Valproate (All indications)

ADHD (Attention deficit hyperactivity 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.
S15237
R62630		 Dreier (Valproate) (Epilepsy) (Controls exposed to LTG), 2023 Attention-deficit/hyperactivity disorder (ADHD) - Corresponding ICD-10 F-chapter - Up to 22 years of age during pregnancy (anytime or not specified) population based cohort propective exposed to other treatment, sick excluded Adjustment: No 3.14 [2.37;4.16] C
excluded (control group) 		106/1,952   95/5,288 201 1,952
ref
S15228
R62513		 Dreier (Valproate) (Epilepsy) (Controls unexposed, sick), 2023 Attention-deficit/hyperactivity disorder (ADHD) - Corresponding ICD-10 F-chapter - Up to 22 years of age during pregnancy (anytime or not specified) population based cohort propective unexposed, sick Adjustment: Yes 1.41 [1.10;1.81] 106/1,952   528/22,203 634 1,952
ref
S9430
R33119		 Wiggs (Valproate), 2020 Attention-deficit/hyperactivity disorder (after 2 years of age) at least 1st trimester population based cohort retrospective unexposed, sick Adjustment: Yes 1.74 [1.28;2.38] -/-   -/11,298 - -
ref
S9404
R32953		 Huber-Mollema (Valproate), 2019 Diagnosis of ADHD throughout pregnancy prospective cohort exposed to other treatment, sick Adjustment: No 1.38 [0.25;7.58] C 2/26   5/88 7 26
ref
S9377
R32811		 Bromley (Valproate) (Controls exposed to Lamotrigine, sick), 2013 Attention deficit hyperactivity disorder (at 6 years old) during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick excluded Adjustment: No 0.60 [0.01;30.84] C
excluded (control group) 		0/50   0/30 0 50
ref
S9380
R32827		 Bromley (Valproate) (Controls unexposed, disease free), 2013 Attention deficit hyperactivity disorder (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
S9383
R32843		 Bromley (Valproate) (Controls unexposed, sick), 2013 Attention deficit hyperactivity disorder (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
S9390
R32860		 Cohen (Valproate), 2013 Children with either ADHD inattentive OR combined types > 1 SD (from the Attention Problems and Hyperactivity scales of the BASC) (Both Parent and Teacher) during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick Adjustment: No 1.84 [0.46;7.35] C 6/28   4/31 10 28
ref
S9278
R32186		 Adab (Valproate), 2004 Attention deficit hyperactivity disorder during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: No 8.31 [0.39;175.93] C 2/63   0/101 2 63
ref
Total 6 studies 1.54 [1.27;1.86] 653 2,119
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 Dreier (Valproate) (Epilepsy) (Controls unexposed, sick), 2023Dreier, 2023 1 1.41[1.10; 1.81]6341,95259%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: lowROB mesure: criticalROB reporting: moderate Wiggs (Valproate), 2020Wiggs, 2020 2 1.74[1.28; 2.38]--38%ROB confusion: seriousROB selection: lowROB classification: lowROB missing: moderateROB mesure: moderateROB reporting: moderate Huber-Mollema (Valproate), 2019Huber-Mollema, 2019 3 1.38[0.25; 7.58]7261%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: criticalROB mesure: moderateROB reporting: moderate Bromley (Valproate) (Controls unexposed, sick), 2013Bromley, 2013 4 0.52[0.01; 26.73]0500%ROB confusion: criticalROB selection: lowROB classification: lowROB missing: moderateROB mesure: moderateROB reporting: moderate Cohen (Valproate), 2013Cohen, 2013 5 1.84[0.46; 7.35]10282%ROB confusion: criticalROB selection: lowROB classification: lowROB missing: criticalROB mesure: lowROB reporting: low Adab (Valproate), 2004Adab, 2004 6 8.31[0.39; 175.93]2630%ROB confusion: criticalROB selection: criticalROB classification: lowROB missing: criticalROB mesure: lowROB reporting: moderate Total (6 studies) I2 = 0% 1.54[1.27; 1.86]6532,1190.220.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Valproate) (Epilepsy) (Controls unexposed, sick; 2: Valproate; 3: Valproate; 4: Valproate) (Controls unexposed, sick; 5: Valproate; 6: Valproate;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.54[1.27; 1.86]6532,1190%NADreier (Valproate) (Epilepsy) (Controls unexposed, sick), 2023 Wiggs (Valproate), 2020 Huber-Mollema (Valproate), 2019 Bromley (Valproate) (Controls unexposed, sick), 2013 Cohen (Valproate), 2013 Adab (Valproate), 2004 6 case control studiescase control studies 0 Type of controls unexposed, sickunexposed, sick 1.54[1.27; 1.87]6362,0650%NADreier (Valproate) (Epilepsy) (Controls unexposed, sick), 2023 Wiggs (Valproate), 2020 Bromley (Valproate) (Controls unexposed, sick), 2013 Adab (Valproate), 2004 4 exposed to other treatment, sickexposed to other treatment, sick 1.64[0.56; 4.81]17540%NAHuber-Mollema (Valproate), 2019 Cohen (Valproate), 2013 2 Tags Adjustment   - No  - No 1.81[0.68; 4.82]191670%NAHuber-Mollema (Valproate), 2019 Bromley (Valproate) (Controls unexposed, sick), 2013 Cohen (Valproate), 2013 Adab (Valproate), 2004 4   - Yes  - Yes 1.53[1.25; 1.88]6341,9527%NADreier (Valproate) (Epilepsy) (Controls unexposed, sick), 2023 Wiggs (Valproate), 2020 2 All studiesAll studies 1.54[1.27; 1.86]6532,1190%NADreier (Valproate) (Epilepsy) (Controls unexposed, sick), 2023 Wiggs (Valproate), 2020 Huber-Mollema (Valproate), 2019 Bromley (Valproate) (Controls unexposed, sick), 2013 Cohen (Valproate), 2013 Adab (Valproate), 2004 60.220.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-4.75.22.4180.000Dreier (Valproate) (Epilepsy) (Controls unexposed, sick), 2023Wiggs (Valproate), 2020Huber-Mollema (Valproate), 2019Bromley (Valproate) (Controls unexposed, sick), 2013Cohen (Valproate), 2013Adab (Valproate), 2004

Asymetry test p-value = 0.6139 (by Egger's regression)

slope=0.3905 (0.1078); intercept=0.2473 (0.4528); t=0.5462; p=0.6139

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 9377, 9380, 15237

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 4.31[0.08; 220.05]-50 -NABromley (Valproate) (Controls unexposed, disease free), 2013 1 unexposed, sick controlsunexposed, sick controls 1.54[1.27; 1.87]6362,0650%NADreier (Valproate) (Epilepsy) (Controls unexposed, sick), 2023 Wiggs (Valproate), 2020 Bromley (Valproate) (Controls unexposed, sick), 2013 Adab (Valproate), 2004 4 exposed to other treatment, sick controlsexposed to other treatment, sick controls 2.99[2.28; 3.92]2182,0560%NADreier (Valproate) (Epilepsy) (Controls exposed to LTG), 2023 Huber-Mollema (Valproate), 2019 Bromley (Valproate) (Controls exposed to Lamotrigine, sick), 2013 Cohen (Valproate), 2013 40.510.01.0