Primidone (Epilepsy)

Major congenital malformations

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.
S7788
R23006		 Vajda (Primidone) (Controls exposed to Lamotrigine, sick), 2019 Fetal malformations at least 1st trimester prospective cohort exposed to other treatment, sick excluded Adjustment: No 6.27 [0.25;158.67] C
excluded (control group) 		0/2   20/406 20 2
ref
S7789
R23007		 Vajda (Primidone) (Controls unexposed, sick), 2019 Fetal malformations at least 1st trimester prospective cohort unexposed, sick Adjustment: No 10.33 [0.38;283.37] C 0/2   5/176 5 2
ref
S7666
R22696		 Tomson (Primidone), 2018 Malformed Offspring at least 1st trimester prospective cohort exposed to other treatment, sick Adjustment: No 2.67 [0.81;8.87] C 3/40   74/2,514 77 40
ref
S6502
R17883		 Bànhidy (Primidone), 2011 Total congenital abnormalities throughout pregnancy case control unexposed, sick Adjustment: No Matched 0.56 [0.12;2.54] C 4/10   12/22 16 10
ref
S6140
R16034		 Kaaja (Primidone), 2003 Major malformation 1st trimester prospective cohort unexposed, sick Adjustment: No 23.70 [1.83;306.18] C 1/6   2/239 3 6
ref
S6681
R18529		 Dean (Primidone), 2002 Major congenital malformations at least 1st trimester retrospective cohort unexposed, sick Adjustment: No 4.73 [0.15;148.81] C 0/2   2/38 2 2
ref
S7174
R26579		 Canger (Primidone), 1999 Severe malformations 1st trimester prospective cohort unexposed, sick Adjustment: No 3.77 [0.17;82.12] C 2/35   0/25 2 35
ref
S6711
R18984		 Samrén (Primidone), 1999 Major congential abnormalities at least 1st trimester retrospective cohort unexposed, disease free Adjustment: No Matched 1.91 [0.11;32.49] C 0/18   29/2,000 29 18
ref
S6710
R18982		 Steegers-Theunissen (Primidone), 1994 Major malformations (ICD9 British Paediatric Association System) during pregnancy (anytime or not specified) excluded prospective cohort unexposed, disease free Adjustment: No 69.67 [1.01;4827.79] C
excluded (exposition period) 		1/1   2/106 3 1
ref
Total 7 studies 2.66 [1.03;6.86] 134 113
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 Vajda (Primidone) (Controls unexposed, sick), 2019Vajda, 2019 1 10.33[0.38; 283.37]527%ROB confusion: criticalROB selection: moderateROB classification: lowROB missing: moderateROB mesure: moderateROB reporting: moderate Tomson (Primidone), 2018Tomson, 2018 2 2.67[0.81; 8.87]774032%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Bànhidy (Primidone), 2011Bànhidy, 2011 3 0.56[0.12; 2.54]161025%ROB confusion: criticalROB selection: criticalROB classification: lowROB missing: lowROB mesure: moderateROB reporting: moderate Kaaja (Primidone), 2003Kaaja, 2003 4 23.70[1.83; 306.18]3611%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Dean (Primidone), 2002Dean, 2002 5 4.73[0.15; 148.81]227%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Canger (Primidone), 1999Canger, 1999 6 3.77[0.17; 82.12]2358%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Samrén (Primidone), 1999Samrén, 1999 7 1.91[0.11; 32.49]291810%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (7 studies) I2 = 22% 2.66[1.03; 6.86]1341130.250.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Primidone) (Controls unexposed, sick; 2: Primidone; 3: Primidone; 4: Primidone; 5: Primidone; 6: Primidone; 7: Primidone;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 3.98[1.63; 9.72]1181030%NAVajda (Primidone) (Controls unexposed, sick), 2019 Tomson (Primidone), 2018 Kaaja (Primidone), 2003 Dean (Primidone), 2002 Canger (Primidone), 1999 Samrén (Primidone), 1999 6 case control studiescase control studies 0.56[0.12; 2.54]1610 -NABànhidy (Primidone), 2011 1 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.91[0.11; 32.49]2918 -NASamrén (Primidone), 1999 1 unexposed, sickunexposed, sick 3.66[0.72; 18.70]285547%NAVajda (Primidone) (Controls unexposed, sick), 2019 Bànhidy (Primidone), 2011 Kaaja (Primidone), 2003 Dean (Primidone), 2002 Canger (Primidone), 1999 5 exposed to other treatment, sickexposed to other treatment, sick 2.67[0.81; 8.87]7740 -NATomson (Primidone), 2018 1 Tags Adjustment   - No  - No 2.66[1.03; 6.86]13411322%NAVajda (Primidone) (Controls unexposed, sick), 2019 Tomson (Primidone), 2018 Bànhidy (Primidone), 2011 Kaaja (Primidone), 2003 Dean (Primidone), 2002 Canger (Primidone), 1999 Samrén (Primidone), 1999 7 MatchedMatched 0.73[0.19; 2.79]45280%NABànhidy (Primidone), 2011 Samrén (Primidone), 1999 2 All studiesAll studies 2.66[1.03; 6.86]13411322%NAVajda (Primidone) (Controls unexposed, sick), 2019 Tomson (Primidone), 2018 Bànhidy (Primidone), 2011 Kaaja (Primidone), 2003 Dean (Primidone), 2002 Canger (Primidone), 1999 Samrén (Primidone), 1999 70.250.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-4.15.12.1110.000Vajda (Primidone) (Controls unexposed, sick), 2019Tomson (Primidone), 2018Bànhidy (Primidone), 2011Kaaja (Primidone), 2003Dean (Primidone), 2002Canger (Primidone), 1999Samrén (Primidone), 1999

Asymetry test p-value = 0.2669 (by Egger's regression)

slope=-0.3489 (1.0680); intercept=1.2837 (1.0277); t=1.2492; p=0.2669

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 7788

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.91[0.11; 32.49]2918 -NASamrén (Primidone), 1999 1 unexposed, sick controlsunexposed, sick controls 3.66[0.72; 18.70]285547%NAVajda (Primidone) (Controls unexposed, sick), 2019 Bànhidy (Primidone), 2011 Kaaja (Primidone), 2003 Dean (Primidone), 2002 Canger (Primidone), 1999 5 exposed to other treatment, sick controlsexposed to other treatment, sick controls 2.96[0.96; 9.12]97420%NAVajda (Primidone) (Controls exposed to Lamotrigine, sick), 2019 Tomson (Primidone), 2018 20.510.01.0