Lamotrigine (Epilepsy) updated on 04-22-2025

Cognitive developmental disorders/delay (> 6 years old)

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.
S17430
R73224		 Madley-Dowd_SE (Lamotrigine) (Controls unexposed, sick), 2024 Intellectual disability (intelligence quotient below 70) - ICD-8/9/10 codes - Mean 5-20 years old (according groups_Followup Gabapentin 5.24 (3.05-9.34)) during pregnancy (anytime or not specified) population based cohort retrospective unexposed, sick Adjustment: Yes Partial overlapping 1.21 [0.83;1.78] 34/2,383   194/10,769 228 2,383
ref
S17251
R72242		 Madley-Dowd_UK (Lamotrigine) (Epilepsy), 2024 Intellectual disability - 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 1.74 [0.55;5.50] -/791   13/4,075 - 791
ref
S15870
R65395		 Dreier, 2023 Intellectual disability - 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 0.85 [0.58;1.24] 34/5,288   184/22,203 218 5,288
ref
S7964
R53712		 Cohen-Israel, 2018 Developmental delay (a majority between 6-12 years old) 1st trimester retrospective cohort unexposed, disease free Adjustment: No Matched 0.57 [0.26;1.26] C 12/83   19/83 31 83
ref
S8322
R53710		 Baker (Controls unexposed, disease free), 2015 Mean child Full scale IQ - Differential ability scales (DAS) (age mean >6 years old) during pregnancy (anytime or not specified) prospective cohort unexposed, disease free excluded Adjustment: No extrapolated (cont. endpoint) 1.84 [0.91;3.72]
excluded (control group) 		-/29   -/210 - 29
ref
S8327
R53711		 Baker (Controls unexposed, sick), 2015 Mean child Full scale IQ - Differential ability scales (DAS) (age mean >6 years old) during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No extrapolated (cont. endpoint) 1.16 [0.44;3.07] -/29   -/25 - 29
ref
S8208
R53713		 Gopinath, 2015 Full Scale IQ < 86 (Wechsler Intelligence Scale for Children (WISC-IV)) (at 10–12 years of age) during pregnancy (anytime or not specified) retrospective cohort (registry) unexposed, sick Adjustment: No 0.39 [0.01;22.88] C 0/1   11/16 11 1
ref
Total 6 studies 0.99 [0.78;1.26] 488 8,575
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 Madley-Dowd_SE (Lamotrigine) (Controls unexposed, sick), 2024Madley-Dowd_SE, 2024 1 1.21[0.83; 1.78]2282,38340%ROB confusion: moderateROB selection: lowROB classification: lowROB missing: lowROB mesure: criticalROB reporting: moderate Madley-Dowd_UK (Lamotrigine) (Epilepsy), 2024Madley-Dowd_UK, 2024 2 1.74[0.55; 5.50]-7914%ROB confusion: moderateROB selection: lowROB classification: criticalROB missing: unclearROB mesure: criticalROB reporting: moderate Dreier, 2023Dreier, 2023 0.85[0.58; 1.24]2185,28840%ROB confusion: seriousROB selection: lowROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Cohen-Israel, 2018Cohen-Israel, 2018 0.57[0.26; 1.26]31839%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: unclearROB mesure: criticalROB reporting: moderate Baker (Controls unexposed, sick), 2015Baker, 2015 3 1.16[0.44; 3.07]-296%ROB confusion: unclearROB selection: lowROB classification: moderateROB missing: moderateROB mesure: lowROB reporting: moderate Gopinath, 2015Gopinath, 2015 0.39[0.01; 22.88]1110%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (6 studies) I2 = 0% 0.99[0.78; 1.26]4888,5750.25.01.0ROB: 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;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 0.99[0.78; 1.26]4888,5750%NAMadley-Dowd_SE (Lamotrigine) (Controls unexposed, sick), 2024 Madley-Dowd_UK (Lamotrigine) (Epilepsy), 2024 Dreier, 2023 Cohen-Israel, 2018 Baker (Controls unexposed, sick), 2015 Gopinath, 2015 6 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 0.57[0.26; 1.26]3183 -NACohen-Israel, 2018 1 unexposed, sickunexposed, sick 1.05[0.81; 1.35]4578,4920%NAMadley-Dowd_SE (Lamotrigine) (Controls unexposed, sick), 2024 Madley-Dowd_UK (Lamotrigine) (Epilepsy), 2024 Dreier, 2023 Baker (Controls unexposed, sick), 2015 Gopinath, 2015 5 Tags Adjustment   - No  - No 0.75[0.41; 1.37]421130%NACohen-Israel, 2018 Baker (Controls unexposed, sick), 2015 Gopinath, 2015 3   - Yes  - Yes 1.05[0.77; 1.43]4468,46219%NAMadley-Dowd_SE (Lamotrigine) (Controls unexposed, sick), 2024 Madley-Dowd_UK (Lamotrigine) (Epilepsy), 2024 Dreier, 2023 3 extrapolated (cont. endpoint)extrapolated (cont. endpoint) 1.16[0.44; 3.06]-29 -NABaker (Controls unexposed, sick), 2015 1 MatchedMatched 0.57[0.26; 1.26]3183 -NACohen-Israel, 2018 1 Partial overlappingPartial overlapping 1.21[0.83; 1.77]2282,383 -NAMadley-Dowd_SE (Lamotrigine) (Controls unexposed, sick), 2024 1 All studiesAll studies 0.99[0.78; 1.26]4888,5750%NAMadley-Dowd_SE (Lamotrigine) (Controls unexposed, sick), 2024 Madley-Dowd_UK (Lamotrigine) (Epilepsy), 2024 Dreier, 2023 Cohen-Israel, 2018 Baker (Controls unexposed, sick), 2015 Gopinath, 2015 60.15.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-4.94.92.4910.000Madley-Dowd_SE (Lamotrigine) (Controls unexposed, sick), 2024Madley-Dowd_UK (Lamotrigine) (Epilepsy), 2024Dreier, 2023Cohen-Israel, 2018Baker (Controls unexposed, sick), 2015Gopinath, 2015

Asymetry test p-value = 0.8547 (by Egger's regression)

slope=0.0315 (0.2534); intercept=-0.1644 (0.8420); t=0.1953; p=0.8547

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 8322

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.04[0.33; 3.28]3111279%NACohen-Israel, 2018 Baker (Controls unexposed, disease free), 2015 2 unexposed, sick controlsunexposed, sick controls 1.05[0.81; 1.35]4618,4920%NAMadley-Dowd_SE (Lamotrigine) (Controls unexposed, sick), 2024 Madley-Dowd_UK (Lamotrigine) (Epilepsy), 2024 Dreier, 2023 Baker (Controls unexposed, sick), 2015 Gopinath, 2015 50.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Veroniki b (NMA) (Cognitive developmental delay)Veroniki b (NMA) (Cognitive developmental delay) 0.79[0.05; 5.12]NA-Wwhatever (meta-analysis)Anyduring pregnancy (anytime or not specified)studies TTT-9 Peron (Epilepsy) (Cognitive developmental del ...Peron (Epilepsy) (Cognitive developmental delay (>6 years old)) 0.75[0.41; 1.37]0%-Wwhatever (meta-analysis)Anyduring pregnancy (anytime or not specified)studies TTT3 metaPregmetaPreg 0.99[0.78; 1.26]0%8,575----Madley-Dowd_SE (Lamotrigine) (Controls unexposed, sick), 2024 Madley-Dowd_UK (Lamotrigine) (Epilepsy), 2024 Dreier, 2023 Cohen-Israel, 2018 Baker (Controls unexposed, sick), 2015 Gopinath, 2015 60.510.01.0