Phenobarbital (All indications) updated on 04-22-2025

Preterm (< 37 weeks)

id	Study   Auto The NAAED (Phenobarbital) (Controls exposed to LTG) (Indications NOS), 2025The NAAED (Phenobarbital) (Controls unexposed, disease free) (Indications NOS), 2025Leite (Phenobarbital) (Epilepsy), 2024Coste (Phenobarbital) (Controls exposed to Lamotrigine, sick), 2020Coste (Phenobarbital) (Controls unexposed, NOS), 2020Kilic (Phenobarbital) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014Kilic (Phenobarbital) (Controls unexposed NOS) (Mixed indications), 2014Kilic (Phenobarbital) (Controls unexposed, sick) (Mixed indications), 2014Endo (Phenobarbital) (Controls unexposed, disease free), 2004Endo (Phenobarbital) (Controls unexposed, sick), 2004Koch (Phenobarbital), 1996Van 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 trimesterPaternal exp. genotoxic window only (0–3 months preconception)Paternal exposure: epigenetic window only (3–xxx months preconception)Paternal exposure: genotoxic/epigenetic window (0–xxx months preconception)Paternal exposure: other window	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 specifiedsiblingwhatever (meta-analysis)	Tags	OR 95%CI	x1/n1 x0/n0	no cases	no exposed	ROB	Ref.
S16192 R79493	The NAAED (Phenobarbital) (Controls exposed to LTG) (Indications NOS), 2025	Preterm (<37 wk)	at least 1st trimester	prospective cohort	exposed to other treatment, sick excluded	Adjustment: No	0.75 [0.43;1.29] C excluded (control group)	15/200   241/2,461	256	200		ref
S16182 R79491	The NAAED (Phenobarbital) (Controls unexposed, disease free) (Indications NOS), 2025	Preterm (<37 wk)	at least 1st trimester	prospective cohort	unexposed, disease free	Adjustment: No	0.48 [0.28;0.83] C	15/200   189/1,311	204	200		ref
S18022 R76117	Leite (Phenobarbital) (Epilepsy), 2024	Premature Delivery <37weeks	during pregnancy (anytime or not specified)	retrospective cohort	unexposed, disease free	Adjustment: No	0.60 [0.24;1.48]	-/70   98/492	-	70		ref
S9160 R31483	Coste (Phenobarbital) (Controls exposed to Lamotrigine, sick), 2020	Gestational age at birth (< 37 WA)	during pregnancy (anytime or not specified)	retrospective cohort (claims database)	exposed to other treatment, sick excluded	Adjustment: No Controls: mixed indications	0.95 [0.38;2.39] C excluded (control group)	5/84   175/2,813	180	84		ref
S9161 R31501	Coste (Phenobarbital) (Controls unexposed, NOS), 2020	Gestational age at birth (< 37 WA)	during pregnancy (anytime or not specified)	retrospective cohort (claims database)	unexposed (general population or NOS)	Adjustment: No	1.12 [0.45;2.77] C	5/84   91,255/1,710,441	91,260	84		ref
S9138 R31383	Kilic (Phenobarbital) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014	Preterm (< 37 weeks)	during pregnancy (anytime or not specified)	population based cohort retrospective	exposed to other treatment, sick excluded	Adjustment: No	1.12 [0.56;2.23] C excluded (control group)	10/96   83/880	93	96		ref
S9139 R31386	Kilic (Phenobarbital) (Controls unexposed NOS) (Mixed indications), 2014	Preterm (< 37 weeks)	during pregnancy (anytime or not specified)	population based cohort retrospective	unexposed (general population or NOS) excluded	Adjustment: No	2.10 [1.20;3.70] excluded (control group)	10/96   33,974/676,834	33,984	96		ref
S9140 R31389	Kilic (Phenobarbital) (Controls unexposed, sick) (Mixed indications), 2014	Preterm (< 37 weeks)	during pregnancy (anytime or not specified)	population based cohort retrospective	unexposed, sick	Adjustment: No Controls: epilepsy indication	1.49 [0.77;2.89] C	10/96   383/5,296	393	96		ref
S9104 R31260	Endo (Phenobarbital) (Controls unexposed, disease free), 2004	Preterm delivery (< week 37)	throughout pregnancy	retrospective cohort	unexposed, disease free excluded	Adjustment: No	0.59 [0.07;4.70] C excluded (control group)	1/10   104/656	105	10		ref
S9105 R31275	Endo (Phenobarbital) (Controls unexposed, sick), 2004	Preterm delivery (< week 37)	throughout pregnancy	retrospective cohort	unexposed, sick	Adjustment: No	0.18 [0.00;12.84] C	1/10   0/1	1	10		ref
S9167 R31545	Koch (Phenobarbital), 1996	Prematurity (< 37 weeks)	during pregnancy (anytime or not specified)	prospective cohort	unexposed (general population or NOS)	Adjustment: No Matched	6.05 [0.21;177.04] C	0/4   1/65	1	4		ref
S9172 R31562	Van der Pol (Phenobarbital) (Controls unexposed, disease free), 1991	Gestational age (≤ 37 wk)	throughout pregnancy	prospective cohort	unexposed, disease free excluded	Adjustment: No Matched	1.16 [0.12;11.40] C excluded (control group)	1/12   4/55	5	12		ref
S9173 R31587	Van der Pol (Phenobarbital) (Controls unexposed, sick), 1991	Gestational age (≤ 37 wk)	throughout pregnancy	prospective cohort	unexposed, sick	Adjustment: No	0.91 [0.07;11.19] C	1/12   2/22	3	12		ref
					Total	7 studies	0.84 [0.50;1.40]		91,862	476
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 9172, 9104, 9138, 9139, 9160, 16192

Umbrella review (other published meta-analyses)