Carbamazepine (All indications)

Spina bifida

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.
S10176
R37248		 Blotière (Carbamazepine) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2019 Spina bifida 1st trimester retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No 5.86 [0.37;93.89] C
excluded (control group) 		1/512   1/2,997 2 512
ref
S9766
R34898		 Blotière (Carbamazepine) (Controls unexposed NOS) (Mixed indications), 2019 Spina bifida 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No 6.00 [0.20;33.50] 1/512   616/1,875,733 617 512
ref
S9643
R35006		 Veiby (Carbamazepine) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014 Spina bifida throughout pregnancy population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No 1.22 [0.02;61.38] C
excluded (control group) 		0/685   0/833 0 685
ref
S9646
R34327		 Veiby (Carbamazepine) (Controls unexposed, sick) (Mixed indications), 2014 Spina bifida throughout pregnancy population based cohort retrospective unexposed, sick Adjustment: No Controls: epilepsy indication 0.79 [0.04;15.25] C 0/685   3/3,773 3 685
ref
S9608
R34066		 Charlton (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2011 Spina bifida 1st trimester retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No 0.31 [0.01;15.93] C
excluded (control group) 		0/311   0/98 0 311
ref
S9609
R34069		 Charlton (Carbamazepine) (Controls unexposed, sick), 2011 Spina bifida 1st trimester retrospective cohort (claims database) unexposed, sick Adjustment: No 0.58 [0.03;12.10] C 0/311   2/902 2 311
ref
S9664
R34408		 Jentink (Carbamazepine), 2010 Spina bifida 1st trimester case control unexposed (general population or NOS) Adjustment: Yes 2.60 [1.20;5.30] 8/-   -/- - -
ref
S9648
R34332		 Viinikainen (Carbamazepine) (Controls unexposed, sick) a, 2006 Spina bifida throughout pregnancy prospective cohort unexposed, sick Adjustment: No 0.72 [0.01;36.90] C 0/72   0/52 0 72
ref
S9652
R34345		 Artama (Carbamazepine), 2005 Spina bifida 1st trimester retrospective cohort (registry) unexposed, sick Adjustment: No 1.17 [0.02;58.86] C 0/805   0/939 0 805
ref
S9666
R34414		 Källén (Carbamazepine), 1994 Spina bifida during pregnancy (anytime or not specified) excluded nested case control unexposed, sick Adjustment: No Matched 39.00 [0.53;2883.82] C
excluded (exposition period) 		2/3   0/6 2 3
ref
S9767
R34921		 Czeizel (Carbamazepine) (Mixed indications), 1992 Spina bifida throughout pregnancy case control unexposed, sick Adjustment: No Controls: epilepsy indication 1.20 [0.07;19.63] C 2/7   1/4 3 7
ref
S9740
R34713		 Van der Pol (Carbamazepine) (Controls unexposed, disease free), 1991 Spina bifida occulta 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
R34738		 Van der Pol (Carbamazepine) (Controls unexposed, sick), 1991 Spina bifida occulta throughout pregnancy prospective cohort unexposed, sick Adjustment: No 0.65 [0.02;17.40] C 0/11   1/22 1 11
ref
Total 8 studies 2.11 [1.12;3.95] 626 2,403
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 Blotière (Carbamazepine) (Controls unexposed NOS) (Mixed indications), 2019Blotière, 2019 1 6.00[0.20; 33.50]6175126%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Veiby (Carbamazepine) (Controls unexposed, sick) (Mixed indications), 2014Veiby, 2014 2 0.79[0.04; 15.25]36854%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: moderateROB reporting: moderate Charlton (Carbamazepine) (Controls unexposed, sick), 2011Charlton, 2011 3 0.58[0.03; 12.10]23114%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Jentink (Carbamazepine), 2010Jentink, 2010 4 2.60[1.20; 5.30]--71%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Viinikainen (Carbamazepine) (Controls unexposed, sick) a, 2006Viinikainen, 2006 5 0.72[0.01; 36.90]0723%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Artama (Carbamazepine), 2005Artama, 2005 6 1.17[0.02; 58.86]08053%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Czeizel (Carbamazepine) (Mixed indications), 1992Czeizel, 1992 7 1.20[0.07; 19.63]375%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Van der Pol (Carbamazepine) (Controls unexposed, sick), 1991Van der Pol, 1991 8 0.65[0.02; 17.40]1114%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Total (8 studies) I2 = 0% 2.11[1.12; 3.95]6262,4030.220.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Carbamazepine) (Controls unexposed NOS) (Mixed indications; 2: Carbamazepine) (Controls unexposed, sick) (Mixed indications; 3: Carbamazepine) (Controls unexposed, sick; 4: Carbamazepine; 5: Carbamazepine) (Controls unexposed, sick) ; 6: Carbamazepine; 7: Carbamazepine) (Mixed indications; 8: Carbamazepine) (Controls unexposed, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.26[0.34; 4.58]6232,3960%NABlotière (Carbamazepine) (Controls unexposed NOS) (Mixed indications), 2019 Veiby (Carbamazepine) (Controls unexposed, sick) (Mixed indications), 2014 Charlton (Carbamazepine) (Controls unexposed, sick), 2011 Viinikainen (Carbamazepine) (Controls unexposed, sick) a, 2006 Artama (Carbamazepine), 2005 Van der Pol (Carbamazepine) (Controls unexposed, sick), 1991 6 case control studiescase control studies 2.47[1.21; 5.06]370%NAJentink (Carbamazepine), 2010 Czeizel (Carbamazepine) (Mixed indications), 1992 2 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 2.77[1.36; 5.66]6175120%NABlotière (Carbamazepine) (Controls unexposed NOS) (Mixed indications), 2019 Jentink (Carbamazepine), 2010 2 unexposed, sickunexposed, sick 0.82[0.22; 3.07]91,8910%NAVeiby (Carbamazepine) (Controls unexposed, sick) (Mixed indications), 2014 Charlton (Carbamazepine) (Controls unexposed, sick), 2011 Viinikainen (Carbamazepine) (Controls unexposed, sick) a, 2006 Artama (Carbamazepine), 2005 Czeizel (Carbamazepine) (Mixed indications), 1992 Van der Pol (Carbamazepine) (Controls unexposed, sick), 1991 6 Tags Adjustment   - No  - No 1.25[0.38; 4.03]6262,4030%NABlotière (Carbamazepine) (Controls unexposed NOS) (Mixed indications), 2019 Veiby (Carbamazepine) (Controls unexposed, sick) (Mixed indications), 2014 Charlton (Carbamazepine) (Controls unexposed, sick), 2011 Viinikainen (Carbamazepine) (Controls unexposed, sick) a, 2006 Artama (Carbamazepine), 2005 Czeizel (Carbamazepine) (Mixed indications), 1992 Van der Pol (Carbamazepine) (Controls unexposed, sick), 1991 7   - Yes  - Yes 2.60[1.24; 5.46]-- -NAJentink (Carbamazepine), 2010 1 Controls   - epilepsy indication  - epilepsy indication 0.98[0.13; 7.52]66920%NAVeiby (Carbamazepine) (Controls unexposed, sick) (Mixed indications), 2014 Czeizel (Carbamazepine) (Mixed indications), 1992 2 All studiesAll studies 2.11[1.12; 3.95]6262,4030%NABlotière (Carbamazepine) (Controls unexposed NOS) (Mixed indications), 2019 Veiby (Carbamazepine) (Controls unexposed, sick) (Mixed indications), 2014 Charlton (Carbamazepine) (Controls unexposed, sick), 2011 Jentink (Carbamazepine), 2010 Viinikainen (Carbamazepine) (Controls unexposed, sick) a, 2006 Artama (Carbamazepine), 2005 Czeizel (Carbamazepine) (Mixed indications), 1992 Van der Pol (Carbamazepine) (Controls unexposed, sick), 1991 80.220.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-4.75.52.4100.000Blotière (Carbamazepine) (Controls unexposed NOS) (Mixed indications), 2019Veiby (Carbamazepine) (Controls unexposed, sick) (Mixed indications), 2014Charlton (Carbamazepine) (Controls unexposed, sick), 2011Jentink (Carbamazepine), 2010Viinikainen (Carbamazepine) (Controls unexposed, sick) a, 2006Artama (Carbamazepine), 2005Czeizel (Carbamazepine) (Mixed indications), 1992Van der Pol (Carbamazepine) (Controls unexposed, sick), 1991

Asymetry test p-value = 0.0640 (by Egger's regression)

slope=1.2433 (0.2770); intercept=-0.6929 (0.3058); t=2.2659; p=0.0640

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 9740, 9608, 9643, 10176

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 2.83[1.40; 5.71]6175230%NABlotière (Carbamazepine) (Controls unexposed NOS) (Mixed indications), 2019 Jentink (Carbamazepine), 2010 Van der Pol (Carbamazepine) (Controls unexposed, disease free), 1991 3 unexposed, sick controlsunexposed, sick controls 0.82[0.22; 3.07]91,8910%NAVeiby (Carbamazepine) (Controls unexposed, sick) (Mixed indications), 2014 Charlton (Carbamazepine) (Controls unexposed, sick), 2011 Viinikainen (Carbamazepine) (Controls unexposed, sick) a, 2006 Artama (Carbamazepine), 2005 Czeizel (Carbamazepine) (Mixed indications), 1992 Van der Pol (Carbamazepine) (Controls unexposed, sick), 1991 6 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.91[0.27; 13.55]21,5080%NABlotière (Carbamazepine) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2019 Veiby (Carbamazepine) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014 Charlton (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2011 30.510.01.0