Topiramate (All indications)

Intrauterine deaths (as a whole or unspecified)

id	Study   Auto Meador (Topiramate) (Controls exposed to Lamotrigine, sick), 2020Meador (Topiramate) (Controls unexposed, disease free), 2020Meador (Topiramate) (Controls unexposed, sick), 2020Trivedi (Topiramate) (Controls exposed to Lamotrigine, sick), 2018Trivedi (Topiramate) (Controls unexposed, sick), 2018Vajda (Topiramate) (Controls exposed to Lamotrigine, sick), 2018Vajda (Topiramate) (Controls unexposed, sick), 2018Arkilo (Topiramate), 2015	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.
S8564 R28485	Meador (Topiramate) (Controls exposed to Lamotrigine, sick), 2020	Fetal loss (Spontaneous miscarriages and fetal death)	1st trimester	prospective cohort	exposed to other treatment, sick excluded	Adjustment: No	2.84 [0.13;62.17] C excluded (control group)	0/6   3/113	3	6		ref
S8565 R28489	Meador (Topiramate) (Controls unexposed, disease free), 2020	Fetal loss (Spontaneous miscarriages and fetal death)	1st trimester	prospective cohort	unexposed, disease free excluded	Adjustment: No	19.18 [0.35;1060.61] C excluded (control group)	0/6   0/106	0	6		ref
S8566 R28493	Meador (Topiramate) (Controls unexposed, sick), 2020	Fetal loss (Spontaneous miscarriages and fetal death)	1st trimester	prospective cohort	unexposed, sick	Adjustment: No	2.64 [0.05;149.97] C	0/6   0/15	0	6		ref
S8578 R28537	Trivedi (Topiramate) (Controls exposed to Lamotrigine, sick), 2018	Spontaneous fetal loss (both spontaneous abortion before 20 weeks of gestation and stillbirths occurring after 20 weeks of gestation)	1st trimester	prospective cohort	exposed to other treatment, sick excluded	Adjustment: No	9.17 [1.91;43.94] C excluded (control group)	5/11   4/48	9	11		ref
S8579 R28538	Trivedi (Topiramate) (Controls unexposed, sick), 2018	Spontaneous fetal loss (both spontaneous abortion before 20 weeks of gestation and stillbirths occurring after 20 weeks of gestation)	1st trimester	prospective cohort	unexposed, sick	Adjustment: Yes	38.86 [5.02;301.19]	5/11   5/178	10	11		ref
S8580 R28539	Vajda (Topiramate) (Controls exposed to Lamotrigine, sick), 2018	Intrauterine foetal death	throughout pregnancy	prospective cohort	exposed to other treatment, sick excluded	Adjustment: No	0.53 [0.07;4.08] C excluded (control group)	1/51   14/382	15	51		ref
S8581 R28540	Vajda (Topiramate) (Controls unexposed, sick), 2018	Intrauterine foetal death	throughout pregnancy	prospective cohort	unexposed, sick	Adjustment: No	3.33 [0.21;52.36]	1/51   1/170	2	51		ref
S8554 R28460	Arkilo (Topiramate), 2015	Unsuccessful pregnancies (miscarriages/stillbirths)	during pregnancy (anytime or not specified)	retrospective cohort	exposed to other treatment, sick	Adjustment: No	2.87 [0.09;91.05] C	0/2   2/24	2	2		ref
					Total	4 studies	9.39 [2.18;40.53]		14	70
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 8578, 8580, 8564, 8565