Topiramate (All indications)

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.
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
S8599
R28627		 Hernández-Díaz (Topiramate) (Mixed indications) (Controls exposed to Lamotrigine, sick), 2014 Preterm (< 37 weeks) during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick excluded Adjustment: No 1.42 [0.96;2.11] C
excluded (control group) 		36/347   119/1,581 155 347
ref
S8600
R28630		 Hernández-Díaz (Topiramate) (Mixed indications) (Controls unexposed, disease free), 2014 Preterm (< 37 weeks) during pregnancy (anytime or not specified) prospective cohort unexposed, disease free Adjustment: No 1.84 [1.10;3.10] C 36/347   27/457 63 347
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 6 studies 1.34 [0.87;2.05] 252,656 3,167
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 Coste (Topiramate) (Controls unexposed, NOS) (Mixed indications), 2020Coste, 2020 1 1.45[1.03; 2.03]91,29147728%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Cohen (Topiramate) (Controls unexposed NOS) (Mixed indications), 2019Cohen, 2019 2 0.89[0.80; 1.00]160,9092,28033%ROB confusion: moderateROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Bank (Topiramate) (Mixed indications) , 2017Bank, 2017 3 35.00[1.16; 1060.29]221%ROB confusion: criticalROB selection: lowROB classification: lowROB missing: lowROB mesure: moderateROB reporting: moderate Arkilo (Topiramate), 2015Arkilo, 2015 4 1.95[0.07; 58.24]322%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Hernández-Díaz (Topiramate) (Mixed indications) (Controls unexposed, disease free), 2014Hernández-Díaz, 2014 5 1.84[1.10; 3.10]6334723%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: moderateROB mesure: moderateROB reporting: moderate Kilic (Topiramate) (Controls unexposed, sick) (Mixed indications), 2014Kilic, 2014 6 1.19[0.47; 2.99]3885913%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Total (6 studies) I2 = 72% 1.34[0.87; 2.05]252,6563,1670.2100.01.0ROB: 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 NOS) (Mixed indications; 3: Topiramate) (Mixed indications; 4: Topiramate; 5: Topiramate) (Mixed indications) (Controls unexposed, disease free; 6: Topiramate) (Controls unexposed, sick) (Mixed indications;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.34[0.87; 2.05]252,6563,16772%NACoste (Topiramate) (Controls unexposed, NOS) (Mixed indications), 2020 Cohen (Topiramate) (Controls unexposed NOS) (Mixed indications), 2019 Bank (Topiramate) (Mixed indications) , 2017 Arkilo (Topiramate), 2015 Hernández-Díaz (Topiramate) (Mixed indications) (Controls unexposed, disease free), 2014 Kilic (Topiramate) (Controls unexposed, sick) (Mixed indications), 2014 6 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.27[0.80; 2.02]252,2633,10485%NACoste (Topiramate) (Controls unexposed, NOS) (Mixed indications), 2020 Cohen (Topiramate) (Controls unexposed NOS) (Mixed indications), 2019 Hernández-Díaz (Topiramate) (Mixed indications) (Controls unexposed, disease free), 2014 3 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 1.56[1.17; 2.07]91,7478873%NACoste (Topiramate) (Controls unexposed, NOS) (Mixed indications), 2020 Bank (Topiramate) (Mixed indications) , 2017 Arkilo (Topiramate), 2015 Hernández-Díaz (Topiramate) (Mixed indications) (Controls unexposed, disease free), 2014 Kilic (Topiramate) (Controls unexposed, sick) (Mixed indications), 2014 5   - Yes  - Yes 0.89[0.80; 1.00]160,9092,280 -NACohen (Topiramate) (Controls unexposed NOS) (Mixed indications), 2019 1 Controls   - epilepsy indication  - epilepsy indication 1.19[0.47; 2.99]38859 -NAKilic (Topiramate) (Controls unexposed, sick) (Mixed indications), 2014 1 All studiesAll studies 1.34[0.87; 2.05]252,6563,16772%NACoste (Topiramate) (Controls unexposed, NOS) (Mixed indications), 2020 Cohen (Topiramate) (Controls unexposed NOS) (Mixed indications), 2019 Bank (Topiramate) (Mixed indications) , 2017 Arkilo (Topiramate), 2015 Hernández-Díaz (Topiramate) (Mixed indications) (Controls unexposed, disease free), 2014 Kilic (Topiramate) (Controls unexposed, sick) (Mixed indications), 2014 60.2100.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-4.34.42.0880.000Coste (Topiramate) (Controls unexposed, NOS) (Mixed indications), 2020Cohen (Topiramate) (Controls unexposed NOS) (Mixed indications), 2019Bank (Topiramate) (Mixed indications) , 2017Arkilo (Topiramate), 2015Hernández-Díaz (Topiramate) (Mixed indications) (Controls unexposed, disease free), 2014Kilic (Topiramate) (Controls unexposed, sick) (Mixed indications), 2014

Asymetry test p-value = 0.0594 (by Egger's regression)

slope=-0.1883 (0.0898); intercept=1.8186 (0.6967); t=2.6102; p=0.0594

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 8599, 8608, 8609, 8592, 10103

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.33[0.87; 2.02]286,2423,16380%NACoste (Topiramate) (Controls unexposed, NOS) (Mixed indications), 2020 Cohen (Topiramate) (Controls unexposed NOS) (Mixed indications), 2019 Hernández-Díaz (Topiramate) (Mixed indications) (Controls unexposed, disease free), 2014 Kilic (Topiramate) (Controls unexposed NOS) (Mixed indications), 2014 4 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 1.14[0.85; 1.54]1,1633,16742%NACoste (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 Hernández-Díaz (Topiramate) (Mixed indications) (Controls exposed to Lamotrigine, sick), 2014 Kilic (Topiramate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014 60.510.01.0