Valproate (Paternal exposure)

Major congenital malformations

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.
S18646
R79249		 Christensen (Controls exposed to LTG/LEV), 2024 Major congenital malformations Paternal exposure: genotoxic/epigenetic window (0–xxx months preconception) population based cohort retrospective exposed to other treatment, sick excluded Adjustment: Yes Paternal ASMs: mono/polytherapy or not specified 0.67 [0.46;0.98]
excluded (control group) 		48/1,336   84/1,663 132 1,336
ref
S18644
R79230		 Christensen (Controls unexposed, general pop), 2024 Major congenital malformations Paternal exposure: genotoxic/epigenetic window (0–xxx months preconception) population based cohort retrospective unexposed (general population or NOS) excluded Adjustment: Yes Paternal ASMs: monotherapy 0.83 [0.59;1.17]
excluded (control group) 		-/1,017   43,855/1,234,017 - 1,017
ref
S18647
R79252		 Christensen (Controls unexposed, sibling), 2024 Major congenital malformations Paternal exposure: genotoxic/epigenetic window (0–xxx months preconception) population based cohort retrospective sibling excluded Adjustment: Yes Paternal ASMs: mono/polytherapy or not specified 0.72 [0.30;1.70]
excluded (control group) 		10/303   16/381 26 303
ref
S18645
R79239		 Christensen (Controls unexposed, sick), 2024 Major congenital malformations Paternal exposure: genotoxic/epigenetic window (0–xxx months preconception) population based cohort retrospective unexposed, sick Adjustment: Yes Paternal ASMs: mono/polytherapy or not specified 0.81 [0.58;1.14] 35/1,052   481/11,308 516 1,052
ref
S18640
R79224		 Tomson, 2020 Major malformations Paternal exposure: genotoxic/epigenetic window (0–xxx months preconception) population based cohort retrospective unexposed, sick Adjustment: Yes Paternal ASMs: monotherapy 0.90 [0.60;1.50] 22/458   121/2,457 143 458
ref
Total 2 studies 0.84 [0.64;1.10] 659 1,510
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 Christensen (Controls unexposed, sick), 2024Christensen, 2024 1 0.81[0.58; 1.14]5161,05265%ROB confusion: seriousROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Tomson, 2020Tomson, 2020 0.90[0.60; 1.50]14345835%ROB confusion: criticalROB selection: unclearROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Total (2 studies) I2 = 0% 0.84[0.64; 1.10]6591,5100.22.01.0ROB: 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 0.84[0.64; 1.10]6591,5100%NAChristensen (Controls unexposed, sick), 2024 Tomson, 2020 2 case control studiescase control studies 0 Type of controls unexposed, sickunexposed, sick 0.84[0.64; 1.10]6591,5100%NAChristensen (Controls unexposed, sick), 2024 Tomson, 2020 2 Tags Adjustment   - Yes  - Yes 0.84[0.64; 1.10]6591,5100%NAChristensen (Controls unexposed, sick), 2024 Tomson, 2020 2 Paternal ASMs   - mono/polytherapy or not specified  - mono/polytherapy or not specified 0.81[0.58; 1.14]5161,052 -NAChristensen (Controls unexposed, sick), 2024 1   - monotherapy  - monotherapy 0.90[0.57; 1.42]143458 -NATomson, 2020 1 All studiesAll studies 0.84[0.64; 1.10]6591,5100%NAChristensen (Controls unexposed, sick), 2024 Tomson, 2020 20.210.01.0

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 18646, 18644, 18647

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 0.83[0.59; 1.17]43,8461,017 -NAChristensen (Controls unexposed, general pop), 2024 1 unexposed, sick controlsunexposed, sick controls 0.84[0.64; 1.10]6591,5100%NAChristensen (Controls unexposed, sick), 2024 Tomson, 2020 2 exposed to other treatment, sick controlsexposed to other treatment, sick controls 0.67[0.46; 0.98]1321,336 -NAChristensen (Controls exposed to LTG/LEV), 2024 1 siblingssiblings 0.72[0.30; 1.71]26303 -NAChristensen (Controls unexposed, sibling), 2024 10.510.01.0