Carbamazepine (All indications)

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.
S15367
R63243		 Bromley (Carbamazepine) (Epilepsy) (Controls exposed to LTG), 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 exposed to other treatment, sick excluded Adjustment: No 0.99 [0.19;5.18] C
excluded (control group) 		2/21   7/73 9 21
ref
S15368
R63256		 Bromley (Carbamazepine) (Epilepsy) (Controls unexposed, sick), 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 1.16 [0.20;6.87] C 2/21   4/48 6 21
ref
S9716
R34581		 Deshmukh (Carbamazepine), 2016 Vineland-II Adaptative Behavior Scales - Low and moderately low in the motor skills domain throughout pregnancy prospective cohort exposed to other treatment, sick Adjustment: Yes 0.81 [0.19;3.41] 8/97   8/104 16 97
ref
S9937
R35713		 Videman (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2016 Griffiths Mental Developmental Scale - Locomotor (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) 0.20 [0.03;1.27]
excluded (control group) 		-/9   -/8 - 9
ref
S9936
R35707		 Videman (Carbamazepine) (Controls unexposed, disease free), 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) 2.37 [0.66;8.52] -/9   -/59 - 9
ref
S9696
R34509		 Bromley (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2013 Dyspraxia (at 6 years old) during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick excluded Adjustment: No 0.19 [0.01;4.87] C
excluded (control group) 		0/50   1/30 1 50
ref
S9699
R34525		 Bromley (Carbamazepine) (Controls unexposed, disease free), 2013 Dyspraxia (at 6 years old) during pregnancy (anytime or not specified) prospective cohort unexposed, disease free excluded Adjustment: No 4.31 [0.08;220.05] C
excluded (control group) 		0/50   0/214 0 50
ref
S9702
R34541		 Bromley (Carbamazepine) (Controls unexposed, sick), 2013 Dyspraxia (at 6 years old) during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No 0.52 [0.01;26.73] C 0/50   0/26 0 50
ref
S9710
R34553		 Cohen (Carbamazepine), 2011 Motor Index score the Bayley Scales of Infant Development (BSID-II)) during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick Adjustment: Yes extrapolated (cont. endpoint) 0.87 [0.45;1.71] -/51   -/62 - 51
ref
S9737
R34693		 Thomas b (Carbamazepine), 2008 Impaired Motor Development Quotient < 84 (The Developmental Assessment Scale (DAS II)) during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No 1.13 [0.47;2.73] C 31/101   9/32 40 101
ref
S9747
R34796		 Viinikainen (Carbamazepine) b, 2006 Touwen's test Neurological dysfunction/impairment throughout pregnancy prospective cohort unexposed, sick Adjustment: No 0.46 [0.04;5.79] C 1/13   2/13 3 13
ref
S9593
R33974		 Adab (Carbamazepine), 2004 Schedule of Growing Skills II (SGSII) locomotion delay during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: No 0.42 [0.01;22.11] C 0/42   0/18 0 42
ref
S9639
R34291		 Ornoy (Carbamazepine), 1996 Combined motor score (of Bayley and McCarthy tests) throughout pregnancy prospective cohort unexposed (general population or NOS) Adjustment: No extrapolated (cont. endpoint) Matched 0.97 [0.45;2.07] -/41   -/47 - 41
ref
Total 9 studies 1.01 [0.69;1.47] 65 425
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 1.16[0.20; 6.87]6215%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: lowROB reporting: low Deshmukh (Carbamazepine), 2016Deshmukh, 2016 2 0.81[0.19; 3.41]16977%ROB confusion: moderateROB selection: lowROB classification: moderateROB missing: criticalROB mesure: moderateROB reporting: moderate Videman (Carbamazepine) (Controls unexposed, disease free), 2016Videman, 2016 3 2.37[0.66; 8.52]-99%ROB confusion: unclearROB selection: lowROB classification: moderateROB missing: criticalROB mesure: lowROB reporting: moderate Bromley (Carbamazepine) (Controls unexposed, sick), 2013Bromley, 2013 4 0.52[0.01; 26.73]0501%ROB confusion: criticalROB selection: lowROB classification: lowROB missing: moderateROB mesure: moderateROB reporting: moderate Cohen (Carbamazepine), 2011Cohen, 2011 5 0.87[0.45; 1.71]-5132%ROB confusion: moderateROB selection: lowROB classification: lowROB missing: criticalROB mesure: lowROB reporting: moderate Thomas b (Carbamazepine), 2008Thomas b, 2008 6 1.13[0.47; 2.73]4010119%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: criticalROB mesure: lowROB reporting: moderate Viinikainen (Carbamazepine) b, 2006Viinikainen, 2006 7 0.46[0.04; 5.79]3132%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: moderateROB mesure: lowROB reporting: moderate Adab (Carbamazepine), 2004Adab, 2004 8 0.42[0.01; 22.11]0421%ROB confusion: criticalROB selection: criticalROB classification: lowROB missing: criticalROB mesure: lowROB reporting: moderate Ornoy (Carbamazepine), 1996Ornoy, 1996 9 0.97[0.45; 2.07]-4125%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Total (9 studies) I2 = 0% 1.01[0.69; 1.47]654250.25.01.0ROB: 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) (Controls unexposed, disease free; 4: Carbamazepine) (Controls unexposed, sick; 5: Carbamazepine; 6: Carbamazepine; 7: Carbamazepine) ; 8: Carbamazepine; 9: Carbamazepine;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.01[0.69; 1.47]654250%NABromley (Carbamazepine) (Epilepsy) (Controls unexposed, sick), 2023 Deshmukh (Carbamazepine), 2016 Videman (Carbamazepine) (Controls unexposed, disease free), 2016 Bromley (Carbamazepine) (Controls unexposed, sick), 2013 Cohen (Carbamazepine), 2011 Thomas b (Carbamazepine), 2008 Viinikainen (Carbamazepine) b, 2006 Adab (Carbamazepine), 2004 Ornoy (Carbamazepine), 1996 9 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.30[0.57; 2.96]-5028%NAVideman (Carbamazepine) (Controls unexposed, disease free), 2016 Ornoy (Carbamazepine), 1996 2 unexposed, sickunexposed, sick 0.99[0.48; 2.05]492270%NABromley (Carbamazepine) (Epilepsy) (Controls unexposed, sick), 2023 Bromley (Carbamazepine) (Controls unexposed, sick), 2013 Thomas b (Carbamazepine), 2008 Viinikainen (Carbamazepine) b, 2006 Adab (Carbamazepine), 2004 5 exposed to other treatment, sickexposed to other treatment, sick 0.86[0.47; 1.57]161480%NADeshmukh (Carbamazepine), 2016 Cohen (Carbamazepine), 2011 2 Tags Adjustment   - No  - No 1.12[0.69; 1.82]492770%NABromley (Carbamazepine) (Epilepsy) (Controls unexposed, sick), 2023 Videman (Carbamazepine) (Controls unexposed, disease free), 2016 Bromley (Carbamazepine) (Controls unexposed, sick), 2013 Thomas b (Carbamazepine), 2008 Viinikainen (Carbamazepine) b, 2006 Adab (Carbamazepine), 2004 Ornoy (Carbamazepine), 1996 7   - Yes  - Yes 0.86[0.47; 1.57]161480%NADeshmukh (Carbamazepine), 2016 Cohen (Carbamazepine), 2011 2 extrapolated (cont. endpoint)extrapolated (cont. endpoint) 1.04[0.65; 1.65]-1010%NAVideman (Carbamazepine) (Controls unexposed, disease free), 2016 Cohen (Carbamazepine), 2011 Ornoy (Carbamazepine), 1996 3 MatchedMatched 0.97[0.45; 2.08]-41 -NAOrnoy (Carbamazepine), 1996 1 All studiesAll studies 1.01[0.69; 1.47]654250%NABromley (Carbamazepine) (Epilepsy) (Controls unexposed, sick), 2023 Deshmukh (Carbamazepine), 2016 Videman (Carbamazepine) (Controls unexposed, disease free), 2016 Bromley (Carbamazepine) (Controls unexposed, sick), 2013 Cohen (Carbamazepine), 2011 Thomas b (Carbamazepine), 2008 Viinikainen (Carbamazepine) b, 2006 Adab (Carbamazepine), 2004 Ornoy (Carbamazepine), 1996 90.25.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-4.84.82.4240.000Bromley (Carbamazepine) (Epilepsy) (Controls unexposed, sick), 2023Deshmukh (Carbamazepine), 2016Videman (Carbamazepine) (Controls unexposed, disease free), 2016Bromley (Carbamazepine) (Controls unexposed, sick), 2013Cohen (Carbamazepine), 2011Thomas b (Carbamazepine), 2008Viinikainen (Carbamazepine) b, 2006Adab (Carbamazepine), 2004Ornoy (Carbamazepine), 1996

Asymetry test p-value = 0.6226 (by Egger's regression)

slope=0.1157 (0.2424); intercept=-0.2148 (0.4174); t=0.5147; p=0.6226

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 9696, 9699, 9937, 15367

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.27[0.66; 2.42]-1000%NAVideman (Carbamazepine) (Controls unexposed, disease free), 2016 Bromley (Carbamazepine) (Controls unexposed, disease free), 2013 Ornoy (Carbamazepine), 1996 3 unexposed, sick controlsunexposed, sick controls 0.99[0.48; 2.05]492270%NABromley (Carbamazepine) (Epilepsy) (Controls unexposed, sick), 2023 Bromley (Carbamazepine) (Controls unexposed, sick), 2013 Thomas b (Carbamazepine), 2008 Viinikainen (Carbamazepine) b, 2006 Adab (Carbamazepine), 2004 5 exposed to other treatment, sick controlsexposed to other treatment, sick controls 0.74[0.43; 1.27]262280%NABromley (Carbamazepine) (Epilepsy) (Controls exposed to LTG), 2023 Deshmukh (Carbamazepine), 2016 Videman (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2016 Bromley (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2013 Cohen (Carbamazepine), 2011 50.510.01.0