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

Cognitive developmental disorders/delay (3-6 years old)

R analysis
id Study   Lib. in paper Exposition period    Study type 
 Control type 
 
Tags OR 95%CI x1/n1 x0/n0 no cases no exposed ROB Ref.
S19376
R82499		 Straub (Controls unexposed, sick) (Phenobarbital) (Epilepsy), 2026 Intellectual disability - ICD-10 codes: F70-F79 - Mean follow up (full cohort): 3.4 years during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed, sick Adjustment: Yes 6.00 [1.22;29.42] -/249   26/8,887 - 249
ref
S9160
R46438		 Coste (Phenobarbital) (Controls exposed to Lamotrigine, sick), 2020 Diagnosis Mental retardation (F70–F79) (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 2.25 [0.29;17.22] C
excluded (control group) 		1/84   15/2,813 16 84
ref
S9161
R46439		 Coste (Phenobarbital) (Controls unexposed, NOS), 2020 Diagnosis Mental retardation (F70–F79) (mean age of 3.6 years old) during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes 3.00 [0.40;21.40] 1/84   3,398/1,710,441 3,399 84
ref
S9165
R46435		 Kasradze (Phenobarbital) (Controls exposed to Lamotrigine, sick), 2017 Full scale IQ (WPPSI-4) (mean age 4-4.5 years old) during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick excluded Adjustment: No extrapolated (cont. endpoint) 0.95 [0.05;17.27]
excluded (control group) 		-/3   -/3 - 3
ref
S9166
R46436		 Kasradze (Phenobarbital) (Controls unexposed, disease free), 2017 Full scale IQ (WPPSI-4) (mean age 4-4.5 years old) during pregnancy (anytime or not specified) prospective cohort unexposed, disease free Adjustment: No extrapolated (cont. endpoint) Matched 19.35 [2.16;173.39] -/3   -/50 - 3
ref
S9174
R46437		 Shankaran (Phenobarbital) (Other indications), 1996 General Cognitive Index (The McCarthy Scales of Children’s Abilities) days before delivery excluded randomized controlled trial unexposed, sick Adjustment: Randomisation extrapolated (cont. endpoint) 0.47 [0.22;0.98]
excluded (exposition period) 		-/41   -/55 - 41
ref
Total 3 studies 6.50 [2.20;19.16] 3,399 336
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

StudyTE95% CIn casesn exposedweightROBABCDEF Straub (Controls unexposed, sick) (Phenobarbital) (Epilepsy), 2026Straub, 2026 1 6.00[1.22; 29.42]-24946%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: unclearROB mesure: criticalROB reporting: moderate Coste (Phenobarbital) (Controls unexposed, NOS), 2020Coste, 2020 2 3.00[0.40; 21.40]3,3998430%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Kasradze (Phenobarbital) (Controls unexposed, disease free), 2017Kasradze, 2017 3 19.35[2.16; 173.39]-324%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: criticalROB mesure: lowROB reporting: moderate Total (3 studies) I2 = 0% 6.50[2.20; 19.16]3,3993360.950.01.0ROB: A: confounding, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, sick) (Phenobarbital) (Epilepsy; 2: Phenobarbital) (Controls unexposed, NOS; 3: Phenobarbital) (Controls unexposed, disease free;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 6.50[2.20; 19.16]3,3993360%NAStraub (Controls unexposed, sick) (Phenobarbital) (Epilepsy), 2026 Coste (Phenobarbital) (Controls unexposed, NOS), 2020 Kasradze (Phenobarbital) (Controls unexposed, disease free), 2017 3 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 7.18[1.16; 44.46]3,3998734%NACoste (Phenobarbital) (Controls unexposed, NOS), 2020 Kasradze (Phenobarbital) (Controls unexposed, disease free), 2017 2 unexposed, sickunexposed, sick 6.00[1.22; 29.46]-249 -NAStraub (Controls unexposed, sick) (Phenobarbital) (Epilepsy), 2026 1 Tags Adjustment   - No  - No 19.35[2.16; 173.37]-3 -NAKasradze (Phenobarbital) (Controls unexposed, disease free), 2017 1   - Yes  - Yes 4.58[1.32; 15.87]3,3993330%NAStraub (Controls unexposed, sick) (Phenobarbital) (Epilepsy), 2026 Coste (Phenobarbital) (Controls unexposed, NOS), 2020 2 extrapolated (cont. endpoint)extrapolated (cont. endpoint) 19.35[2.16; 173.37]-3 -NAKasradze (Phenobarbital) (Controls unexposed, disease free), 2017 1 MatchedMatched 19.35[2.16; 173.37]-3 -NAKasradze (Phenobarbital) (Controls unexposed, disease free), 2017 1 All studiesAll studies 6.50[2.20; 19.16]3,3993360%NAStraub (Controls unexposed, sick) (Phenobarbital) (Epilepsy), 2026 Coste (Phenobarbital) (Controls unexposed, NOS), 2020 Kasradze (Phenobarbital) (Controls unexposed, disease free), 2017 30.550.01.0

Publication bias and p-hacking diagnosis

funnel plot

Funnel plot not drawn. Less than 3 points.

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

not enought points

p values plot

Funnel plot not drawn. Less than 3 points.

Sub-groups analysis using all included studies

excluded 9165, 9160

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 7.18[1.16; 44.46]3,3998734%NACoste (Phenobarbital) (Controls unexposed, NOS), 2020 Kasradze (Phenobarbital) (Controls unexposed, disease free), 2017 2 unexposed, sick controlsunexposed, sick controls 6.00[1.22; 29.46]17249 -NAStraub (Controls unexposed, sick) (Phenobarbital) (Epilepsy), 2026 1 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.70[0.32; 9.02]16870%NACoste (Phenobarbital) (Controls exposed to Lamotrigine, sick), 2020 Kasradze (Phenobarbital) (Controls exposed to Lamotrigine, sick), 2017 20.510.01.0