Valproate (All indications) updated on 04-22-2025

Neonatal medical care

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.
S18706
R79590		 Mazzone (Valproate) (Controls exposed to LTG) (Mixed indications), 2025 Neonatal intensive care unit admission during pregnancy (anytime or not specified) population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No 1.37 [0.95;1.97] C
excluded (control group) 		43/315   152/1,469 195 315
ref
S18708
R79606		 Mazzone (Valproate) (Controls unexposed, NOS) (Mixed indications), 2025 Neonatal intensive care unit admission during pregnancy (anytime or not specified) population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes 1.96 [1.29;2.97] 43/315   44,768/624,794 44,811 315
ref
S9287
R32243		 Aydin (Valproate) (Controls exposed to Lamotrigine, sick), 2020 Neonatal intensive care unit (NICU) throughout pregnancy retrospective cohort exposed to other treatment, sick excluded Adjustment: No 0.09 [0.00;2.17] C
excluded (control group) 		0/11   2/7 2 11
ref
S9288
R32253		 Aydin (Valproate) (Controls unexposed, sick), 2020 Neonatal intensive care unit (NICU) throughout pregnancy retrospective cohort unexposed, sick Adjustment: No 0.37 [0.02;8.48] C 0/11   2/22 2 11
ref
S9324
R32504		 Putignano (Valproate), 2019 Intensive care unit (ICU) stay during pregnancy (anytime or not specified) retrospective cohort unexposed (general population or NOS) Adjustment: No Matched 1.40 [0.07;29.36] C 0/131   2/917 2 131
ref
S9314
R32449		 Bank (Valproate) (Mixed indications), 2017 Admission to neonatal intensive care unit (NICU) or Special Care Nursery during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick Adjustment: No 0.41 [0.02;8.43] C 0/6   6/36 6 6
ref
S9283
R32203		 Artama (Valproate) (Controls exposed to Lamotrigine, sick), 2013 Admission to neonatal care unit 3rd trimester population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No 1.22 [0.75;1.97] C
excluded (control group) 		110/600   24/154 134 600
ref
S9284
R32215		 Artama (Valproate) (Controls unexposed, disease free), 2013 Admission to neonatal care unit 3rd trimester population based cohort retrospective unexposed, disease free excluded Adjustment: Yes 2.59 [2.09;3.21]
excluded (control group) 		110/600   49,612/689,482 49,722 600
ref
S9285
R32227		 Artama (Valproate) (Controls unexposed, sick), 2013 Admission to neonatal care unit 3rd trimester population based cohort retrospective unexposed, sick Adjustment: Yes 2.02 [1.53;2.67] 110/600   152/1,708 262 600
ref
S9328
R32527		 Viinikainen (Valproate) (Controls unexposed, disease free) a, 2006 Admission to a neonatal unit throughout pregnancy prospective cohort unexposed, disease free Adjustment: No 2.10 [0.73;6.06] C 4/28   1,822/24,778 1,826 28
ref
S9297
R32322		 D'Souza (Valproate) (Controls unexposed, disease free), 1991 Idiopathic respiratory distress throughout pregnancy prospective cohort unexposed, disease free excluded Adjustment: No Matched 123.00 [1.00;15058.31] C
excluded (control group) 		0/1   0/62 0 1
ref
S9298
R32351		 D'Souza (Valproate) (Controls unexposed, sick), 1991 Idiopathic respiratory distress throughout pregnancy prospective cohort unexposed, sick Adjustment: No 15.00 [0.12;1923.88] C 0/1   0/8 0 1
ref
Total 7 studies 1.98 [1.58;2.47] 46,909 1,092
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 Mazzone (Valproate) (Controls unexposed, NOS) (Mixed indications), 2025Mazzone, 2025 1 1.96[1.29; 2.97]44,81131529%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Aydin (Valproate) (Controls unexposed, sick), 2020Aydin, 2020 2 0.37[0.02; 8.48]2111%ROB confusion: criticalROB selection: criticalROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Putignano (Valproate), 2019Putignano, 2019 3 1.40[0.07; 29.36]21311%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Bank (Valproate) (Mixed indications), 2017Bank, 2017 4 0.41[0.02; 8.43]661%ROB confusion: criticalROB selection: lowROB classification: lowROB missing: lowROB mesure: moderateROB reporting: moderate Artama (Valproate) (Controls unexposed, sick), 2013Artama, 2013 5 2.02[1.53; 2.67]26260065%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Viinikainen (Valproate) (Controls unexposed, disease free) a, 2006Viinikainen, 2006 6 2.10[0.73; 6.06]1,826284%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate D'Souza (Valproate) (Controls unexposed, sick), 1991D'Souza, 1991 7 15.00[0.12; 1923.88]010%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (7 studies) I2 = 0% 1.98[1.58; 2.47]46,9091,0920.250.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Valproate) (Controls unexposed, NOS) (Mixed indications; 2: Valproate) (Controls unexposed, sick; 3: Valproate; 4: Valproate) (Mixed indications; 5: Valproate) (Controls unexposed, sick; 6: Valproate) (Controls unexposed, disease free) ; 7: Valproate) (Controls unexposed, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.98[1.58; 2.47]46,9091,0920%NAMazzone (Valproate) (Controls unexposed, NOS) (Mixed indications), 2025 Aydin (Valproate) (Controls unexposed, sick), 2020 Putignano (Valproate), 2019 Bank (Valproate) (Mixed indications), 2017 Artama (Valproate) (Controls unexposed, sick), 2013 Viinikainen (Valproate) (Controls unexposed, disease free) a, 2006 D'Souza (Valproate) (Controls unexposed, sick), 1991 7 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.97[1.34; 2.89]46,6394740%NAMazzone (Valproate) (Controls unexposed, NOS) (Mixed indications), 2025 Putignano (Valproate), 2019 Viinikainen (Valproate) (Controls unexposed, disease free) a, 2006 3 unexposed, sickunexposed, sick 2.01[1.52; 2.65]2646120%NAAydin (Valproate) (Controls unexposed, sick), 2020 Artama (Valproate) (Controls unexposed, sick), 2013 D'Souza (Valproate) (Controls unexposed, sick), 1991 3 exposed to other treatment, sickexposed to other treatment, sick 0.41[0.02; 8.43]66 -NABank (Valproate) (Mixed indications), 2017 1 Tags Adjustment   - No  - No 1.63[0.67; 3.99]1,8361770%NAAydin (Valproate) (Controls unexposed, sick), 2020 Putignano (Valproate), 2019 Bank (Valproate) (Mixed indications), 2017 Viinikainen (Valproate) (Controls unexposed, disease free) a, 2006 D'Souza (Valproate) (Controls unexposed, sick), 1991 5   - Yes  - Yes 2.00[1.59; 2.52]45,0739150%NAMazzone (Valproate) (Controls unexposed, NOS) (Mixed indications), 2025 Artama (Valproate) (Controls unexposed, sick), 2013 2 MatchedMatched 1.40[0.07; 29.36]2131 -NAPutignano (Valproate), 2019 1 All studiesAll studies 1.98[1.58; 2.47]46,9091,0920%NAMazzone (Valproate) (Controls unexposed, NOS) (Mixed indications), 2025 Aydin (Valproate) (Controls unexposed, sick), 2020 Putignano (Valproate), 2019 Bank (Valproate) (Mixed indications), 2017 Artama (Valproate) (Controls unexposed, sick), 2013 Viinikainen (Valproate) (Controls unexposed, disease free) a, 2006 D'Souza (Valproate) (Controls unexposed, sick), 1991 70.150.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-5.86.52.9720.000Mazzone (Valproate) (Controls unexposed, NOS) (Mixed indications), 2025Aydin (Valproate) (Controls unexposed, sick), 2020Putignano (Valproate), 2019Bank (Valproate) (Mixed indications), 2017Artama (Valproate) (Controls unexposed, sick), 2013Viinikainen (Valproate) (Controls unexposed, disease free) a, 2006D'Souza (Valproate) (Controls unexposed, sick), 1991

Asymetry test p-value = 0.4021 (by Egger's regression)

slope=0.7507 (0.1108); intercept=-0.3353 (0.3664); t=0.9152; p=0.4021

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 9297, 9283, 9284, 9287, 18706

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 2.42[1.98; 2.97]96,3611,0753%NAMazzone (Valproate) (Controls unexposed, NOS) (Mixed indications), 2025 Putignano (Valproate), 2019 Artama (Valproate) (Controls unexposed, disease free), 2013 Viinikainen (Valproate) (Controls unexposed, disease free) a, 2006 D'Souza (Valproate) (Controls unexposed, disease free), 1991 5 unexposed, sick controlsunexposed, sick controls 2.01[1.52; 2.65]2646120%NAAydin (Valproate) (Controls unexposed, sick), 2020 Artama (Valproate) (Controls unexposed, sick), 2013 D'Souza (Valproate) (Controls unexposed, sick), 1991 3 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.25[0.89; 1.76]33793212%NAMazzone (Valproate) (Controls exposed to LTG) (Mixed indications), 2025 Aydin (Valproate) (Controls exposed to Lamotrigine, sick), 2020 Bank (Valproate) (Mixed indications), 2017 Artama (Valproate) (Controls exposed to Lamotrigine, sick), 2013 40.510.01.0