Lamotrigine (Epilepsy)

Language 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
R65211		 Bromley (Lamotrigine) (Epilepsy), 2023 Language 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 0.87 [0.19;4.07] C 4/73   3/48 7 73
ref
S15848
R65253		 Meador, 2023 Verbal Index score - Average scores on 2 subtests of Differential Ability Scales­II (DAS­II), Expressive Communication and Auditory Comprehension subscales of Preschool Language Scale­5 (PLS­5), and Peabody Picture Vocabulary Test­ (PPVT­4) - At age 3 years during pregnancy (anytime or not specified) prospective cohort unexposed, disease free Adjustment: Yes extrapolated (cont. endpoint) 1.01 [0.61;1.69] -/90   -/106 - 90
ref
S7701
R22879		 Husebye (Controls unexposed, disease free), 2020 Language impairment age 8 years (Language 20) during pregnancy (anytime or not specified) population based cohort propective unexposed, disease free excluded Adjustment: Yes 1.20 [0.60;2.60]
excluded (control group) 		9/41   8,250/42,550 8,259 41
ref
S7706
R22889		 Husebye (Controls unexposed, sick), 2020 Language impairment age 8 years (Language 20) during pregnancy (anytime or not specified) population based cohort propective unexposed, sick Adjustment: No 0.92 [0.40;2.12] C 9/41   35/150 44 41
ref
S7964
R24617		 Cohen-Israel, 2018 Speech delay (a majority between 6-12 years old) 1st trimester retrospective cohort unexposed, disease free Adjustment: No Matched 0.35 [0.13;0.96] C 6/83   15/83 21 83
ref
S7277
R21055		 Kasradze, 2017 Verbal comprehension (VCI) (WPPSI-4) (mean age 4-4.5 years old) during pregnancy (anytime or not specified) prospective cohort unexposed, disease free Adjustment: No extrapolated (cont. endpoint) Matched 22.98 [2.54;207.85] -/3   -/50 - 3
ref
S9948
R35781		 Videman, 2016 Griffiths Mental Developmental Scale - Hearing and speech (at the age of 7 months) during pregnancy (anytime or not specified) prospective cohort unexposed, disease free Adjustment: No extrapolated (cont. endpoint) 2.39 [0.62;9.19] -/8   -/59 - 8
ref
S8322
R26345		 Baker (Controls unexposed, disease free), 2015 Mean child verbal IQ - Differential ability scales (DAS) (age mean >6 years old) during pregnancy (anytime or not specified) prospective cohort unexposed, disease free excluded Adjustment: No extrapolated (cont. endpoint) 1.82 [0.90;3.68]
excluded (control group) 		-/29   -/210 - 29
ref
S8327
R26371		 Baker (Controls unexposed, sick), 2015 Mean child verbal IQ - Differential ability scales (DAS) (age mean >6 years old) during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No extrapolated (cont. endpoint) 1.00 [0.38;2.64] -/29   -/25 - 29
ref
S6295
R24817		 Rihtman, 2013 Stanford Binet Intelligence Scales, Fifth Edition (SB5) - Verbal IQ (VIQ) (mean age 4-5 years old) at least 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No extrapolated (cont. endpoint) 1.42 [0.67;2.98] -/41   -/52 - 41
ref
Total 8 studies 1.12 [0.69;1.84] 72 368
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 0.87[0.19; 4.07]7737%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: lowROB reporting: low Meador, 2023Meador, 2023 1.01[0.61; 1.69]-9021%ROB confusion: seriousROB selection: moderateROB classification: lowROB missing: moderateROB mesure: lowROB reporting: low Husebye (Controls unexposed, sick), 2020Husebye, 2020 2 0.92[0.40; 2.12]444115%ROB confusion: unclearROB selection: lowROB classification: lowROB missing: criticalROB mesure: moderateROB reporting: moderate Cohen-Israel, 2018Cohen-Israel, 2018 0.35[0.13; 0.96]218313%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: unclearROB mesure: criticalROB reporting: moderate Kasradze, 2017Kasradze, 2017 22.98[2.54; 207.85]-34%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: criticalROB mesure: lowROB reporting: moderate Videman, 2016Videman, 2016 2.39[0.62; 9.19]-89%ROB confusion: unclearROB selection: lowROB classification: moderateROB missing: criticalROB mesure: lowROB reporting: moderate Baker (Controls unexposed, sick), 2015Baker, 2015 3 1.00[0.38; 2.64]-2913%ROB confusion: unclearROB selection: lowROB classification: moderateROB missing: moderateROB mesure: lowROB reporting: moderate Rihtman, 2013Rihtman, 2013 1.42[0.67; 2.98]-4117%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Total (8 studies) I2 = 51% 1.12[0.69; 1.84]723680.250.01.0ROB: 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;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.12[0.69; 1.84]7236851%NABromley (Lamotrigine) (Epilepsy), 2023 Meador, 2023 Husebye (Controls unexposed, sick), 2020 Cohen-Israel, 2018 Kasradze, 2017 Videman, 2016 Baker (Controls unexposed, sick), 2015 Rihtman, 2013 8 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.37[0.61; 3.08]2122572%NAMeador, 2023 Cohen-Israel, 2018 Kasradze, 2017 Videman, 2016 Rihtman, 2013 5 unexposed, sickunexposed, sick 0.94[0.53; 1.69]511430%NABromley (Lamotrigine) (Epilepsy), 2023 Husebye (Controls unexposed, sick), 2020 Baker (Controls unexposed, sick), 2015 3 Tags Adjustment   - No  - No 1.20[0.63; 2.29]7227858%NABromley (Lamotrigine) (Epilepsy), 2023 Husebye (Controls unexposed, sick), 2020 Cohen-Israel, 2018 Kasradze, 2017 Videman, 2016 Baker (Controls unexposed, sick), 2015 Rihtman, 2013 7   - Yes  - Yes 1.01[0.61; 1.68]-90 -NAMeador, 2023 1 extrapolated (cont. endpoint)extrapolated (cont. endpoint) 1.54[0.82; 2.87]-17153%NAMeador, 2023 Kasradze, 2017 Videman, 2016 Baker (Controls unexposed, sick), 2015 Rihtman, 2013 5 MatchedMatched 2.53[0.04; 150.21]218691%NACohen-Israel, 2018 Kasradze, 2017 2 All studiesAll studies 1.12[0.69; 1.84]7236851%NABromley (Lamotrigine) (Epilepsy), 2023 Meador, 2023 Husebye (Controls unexposed, sick), 2020 Cohen-Israel, 2018 Kasradze, 2017 Videman, 2016 Baker (Controls unexposed, sick), 2015 Rihtman, 2013 80.150.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-3.83.81.3480.000Bromley (Lamotrigine) (Epilepsy), 2023Meador, 2023Husebye (Controls unexposed, sick), 2020Cohen-Israel, 2018Kasradze, 2017Videman, 2016Baker (Controls unexposed, sick), 2015Rihtman, 2013

Asymetry test p-value = 0.3175 (by Egger's regression)

slope=-0.5239 (0.5775); intercept=1.4026 (1.2865); t=1.0902; p=0.3175

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 8322, 7701

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.34[0.79; 2.26]8,28029562%NAMeador, 2023 Husebye (Controls unexposed, disease free), 2020 Cohen-Israel, 2018 Kasradze, 2017 Videman, 2016 Baker (Controls unexposed, disease free), 2015 Rihtman, 2013 7 unexposed, sick controlsunexposed, sick controls 0.94[0.53; 1.69]511430%NABromley (Lamotrigine) (Epilepsy), 2023 Husebye (Controls unexposed, sick), 2020 Baker (Controls unexposed, sick), 2015 30.510.01.0