Lamotrigine (Epilepsy)

Psychomotor developmental disorders/delay

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
R65212		 Bromley (Lamotrigine) (Epilepsy), 2023 Motor mean score ≤ 86 (below average performance of the cohort mean) - Bayley Scales of Infant and Toddler Development - At 24 months of age during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No 1.17 [0.32;4.22] C 7/73   4/48 11 73
ref
S7964
R24618		 Cohen-Israel, 2018 Motor delay (a majority between 6-12 years old) 1st trimester retrospective cohort unexposed, disease free Adjustment: No Matched 0.20 [0.01;4.13] C 0/83   2/83 2 83
ref
S9948
R35779		 Videman, 2016 Griffiths Mental Developmental Scale - Locomotor (at the age of 7 months) during pregnancy (anytime or not specified) prospective cohort unexposed, disease free Adjustment: No extrapolated (cont. endpoint) 4.30 [1.10;16.79] -/8   -/59 - 8
ref
S6604
R18111		 Bromley (Controls unexposed, disease free), 2013 Dyspraxia (at 6 years old) during pregnancy (anytime or not specified) prospective cohort unexposed, disease free excluded Adjustment: No 22.47 [0.89;564.98] C
excluded (control group) 		1/30   0/214 1 30
ref
S6603
R18108		 Bromley (Controls unexposed, sick), 2013 Dyspraxia (at 6 years old) during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No 2.68 [0.10;68.88] C 1/30   0/26 1 30
ref
S6295
R24824		 Rihtman, 2013 Miller Function and Participation Scales (MFUN) - Fine Motor (Preschool children: mean age 4-5y) at least 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No extrapolated (cont. endpoint) 2.79 [1.31;5.92] -/42   -/52 - 42
ref
Total 5 studies 2.21 [1.14;4.32] 14 236
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 1.17[0.32; 4.22]117322%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: lowROB reporting: low Cohen-Israel, 2018Cohen-Israel, 2018 0.20[0.01; 4.13]2835%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: unclearROB mesure: criticalROB reporting: moderate Videman, 2016Videman, 2016 4.30[1.10; 16.79]-820%ROB confusion: unclearROB selection: lowROB classification: moderateROB missing: criticalROB mesure: lowROB reporting: moderate Bromley (Controls unexposed, sick), 2013Bromley, 2013 2 2.68[0.10; 68.88]1304%ROB confusion: criticalROB selection: lowROB classification: lowROB missing: moderateROB mesure: moderateROB reporting: moderate Rihtman, 2013Rihtman, 2013 2.79[1.31; 5.92]-4249%ROB confusion: moderateROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Total (5 studies) I2 = 14% 2.21[1.14; 4.32]142360.010.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

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

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 2.21[1.14; 4.32]1423614%NABromley (Lamotrigine) (Epilepsy), 2023 Cohen-Israel, 2018 Videman, 2016 Bromley (Controls unexposed, sick), 2013 Rihtman, 2013 5 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 2.47[0.88; 6.93]213339%NACohen-Israel, 2018 Videman, 2016 Rihtman, 2013 3 unexposed, sickunexposed, sick 1.31[0.40; 4.32]121030%NABromley (Lamotrigine) (Epilepsy), 2023 Bromley (Controls unexposed, sick), 2013 2 Tags Adjustment   - No  - No 2.21[1.14; 4.32]1423614%NABromley (Lamotrigine) (Epilepsy), 2023 Cohen-Israel, 2018 Videman, 2016 Bromley (Controls unexposed, sick), 2013 Rihtman, 2013 5 extrapolated (cont. endpoint)extrapolated (cont. endpoint) 3.09[1.60; 5.97]-500%NAVideman, 2016 Rihtman, 2013 2 MatchedMatched 0.20[0.01; 4.13]283 -NACohen-Israel, 2018 1 All studiesAll studies 2.21[1.14; 4.32]1423614%NABromley (Lamotrigine) (Epilepsy), 2023 Cohen-Israel, 2018 Videman, 2016 Bromley (Controls unexposed, sick), 2013 Rihtman, 2013 50.010.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-3.94.71.9870.000Bromley (Lamotrigine) (Epilepsy), 2023Cohen-Israel, 2018Videman, 2016Bromley (Controls unexposed, sick), 2013Rihtman, 2013

Asymetry test p-value = 0.3808 (by Egger's regression)

slope=1.4324 (0.6576); intercept=-1.0408 (1.0154); t=1.0249; p=0.3808

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 6604

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 2.96[1.04; 8.44]316339%NACohen-Israel, 2018 Videman, 2016 Bromley (Controls unexposed, disease free), 2013 Rihtman, 2013 4 unexposed, sick controlsunexposed, sick controls 1.31[0.40; 4.32]121030%NABromley (Lamotrigine) (Epilepsy), 2023 Bromley (Controls unexposed, sick), 2013 20.510.01.0