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.
S19447
R82910
Karayagmurlu (Controls unexposed, disease free) (Lamotrigine) (Epilepsy), 2026 Autism Spectrum Disorder - DSM-5 clinical evaluation conducted by an experienced child and adolescent psychiatrist - Aged 2–6 years during pregnancy (anytime or not specified) retrospective cohort unexposed, disease free excluded Adjustment: No 9.55 [0.17;530.22] C
excluded (control group)
0/6   0/53 0 6
ref
S19451
R82918
Karayagmurlu (Controls unexposed, sick) (Lamotrigine) (Epilepsy), 2026 Autism Spectrum Disorder - DSM-5 clinical evaluation conducted by an experienced child and adolescent psychiatrist - Aged 2–6 years during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: No 3.36 [0.06;189.98] C 0/6   0/19 0 6
ref
S19477
R83183
Straub (Lamotrigine) (Epilepsy), 2026 Autism spectrum disorder - ICD-10 codes: F84.x (except F84.2, F84.3) - Mean follow up (full cohort): 3.4 years during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed, sick Adjustment: Yes 0.96 [0.63;1.47] 34/3,273   106/8,887 140 3,273
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 8 studies 0.92 [0.78;1.09] 1,142 11,930
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 Karayagmurlu (Controls unexposed, sick) (Lamotrigine) (Epilepsy), 2026Karayagmurlu, 2026 1 3.36[0.06; 189.98]060%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Straub (Lamotrigine) (Epilepsy), 2026Straub, 2026 2 0.96[0.63; 1.47]1403,27316%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: unclearROB mesure: criticalROB reporting: moderate Madley-Dowd_SE (Lamotrigine) (Controls unexposed, sick), 2024Madley-Dowd_SE, 2024 3 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 4 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]3875,28836%ROB confusion: seriousROB selection: lowROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Bjørk (Controls unexposed, sick), 2018Bjørk, 2018 5 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 6 2.68[0.10; 68.88]1300%ROB confusion: criticalROB selection: lowROB classification: lowROB missing: moderateROB mesure: moderateROB reporting: moderate Total (8 studies) I2 = 0% 0.92[0.78; 1.09]1,14211,9300.210.01.0ROB: A: confounding, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, sick) (Lamotrigine) (Epilepsy; 2: Lamotrigine) (Epilepsy; 3: Lamotrigine) (Controls unexposed, sick; 4: Lamotrigine) (Epilepsy; 5: Controls unexposed, sick; 6: Controls unexposed, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 0.92[0.78; 1.09]1,14211,9300%NAKarayagmurlu (Controls unexposed, sick) (Lamotrigine) (Epilepsy), 2026 Straub (Lamotrigine) (Epilepsy), 2026 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 8 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[0.78; 1.09]1,14111,8470%NAKarayagmurlu (Controls unexposed, sick) (Lamotrigine) (Epilepsy), 2026 Straub (Lamotrigine) (Epilepsy), 2026 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 7 Tags Adjustment   - No  - No 1.79[0.91; 3.52]421950%NAKarayagmurlu (Controls unexposed, sick) (Lamotrigine) (Epilepsy), 2026 Bjørk (Controls unexposed, sick), 2018 Cohen-Israel, 2018 Bromley (Controls unexposed, sick), 2013 4   - Yes  - Yes 0.88[0.74; 1.05]1,10011,7350%NAStraub (Lamotrigine) (Epilepsy), 2026 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 0.92[0.78; 1.09]1,14211,9300%NAKarayagmurlu (Controls unexposed, sick) (Lamotrigine) (Epilepsy), 2026 Straub (Lamotrigine) (Epilepsy), 2026 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 80.110.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-4.84.82.4700.000Karayagmurlu (Controls unexposed, sick) (Lamotrigine) (Epilepsy), 2026Straub (Lamotrigine) (Epilepsy), 2026Madley-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 = 0.2180 (by Egger's regression)

slope=-0.2254 (0.1272); intercept=0.7178 (0.5216); t=1.3761; p=0.2180

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 6604, 9930, 19447

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.98[1.13; 3.48]6,9261950%NAKarayagmurlu (Controls unexposed, disease free) (Lamotrigine) (Epilepsy), 2026 Bjørk (Controls unexposed, disease free), 2018 Cohen-Israel, 2018 Bromley (Controls unexposed, disease free), 2013 4 unexposed, sick controlsunexposed, sick controls 0.92[0.78; 1.09]1,14111,8470%NAKarayagmurlu (Controls unexposed, sick) (Lamotrigine) (Epilepsy), 2026 Straub (Lamotrigine) (Epilepsy), 2026 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 70.510.01.0

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 0.92[0.78; 1.09]0%11,930----Karayagmurlu (Controls unexposed, sick) (Lamotrigine) (Epilepsy), 2026 Straub (Lamotrigine) (Epilepsy), 2026 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 80.510.01.0