Carbamazepine (All indications)

Cognitive developmental disorders/delay (3-6 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.
S9776
R46398		 Coste (Carbamazepine) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2020 Diagnosis Mental retardation (F70–F79) (mean age of 3.7 years old) during pregnancy (anytime or not specified) retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: Yes 0.60 [0.10;2.90]
excluded (control group) 		2/502   15/2,916 17 502
ref
S9777
R46399		 Coste (Carbamazepine) (Controls unexposed, NOS) (Mixed indications), 2020 Diagnosis Mental retardation (F70–F79) (mean age of 3.6 years old) during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes 1.60 [0.40;6.60] 2/468   3,385/1,707,707 3,387 468
ref
S9727
R46395		 Kasradze (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2017 Full scale IQ (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) 0.18 [0.02;1.80]
excluded (control group) 		-/16   -/3 - 16
ref
S9728
R46396		 Kasradze (Carbamazepine) (Controls unexposed, disease free), 2017 Full scale IQ (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 5.75 [1.98;16.71] -/16   -/50 - 16
ref
S9716
R46394		 Deshmukh (Carbamazepine), 2016 Vineland-II Adaptative Behavior Scales - Low and moderately low in the overall ABC (Adaptative Behavior Composite) throughout pregnancy prospective cohort exposed to other treatment, sick Adjustment: Yes 1.46 [0.24;9.03] 5/97   3/104 8 97
ref
S9732
R46397		 Meador (Carbamazepine), 2013 IQ <85 (DAS) (at 4.5 years old) during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick Adjustment: Yes 1.40 [0.42;4.59] C 6/54   6/73 12 54
ref
S9712
R46392		 Cummings (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2011 Mild or significant delay (score ≥1, <2 SD or ≥2 SD below the mean) (Bayley Scales of Infant Development or the Griffiths Scale) (mean age in years: m1=3.0 and m0=2.7) throughout pregnancy retrospective cohort (registry) exposed to other treatment, sick excluded Adjustment: No 8.72 [1.06;71.65] C
excluded (control group) 		10/49   1/35 11 49
ref
S9713
R46393		 Cummings (Carbamazepine) (Controls unexposed, disease free), 2011 Mild or significant delay (score ≥1, <2 SD or ≥2 SD below the mean) (Bayley Scales of Infant Development or the Griffiths Scale) (mean age in years: m1=3.0 and m0=4.3) throughout pregnancy retrospective cohort (registry) unexposed, disease free Adjustment: Yes 7.70 [1.40;43.10] 10/49   2/44 12 49
ref
Total 5 studies 2.75 [1.33;5.68] 3,419 684
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 Coste (Carbamazepine) (Controls unexposed, NOS) (Mixed indications), 2020Coste, 2020 1 1.60[0.40; 6.60]3,38746820%ROB confusion: seriousROB selection: moderateROB classification: criticalROB missing: moderateROB mesure: criticalROB reporting: moderate Kasradze (Carbamazepine) (Controls unexposed, disease free), 2017Kasradze, 2017 2 5.75[1.98; 16.71]-1628%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: criticalROB mesure: lowROB reporting: moderate Deshmukh (Carbamazepine), 2016Deshmukh, 2016 3 1.46[0.24; 9.03]89713%ROB confusion: moderateROB selection: lowROB classification: moderateROB missing: criticalROB mesure: moderateROB reporting: moderate Meador (Carbamazepine), 2013Meador, 2013 4 1.40[0.42; 4.59]125425%ROB confusion: moderateROB selection: lowROB classification: lowROB missing: moderateROB mesure: lowROB reporting: low Cummings (Carbamazepine) (Controls unexposed, disease free), 2011Cummings, 2011 5 7.70[1.40; 43.10]124914%ROB confusion: moderateROB selection: lowROB classification: moderateROB missing: unclearROB mesure: lowROB reporting: moderate Total (5 studies) I2 = 27% 2.75[1.33; 5.68]3,4196840.520.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Carbamazepine) (Controls unexposed, NOS) (Mixed indications; 2: Carbamazepine) (Controls unexposed, disease free; 3: Carbamazepine; 4: Carbamazepine; 5: Carbamazepine) (Controls unexposed, disease free;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 2.75[1.33; 5.68]3,41968427%NACoste (Carbamazepine) (Controls unexposed, NOS) (Mixed indications), 2020 Kasradze (Carbamazepine) (Controls unexposed, disease free), 2017 Deshmukh (Carbamazepine), 2016 Meador (Carbamazepine), 2013 Cummings (Carbamazepine) (Controls unexposed, disease free), 2011 5 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 4.12[1.68; 10.08]3,39953324%NACoste (Carbamazepine) (Controls unexposed, NOS) (Mixed indications), 2020 Kasradze (Carbamazepine) (Controls unexposed, disease free), 2017 Cummings (Carbamazepine) (Controls unexposed, disease free), 2011 3 exposed to other treatment, sickexposed to other treatment, sick 1.41[0.52; 3.83]201510%NADeshmukh (Carbamazepine), 2016 Meador (Carbamazepine), 2013 2 Tags Adjustment   - No  - No 5.75[1.98; 16.70]-16 -NAKasradze (Carbamazepine) (Controls unexposed, disease free), 2017 1   - Yes  - Yes 2.00[0.96; 4.16]3,4196680%NACoste (Carbamazepine) (Controls unexposed, NOS) (Mixed indications), 2020 Deshmukh (Carbamazepine), 2016 Meador (Carbamazepine), 2013 Cummings (Carbamazepine) (Controls unexposed, disease free), 2011 4 extrapolated (cont. endpoint)extrapolated (cont. endpoint) 5.75[1.98; 16.70]-16 -NAKasradze (Carbamazepine) (Controls unexposed, disease free), 2017 1 MatchedMatched 5.75[1.98; 16.70]-16 -NAKasradze (Carbamazepine) (Controls unexposed, disease free), 2017 1 All studiesAll studies 2.75[1.33; 5.68]3,41968427%NACoste (Carbamazepine) (Controls unexposed, NOS) (Mixed indications), 2020 Kasradze (Carbamazepine) (Controls unexposed, disease free), 2017 Deshmukh (Carbamazepine), 2016 Meador (Carbamazepine), 2013 Cummings (Carbamazepine) (Controls unexposed, disease free), 2011 50.520.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-2.43.21.1110.000Coste (Carbamazepine) (Controls unexposed, NOS) (Mixed indications), 2020Kasradze (Carbamazepine) (Controls unexposed, disease free), 2017Deshmukh (Carbamazepine), 2016Meador (Carbamazepine), 2013Cummings (Carbamazepine) (Controls unexposed, disease free), 2011

Asymetry test p-value = 0.8041 (by Egger's regression)

slope=1.5806 (2.0716); intercept=-0.8136 (3.0047); t=0.2708; p=0.8041

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 9712, 9727, 9776

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 4.12[1.68; 10.08]3,39953324%NACoste (Carbamazepine) (Controls unexposed, NOS) (Mixed indications), 2020 Kasradze (Carbamazepine) (Controls unexposed, disease free), 2017 Cummings (Carbamazepine) (Controls unexposed, disease free), 2011 3 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.17[0.42; 3.27]4871842%NACoste (Carbamazepine) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2020 Kasradze (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2017 Deshmukh (Carbamazepine), 2016 Meador (Carbamazepine), 2013 Cummings (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2011 50.510.01.0