Carbamazepine (All indications)

Hypospadias

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
R62339		 Cohen (Carbamazepine) (Mixed indications) (Controls unexposed, NOS), 2023 Hypospadias 1st trimester population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Partial overlapping 1.64 [0.86;3.14] -/2,674   -/4,866,362 - 2,674
ref
S10176
R37263		 Blotière (Carbamazepine) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2019 Hypospadias 1st trimester retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No 1.68 [0.35;8.09] C
excluded (control group) 		2/512   7/2,997 9 512
ref
S9766
R34913		 Blotière (Carbamazepine) (Controls unexposed NOS) (Mixed indications), 2019 Hypospadias 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No 1.90 [0.20;7.00] 2/512   3,371/1,875,733 3,373 512
ref
S9678
R34451		 Tomson (Carbamazepine), 2018 Hypospadias at least 1st trimester prospective cohort exposed to other treatment, sick Adjustment: No 2.15 [0.78;5.92] C 10/1,957   6/2,514 16 1,957
ref
S9655
R34365		 Campbell (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2014 Hypospadias and genitourinary tract defects 1st trimester prospective cohort exposed to other treatment, sick Adjustment: No 0.63 [0.22;1.85] C 5/1,657   10/2,098 15 1,657
ref
S9643
R34314		 Veiby (Carbamazepine) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014 Hypospadias throughout pregnancy population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No Partial overlapping 0.61 [0.11;3.32] C
excluded (control group) 		2/685   4/833 6 685
ref
S9645
R34324		 Veiby (Carbamazepine) (Controls unexposed, disease free) (Mixed indications), 2014 Hypospadias throughout pregnancy population based cohort retrospective unexposed, disease free Adjustment: No Partial overlapping 1.46 [0.36;5.86] C 2/685   1,543/771,412 1,545 685
ref
S9625
R34227		 Källén (Carbamazepine) (Controls exposed to Lamotrigine, sick) (Indications NOS), 2013 Hypospadias early pregnancy population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No Partial overlapping 1.20 [0.29;5.02] C
excluded (control group) 		5/1,511   3/1,084 8 1,511
ref
S9626
R34235		 Källén (Carbamazepine) (Controls unexposed, NOS) (Indications NOS), 2013 Hypospadias early pregnancy population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Partial overlapping 0.96 [0.31;2.24] 5/1,511   4,552/1,575,847 4,557 1,511
ref
S9619
R34194		 Hernández-Díaz (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2012 Hypospadias 1st trimester prospective cohort exposed to other treatment, sick Adjustment: No Controls: mixed indications 4.54 [0.18;111.60] C 1/1,033   0/1,562 1 1,033
ref
S9653
R34360		 Bànhidy (Carbamazepine), 2011 Hypospadias throughout pregnancy case control unexposed, sick Adjustment: No Matched 0.33 [0.03;3.78] C 1/11   3/13 4 11
ref
S9664
R34411		 Jentink (Carbamazepine), 2010 Hypospadias 1st trimester case control unexposed (general population or NOS) Adjustment: Yes 0.70 [0.30;1.60] 6/-   -/- - -
ref
S9612
R34094		 D'Souza (Carbamazepine) (Controls unexposed, disease free), 1991 Hypospadias 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
R34123		 D'Souza (Carbamazepine) (Controls unexposed, sick), 1991 Hypospadias throughout pregnancy prospective cohort unexposed, sick Adjustment: No 3.00 [0.05;194.76] C 0/3   0/8 0 3
ref
S9740
R34720		 Van der Pol (Carbamazepine) (Controls unexposed, disease free), 1991 Hypospadias throughout pregnancy prospective cohort unexposed, disease free excluded Adjustment: No Matched 5.19 [0.10;276.47] C
excluded (control group) 		0/11   0/55 0 11
ref
S9741
R34745		 Van der Pol (Carbamazepine) (Controls unexposed, sick), 1991 Hypospadias throughout pregnancy prospective cohort unexposed, sick Adjustment: No 2.05 [0.04;110.56] C 0/11   0/22 0 11
ref
Total 11 studies 1.20 [0.84;1.71] 9,511 10,054
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 1.64[0.86; 3.14]-2,67430%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Blotière (Carbamazepine) (Controls unexposed NOS) (Mixed indications), 2019Blotière, 2019 2 1.90[0.20; 7.00]3,3735124%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Tomson (Carbamazepine), 2018Tomson, 2018 3 2.15[0.78; 5.92]161,95712%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Campbell (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2014Campbell, 2014 4 0.63[0.22; 1.85]151,65711%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Veiby (Carbamazepine) (Controls unexposed, disease free) (Mixed indications), 2014Veiby, 2014 5 1.46[0.36; 5.86]1,5456857%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: moderateROB reporting: moderate Källén (Carbamazepine) (Controls unexposed, NOS) (Indications NOS), 2013Källén, 2013 6 0.96[0.31; 2.24]4,5571,51113%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Hernández-Díaz (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2012Hernández-Díaz, 2012 7 4.54[0.18; 111.60]11,0331%ROB confusion: moderateROB selection: lowROB classification: moderateROB missing: moderateROB mesure: moderateROB reporting: moderate Bànhidy (Carbamazepine), 2011Bànhidy, 2011 8 0.33[0.03; 3.78]4112%ROB confusion: criticalROB selection: criticalROB classification: lowROB missing: lowROB mesure: moderateROB reporting: moderate Jentink (Carbamazepine), 2010Jentink, 2010 9 0.70[0.30; 1.60]--18%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA D'Souza (Carbamazepine) (Controls unexposed, sick), 1991D'Souza, 1991 10 3.00[0.05; 194.76]031%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Van der Pol (Carbamazepine) (Controls unexposed, sick), 1991Van der Pol, 1991 11 2.05[0.04; 110.56]0111%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Total (11 studies) I2 = 0% 1.20[0.84; 1.71]9,51110,0540.210.01.0ROB: 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 NOS) (Mixed indications; 3: Carbamazepine; 4: Carbamazepine) (Controls exposed to Lamotrigine, sick; 5: Carbamazepine) (Controls unexposed, disease free) (Mixed indications; 6: Carbamazepine) (Controls unexposed, NOS) (Indications NOS; 7: Carbamazepine) (Controls exposed to Lamotrigine, sick; 8: Carbamazepine; 9: Carbamazepine; 10: Carbamazepine) (Controls unexposed, sick; 11: Carbamazepine) (Controls unexposed, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.40[0.94; 2.09]9,50710,0430%NACohen (Carbamazepine) (Mixed indications) (Controls unexposed, NOS), 2023 Blotière (Carbamazepine) (Controls unexposed NOS) (Mixed indications), 2019 Tomson (Carbamazepine), 2018 Campbell (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2014 Veiby (Carbamazepine) (Controls unexposed, disease free) (Mixed indications), 2014 Källén (Carbamazepine) (Controls unexposed, NOS) (Indications NOS), 2013 Hernández-Díaz (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2012 D'Souza (Carbamazepine) (Controls unexposed, sick), 1991 Van der Pol (Carbamazepine) (Controls unexposed, sick), 1991 9 case control studiescase control studies 0.65[0.29; 1.43]4110%NABànhidy (Carbamazepine), 2011 Jentink (Carbamazepine), 2010 2 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.20[0.79; 1.82]9,4755,3820%NACohen (Carbamazepine) (Mixed indications) (Controls unexposed, NOS), 2023 Blotière (Carbamazepine) (Controls unexposed NOS) (Mixed indications), 2019 Veiby (Carbamazepine) (Controls unexposed, disease free) (Mixed indications), 2014 Källén (Carbamazepine) (Controls unexposed, NOS) (Indications NOS), 2013 Jentink (Carbamazepine), 2010 5 unexposed, sickunexposed, sick 0.76[0.12; 4.89]4250%NABànhidy (Carbamazepine), 2011 D'Souza (Carbamazepine) (Controls unexposed, sick), 1991 Van der Pol (Carbamazepine) (Controls unexposed, sick), 1991 3 exposed to other treatment, sickexposed to other treatment, sick 1.34[0.48; 3.71]324,64739%NATomson (Carbamazepine), 2018 Campbell (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2014 Hernández-Díaz (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2012 3 Tags Adjustment   - No  - No 1.31[0.74; 2.31]4,9545,8690%NABlotière (Carbamazepine) (Controls unexposed NOS) (Mixed indications), 2019 Tomson (Carbamazepine), 2018 Campbell (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2014 Veiby (Carbamazepine) (Controls unexposed, disease free) (Mixed indications), 2014 Hernández-Díaz (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2012 Bànhidy (Carbamazepine), 2011 D'Souza (Carbamazepine) (Controls unexposed, sick), 1991 Van der Pol (Carbamazepine) (Controls unexposed, sick), 1991 8   - Yes  - Yes 1.11[0.65; 1.89]4,5574,18524%NACohen (Carbamazepine) (Mixed indications) (Controls unexposed, NOS), 2023 Källén (Carbamazepine) (Controls unexposed, NOS) (Indications NOS), 2013 Jentink (Carbamazepine), 2010 3 Controls   - mixed indications  - mixed indications 4.54[0.18; 111.60]11,033 -NAHernández-Díaz (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2012 1 MatchedMatched 0.33[0.03; 3.78]411 -NABànhidy (Carbamazepine), 2011 1 Partial overlappingPartial overlapping 1.40[0.85; 2.33]6,1024,8700%NACohen (Carbamazepine) (Mixed indications) (Controls unexposed, NOS), 2023 Veiby (Carbamazepine) (Controls unexposed, disease free) (Mixed indications), 2014 Källén (Carbamazepine) (Controls unexposed, NOS) (Indications NOS), 2013 3 All studiesAll studies 1.20[0.84; 1.71]9,51110,0540%NACohen (Carbamazepine) (Mixed indications) (Controls unexposed, NOS), 2023 Blotière (Carbamazepine) (Controls unexposed NOS) (Mixed indications), 2019 Tomson (Carbamazepine), 2018 Campbell (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2014 Veiby (Carbamazepine) (Controls unexposed, disease free) (Mixed indications), 2014 Källén (Carbamazepine) (Controls unexposed, NOS) (Indications NOS), 2013 Hernández-Díaz (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2012 Bànhidy (Carbamazepine), 2011 Jentink (Carbamazepine), 2010 D'Souza (Carbamazepine) (Controls unexposed, sick), 1991 Van der Pol (Carbamazepine) (Controls unexposed, sick), 1991 110.110.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-5.05.22.5550.000Cohen (Carbamazepine) (Mixed indications) (Controls unexposed, NOS), 2023Blotière (Carbamazepine) (Controls unexposed NOS) (Mixed indications), 2019Tomson (Carbamazepine), 2018Campbell (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2014Veiby (Carbamazepine) (Controls unexposed, disease free) (Mixed indications), 2014Källén (Carbamazepine) (Controls unexposed, NOS) (Indications NOS), 2013Hernández-Díaz (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2012Bànhidy (Carbamazepine), 2011Jentink (Carbamazepine), 2010D'Souza (Carbamazepine) (Controls unexposed, sick), 1991Van der Pol (Carbamazepine) (Controls unexposed, sick), 1991

Asymetry test p-value = 0.7685 (by Egger's regression)

slope=0.0913 (0.3450); intercept=0.1738 (0.5729); t=0.3033; p=0.7685

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 9612, 9740, 9625, 9643, 10176

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.26[0.83; 1.90]9,4755,3960%NACohen (Carbamazepine) (Mixed indications) (Controls unexposed, NOS), 2023 Blotière (Carbamazepine) (Controls unexposed NOS) (Mixed indications), 2019 Veiby (Carbamazepine) (Controls unexposed, disease free) (Mixed indications), 2014 Källén (Carbamazepine) (Controls unexposed, NOS) (Indications NOS), 2013 Jentink (Carbamazepine), 2010 D'Souza (Carbamazepine) (Controls unexposed, disease free), 1991 Van der Pol (Carbamazepine) (Controls unexposed, disease free), 1991 7 unexposed, sick controlsunexposed, sick controls 0.76[0.12; 4.89]4250%NABànhidy (Carbamazepine), 2011 D'Souza (Carbamazepine) (Controls unexposed, sick), 1991 Van der Pol (Carbamazepine) (Controls unexposed, sick), 1991 3 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.21[0.69; 2.13]557,3550%NABlotière (Carbamazepine) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2019 Tomson (Carbamazepine), 2018 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 Hernández-Díaz (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2012 60.510.01.0