Lamotrigine (All indications)

Low Apgar score (< 7) (at 5 min)

id	Study   Auto Christensen (Lamotrigine) (Controls unexposed NOS) (Mixed indications), 2015Christensen (Lamotrigine) (Controls unexposed, sick) (Mixed indications), 2015Artama (Lamotrigine) (Controls unexposed, disease free), 2013Artama (Lamotrigine) (Controls unexposed, sick), 2013Veiby (Lamotrigine) (Controls unexposed, disease free) b, 2013Veiby (Lamotrigine) (Controls unexposed, sick) b, 2013Borthen (Lamotrigine) (Controls unexposed, disease free), 2010Borthen (Lamotrigine) (Controls unexposed, sick), 2010	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.
S8961 R30349	Christensen (Lamotrigine) (Controls unexposed NOS) (Mixed indications), 2015	Low Apgar score (≤ 7) at 5 min	during pregnancy (anytime or not specified)	population based cohort propective	unexposed (general population or NOS) excluded	Adjustment: No	0.88 [0.47;1.62] excluded (control group)	10/875   8,797/674,115	8,807	875		ref
S8962 R30350	Christensen (Lamotrigine) (Controls unexposed, sick) (Mixed indications), 2015	Low Apgar score (≤ 7) at 5 min	during pregnancy (anytime or not specified)	population based cohort propective	unexposed, sick	Adjustment: No	0.90 [0.46;1.75] C	10/875   67/5,261	77	875		ref
S8902 R30058	Artama (Lamotrigine) (Controls unexposed, disease free), 2013	5-min Apgar <7	3rd trimester	population based cohort retrospective	unexposed, disease free excluded	Adjustment: Yes	1.69 [0.53;5.36] excluded (control group)	3/132   3,014/269,151	3,017	132		ref
S8903 R30070	Artama (Lamotrigine) (Controls unexposed, sick), 2013	5-min Apgar <7	3rd trimester	population based cohort retrospective	unexposed, sick	Adjustment: Yes	1.89 [0.46;7.76]	3/132   3/652	6	132		ref
S8953 R30310	Veiby (Lamotrigine) (Controls unexposed, disease free) b, 2013	Low Apgar score (< 7 at 5 min)	during pregnancy (anytime or not specified)	prospective cohort	unexposed, disease free excluded	Adjustment: No	1.20 [0.30;4.80] excluded (control group)	2/103   1,710/106,899	1,712	103		ref
S8954 R30324	Veiby (Lamotrigine) (Controls unexposed, sick) b, 2013	Low Apgar score (< 7 at 5 min)	during pregnancy (anytime or not specified)	prospective cohort	unexposed, sick	Adjustment: No	0.83 [0.18;3.90] C	2/103   9/386	11	103		ref
S8957 R30338	Borthen (Lamotrigine) (Controls unexposed, disease free), 2010	Apgar < 7 after 5 minutes	during pregnancy (anytime or not specified)	population based cohort retrospective	unexposed, disease free excluded	Adjustment: Yes	1.90 [0.90;4.00] excluded (control group)	7/233   6,022/362,302	6,029	233		ref
S8959 R30346	Borthen (Lamotrigine) (Controls unexposed, sick), 2010	Apgar < 7 after 5 minutes	during pregnancy (anytime or not specified)	population based cohort retrospective	unexposed, sick	Adjustment: No	1.89 [0.82;4.36] C	7/233   30/1,863	37	233		ref
					Total	4 studies	1.22 [0.76;1.94]		131	1,343
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 8957, 8902, 8953, 8961