Carbamazepine (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.
S15365
R63216		 Bromley (Carbamazepine) (Epilepsy) (Controls exposed to LTG), 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 exposed to other treatment, sick excluded Adjustment: No 1.82 [0.31;10.68] C
excluded (control group) 		2/21   4/73 6 21
ref
S15366
R63229		 Bromley (Carbamazepine) (Epilepsy) (Controls unexposed, sick), 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 1.58 [0.24;10.22] C 2/21   3/48 5 21
ref
S12896
R48728		 Adams (Carbamazepine), 2022 Verbal IQ - The Wechsler Intelligence Scale for Children, 3rd Edition (WISC-III) (mean >6 years old) during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: No extrapolated (cont. endpoint) Matched 2.72 [1.22;6.06] -/41   -/41 - 41
ref
S15377
R63351		 Thomas (Carbamazepine), 2022 Verbal IQ/Verbal comprehension index (VCI) - Wechsler Intelligence Scale for Children or Adult - Ages 13 to 21 years (mean of 16.5 ± 2.2 years) during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No extrapolated (cont. endpoint) 2.61 [0.76;8.95] -/38   -/11 - 38
ref
S12800
R48223		 Meador (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2021 Language Score in 2 years old children with the Bayley Scales of Infant and Toddler Development (BSID-III) 3rd trimester prospective cohort exposed to other treatment, sick excluded Adjustment: Yes extrapolated (cont. endpoint) 1.18 [0.40;3.52]
excluded (control group) 		-/12   -/93 - 12
ref
S12801
R48224		 Meador (Carbamazepine) (Controls unexposed, disease free), 2021 Language Score in 2 years old children with the Bayley Scales of Infant and Toddler Development (BSID-III) 3rd trimester prospective cohort unexposed, disease free Adjustment: Yes extrapolated (cont. endpoint) 1.15 [0.39;3.45] -/12   -/87 - 12
ref
S10075
R36698		 Coste (Carbamazepine), 2020 Visits to a speech therapist (mean age of 3.7 years old) during pregnancy (anytime or not specified) retrospective cohort (claims database) exposed to other treatment, sick Adjustment: Yes 0.20 [0.10;0.70] 4/176   122/2,108 126 176
ref
S7710
R22897		 Husebye (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2020 Language impairment age 8 years (Language 20) during pregnancy (anytime or not specified) population based cohort propective exposed to other treatment, sick excluded Adjustment: No 2.74 [0.90;8.28] C
excluded (control group) 		10/23   9/41 19 23
ref
S7700
R22877		 Husebye (Carbamazepine) (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 3.80 [1.60;9.00]
excluded (control group) 		10/23   8,250/42,550 8,260 23
ref
S7704
R22885		 Husebye (Carbamazepine) (Controls unexposed, sick), 2020 Language impairment age 8 years during pregnancy (anytime or not specified) population based cohort propective unexposed, sick Adjustment: No 2.53 [1.02;6.26] C 10/23   35/150 45 23
ref
S7279
R21061		 Kasradze (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2017 Verbal comprehension (VCI) (WPPSI-4) (mean age 4-4.5 years old) during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick excluded Adjustment: No extrapolated (cont. endpoint) 0.13 [0.01;1.41]
excluded (control group) 		-/16   -/3 - 16
ref
S5496
R19155		 Kasradze (Carbamazepine) (Controls unexposed, disease free), 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 3.53 [1.24;10.04] -/16   -/50 - 16
ref
S8042
R24925		 Deshmukh (Carbamazepine), 2016 Vineland-II Adaptative Behavior Scales - Low and moderately low in the communication domain throughout pregnancy prospective cohort exposed to other treatment, sick Adjustment: Yes 2.91 [0.64;13.21] 10/97   8/104 18 97
ref
S9938
R35721		 Videman (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2016 Griffiths Mental Developmental Scale - Hearing and speech (at the age of 7 months) during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick excluded Adjustment: No extrapolated (cont. endpoint) 2.69 [0.46;15.78]
excluded (control group) 		-/9   -/8 - 9
ref
S9935
R35703		 Videman (Carbamazepine) (Controls unexposed, disease free), 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) 15.07 [3.88;58.47] -/9   -/59 - 9
ref
S8324
R26357		 Baker (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2015 Mean child verbal IQ - Differential ability scales (DAS) (age mean >6 years old) during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick excluded Adjustment: No extrapolated (cont. endpoint) 1.13 [0.49;2.60]
excluded (control group) 		-/50   -/29 - 50
ref
S8254
R26077		 Baker (Carbamazepine) (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) 2.05 [1.17;3.59]
excluded (control group) 		-/50   -/210 - 50
ref
S8326
R26366		 Baker (Carbamazepine) (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) 1.14 [0.48;2.71] -/50   -/25 - 50
ref
S386
R20452		 Meador (Carbamazepine), 2013 Verbal index score (at age 6 years old) (Created by averaging standard scores) during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick Adjustment: Yes extrapolated (cont. endpoint) 1.19 [0.64;2.20] -/61   -/74 - 61
ref
S6188
R20065		 Nadebaum (Carbamazepine), 2011 Total language delay (CELF-4) (core language ≤ 85) during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick Adjustment: No 4.02 [0.20;78.92] C 6/34   0/9 6 34
ref
S7227
R20745		 Eriksson (Carbamazepine), 2005 Mean Verbal IQ (VIQ) (Wechsler Intelligence Scale for Children (WISC-III)) throughout pregnancy prospective cohort unexposed, sick Adjustment: No extrapolated (cont. endpoint) 1.21 [0.30;4.90] -/13   -/13 - 13
ref
S5541
R24916		 Adab (Carbamazepine), 2004 Verbal IQ (VIQ) less than low average (≤ 89) (Wechsler Intelligence Scale for Children (WISC)) during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: No 0.56 [0.27;1.14] C 18/52   39/80 57 52
ref
S7236
R20862		 Gaily (Carbamazepine) (Controls unexposed, disease free), 2004 Verbal IQ score (Wechsler Preschool and Primary Scale of Intelligence Revised (WPPSI-R) or Wechsler Intelligence Scale for Children Revised (WISC-R)) 2nd and/or 3rd trimester prospective cohort unexposed, disease free excluded Adjustment: No extrapolated (cont. endpoint) 0.86 [0.53;1.40]
excluded (control group) 		-/86   -/139 - 86
ref
S5557
R19870		 Gaily (Carbamazepine) (Controls unexposed, sick), 2004 Verbal IQ score (Wechsler Preschool and Primary Scale of Intelligence Revised (WPPSI-R) or Wechsler Intelligence Scale for Children Revised (WISC-R)) 2nd and/or 3rd trimester prospective cohort unexposed, sick Adjustment: No extrapolated (cont. endpoint) 0.82 [0.43;1.59] -/86   -/44 - 86
ref
Total 15 studies 1.52 [0.94;2.45] 257 729
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 (Carbamazepine) (Epilepsy) (Controls unexposed, sick), 2023Bromley, 2023 1 1.58[0.24; 10.22]5214%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: lowROB reporting: low Adams (Carbamazepine), 2022Adams, 2022 2 2.72[1.22; 6.06]-418%ROB confusion: seriousROB selection: moderateROB classification: criticalROB missing: lowROB mesure: lowROB reporting: moderate Thomas (Carbamazepine), 2022Thomas, 2022 3 2.61[0.76; 8.95]-386%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: criticalROB mesure: lowROB reporting: moderate Meador (Carbamazepine) (Controls unexposed, disease free), 2021Meador, 2021 4 1.15[0.39; 3.45]-127%ROB confusion: moderateROB selection: lowROB classification: lowROB missing: moderateROB mesure: moderateROB reporting: low Coste (Carbamazepine), 2020Coste, 2020 5 0.20[0.10; 0.70]1261767%ROB confusion: seriousROB selection: moderateROB classification: criticalROB missing: moderateROB mesure: criticalROB reporting: moderate Husebye (Carbamazepine) (Controls unexposed, sick), 2020Husebye, 2020 6 2.53[1.02; 6.26]45238%ROB confusion: unclearROB selection: lowROB classification: lowROB missing: lowROB mesure: moderateROB reporting: moderate Kasradze (Carbamazepine) (Controls unexposed, disease free), 2017Kasradze, 2017 7 3.53[1.24; 10.04]-167%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: criticalROB mesure: lowROB reporting: moderate Deshmukh (Carbamazepine), 2016Deshmukh, 2016 8 2.91[0.64; 13.21]18975%ROB confusion: moderateROB selection: lowROB classification: moderateROB missing: criticalROB mesure: moderateROB reporting: moderate Videman (Carbamazepine) (Controls unexposed, disease free), 2016Videman, 2016 9 15.07[3.88; 58.47]-96%ROB confusion: unclearROB selection: lowROB classification: moderateROB missing: criticalROB mesure: lowROB reporting: moderate Baker (Carbamazepine) (Controls unexposed, sick), 2015Baker, 2015 10 1.14[0.48; 2.71]-508%ROB confusion: unclearROB selection: lowROB classification: moderateROB missing: moderateROB mesure: lowROB reporting: moderate Meador (Carbamazepine), 2013Meador, 2013 11 1.19[0.64; 2.20]-619%ROB confusion: moderateROB selection: lowROB classification: lowROB missing: moderateROB mesure: lowROB reporting: low Nadebaum (Carbamazepine), 2011Nadebaum, 2011 12 4.02[0.20; 78.92]6342%ROB confusion: criticalROB selection: lowROB classification: lowROB missing: criticalROB mesure: lowROB reporting: moderate Eriksson (Carbamazepine), 2005Eriksson, 2005 13 1.21[0.30; 4.90]-136%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: moderateROB mesure: lowROB reporting: moderate Adab (Carbamazepine), 2004Adab, 2004 14 0.56[0.27; 1.14]57529%ROB confusion: criticalROB selection: criticalROB classification: lowROB missing: criticalROB mesure: lowROB reporting: moderate Gaily (Carbamazepine) (Controls unexposed, sick), 2004Gaily, 2004 15 0.82[0.43; 1.59]-869%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: criticalROB mesure: lowROB reporting: moderate Total (15 studies) I2 = 70% 1.52[0.94; 2.45]2577290.250.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Carbamazepine) (Epilepsy) (Controls unexposed, sick; 2: Carbamazepine; 3: Carbamazepine; 4: Carbamazepine) (Controls unexposed, disease free; 5: Carbamazepine; 6: Carbamazepine) (Controls unexposed, sick; 7: Carbamazepine) (Controls unexposed, disease free; 8: Carbamazepine; 9: Carbamazepine) (Controls unexposed, disease free; 10: Carbamazepine) (Controls unexposed, sick; 11: Carbamazepine; 12: Carbamazepine; 13: Carbamazepine; 14: Carbamazepine; 15: Carbamazepine) (Controls unexposed, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.52[0.94; 2.45]25772970%NABromley (Carbamazepine) (Epilepsy) (Controls unexposed, sick), 2023 Adams (Carbamazepine), 2022 Thomas (Carbamazepine), 2022 Meador (Carbamazepine) (Controls unexposed, disease free), 2021 Coste (Carbamazepine), 2020 Husebye (Carbamazepine) (Controls unexposed, sick), 2020 Kasradze (Carbamazepine) (Controls unexposed, disease free), 2017 Deshmukh (Carbamazepine), 2016 Videman (Carbamazepine) (Controls unexposed, disease free), 2016 Baker (Carbamazepine) (Controls unexposed, sick), 2015 Meador (Carbamazepine), 2013 Nadebaum (Carbamazepine), 2011 Eriksson (Carbamazepine), 2005 Adab (Carbamazepine), 2004 Gaily (Carbamazepine) (Controls unexposed, sick), 2004 15 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 3.75[0.95; 14.77]-3776%NAMeador (Carbamazepine) (Controls unexposed, disease free), 2021 Kasradze (Carbamazepine) (Controls unexposed, disease free), 2017 Videman (Carbamazepine) (Controls unexposed, disease free), 2016 3 unexposed, sickunexposed, sick 1.34[0.84; 2.15]10732449%NABromley (Carbamazepine) (Epilepsy) (Controls unexposed, sick), 2023 Adams (Carbamazepine), 2022 Thomas (Carbamazepine), 2022 Husebye (Carbamazepine) (Controls unexposed, sick), 2020 Baker (Carbamazepine) (Controls unexposed, sick), 2015 Eriksson (Carbamazepine), 2005 Adab (Carbamazepine), 2004 Gaily (Carbamazepine) (Controls unexposed, sick), 2004 8 exposed to other treatment, sickexposed to other treatment, sick 1.00[0.28; 3.59]15036877%NACoste (Carbamazepine), 2020 Deshmukh (Carbamazepine), 2016 Meador (Carbamazepine), 2013 Nadebaum (Carbamazepine), 2011 4 Tags Adjustment   - No  - No 1.88[1.09; 3.24]11338366%NABromley (Carbamazepine) (Epilepsy) (Controls unexposed, sick), 2023 Adams (Carbamazepine), 2022 Thomas (Carbamazepine), 2022 Husebye (Carbamazepine) (Controls unexposed, sick), 2020 Kasradze (Carbamazepine) (Controls unexposed, disease free), 2017 Videman (Carbamazepine) (Controls unexposed, disease free), 2016 Baker (Carbamazepine) (Controls unexposed, sick), 2015 Nadebaum (Carbamazepine), 2011 Eriksson (Carbamazepine), 2005 Adab (Carbamazepine), 2004 Gaily (Carbamazepine) (Controls unexposed, sick), 2004 11   - Yes  - Yes 0.88[0.32; 2.43]14434676%NAMeador (Carbamazepine) (Controls unexposed, disease free), 2021 Coste (Carbamazepine), 2020 Deshmukh (Carbamazepine), 2016 Meador (Carbamazepine), 2013 4 extrapolated (cont. endpoint)extrapolated (cont. endpoint) 1.84[1.11; 3.05]-32662%NAAdams (Carbamazepine), 2022 Thomas (Carbamazepine), 2022 Meador (Carbamazepine) (Controls unexposed, disease free), 2021 Kasradze (Carbamazepine) (Controls unexposed, disease free), 2017 Videman (Carbamazepine) (Controls unexposed, disease free), 2016 Baker (Carbamazepine) (Controls unexposed, sick), 2015 Meador (Carbamazepine), 2013 Eriksson (Carbamazepine), 2005 Gaily (Carbamazepine) (Controls unexposed, sick), 2004 9 MatchedMatched 3.00[1.59; 5.66]-570%NAAdams (Carbamazepine), 2022 Kasradze (Carbamazepine) (Controls unexposed, disease free), 2017 2 All studiesAll studies 1.52[0.94; 2.45]25772970%NABromley (Carbamazepine) (Epilepsy) (Controls unexposed, sick), 2023 Adams (Carbamazepine), 2022 Thomas (Carbamazepine), 2022 Meador (Carbamazepine) (Controls unexposed, disease free), 2021 Coste (Carbamazepine), 2020 Husebye (Carbamazepine) (Controls unexposed, sick), 2020 Kasradze (Carbamazepine) (Controls unexposed, disease free), 2017 Deshmukh (Carbamazepine), 2016 Videman (Carbamazepine) (Controls unexposed, disease free), 2016 Baker (Carbamazepine) (Controls unexposed, sick), 2015 Meador (Carbamazepine), 2013 Nadebaum (Carbamazepine), 2011 Eriksson (Carbamazepine), 2005 Adab (Carbamazepine), 2004 Gaily (Carbamazepine) (Controls unexposed, sick), 2004 150.150.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-3.64.01.8230.000Bromley (Carbamazepine) (Epilepsy) (Controls unexposed, sick), 2023Adams (Carbamazepine), 2022Thomas (Carbamazepine), 2022Meador (Carbamazepine) (Controls unexposed, disease free), 2021Coste (Carbamazepine), 2020Husebye (Carbamazepine) (Controls unexposed, sick), 2020Kasradze (Carbamazepine) (Controls unexposed, disease free), 2017Deshmukh (Carbamazepine), 2016Videman (Carbamazepine) (Controls unexposed, disease free), 2016Baker (Carbamazepine) (Controls unexposed, sick), 2015Meador (Carbamazepine), 2013Nadebaum (Carbamazepine), 2011Eriksson (Carbamazepine), 2005Adab (Carbamazepine), 2004Gaily (Carbamazepine) (Controls unexposed, sick), 2004

Asymetry test p-value = 0.1504 (by Egger's regression)

slope=-0.6681 (0.6452); intercept=2.0184 (1.3207); t=1.5282; p=0.1504

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 7236, 8324, 8254, 9938, 7279, 7710, 7700, 12800, 15365

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 2.44[1.19; 4.99]8,26019679%NAMeador (Carbamazepine) (Controls unexposed, disease free), 2021 Husebye (Carbamazepine) (Controls unexposed, disease free), 2020 Kasradze (Carbamazepine) (Controls unexposed, disease free), 2017 Videman (Carbamazepine) (Controls unexposed, disease free), 2016 Baker (Carbamazepine) (Controls unexposed, disease free), 2015 Gaily (Carbamazepine) (Controls unexposed, disease free), 2004 6 unexposed, sick controlsunexposed, sick controls 1.34[0.84; 2.15]10732449%NABromley (Carbamazepine) (Epilepsy) (Controls unexposed, sick), 2023 Adams (Carbamazepine), 2022 Thomas (Carbamazepine), 2022 Husebye (Carbamazepine) (Controls unexposed, sick), 2020 Baker (Carbamazepine) (Controls unexposed, sick), 2015 Eriksson (Carbamazepine), 2005 Adab (Carbamazepine), 2004 Gaily (Carbamazepine) (Controls unexposed, sick), 2004 8 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.15[0.63; 2.10]17549957%NABromley (Carbamazepine) (Epilepsy) (Controls exposed to LTG), 2023 Meador (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2021 Coste (Carbamazepine), 2020 Husebye (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2020 Kasradze (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2017 Deshmukh (Carbamazepine), 2016 Videman (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2016 Baker (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2015 Meador (Carbamazepine), 2013 Nadebaum (Carbamazepine), 2011 100.510.01.0