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

Intrauterine deaths (as a whole or unspecified)

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.
S18754
R79762		 Moore (Lamotrigine) (Mixed indications), 2025 Pregnancy loss (pregnancy outcome other than live birth at any gestation, including spontaneous loss (miscarriage, stillbirth) and termination of pregnancy) during pregnancy (anytime or not specified) population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Matched 1.10 [0.98;1.24] 481/1,976   3,992/19,389 4,473 1,976
ref
S16201
R67131		 Vajda (Lamotrigine) (Epilepsy), 2024 Intra uterine foetal death (including both spontaneous abortions and stillbirths, but not elective termination) during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No 9.88 [0.58;169.82] C 10/326   0/149 10 326
ref
S8911
R30114		 Meador (Lamotrigine) (Controls unexposed, disease free), 2020 Fetal loss (Spontaneous miscarriages and fetal death) 1st trimester prospective cohort unexposed, disease free excluded Adjustment: No 6.74 [0.34;132.16] C
excluded (control group) 		3/113   0/106 3 113
ref
S8912
R30118		 Meador (Lamotrigine) (Controls unexposed, sick), 2020 Fetal loss (Spontaneous miscarriages and fetal death) 1st trimester prospective cohort unexposed, sick Adjustment: No 0.93 [0.05;18.87] C 3/113   0/15 3 113
ref
S12464
R46887		 Kernizan, 2019 Fetal demise during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: No 1.20 [0.06;23.68] C 0/13   4/140 4 13
ref
S8927
R30168		 Trivedi (Lamotrigine), 2018 Spontaneous fetal loss (both spontaneous abortion before 20 weeks of gestation and stillbirths occurring after 20 weeks of gestation) 1st trimester prospective cohort unexposed, sick Adjustment: Yes 13.33 [1.41;125.78] 4/48   5/178 9 48
ref
S8913
R30121		 Miškov (Lamotrigine) (Controls unexposed, disease free), 2016 Fetal loss during pregnancy (anytime or not specified) prospective cohort unexposed, disease free excluded Adjustment: No 35.31 [1.85;672.61] C
excluded (control group) 		4/37   0/128 4 37
ref
S8914
R30127		 Miškov (Lamotrigine) (Controls unexposed, sick), 2016 Fetal loss during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No 0.97 [0.04;22.01] C 4/37   0/4 4 37
ref
S8972
R30407		 Holmes (Lamotrigine) (Mixed indications), 2011 Intrauterine death as a whole 1st trimester prospective cohort unexposed, disease free Adjustment: No 1.81 [0.23;14.38] C 9/948   1/190 10 948
ref
Total 7 studies 1.56 [0.79;3.08] 4,513 3,461
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 Moore (Lamotrigine) (Mixed indications), 2025Moore, 2025 1 1.10[0.98; 1.24]4,4731,97664%ROB confusion: seriousROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: low Vajda (Lamotrigine) (Epilepsy), 2024Vajda, 2024 2 9.88[0.58; 169.82]103265%ROB confusion: criticalROB selection: criticalROB classification: unclearROB missing: unclearROB mesure: criticalROB reporting: moderate Meador (Lamotrigine) (Controls unexposed, sick), 2020Meador, 2020 3 0.93[0.05; 18.87]31135%ROB confusion: unclearROB selection: lowROB classification: lowROB missing: lowROB mesure: moderateROB reporting: low Kernizan, 2019Kernizan, 2019 1.20[0.06; 23.68]4135%ROB confusion: criticalROB selection: unclearROB classification: unclearROB missing: unclearROB mesure: unclearROB reporting: moderate Trivedi (Lamotrigine), 2018Trivedi, 2018 4 13.33[1.41; 125.78]9488%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Miškov (Lamotrigine) (Controls unexposed, sick), 2016Miškov, 2016 5 0.97[0.04; 22.01]4374%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: criticalROB mesure: moderateROB reporting: moderate Holmes (Lamotrigine) (Mixed indications), 2011Holmes, 2011 6 1.81[0.23; 14.38]109489%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: moderateROB mesure: moderateROB reporting: moderate Total (7 studies) I2 = 17% 1.56[0.79; 3.08]4,5133,4610.250.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

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

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.56[0.79; 3.08]4,5133,46117%NAMoore (Lamotrigine) (Mixed indications), 2025 Vajda (Lamotrigine) (Epilepsy), 2024 Meador (Lamotrigine) (Controls unexposed, sick), 2020 Kernizan, 2019 Trivedi (Lamotrigine), 2018 Miškov (Lamotrigine) (Controls unexposed, sick), 2016 Holmes (Lamotrigine) (Mixed indications), 2011 7 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.10[0.98; 1.24]4,4832,9240%NAMoore (Lamotrigine) (Mixed indications), 2025 Holmes (Lamotrigine) (Mixed indications), 2011 2 unexposed, sickunexposed, sick 3.48[1.00; 12.04]305370%NAVajda (Lamotrigine) (Epilepsy), 2024 Meador (Lamotrigine) (Controls unexposed, sick), 2020 Kernizan, 2019 Trivedi (Lamotrigine), 2018 Miškov (Lamotrigine) (Controls unexposed, sick), 2016 5 Tags Adjustment   - No  - No 1.88[0.56; 6.32]311,4370%NAVajda (Lamotrigine) (Epilepsy), 2024 Meador (Lamotrigine) (Controls unexposed, sick), 2020 Kernizan, 2019 Miškov (Lamotrigine) (Controls unexposed, sick), 2016 Holmes (Lamotrigine) (Mixed indications), 2011 5   - Yes  - Yes 2.95[0.27; 32.15]4,4822,02479%NAMoore (Lamotrigine) (Mixed indications), 2025 Trivedi (Lamotrigine), 2018 2 MatchedMatched 1.10[0.98; 1.24]4,4731,976 -NAMoore (Lamotrigine) (Mixed indications), 2025 1 All studiesAll studies 1.56[0.79; 3.08]4,5133,46117%NAMoore (Lamotrigine) (Mixed indications), 2025 Vajda (Lamotrigine) (Epilepsy), 2024 Meador (Lamotrigine) (Controls unexposed, sick), 2020 Kernizan, 2019 Trivedi (Lamotrigine), 2018 Miškov (Lamotrigine) (Controls unexposed, sick), 2016 Holmes (Lamotrigine) (Mixed indications), 2011 70.250.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-3.74.21.9120.000Moore (Lamotrigine) (Mixed indications), 2025Vajda (Lamotrigine) (Epilepsy), 2024Meador (Lamotrigine) (Controls unexposed, sick), 2020Kernizan, 2019Trivedi (Lamotrigine), 2018Miškov (Lamotrigine) (Controls unexposed, sick), 2016Holmes (Lamotrigine) (Mixed indications), 2011

Asymetry test p-value = 0.1506 (by Egger's regression)

slope=0.0546 (0.0650); intercept=0.6987 (0.4120); t=1.6961; p=0.1506

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 8913, 8911

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 2.77[0.67; 11.37]4,4903,07457%NAMoore (Lamotrigine) (Mixed indications), 2025 Meador (Lamotrigine) (Controls unexposed, disease free), 2020 Miškov (Lamotrigine) (Controls unexposed, disease free), 2016 Holmes (Lamotrigine) (Mixed indications), 2011 4 unexposed, sick controlsunexposed, sick controls 3.48[1.00; 12.04]305370%NAVajda (Lamotrigine) (Epilepsy), 2024 Meador (Lamotrigine) (Controls unexposed, sick), 2020 Kernizan, 2019 Trivedi (Lamotrigine), 2018 Miškov (Lamotrigine) (Controls unexposed, sick), 2016 50.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Veroniki a (NMA) (Combined fetal losses)Veroniki a (NMA) (Combined fetal losses) 1.38[0.70; 2.88]-Wwhatever (meta-analysis)Anyduring pregnancy (anytime or not specified)studies TTT8 metaPregmetaPreg 1.56[0.79; 3.08]17%3,461----Moore (Lamotrigine) (Mixed indications), 2025 Vajda (Lamotrigine) (Epilepsy), 2024 Meador (Lamotrigine) (Controls unexposed, sick), 2020 Kernizan, 2019 Trivedi (Lamotrigine), 2018 Miškov (Lamotrigine) (Controls unexposed, sick), 2016 Holmes (Lamotrigine) (Mixed indications), 2011 70.510.01.0