Lamotrigine (Epilepsy) updated on 04-22-2025

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.
S12723
R47992		 Bjørk (Controls unexposed, NOS), 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 Median follow up lamotrigine 5.1 (2.4-8.5) years old during pregnancy (anytime or not specified) population based cohort retrospective unexposed (general population or NOS) excluded Adjustment: No 1.04 [0.84;1.30] C
excluded (control group) 		81/5,073   68,295/4,463,879 68,376 5,073
ref
S12722
R47989		 Bjørk (Controls unexposed, sick), 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 - Median follow up lamotrigine 5.1 (2.4-8.5) years old during pregnancy (anytime or not specified) population based cohort retrospective unexposed, sick Adjustment: Yes 0.83 [0.65;1.06] 81/5,073   443/21,634 524 5,073
ref
S8124
R24954		 Charlton (Controls unexposed, disease free), 2017 Neurodevelopmental disorders (at 6 years old) during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed, disease free excluded Adjustment: No Matched 0.42 [0.03;6.86] C
excluded (control group) 		0/122   58/6,048 58 122
ref
S8127
R24957		 Charlton (Controls unexposed, sick), 2017 Neurodevelopmental disorders (at 6 years old) during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed, sick Adjustment: No 0.20 [0.01;3.47] C 0/122   9/472 9 122
ref
S6604
R18109		 Bromley (Controls unexposed, disease free), 2013 Neurodevelopmental disorder (at 6 years old) during pregnancy (anytime or not specified) prospective cohort unexposed, disease free excluded Adjustment: Yes 4.06 [0.55;22.20]
excluded (control group) 		2/30   4/214 6 30
ref
S6603
R18106		 Bromley (Controls unexposed, sick), 2013 Neurodevelopmental disorder (at 6 years old) during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No 4.64 [0.21;101.27] C 2/30   0/26 2 30
ref
S6295
R24816		 Rihtman, 2013 Children: special education (mean age 4-5 years old) at least 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No 1.24 [0.08;20.50] C 1/42   1/52 2 42
ref
S6673
R18469		 Dean, 2007 Neurodevelopmental disorder (mean age in years: m1=1.5 and m0=15.25) during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: No 1.73 [0.07;40.78] C 0/4   3/46 3 4
ref
Total 5 studies 0.84 [0.66;1.06] 540 5,271
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 (Controls unexposed, sick), 2022Bjørk, 2022 1 0.83[0.65; 1.06]5245,07397%ROB confusion: seriousROB selection: lowROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Charlton (Controls unexposed, sick), 2017Charlton, 2017 2 0.20[0.01; 3.47]91221%ROB confusion: unclearROB selection: lowROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Bromley (Controls unexposed, sick), 2013Bromley, 2013 3 4.64[0.21; 101.27]2301%ROB confusion: criticalROB selection: lowROB classification: lowROB missing: moderateROB mesure: moderateROB reporting: moderate Rihtman, 2013Rihtman, 2013 1.24[0.08; 20.50]2421%ROB confusion: moderateROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Dean, 2007Dean, 2007 1.73[0.07; 40.78]341%ROB confusion: criticalROB selection: criticalROB classification: lowROB missing: criticalROB mesure: criticalROB reporting: moderate Total (5 studies) I2 = 0% 0.84[0.66; 1.06]5405,2710.210.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, sick; 2: Controls unexposed, sick; 3: Controls unexposed, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 0.84[0.66; 1.06]5405,2710%NABjørk (Controls unexposed, sick), 2022 Charlton (Controls unexposed, sick), 2017 Bromley (Controls unexposed, sick), 2013 Rihtman, 2013 Dean, 2007 5 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.24[0.08; 20.50]242 -NARihtman, 2013 1 unexposed, sickunexposed, sick 0.83[0.65; 1.06]5385,2290%NABjørk (Controls unexposed, sick), 2022 Charlton (Controls unexposed, sick), 2017 Bromley (Controls unexposed, sick), 2013 Dean, 2007 4 Tags Adjustment   - No  - No 1.11[0.25; 4.87]161980%NACharlton (Controls unexposed, sick), 2017 Bromley (Controls unexposed, sick), 2013 Rihtman, 2013 Dean, 2007 4   - Yes  - Yes 0.83[0.65; 1.06]5245,073 -NABjørk (Controls unexposed, sick), 2022 1 All studiesAll studies 0.84[0.66; 1.06]5405,2710%NABjørk (Controls unexposed, sick), 2022 Charlton (Controls unexposed, sick), 2017 Bromley (Controls unexposed, sick), 2013 Rihtman, 2013 Dean, 2007 50.110.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-3.83.61.9330.000Bjørk (Controls unexposed, sick), 2022Charlton (Controls unexposed, sick), 2017Bromley (Controls unexposed, sick), 2013Rihtman, 2013Dean, 2007

Asymetry test p-value = 0.6552 (by Egger's regression)

slope=-0.2169 (0.1317); intercept=0.2364 (0.4786); t=0.4940; p=0.6552

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 6604, 8124, 12723

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.06[0.85; 1.32]68,4425,2670%NABjørk (Controls unexposed, NOS), 2022 Charlton (Controls unexposed, disease free), 2017 Bromley (Controls unexposed, disease free), 2013 Rihtman, 2013 4 unexposed, sick controlsunexposed, sick controls 0.83[0.65; 1.06]5385,2290%NABjørk (Controls unexposed, sick), 2022 Charlton (Controls unexposed, sick), 2017 Bromley (Controls unexposed, sick), 2013 Dean, 2007 40.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Peron (Epilepsy) (Neuro-developmental disorde ...Peron (Epilepsy) (Neuro-developmental disorders as a whole) 0.84[0.66; 1.06]0%-Wwhatever (meta-analysis)Anyduring pregnancy (anytime or not specified)studies TTT5 metaPregmetaPreg 0.84[0.66; 1.06]0%5,271----Bjørk (Controls unexposed, sick), 2022 Charlton (Controls unexposed, sick), 2017 Bromley (Controls unexposed, sick), 2013 Rihtman, 2013 Dean, 2007 50.510.01.0