Lamotrigine (Epilepsy)

Major congenital malformations

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
R65208		 Bromley (Lamotrigine) (Epilepsy), 2023 Major congenital anomaly during pregnancy (anytime or not specified) excluded prospective cohort unexposed, sick Adjustment: No 0.75 [0.15;3.81] C
excluded (exposition period) 		3/106   3/80 6 106
ref
S15853
R65262		 Li, 2023 Major congenital malformation during pregnancy (anytime or not specified) excluded prospective cohort unexposed, sick Adjustment: No 0.44 [0.02;7.80] C
excluded (exposition period) 		0/38   7/253 7 38
ref
S12679
R47914		 Alsfouk, 2021 Major congenital malformation during pregnancy (anytime or not specified) excluded retrospective cohort unexposed, sick Adjustment: No 4.46 [0.37;53.71] C
excluded (exposition period) 		2/15   1/30 3 15
ref
S12515
R47140		 Hosny, 2021 Major birth defects 1st trimester prospective cohort unexposed, sick Adjustment: No 2.60 [0.08;82.80] C 0/3   1/21 1 3
ref
S7546
R22589		 Thomas (Controls unexposed, disease free), 2021 Major congenital malformations 1st trimester prospective cohort unexposed, disease free excluded Adjustment: No 0.76 [0.10;5.75]
excluded (control group) 		1/38   11/319 12 38
ref
S7514
R47116		 Thomas (Controls unexposed, sick), 2021 Major congenital malformations 1st trimester prospective cohort unexposed, sick Adjustment: Yes 0.50 [0.10;3.70] 1/50   16/340 17 50
ref
S8003
R24374		 AlSheikh, 2020 Fetal/neonatal malformation during pregnancy (anytime or not specified) excluded prospective cohort unexposed, sick Adjustment: No 0.11 [0.00;3.08] C
excluded (exposition period) 		0/20   1/8 1 20
ref
S7494
R22419		 Meador (Controls unexposed, disease free), 2020 Major congenital malformations 1st trimester prospective cohort unexposed, disease free excluded Adjustment: No 2.48 [0.47;13.05] C
excluded (control group) 		5/110   2/106 7 110
ref
S7500
R22437		 Meador (Controls unexposed, sick), 2020 Major congenital malformations 1st trimester prospective cohort unexposed, sick Adjustment: No 0.67 [0.07;6.13] C 5/110   1/15 6 110
ref
S7776
R22985		 Vajda, 2019 Fetal malformations at least 1st trimester prospective cohort unexposed, sick Adjustment: No 1.75 [0.66;4.55] 20/406   5/176 25 406
ref
S7719
R22910		 Diav-Citrin, 2017 Major anomalies excluding chromosomal or genetic anomalies at least 1st trimester prospective cohort unexposed, disease free Adjustment: No 2.04 [0.81;5.13] C 6/114   22/828 28 114
ref
S8037
R24447		 He, 2017 Congenital malformations during pregnancy (anytime or not specified) excluded prospective cohort unexposed, sick Adjustment: No 4.07 [0.07;222.16] C
excluded (exposition period) 		0/8   0/31 0 8
ref
S9821
R35913		 Petersen (Controls unexposed NOS), 2017 Major congenital malformation 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) excluded Adjustment: Yes 0.95 [0.51;1.79]
excluded (control group) 		10/357   5,315/239,151 5,325 357
ref
S9992
R35914		 Petersen (Controls unexposed, sick), 2017 Major congenital malformation 1st trimester retrospective cohort (claims database) unexposed, sick Adjustment: Yes 0.88 [0.44;1.75] 9/344   86/2,844 95 344
ref
S10269
R37612		 Razaz (Controls unexposed, disease free), 2017 Major malformations during pregnancy (anytime or not specified) population based cohort retrospective unexposed, disease free excluded Adjustment: No 1.35 [0.88;2.07] C
excluded (control group) 		22/503   46,632/1,424,279 46,654 503
ref
S10268
R37611		 Razaz (Controls unexposed, sick), 2017 Major malformations during pregnancy (anytime or not specified) excluded population based cohort retrospective unexposed, sick Adjustment: No 0.94 [0.58;1.51] C
excluded (exposition period) 		22/503   87/1,868 109 503
ref
S6959
R19692		 Vanya (Controls unexposed, sick), 2015 Major congenital malformations throughout pregnancy retrospective cohort unexposed, sick Adjustment: No 3.55 [0.06;199.99] C 0/6   0/20 0 6
ref
S8234
R25969		 Campbell, 2014 Major malformations 1st trimester prospective cohort unexposed, sick Adjustment: No 0.97 [0.52;1.80] C 49/2,098   13/541 62 2,098
ref
S6328
R17150		 Veiby (Controls unexposed, disease free), 2014 Major malformations throughout pregnancy population based cohort retrospective unexposed, disease free excluded Adjustment: Yes 1.48 [0.97;2.24]
excluded (control group) 		23/593   22,371/771,412 22,394 593
ref
S6329
R17151		 Veiby (Controls unexposed, sick), 2014 Major malformations throughout pregnancy population based cohort retrospective unexposed, sick Adjustment: No 1.40 [0.88;2.21] C 23/593   106/3,773 129 593
ref
S6523
R17977		 Cassina, 2013 Major congenital anomalies 1st trimester prospective cohort unexposed, disease free Adjustment: No 0.68 [0.04;11.48] C 0/23   25/803 25 23
ref
S8135
R24987		 Charlton, 2011 Major congenital malformations 1st trimester retrospective cohort (claims database) unexposed, sick Adjustment: No 1.26 [0.38;4.17] 3/98   22/902 25 98
ref
S9843
R35294		 Mawer (Controls unexposed, disease free), 2010 Major malformations 1st trimester prospective cohort unexposed, disease free excluded Adjustment: No Matched 2.66 [0.52;13.68]
excluded (control group) 		2/37   6/285 8 37
ref
S9844
R35300		 Mawer (Controls unexposed, sick), 2010 Major malformations 1st trimester prospective cohort unexposed, sick Adjustment: No 2.29 [0.20;26.30] C 2/37   1/41 3 37
ref
S8119
R25483		 Holmes, 2008 Major malformations 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No 1.40 [0.90;2.30] 16/684   24/1,477 40 684
ref
S6673
R18471		 Dean, 2007 Major malformation during pregnancy (anytime or not specified) excluded retrospective cohort unexposed, sick Adjustment: No 1.73 [0.07;40.78] C
excluded (exposition period) 		0/4   3/46 3 4
ref
Total 13 studies 1.27 [1.00;1.61] 456 4,566
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 Hosny, 2021Hosny, 2021 2.60[0.08; 82.80]130%ROB confusion: criticalROB selection: moderateROB classification: unclearROB missing: lowROB mesure: unclearROB reporting: moderate Thomas (Controls unexposed, sick), 2021Thomas, 2021 1 0.50[0.10; 3.70]17502%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Meador (Controls unexposed, sick), 2020Meador, 2020 2 0.67[0.07; 6.13]61101%ROB confusion: unclearROB selection: lowROB classification: lowROB missing: lowROB mesure: moderateROB reporting: low Vajda, 2019Vajda, 2019 1.75[0.66; 4.55]254066%ROB confusion: criticalROB selection: moderateROB classification: lowROB missing: moderateROB mesure: moderateROB reporting: moderate Diav-Citrin, 2017Diav-Citrin, 2017 2.04[0.81; 5.13]281147%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Petersen (Controls unexposed, sick), 2017Petersen, 2017 3 0.88[0.44; 1.75]9534412%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Vanya (Controls unexposed, sick), 2015Vanya, 2015 4 3.55[0.06; 199.99]060%ROB confusion: criticalROB selection: criticalROB classification: unclearROB missing: unclearROB mesure: unclearROB reporting: moderate Campbell, 2014Campbell, 2014 0.97[0.52; 1.80]622,09815%ROB confusion: unclearROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Veiby (Controls unexposed, sick), 2014Veiby, 2014 5 1.40[0.88; 2.21]12959327%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: moderateROB reporting: moderate Cassina, 2013Cassina, 2013 0.68[0.04; 11.48]25231%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Charlton, 2011Charlton, 2011 1.26[0.38; 4.17]25984%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Mawer (Controls unexposed, sick), 2010Mawer, 2010 6 2.29[0.20; 26.30]3371%ROB confusion: criticalROB selection: moderateROB classification: lowROB missing: moderateROB mesure: moderateROB reporting: moderate Holmes, 2008Holmes, 2008 1.40[0.90; 2.30]4068425%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: moderateROB reporting: moderate Total (13 studies) I2 = 0% 1.27[1.00; 1.61]4564,5660.210.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, sick; 2: Controls unexposed, sick; 3: Controls unexposed, sick; 4: Controls unexposed, sick; 5: Controls unexposed, sick; 6: Controls unexposed, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.27[1.00; 1.61]4564,5660%NAHosny, 2021 Thomas (Controls unexposed, sick), 2021 Meador (Controls unexposed, sick), 2020 Vajda, 2019 Diav-Citrin, 2017 Petersen (Controls unexposed, sick), 2017 Vanya (Controls unexposed, sick), 2015 Campbell, 2014 Veiby (Controls unexposed, sick), 2014 Cassina, 2013 Charlton, 2011 Mawer (Controls unexposed, sick), 2010 Holmes, 2008 13 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.49[0.98; 2.25]938210%NADiav-Citrin, 2017 Cassina, 2013 Holmes, 2008 3 unexposed, sickunexposed, sick 1.18[0.88; 1.57]3633,7450%NAHosny, 2021 Thomas (Controls unexposed, sick), 2021 Meador (Controls unexposed, sick), 2020 Vajda, 2019 Petersen (Controls unexposed, sick), 2017 Vanya (Controls unexposed, sick), 2015 Campbell, 2014 Veiby (Controls unexposed, sick), 2014 Charlton, 2011 Mawer (Controls unexposed, sick), 2010 10 Tags Adjustment   - No  - No 1.36[1.06; 1.76]3444,1720%NAHosny, 2021 Meador (Controls unexposed, sick), 2020 Vajda, 2019 Diav-Citrin, 2017 Vanya (Controls unexposed, sick), 2015 Campbell, 2014 Veiby (Controls unexposed, sick), 2014 Cassina, 2013 Charlton, 2011 Mawer (Controls unexposed, sick), 2010 Holmes, 2008 11   - Yes  - Yes 0.82[0.43; 1.56]1123940%NAThomas (Controls unexposed, sick), 2021 Petersen (Controls unexposed, sick), 2017 2 All studiesAll studies 1.27[1.00; 1.61]4564,5660%NAHosny, 2021 Thomas (Controls unexposed, sick), 2021 Meador (Controls unexposed, sick), 2020 Vajda, 2019 Diav-Citrin, 2017 Petersen (Controls unexposed, sick), 2017 Vanya (Controls unexposed, sick), 2015 Campbell, 2014 Veiby (Controls unexposed, sick), 2014 Cassina, 2013 Charlton, 2011 Mawer (Controls unexposed, sick), 2010 Holmes, 2008 130.210.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-4.85.12.4690.000Hosny, 2021Thomas (Controls unexposed, sick), 2021Meador (Controls unexposed, sick), 2020Vajda, 2019Diav-Citrin, 2017Petersen (Controls unexposed, sick), 2017Vanya (Controls unexposed, sick), 2015Campbell, 2014Veiby (Controls unexposed, sick), 2014Cassina, 2013Charlton, 2011Mawer (Controls unexposed, sick), 2010Holmes, 2008

Asymetry test p-value = 0.9284 (by Egger's regression)

slope=0.2529 (0.1554); intercept=-0.0329 (0.3573); t=0.0920; p=0.9284

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 9843, 6328, 9821, 10269, 7494, 7546

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.40[1.08; 1.81]27,8391,9560%NAThomas (Controls unexposed, disease free), 2021 Meador (Controls unexposed, disease free), 2020 Diav-Citrin, 2017 Petersen (Controls unexposed NOS), 2017 Veiby (Controls unexposed, disease free), 2014 Cassina, 2013 Mawer (Controls unexposed, disease free), 2010 Holmes, 2008 8 unexposed, sick controlsunexposed, sick controls 1.18[0.88; 1.57]3633,7450%NAHosny, 2021 Thomas (Controls unexposed, sick), 2021 Meador (Controls unexposed, sick), 2020 Vajda, 2019 Petersen (Controls unexposed, sick), 2017 Vanya (Controls unexposed, sick), 2015 Campbell, 2014 Veiby (Controls unexposed, sick), 2014 Charlton, 2011 Mawer (Controls unexposed, sick), 2010 100.510.01.0

Umbrella review (other published meta-analyses)

Published MATE95% CIn exposedkI2Control groupExposition period Veroniki (NMA)Veroniki (NMA) 0.96[0.72; 1.25]-whatever (meta-analysis)during pregnancy (anytime or not specified)studies17 WestonWeston 1.68[0.78; 3.65]0-unexposed, disease freeduring pregnancy (anytime or not specified)studies3 WestonWeston 1.07[0.64; 1.77]0-unexposed, sickduring pregnancy (anytime or not specified)studies3 ParientePariente 1.15[0.62; 2.16]0-unexposed, sickduring pregnancy (anytime or not specified)studies3 ParientePariente 1.25[0.89; 1.74]0-unexposed, disease freeduring pregnancy (anytime or not specified)studies3 metaPregmetaPreg 1.27[1.00; 1.61]0%4,566--Hosny, 2021 Thomas (Controls unexposed, sick), 2021 Meador (Controls unexposed, sick), 2020 Vajda, 2019 Diav-Citrin, 2017 Petersen (Controls unexposed, sick), 2017 Vanya (Controls unexposed, sick), 2015 Campbell, 2014 Veiby (Controls unexposed, sick), 2014 Cassina, 2013 Charlton, 2011 Mawer (Controls unexposed, sick), 2010 Holmes, 2008 130.510.01.0