded (control group) 		3/361   3/315 6 361
ref
S10291
R37680		 Vajda (Carbamazepine) (Controls unexposed, sick), 2013 Cardiac Malformations at least 1st trimester prospective cohort unexposed, sick Adjustment: No 1.22 [0.13;11.86] C 3/361   1/147 4 361
ref
S9619
R34196		 Hernández-Díaz (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2012 Cardiovascular anomalies 1st trimester prospective cohort exposed to other treatment, sick Adjustment: No Controls: mixed indications 1.51 [0.30;7.51] C 3/1,033   3/1,562 6 1,033
ref
S9653
R34359		 Bànhidy (Carbamazepine), 2011 Cardiovascular congenital abnormalities throughout pregnancy case control unexposed, sick Adjustment: No Matched 0.80 [0.16;3.88] C 4/14   5/15 9 14
ref
S9628
R35307		 Mawer (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2010 Cardiac Malformations 1st trimester prospective cohort exposed to other treatment, sick excluded Adjustment: No 0.56 [0.01;28.68] C
excluded (control group) 		0/66   0/37 0 66
ref
S9629
R35311		 Mawer (Carbamazepine) (Controls unexposed, disease free), 2010 Cardiac Malformations 1st trimester prospective cohort unexposed, disease free excluded Adjustment: No Matched 1.44 [0.06;35.82] C
excluded (control group) 		0/66   1/285 1 66
ref
S9630
R35315		 Mawer (Carbamazepine) (Controls unexposed, sick), 2010 Cardiac Malformations 1st trimester prospective cohort unexposed, sick Adjustment: No 0.62 [0.01;31.78] C 0/66   0/41 0 66
ref
S9652
R34348		 Artama (Carbamazepine), 2005 Cardiovascular 1st trimester retrospective cohort (registry) unexposed, sick Adjustment: No 0.50 [0.13;1.93] C 3/805   7/939 10 805
ref
S9657
R34382		 Canger (Carbamazepine), 1999 Cardiac malformations 1st trimester prospective cohort unexposed, sick Adjustment: No 0.22 [0.00;11.25] C 0/113   0/25 0 113
ref
S9612
R34090		 D'Souza (Carbamazepine) (Controls unexposed, disease free), 1991 Heart disease throughout pregnancy prospective cohort unexposed, disease free excluded Adjustment: No Matched 24.60 [0.40;1512.72] C
excluded (control group) 		0/3   0/62 0 3
ref
S9613
R34119		 D'Souza (Carbamazepine) (Controls unexposed, sick), 1991 Heart disease throughout pregnancy prospective cohort unexposed, sick Adjustment: No 0.87 [0.03;29.20] C 0/3   1/8 1 3
ref
S9740
R34718		 Van der Pol (Carbamazepine) (Controls unexposed, disease free), 1991 Cardiac anomaly throughout pregnancy prospective cohort unexposed, disease free excluded Adjustment: No Matched 5.40 [0.31;93.62] C
excluded (control group) 		1/11   1/55 2 11
ref
S9741
R34743		 Van der Pol (Carbamazepine) (Controls unexposed, sick), 1991 Cardiac anomaly throughout pregnancy prospective cohort unexposed, sick Adjustment: No 6.79 [0.25;182.34] C 1/11   0/22 1 11
ref
Total 15 studies 1.06 [0.76;1.47] 18,341 11,723
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 (Carbamazepine) (Mixed indications) (Controls unexposed, NOS), 2023Cohen, 2023 1 0.76[0.54; 1.08]-2,67420%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Thomas (Carbamazepine) (Controls unexposed, sick), 2021Thomas, 2021 2 0.53[0.20; 1.45]164908%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Tomson (Carbamazepine), 2018Tomson, 2018 3 2.42[1.29; 4.54]431,95713%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Ban (Carbamazepine) (Mixed indications) (Controls unexposed NOS), 2015Ban, 2015 4 2.21[0.76; 6.40]2,0473437%ROB confusion: seriousROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Campbell (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2014Campbell, 2014 5 1.98[0.85; 4.58]231,65710%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Veiby (Carbamazepine) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014Veiby, 2014 6 0.93[0.41; 2.14]2368510%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: moderateROB reporting: moderate Källén (Carbamazepine) (Controls unexposed, NOS) (Indications NOS), 2013Källén, 2013 7 0.70[0.41; 1.21]16,1581,51115%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Vajda (Carbamazepine) (Controls unexposed, sick), 2013Vajda, 2013 8 1.22[0.13; 11.86]43612%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Hernández-Díaz (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2012Hernández-Díaz, 2012 9 1.51[0.30; 7.51]61,0334%ROB confusion: moderateROB selection: lowROB classification: moderateROB missing: moderateROB mesure: moderateROB reporting: moderate Bànhidy (Carbamazepine), 2011Bànhidy, 2011 10 0.80[0.16; 3.88]9144%ROB confusion: criticalROB selection: criticalROB classification: lowROB missing: lowROB mesure: moderateROB reporting: moderate Mawer (Carbamazepine) (Controls unexposed, sick), 2010Mawer, 2010 11 0.62[0.01; 31.78]0661%ROB confusion: criticalROB selection: moderateROB classification: lowROB missing: moderateROB mesure: moderateROB reporting: moderate Artama (Carbamazepine), 2005Artama, 2005 12 0.50[0.13; 1.93]108055%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Canger (Carbamazepine), 1999Canger, 1999 13 0.22[0.00; 11.25]01131%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA D'Souza (Carbamazepine) (Controls unexposed, sick), 1991D'Souza, 1991 14 0.87[0.03; 29.20]131%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Van der Pol (Carbamazepine) (Controls unexposed, sick), 1991Van der Pol, 1991 15 6.79[0.25; 182.34]1111%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Total (15 studies) I2 = 34% 1.06[0.76; 1.47]18,34111,7230.220.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Carbamazepine) (Mixed indications) (Controls unexposed, NOS; 2: Carbamazepine) (Controls unexposed, sick; 3: Carbamazepine; 4: Carbamazepine) (Mixed indications) (Controls unexposed NOS; 5: Carbamazepine) (Controls exposed to Lamotrigine, sick; 6: Carbamazepine) (Controls exposed to Lamotrigine, sick) (Mixed indications; 7: Carbamazepine) (Controls unexposed, NOS) (Indications NOS; 8: Carbamazepine) (Controls unexposed, sick; 9: Carbamazepine) (Controls exposed to Lamotrigine, sick; 10: Carbamazepine; 11: Carbamazepine) (Controls unexposed, sick; 12: Carbamazepine; 13: Carbamazepine; 14: Carbamazepine) (Controls unexposed, sick; 15: Carbamazepine) (Controls unexposed, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.07[0.76; 1.52]18,33211,70938%NACohen (Carbamazepine) (Mixed indications) (Controls unexposed, NOS), 2023 Thomas (Carbamazepine) (Controls unexposed, sick), 2021 Tomson (Carbamazepine), 2018 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 Källén (Carbamazepine) (Controls unexposed, NOS) (Indications NOS), 2013 Vajda (Carbamazepine) (Controls unexposed, sick), 2013 Hernández-Díaz (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2012 Mawer (Carbamazepine) (Controls unexposed, sick), 2010 Artama (Carbamazepine), 2005 Canger (Carbamazepine), 1999 D'Souza (Carbamazepine) (Controls unexposed, sick), 1991 Van der Pol (Carbamazepine) (Controls unexposed, sick), 1991 14 case control studiescase control studies 0.80[0.16; 3.88]914 -NABànhidy (Carbamazepine), 2011 1 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 0.86[0.55; 1.36]18,2054,52848%NACohen (Carbamazepine) (Mixed indications) (Controls unexposed, NOS), 2023 Ban (Carbamazepine) (Mixed indications) (Controls unexposed NOS), 2015 Källén (Carbamazepine) (Controls unexposed, NOS) (Indications NOS), 2013 3 unexposed, sickunexposed, sick 0.66[0.35; 1.25]411,8630%NAThomas (Carbamazepine) (Controls unexposed, sick), 2021 Vajda (Carbamazepine) (Controls unexposed, sick), 2013 Bànhidy (Carbamazepine), 2011 Mawer (Carbamazepine) (Controls unexposed, sick), 2010 Artama (Carbamazepine), 2005 Canger (Carbamazepine), 1999 D'Souza (Carbamazepine) (Controls unexposed, sick), 1991 Van der Pol (Carbamazepine) (Controls unexposed, sick), 1991 8 exposed to other treatment, sickexposed to other treatment, sick 1.74[1.11; 2.71]955,33210%NATomson (Carbamazepine), 2018 Campbell (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2014 Veiby (Carbamazepine) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014 Hernández-Díaz (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2012 4 Tags Adjustment   - No  - No 1.24[0.83; 1.85]1367,19513%NAThomas (Carbamazepine) (Controls unexposed, sick), 2021 Tomson (Carbamazepine), 2018 Campbell (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2014 Veiby (Carbamazepine) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014 Vajda (Carbamazepine) (Controls unexposed, sick), 2013 Hernández-Díaz (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2012 Bànhidy (Carbamazepine), 2011 Mawer (Carbamazepine) (Controls unexposed, sick), 2010 Artama (Carbamazepine), 2005 Canger (Carbamazepine), 1999 D'Souza (Carbamazepine) (Controls unexposed, sick), 1991 Van der Pol (Carbamazepine) (Controls unexposed, sick), 1991 12   - Yes  - Yes 0.86[0.55; 1.36]18,2054,52848%NACohen (Carbamazepine) (Mixed indications) (Controls unexposed, NOS), 2023 Ban (Carbamazepine) (Mixed indications) (Controls unexposed NOS), 2015 Källén (Carbamazepine) (Controls unexposed, NOS) (Indications NOS), 2013 3 Controls   - mixed indications  - mixed indications 1.51[0.30; 7.51]61,033 -NAHernández-Díaz (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2012 1 MatchedMatched 0.80[0.16; 3.88]914 -NABànhidy (Carbamazepine), 2011 1 Partial overlappingPartial overlapping 0.74[0.55; 0.99]16,1584,1850%NACohen (Carbamazepine) (Mixed indications) (Controls unexposed, NOS), 2023 Källén (Carbamazepine) (Controls unexposed, NOS) (Indications NOS), 2013 2 All studiesAll studies 1.06[0.76; 1.47]18,34111,72334%NACohen (Carbamazepine) (Mixed indications) (Controls unexposed, NOS), 2023 Thomas (Carbamazepine) (Controls unexposed, sick), 2021 Tomson (Carbamazepine), 2018 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 Källén (Carbamazepine) (Controls unexposed, NOS) (Indications NOS), 2013 Vajda (Carbamazepine) (Controls unexposed, sick), 2013 Hernández-Díaz (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2012 Bànhidy (Carbamazepine), 2011 Mawer (Carbamazepine) (Controls unexposed, sick), 2010 Artama (Carbamazepine), 2005 Canger (Carbamazepine), 1999 D'Souza (Carbamazepine) (Controls unexposed, sick), 1991 Van der Pol (Carbamazepine) (Controls unexposed, sick), 1991 150.120.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-4.74.82.4150.000Cohen (Carbamazepine) (Mixed indications) (Controls unexposed, NOS), 2023Thomas (Carbamazepine) (Controls unexposed, sick), 2021Tomson (Carbamazepine), 2018Ban (Carbamazepine) (Mixed indications) (Controls unexposed NOS), 2015Campbell (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2014Veiby (Carbamazepine) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014Källén (Carbamazepine) (Controls unexposed, NOS) (Indications NOS), 2013Vajda (Carbamazepine) (Controls unexposed, sick), 2013Hernández-Díaz (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2012Bànhidy (Carbamazepine), 2011Mawer (Carbamazepine) (Controls unexposed, sick), 2010Artama (Carbamazepine), 2005Canger (Carbamazepine), 1999D'Souza (Carbamazepine) (Controls unexposed, sick), 1991Van der Pol (Carbamazepine) (Controls unexposed, sick), 1991

Asymetry test p-value = 0.5492 (by Egger's regression)

slope=-0.1436 (0.2351); intercept=0.3341 (0.5433); t=0.6149; p=0.5492

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 9612, 9740, 9628, 9629, 9625, 10290, 9763, 12856

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.00[0.60; 1.67]18,2084,60839%NACohen (Carbamazepine) (Mixed indications) (Controls unexposed, NOS), 2023 Ban (Carbamazepine) (Mixed indications) (Controls unexposed NOS), 2015 Källén (Carbamazepine) (Controls unexposed, NOS) (Indications NOS), 2013 Mawer (Carbamazepine) (Controls unexposed, disease free), 2010 D'Souza (Carbamazepine) (Controls unexposed, disease free), 1991 Van der Pol (Carbamazepine) (Controls unexposed, disease free), 1991 6 unexposed, sick controlsunexposed, sick controls 0.66[0.35; 1.25]411,8630%NAThomas (Carbamazepine) (Controls unexposed, sick), 2021 Vajda (Carbamazepine) (Controls unexposed, sick), 2013 Bànhidy (Carbamazepine), 2011 Mawer (Carbamazepine) (Controls unexposed, sick), 2010 Artama (Carbamazepine), 2005 Canger (Carbamazepine), 1999 D'Souza (Carbamazepine) (Controls unexposed, sick), 1991 Van der Pol (Carbamazepine) (Controls unexposed, sick), 1991 8 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.36[0.97; 1.90]1458,1030%NAThomas (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2021 Tomson (Carbamazepine), 2018 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 Källén (Carbamazepine) (Controls exposed to Lamotrigine, sick) (Indications NOS), 2013 Vajda (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2013 Hernández-Díaz (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2012 Mawer (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2010 90.510.01.0