Topiramate (All indications)

Language disorders/delay

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.
S12810
R48233		 Meador (Topiramate) (Controls exposed to Lamotrigine, sick), 2021 Language Score in 2 years old children with the Bayley Scales of Infant and Toddler Development (BSID-III) 3rd trimester prospective cohort exposed to other treatment, sick excluded Adjustment: Yes extrapolated (cont. endpoint) 2.58 [0.50;13.27]
excluded (control group) 		-/5   -/93 - 5
ref
S12811
R48234		 Meador (Topiramate) (Controls unexposed, disease free), 2021 Language Score in 2 years old children with the Bayley Scales of Infant and Toddler Development (BSID-III) 3rd trimester prospective cohort unexposed, disease free Adjustment: Yes extrapolated (cont. endpoint) 2.49 [0.48;12.82] -/5   -/87 - 5
ref
S10103
R36820		 Coste (Topiramate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2020 Visits to a speech therapist (mean age of 3.7 years old) during pregnancy (anytime or not specified) retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: Yes 1.20 [0.80;1.80]
excluded (control group) 		33/477   157/2,916 190 477
ref
S8613
R28742		 Coste (Topiramate) (Controls unexposed, NOS) (Mixed indications), 2020 Health care utilization: Speech therapy (mean age of 3.6 years old) during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes 1.40 [1.00;2.00] 33/477   72,012/1,710,441 72,045 477
ref
S8583
R28561		 Husebye (Topiramate) (Controls exposed to Lamotrigine, sick), 2020 Language impairment age 8 years (Language 20) during pregnancy (anytime or not specified) population based cohort propective exposed to other treatment, sick excluded Adjustment: No 1.19 [0.11;12.82] C
excluded (control group) 		1/4   9/41 10 4
ref
S8584
R28563		 Husebye (Topiramate) (Controls unexposed, disease free), 2020 Language impairment age 8 years (Language 20) during pregnancy (anytime or not specified) population based cohort propective unexposed, disease free excluded Adjustment: Yes 1.10 [0.10;10.90]
excluded (control group) 		1/4   8,250/42,550 8,251 4
ref
S8585
R28565		 Husebye (Topiramate) (Controls unexposed, sick), 2020 Language impairment age 8 years (Language 20) during pregnancy (anytime or not specified) population based cohort propective unexposed, sick Adjustment: No 1.10 [0.11;10.87] C 1/4   35/150 36 4
ref
S8582
R28544		 Bromley (Topiramate), 2016 Verbal abilities <85 (Wechsler Preschool and Primary Scale of Intelligence (WPPSI) / Wechsler Intelligence Scale for Children (WISC)) (5-9 years old) during pregnancy (anytime or not specified) retrospective cohort (registry) unexposed, sick Adjustment: No 1.59 [0.33;7.69] C 3/27   4/55 7 27
ref
S8615
R28766		 Rihtman (Topiramate) (Mixed indications), 2012 Verbal IQ (Stanford Binet) (mean age around 4 years old) at least 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No extrapolated (cont. endpoint) Matched 5.71 [1.23;26.53] -/9   -/18 - 9
ref
Total 5 studies 1.52 [1.10;2.10] 72,088 522
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 Meador (Topiramate) (Controls unexposed, disease free), 2021Meador, 2021 1 2.49[0.48; 12.82]-54%ROB confusion: moderateROB selection: lowROB classification: lowROB missing: moderateROB mesure: moderateROB reporting: low Coste (Topiramate) (Controls unexposed, NOS) (Mixed indications), 2020Coste, 2020 2 1.40[1.00; 2.00]72,04547786%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Husebye (Topiramate) (Controls unexposed, sick), 2020Husebye, 2020 3 1.10[0.11; 10.87]3642%ROB confusion: unclearROB selection: lowROB classification: lowROB missing: criticalROB mesure: moderateROB reporting: moderate Bromley (Topiramate), 2016Bromley, 2016 4 1.59[0.33; 7.69]7274%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Rihtman (Topiramate) (Mixed indications), 2012Rihtman, 2012 5 5.71[1.23; 26.53]-94%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (5 studies) I2 = 0% 1.52[1.10; 2.10]72,0885220.520.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

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

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.52[1.10; 2.10]72,0885220%NAMeador (Topiramate) (Controls unexposed, disease free), 2021 Coste (Topiramate) (Controls unexposed, NOS) (Mixed indications), 2020 Husebye (Topiramate) (Controls unexposed, sick), 2020 Bromley (Topiramate), 2016 Rihtman (Topiramate) (Mixed indications), 2012 5 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 2.06[0.91; 4.65]72,04549141%NAMeador (Topiramate) (Controls unexposed, disease free), 2021 Coste (Topiramate) (Controls unexposed, NOS) (Mixed indications), 2020 Rihtman (Topiramate) (Mixed indications), 2012 3 unexposed, sickunexposed, sick 1.41[0.39; 5.18]43310%NAHusebye (Topiramate) (Controls unexposed, sick), 2020 Bromley (Topiramate), 2016 2 Tags Adjustment   - No  - No 2.53[0.94; 6.81]43400%NAHusebye (Topiramate) (Controls unexposed, sick), 2020 Bromley (Topiramate), 2016 Rihtman (Topiramate) (Mixed indications), 2012 3   - Yes  - Yes 1.43[1.02; 2.01]72,0454820%NAMeador (Topiramate) (Controls unexposed, disease free), 2021 Coste (Topiramate) (Controls unexposed, NOS) (Mixed indications), 2020 2 extrapolated (cont. endpoint)extrapolated (cont. endpoint) 3.88[1.26; 11.90]-140%NAMeador (Topiramate) (Controls unexposed, disease free), 2021 Rihtman (Topiramate) (Mixed indications), 2012 2 MatchedMatched 5.71[1.23; 26.52]-9 -NARihtman (Topiramate) (Mixed indications), 2012 1 All studiesAll studies 1.52[1.10; 2.10]72,0885220%NAMeador (Topiramate) (Controls unexposed, disease free), 2021 Coste (Topiramate) (Controls unexposed, NOS) (Mixed indications), 2020 Husebye (Topiramate) (Controls unexposed, sick), 2020 Bromley (Topiramate), 2016 Rihtman (Topiramate) (Mixed indications), 2012 50.520.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-2.83.21.4050.000Meador (Topiramate) (Controls unexposed, disease free), 2021Coste (Topiramate) (Controls unexposed, NOS) (Mixed indications), 2020Husebye (Topiramate) (Controls unexposed, sick), 2020Bromley (Topiramate), 2016Rihtman (Topiramate) (Mixed indications), 2012

Asymetry test p-value = 0.3179 (by Egger's regression)

slope=0.2241 (0.2194); intercept=0.7164 (0.5995); t=1.1950; p=0.3179

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 10103, 8583, 8584, 12810

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.71[1.00; 2.93]80,29649514%NAMeador (Topiramate) (Controls unexposed, disease free), 2021 Coste (Topiramate) (Controls unexposed, NOS) (Mixed indications), 2020 Husebye (Topiramate) (Controls unexposed, disease free), 2020 Rihtman (Topiramate) (Mixed indications), 2012 4 unexposed, sick controlsunexposed, sick controls 1.41[0.39; 5.18]43310%NAHusebye (Topiramate) (Controls unexposed, sick), 2020 Bromley (Topiramate), 2016 2 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.25[0.85; 1.85]2004860%NAMeador (Topiramate) (Controls exposed to Lamotrigine, sick), 2021 Coste (Topiramate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2020 Husebye (Topiramate) (Controls exposed to Lamotrigine, sick), 2020 30.510.01.0