Lamotrigine (All indications)

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.
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
S8928
R30169		 Vajda (Lamotrigine), 2018 Intrauterine foetal death throughout pregnancy prospective cohort unexposed, sick Adjustment: No 6.23 [0.83;47.00] 14/382   1/170 15 382
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 6 studies 3.03 [1.12;8.22] 45 1,541
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 Meador (Lamotrigine) (Controls unexposed, sick), 2020Meador, 2020 1 0.93[0.05; 18.87]311311%ROB confusion: unclearROB selection: lowROB classification: lowROB missing: lowROB mesure: moderateROB reporting: low Kernizan, 2019Kernizan, 2019 1.20[0.06; 23.68]41311%ROB confusion: criticalROB selection: unclearROB classification: unclearROB missing: unclearROB mesure: unclearROB reporting: moderate Trivedi (Lamotrigine), 2018Trivedi, 2018 2 13.33[1.41; 125.78]94820%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Vajda (Lamotrigine), 2018Vajda, 2018 3 6.23[0.83; 47.00]1538224%ROB confusion: criticalROB selection: moderateROB classification: lowROB missing: lowROB mesure: moderateROB reporting: moderate Miškov (Lamotrigine) (Controls unexposed, sick), 2016Miškov, 2016 4 0.97[0.04; 22.01]43710%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: criticalROB mesure: moderateROB reporting: moderate Holmes (Lamotrigine) (Mixed indications), 2011Holmes, 2011 5 1.81[0.23; 14.38]1094823%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: moderateROB mesure: moderateROB reporting: moderate Total (6 studies) I2 = 0% 3.03[1.12; 8.22]451,5410.250.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

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

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 3.03[1.12; 8.22]451,5410%NAMeador (Lamotrigine) (Controls unexposed, sick), 2020 Kernizan, 2019 Trivedi (Lamotrigine), 2018 Vajda (Lamotrigine), 2018 Miškov (Lamotrigine) (Controls unexposed, sick), 2016 Holmes (Lamotrigine) (Mixed indications), 2011 6 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.81[0.23; 14.38]10948 -NAHolmes (Lamotrigine) (Mixed indications), 2011 1 unexposed, sickunexposed, sick 3.54[1.13; 11.07]355930%NAMeador (Lamotrigine) (Controls unexposed, sick), 2020 Kernizan, 2019 Trivedi (Lamotrigine), 2018 Vajda (Lamotrigine), 2018 Miškov (Lamotrigine) (Controls unexposed, sick), 2016 5 Tags Adjustment   - No  - No 2.10[0.69; 6.41]361,4930%NAMeador (Lamotrigine) (Controls unexposed, sick), 2020 Kernizan, 2019 Vajda (Lamotrigine), 2018 Miškov (Lamotrigine) (Controls unexposed, sick), 2016 Holmes (Lamotrigine) (Mixed indications), 2011 5   - Yes  - Yes 13.33[1.41; 125.90]948 -NATrivedi (Lamotrigine), 2018 1 All studiesAll studies 3.03[1.12; 8.22]451,5410%NAMeador (Lamotrigine) (Controls unexposed, sick), 2020 Kernizan, 2019 Trivedi (Lamotrigine), 2018 Vajda (Lamotrigine), 2018 Miškov (Lamotrigine) (Controls unexposed, sick), 2016 Holmes (Lamotrigine) (Mixed indications), 2011 60.250.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-3.74.91.9120.000Meador (Lamotrigine) (Controls unexposed, sick), 2020Kernizan, 2019Trivedi (Lamotrigine), 2018Vajda (Lamotrigine), 2018Miškov (Lamotrigine) (Controls unexposed, sick), 2016Holmes (Lamotrigine) (Mixed indications), 2011

Asymetry test p-value = 0.1477 (by Egger's regression)

slope=4.7275 (2.0547); intercept=-2.9482 (1.6458); t=1.7913; p=0.1477

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) 5.82[1.03; 32.81]171,09824%NAMeador (Lamotrigine) (Controls unexposed, disease free), 2020 Miškov (Lamotrigine) (Controls unexposed, disease free), 2016 Holmes (Lamotrigine) (Mixed indications), 2011 3 unexposed, sick controlsunexposed, sick controls 3.54[1.13; 11.07]355930%NAMeador (Lamotrigine) (Controls unexposed, sick), 2020 Kernizan, 2019 Trivedi (Lamotrigine), 2018 Vajda (Lamotrigine), 2018 Miškov (Lamotrigine) (Controls unexposed, sick), 2016 50.510.01.0

Umbrella review (other published meta-analyses)

Published MATE95% CIn exposedkI2Control groupExposition period Veroniki (NMA)Veroniki (NMA) 1.38[0.70; 2.88]-whatever (meta-analysis)during pregnancy (anytime or not specified)studies8 metaPregmetaPreg 3.03[1.12; 8.22]0%1,541--Meador (Lamotrigine) (Controls unexposed, sick), 2020 Kernizan, 2019 Trivedi (Lamotrigine), 2018 Vajda (Lamotrigine), 2018 Miškov (Lamotrigine) (Controls unexposed, sick), 2016 Holmes (Lamotrigine) (Mixed indications), 2011 60.510.01.0