Lamotrigine (Epilepsy)

Small for gestational age (weight)

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
R65204		 Bromley (Lamotrigine) (Epilepsy), 2023 Small for gestation (calculated using gender-specific scales) during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No 0.72 [0.31;1.65] C 13/106   13/80 26 106
ref
S12548
R47238		 Dreier, 2021 Small for gestational age (birth weight below the 10th percentile for GA, sex and country) during pregnancy (anytime or not specified) population based cohort retrospective unexposed, sick Adjustment: Yes 0.97 [0.87;1.08] -/4,679   -/- - 4,679
ref
S12612
R47530		 Van Marter (Controls unexposed, disease free), 2021 Small for gestational age (weight for gestational age <10th percentile) at least 1st trimester prospective cohort unexposed, disease free excluded Adjustment: No 0.10 [0.01;0.79] C
excluded (control group) 		1/106   9/102 10 106
ref
S12614
R47542		 Van Marter (Controls unexposed, sick), 2021 Small for gestational age (weight for gestational age <10th percentile) at least 1st trimester prospective cohort unexposed, sick Adjustment: No 0.39 [0.02;10.00] C 1/106   0/14 1 106
ref
S8077
R24650		 Aydin, 2020 Small for gestational age (birth weight) throughout pregnancy retrospective cohort unexposed, sick Adjustment: No 3.31 [0.06;183.69] C 0/7   0/22 0 7
ref
S7996
R24599		 Cohen, 2019 Small for gestational age (ICD-9 656.5, 764.0, 764.1, 764.9) early pregnancy retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes 0.91 [0.49;1.67] -/-   41,653/1,440,631 41,644 -
ref
S5912
R14924		 Artama (Controls unexposed, disease free), 2013 Small for gestational age (weight) during pregnancy (anytime or not specified) population based cohort retrospective unexposed, disease free excluded Adjustment: Yes 0.49 [0.12;1.97]
excluded (control group) 		2/173   14,079/719,509 14,081 173
ref
S5920
R15020		 Artama (Controls unexposed, sick), 2013 Small for gestational age (weight) during pregnancy (anytime or not specified) population based cohort retrospective unexposed, sick Adjustment: Yes 0.42 [0.10;1.81] 2/173   42/1,793 44 173
ref
S6394
R17471		 Veiby (Controls unexposed, disease free) b, 2013 Small for gestational age (SGA) birth weight during pregnancy (anytime or not specified) prospective cohort unexposed, disease free excluded Adjustment: Yes 0.60 [0.20;1.40]
excluded (control group) 		5/103   8,017/106,899 8,022 103
ref
S6393
R17452		 Veiby (Controls unexposed, sick) b, 2013 Small for gestational age (SGA) birth weight during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No 0.58 [0.22;1.54] C 5/103   31/386 36 103
ref
Total 7 studies 0.95 [0.86;1.06] 41,751 5,174
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 0.72[0.31; 1.65]261062%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: moderateROB reporting: low Dreier, 2021Dreier, 2021 0.97[0.87; 1.08]-4,67994%ROB confusion: unclearROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Van Marter (Controls unexposed, sick), 2021Van Marter, 2021 2 0.39[0.02; 10.00]11060%ROB confusion: criticalROB selection: lowROB classification: lowROB missing: lowROB mesure: moderateROB reporting: low Aydin, 2020Aydin, 2020 3.31[0.06; 183.69]070%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Cohen, 2019Cohen, 2019 0.91[0.49; 1.67]41,644-3%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Artama (Controls unexposed, sick), 2013Artama, 2013 3 0.42[0.10; 1.81]441731%ROB confusion: moderateROB selection: lowROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Veiby (Controls unexposed, sick) b, 2013Veiby, 2013 4 0.58[0.22; 1.54]361031%ROB confusion: unclearROB selection: lowROB classification: lowROB missing: moderateROB mesure: moderateROB reporting: moderate Total (7 studies) I2 = 0% 0.95[0.86; 1.06]41,7515,1740.210.01.0ROB: 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) ;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 0.95[0.86; 1.06]41,7515,1740%NABromley (Lamotrigine) (Epilepsy), 2023 Dreier, 2021 Van Marter (Controls unexposed, sick), 2021 Aydin, 2020 Cohen, 2019 Artama (Controls unexposed, sick), 2013 Veiby (Controls unexposed, sick) b, 2013 7 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 0.91[0.49; 1.68]41,644- -NACohen, 2019 1 unexposed, sickunexposed, sick 0.96[0.86; 1.06]1075,1740%NABromley (Lamotrigine) (Epilepsy), 2023 Dreier, 2021 Van Marter (Controls unexposed, sick), 2021 Aydin, 2020 Artama (Controls unexposed, sick), 2013 Veiby (Controls unexposed, sick) b, 2013 6 Tags Adjustment   - No  - No 0.67[0.36; 1.24]633220%NABromley (Lamotrigine) (Epilepsy), 2023 Van Marter (Controls unexposed, sick), 2021 Aydin, 2020 Veiby (Controls unexposed, sick) b, 2013 4   - Yes  - Yes 0.96[0.87; 1.07]41,6884,8520%NADreier, 2021 Cohen, 2019 Artama (Controls unexposed, sick), 2013 3 All studiesAll studies 0.95[0.86; 1.06]41,7515,1740%NABromley (Lamotrigine) (Epilepsy), 2023 Dreier, 2021 Van Marter (Controls unexposed, sick), 2021 Aydin, 2020 Cohen, 2019 Artama (Controls unexposed, sick), 2013 Veiby (Controls unexposed, sick) b, 2013 70.110.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-4.84.82.4590.000Bromley (Lamotrigine) (Epilepsy), 2023Dreier, 2021Van Marter (Controls unexposed, sick), 2021Aydin, 2020Cohen, 2019Artama (Controls unexposed, sick), 2013Veiby (Controls unexposed, sick) b, 2013

Asymetry test p-value = 0.1295 (by Egger's regression)

slope=-0.0045 (0.0417); intercept=-0.5356 (0.2954); t=1.8134; p=0.1295

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 5912, 6394, 12612

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 0.60[0.31; 1.15]63,75738232%NAVan Marter (Controls unexposed, disease free), 2021 Cohen, 2019 Artama (Controls unexposed, disease free), 2013 Veiby (Controls unexposed, disease free) b, 2013 4 unexposed, sick controlsunexposed, sick controls 0.96[0.86; 1.06]1075,1740%NABromley (Lamotrigine) (Epilepsy), 2023 Dreier, 2021 Van Marter (Controls unexposed, sick), 2021 Aydin, 2020 Artama (Controls unexposed, sick), 2013 Veiby (Controls unexposed, sick) b, 2013 60.510.01.0