Lamotrigine (All indications) updated on 04-22-2025

Limb defects

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.
S17498
R73514		 Wiggs (Epilepsy) (Lamotrigine), 2024 Musculoskeletal system malformations early pregnancy population based cohort retrospective unexposed, sick Adjustment: Yes 1.05 [0.72;1.52] -/1,412   -/9,364 - 1,412
ref
S8924
R48252		 Thomas (Lamotrigine) (Controls unexposed, sick), 2021 Skeletal malformations 1st trimester prospective cohort unexposed, sick Adjustment: No 1.36 [0.06;28.82] C 0/50   2/340 2 50
ref
S8969
R30375		 Ban (Lamotrigine) (Mixed indications), 2015 Limb anomaly 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No 1.50 [0.37;6.02] C 2/273   1,263/257,153 1,265 273
ref
S10292
R37691		 Vajda (Lamotrigine), 2013 Skeletal / Limb Malformations at least 1st trimester prospective cohort unexposed, sick Adjustment: No 0.15 [0.01;3.81] C 0/315   1/147 1 315
ref
S8909
R35289		 Mawer (Lamotrigine) (Controls unexposed, disease free), 2010 Skeletal / Limb Malformations 1st trimester prospective cohort unexposed, disease free excluded Adjustment: No Matched 24.04 [0.96;601.51] C
excluded (control group) 		1/37   0/285 1 37
ref
S8910
R35293		 Mawer (Lamotrigine) (Controls unexposed, sick), 2010 Skeletal / Limb Malformations 1st trimester prospective cohort unexposed, sick Adjustment: No Matched 3.42 [0.14;86.71] C 1/37   0/41 1 37
ref
Total 5 studies 1.07 [0.75;1.52] 1,269 2,087
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 Wiggs (Epilepsy) (Lamotrigine), 2024Wiggs, 2024 1 1.05[0.72; 1.52]-1,41290%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Thomas (Lamotrigine) (Controls unexposed, sick), 2021Thomas, 2021 2 1.36[0.06; 28.82]2501%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Ban (Lamotrigine) (Mixed indications), 2015Ban, 2015 3 1.50[0.37; 6.02]1,2652736%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Vajda (Lamotrigine), 2013Vajda, 2013 4 0.15[0.01; 3.81]13151%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Mawer (Lamotrigine) (Controls unexposed, sick), 2010Mawer, 2010 5 3.42[0.14; 86.71]1371%ROB confusion: criticalROB selection: moderateROB classification: lowROB missing: moderateROB mesure: moderateROB reporting: moderate Total (5 studies) I2 = 0% 1.07[0.75; 1.52]1,2692,0870.010.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

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

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.07[0.75; 1.52]1,2692,0870%NAWiggs (Epilepsy) (Lamotrigine), 2024 Thomas (Lamotrigine) (Controls unexposed, sick), 2021 Ban (Lamotrigine) (Mixed indications), 2015 Vajda (Lamotrigine), 2013 Mawer (Lamotrigine) (Controls unexposed, sick), 2010 5 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.50[0.37; 6.02]1,265273 -NABan (Lamotrigine) (Mixed indications), 2015 1 unexposed, sickunexposed, sick 1.04[0.72; 1.50]41,8140%NAWiggs (Epilepsy) (Lamotrigine), 2024 Thomas (Lamotrigine) (Controls unexposed, sick), 2021 Vajda (Lamotrigine), 2013 Mawer (Lamotrigine) (Controls unexposed, sick), 2010 4 Tags Adjustment   - No  - No 1.24[0.41; 3.76]1,2696750%NAThomas (Lamotrigine) (Controls unexposed, sick), 2021 Ban (Lamotrigine) (Mixed indications), 2015 Vajda (Lamotrigine), 2013 Mawer (Lamotrigine) (Controls unexposed, sick), 2010 4   - Yes  - Yes 1.05[0.72; 1.53]-1,412 -NAWiggs (Epilepsy) (Lamotrigine), 2024 1 MatchedMatched 3.42[0.14; 86.71]137 -NAMawer (Lamotrigine) (Controls unexposed, sick), 2010 1 All studiesAll studies 1.07[0.75; 1.52]1,2692,0870%NAWiggs (Epilepsy) (Lamotrigine), 2024 Thomas (Lamotrigine) (Controls unexposed, sick), 2021 Ban (Lamotrigine) (Mixed indications), 2015 Vajda (Lamotrigine), 2013 Mawer (Lamotrigine) (Controls unexposed, sick), 2010 50.010.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-3.93.91.9790.000Wiggs (Epilepsy) (Lamotrigine), 2024Thomas (Lamotrigine) (Controls unexposed, sick), 2021Ban (Lamotrigine) (Mixed indications), 2015Vajda (Lamotrigine), 2013Mawer (Lamotrigine) (Controls unexposed, sick), 2010

Asymetry test p-value = 0.9661 (by Egger's regression)

slope=0.0593 (0.2108); intercept=0.0241 (0.5219); t=0.0461; p=0.9661

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 8909

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 4.04[0.30; 54.91]1,26631058%NABan (Lamotrigine) (Mixed indications), 2015 Mawer (Lamotrigine) (Controls unexposed, disease free), 2010 2 unexposed, sick controlsunexposed, sick controls 1.04[0.72; 1.50]41,8140%NAWiggs (Epilepsy) (Lamotrigine), 2024 Thomas (Lamotrigine) (Controls unexposed, sick), 2021 Vajda (Lamotrigine), 2013 Mawer (Lamotrigine) (Controls unexposed, sick), 2010 40.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Weston (Skeletal / Limb Malformations)Weston (Skeletal / Limb Malformations) 0.72[0.12; 4.12]40-U,Sunexposed, sickAnyduring pregnancy (anytime or not specified)studies TTT2 Weston (Skeletal / Limb Malformations)Weston (Skeletal / Limb Malformations) Out of scale23.12[0.96; 558.25]NA-U,DFunexposed, disease freeAnyduring pregnancy (anytime or not specified)studies TTT1 Bromley (Lamotrigine) (All indications) (Skel ...Bromley (Lamotrigine) (All indications) (Skeletal / Limb Malformations (Cohort studies)) Out of scale11.29[2.37; 53.91]0%-U,GPunexposed (general population or NOS)Anyduring pregnancy (anytime or not specified)studies TTT5 Bromley (Lamotrigine) (All indications) (Skel ...Bromley (Lamotrigine) (All indications) (Skeletal / Limb Malformations (Cohort studies)) 0.75[0.20; 2.89]0%-U,Sunexposed, sickAnyduring pregnancy (anytime or not specified)studies TTT5 metaPregmetaPreg 1.07[0.75; 1.52]0%2,087----Wiggs (Epilepsy) (Lamotrigine), 2024 Thomas (Lamotrigine) (Controls unexposed, sick), 2021 Ban (Lamotrigine) (Mixed indications), 2015 Vajda (Lamotrigine), 2013 Mawer (Lamotrigine) (Controls unexposed, sick), 2010 50.510.01.0