Phenobarbital (Epilepsy)

Neuro-developmental disorders (as a whole)

id	Study   Auto Coste (Phenobarbital) (Controls exposed to Lamotrigine, sick), 2020Coste (Phenobarbital) (Controls unexposed, NOS), 2020Dean (Phenobarbital) (Controls exposed to Lamotrigine, sick), 2007Dean (Phenobarbital) (Controls unexposed, sick), 2007Katz (Phenobarbital), 2001Van der Pol (Phenobarbital) (Controls unexposed, disease free), 1991Van der Pol (Phenobarbital) (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.
S7981 R24260	Coste (Phenobarbital) (Controls exposed to Lamotrigine, sick), 2020	Diagnosis Disorders of psychological development (F80–F89) (mean age of 3.6 years old)	during pregnancy (anytime or not specified)	retrospective cohort (claims database)	exposed to other treatment, sick excluded	Adjustment: No Controls: mixed indications	1.24 [0.17;9.26] C excluded (control group)	1/84   27/2,813	28	84		ref
S7809 R23151	Coste (Phenobarbital) (Controls unexposed, NOS), 2020	Diagnosis Disorders of psychological development (F80–F89) (mean age of 3.6 years old)	during pregnancy (anytime or not specified)	retrospective cohort (claims database)	unexposed (general population or NOS)	Adjustment: Yes	0.90 [0.10;6.70]	1/84   10,010/1,710,441	10,011	84		ref
S6675 R18474	Dean (Phenobarbital) (Controls exposed to Lamotrigine, sick), 2007	Neurodevelopmental disorder (mean age in years: m1=16.25 and m0=1.5)	during pregnancy (anytime or not specified)	retrospective cohort	exposed to other treatment, sick excluded	Adjustment: No	1.24 [0.06;26.43] C excluded (control group)	7/50   0/4	7	50		ref
S6670 R18463	Dean (Phenobarbital) (Controls unexposed, sick), 2007	Neurodevelopmental disorder (mean age in years: m1=16.25 and m0=15.25)	during pregnancy (anytime or not specified)	retrospective cohort	unexposed, sick	Adjustment: No	2.33 [0.57;9.62] C	7/50   3/46	10	50		ref
S6792 R19173	Katz (Phenobarbital), 2001	Developmental delay (Based on the DSM-IV-TR criteria)	during pregnancy (anytime or not specified)	retrospective cohort	exposed to other treatment, sick	Adjustment: No	0.56 [0.01;37.57] C	0/5   0/3	0	5		ref
S5526 R19259	Van der Pol (Phenobarbital) (Controls unexposed, disease free), 1991	Nonoptimal school career	throughout pregnancy	prospective cohort	unexposed, disease free excluded	Adjustment: No Matched	2.20 [0.55;8.77] C excluded (control group)	4/12   10/54	14	12		ref
S6824 R19310	Van der Pol (Phenobarbital) (Controls unexposed, sick), 1991	Nonoptimal school career	throughout pregnancy	prospective cohort	unexposed, sick	Adjustment: No	1.70 [0.36;8.09] C	4/12   5/22	9	12		ref
					Total	4 studies	1.63 [0.65;4.08]		10,030	151
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 5526, 6675, 7981