Clonazepam (Epilepsy) updated on 02-10-2025

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.
S16578
R69638		 Battino (Epilepsy), 2024 Major congenital malformations (MCMs) early pregnancy prospective cohort exposed to other treatment, sick Adjustment: No 0.31 [0.02;4.98] C 0/52   110/3,584 110 52
ref
S7777
R35187		 Vajda (Epilepsy) (Controls exposed to Lamotrigine, sick), 2024 Fetal malformations early pregnancy prospective cohort exposed to other treatment, sick excluded Adjustment: No 0.98 [0.13;7.66] C
excluded (control group) 		1/24   20/473 21 24
ref
S7778
R35188		 Vajda (Epilepsy) (Controls unexposed, sick), 2024 Fetal malformations at least 1st trimester prospective cohort unexposed, sick Adjustment: No 1.20 [0.15;9.31] 1/24   7/201 8 24
ref
S12876
R48644		 Thomas (Epilepsy) (Controls exposed to Lamotrigine, sick), 2021 Major congenital malformations 1st trimester prospective cohort exposed to other treatment, sick excluded Adjustment: No 4.62 [0.16;135.60] C
excluded (control group) 		0/4   1/50 1 4
ref
S12877
R48654		 Thomas (Epilepsy) (Controls unexposed, sick), 2021 Major congenital malformations 1st trimester prospective cohort unexposed, sick Adjustment: No 2.80 [0.14;56.50] C 0/4   16/340 16 4
ref
S16167
R75507		 Guveli (Epilepsy), 2017 Major malformations during pregnancy (anytime or not specified) excluded retrospective cohort unexposed, sick Adjustment: No 5.44 [0.15;199.32] C
excluded (exposition period) 		0/2   1/26 1 2
ref
S6324
R26928		 Veiby (Epilepsy) (Controls exposed to Lamotrigine, sick), 2014 Major malformations throughout pregnancy population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No 0.64 [0.08;4.83] C
excluded (control group) 		1/40   23/593 24 40
ref
S6325
R26929		 Veiby (Epilepsy) (Controls unexposed, disease free), 2014 Major malformations throughout pregnancy population based cohort retrospective unexposed, disease free excluded Adjustment: Yes 0.99 [0.14;7.22]
excluded (control group) 		1/40   22,371/771,412 22,372 40
ref
S6326
R26930		 Veiby (Epilepsy) (Controls unexposed, sick), 2014 Major malformations throughout pregnancy population based cohort retrospective unexposed, sick Adjustment: No 0.89 [0.12;6.52] C 1/40   106/3,773 107 40
ref
S6494
R35115		 Bànhidy (Epilepsy), 2011 Total congenital abnormalities throughout pregnancy case control unexposed, sick Adjustment: No Matched 0.28 [0.01;7.57] C 0/1   12/22 12 1
ref
S6067
R26924		 Morrow (Epilepsy) (Controls exposed to Lamotrigine, sick), 2006 Major congenital malformation 1st trimester prospective cohort exposed to other treatment, sick excluded Adjustment: No 1.71 [0.10;30.62] C
excluded (control group) 		0/9   21/647 21 9
ref
S6068
R26925		 Morrow (Epilepsy) (Controls unexposed, sick), 2006 Major congenital malformation 1st trimester prospective cohort unexposed, sick Adjustment: No 1.51 [0.08;28.41] C 0/9   8/227 8 9
ref
S8222
R25758		 Endo (Epilepsy) (Controls unexposed, disease free), 2004 Congenital malformations throughout pregnancy retrospective cohort unexposed, disease free excluded Adjustment: No 22.85 [0.45;1173.45] C
excluded (control group) 		0/1   27/656 27 1
ref
S8224
R25788		 Endo (Epilepsy) (Controls unexposed, sick), 2004 Congenital malformations throughout pregnancy retrospective cohort unexposed, sick Adjustment: No 1.00 [0.00;255.63] C 0/1   0/1 0 1
ref
S6138
R26921		 Kaaja (Epilepsy), 2003 Major malformation 1st trimester prospective cohort unexposed, sick Adjustment: No 3.78 [0.17;83.10] C 0/13   2/239 2 13
ref
S6927
R26919		 Hvas (Epilepsy) (Controls unexposed, disease free), 2000 Major congenital malformations 1st trimester prospective cohort unexposed, disease free excluded Adjustment: No 2.89 [0.17;48.65] C
excluded (control group) 		0/15   280/23,827 280 15
ref
S6923
R26920		 Hvas (Epilepsy) (Controls unexposed, sick), 2000 Major congenital malformations 1st trimester prospective cohort unexposed, sick Adjustment: No 7.28 [0.14;381.01] C 0/15   0/106 0 15
ref
S8352
R26466		 Al Bunyan (Epilepsy), 1999 Congenital malformations during pregnancy (anytime or not specified) excluded retrospective cohort unexposed, sick Adjustment: No 19.00 [0.15;2409.97] C
excluded (exposition period) 		0/1   0/10 0 1
ref
S328
R17704		 Canger (Epilepsy), 1999 All type of malformation 1st trimester prospective cohort unexposed, sick Adjustment: No 4.45 [0.08;250.02] C 0/6   0/25 0 6
ref
S7396
R26926		 Samrén (Epilepsy), 1999 Major congential abnormalities at least 1st trimester retrospective cohort unexposed, disease free Adjustment: No Matched 3.93 [0.22;69.67] C 0/9   29/2,000 29 9
ref
S6688
R18666		 D'Souza (Epilepsy) (Controls unexposed, disease free), 1991 Congenital anomalies throughout pregnancy prospective cohort unexposed, disease free excluded Adjustment: No Matched 123.00 [1.00;15058.31] C
excluded (control group) 		0/1   0/62 0 1
ref
S6696
R18827		 D'Souza (Epilepsy) (Controls unexposed, sick), 1991 Congenital anomalies throughout pregnancy prospective cohort unexposed, sick Adjustment: No 4.33 [0.06;320.42] C 0/1   1/8 1 1
ref
S6165
R16404		 Robert (Epilepsy), 1986 Congenital malformations (minor and major) 1st trimester retrospective cohort unexposed, sick Adjustment: No 6.78 [0.12;386.32] C 0/1   4/35 4 1
ref
Total 13 studies 1.55 [0.67;3.56] 297 176
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 Battino (Epilepsy), 2024Battino, 2024 1 0.31[0.02; 4.98]110529%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: moderateROB reporting: moderate Vajda (Epilepsy) (Controls unexposed, sick), 2024Vajda, 2024 2 1.20[0.15; 9.31]82417%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: moderateROB reporting: moderate Thomas (Epilepsy) (Controls unexposed, sick), 2021Thomas, 2021 3 2.80[0.14; 56.50]1648%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Veiby (Epilepsy) (Controls unexposed, sick), 2014Veiby, 2014 4 0.89[0.12; 6.52]1074018%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: moderateROB reporting: moderate Bànhidy (Epilepsy), 2011Bànhidy, 2011 5 0.28[0.01; 7.57]1216%ROB confusion: criticalROB selection: criticalROB classification: lowROB missing: lowROB mesure: moderateROB reporting: moderate Morrow (Epilepsy) (Controls unexposed, sick), 2006Morrow, 2006 6 1.51[0.08; 28.41]898%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: criticalROB reporting: moderate Endo (Epilepsy) (Controls unexposed, sick), 2004Endo, 2004 7 1.00[0.00; 255.63]012%ROB confusion: criticalROB selection: unclearROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Kaaja (Epilepsy), 2003Kaaja, 2003 8 3.78[0.17; 83.10]2137%ROB confusion: criticalROB selection: moderateROB classification: lowROB missing: lowROB mesure: moderateROB reporting: moderate Hvas (Epilepsy) (Controls unexposed, sick), 2000Hvas, 2000 9 7.28[0.14; 381.01]0154%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: lowROB mesure: criticalROB reporting: moderate Canger (Epilepsy), 1999Canger, 1999 10 4.45[0.08; 250.02]064%ROB confusion: criticalROB selection: moderateROB classification: lowROB missing: unclearROB mesure: criticalROB reporting: moderate Samrén (Epilepsy), 1999Samrén, 1999 11 3.93[0.22; 69.67]2998%ROB confusion: criticalROB selection: unclearROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate D'Souza (Epilepsy) (Controls unexposed, sick), 1991D'Souza, 1991 12 4.33[0.06; 320.42]114%ROB confusion: criticalROB selection: unclearROB classification: lowROB missing: unclearROB mesure: lowROB reporting: moderate Robert (Epilepsy), 1986Robert, 1986 13 6.78[0.12; 386.32]414%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: unclearROB mesure: unclearROB reporting: moderate Total (13 studies) I2 = 0% 1.55[0.67; 3.56]2971760.220.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Epilepsy; 2: Epilepsy) (Controls unexposed, sick; 3: Epilepsy) (Controls unexposed, sick; 4: Epilepsy) (Controls unexposed, sick; 5: Epilepsy; 6: Epilepsy) (Controls unexposed, sick; 7: Epilepsy) (Controls unexposed, sick; 8: Epilepsy; 9: Epilepsy) (Controls unexposed, sick; 10: Epilepsy; 11: Epilepsy; 12: Epilepsy) (Controls unexposed, sick; 13: Epilepsy;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.74[0.73; 4.12]2851750%NABattino (Epilepsy), 2024 Vajda (Epilepsy) (Controls unexposed, sick), 2024 Thomas (Epilepsy) (Controls unexposed, sick), 2021 Veiby (Epilepsy) (Controls unexposed, sick), 2014 Morrow (Epilepsy) (Controls unexposed, sick), 2006 Endo (Epilepsy) (Controls unexposed, sick), 2004 Kaaja (Epilepsy), 2003 Hvas (Epilepsy) (Controls unexposed, sick), 2000 Canger (Epilepsy), 1999 Samrén (Epilepsy), 1999 D'Souza (Epilepsy) (Controls unexposed, sick), 1991 Robert (Epilepsy), 1986 12 case control studiescase control studies 0.28[0.01; 7.57]121 -NABànhidy (Epilepsy), 2011 1 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 3.93[0.22; 69.67]299 -NASamrén (Epilepsy), 1999 1 unexposed, sickunexposed, sick 1.68[0.67; 4.20]1581150%NAVajda (Epilepsy) (Controls unexposed, sick), 2024 Thomas (Epilepsy) (Controls unexposed, sick), 2021 Veiby (Epilepsy) (Controls unexposed, sick), 2014 Bànhidy (Epilepsy), 2011 Morrow (Epilepsy) (Controls unexposed, sick), 2006 Endo (Epilepsy) (Controls unexposed, sick), 2004 Kaaja (Epilepsy), 2003 Hvas (Epilepsy) (Controls unexposed, sick), 2000 Canger (Epilepsy), 1999 D'Souza (Epilepsy) (Controls unexposed, sick), 1991 Robert (Epilepsy), 1986 11 exposed to other treatment, sickexposed to other treatment, sick 0.31[0.02; 4.98]11052 -NABattino (Epilepsy), 2024 1 Tags Adjustment   - No  - No 1.55[0.67; 3.56]2971760%NABattino (Epilepsy), 2024 Vajda (Epilepsy) (Controls unexposed, sick), 2024 Thomas (Epilepsy) (Controls unexposed, sick), 2021 Veiby (Epilepsy) (Controls unexposed, sick), 2014 Bànhidy (Epilepsy), 2011 Morrow (Epilepsy) (Controls unexposed, sick), 2006 Endo (Epilepsy) (Controls unexposed, sick), 2004 Kaaja (Epilepsy), 2003 Hvas (Epilepsy) (Controls unexposed, sick), 2000 Canger (Epilepsy), 1999 Samrén (Epilepsy), 1999 D'Souza (Epilepsy) (Controls unexposed, sick), 1991 Robert (Epilepsy), 1986 13 MatchedMatched 1.19[0.09; 15.87]411029%NABànhidy (Epilepsy), 2011 Samrén (Epilepsy), 1999 2 All studiesAll studies 1.55[0.67; 3.56]2971760%NABattino (Epilepsy), 2024 Vajda (Epilepsy) (Controls unexposed, sick), 2024 Thomas (Epilepsy) (Controls unexposed, sick), 2021 Veiby (Epilepsy) (Controls unexposed, sick), 2014 Bànhidy (Epilepsy), 2011 Morrow (Epilepsy) (Controls unexposed, sick), 2006 Endo (Epilepsy) (Controls unexposed, sick), 2004 Kaaja (Epilepsy), 2003 Hvas (Epilepsy) (Controls unexposed, sick), 2000 Canger (Epilepsy), 1999 Samrén (Epilepsy), 1999 D'Souza (Epilepsy) (Controls unexposed, sick), 1991 Robert (Epilepsy), 1986 130.120.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-6.77.13.3940.000Battino (Epilepsy), 2024Vajda (Epilepsy) (Controls unexposed, sick), 2024Thomas (Epilepsy) (Controls unexposed, sick), 2021Veiby (Epilepsy) (Controls unexposed, sick), 2014Bànhidy (Epilepsy), 2011Morrow (Epilepsy) (Controls unexposed, sick), 2006Endo (Epilepsy) (Controls unexposed, sick), 2004Kaaja (Epilepsy), 2003Hvas (Epilepsy) (Controls unexposed, sick), 2000Canger (Epilepsy), 1999Samrén (Epilepsy), 1999D'Souza (Epilepsy) (Controls unexposed, sick), 1991Robert (Epilepsy), 1986

Asymetry test p-value = 0.1524 (by Egger's regression)

slope=-1.0072 (0.9751); intercept=0.9762 (0.6348); t=1.5378; p=0.1524

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 6688, 6927, 8222, 6067, 6324, 6325, 12876, 7777

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 3.53[0.87; 14.32]22,7086612%NAVeiby (Epilepsy) (Controls unexposed, disease free), 2014 Endo (Epilepsy) (Controls unexposed, disease free), 2004 Hvas (Epilepsy) (Controls unexposed, disease free), 2000 Samrén (Epilepsy), 1999 D'Souza (Epilepsy) (Controls unexposed, disease free), 1991 5 unexposed, sick controlsunexposed, sick controls 1.68[0.67; 4.20]1581150%NAVajda (Epilepsy) (Controls unexposed, sick), 2024 Thomas (Epilepsy) (Controls unexposed, sick), 2021 Veiby (Epilepsy) (Controls unexposed, sick), 2014 Bànhidy (Epilepsy), 2011 Morrow (Epilepsy) (Controls unexposed, sick), 2006 Endo (Epilepsy) (Controls unexposed, sick), 2004 Kaaja (Epilepsy), 2003 Hvas (Epilepsy) (Controls unexposed, sick), 2000 Canger (Epilepsy), 1999 D'Souza (Epilepsy) (Controls unexposed, sick), 1991 Robert (Epilepsy), 1986 11 exposed to other treatment, sick controlsexposed to other treatment, sick controls 0.92[0.30; 2.78]1771290%NABattino (Epilepsy), 2024 Vajda (Epilepsy) (Controls exposed to Lamotrigine, sick), 2024 Thomas (Epilepsy) (Controls exposed to Lamotrigine, sick), 2021 Veiby (Epilepsy) (Controls exposed to Lamotrigine, sick), 2014 Morrow (Epilepsy) (Controls exposed to Lamotrigine, sick), 2006 50.510.01.0