Lamotrigine (Epilepsy) updated on 04-22-2025

ASD (Autism spectrum disorder): Diagnosis/Risk

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.
S16762
R70391		 Hernandez-Diaz, 2024 Autism spectrum disorder (ASD) - At least two visits with codes for ASD - Median follow-up was 2 years 2nd and/or 3rd trimester retrospective cohort (claims database) unexposed, sick Adjustment: Yes 0.93 [0.60;1.44] 32/3,134   102/8,815 134 3,134
ref
S17430
R73223		 Madley-Dowd_SE (Lamotrigine) (Controls unexposed, sick), 2024 Autism - ICD-8/9/10 codes - Mean 5-20 years old (according groups) during pregnancy (anytime or not specified) population based cohort retrospective unexposed, sick Adjustment: Yes Partial overlapping 0.81 [0.60;1.09] 53/2,383   425/10,769 478 2,383
ref
S17251
R72249		 Madley-Dowd_UK (Lamotrigine) (Epilepsy), 2024 Autism - ICD10 codes - Median 6.18 (3.53-9.94) years old during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed, sick Adjustment: Yes 1.07 [0.62;1.85] 17/791   78/4,075 95 791
ref
S15870
R65394		 Dreier, 2023 Autism spectrum disorder - Corresponding ICD-10 F-chapter - Up to 22 years of age during pregnancy (anytime or not specified) population based cohort propective unexposed, sick Adjustment: Yes 0.86 [0.65;1.14] 64/5,288   323/22,203 387 5,288
ref
S9930
R39724		 Bjørk (Controls unexposed, disease free), 2018 Autistic traits at 18 months and/or at 36 months (M-CHAT <2/6 critical or <3/23 or SCQ >13) during pregnancy (anytime or not specified) population based cohort propective unexposed, disease free excluded Adjustment: No 2.05 [1.13;3.72] C
excluded (control group) 		13/76   6,907/75,497 6,920 76
ref
S9974
R39725		 Bjørk (Controls unexposed, sick), 2018 Autistic traits at 18 months and/or at 36 months (M-CHAT <2/6 critical or <3/23 or SCQ >13) during pregnancy (anytime or not specified) population based cohort propective unexposed, sick Adjustment: No 1.87 [0.91;3.84] C 13/76   27/272 40 76
ref
S7964
R39753		 Cohen-Israel, 2018 Autism - Medical files and by a telephone interview using an ad-hoc questionnaire - A majority between 6-12 years old 1st trimester retrospective cohort unexposed, disease free Adjustment: No Matched 0.33 [0.01;8.20] C 0/83   1/83 1 83
ref
S6604
R39735		 Bromley (Controls unexposed, disease free), 2013 Autistic Spectrum Disorders (at 6 years old) during pregnancy (anytime or not specified) prospective cohort unexposed, disease free excluded Adjustment: No 1.81 [0.20;16.76] C
excluded (control group) 		1/30   4/214 5 30
ref
S6603
R39737		 Bromley (Controls unexposed, sick), 2013 Autistic Spectrum Disorders (at 6 years old) during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No 2.68 [0.10;68.88] C 1/30   0/26 1 30
ref
Total 7 studies 0.91 [0.77;1.08] 1,136 11,785
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 Hernandez-Diaz, 2024Hernandez-Diaz, 2024 0.93[0.60; 1.44]1343,13415%ROB confusion: moderateROB selection: moderateROB classification: moderateROB missing: criticalROB mesure: criticalROB reporting: moderate Madley-Dowd_SE (Lamotrigine) (Controls unexposed, sick), 2024Madley-Dowd_SE, 2024 1 0.81[0.60; 1.09]4782,38332%ROB confusion: moderateROB selection: lowROB classification: lowROB missing: lowROB mesure: criticalROB reporting: moderate Madley-Dowd_UK (Lamotrigine) (Epilepsy), 2024Madley-Dowd_UK, 2024 2 1.07[0.62; 1.85]9579110%ROB confusion: moderateROB selection: lowROB classification: criticalROB missing: unclearROB mesure: criticalROB reporting: moderate Dreier, 2023Dreier, 2023 0.86[0.65; 1.14]3875,28837%ROB confusion: seriousROB selection: lowROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Bjørk (Controls unexposed, sick), 2018Bjørk, 2018 3 1.87[0.91; 3.84]40766%ROB confusion: unclearROB selection: lowROB classification: lowROB missing: lowROB mesure: moderateROB reporting: moderate Cohen-Israel, 2018Cohen-Israel, 2018 0.33[0.01; 8.20]1830%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: unclearROB mesure: criticalROB reporting: moderate Bromley (Controls unexposed, sick), 2013Bromley, 2013 4 2.68[0.10; 68.88]1300%ROB confusion: criticalROB selection: lowROB classification: lowROB missing: moderateROB mesure: moderateROB reporting: moderate Total (7 studies) I2 = 0% 0.91[0.77; 1.08]1,13611,7850.210.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Lamotrigine) (Controls unexposed, sick; 2: Lamotrigine) (Epilepsy; 3: Controls unexposed, sick; 4: Controls unexposed, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 0.91[0.77; 1.08]1,13611,7850%NAHernandez-Diaz, 2024 Madley-Dowd_SE (Lamotrigine) (Controls unexposed, sick), 2024 Madley-Dowd_UK (Lamotrigine) (Epilepsy), 2024 Dreier, 2023 Bjørk (Controls unexposed, sick), 2018 Cohen-Israel, 2018 Bromley (Controls unexposed, sick), 2013 7 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 0.33[0.01; 8.20]183 -NACohen-Israel, 2018 1 unexposed, sickunexposed, sick 0.92[0.77; 1.11]1,13511,7027%NAHernandez-Diaz, 2024 Madley-Dowd_SE (Lamotrigine) (Controls unexposed, sick), 2024 Madley-Dowd_UK (Lamotrigine) (Epilepsy), 2024 Dreier, 2023 Bjørk (Controls unexposed, sick), 2018 Bromley (Controls unexposed, sick), 2013 6 Tags Adjustment   - No  - No 1.76[0.89; 3.49]421890%NABjørk (Controls unexposed, sick), 2018 Cohen-Israel, 2018 Bromley (Controls unexposed, sick), 2013 3   - Yes  - Yes 0.87[0.73; 1.04]1,09411,5960%NAHernandez-Diaz, 2024 Madley-Dowd_SE (Lamotrigine) (Controls unexposed, sick), 2024 Madley-Dowd_UK (Lamotrigine) (Epilepsy), 2024 Dreier, 2023 4 MatchedMatched 0.33[0.01; 8.20]183 -NACohen-Israel, 2018 1 Partial overlappingPartial overlapping 0.81[0.60; 1.09]4782,383 -NAMadley-Dowd_SE (Lamotrigine) (Controls unexposed, sick), 2024 1 All studiesAll studies 0.91[0.77; 1.08]1,13611,7850%NAHernandez-Diaz, 2024 Madley-Dowd_SE (Lamotrigine) (Controls unexposed, sick), 2024 Madley-Dowd_UK (Lamotrigine) (Epilepsy), 2024 Dreier, 2023 Bjørk (Controls unexposed, sick), 2018 Cohen-Israel, 2018 Bromley (Controls unexposed, sick), 2013 70.110.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-3.93.81.9870.000Hernandez-Diaz, 2024Madley-Dowd_SE (Lamotrigine) (Controls unexposed, sick), 2024Madley-Dowd_UK (Lamotrigine) (Epilepsy), 2024Dreier, 2023Bjørk (Controls unexposed, sick), 2018Cohen-Israel, 2018Bromley (Controls unexposed, sick), 2013

Asymetry test p-value = 0.3351 (by Egger's regression)

slope=-0.2309 (0.1542); intercept=0.7165 (0.6721); t=1.0661; p=0.3351

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 6604, 9930

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.92[1.09; 3.39]6,9261890%NABjørk (Controls unexposed, disease free), 2018 Cohen-Israel, 2018 Bromley (Controls unexposed, disease free), 2013 3 unexposed, sick controlsunexposed, sick controls 0.92[0.77; 1.11]1,13511,7027%NAHernandez-Diaz, 2024 Madley-Dowd_SE (Lamotrigine) (Controls unexposed, sick), 2024 Madley-Dowd_UK (Lamotrigine) (Epilepsy), 2024 Dreier, 2023 Bjørk (Controls unexposed, sick), 2018 Bromley (Controls unexposed, sick), 2013 60.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Veroniki (MA) (Autism Dyspraxia)Veroniki (MA) (Autism Dyspraxia) Out of scale13.77[2.06; 188.00]-Wwhatever (meta-analysis)T11st trimesterstudies TTT2 Veroniki b (NMA) (Autism/dyspraxia)Veroniki b (NMA) (Autism/dyspraxia) Out of scale10.24[1.25; 171.40]NA-Wwhatever (meta-analysis)Anyduring pregnancy (anytime or not specified)studies TTT-9 Veroniki (NMA) (Autism/Dyspraxia - Epilepsy only)Veroniki (NMA) (Autism/Dyspraxia - Epilepsy only) Out of scale10.24[1.25; 171.40]-Wwhatever (meta-analysis)Anyduring pregnancy (anytime or not specified)studies TTT-9 Peron (Epilepsy) (Diagnosis or risk of ASD)Peron (Epilepsy) (Diagnosis or risk of ASD) 0.97[0.61; 1.53]30%-Wwhatever (meta-analysis)Anyduring pregnancy (anytime or not specified)studies TTT5 metaPregmetaPreg 0.91[0.77; 1.08]0%11,785----Hernandez-Diaz, 2024 Madley-Dowd_SE (Lamotrigine) (Controls unexposed, sick), 2024 Madley-Dowd_UK (Lamotrigine) (Epilepsy), 2024 Dreier, 2023 Bjørk (Controls unexposed, sick), 2018 Cohen-Israel, 2018 Bromley (Controls unexposed, sick), 2013 70.510.01.0