Carbamazepine (All indications)

Cleft lip with or without cleft palate

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
R37259		 Blotière (Carbamazepine) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2019 Cleft lip with or without cleft palate 1st trimester retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No 1.17 [0.06;24.43] C
excluded (control group) 		0/512   2/2,997 2 512
ref
S9766
R34909		 Blotière (Carbamazepine) (Controls unexposed NOS) (Mixed indications), 2019 Cleft lip with or without cleft palate 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No 1.12 [0.07;17.92] C 0/512   1,637/1,875,733 1,637 512
ref
S10291
R37677		 Vajda (Carbamazepine) (Controls unexposed, sick), 2013 Palate/lip malformation at least 1st trimester prospective cohort unexposed, sick Adjustment: No 0.41 [0.01;20.58] C 0/361   0/147 0 361
ref
S9664
R34409		 Jentink (Carbamazepine), 2010 Cleft lip (with or without palate) 1st trimester case control unexposed (general population or NOS) Adjustment: Yes no data 1/-   -/- - -
ref
S9648
R34335		 Viinikainen (Carbamazepine) (Controls unexposed, sick) a, 2006 Cleft lip throughout pregnancy prospective cohort unexposed, sick Adjustment: No 2.19 [0.09;54.89] C 1/72   0/52 1 72
ref
S9652
R34349		 Artama (Carbamazepine), 2005 Cleft lip/ cleft palate 1st trimester retrospective cohort (registry) unexposed, sick Adjustment: No 0.23 [0.01;4.86] C 0/805   2/939 2 805
ref
Total 5 studies 0.73 [0.15;3.55] 1,640 1,750
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 1.12[0.07; 17.92]1,63751233%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Vajda (Carbamazepine) (Controls unexposed, sick), 2013Vajda, 2013 2 0.41[0.01; 20.58]036116%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Jentink (Carbamazepine), 2010Jentink, 2010 3 0.20[0.00; 1.30]--0%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Viinikainen (Carbamazepine) (Controls unexposed, sick) a, 2006Viinikainen, 2006 4 2.19[0.09; 54.89]17224%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Artama (Carbamazepine), 2005Artama, 2005 5 0.23[0.01; 4.86]280527%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (5 studies) I2 = 0% 0.73[0.15; 3.55]1,6401,7500.25.01.0ROB: 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; 3: Carbamazepine; 4: Carbamazepine) (Controls unexposed, sick) ; 5: Carbamazepine;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 0.73[0.15; 3.55]1,6401,7500%NABlotière (Carbamazepine) (Controls unexposed NOS) (Mixed indications), 2019 Vajda (Carbamazepine) (Controls unexposed, sick), 2013 Viinikainen (Carbamazepine) (Controls unexposed, sick) a, 2006 Artama (Carbamazepine), 2005 4 case control studiescase control studies Jentink (Carbamazepine), 2010 1 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.12[0.07; 17.92]1,6375120%NABlotière (Carbamazepine) (Controls unexposed NOS) (Mixed indications), 2019 Jentink (Carbamazepine), 2010 2 unexposed, sickunexposed, sick 0.59[0.09; 4.07]31,2380%NAVajda (Carbamazepine) (Controls unexposed, sick), 2013 Viinikainen (Carbamazepine) (Controls unexposed, sick) a, 2006 Artama (Carbamazepine), 2005 3 Tags Adjustment   - No  - No 0.73[0.15; 3.55]1,6401,7500%NABlotière (Carbamazepine) (Controls unexposed NOS) (Mixed indications), 2019 Vajda (Carbamazepine) (Controls unexposed, sick), 2013 Viinikainen (Carbamazepine) (Controls unexposed, sick) a, 2006 Artama (Carbamazepine), 2005 4   - Yes  - Yes Jentink (Carbamazepine), 2010 1 All studiesAll studies 0.73[0.15; 3.55]1,6401,7500%NABlotière (Carbamazepine) (Controls unexposed NOS) (Mixed indications), 2019 Vajda (Carbamazepine) (Controls unexposed, sick), 2013 Jentink (Carbamazepine), 2010 Viinikainen (Carbamazepine) (Controls unexposed, sick) a, 2006 Artama (Carbamazepine), 2005 50.15.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-4.94.62.5000.000Blotière (Carbamazepine) (Controls unexposed NOS) (Mixed indications), 2019Vajda (Carbamazepine) (Controls unexposed, sick), 2013Jentink (Carbamazepine), 2010Viinikainen (Carbamazepine) (Controls unexposed, sick) a, 2006Artama (Carbamazepine), 2005

Asymetry test p-value = 0.9350 (by Egger's regression)

slope=-0.2298 (1.0926); intercept=-0.0536 (0.6054); t=0.0885; p=0.9350

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 10176

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.12[0.07; 17.92]1,637512 -NABlotière (Carbamazepine) (Controls unexposed NOS) (Mixed indications), 2019 1 unexposed, sick controlsunexposed, sick controls 0.59[0.09; 4.07]31,2380%NAVajda (Carbamazepine) (Controls unexposed, sick), 2013 Viinikainen (Carbamazepine) (Controls unexposed, sick) a, 2006 Artama (Carbamazepine), 2005 3 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.17[0.06; 24.43]2512 -NABlotière (Carbamazepine) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2019 10.510.01.0