Primidone (All indications)

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.
S9475
R33330		 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
S9476
R33331		 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
S9474
R33328		 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
S9458
R33285		 Källén (Primidone) (Controls exposed to Lamotrigine, sick) (Indications NOS), 2013 Relatively severe malformations early pregnancy population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No 1.64 [0.09;28.97] C
excluded (control group) 		0/9   37/1,084 37 9
ref
S9459
R33287		 Källén (Primidone) (Controls unexposed, NOS) (Indications NOS), 2013 Relatively severe malformations early pregnancy population based cohort retrospective unexposed (general population or NOS) Adjustment: No 1.81 [0.10;31.43] C 0/9   49,499/1,575,847 49,499 9
ref
S9461
R33297		 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
S9466
R33315		 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
S9457
R33269		 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
S9464
R33312		 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
S9472
R33324		 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
S9473
R33326		 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 8 studies 2.45 [1.08;5.52] 49,633 122
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]526%ROB confusion: criticalROB selection: moderateROB classification: lowROB missing: moderateROB mesure: moderateROB reporting: moderate Tomson (Primidone), 2018Tomson, 2018 2 2.67[0.81; 8.87]774034%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Källén (Primidone) (Controls unexposed, NOS) (Indications NOS), 2013Källén, 2013 3 1.81[0.10; 31.43]49,49998%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Bànhidy (Primidone), 2011Bànhidy, 2011 4 0.56[0.12; 2.54]161024%ROB confusion: criticalROB selection: criticalROB classification: lowROB missing: lowROB mesure: moderateROB reporting: moderate Kaaja (Primidone), 2003Kaaja, 2003 5 23.70[1.83; 306.18]369%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Dean (Primidone), 2002Dean, 2002 6 4.73[0.15; 148.81]225%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Canger (Primidone), 1999Canger, 1999 7 3.77[0.17; 82.12]2357%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Samrén (Primidone), 1999Samrén, 1999 8 1.91[0.11; 32.49]29188%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (8 studies) I2 = 9% 2.45[1.08; 5.52]49,6331220.250.01.0ROB: 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) (Controls unexposed, NOS) (Indications NOS; 4: Primidone; 5: Primidone; 6: Primidone; 7: Primidone; 8: Primidone;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 3.71[1.58; 8.70]49,6171120%NAVajda (Primidone) (Controls unexposed, sick), 2019 Tomson (Primidone), 2018 Källén (Primidone) (Controls unexposed, NOS) (Indications NOS), 2013 Kaaja (Primidone), 2003 Dean (Primidone), 2002 Canger (Primidone), 1999 Samrén (Primidone), 1999 7 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) 1.86[0.25; 13.90]49,528270%NAKällén (Primidone) (Controls unexposed, NOS) (Indications NOS), 2013 Samrén (Primidone), 1999 2 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 2.45[1.08; 5.52]49,6331229%NAVajda (Primidone) (Controls unexposed, sick), 2019 Tomson (Primidone), 2018 Källén (Primidone) (Controls unexposed, NOS) (Indications NOS), 2013 Bànhidy (Primidone), 2011 Kaaja (Primidone), 2003 Dean (Primidone), 2002 Canger (Primidone), 1999 Samrén (Primidone), 1999 8 MatchedMatched 0.73[0.19; 2.79]45280%NABànhidy (Primidone), 2011 Samrén (Primidone), 1999 2 All studiesAll studies 2.45[1.08; 5.52]49,6331229%NAVajda (Primidone) (Controls unexposed, sick), 2019 Tomson (Primidone), 2018 Källén (Primidone) (Controls unexposed, NOS) (Indications NOS), 2013 Bànhidy (Primidone), 2011 Kaaja (Primidone), 2003 Dean (Primidone), 2002 Canger (Primidone), 1999 Samrén (Primidone), 1999 80.250.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-4.15.02.1110.000Vajda (Primidone) (Controls unexposed, sick), 2019Tomson (Primidone), 2018Källén (Primidone) (Controls unexposed, NOS) (Indications NOS), 2013Bànhidy (Primidone), 2011Kaaja (Primidone), 2003Dean (Primidone), 2002Canger (Primidone), 1999Samrén (Primidone), 1999

Asymetry test p-value = 0.2706 (by Egger's regression)

slope=-0.2464 (0.9870); intercept=1.1164 (0.9202); t=1.2132; p=0.2706

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 9458, 9475

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.86[0.25; 13.90]49,528270%NAKällén (Primidone) (Controls unexposed, NOS) (Indications NOS), 2013 Samrén (Primidone), 1999 2 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 2.74[0.96; 7.80]134510%NAVajda (Primidone) (Controls exposed to Lamotrigine, sick), 2019 Tomson (Primidone), 2018 Källén (Primidone) (Controls exposed to Lamotrigine, sick) (Indications NOS), 2013 30.510.01.0