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

Preterm (< 37 weeks)

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.
S18704
R79571		 Mazzone (Topiramate) (Controls exposed to LTG) (Mixed indications), 2025 Preterm birth during pregnancy (anytime or not specified) population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No 1.13 [0.77;1.67] C
excluded (control group) 		37/391   124/1,469 161 391
ref
S18705
R79578		 Mazzone (Topiramate) (Controls unexposed, NOS) (Mixed indications), 2025 Preterm birth during pregnancy (anytime or not specified) population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes 1.20 [0.74;1.96] 37/391   36,613/624,794 36,650 391
ref
S16187
R79427		 The NAAED (Topiramate) (Controls exposed to LTG) (Indications NOS), 2025 Preterm (<37 wk) at least 1st trimester prospective cohort exposed to other treatment, sick excluded Adjustment: No 1.18 [0.87;1.60] C
excluded (control group) 		58/510   241/2,461 299 510
ref
S16177
R79441		 The NAAED (Topiramate) (Controls unexposed, disease free) (Indications NOS), 2025 Preterm (<37 wk) at least 1st trimester prospective cohort unexposed, disease free Adjustment: No 0.76 [0.56;1.04] C 58/510   189/1,311 247 510
ref
S10103
R36814		 Coste (Topiramate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2020 Gestational age at birth (< 37 WA) during pregnancy (anytime or not specified) retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No 1.23 [0.85;1.78] C
excluded (control group) 		36/477   182/2,916 218 477
ref
S8613
R28732		 Coste (Topiramate) (Controls unexposed, NOS) (Mixed indications), 2020 Gestational age at birth (< 37 WA) during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No 1.45 [1.03;2.03] C 36/477   91,255/1,710,441 91,291 477
ref
S8592
R28597		 Cohen (Topiramate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2019 Preterm birth (ICD-9 644.2, 774.2, 776.6, 362.20, 362.22, 362.27, 765 excluding 765.20, 765.29) early pregnancy retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: Yes 0.90 [0.70;1.17]
excluded (control group) 		305/2,280   392/2,682 697 2,280
ref
S8593
R28604		 Cohen (Topiramate) (Controls unexposed NOS) (Mixed indications), 2019 Preterm birth (ICD-9 644.2, 774.2, 776.6, 362.20, 362.22, 362.27, 765 excluding 765.20, 765.29) early pregnancy retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes 0.89 [0.80;1.00] 305/2,280   160,604/1,440,631 160,909 2,280
ref
S8602
R28634		 Bank (Topiramate) (Mixed indications) , 2017 Premature (<37 weeks gestation) during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick Adjustment: No 35.00 [1.16;1060.29] C 1/2   1/36 2 2
ref
S8554
R28459		 Arkilo (Topiramate), 2015 Premature delivery during pregnancy (anytime or not specified) retrospective cohort exposed to other treatment, sick Adjustment: No 1.95 [0.07;58.24] C 0/2   3/24 3 2
ref
S8608
R28702		 Kilic (Topiramate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014 Preterm (< 37 weeks) during pregnancy (anytime or not specified) population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No 0.89 [0.35;2.28] C
excluded (control group) 		5/59   83/880 88 59
ref
S8609
R28705		 Kilic (Topiramate) (Controls unexposed NOS) (Mixed indications), 2014 Preterm (< 37 weeks) during pregnancy (anytime or not specified) population based cohort retrospective unexposed (general population or NOS) excluded Adjustment: No 1.75 [0.70;4.38] C
excluded (control group) 		5/59   33,974/676,834 33,979 59
ref
S8610
R28708		 Kilic (Topiramate) (Controls unexposed, sick) (Mixed indications), 2014 Preterm (< 37 weeks) during pregnancy (anytime or not specified) population based cohort retrospective unexposed, sick Adjustment: No Controls: epilepsy indication 1.19 [0.47;2.99] C 5/59   383/5,296 388 59
ref
Total 7 studies 1.05 [0.80;1.36] 289,490 3,721
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 Mazzone (Topiramate) (Controls unexposed, NOS) (Mixed indications), 2025Mazzone, 2025 1 1.20[0.74; 1.96]36,65039116%ROB confusion: seriousROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate The NAAED (Topiramate) (Controls unexposed, disease free) (Indications NOS), 2025The NAAED, 2025 2 0.76[0.56; 1.04]24751023%ROB confusion: criticalROB selection: unclearROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: low Coste (Topiramate) (Controls unexposed, NOS) (Mixed indications), 2020Coste, 2020 3 1.45[1.03; 2.03]91,29147722%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Cohen (Topiramate) (Controls unexposed NOS) (Mixed indications), 2019Cohen, 2019 4 0.89[0.80; 1.00]160,9092,28032%ROB confusion: moderateROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Bank (Topiramate) (Mixed indications) , 2017Bank, 2017 5 35.00[1.16; 1060.29]221%ROB confusion: criticalROB selection: lowROB classification: lowROB missing: lowROB mesure: moderateROB reporting: moderate Arkilo (Topiramate), 2015Arkilo, 2015 6 1.95[0.07; 58.24]321%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Kilic (Topiramate) (Controls unexposed, sick) (Mixed indications), 2014Kilic, 2014 7 1.19[0.47; 2.99]388597%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Total (7 studies) I2 = 59% 1.05[0.80; 1.36]289,4903,7210.2100.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Topiramate) (Controls unexposed, NOS) (Mixed indications; 2: Topiramate) (Controls unexposed, disease free) (Indications NOS; 3: Topiramate) (Controls unexposed, NOS) (Mixed indications; 4: Topiramate) (Controls unexposed NOS) (Mixed indications; 5: Topiramate) (Mixed indications; 6: Topiramate; 7: Topiramate) (Controls unexposed, sick) (Mixed indications;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.05[0.80; 1.36]289,4903,72159%NAMazzone (Topiramate) (Controls unexposed, NOS) (Mixed indications), 2025 The NAAED (Topiramate) (Controls unexposed, disease free) (Indications NOS), 2025 Coste (Topiramate) (Controls unexposed, NOS) (Mixed indications), 2020 Cohen (Topiramate) (Controls unexposed NOS) (Mixed indications), 2019 Bank (Topiramate) (Mixed indications) , 2017 Arkilo (Topiramate), 2015 Kilic (Topiramate) (Controls unexposed, sick) (Mixed indications), 2014 7 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.01[0.78; 1.30]289,0973,65869%NAMazzone (Topiramate) (Controls unexposed, NOS) (Mixed indications), 2025 The NAAED (Topiramate) (Controls unexposed, disease free) (Indications NOS), 2025 Coste (Topiramate) (Controls unexposed, NOS) (Mixed indications), 2020 Cohen (Topiramate) (Controls unexposed NOS) (Mixed indications), 2019 4 unexposed, sickunexposed, sick 1.19[0.47; 2.99]38859 -NAKilic (Topiramate) (Controls unexposed, sick) (Mixed indications), 2014 1 exposed to other treatment, sickexposed to other treatment, sick 8.23[0.49; 139.21]5428%NABank (Topiramate) (Mixed indications) , 2017 Arkilo (Topiramate), 2015 2 Tags Adjustment   - No  - No 1.19[0.69; 2.05]91,9311,05066%NAThe NAAED (Topiramate) (Controls unexposed, disease free) (Indications NOS), 2025 Coste (Topiramate) (Controls unexposed, NOS) (Mixed indications), 2020 Bank (Topiramate) (Mixed indications) , 2017 Arkilo (Topiramate), 2015 Kilic (Topiramate) (Controls unexposed, sick) (Mixed indications), 2014 5   - Yes  - Yes 0.94[0.75; 1.17]197,5592,67127%NAMazzone (Topiramate) (Controls unexposed, NOS) (Mixed indications), 2025 Cohen (Topiramate) (Controls unexposed NOS) (Mixed indications), 2019 2 Controls   - epilepsy indication  - epilepsy indication 1.19[0.47; 2.99]38859 -NAKilic (Topiramate) (Controls unexposed, sick) (Mixed indications), 2014 1 All studiesAll studies 1.05[0.80; 1.36]289,4903,72159%NAMazzone (Topiramate) (Controls unexposed, NOS) (Mixed indications), 2025 The NAAED (Topiramate) (Controls unexposed, disease free) (Indications NOS), 2025 Coste (Topiramate) (Controls unexposed, NOS) (Mixed indications), 2020 Cohen (Topiramate) (Controls unexposed NOS) (Mixed indications), 2019 Bank (Topiramate) (Mixed indications) , 2017 Arkilo (Topiramate), 2015 Kilic (Topiramate) (Controls unexposed, sick) (Mixed indications), 2014 70.2100.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-4.34.32.0880.000Mazzone (Topiramate) (Controls unexposed, NOS) (Mixed indications), 2025The NAAED (Topiramate) (Controls unexposed, disease free) (Indications NOS), 2025Coste (Topiramate) (Controls unexposed, NOS) (Mixed indications), 2020Cohen (Topiramate) (Controls unexposed NOS) (Mixed indications), 2019Bank (Topiramate) (Mixed indications) , 2017Arkilo (Topiramate), 2015Kilic (Topiramate) (Controls unexposed, sick) (Mixed indications), 2014

Asymetry test p-value = 0.1271 (by Egger's regression)

slope=-0.1887 (0.0915); intercept=1.2684 (0.6939); t=1.8278; p=0.1271

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 8608, 8609, 8592, 10103, 18704, 16187

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.04[0.81; 1.35]323,0763,71765%NAMazzone (Topiramate) (Controls unexposed, NOS) (Mixed indications), 2025 The NAAED (Topiramate) (Controls unexposed, disease free) (Indications NOS), 2025 Coste (Topiramate) (Controls unexposed, NOS) (Mixed indications), 2020 Cohen (Topiramate) (Controls unexposed NOS) (Mixed indications), 2019 Kilic (Topiramate) (Controls unexposed NOS) (Mixed indications), 2014 5 unexposed, sick controlsunexposed, sick controls 1.19[0.47; 2.99]38859 -NAKilic (Topiramate) (Controls unexposed, sick) (Mixed indications), 2014 1 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.08[0.90; 1.30]1,4683,72115%NAMazzone (Topiramate) (Controls exposed to LTG) (Mixed indications), 2025 The NAAED (Topiramate) (Controls exposed to LTG) (Indications NOS), 2025 Coste (Topiramate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2020 Cohen (Topiramate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2019 Bank (Topiramate) (Mixed indications) , 2017 Arkilo (Topiramate), 2015 Kilic (Topiramate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014 70.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Veroniki a (NMA) (All indications) (Preterm birth)Veroniki a (NMA) (All indications) (Preterm birth) 1.38[0.73; 2.35]NA-Wwhatever (meta-analysis)Anyduring pregnancy (anytime or not specified)studies TTT-9 metaPregmetaPreg 1.05[0.80; 1.36]59%3,721----Mazzone (Topiramate) (Controls unexposed, NOS) (Mixed indications), 2025 The NAAED (Topiramate) (Controls unexposed, disease free) (Indications NOS), 2025 Coste (Topiramate) (Controls unexposed, NOS) (Mixed indications), 2020 Cohen (Topiramate) (Controls unexposed NOS) (Mixed indications), 2019 Bank (Topiramate) (Mixed indications) , 2017 Arkilo (Topiramate), 2015 Kilic (Topiramate) (Controls unexposed, sick) (Mixed indications), 2014 70.510.01.0