Carbamazepine (All indications)

Severe cognitive developmental delay (Mental retardation) (> 6 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.
S12749
R48104
Bjørk (Carbamazepine) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2022 Diagnosis of intellectual disability (ID): mild ID (F70), moderate ID (F71), severe ID (F72), and profound ID (F73) (between 6.1 and 7.9 years old) during pregnancy (anytime or not specified) population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No 3.28 [1.99;5.41] C
excluded (control group)
36/3,256   27/7,950 63 3,256
ref
S12748
R48101
Bjørk (Carbamazepine) (Controls unexposed NOS) (Mixed indications), 2022 Diagnosis of intellectual disability (ID): mild ID (F70), moderate ID (F71), severe ID (F72), and profound ID (F73) (between 6.1 and 7.9 years old) during pregnancy (anytime or not specified) population based cohort retrospective unexposed (general population or NOS) excluded Adjustment: Yes 2.01 [1.45;2.79]
excluded (control group)
36/3,256   16,384/4,463,879 16,420 3,256
ref
S12747
R48098
Bjørk (Carbamazepine) (Controls unexposed, sick) (Mixed indications), 2022 Diagnosis of intellectual disability (ID): mild ID (F70), moderate ID (F71), severe ID (F72), and profound ID (F73) (between 6.1 and 7.9 years old) during pregnancy (anytime or not specified) population based cohort retrospective unexposed, sick Adjustment: No Controls: epilepsy indication 1.73 [1.20;2.50] C 36/3,256   139/21,634 175 3,256
ref
S9732
R34654
Meador (Carbamazepine), 2013 IQ <70 (DAS) (at 6 years old) during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick Adjustment: Yes 3.71 [0.15;92.65] C 1/61   0/74 1 61
ref
S9738
R34694
Titze (Carbamazepine) (Controls unexposed, disease free), 2008 Learning disability (IQ<70) (German versions of the revised Wechsler Intelligence Scales for children and for adults) during pregnancy (anytime or not specified) prospective cohort unexposed, disease free excluded Adjustment: No Matched 13.86 [0.24;809.27] C
excluded (control group)
0/4   0/49 0 4
ref
S9739
R34695
Titze (Carbamazepine) (Controls unexposed, sick), 2008 Learning disability (IQ<70) (German versions of the revised Wechsler Intelligence Scales for children and for adults) during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No 1.10 [0.04;33.38] C 0/4   1/13 1 4
ref
S9747
R34799
Viinikainen (Carbamazepine) b, 2006 Full Scale IQ (FIQ) < 2SD (Wechsler Intelligence Scale for Children (WISC-III)) throughout pregnancy prospective cohort unexposed, sick Adjustment: No 1.00 [0.02;54.47] C 0/13   0/13 0 13
ref
S9748
R34809
Vinten (Carbamazepine), 2005 IQ score <69 (Wechsler Intelligence Scale for Children (WISC-III)) (Aged between 6 and 16 years) during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: No 1.03 [0.28;3.83] C 4/52   6/80 10 52
ref
S9720
R34597
Gaily (Carbamazepine) (Controls unexposed, disease free), 2004 Mental retardation (Verbal and nonverbal IQ <70) 2nd and/or 3rd trimester prospective cohort unexposed, disease free excluded Adjustment: No 0.54 [0.06;5.29] C
excluded (control group)
1/86   3/141 4 86
ref
S9721
R34601
Gaily (Carbamazepine) (Controls unexposed, sick), 2004 Mental retardation (Verbal and nonverbal IQ <70) 2nd and/or 3rd trimester prospective cohort unexposed, sick Adjustment: No 0.25 [0.02;2.87] C 1/86   2/45 3 86
ref
Total 6 studies 1.60 [1.14;2.27] 190 3,472
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 Bjørk (Carbamazepine) (Controls unexposed, sick) (Mixed indications), 2022Bjørk, 2022 1 1.73[1.20; 2.50]1753,25688%ROB confusion: unclearROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Meador (Carbamazepine), 2013Meador, 2013 2 3.71[0.15; 92.65]1611%ROB confusion: moderateROB selection: lowROB classification: lowROB missing: moderateROB mesure: lowROB reporting: low Titze (Carbamazepine) (Controls unexposed, sick), 2008Titze, 2008 3 1.10[0.04; 33.38]141%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: moderateROB reporting: moderate Viinikainen (Carbamazepine) b, 2006Viinikainen, 2006 4 1.00[0.02; 54.47]0131%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: moderateROB mesure: lowROB reporting: moderate Vinten (Carbamazepine), 2005Vinten, 2005 5 1.03[0.28; 3.83]10527%ROB confusion: criticalROB selection: criticalROB classification: lowROB missing: criticalROB mesure: lowROB reporting: moderate Gaily (Carbamazepine) (Controls unexposed, sick), 2004Gaily, 2004 6 0.25[0.02; 2.87]3862%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: criticalROB mesure: lowROB reporting: moderate Total (6 studies) I2 = 0% 1.60[1.14; 2.27]1903,4720.210.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Carbamazepine) (Controls unexposed, sick) (Mixed indications; 2: Carbamazepine; 3: Carbamazepine) (Controls unexposed, sick; 4: Carbamazepine) ; 5: Carbamazepine; 6: Carbamazepine) (Controls unexposed, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.60[1.14; 2.27]1903,4720%NABjørk (Carbamazepine) (Controls unexposed, sick) (Mixed indications), 2022 Meador (Carbamazepine), 2013 Titze (Carbamazepine) (Controls unexposed, sick), 2008 Viinikainen (Carbamazepine) b, 2006 Vinten (Carbamazepine), 2005 Gaily (Carbamazepine) (Controls unexposed, sick), 2004 6 case control studiescase control studies 0 Type of controls unexposed, sickunexposed, sick 1.59[1.12; 2.25]1893,4110%NABjørk (Carbamazepine) (Controls unexposed, sick) (Mixed indications), 2022 Titze (Carbamazepine) (Controls unexposed, sick), 2008 Viinikainen (Carbamazepine) b, 2006 Vinten (Carbamazepine), 2005 Gaily (Carbamazepine) (Controls unexposed, sick), 2004 5 exposed to other treatment, sickexposed to other treatment, sick 3.71[0.15; 92.65]161 -NAMeador (Carbamazepine), 2013 1 Tags Adjustment   - No  - No 1.59[1.12; 2.25]1893,4110%NABjørk (Carbamazepine) (Controls unexposed, sick) (Mixed indications), 2022 Titze (Carbamazepine) (Controls unexposed, sick), 2008 Viinikainen (Carbamazepine) b, 2006 Vinten (Carbamazepine), 2005 Gaily (Carbamazepine) (Controls unexposed, sick), 2004 5   - Yes  - Yes 3.71[0.15; 92.65]161 -NAMeador (Carbamazepine), 2013 1 Controls   - epilepsy indication  - epilepsy indication 1.73[1.20; 2.50]1753,256 -NABjørk (Carbamazepine) (Controls unexposed, sick) (Mixed indications), 2022 1 All studiesAll studies 1.60[1.14; 2.27]1903,4720%NABjørk (Carbamazepine) (Controls unexposed, sick) (Mixed indications), 2022 Meador (Carbamazepine), 2013 Titze (Carbamazepine) (Controls unexposed, sick), 2008 Viinikainen (Carbamazepine) b, 2006 Vinten (Carbamazepine), 2005 Gaily (Carbamazepine) (Controls unexposed, sick), 2004 60.110.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-4.85.32.4480.000Bjørk (Carbamazepine) (Controls unexposed, sick) (Mixed indications), 2022Meador (Carbamazepine), 2013Titze (Carbamazepine) (Controls unexposed, sick), 2008Viinikainen (Carbamazepine) b, 2006Vinten (Carbamazepine), 2005Gaily (Carbamazepine) (Controls unexposed, sick), 2004

Asymetry test p-value = 0.2877 (by Egger's regression)

slope=0.6207 (0.1806); intercept=-0.5120 (0.4179); t=1.2253; p=0.2877

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 9720, 9738, 12749, 12748

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.93[1.07; 3.45]16,4243,3466%NABjørk (Carbamazepine) (Controls unexposed NOS) (Mixed indications), 2022 Titze (Carbamazepine) (Controls unexposed, disease free), 2008 Gaily (Carbamazepine) (Controls unexposed, disease free), 2004 3 unexposed, sick controlsunexposed, sick controls 1.59[1.12; 2.25]1893,4110%NABjørk (Carbamazepine) (Controls unexposed, sick) (Mixed indications), 2022 Titze (Carbamazepine) (Controls unexposed, sick), 2008 Viinikainen (Carbamazepine) b, 2006 Vinten (Carbamazepine), 2005 Gaily (Carbamazepine) (Controls unexposed, sick), 2004 5 exposed to other treatment, sick controlsexposed to other treatment, sick controls 3.29[2.01; 5.40]643,3170%NABjørk (Carbamazepine) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2022 Meador (Carbamazepine), 2013 20.510.01.0