Lamotrigine (Epilepsy) updated on 04-22-2025

Cognitive developmental disorders/delay (3-6 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.
S12723
R73454		 Bjørk (Controls unexposed, NOS), 2022 Diagnosis of intellectual disability (ID): mild ID (F70), moderate ID (F71), severe ID (F72), and profound ID (F73) - 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 1.13 [0.73;1.73] C
excluded (control group) 		21/5,073   16,384/4,463,879 16,405 5,073
ref
S12722
R73455		 Bjørk (Controls unexposed, sick), 2022 Diagnosis of intellectual disability (ID): mild ID (F70), moderate ID (F71), severe ID (F72), and profound ID (F73) - 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 0.73 [0.46;1.16] 21/5,073   139/21,634 160 5,073
ref
S7277
R48894		 Kasradze, 2017 Full scale IQ - Wechsler Preschool and Primary Scale of Intelligence (WPPSI-4) (mean age 4-4.5 years old) during pregnancy (anytime or not specified) prospective cohort unexposed, disease free Adjustment: No extrapolated (cont. endpoint) Matched 30.10 [3.28;276.62] -/3   -/50 - 3
ref
S6295
R48895		 Rihtman, 2013 Stanford Binet Intelligence Scales, Fifth Edition (SB5) - GIQ (mean age 4-5 years old) at least 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No extrapolated (cont. endpoint) 1.65 [0.78;3.49] -/41   -/52 - 41
ref
S6940
R48893		 Cummings, 2011 Mild or significant delay (score ≥1, <2 SD or ≥2 SD below the mean) (Bayley Scales of Infant Development or the Griffiths Scale) (mean age in years: m1=2.7 and m0=4.3) throughout pregnancy retrospective cohort (registry) unexposed, disease free Adjustment: Yes 1.10 [0.10;13.70] 1/35   2/44 3 35
ref
Total 4 studies 1.80 [0.60;5.41] 163 5,152
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 0.73[0.46; 1.16]1605,07337%ROB confusion: seriousROB selection: lowROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Kasradze, 2017Kasradze, 2017 30.10[3.28; 276.62]-315%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: criticalROB mesure: lowROB reporting: moderate Rihtman, 2013Rihtman, 2013 1.65[0.78; 3.49]-4134%ROB confusion: moderateROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Cummings, 2011Cummings, 2011 1.10[0.10; 13.70]33513%ROB confusion: moderateROB selection: lowROB classification: moderateROB missing: unclearROB mesure: lowROB reporting: moderate Total (4 studies) I2 = 76% 1.80[0.60; 5.41]1635,1520.2100.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.80[0.60; 5.41]1635,15276%NABjørk (Controls unexposed, sick), 2022 Kasradze, 2017 Rihtman, 2013 Cummings, 2011 4 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 3.39[0.56; 20.57]37968%NAKasradze, 2017 Rihtman, 2013 Cummings, 2011 3 unexposed, sickunexposed, sick 0.73[0.46; 1.16]1605,073 -NABjørk (Controls unexposed, sick), 2022 1 Tags Adjustment   - No  - No 5.80[0.35; 97.25]-4483%NAKasradze, 2017 Rihtman, 2013 2   - Yes  - Yes 0.74[0.47; 1.17]1635,1080%NABjørk (Controls unexposed, sick), 2022 Cummings, 2011 2 extrapolated (cont. endpoint)extrapolated (cont. endpoint) 5.80[0.35; 97.25]-4483%NAKasradze, 2017 Rihtman, 2013 2 MatchedMatched 30.10[3.28; 276.42]-3 -NAKasradze, 2017 1 All studiesAll studies 1.80[0.60; 5.41]1635,15276%NABjørk (Controls unexposed, sick), 2022 Kasradze, 2017 Rihtman, 2013 Cummings, 2011 40.2100.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-4.14.11.5060.000Bjørk (Controls unexposed, sick), 2022Kasradze, 2017Rihtman, 2013Cummings, 2011

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

not enought points

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 12723

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.91[0.78; 4.65]16,4085,15265%NABjørk (Controls unexposed, NOS), 2022 Kasradze, 2017 Rihtman, 2013 Cummings, 2011 4 unexposed, sick controlsunexposed, sick controls 0.73[0.46; 1.16]1605,073 -NABjørk (Controls unexposed, sick), 2022 10.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Peron (Epilepsy) (Cognitive developmental del ...Peron (Epilepsy) (Cognitive developmental delay (3-6 years old)) 3.39[0.56; 20.57]68%-Wwhatever (meta-analysis)Anyduring pregnancy (anytime or not specified)studies TTT3 metaPregmetaPreg 1.80[0.60; 5.41]76%5,152----Bjørk (Controls unexposed, sick), 2022 Kasradze, 2017 Rihtman, 2013 Cummings, 2011 40.510.01.0