Carbamazepine (All indications)

ASD (Autism spectrum disorder): Diagnosis

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
R48103		 Bjørk (Carbamazepine) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2022 Diagnosis of childhood autism (F84.0), atypical autism (F84.1), and Asperger syndrome (F84.5) (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 1.22 [0.84;1.78] C
excluded (control group) 		41/3,256   82/7,950 123 3,256
ref
S12748
R48100		 Bjørk (Carbamazepine) (Controls unexposed NOS) (Mixed indications), 2022 Diagnosis of childhood autism (F84.0), atypical autism (F84.1), and Asperger syndrome (F84.5) (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 1.36 [1.00;1.85]
excluded (control group) 		41/3,256   38,437/4,463,879 38,478 3,256
ref
S12747
R48097		 Bjørk (Carbamazepine) (Controls unexposed, sick) (Mixed indications), 2022 Diagnosis of childhood autism (F84.0), atypical autism (F84.1), and Asperger syndrome (F84.5) (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 1.02 [0.73;1.42] C 41/3,256   267/21,634 308 3,256
ref
S9776
R34963		 Coste (Carbamazepine) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2020 Diagnosis Pervasive developmental disorders (F84) (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 1.30 [0.30;5.00]
excluded (control group) 		3/502   11/2,916 14 502
ref
S9777
R34981		 Coste (Carbamazepine) (Controls unexposed, NOS) (Mixed indications), 2020 Diagnosis Pervasive developmental disorders (F84) (mean age of 3.6 years old) during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes 1.70 [0.50;5.20] 3/468   4,254/1,707,707 4,257 468
ref
S9749
R34810		 Wiggs (Carbamazepine), 2020 Austism Spectrum Disorder (after 2 years of age) at least 1st trimester population based cohort retrospective unexposed, sick Adjustment: Yes 1.26 [0.88;1.79] -/-   -/11,298 - -
ref
S9723
R34604		 Huber-Mollema (Carbamazepine), 2019 Diagnosis of autism spectrum disorder throughout pregnancy prospective cohort exposed to other treatment, sick Adjustment: No 1.20 [0.21;6.85] C 2/37   4/88 6 37
ref
S9750
R34812		 Wood (Carbamazepine), 2015 Score >30 (CARS) during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick Adjustment: No 0.78 [0.03;21.03] C 1/34   0/9 1 34
ref
S9696
R35905		 Bromley (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2013 Autistic Spectrum Disorders (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
R35906		 Bromley (Carbamazepine) (Controls unexposed, disease free), 2013 Autistic Spectrum Disorders (at 6 years old) during pregnancy (anytime or not specified) prospective cohort unexposed, disease free excluded Adjustment: No 0.47 [0.02;8.88] C
excluded (control group) 		0/50   4/214 4 50
ref
S9702
R35907		 Bromley (Carbamazepine) (Controls unexposed, sick), 2013 Autistic Spectrum Disorders (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
Total 6 studies 1.14 [0.90;1.44] 4,572 3,845
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 1.02[0.73; 1.42]3083,25650%ROB confusion: unclearROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Coste (Carbamazepine) (Controls unexposed, NOS) (Mixed indications), 2020Coste, 2020 2 1.70[0.50; 5.20]4,2574684%ROB confusion: moderateROB selection: moderateROB classification: criticalROB missing: moderateROB mesure: criticalROB reporting: moderate Wiggs (Carbamazepine), 2020Wiggs, 2020 3 1.26[0.88; 1.79]--43%ROB confusion: moderateROB selection: lowROB classification: lowROB missing: moderateROB mesure: moderateROB reporting: moderate Huber-Mollema (Carbamazepine), 2019Huber-Mollema, 2019 4 1.20[0.21; 6.85]6372%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: criticalROB mesure: moderateROB reporting: moderate Wood (Carbamazepine), 2015Wood, 2015 5 0.78[0.03; 21.03]1341%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: criticalROB mesure: lowROB reporting: moderate Bromley (Carbamazepine) (Controls unexposed, sick), 2013Bromley, 2013 6 0.52[0.01; 26.73]0500%ROB confusion: criticalROB selection: lowROB classification: lowROB missing: moderateROB mesure: moderateROB reporting: moderate Total (6 studies) I2 = 0% 1.14[0.90; 1.44]4,5723,8450.25.01.0ROB: 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) (Controls unexposed, NOS) (Mixed indications; 3: Carbamazepine; 4: Carbamazepine; 5: Carbamazepine; 6: Carbamazepine) (Controls unexposed, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.14[0.90; 1.44]4,5723,8450%NABjørk (Carbamazepine) (Controls unexposed, sick) (Mixed indications), 2022 Coste (Carbamazepine) (Controls unexposed, NOS) (Mixed indications), 2020 Wiggs (Carbamazepine), 2020 Huber-Mollema (Carbamazepine), 2019 Wood (Carbamazepine), 2015 Bromley (Carbamazepine) (Controls unexposed, sick), 2013 6 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.70[0.53; 5.48]4,257468 -NACoste (Carbamazepine) (Controls unexposed, NOS) (Mixed indications), 2020 1 unexposed, sickunexposed, sick 1.12[0.88; 1.43]3083,3060%NABjørk (Carbamazepine) (Controls unexposed, sick) (Mixed indications), 2022 Wiggs (Carbamazepine), 2020 Bromley (Carbamazepine) (Controls unexposed, sick), 2013 3 exposed to other treatment, sickexposed to other treatment, sick 1.09[0.23; 5.10]7710%NAHuber-Mollema (Carbamazepine), 2019 Wood (Carbamazepine), 2015 2 Tags Adjustment   - No  - No 1.02[0.74; 1.41]3153,3770%NABjørk (Carbamazepine) (Controls unexposed, sick) (Mixed indications), 2022 Huber-Mollema (Carbamazepine), 2019 Wood (Carbamazepine), 2015 Bromley (Carbamazepine) (Controls unexposed, sick), 2013 4   - Yes  - Yes 1.29[0.92; 1.81]4,2574680%NACoste (Carbamazepine) (Controls unexposed, NOS) (Mixed indications), 2020 Wiggs (Carbamazepine), 2020 2 Controls   - epilepsy indication  - epilepsy indication 1.02[0.73; 1.42]3083,256 -NABjørk (Carbamazepine) (Controls unexposed, sick) (Mixed indications), 2022 1 All studiesAll studies 1.14[0.90; 1.44]4,5723,8450%NABjørk (Carbamazepine) (Controls unexposed, sick) (Mixed indications), 2022 Coste (Carbamazepine) (Controls unexposed, NOS) (Mixed indications), 2020 Wiggs (Carbamazepine), 2020 Huber-Mollema (Carbamazepine), 2019 Wood (Carbamazepine), 2015 Bromley (Carbamazepine) (Controls unexposed, sick), 2013 60.25.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-4.74.92.4180.000Bjørk (Carbamazepine) (Controls unexposed, sick) (Mixed indications), 2022Coste (Carbamazepine) (Controls unexposed, NOS) (Mixed indications), 2020Wiggs (Carbamazepine), 2020Huber-Mollema (Carbamazepine), 2019Wood (Carbamazepine), 2015Bromley (Carbamazepine) (Controls unexposed, sick), 2013

Asymetry test p-value = 0.9987 (by Egger's regression)

slope=0.1312 (0.1058); intercept=0.0006 (0.3621); t=0.0018; p=0.9987

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 9696, 9699, 9776, 12749, 12748

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.36[1.02; 1.83]42,7393,7740%NABjørk (Carbamazepine) (Controls unexposed NOS) (Mixed indications), 2022 Coste (Carbamazepine) (Controls unexposed, NOS) (Mixed indications), 2020 Bromley (Carbamazepine) (Controls unexposed, disease free), 2013 3 unexposed, sick controlsunexposed, sick controls 1.12[0.88; 1.43]3083,3060%NABjørk (Carbamazepine) (Controls unexposed, sick) (Mixed indications), 2022 Wiggs (Carbamazepine), 2020 Bromley (Carbamazepine) (Controls unexposed, sick), 2013 3 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.19[0.84; 1.70]1453,8790%NABjørk (Carbamazepine) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2022 Coste (Carbamazepine) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2020 Huber-Mollema (Carbamazepine), 2019 Wood (Carbamazepine), 2015 Bromley (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2013 50.510.01.0