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

Cleft lip with or without cleft palate

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.
S19325
R81925		 Kim (Controls exposed to LTG) (Topiramate) (Indications NOS), 2026 Cleft lip with or without cleft palate 1st trimester population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No 1.42 [0.09;22.71] C
excluded (control group) 		1/507   1/718 2 507
ref
S19318
R81860		 Kim (Controls unexposed, NOS) (Topiramate) (Indications NOS), 2026 Cleft lip with or without cleft palate 1st trimester population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes 2.08 [0.27;16.01] 1/507   1,910/2,489,078 1,911 507
ref
S10173
R37190		 Blotière (Topiramate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2019 Cleft lip with or without cleft palate 1st trimester retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No 8.74 [1.46;52.44] C
excluded (control group) 		3/517   2/2,997 5 517
ref
S10048
R36441		 Blotière (Topiramate) (Controls unexposed NOS) (Mixed indications), 2019 Cleft lip with or without cleft palate 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No 6.80 [1.40;20.00] 3/517   1,637/1,875,733 1,640 517
ref
S8616
R28777		 Mines (Topiramate) (Other indications), 2014 Cleft lip with or without cleft palate 1st trimester retrospective cohort (claims database) unexposed, sick Adjustment: No 2.80 [1.00;7.90] 5/1,745   14/13,512 19 1,745
ref
S10298
R37724		 Vajda (Topiramate) (Controls unexposed, sick), 2013 Palate/lip malformation at least 1st trimester prospective cohort unexposed, sick Adjustment: No 3.37 [0.07;172.23] C 0/44   0/147 0 44
ref
S8568
R28503		 Margulis (Topiramate) (Mixed indication), 2012 Cleft lip with or without cleft palate 1st trimester case control unexposed (general population or NOS) Adjustment: No Matched 5.36 [1.49;20.07] 7/13   3,034/18,401 3,041 13
ref
Total 5 studies 3.95 [2.07;7.54] 6,611 2,826
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 Kim (Controls unexposed, NOS) (Topiramate) (Indications NOS), 2026Kim, 2026 1 2.08[0.27; 16.01]1,91150710%ROB confusion: seriousROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Blotière (Topiramate) (Controls unexposed NOS) (Mixed indications), 2019Blotière, 2019 2 6.80[1.40; 20.00]1,64051724%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Mines (Topiramate) (Other indications), 2014Mines, 2014 3 2.80[1.00; 7.90]191,74539%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Vajda (Topiramate) (Controls unexposed, sick), 2013Vajda, 2013 4 3.37[0.07; 172.23]0443%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Margulis (Topiramate) (Mixed indication), 2012Margulis, 2012 5 5.36[1.49; 20.07]3,0411325%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (5 studies) I2 = 0% 3.95[2.07; 7.54]6,6112,8260.920.01.0ROB: A: confounding, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, NOS) (Topiramate) (Indications NOS; 2: Topiramate) (Controls unexposed NOS) (Mixed indications; 3: Topiramate) (Other indications; 4: Topiramate) (Controls unexposed, sick; 5: Topiramate) (Mixed indication;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 3.58[1.70; 7.53]3,5702,8130%NAKim (Controls unexposed, NOS) (Topiramate) (Indications NOS), 2026 Blotière (Topiramate) (Controls unexposed NOS) (Mixed indications), 2019 Mines (Topiramate) (Other indications), 2014 Vajda (Topiramate) (Controls unexposed, sick), 2013 4 case control studiescase control studies 5.36[1.46; 19.67]3,04113 -NAMargulis (Topiramate) (Mixed indication), 2012 1 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 5.02[2.15; 11.69]6,5921,0370%NAKim (Controls unexposed, NOS) (Topiramate) (Indications NOS), 2026 Blotière (Topiramate) (Controls unexposed NOS) (Mixed indications), 2019 Margulis (Topiramate) (Mixed indication), 2012 3 unexposed, sickunexposed, sick 2.83[1.04; 7.70]191,7890%NAMines (Topiramate) (Other indications), 2014 Vajda (Topiramate) (Controls unexposed, sick), 2013 2 Tags Adjustment   - No  - No 4.24[2.15; 8.38]4,7002,3190%NABlotière (Topiramate) (Controls unexposed NOS) (Mixed indications), 2019 Mines (Topiramate) (Other indications), 2014 Vajda (Topiramate) (Controls unexposed, sick), 2013 Margulis (Topiramate) (Mixed indication), 2012 4   - Yes  - Yes 2.08[0.27; 16.02]1,911507 -NAKim (Controls unexposed, NOS) (Topiramate) (Indications NOS), 2026 1 MatchedMatched 5.36[1.46; 19.67]3,04113 -NAMargulis (Topiramate) (Mixed indication), 2012 1 All studiesAll studies 3.95[2.07; 7.54]6,6112,8260%NAKim (Controls unexposed, NOS) (Topiramate) (Indications NOS), 2026 Blotière (Topiramate) (Controls unexposed NOS) (Mixed indications), 2019 Mines (Topiramate) (Other indications), 2014 Vajda (Topiramate) (Controls unexposed, sick), 2013 Margulis (Topiramate) (Mixed indication), 2012 50.520.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-4.76.12.4090.000Kim (Controls unexposed, NOS) (Topiramate) (Indications NOS), 2026Blotière (Topiramate) (Controls unexposed NOS) (Mixed indications), 2019Mines (Topiramate) (Other indications), 2014Vajda (Topiramate) (Controls unexposed, sick), 2013Margulis (Topiramate) (Mixed indication), 2012

Asymetry test p-value = 0.8884 (by Egger's regression)

slope=1.4715 (0.6824); intercept=-0.1413 (0.9262); t=0.1526; p=0.8884

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 10173, 19325

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 5.02[2.15; 11.69]6,5921,0370%NAKim (Controls unexposed, NOS) (Topiramate) (Indications NOS), 2026 Blotière (Topiramate) (Controls unexposed NOS) (Mixed indications), 2019 Margulis (Topiramate) (Mixed indication), 2012 3 unexposed, sick controlsunexposed, sick controls 2.83[1.04; 7.70]191,7890%NAMines (Topiramate) (Other indications), 2014 Vajda (Topiramate) (Controls unexposed, sick), 2013 2 exposed to other treatment, sick controlsexposed to other treatment, sick controls 4.85[0.91; 25.73]71,02414%NAKim (Controls exposed to LTG) (Topiramate) (Indications NOS), 2026 Blotière (Topiramate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2019 20.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Veroniki a (MA) (All indications) (Cleft Lip/ ...Veroniki a (MA) (All indications) (Cleft Lip/Palate) 5.86[1.94; 16.86]NA-Eexposed to other treatment, sickT11st trimesterstudies TTT2 Veroniki a (NMA) (All indications) (Cleft lip ...Veroniki a (NMA) (All indications) (Cleft lip/palate) 6.12[1.89; 19.05]NA-Wwhatever (meta-analysis)T11st trimesterstudies TTT-9 metaPregmetaPreg 3.95[2.07; 7.54]0%2,826----Kim (Controls unexposed, NOS) (Topiramate) (Indications NOS), 2026 Blotière (Topiramate) (Controls unexposed NOS) (Mixed indications), 2019 Mines (Topiramate) (Other indications), 2014 Vajda (Topiramate) (Controls unexposed, sick), 2013 Margulis (Topiramate) (Mixed indication), 2012 50.510.01.0