Lamotrigine (All indications)

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.
S15218
R62400		 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
S15277
R62814		 Meador (Lamotrigine), 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
S8978
R30441		 Coste (Lamotrigine) (Controls unexposed NOS) (Mixed indications), 2020 Health care utilization: Speech therapy (mean age of 3.6 years old) during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes 1.20 [1.00;1.40] 149/2,813   71,832/1,707,707 71,981 2,813
ref
S8947
R30244		 Husebye (Lamotrigine) (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
S8949
R30249		 Husebye (Lamotrigine) (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
S8941
R30226		 Cohen-Israel (Lamotrigine), 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
S8950
R30251		 Kasradze (Lamotrigine), 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
S9947
R35775		 Videman (Lamotrigine), 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
S8929
R30171		 Baker (Lamotrigine) (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
S8930
R30176		 Baker (Lamotrigine) (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
S8952
R30278		 Rihtman (Lamotrigine), 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 9 studies 1.12 [0.79;1.58] 72,053 3,181
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]7734%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: lowROB reporting: low Meador (Lamotrigine), 2023Meador, 2023 2 1.01[0.61; 1.69]-9018%ROB confusion: seriousROB selection: moderateROB classification: lowROB missing: moderateROB mesure: lowROB reporting: low Coste (Lamotrigine) (Controls unexposed NOS) (Mixed indications), 2020Coste, 2020 3 1.20[1.00; 1.40]71,9812,81329%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: criticalROB reporting: moderate Husebye (Lamotrigine) (Controls unexposed, sick), 2020Husebye, 2020 4 0.92[0.40; 2.12]444111%ROB confusion: unclearROB selection: lowROB classification: lowROB missing: criticalROB mesure: moderateROB reporting: moderate Cohen-Israel (Lamotrigine), 2018Cohen-Israel, 2018 5 0.35[0.13; 0.96]21839%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: criticalROB reporting: moderate Kasradze (Lamotrigine), 2017Kasradze, 2017 6 22.98[2.54; 207.85]-32%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: criticalROB mesure: lowROB reporting: moderate Videman (Lamotrigine), 2016Videman, 2016 7 2.39[0.62; 9.19]-85%ROB confusion: unclearROB selection: lowROB classification: moderateROB missing: criticalROB mesure: lowROB reporting: moderate Baker (Lamotrigine) (Controls unexposed, sick), 2015Baker, 2015 8 1.00[0.38; 2.64]-299%ROB confusion: unclearROB selection: lowROB classification: moderateROB missing: moderateROB mesure: lowROB reporting: moderate Rihtman (Lamotrigine), 2013Rihtman, 2013 9 1.42[0.67; 2.98]-4113%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Total (9 studies) I2 = 46% 1.12[0.79; 1.58]72,0533,1810.250.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Lamotrigine) (Epilepsy; 2: Lamotrigine; 3: Lamotrigine) (Controls unexposed NOS) (Mixed indications; 4: Lamotrigine) (Controls unexposed, sick; 5: Lamotrigine; 6: Lamotrigine; 7: Lamotrigine; 8: Lamotrigine) (Controls unexposed, sick; 9: Lamotrigine;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.12[0.79; 1.58]72,0533,18146%NABromley (Lamotrigine) (Epilepsy), 2023 Meador (Lamotrigine), 2023 Coste (Lamotrigine) (Controls unexposed NOS) (Mixed indications), 2020 Husebye (Lamotrigine) (Controls unexposed, sick), 2020 Cohen-Israel (Lamotrigine), 2018 Kasradze (Lamotrigine), 2017 Videman (Lamotrigine), 2016 Baker (Lamotrigine) (Controls unexposed, sick), 2015 Rihtman (Lamotrigine), 2013 9 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.21[0.75; 1.96]72,0023,03865%NAMeador (Lamotrigine), 2023 Coste (Lamotrigine) (Controls unexposed NOS) (Mixed indications), 2020 Cohen-Israel (Lamotrigine), 2018 Kasradze (Lamotrigine), 2017 Videman (Lamotrigine), 2016 Rihtman (Lamotrigine), 2013 6 unexposed, sickunexposed, sick 0.94[0.53; 1.69]511430%NABromley (Lamotrigine) (Epilepsy), 2023 Husebye (Lamotrigine) (Controls unexposed, sick), 2020 Baker (Lamotrigine) (Controls unexposed, sick), 2015 3 Tags Adjustment   - No  - No 1.20[0.63; 2.29]7227858%NABromley (Lamotrigine) (Epilepsy), 2023 Husebye (Lamotrigine) (Controls unexposed, sick), 2020 Cohen-Israel (Lamotrigine), 2018 Kasradze (Lamotrigine), 2017 Videman (Lamotrigine), 2016 Baker (Lamotrigine) (Controls unexposed, sick), 2015 Rihtman (Lamotrigine), 2013 7   - Yes  - Yes 1.18[1.01; 1.38]71,9812,9030%NAMeador (Lamotrigine), 2023 Coste (Lamotrigine) (Controls unexposed NOS) (Mixed indications), 2020 2 extrapolated (cont. endpoint)extrapolated (cont. endpoint) 1.54[0.82; 2.87]-17153%NAMeador (Lamotrigine), 2023 Kasradze (Lamotrigine), 2017 Videman (Lamotrigine), 2016 Baker (Lamotrigine) (Controls unexposed, sick), 2015 Rihtman (Lamotrigine), 2013 5 MatchedMatched 2.53[0.04; 150.21]218691%NACohen-Israel (Lamotrigine), 2018 Kasradze (Lamotrigine), 2017 2 All studiesAll studies 1.12[0.79; 1.58]72,0533,18146%NABromley (Lamotrigine) (Epilepsy), 2023 Meador (Lamotrigine), 2023 Coste (Lamotrigine) (Controls unexposed NOS) (Mixed indications), 2020 Husebye (Lamotrigine) (Controls unexposed, sick), 2020 Cohen-Israel (Lamotrigine), 2018 Kasradze (Lamotrigine), 2017 Videman (Lamotrigine), 2016 Baker (Lamotrigine) (Controls unexposed, sick), 2015 Rihtman (Lamotrigine), 2013 90.150.01.0

Publication bias and p-hacking diagnosis

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

Asymetry test p-value = 0.8954 (by Egger's regression)

slope=0.1389 (0.1550); intercept=0.0933 (0.6843); t=0.1364; p=0.8954

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 8929, 8947

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.26[0.88; 1.80]80,2613,10855%NAMeador (Lamotrigine), 2023 Coste (Lamotrigine) (Controls unexposed NOS) (Mixed indications), 2020 Husebye (Lamotrigine) (Controls unexposed, disease free), 2020 Cohen-Israel (Lamotrigine), 2018 Kasradze (Lamotrigine), 2017 Videman (Lamotrigine), 2016 Baker (Lamotrigine) (Controls unexposed, disease free), 2015 Rihtman (Lamotrigine), 2013 8 unexposed, sick controlsunexposed, sick controls 0.94[0.53; 1.69]511430%NABromley (Lamotrigine) (Epilepsy), 2023 Husebye (Lamotrigine) (Controls unexposed, sick), 2020 Baker (Lamotrigine) (Controls unexposed, sick), 2015 30.510.01.0