Valproate (All indications)

Low birth weight (< 2500g)

id	Study   Auto Coste (Valproate) (Controls exposed to Lamotrigine, sick), 2020Coste (Valproate) (Controls unexposed, NOS), 2020Wen (Valproate) (Mixed indications), 2017Kilic (Valproate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014Kilic (Valproate) (Controls unexposed NOS) (Mixed indications), 2014Kilic (Valproate) (Controls unexposed, sick) (Mixed indications), 2014Artama (Valproate) (Controls exposed to Lamotrigine, sick), 2013Artama (Valproate) (Controls unexposed, disease free), 2013Artama (Valproate) (Controls unexposed, sick), 2013Veiby (Valproate) (Controls exposed to Lamotrigine, sick) b, 2013Veiby (Valproate) (Controls unexposed, disease free) b, 2013Veiby (Valproate) (Controls unexposed, sick) b, 2013Kini (Valproate) (Controls unexposed, sick), 2006	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.
S9391 R32874	Coste (Valproate) (Controls exposed to Lamotrigine, sick), 2020	Weight at birth <2500 g	during pregnancy (anytime or not specified)	retrospective cohort (claims database)	exposed to other treatment, sick excluded	Adjustment: No	1.51 [1.14;2.00] C excluded (control group)	88/991   128/2,108	216	991		ref
S9392 R32892	Coste (Valproate) (Controls unexposed, NOS), 2020	Weight at birth <2500 g	during pregnancy (anytime or not specified)	retrospective cohort (claims database)	unexposed (general population or NOS)	Adjustment: No	1.73 [1.39;2.15] C	88/991   91,455/1,710,441	91,543	991		ref
S9441 R33153	Wen (Valproate) (Mixed indications), 2017	Low birth weight ( 1500 - 2500 g)	during pregnancy (anytime or not specified)	retrospective cohort (claims database)	unexposed (general population or NOS)	Adjustment: No	1.65 [1.08;2.53] C	24/226   2,945/43,956	2,969	226		ref
S9445 R33170	Kilic (Valproate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014	Low birth weight (< 2500 g)	during pregnancy (anytime or not specified)	population based cohort retrospective	exposed to other treatment, sick excluded	Adjustment: No	1.19 [0.71;2.01] C excluded (control group)	22/340   48/876	70	340		ref
S9446 R33173	Kilic (Valproate) (Controls unexposed NOS) (Mixed indications), 2014	Low birth weight (< 2500 g)	during pregnancy (anytime or not specified)	population based cohort retrospective	unexposed (general population or NOS) excluded	Adjustment: Yes	1.70 [1.10;2.60] excluded (control group)	22/340   23,503/673,844	23,525	340		ref
S9447 R33176	Kilic (Valproate) (Controls unexposed, sick) (Mixed indications), 2014	Low birth weight (< 2500 g)	during pregnancy (anytime or not specified)	population based cohort retrospective	unexposed, sick	Adjustment: No Controls: epilepsy indication	1.40 [0.89;2.19] C	22/340   249/5,275	271	340		ref
S9283 R32210	Artama (Valproate) (Controls exposed to Lamotrigine, sick), 2013	Low birth weight (< 2500g)	during pregnancy (anytime or not specified)	population based cohort retrospective	exposed to other treatment, sick excluded	Adjustment: No	1.15 [0.47;2.83] C excluded (control group)	28/703   6/173	34	703		ref
S9284 R32222	Artama (Valproate) (Controls unexposed, disease free), 2013	Low birth weight (< 2500g)	during pregnancy (anytime or not specified)	population based cohort retrospective	unexposed, disease free excluded	Adjustment: Yes	1.14 [0.78;1.67] excluded (control group)	28/703   21,546/719,509	21,574	703		ref
S9285 R32234	Artama (Valproate) (Controls unexposed, sick), 2013	Low birth weight (< 2500g)	during pregnancy (anytime or not specified)	population based cohort retrospective	unexposed, sick	Adjustment: Yes	1.00 [0.63;1.61]	28/703   65/1,793	93	703		ref
S9424 R33070	Veiby (Valproate) (Controls exposed to Lamotrigine, sick) b, 2013	Low birth weight (< 2500 grams)	during pregnancy (anytime or not specified)	prospective cohort	exposed to other treatment, sick excluded	Adjustment: No	1.31 [0.31;5.51] C excluded (control group)	3/40   6/103	9	40		ref
S9426 R33088	Veiby (Valproate) (Controls unexposed, disease free) b, 2013	Low birth weight (< 2500 grams)	during pregnancy (anytime or not specified)	prospective cohort	unexposed, disease free excluded	Adjustment: Yes	1.30 [0.30;5.30] excluded (control group)	3/40   5,024/106,899	5,027	40		ref
S9427 R33102	Veiby (Valproate) (Controls unexposed, sick) b, 2013	Low birth weight (< 2500 grams)	during pregnancy (anytime or not specified)	prospective cohort	unexposed, sick	Adjustment: No	1.88 [0.52;6.73] C	3/40   16/386	19	40		ref
S9346 R32596	Kini (Valproate) (Controls unexposed, sick), 2006	Birth weight <2500 g	during pregnancy (anytime or not specified)	retrospective cohort	unexposed, sick	Adjustment: No	0.86 [0.30;2.46] C	6/63   11/101	17	63		ref
					Total	6 studies	1.49 [1.23;1.82]		94,912	2,363
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 9283, 9284, 9424, 9426, 9445, 9446, 9391