Valproate (All indications)

ASD (Autism spectrum disorder): Risk

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.
S9404
R32971		 Huber-Mollema (Valproate), 2019 Autistic behavior (Social Emotional Questionnaire) (Completed by mothers) Clinical cutoff throughout pregnancy prospective cohort exposed to other treatment, sick Adjustment: No 1.73 [0.30;10.02] C 2/26   4/87 6 26
ref
S9981
R35864		 Bjørk (Valproate) (Controls exposed to Lamotrigine, sick), 2018 Autistic traits at 18 months and/or at 36 months (M-CHAT <2/6 critical or <3/23 or SCQ >13) during pregnancy (anytime or not specified) population based cohort propective exposed to other treatment, sick excluded Adjustment: No 0.61 [0.16;2.31] C
excluded (control group) 		3/27   13/76 16 27
ref
S9982
R35865		 Bjørk (Valproate) (Controls unexposed, disease free), 2018 Autistic traits at 18 months and/or at 36 months (M-CHAT <2/6 critical or <3/23 or SCQ >13) during pregnancy (anytime or not specified) population based cohort propective unexposed, disease free excluded Adjustment: No 1.24 [0.37;4.12] C
excluded (control group) 		3/27   6,907/75,497 6,910 27
ref
S9983
R35866		 Bjørk (Valproate) (Controls unexposed, sick), 2018 Autistic traits at 18 months and/or at 36 months (M-CHAT <2/6 critical or <3/23 or SCQ >13) during pregnancy (anytime or not specified) population based cohort propective unexposed, sick Adjustment: No 1.13 [0.32;4.02] C 3/27   27/272 30 27
ref
S9431
R33121		 Wood (Valproate), 2015 Score 27-29 (CARS) during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick Adjustment: No 1.04 [0.04;28.06] C 1/26   0/9 1 26
ref
Total 3 studies 1.28 [0.48;3.42] 37 79
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 Huber-Mollema (Valproate), 2019Huber-Mollema, 2019 1 1.73[0.30; 10.02]62631%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: criticalROB mesure: moderateROB reporting: moderate Bjørk (Valproate) (Controls unexposed, sick), 2018Bjørk, 2018 2 1.13[0.32; 4.02]302760%ROB confusion: unclearROB selection: lowROB classification: lowROB missing: lowROB mesure: moderateROB reporting: moderate Wood (Valproate), 2015Wood, 2015 3 1.04[0.04; 28.06]1269%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: criticalROB mesure: lowROB reporting: moderate Total (3 studies) I2 = 0% 1.28[0.48; 3.42]37790.55.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Valproate; 2: Valproate) (Controls unexposed, sick; 3: Valproate;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.28[0.48; 3.42]37790%NAHuber-Mollema (Valproate), 2019 Bjørk (Valproate) (Controls unexposed, sick), 2018 Wood (Valproate), 2015 3 case control studiescase control studies 0 Type of controls unexposed, sickunexposed, sick 1.13[0.32; 4.02]3027 -NABjørk (Valproate) (Controls unexposed, sick), 2018 1 exposed to other treatment, sickexposed to other treatment, sick 1.55[0.33; 7.28]7520%NAHuber-Mollema (Valproate), 2019 Wood (Valproate), 2015 2 Tags Adjustment   - No  - No 1.28[0.48; 3.42]37790%NAHuber-Mollema (Valproate), 2019 Bjørk (Valproate) (Controls unexposed, sick), 2018 Wood (Valproate), 2015 3 All studiesAll studies 1.28[0.48; 3.42]37790%NAHuber-Mollema (Valproate), 2019 Bjørk (Valproate) (Controls unexposed, sick), 2018 Wood (Valproate), 2015 30.55.01.0

Publication bias and p-hacking diagnosis

funnel plot

Funnel plot not drawn. Less than 3 points.

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

not enought points

p values plot

Funnel plot not drawn. Less than 3 points.

Sub-groups analysis using all included studies

excluded 9981, 9982

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.24[0.37; 4.12]6,91027 -NABjørk (Valproate) (Controls unexposed, disease free), 2018 1 unexposed, sick controlsunexposed, sick controls 1.13[0.32; 4.02]3027 -NABjørk (Valproate) (Controls unexposed, sick), 2018 1 exposed to other treatment, sick controlsexposed to other treatment, sick controls 0.90[0.33; 2.49]23790%NAHuber-Mollema (Valproate), 2019 Bjørk (Valproate) (Controls exposed to Lamotrigine, sick), 2018 Wood (Valproate), 2015 30.510.01.0