Primidone AND Phenobarbital (Epilepsy) updated on 04-22-2025

Congenital heart defects

id	Study   Auto Thomas (Phenobarbital) (Controls exposed to Lamotrigine, sick), 2021Thomas (Phenobarbital) (Controls unexposed, sick), 2021Tomson (Phenobarbital or Primidone), 2018Hernández-Díaz (Phenobarbital), 2012Bànhidy (Phenobarbital or Primidone), 2011D'Souza (Phenobarbital) (Controls unexposed, disease free), 1991D'Souza (Phenobarbital) (Controls unexposed, sick), 1991Van 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.
S12840 R48387	Thomas (Phenobarbital) (Controls exposed to Lamotrigine, sick), 2021	Cardiac malformations	1st trimester	prospective cohort	exposed to other treatment, sick excluded	Adjustment: No	2.24 [0.26;19.12] C excluded (control group)	6/137   1/50	7	137		ref
S12845 R48421	Thomas (Phenobarbital) (Controls unexposed, sick), 2021	Cardiac malformations	1st trimester	prospective cohort	unexposed, sick	Adjustment: No	1.68 [0.59;4.83] C	6/137   9/340	15	137		ref
S8694 R29312	Tomson (Phenobarbital or Primidone), 2018	Cardiac malformations	at least 1st trimester	prospective cohort	exposed to other treatment, sick	Adjustment: No	4.66 [1.96;11.09] C	8/294   15/2,514	23	294		ref
S8656 R29149	Hernández-Díaz (Phenobarbital), 2012	Cardiovascular anomalies	1st trimester	prospective cohort	exposed to other treatment, sick	Adjustment: No Controls: mixed indications	13.39 [3.18;56.48] C	5/199   3/1,562	8	199		ref
S8671 R29203	Bànhidy (Phenobarbital or Primidone), 2011	Cardiovascular congenital abnormalities	throughout pregnancy	case control	unexposed, sick	Adjustment: No Matched	0.16 [0.01;3.56] C	0/6   5/15	5	6		ref
S8650 R29046	D'Souza (Phenobarbital) (Controls unexposed, disease free), 1991	Heart disease	throughout pregnancy	prospective cohort	unexposed, disease free excluded	Adjustment: No Matched	73.80 [2.36;2304.87] C excluded (control group)	1/4   0/62	1	4		ref
S8651 R29075	D'Souza (Phenobarbital) (Controls unexposed, sick), 1991	Heart disease	throughout pregnancy	prospective cohort	unexposed, sick	Adjustment: No	2.33 [0.11;50.99] C	1/4   1/8	2	4		ref
S8714 R29428	Van der Pol (Phenobarbital) (Controls unexposed, disease free), 1991	Cardiac anomaly	throughout pregnancy	prospective cohort	unexposed, disease free excluded	Adjustment: No Matched	1.55 [0.06;40.54] C excluded (control group)	0/12   1/55	1	12		ref
S8715 R29453	Van der Pol (Phenobarbital) (Controls unexposed, sick), 1991	Cardiac anomaly	throughout pregnancy	prospective cohort	unexposed, sick	Adjustment: No	1.87 [0.03;100.54] C	0/12   0/22	0	12		ref
					Total	6 studies	3.07 [1.18;8.01]		53	652
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 8650, 8714, 12840