Valproate (Paternal exposure)

Learning disorders

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.
S18944
R80554		 Meng_Taiwan (Controls unexposed, sick), 2026 Specific Learning Disorders - At least 2 diagnoses on different dates ICD-9 and ICD-10: ICD-10: F81.0x, F81.2x, F81.8x, R48.0x - Follow up: between 6 and 12 years. Paternal exposure: genotoxic/epigenetic window (0–xxx months preconception) population based cohort retrospective unexposed, sick Adjustment: Yes Paternal ASMs: monotherapy 1.23 [0.49;3.06] 5/543   2,357/500,498 2,362 543
ref
S18654
R79281		 Botton, 2025 Learning disorders - ICD10: F81.0, F81.2, F81.8x and/or therapy - Median follow up (years): 11.9 (IQR [10.3 - 13.3]) for valproate; 11.2 (IQR [9.9 - 12.8]) for control Paternal exposure: genotoxic/epigenetic window (0–xxx months preconception) retrospective cohort (claims database) exposed to other treatment, sick Adjustment: Yes Paternal ASMs: monotherapy 1.06 [0.75;1.50] 112/3,484   57/2,041 169 3,484
ref
Total 2 studies 1.08 [0.78;1.49] 2,531 4,027
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 Meng_Taiwan (Controls unexposed, sick), 2026Meng_Taiwan, 2026 1 1.23[0.49; 3.06]2,36254313%ROB confusion: moderateROB selection: lowROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: low Botton, 2025Botton, 2025 1.06[0.75; 1.50]1693,48487%ROB confusion: moderateROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: criticalROB reporting: moderate Total (2 studies) I2 = 0% 1.08[0.78; 1.49]2,5314,0270.55.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.08[0.78; 1.49]2,5314,0270%NAMeng_Taiwan (Controls unexposed, sick), 2026 Botton, 2025 2 case control studiescase control studies 0 Type of controls unexposed, sickunexposed, sick 1.23[0.49; 3.07]2,362543 -NAMeng_Taiwan (Controls unexposed, sick), 2026 1 exposed to other treatment, sickexposed to other treatment, sick 1.06[0.75; 1.50]1693,484 -NABotton, 2025 1 Tags Adjustment   - Yes  - Yes 1.08[0.78; 1.49]2,5314,0270%NAMeng_Taiwan (Controls unexposed, sick), 2026 Botton, 2025 2 Paternal ASMs   - monotherapy  - monotherapy 1.08[0.78; 1.49]2,5314,0270%NAMeng_Taiwan (Controls unexposed, sick), 2026 Botton, 2025 2 All studiesAll studies 1.08[0.78; 1.49]2,5314,0270%NAMeng_Taiwan (Controls unexposed, sick), 2026 Botton, 2025 20.55.01.0

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

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed, sick controlsunexposed, sick controls 1.23[0.49; 3.07]2,362543 -NAMeng_Taiwan (Controls unexposed, sick), 2026 1 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.06[0.75; 1.50]1693,484 -NABotton, 2025 10.510.01.0