Phenobarbital (All indications)

Preterm (< 37 weeks)

R analysis

id	Study	Lib. in paper	Exposition period	Study type All studies Case control excluded Only case control	Control type	Tags	OR 95%CI	x1/n1 x0/n0	no cases	no exposed	ROB	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	5 studies	1.34 [0.80;2.23]		91,658	206
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

1: Phenobarbital) (Controls unexposed, NOS; 2: Phenobarbital) (Controls unexposed, sick) (Mixed indications; 3: Phenobarbital) (Controls unexposed, sick; 4: Phenobarbital; 5: Phenobarbital) (Controls unexposed, sick;

Sensitivity analysis

Publication bias and p-hacking diagnosis

funnel plot

Asymetry test p-value = 0.7239 (by Egger's regression)

slope=0.4013 (0.3546); intercept=-0.2351 (0.6058); t=0.3881; p=0.7239

p values plot

Sub-groups analysis using all included studies

excluded 9172, 9104, 9138, 9139, 9160

S9160 R31483	Coste (Phenobarbital) (Controls exposed to Lamotrigine, sick), 2020	Gestational age at birth (< 37 WA) (90)	during pregnancy (anytime or not specified)	exposed to other treatment, sick	0.95 [0.38;2.39]	5/84 175/2813
S9161 R31501	Coste (Phenobarbital) (Controls unexposed, NOS), 2020	Gestational age at birth (< 37 WA) (90)	during pregnancy (anytime or not specified)	unexposed (general population or NOS)	1.12 [0.45;2.77]	5/84 91255/1710441
S9138 R31383	Kilic (Phenobarbital) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014	Preterm (< 37 weeks) (90)	during pregnancy (anytime or not specified)	exposed to other treatment, sick	1.12 [0.56;2.23]	10/96 83/880
S9139 R31386	Kilic (Phenobarbital) (Controls unexposed NOS) (Mixed indications), 2014	Preterm (< 37 weeks) (90)	during pregnancy (anytime or not specified)	unexposed (general population or NOS)	2.10 [1.20;3.70]	10/96 33974/676834
S9140 R31389	Kilic (Phenobarbital) (Controls unexposed, sick) (Mixed indications), 2014	Preterm (< 37 weeks) (90)	during pregnancy (anytime or not specified)	unexposed, sick	1.49 [0.77;2.89]	10/96 383/5296
S9104 R31260	Endo (Phenobarbital) (Controls unexposed, disease free), 2004	Preterm delivery (< week 37) (90)	throughout pregnancy	unexposed, disease free	0.59 [0.07;4.70]	1/10 104/656
S9105 R31275	Endo (Phenobarbital) (Controls unexposed, sick), 2004	Preterm delivery (< week 37) (90)	throughout pregnancy	unexposed, sick	0.18 [0.00;12.84]	1/10 0/1
S9167 R31545	Koch (Phenobarbital), 1996	Prematurity (< 37 weeks) (90)	during pregnancy (anytime or not specified)	unexposed (general population or NOS)	6.05 [0.21;177.04]	0/4 1/65
S9172 R31562	Van der Pol (Phenobarbital) (Controls unexposed, disease free), 1991	Gestational age (≤ 37 wk) (90)	throughout pregnancy	unexposed, disease free	1.16 [0.12;11.40]	1/12 4/55
S9173 R31587	Van der Pol (Phenobarbital) (Controls unexposed, sick), 1991	Gestational age (≤ 37 wk) (90)	throughout pregnancy	unexposed, sick	0.91 [0.07;11.19]	1/12 2/22