Primidone AND Phenobarbital (All indications) updated on 04-22-2025

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.
S10043
R36330		 Blotière (Phenobarbital) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2019 Hypospadias 1st trimester retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No 2.51 [0.14;44.28] C
excluded (control group) 		0/80   7/2,997 7 80
ref
S10044
R36353		 Blotière (Phenobarbital) (Controls unexposed NOS) (Mixed indications), 2019 Hypospadias 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No 3.49 [0.22;56.34] C 0/80   3,371/1,875,733 3,371 80
ref
S9586
R33945		 Tomson (Phenobarbital or Primidone), 2018 Hypospadias at least 1st trimester prospective cohort exposed to other treatment, sick Adjustment: No 1.43 [0.17;11.89] C 1/294   6/2,514 7 294
ref
S10235
R37497		 Hernández-Díaz (Phenobarbital) (Controls exposed to Lamotrigine, sick), 2012 Hypospadias 1st trimester prospective cohort exposed to other treatment, sick Adjustment: No Controls: mixed indications 23.72 [0.96;584.27] C 1/199   0/1,562 1 199
ref
S9575
R33916		 Bànhidy (Phenobarbital or Primidone), 2011 Hypospadias throughout pregnancy case control unexposed, sick Adjustment: No Matched 0.29 [0.01;7.14] C 0/6   3/13 3 6
ref
S9488
R33373		 D'Souza (Phenobarbital) (Controls unexposed, disease free), 1991 Hypospadias throughout pregnancy prospective cohort unexposed, disease free excluded Adjustment: No Matched 17.57 [0.30;1024.08] C
excluded (control group) 		0/4   0/62 0 4
ref
S9489
R33402		 D'Souza (Phenobarbital) (Controls unexposed, sick), 1991 Hypospadias throughout pregnancy prospective cohort unexposed, sick Adjustment: No 2.14 [0.03;131.94] C 0/4   0/8 0 4
ref
S9564
R33844		 Van der Pol (Phenobarbital) (Controls unexposed, disease free), 1991 Hypospadias throughout pregnancy prospective cohort unexposed, disease free excluded Adjustment: No Matched 4.74 [0.09;251.42] C
excluded (control group) 		0/12   0/55 0 12
ref
S9565
R33869		 Van der Pol (Phenobarbital) (Controls unexposed, sick), 1991 Hypospadias throughout pregnancy prospective cohort unexposed, sick Adjustment: No 1.87 [0.03;100.54] C 0/12   0/22 0 12
ref
Total 6 studies 2.15 [0.63;7.31] 3,382 595
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 (Phenobarbital) (Controls unexposed NOS) (Mixed indications), 2019Blotière, 2019 1 3.49[0.22; 56.34]3,3718019%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Tomson (Phenobarbital or Primidone), 2018Tomson, 2018 2 1.43[0.17; 11.89]729433%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Hernández-Díaz (Phenobarbital) (Controls exposed to Lamotrigine, sick), 2012Hernández-Díaz, 2012 3 23.72[0.96; 584.27]119915%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: moderateROB reporting: moderate Bànhidy (Phenobarbital or Primidone), 2011Bànhidy, 2011 4 0.29[0.01; 7.14]3615%ROB confusion: criticalROB selection: criticalROB classification: lowROB missing: lowROB mesure: moderateROB reporting: moderate D'Souza (Phenobarbital) (Controls unexposed, sick), 1991D'Souza, 1991 5 2.14[0.03; 131.94]049%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Van der Pol (Phenobarbital) (Controls unexposed, sick), 1991Van der Pol, 1991 6 1.87[0.03; 100.54]0129%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Total (6 studies) I2 = 0% 2.15[0.63; 7.31]3,3825950.250.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

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

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 3.03[0.81; 11.39]3,3795890%NABlotière (Phenobarbital) (Controls unexposed NOS) (Mixed indications), 2019 Tomson (Phenobarbital or Primidone), 2018 Hernández-Díaz (Phenobarbital) (Controls exposed to Lamotrigine, sick), 2012 D'Souza (Phenobarbital) (Controls unexposed, sick), 1991 Van der Pol (Phenobarbital) (Controls unexposed, sick), 1991 5 case control studiescase control studies 0.29[0.01; 7.14]36 -NABànhidy (Phenobarbital or Primidone), 2011 1 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 3.49[0.22; 56.34]3,37180 -NABlotière (Phenobarbital) (Controls unexposed NOS) (Mixed indications), 2019 1 unexposed, sickunexposed, sick 0.85[0.10; 7.16]3220%NABànhidy (Phenobarbital or Primidone), 2011 D'Souza (Phenobarbital) (Controls unexposed, sick), 1991 Van der Pol (Phenobarbital) (Controls unexposed, sick), 1991 3 exposed to other treatment, sickexposed to other treatment, sick 4.45[0.30; 66.56]849351%NATomson (Phenobarbital or Primidone), 2018 Hernández-Díaz (Phenobarbital) (Controls exposed to Lamotrigine, sick), 2012 2 Tags Adjustment   - No  - No 2.15[0.63; 7.31]3,3825950%NABlotière (Phenobarbital) (Controls unexposed NOS) (Mixed indications), 2019 Tomson (Phenobarbital or Primidone), 2018 Hernández-Díaz (Phenobarbital) (Controls exposed to Lamotrigine, sick), 2012 Bànhidy (Phenobarbital or Primidone), 2011 D'Souza (Phenobarbital) (Controls unexposed, sick), 1991 Van der Pol (Phenobarbital) (Controls unexposed, sick), 1991 6 Controls   - mixed indications  - mixed indications 23.72[0.96; 584.27]1199 -NAHernández-Díaz (Phenobarbital) (Controls exposed to Lamotrigine, sick), 2012 1 MatchedMatched 0.29[0.01; 7.14]36 -NABànhidy (Phenobarbital or Primidone), 2011 1 All studiesAll studies 2.15[0.63; 7.31]3,3825950%NABlotière (Phenobarbital) (Controls unexposed NOS) (Mixed indications), 2019 Tomson (Phenobarbital or Primidone), 2018 Hernández-Díaz (Phenobarbital) (Controls exposed to Lamotrigine, sick), 2012 Bànhidy (Phenobarbital or Primidone), 2011 D'Souza (Phenobarbital) (Controls unexposed, sick), 1991 Van der Pol (Phenobarbital) (Controls unexposed, sick), 1991 60.150.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-4.95.72.5230.000Blotière (Phenobarbital) (Controls unexposed NOS) (Mixed indications), 2019Tomson (Phenobarbital or Primidone), 2018Hernández-Díaz (Phenobarbital) (Controls exposed to Lamotrigine, sick), 2012Bànhidy (Phenobarbital or Primidone), 2011D'Souza (Phenobarbital) (Controls unexposed, sick), 1991Van der Pol (Phenobarbital) (Controls unexposed, sick), 1991

Asymetry test p-value = 0.8237 (by Egger's regression)

slope=0.1487 (2.6710); intercept=0.4158 (1.7480); t=0.2379; p=0.8237

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 9488, 9564, 10043

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 5.55[0.76; 40.46]3,371960%NABlotière (Phenobarbital) (Controls unexposed NOS) (Mixed indications), 2019 D'Souza (Phenobarbital) (Controls unexposed, disease free), 1991 Van der Pol (Phenobarbital) (Controls unexposed, disease free), 1991 3 unexposed, sick controlsunexposed, sick controls 0.85[0.10; 7.16]3220%NABànhidy (Phenobarbital or Primidone), 2011 D'Souza (Phenobarbital) (Controls unexposed, sick), 1991 Van der Pol (Phenobarbital) (Controls unexposed, sick), 1991 3 exposed to other treatment, sick controlsexposed to other treatment, sick controls 3.15[0.67; 14.73]155734%NABlotière (Phenobarbital) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2019 Tomson (Phenobarbital or Primidone), 2018 Hernández-Díaz (Phenobarbital) (Controls exposed to Lamotrigine, sick), 2012 30.510.01.0