Lamotrigine (Epilepsy)

Preterm (< 37 weeks)

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.
S15841
R65203		 Bromley (Lamotrigine) (Epilepsy), 2023 Preterm birth (gestational age < 37 weeks) during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No 1.03 [0.45;2.39] C 15/106   11/80 26 106
ref
S12612
R47531		 Van Marter (Controls unexposed, disease free), 2021 Premature (≤36 wk) at least 1st trimester prospective cohort unexposed, disease free excluded Adjustment: No 0.77 [0.31;1.94] C
excluded (control group) 		9/110   11/106 20 110
ref
S12614
R47543		 Van Marter (Controls unexposed, sick), 2021 Premature (≤36 wk) at least 1st trimester prospective cohort unexposed, sick Adjustment: No 1.25 [0.15;10.61] C 9/110   1/15 10 110
ref
S8077
R24648		 Aydin, 2020 Preterm delivery (before 37 weeks of gestation) throughout pregnancy retrospective cohort unexposed, sick Adjustment: No 0.60 [0.03;14.19] C 0/7   2/22 2 7
ref
S7996
R24600		 Cohen, 2019 Preterm birth (ICD-9 644.2, 774.2, 776.6, 362.20, 362.22, 362.27, 765 excluding 765.20, 765.29) early pregnancy retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes 0.92 [0.67;1.27] -/-   160,604/1,440,631 160,595 -
ref
S5546
R18858		 Miškov (Controls unexposed, disease free), 2016 Premature deliveries during pregnancy (anytime or not specified) prospective cohort unexposed, disease free excluded Adjustment: No 2.58 [0.45;14.91] C
excluded (control group) 		2/26   4/128 6 26
ref
S7411
R21809		 Miškov (Controls unexposed, sick), 2016 Premature deliveries during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No 0.74 [0.03;18.97] C 2/26   0/4 2 26
ref
S5912
R14922		 Artama (Controls unexposed, disease free), 2013 Preterm birth (<37 gestational weeks) during pregnancy (anytime or not specified) population based cohort retrospective unexposed, disease free excluded Adjustment: Yes 0.98 [0.48;2.00]
excluded (control group) 		8/173   30,027/719,509 30,035 173
ref
S5920
R15018		 Artama (Controls unexposed, sick), 2013 Preterm birth (<37 gestational weeks) during pregnancy (anytime or not specified) population based cohort retrospective unexposed, sick Adjustment: Yes 1.00 [0.46;2.16] 8/173   85/1,793 93 173
ref
S6394
R17469		 Veiby (Controls unexposed, disease free) b, 2013 Preterm delivery (< 37 weeks) during pregnancy (anytime or not specified) prospective cohort unexposed, disease free excluded Adjustment: No 0.90 [0.40;2.00]
excluded (control group) 		7/103   7,269/106,899 7,276 103
ref
S6393
R17450		 Veiby (Controls unexposed, sick) b, 2013 Preterm delivery (< 37 weeks) during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No 0.87 [0.37;2.03] C 7/103   30/386 37 103
ref
S6940
R19598		 Cummings, 2011 Preterm (35-37 weeks) throughout pregnancy retrospective cohort (registry) unexposed, disease free Adjustment: No 16.22 [0.86;304.56] C 5/35   0/44 5 35
ref
Total 8 studies 0.96 [0.74;1.24] 160,770 560
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 Bromley (Lamotrigine) (Epilepsy), 2023Bromley, 2023 1 1.03[0.45; 2.39]2610610%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: moderateROB reporting: low Van Marter (Controls unexposed, sick), 2021Van Marter, 2021 2 1.25[0.15; 10.61]101101%ROB confusion: criticalROB selection: lowROB classification: lowROB missing: lowROB mesure: moderateROB reporting: low Aydin, 2020Aydin, 2020 0.60[0.03; 14.19]271%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Cohen, 2019Cohen, 2019 0.92[0.67; 1.27]160,595-66%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Miškov (Controls unexposed, sick), 2016Miškov, 2016 3 0.74[0.03; 18.97]2261%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: criticalROB mesure: moderateROB reporting: moderate Artama (Controls unexposed, sick), 2013Artama, 2013 4 1.00[0.46; 2.16]9317311%ROB confusion: moderateROB selection: lowROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Veiby (Controls unexposed, sick) b, 2013Veiby, 2013 5 0.87[0.37; 2.03]371039%ROB confusion: unclearROB selection: lowROB classification: lowROB missing: moderateROB mesure: moderateROB reporting: moderate Cummings, 2011Cummings, 2011 16.22[0.86; 304.56]5351%ROB confusion: unclearROB selection: lowROB classification: moderateROB missing: unclearROB mesure: lowROB reporting: moderate Total (8 studies) I2 = 0% 0.96[0.74; 1.24]160,7705600.250.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

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

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 0.96[0.74; 1.24]160,7705600%NABromley (Lamotrigine) (Epilepsy), 2023 Van Marter (Controls unexposed, sick), 2021 Aydin, 2020 Cohen, 2019 Miškov (Controls unexposed, sick), 2016 Artama (Controls unexposed, sick), 2013 Veiby (Controls unexposed, sick) b, 2013 Cummings, 2011 8 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 2.63[0.18; 39.44]160,6003572%NACohen, 2019 Cummings, 2011 2 unexposed, sickunexposed, sick 0.96[0.61; 1.51]1705250%NABromley (Lamotrigine) (Epilepsy), 2023 Van Marter (Controls unexposed, sick), 2021 Aydin, 2020 Miškov (Controls unexposed, sick), 2016 Artama (Controls unexposed, sick), 2013 Veiby (Controls unexposed, sick) b, 2013 6 Tags Adjustment   - No  - No 1.04[0.60; 1.81]823870%NABromley (Lamotrigine) (Epilepsy), 2023 Van Marter (Controls unexposed, sick), 2021 Aydin, 2020 Miškov (Controls unexposed, sick), 2016 Veiby (Controls unexposed, sick) b, 2013 Cummings, 2011 6   - Yes  - Yes 0.93[0.69; 1.25]160,6881730%NACohen, 2019 Artama (Controls unexposed, sick), 2013 2 All studiesAll studies 0.96[0.74; 1.24]160,7705600%NABromley (Lamotrigine) (Epilepsy), 2023 Van Marter (Controls unexposed, sick), 2021 Aydin, 2020 Cohen, 2019 Miškov (Controls unexposed, sick), 2016 Artama (Controls unexposed, sick), 2013 Veiby (Controls unexposed, sick) b, 2013 Cummings, 2011 80.250.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-3.93.81.9820.000Bromley (Lamotrigine) (Epilepsy), 2023Van Marter (Controls unexposed, sick), 2021Aydin, 2020Cohen, 2019Miškov (Controls unexposed, sick), 2016Artama (Controls unexposed, sick), 2013Veiby (Controls unexposed, sick) b, 2013Cummings, 2011

Asymetry test p-value = 0.2994 (by Egger's regression)

slope=-0.1729 (0.1483); intercept=0.4486 (0.3950); t=1.1358; p=0.2994

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 5912, 6394, 5546, 12612

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 0.96[0.73; 1.26]197,9374472%NAVan Marter (Controls unexposed, disease free), 2021 Cohen, 2019 Miškov (Controls unexposed, disease free), 2016 Artama (Controls unexposed, disease free), 2013 Veiby (Controls unexposed, disease free) b, 2013 Cummings, 2011 6 unexposed, sick controlsunexposed, sick controls 0.96[0.61; 1.51]1705250%NABromley (Lamotrigine) (Epilepsy), 2023 Van Marter (Controls unexposed, sick), 2021 Aydin, 2020 Miškov (Controls unexposed, sick), 2016 Artama (Controls unexposed, sick), 2013 Veiby (Controls unexposed, sick) b, 2013 60.510.01.0

Umbrella review (other published meta-analyses)

Published MATE95% CIn exposedkI2Control groupExposition period Veroniki (NMA)Veroniki (NMA) 1.05[0.70; 1.48]-whatever (meta-analysis)during pregnancy (anytime or not specified)studies10 metaPregmetaPreg 0.96[0.74; 1.24]0%560--Bromley (Lamotrigine) (Epilepsy), 2023 Van Marter (Controls unexposed, sick), 2021 Aydin, 2020 Cohen, 2019 Miškov (Controls unexposed, sick), 2016 Artama (Controls unexposed, sick), 2013 Veiby (Controls unexposed, sick) b, 2013 Cummings, 2011 80.510.01.0