Ethosuximide (All indications) updated on 04-22-2025

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.
S16580
R69641		 Battino (Ethosuximide) (Epilepsy), 2024 Major congenital malformations (MCMs) early pregnancy prospective cohort exposed to other treatment, sick Adjustment: No 0.90 [0.05;15.03] C 0/18   110/3,584 110 18
ref
S9790
R35053		 Vajda (Ethosuximide) (Controls exposed to Lamotrigine, sick), 2019 Fetal malformations at least 1st trimester prospective cohort exposed to other treatment, sick excluded Adjustment: No 2.09 [0.11;40.14] C
excluded (control group) 		0/5   20/406 20 5
ref
S9791
R35054		 Vajda (Ethosuximide) (Controls unexposed, sick), 2019 Fetal malformations at least 1st trimester prospective cohort unexposed, sick Adjustment: No 3.44 [0.16;72.20] C 0/5   5/176 5 5
ref
S9780
R35024		 Källén (Ethosuximide) (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 2.57 [0.32;20.45] C
excluded (control group) 		1/12   37/1,084 38 12
ref
S9781
R35026		 Källén (Ethsuximide) (Controls unexposed, NOS) (Indications NOS), 2013 Relatively severe malformations early pregnancy population based cohort retrospective unexposed (general population or NOS) Adjustment: No 2.80 [0.36;21.71] C 1/12   49,499/1,575,847 49,500 12
ref
S9782
R35034		 Bànhidy (Ethosuximide), 2011 Total congenital abnormalities throughout pregnancy case control unexposed, sick Adjustment: No Matched 4.13 [0.18;96.94] C 2/2   12/22 14 2
ref
S9786
R35039		 Morrow (Ethosuximide) (Controls exposed to Lamotrigine, sick), 2006 Major congenital malformation 1st trimester prospective cohort exposed to other treatment, sick excluded Adjustment: No 1.26 [0.07;22.17] C
excluded (control group) 		0/12   21/647 21 12
ref
S9787
R35047		 Morrow (Ethosuximide) (Controls unexposed, sick), 2006 Major congenital malformation 1st trimester prospective cohort unexposed, sick Adjustment: No 1.12 [0.06;20.58] C 0/12   8/227 8 12
ref
S9783
R35035		 Kaaja (Ethosuximide), 2003 Major malformation 1st trimester prospective cohort unexposed, sick Adjustment: No 31.53 [1.02;978.23] C 0/2   2/239 2 2
ref
S9779
R35008		 Dean (Ethosuximide), 2002 Major congenital malformations at least 1st trimester retrospective cohort unexposed, sick Adjustment: No 2.03 [0.08;51.22] C 0/4   2/38 2 4
ref
S9788
R35049		 Samrén (Ethosuximide), 1999 Major congenial 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
Total 8 studies 2.87 [1.05;7.84] 49,670 64
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 (Ethosuximide) (Epilepsy), 2024Battino, 2024 1 0.90[0.05; 15.03]1101813%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: moderateROB reporting: moderate Vajda (Ethosuximide) (Controls unexposed, sick), 2019Vajda, 2019 2 3.44[0.16; 72.20]5511%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Källén (Ethsuximide) (Controls unexposed, NOS) (Indications NOS), 2013Källén, 2013 3 2.80[0.36; 21.71]49,5001224%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Bànhidy (Ethosuximide), 2011Bànhidy, 2011 4 4.13[0.18; 96.94]14210%ROB confusion: criticalROB selection: criticalROB classification: lowROB missing: lowROB mesure: moderateROB reporting: NA Morrow (Ethosuximide) (Controls unexposed, sick), 2006Morrow, 2006 5 1.12[0.06; 20.58]81212%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Kaaja (Ethosuximide), 2003Kaaja, 2003 6 31.53[1.02; 978.23]229%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Dean (Ethosuximide), 2002Dean, 2002 7 2.03[0.08; 51.22]2410%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Samrén (Ethosuximide), 1999Samrén, 1999 8 3.93[0.22; 69.67]29912%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (8 studies) I2 = 0% 2.87[1.05; 7.84]49,670640.2100.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Ethosuximide) (Epilepsy; 2: Ethosuximide) (Controls unexposed, sick; 3: Ethsuximide) (Controls unexposed, NOS) (Indications NOS; 4: Ethosuximide; 5: Ethosuximide) (Controls unexposed, sick; 6: Ethosuximide; 7: Ethosuximide; 8: Ethosuximide;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 2.76[0.96; 7.95]49,656620%NABattino (Ethosuximide) (Epilepsy), 2024 Vajda (Ethosuximide) (Controls unexposed, sick), 2019 Källén (Ethsuximide) (Controls unexposed, NOS) (Indications NOS), 2013 Morrow (Ethosuximide) (Controls unexposed, sick), 2006 Kaaja (Ethosuximide), 2003 Dean (Ethosuximide), 2002 Samrén (Ethosuximide), 1999 7 case control studiescase control studies 4.13[0.18; 96.94]142 -NABànhidy (Ethosuximide), 2011 1 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 3.14[0.59; 16.64]49,529210%NAKällén (Ethsuximide) (Controls unexposed, NOS) (Indications NOS), 2013 Samrén (Ethosuximide), 1999 2 unexposed, sickunexposed, sick 3.60[0.88; 14.67]31250%NAVajda (Ethosuximide) (Controls unexposed, sick), 2019 Bànhidy (Ethosuximide), 2011 Morrow (Ethosuximide) (Controls unexposed, sick), 2006 Kaaja (Ethosuximide), 2003 Dean (Ethosuximide), 2002 5 exposed to other treatment, sickexposed to other treatment, sick 0.90[0.05; 15.03]11018 -NABattino (Ethosuximide) (Epilepsy), 2024 1 Tags Adjustment   - No  - No 2.87[1.05; 7.84]49,670640%NABattino (Ethosuximide) (Epilepsy), 2024 Vajda (Ethosuximide) (Controls unexposed, sick), 2019 Källén (Ethsuximide) (Controls unexposed, NOS) (Indications NOS), 2013 Bànhidy (Ethosuximide), 2011 Morrow (Ethosuximide) (Controls unexposed, sick), 2006 Kaaja (Ethosuximide), 2003 Dean (Ethosuximide), 2002 Samrén (Ethosuximide), 1999 8 MatchedMatched 4.02[0.48; 33.67]43110%NABànhidy (Ethosuximide), 2011 Samrén (Ethosuximide), 1999 2 All studiesAll studies 2.87[1.05; 7.84]49,670640%NABattino (Ethosuximide) (Epilepsy), 2024 Vajda (Ethosuximide) (Controls unexposed, sick), 2019 Källén (Ethsuximide) (Controls unexposed, NOS) (Indications NOS), 2013 Bànhidy (Ethosuximide), 2011 Morrow (Ethosuximide) (Controls unexposed, sick), 2006 Kaaja (Ethosuximide), 2003 Dean (Ethosuximide), 2002 Samrén (Ethosuximide), 1999 80.2100.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-4.15.22.1030.000Battino (Ethosuximide) (Epilepsy), 2024Vajda (Ethosuximide) (Controls unexposed, sick), 2019Källén (Ethsuximide) (Controls unexposed, NOS) (Indications NOS), 2013Bànhidy (Ethosuximide), 2011Morrow (Ethosuximide) (Controls unexposed, sick), 2006Kaaja (Ethosuximide), 2003Dean (Ethosuximide), 2002Samrén (Ethosuximide), 1999

Asymetry test p-value = 0.4637 (by Egger's regression)

slope=-0.6177 (2.1667); intercept=1.1704 (1.4958); t=0.7824; p=0.4637

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 9786, 9780, 9790

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 3.14[0.59; 16.64]49,529210%NAKällén (Ethsuximide) (Controls unexposed, NOS) (Indications NOS), 2013 Samrén (Ethosuximide), 1999 2 unexposed, sick controlsunexposed, sick controls 3.60[0.88; 14.67]31250%NAVajda (Ethosuximide) (Controls unexposed, sick), 2019 Bànhidy (Ethosuximide), 2011 Morrow (Ethosuximide) (Controls unexposed, sick), 2006 Kaaja (Ethosuximide), 2003 Dean (Ethosuximide), 2002 5 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.71[0.47; 6.25]189470%NABattino (Ethosuximide) (Epilepsy), 2024 Vajda (Ethosuximide) (Controls exposed to Lamotrigine, sick), 2019 Källén (Ethosuximide) (Controls exposed to Lamotrigine, sick) (Indications NOS), 2013 Morrow (Ethosuximide) (Controls exposed to Lamotrigine, sick), 2006 40.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Veroniki a (MA) (All indications) (Overall Ma ...Veroniki a (MA) (All indications) (Overall Major Congenital Malformations) 2.86[0.87; 8.87]NA-Wwhatever (meta-analysis)T11st trimesterstudies TTT7 Veroniki a (NMA) (All indications) (Overall m ...Veroniki a (NMA) (All indications) (Overall major congenital malformations) 3.04[1.23; 7.07]NA-Wwhatever (meta-analysis)T11st trimesterstudies TTT7 metaPregmetaPreg 2.87[1.05; 7.84]0%64----Battino (Ethosuximide) (Epilepsy), 2024 Vajda (Ethosuximide) (Controls unexposed, sick), 2019 Källén (Ethsuximide) (Controls unexposed, NOS) (Indications NOS), 2013 Bànhidy (Ethosuximide), 2011 Morrow (Ethosuximide) (Controls unexposed, sick), 2006 Kaaja (Ethosuximide), 2003 Dean (Ethosuximide), 2002 Samrén (Ethosuximide), 1999 80.510.01.0