Carbamazepine (All indications)

Cognitive developmental disorders/delay (< 3 years old)

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.
S15367
R63241		 Bromley (Carbamazepine) (Epilepsy) (Controls exposed to LTG), 2023 Cognitive mean score ≤ 88 (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 3.74 [0.49;28.29] C
excluded (control group) 		2/21   2/73 4 21
ref
S15368
R63254		 Bromley (Carbamazepine) (Epilepsy) (Controls unexposed, sick), 2023 Cognitive mean score ≤ 88 (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 2.42 [0.32;18.46] C 2/21   2/48 4 21
ref
S9937
R53391		 Videman (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2016 Griffiths Mental Developmental Scale - General quotient (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) 1.00 [0.18;5.63]
excluded (control group) 		-/9   -/8 - 9
ref
S9936
R53392		 Videman (Carbamazepine) (Controls unexposed, disease free), 2016 Griffiths Mental Developmental Scale - General quotient (at the age of 7 months) during pregnancy (anytime or not specified) prospective cohort unexposed, disease free Adjustment: No extrapolated (cont. endpoint) 4.58 [1.25;16.81] -/9   -/59 - 9
ref
S9732
R53388		 Meador (Carbamazepine), 2013 the Bayley Scales of Infant Development (BSID) <85 (at 2 years old) during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick Adjustment: Yes 2.36 [0.97;5.73] C 15/48   11/68 26 48
ref
S9695
R53385		 Bromley (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2010 Overall ability below average performance (≤ 84) (Griffiths) (mean age 10 months old) during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick excluded Adjustment: No 1.16 [0.34;3.91] C
excluded (control group) 		8/48   5/34 13 48
ref
S9698
R53386		 Bromley (Carbamazepine) (Controls unexposed, disease free), 2010 Overall ability below average performance (≤ 84) (Griffiths) (mean age 10 months old) during pregnancy (anytime or not specified) prospective cohort unexposed, disease free excluded Adjustment: No Matched 2.36 [0.96;5.79] C
excluded (control group) 		8/48   18/230 26 48
ref
S9701
R53387		 Bromley (Carbamazepine) (Controls unexposed, sick), 2010 Overall ability below average performance (≤ 84) (Griffiths) (mean age 10 months old) during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No 2.50 [0.49;12.74] C 8/48   2/27 10 48
ref
S9737
R53390		 Thomas b (Carbamazepine), 2008 Impaired Mental Development Quotient < 84 (The Developmental Assessment Scale (DAS II)) during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No 0.93 [0.39;2.20] C 30/101   10/32 40 101
ref
S9651
R53393		 Wide (Carbamazepine), 2000 Griffiths test total score (SD estimated) throughout pregnancy prospective cohort unexposed (general population or NOS) Adjustment: No extrapolated (cont. endpoint) Matched 0.34 [0.15;0.81] -/35   -/35 - 35
ref
S9639
R53389		 Ornoy (Carbamazepine), 1996 Mental developmental index (MDI) (Bayley) OR (general cognitive index (GCI) (McCarthy) score ≤80 throughout pregnancy prospective cohort unexposed (general population or NOS) Adjustment: No Matched 14.41 [0.77;269.27] C 5/41   0/47 5 41
ref
Total 7 studies 1.71 [0.73;4.01] 85 303
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 2.42[0.32; 18.46]42110%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: lowROB reporting: low Videman (Carbamazepine) (Controls unexposed, disease free), 2016Videman, 2016 2 4.58[1.25; 16.81]-915%ROB confusion: unclearROB selection: lowROB classification: moderateROB missing: criticalROB mesure: lowROB reporting: moderate Meador (Carbamazepine), 2013Meador, 2013 3 2.36[0.97; 5.73]264819%ROB confusion: moderateROB selection: lowROB classification: lowROB missing: moderateROB mesure: lowROB reporting: low Bromley (Carbamazepine) (Controls unexposed, sick), 2010Bromley, 2010 4 2.50[0.49; 12.74]104813%ROB confusion: moderateROB selection: lowROB classification: lowROB missing: moderateROB mesure: lowROB reporting: moderate Thomas b (Carbamazepine), 2008Thomas b, 2008 5 0.93[0.39; 2.20]4010119%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: criticalROB mesure: lowROB reporting: moderate Wide (Carbamazepine), 2000Wide, 2000 6 0.34[0.15; 0.81]-3519%ROB confusion: criticalROB selection: lowROB classification: lowROB missing: moderateROB mesure: lowROB reporting: moderate Ornoy (Carbamazepine), 1996Ornoy, 1996 7 14.41[0.77; 269.27]5416%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Total (7 studies) I2 = 69% 1.71[0.73; 4.01]853030.250.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Carbamazepine) (Epilepsy) (Controls unexposed, sick; 2: Carbamazepine) (Controls unexposed, disease free; 3: Carbamazepine; 4: Carbamazepine) (Controls unexposed, sick; 5: Carbamazepine; 6: Carbamazepine; 7: Carbamazepine;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.71[0.73; 4.01]8530369%NABromley (Carbamazepine) (Epilepsy) (Controls unexposed, sick), 2023 Videman (Carbamazepine) (Controls unexposed, disease free), 2016 Meador (Carbamazepine), 2013 Bromley (Carbamazepine) (Controls unexposed, sick), 2010 Thomas b (Carbamazepine), 2008 Wide (Carbamazepine), 2000 Ornoy (Carbamazepine), 1996 7 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 2.19[0.23; 21.25]58586%NAVideman (Carbamazepine) (Controls unexposed, disease free), 2016 Wide (Carbamazepine), 2000 Ornoy (Carbamazepine), 1996 3 unexposed, sickunexposed, sick 1.26[0.62; 2.58]541700%NABromley (Carbamazepine) (Epilepsy) (Controls unexposed, sick), 2023 Bromley (Carbamazepine) (Controls unexposed, sick), 2010 Thomas b (Carbamazepine), 2008 3 exposed to other treatment, sickexposed to other treatment, sick 2.36[0.97; 5.73]2648 -NAMeador (Carbamazepine), 2013 1 Tags Adjustment   - No  - No 1.65[0.60; 4.55]5925570%NABromley (Carbamazepine) (Epilepsy) (Controls unexposed, sick), 2023 Videman (Carbamazepine) (Controls unexposed, disease free), 2016 Bromley (Carbamazepine) (Controls unexposed, sick), 2010 Thomas b (Carbamazepine), 2008 Wide (Carbamazepine), 2000 Ornoy (Carbamazepine), 1996 6   - Yes  - Yes 2.36[0.97; 5.73]2648 -NAMeador (Carbamazepine), 2013 1 extrapolated (cont. endpoint)extrapolated (cont. endpoint) 1.19[0.09; 15.17]-4491%NAVideman (Carbamazepine) (Controls unexposed, disease free), 2016 Wide (Carbamazepine), 2000 2 MatchedMatched 1.68[0.04; 63.68]57683%NAWide (Carbamazepine), 2000 Ornoy (Carbamazepine), 1996 2 All studiesAll studies 1.71[0.73; 4.01]8530369%NABromley (Carbamazepine) (Epilepsy) (Controls unexposed, sick), 2023 Videman (Carbamazepine) (Controls unexposed, disease free), 2016 Meador (Carbamazepine), 2013 Bromley (Carbamazepine) (Controls unexposed, sick), 2010 Thomas b (Carbamazepine), 2008 Wide (Carbamazepine), 2000 Ornoy (Carbamazepine), 1996 70.150.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-3.54.11.7930.000Bromley (Carbamazepine) (Epilepsy) (Controls unexposed, sick), 2023Videman (Carbamazepine) (Controls unexposed, disease free), 2016Meador (Carbamazepine), 2013Bromley (Carbamazepine) (Controls unexposed, sick), 2010Thomas b (Carbamazepine), 2008Wide (Carbamazepine), 2000Ornoy (Carbamazepine), 1996

Asymetry test p-value = 0.1336 (by Egger's regression)

slope=-1.2924 (0.9164); intercept=2.8100 (1.5705); t=1.7892; p=0.1336

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 9695, 9698, 9937, 15367

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 2.05[0.47; 8.99]3113383%NAVideman (Carbamazepine) (Controls unexposed, disease free), 2016 Bromley (Carbamazepine) (Controls unexposed, disease free), 2010 Wide (Carbamazepine), 2000 Ornoy (Carbamazepine), 1996 4 unexposed, sick controlsunexposed, sick controls 1.26[0.62; 2.58]541700%NABromley (Carbamazepine) (Epilepsy) (Controls unexposed, sick), 2023 Bromley (Carbamazepine) (Controls unexposed, sick), 2010 Thomas b (Carbamazepine), 2008 3 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.82[0.97; 3.41]431260%NABromley (Carbamazepine) (Epilepsy) (Controls exposed to LTG), 2023 Videman (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2016 Meador (Carbamazepine), 2013 Bromley (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2010 40.510.01.0