Valproate (Epilepsy)

Neonatal medical care

id	Study   Auto Aydin (Valproate) (Controls exposed to Lamotrigine, sick), 2020Aydin (Valproate) (Controls unexposed, sick), 2020Putignano (Valproate), 2019Artama (Valproate) (Controls exposed to Lamotrigine, sick), 2013Artama (Valproate) (Controls unexposed, disease free), 2013Artama (Valproate) (Controls unexposed, sick), 2013Viinikainen (Valproate) (Controls unexposed, disease free) a, 2006D'Souza (Valproate) (Controls unexposed, disease free), 1991D'Souza (Valproate) (Controls unexposed, sick), 1991	Lib. in paper	Exposition period  Auto during pregnancy (anytime or not specified)1st trimester2nd trimester3rd trimester2nd and/or 3rd trimesterthroughout pregnancyearly pregnancydays before deliverylate pregnancypreconception-onlypericonceptionalpreconceptional for kinetic reasonat least 1st trimester3 months (or more) before pregnancy or during pregnancy1st and 2nd trimester3 months or more before pregnancy or1st trimester	Study type  All studies Case control excluded Only case control	Control type    Auto unexposed (general population or NOS)unexposed, sickunexposed, disease freeexposed to other treatment, sicknot specifiedwhatever (meta-analysis)	Tags	OR 95%CI	x1/n1 x0/n0	no cases	no exposed	ROB	Ref.
S8087 R24745	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
S7922 R24607	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
S7460 R25142	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
S5931 R15125	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
S5911 R14904	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
S5919 R15000	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
S6169 R16234	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
S6687 R18662	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
S6695 R18823	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	5 studies	2.01 [1.54;2.62]		2,092	771
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

Sensitivity analysis

Publication bias and p-hacking diagnosis

Sub-groups analysis using all included studies

excluded 6687, 5931, 5911, 8087