Topiramate (All indications)

Neuro-developmental disorders (as a whole)

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.
S12715
R47970		 Bjørk (Topiramate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2022 Neurodevelopmental Disorder (ND): any diagnoses of autism spectrum disorder (F84.0, F84.1, F84.5) or intellectual disability (F70, F71, F72, F73) plus F84.3, F84.4, F84.8, F84.9, F79 (between 6.1 and 7.9 years old) during pregnancy (anytime or not specified) population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No 2.07 [1.22;3.50] C
excluded (control group) 		16/471   133/7,950 149 471
ref
S12716
R47973		 Bjørk (Topiramate) (Controls unexposed NOS) (Mixed indications), 2022 Neurodevelopmental Disorder (ND): any diagnoses of autism spectrum disorder (F84.0, F84.1, F84.5) or intellectual disability (F70, F71, F72, F73) plus F84.3, F84.4, F84.8, F84.9, F79 (between 6.1 and 7.9 years old) during pregnancy (anytime or not specified) population based cohort retrospective unexposed (general population or NOS) excluded Adjustment: Yes 2.29 [1.40;3.74]
excluded (control group) 		16/471   68,295/4,463,879 68,311 471
ref
S12718
R47979		 Bjørk (Topiramate) (Controls unexposed, sick) (Mixed indications), 2022 Neurodevelopmental Disorder (ND): any diagnoses of autism spectrum disorder (F84.0, F84.1, F84.5) or intellectual disability (F70, F71, F72, F73) plus F84.3, F84.4, F84.8, F84.9, F79 (between 6.1 and 7.9 years old) during pregnancy (anytime or not specified) population based cohort retrospective unexposed, sick Adjustment: No Controls: epilepsy indication 1.68 [1.01;2.79] C 16/471   443/21,634 459 471
ref
S8613
R28740		 Coste (Topiramate) (Controls unexposed, NOS) (Mixed indications), 2020 Diagnosis Disorders of psychological development (F80–F89) (mean age of 3.6 years old) during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes 0.80 [0.30;2.60] 3/477   10,010/1,710,441 10,013 477
ref
S8554
R28463		 Arkilo (Topiramate), 2015 Abnormal development (At 2 years of age, assessed by developmental specialists) during pregnancy (anytime or not specified) retrospective cohort exposed to other treatment, sick Adjustment: No 2.87 [0.09;91.05] C 0/2   2/24 2 2
ref
Total 3 studies 1.49 [0.94;2.35] 10,474 950
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 Bjørk (Topiramate) (Controls unexposed, sick) (Mixed indications), 2022Bjørk, 2022 1 1.68[1.01; 2.79]45947180%ROB confusion: unclearROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Coste (Topiramate) (Controls unexposed, NOS) (Mixed indications), 2020Coste, 2020 2 0.80[0.30; 2.60]10,01347718%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Arkilo (Topiramate), 2015Arkilo, 2015 3 2.87[0.09; 91.05]222%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Total (3 studies) I2 = 0% 1.49[0.94; 2.35]10,4749500.210.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Topiramate) (Controls unexposed, sick) (Mixed indications; 2: Topiramate) (Controls unexposed, NOS) (Mixed indications; 3: Topiramate;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.49[0.94; 2.35]10,4749500%NABjørk (Topiramate) (Controls unexposed, sick) (Mixed indications), 2022 Coste (Topiramate) (Controls unexposed, NOS) (Mixed indications), 2020 Arkilo (Topiramate), 2015 3 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 0.80[0.27; 2.36]10,013477 -NACoste (Topiramate) (Controls unexposed, NOS) (Mixed indications), 2020 1 unexposed, sickunexposed, sick 1.68[1.01; 2.79]459471 -NABjørk (Topiramate) (Controls unexposed, sick) (Mixed indications), 2022 1 exposed to other treatment, sickexposed to other treatment, sick 2.87[0.09; 91.05]22 -NAArkilo (Topiramate), 2015 1 Tags Adjustment   - No  - No 1.70[1.03; 2.81]4614730%NABjørk (Topiramate) (Controls unexposed, sick) (Mixed indications), 2022 Arkilo (Topiramate), 2015 2   - Yes  - Yes 0.80[0.27; 2.36]10,013477 -NACoste (Topiramate) (Controls unexposed, NOS) (Mixed indications), 2020 1 Controls   - epilepsy indication  - epilepsy indication 1.68[1.01; 2.79]459471 -NABjørk (Topiramate) (Controls unexposed, sick) (Mixed indications), 2022 1 All studiesAll studies 1.49[0.94; 2.35]10,4749500%NABjørk (Topiramate) (Controls unexposed, sick) (Mixed indications), 2022 Coste (Topiramate) (Controls unexposed, NOS) (Mixed indications), 2020 Arkilo (Topiramate), 2015 30.210.01.0

Publication bias and p-hacking diagnosis

funnel plot

Funnel plot not drawn. Less than 3 points.

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

not enought points

p values plot

Funnel plot not drawn. Less than 3 points.

Sub-groups analysis using all included studies

excluded 12715, 12716

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.52[0.55; 4.15]78,32494867%NABjørk (Topiramate) (Controls unexposed NOS) (Mixed indications), 2022 Coste (Topiramate) (Controls unexposed, NOS) (Mixed indications), 2020 2 unexposed, sick controlsunexposed, sick controls 1.68[1.01; 2.79]459471 -NABjørk (Topiramate) (Controls unexposed, sick) (Mixed indications), 2022 1 exposed to other treatment, sick controlsexposed to other treatment, sick controls 2.08[1.24; 3.51]1514730%NABjørk (Topiramate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2022 Arkilo (Topiramate), 2015 20.510.01.0