Topiramate (All indications)

Small for gestational age (weight)

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.
S12543
R47233		 Dreier (Topiramate), 2021 Small for gestational age (birth weight below the 10th percentile for GA, sex and country) during pregnancy (anytime or not specified) population based cohort retrospective unexposed, sick Adjustment: Yes 1.61 [1.10;2.36] -/217   -/- - 217
ref
S8613
R28735		 Coste (Topiramate) (Controls unexposed, NOS) (Mixed indications), 2020 Small for gestational age (weight) during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No 1.20 [0.91;1.59] C 55/477   167,376/1,710,441 167,431 477
ref
S8592
R28596		 Cohen (Topiramate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2019 Small for gestational age (ICD-9 656.5, 764.0, 764.1, 764.9) early pregnancy retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: Yes 1.43 [0.96;2.12]
excluded (control group) 		88/2,280   106/2,682 194 2,280
ref
S8593
R28603		 Cohen (Topiramate) (Controls unexposed NOS) (Mixed indications), 2019 Small for gestational age (ICD-9 656.5, 764.0, 764.1, 764.9) early pregnancy retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes 0.95 [0.76;1.17] 88/2,280   41,653/1,440,631 41,741 2,280
ref
S8602
R28635		 Bank (Topiramate) (Mixed indications) , 2017 Small for Gestational Age birthweight (<10th percentile) during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick Adjustment: No 11.00 [0.54;223.91] C 1/2   3/36 4 2
ref
S8601
R28633		 Hernández-Díaz (Topiramate), 2017 Small for gestational age during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick Adjustment: Yes 2.40 [1.80;3.10] -/394   -/1,799 - 394
ref
S8608
R28701		 Kilic (Topiramate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014 Small for gestational age (birth weight <10% percentile for the gestational birth week) during pregnancy (anytime or not specified) population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No 2.09 [1.02;4.28] C
excluded (control group) 		10/59   78/876 88 59
ref
S8609
R28704		 Kilic (Topiramate) (Controls unexposed NOS) (Mixed indications), 2014 Small for gestational age (birth weight <10% percentile for the gestational birth week) during pregnancy (anytime or not specified) population based cohort retrospective unexposed (general population or NOS) excluded Adjustment: No 1.91 [0.97;3.77] C
excluded (control group) 		10/59   65,118/673,844 65,128 59
ref
S8610
R28707		 Kilic (Topiramate) (Controls unexposed, sick) (Mixed indications), 2014 Small for gestational age (birth weight <10% percentile for the gestational birth week) during pregnancy (anytime or not specified) population based cohort retrospective unexposed, sick Adjustment: No Controls: epilepsy indication 1.61 [0.81;3.19] C 10/59   594/5,275 604 59
ref
S8595
R28612		 Veiby (Topiramate) (Controls unexposed, disease free) (Mixed indications), 2014 Small for gestational age (SGA) birth weight < 10th percentile throughout pregnancy population based cohort retrospective unexposed, disease free excluded Adjustment: Yes 3.29 [1.70;6.39]
excluded (control group) 		12/48   68,656/771,412 68,668 48
ref
S8596
R28615		 Veiby (Topiramate) (Controls unexposed, sick) (Mixed indications), 2014 Small for gestational age (SGA) birth weight < 10th percentile throughout pregnancy population based cohort retrospective unexposed, sick Adjustment: No Controls: epilepsy indication 2.90 [1.50;5.62] C 12/48   389/3,773 401 48
ref
Total 7 studies 1.64 [1.13;2.38] 210,181 3,477
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 Dreier (Topiramate), 2021Dreier, 2021 1 1.61[1.10; 2.36]-21717%ROB confusion: unclearROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Coste (Topiramate) (Controls unexposed, NOS) (Mixed indications), 2020Coste, 2020 2 1.20[0.91; 1.59]167,43147719%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Cohen (Topiramate) (Controls unexposed NOS) (Mixed indications), 2019Cohen, 2019 3 0.95[0.76; 1.17]41,7412,28019%ROB confusion: moderateROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Bank (Topiramate) (Mixed indications) , 2017Bank, 2017 4 11.00[0.54; 223.91]421%ROB confusion: criticalROB selection: lowROB classification: lowROB missing: lowROB mesure: moderateROB reporting: moderate Hernández-Díaz (Topiramate), 2017Hernández-Díaz, 2017 5 2.40[1.80; 3.10]-39419%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Kilic (Topiramate) (Controls unexposed, sick) (Mixed indications), 2014Kilic, 2014 6 1.61[0.81; 3.19]6045912%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Veiby (Topiramate) (Controls unexposed, sick) (Mixed indications), 2014Veiby, 2014 7 2.90[1.50; 5.62]4014813%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: moderateROB reporting: moderate Total (7 studies) I2 = 83% 1.64[1.13; 2.38]210,1813,4770.250.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

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

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.64[1.13; 2.38]210,1813,47783%NADreier (Topiramate), 2021 Coste (Topiramate) (Controls unexposed, NOS) (Mixed indications), 2020 Cohen (Topiramate) (Controls unexposed NOS) (Mixed indications), 2019 Bank (Topiramate) (Mixed indications) , 2017 Hernández-Díaz (Topiramate), 2017 Kilic (Topiramate) (Controls unexposed, sick) (Mixed indications), 2014 Veiby (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) 1.05[0.84; 1.32]209,1722,75741%NACoste (Topiramate) (Controls unexposed, NOS) (Mixed indications), 2020 Cohen (Topiramate) (Controls unexposed NOS) (Mixed indications), 2019 2 unexposed, sickunexposed, sick 1.85[1.31; 2.60]1,00532418%NADreier (Topiramate), 2021 Kilic (Topiramate) (Controls unexposed, sick) (Mixed indications), 2014 Veiby (Topiramate) (Controls unexposed, sick) (Mixed indications), 2014 3 exposed to other treatment, sickexposed to other treatment, sick 2.43[1.85; 3.19]43960%NABank (Topiramate) (Mixed indications) , 2017 Hernández-Díaz (Topiramate), 2017 2 Tags Adjustment   - No  - No 1.78[1.03; 3.09]168,44058661%NACoste (Topiramate) (Controls unexposed, NOS) (Mixed indications), 2020 Bank (Topiramate) (Mixed indications) , 2017 Kilic (Topiramate) (Controls unexposed, sick) (Mixed indications), 2014 Veiby (Topiramate) (Controls unexposed, sick) (Mixed indications), 2014 4   - Yes  - Yes 1.53[0.83; 2.82]41,7412,89193%NADreier (Topiramate), 2021 Cohen (Topiramate) (Controls unexposed NOS) (Mixed indications), 2019 Hernández-Díaz (Topiramate), 2017 3 Controls   - epilepsy indication  - epilepsy indication 2.17[1.22; 3.87]1,00510732%NAKilic (Topiramate) (Controls unexposed, sick) (Mixed indications), 2014 Veiby (Topiramate) (Controls unexposed, sick) (Mixed indications), 2014 2 All studiesAll studies 1.64[1.13; 2.38]210,1813,47783%NADreier (Topiramate), 2021 Coste (Topiramate) (Controls unexposed, NOS) (Mixed indications), 2020 Cohen (Topiramate) (Controls unexposed NOS) (Mixed indications), 2019 Bank (Topiramate) (Mixed indications) , 2017 Hernández-Díaz (Topiramate), 2017 Kilic (Topiramate) (Controls unexposed, sick) (Mixed indications), 2014 Veiby (Topiramate) (Controls unexposed, sick) (Mixed indications), 2014 70.250.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-3.64.11.8450.000Dreier (Topiramate), 2021Coste (Topiramate) (Controls unexposed, NOS) (Mixed indications), 2020Cohen (Topiramate) (Controls unexposed NOS) (Mixed indications), 2019Bank (Topiramate) (Mixed indications) , 2017Hernández-Díaz (Topiramate), 2017Kilic (Topiramate) (Controls unexposed, sick) (Mixed indications), 2014Veiby (Topiramate) (Controls unexposed, sick) (Mixed indications), 2014

Asymetry test p-value = 0.2563 (by Egger's regression)

slope=-0.0176 (0.3183); intercept=2.3226 (1.8126); t=1.2814; p=0.2563

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 8608, 8609, 8595, 8592

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.47[0.96; 2.27]342,9682,86480%NACoste (Topiramate) (Controls unexposed, NOS) (Mixed indications), 2020 Cohen (Topiramate) (Controls unexposed NOS) (Mixed indications), 2019 Kilic (Topiramate) (Controls unexposed NOS) (Mixed indications), 2014 Veiby (Topiramate) (Controls unexposed, disease free) (Mixed indications), 2014 4 unexposed, sick controlsunexposed, sick controls 1.85[1.31; 2.60]1,00532418%NADreier (Topiramate), 2021 Kilic (Topiramate) (Controls unexposed, sick) (Mixed indications), 2014 Veiby (Topiramate) (Controls unexposed, sick) (Mixed indications), 2014 3 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.99[1.38; 2.88]2862,73547%NACohen (Topiramate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2019 Bank (Topiramate) (Mixed indications) , 2017 Hernández-Díaz (Topiramate), 2017 Kilic (Topiramate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014 40.510.01.0