Primidone (All indications)

All congenital malformations (majors, minors, majors and minors, or unspecified)

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
R35165		 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
R35166		 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
R33329		 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
R33286		 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
R33288		 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
R35125		 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
S9455
R33261		 Burja (Primidone) (Controls unexposed, disease free), 2006 Congenital malformation during pregnancy (anytime or not specified) retrospective cohort (registry) unexposed, disease free excluded Adjustment: No 37.36 [0.68;2061.38] C
excluded (control group) 		0/1   5/211 5 1
ref
S9456
R33266		 Burja (Primidone) (Controls unexposed, sick), 2006 Congenital malformation during pregnancy (anytime or not specified) excluded retrospective cohort (registry) unexposed, sick Adjustment: No 63.00 [0.51;7760.63] C
excluded (exposition period) 		0/1   0/32 0 1
ref
S9466
R33316		 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
R33284		 Dean (Primidone), 2002 Congenital malformations (major and minor) at least 1st trimester retrospective cohort unexposed, sick Adjustment: No 1.36 [0.05;36.71] C 0/2   7/38 7 2
ref
S9464
R33313		 Canger (Primidone), 1999 All type of malformation 1st trimester prospective cohort unexposed, sick Adjustment: No 5.44 [0.27;110.44] C 3/35   0/25 3 35
ref
S9467
R33317		 Kaneko (Primidone), 1999 Malformations throughout pregnancy prospective cohort unexposed, sick Adjustment: No 5.28 [1.19;23.40] C 5/35   3/98 8 35
ref
S9472
R33325		 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
R33327		 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
S9470
R33320		 Lowe (Primidone) (Controls unexposed, disease free), 1973 Malformations 1st trimester population based cohort retrospective unexposed, disease free excluded Adjustment: No 5.08 [0.26;98.39] C
excluded (control group) 		0/4   865/31,632 865 4
ref
S9471
R33322		 Lowe (Primidone) (Controls unexposed, sick), 1973 Malformations 1st trimester population based cohort retrospective unexposed, sick Adjustment: No 4.39 [0.19;102.26] C 0/4   3/111 3 4
ref
Total 10 studies 2.74 [1.43;5.24] 49,650 161
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]524%ROB confusion: criticalROB selection: moderateROB classification: lowROB missing: moderateROB mesure: moderateROB reporting: moderate Tomson (Primidone), 2018Tomson, 2018 2 2.67[0.81; 8.87]774029%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]49,49995%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Bànhidy (Primidone), 2011Bànhidy, 2011 4 0.56[0.12; 2.54]161018%ROB confusion: criticalROB selection: criticalROB classification: lowROB missing: lowROB mesure: moderateROB reporting: moderate Kaaja (Primidone), 2003Kaaja, 2003 5 23.70[1.83; 306.18]366%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Dean (Primidone), 2002Dean, 2002 6 1.36[0.05; 36.71]724%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Canger (Primidone), 1999Canger, 1999 7 5.44[0.27; 110.44]3355%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Kaneko (Primidone), 1999Kaneko, 1999 8 5.28[1.19; 23.40]83519%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Samrén (Primidone), 1999Samrén, 1999 9 1.91[0.11; 32.49]29185%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Lowe (Primidone) (Controls unexposed, sick), 1973Lowe, 1973 10 4.39[0.19; 102.26]344%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (10 studies) I2 = 0% 2.74[1.43; 5.24]49,6501610.250.01.0ROB: 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; 9: Primidone; 10: Primidone) (Controls unexposed, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 3.91[1.91; 8.02]49,6341510%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 Kaneko (Primidone), 1999 Samrén (Primidone), 1999 Lowe (Primidone) (Controls unexposed, sick), 1973 9 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 3.42[1.16; 10.13]459432%NAVajda (Primidone) (Controls unexposed, sick), 2019 Bànhidy (Primidone), 2011 Kaaja (Primidone), 2003 Dean (Primidone), 2002 Canger (Primidone), 1999 Kaneko (Primidone), 1999 Lowe (Primidone) (Controls unexposed, sick), 1973 7 exposed to other treatment, sickexposed to other treatment, sick 2.67[0.81; 8.87]7740 -NATomson (Primidone), 2018 1 Tags Adjustment   - No  - No 2.74[1.43; 5.24]49,6501610%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 Kaneko (Primidone), 1999 Samrén (Primidone), 1999 Lowe (Primidone) (Controls unexposed, sick), 1973 10 MatchedMatched 0.73[0.19; 2.79]45280%NABànhidy (Primidone), 2011 Samrén (Primidone), 1999 2 All studiesAll studies 2.74[1.43; 5.24]49,6501610%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 Kaneko (Primidone), 1999 Samrén (Primidone), 1999 Lowe (Primidone) (Controls unexposed, sick), 1973 100.250.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-4.05.02.0270.000Vajda (Primidone) (Controls unexposed, sick), 2019Tomson (Primidone), 2018Källén (Primidone) (Controls unexposed, NOS) (Indications NOS), 2013Bànhidy (Primidone), 2011Kaaja (Primidone), 2003Dean (Primidone), 2002Canger (Primidone), 1999Kaneko (Primidone), 1999Samrén (Primidone), 1999Lowe (Primidone) (Controls unexposed, sick), 1973

Asymetry test p-value = 0.4372 (by Egger's regression)

slope=0.3325 (0.8917); intercept=0.6964 (0.8517); t=0.8177; p=0.4372

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 9470, 9455, 9458, 9475

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 2.55[0.48; 13.48]50,393310%NAKällén (Primidone) (Controls unexposed, NOS) (Indications NOS), 2013 Samrén (Primidone), 1999 Lowe (Primidone) (Controls unexposed, disease free), 1973 3 unexposed, sick controlsunexposed, sick controls 3.42[1.16; 10.13]459432%NAVajda (Primidone) (Controls unexposed, sick), 2019 Bànhidy (Primidone), 2011 Kaaja (Primidone), 2003 Dean (Primidone), 2002 Canger (Primidone), 1999 Kaneko (Primidone), 1999 Lowe (Primidone) (Controls unexposed, sick), 1973 7 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