Lamotrigine (All indications)

Congenital heart 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.
S15197
R62329		 Cohen (Lamotrigine) (Mixed indications), 2023 Cardiac system malformation 1st trimester population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Partial overlapping 0.96 [0.81;1.13] -/8,339   -/4,866,362 - 8,339
ref
S8924
R48249		 Thomas (Lamotrigine) (Controls unexposed, sick), 2021 Cardiac malformations 1st trimester prospective cohort unexposed, sick Adjustment: No 0.75 [0.09;6.05] C 1/50   9/340 10 50
ref
S8920
R35918		 Diav-Citrin (Lamotrigine), 2017 Cardiovascular anomalies without chromosomal anomalies at least 1st trimester prospective cohort unexposed, disease free Adjustment: No 2.46 [0.66;9.22] C 3/114   9/828 12 114
ref
S8969
R30374		 Ban (Lamotrigine) (Mixed indications), 2015 Heart anomaly 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: Yes 3.33 [1.25;8.89] 7/273   2,041/257,153 2,048 273
ref
S8908
R30103		 Källén (Lamotrigine) (Indications NOS), 2013 Any cardiac defect early pregnancy population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Partial overlapping 0.81 [0.44;1.50] 10/1,084   16,145/1,575,847 16,155 1,084
ref
S10292
R37689		 Vajda (Lamotrigine), 2013 Cardiac Malformations at least 1st trimester prospective cohort unexposed, sick Adjustment: No 1.40 [0.14;13.61] C 3/315   1/147 4 315
ref
S8909
R35287		 Mawer (Lamotrigine) (Controls unexposed, disease free), 2010 Cardiac Malformations 1st trimester prospective cohort unexposed, disease free excluded Adjustment: No Matched 2.59 [0.10;64.75] C
excluded (control group) 		0/37   1/285 1 37
ref
S8910
R35291		 Mawer (Lamotrigine) (Controls unexposed, sick), 2010 Cardiac Malformations 1st trimester prospective cohort unexposed, sick Adjustment: No Matched 1.11 [0.02;57.36] C 0/37   0/41 0 37
ref
Total 7 studies 1.16 [0.78;1.71] 18,229 10,212
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 Cohen (Lamotrigine) (Mixed indications), 2023Cohen, 2023 1 0.96[0.81; 1.13]-8,33950%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Thomas (Lamotrigine) (Controls unexposed, sick), 2021Thomas, 2021 2 0.75[0.09; 6.05]10503%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Diav-Citrin (Lamotrigine), 2017Diav-Citrin, 2017 3 2.46[0.66; 9.22]121147%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Ban (Lamotrigine) (Mixed indications), 2015Ban, 2015 4 3.33[1.25; 8.89]2,04827312%ROB confusion: seriousROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Källén (Lamotrigine) (Indications NOS), 2013Källén, 2013 5 0.81[0.44; 1.50]16,1551,08423%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Vajda (Lamotrigine), 2013Vajda, 2013 6 1.40[0.14; 13.61]43153%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Mawer (Lamotrigine) (Controls unexposed, sick), 2010Mawer, 2010 7 1.11[0.02; 57.36]0371%ROB confusion: criticalROB selection: moderateROB classification: lowROB missing: moderateROB mesure: moderateROB reporting: moderate Total (7 studies) I2 = 29% 1.16[0.78; 1.71]18,22910,2120.210.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Lamotrigine) (Mixed indications; 2: Lamotrigine) (Controls unexposed, sick; 3: Lamotrigine; 4: Lamotrigine) (Mixed indications; 5: Lamotrigine) (Indications NOS; 6: Lamotrigine; 7: Lamotrigine) (Controls unexposed, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.16[0.78; 1.71]18,22910,21229%NACohen (Lamotrigine) (Mixed indications), 2023 Thomas (Lamotrigine) (Controls unexposed, sick), 2021 Diav-Citrin (Lamotrigine), 2017 Ban (Lamotrigine) (Mixed indications), 2015 Källén (Lamotrigine) (Indications NOS), 2013 Vajda (Lamotrigine), 2013 Mawer (Lamotrigine) (Controls unexposed, sick), 2010 7 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.28[0.75; 2.20]18,2159,81064%NACohen (Lamotrigine) (Mixed indications), 2023 Diav-Citrin (Lamotrigine), 2017 Ban (Lamotrigine) (Mixed indications), 2015 Källén (Lamotrigine) (Indications NOS), 2013 4 unexposed, sickunexposed, sick 1.01[0.24; 4.25]144020%NAThomas (Lamotrigine) (Controls unexposed, sick), 2021 Vajda (Lamotrigine), 2013 Mawer (Lamotrigine) (Controls unexposed, sick), 2010 3 Tags Adjustment   - No  - No 1.64[0.62; 4.32]265160%NAThomas (Lamotrigine) (Controls unexposed, sick), 2021 Diav-Citrin (Lamotrigine), 2017 Vajda (Lamotrigine), 2013 Mawer (Lamotrigine) (Controls unexposed, sick), 2010 4   - Yes  - Yes 1.17[0.66; 2.06]18,2039,69669%NACohen (Lamotrigine) (Mixed indications), 2023 Ban (Lamotrigine) (Mixed indications), 2015 Källén (Lamotrigine) (Indications NOS), 2013 3 MatchedMatched 1.11[0.02; 57.36]-37 -NAMawer (Lamotrigine) (Controls unexposed, sick), 2010 1 Partial overlappingPartial overlapping 0.95[0.81; 1.11]16,1559,4230%NACohen (Lamotrigine) (Mixed indications), 2023 Källén (Lamotrigine) (Indications NOS), 2013 2 All studiesAll studies 1.16[0.78; 1.71]18,22910,21229%NACohen (Lamotrigine) (Mixed indications), 2023 Thomas (Lamotrigine) (Controls unexposed, sick), 2021 Diav-Citrin (Lamotrigine), 2017 Ban (Lamotrigine) (Mixed indications), 2015 Källén (Lamotrigine) (Indications NOS), 2013 Vajda (Lamotrigine), 2013 Mawer (Lamotrigine) (Controls unexposed, sick), 2010 70.210.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-4.74.92.4160.000Cohen (Lamotrigine) (Mixed indications), 2023Thomas (Lamotrigine) (Controls unexposed, sick), 2021Diav-Citrin (Lamotrigine), 2017Ban (Lamotrigine) (Mixed indications), 2015Källén (Lamotrigine) (Indications NOS), 2013Vajda (Lamotrigine), 2013Mawer (Lamotrigine) (Controls unexposed, sick), 2010

Asymetry test p-value = 0.2907 (by Egger's regression)

slope=-0.0932 (0.1173); intercept=0.6560 (0.5555); t=1.1809; p=0.2907

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) 1.28[0.77; 2.12]18,2169,84753%NACohen (Lamotrigine) (Mixed indications), 2023 Diav-Citrin (Lamotrigine), 2017 Ban (Lamotrigine) (Mixed indications), 2015 Källén (Lamotrigine) (Indications NOS), 2013 Mawer (Lamotrigine) (Controls unexposed, disease free), 2010 5 unexposed, sick controlsunexposed, sick controls 1.01[0.24; 4.25]144020%NAThomas (Lamotrigine) (Controls unexposed, sick), 2021 Vajda (Lamotrigine), 2013 Mawer (Lamotrigine) (Controls unexposed, sick), 2010 30.510.01.0

Umbrella review (other published meta-analyses)

Published MATE95% CIn exposedkI2Control groupExposition period Veroniki (NMA)Veroniki (NMA) 0.55[0.32; 0.95]0-whatever (meta-analysis)during pregnancy (anytime or not specified)studies12 WestonWeston 2.57[0.11; 62.03]NA-unexposed, disease freeduring pregnancy (anytime or not specified)studies1 WestonWeston 1.40[0.15; 13.35]0-unexposed, sickduring pregnancy (anytime or not specified)studies2 Veroniki (MA)Veroniki (MA) 1.73[0.05; 21.66]-whatever (meta-analysis)1st trimesterstudies2 metaPregmetaPreg 1.16[0.78; 1.71]29%10,212--Cohen (Lamotrigine) (Mixed indications), 2023 Thomas (Lamotrigine) (Controls unexposed, sick), 2021 Diav-Citrin (Lamotrigine), 2017 Ban (Lamotrigine) (Mixed indications), 2015 Källén (Lamotrigine) (Indications NOS), 2013 Vajda (Lamotrigine), 2013 Mawer (Lamotrigine) (Controls unexposed, sick), 2010 70.510.01.0