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

Language disorders/delay

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.
S19383
R82298		 Straub (Controls exposed to LTG) (Phenobarbital) (Epilepsy), 2026 Speech or language disorder - ICD-10 codes: F80.xx (except F80.4), H93.25 - Mean follow up (full cohort): 3.4 years during pregnancy (anytime or not specified) retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No 0.90 [0.49;1.63] C
excluded (control group) 		12/249   175/3,273 187 249
ref
S19376
R82234		 Straub (Controls unexposed, sick) (Phenobarbital) (Epilepsy), 2026 Speech or language disorder - ICD-10 codes: F80.xx (except F80.4), H93.25 - Mean follow up (full cohort): 3.4 years during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed, sick Adjustment: Yes 0.75 [0.34;1.66] 12/249   456/8,887 468 249
ref
S12892
R48716		 Adams (Phenobarbital), 2022 Verbal IQ - The Wechsler Intelligence Scale for Children, 3rd Edition (WISC-III) (mean >6 years old) during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: No Matched 3.33 [1.37;8.07] -/34   -/34 - 34
ref
S15273
R62782		 Thomas a (Phenobarbitone), 2022 Verbal IQ/Verbal comprehension index (VCI) - Wechsler Intelligence Scale for Children or Adult - Ages 13 to 21 years (mean of 16.5 ± 2.2 years) during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No extrapolated (cont. endpoint) 2.58 [0.57;11.73] -/12   -/11 - 12
ref
S9160
R31493		 Coste (Phenobarbital) (Controls exposed to Lamotrigine, sick), 2020 Health care utilization: Speech therapy (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 1.63 [0.74;3.59] C
excluded (control group) 		7/84   149/2,813 156 84
ref
S9161
R31511		 Coste (Phenobarbital) (Controls unexposed, NOS), 2020 Health care utilization: Speech therapy (mean age of 3.6 years old) during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes 1.50 [0.70;3.20] 7/84   72,012/1,710,441 72,019 84
ref
S9165
R31537		 Kasradze (Phenobarbital) (Controls exposed to Lamotrigine, sick), 2017 Verbal comprehension (VCI) (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) 0.86 [0.05;15.71]
excluded (control group) 		-/3   -/3 - 3
ref
S9166
R31540		 Kasradze (Phenobarbital) (Controls unexposed, disease free), 2017 Verbal comprehension (VCI) (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 10.88 [1.25;94.80] -/3   -/50 - 3
ref
S9174
R31612		 Shankaran (Phenobarbital) (Other indications), 1996 Language delay at 24 months days before delivery excluded randomized controlled trial unexposed, sick Adjustment: Randomisation 1.04 [0.40;2.68] C
excluded (exposition period) 		10/41   13/55 23 41
ref
Total 5 studies 1.95 [0.94;4.07] 72,487 382
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 0.75[0.34; 1.66]46824926%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: unclearROB mesure: criticalROB reporting: moderate Adams (Phenobarbital), 2022Adams, 2022 2 3.33[1.37; 8.07]-3424%ROB confusion: seriousROB selection: moderateROB classification: criticalROB missing: lowROB mesure: lowROB reporting: moderate Thomas a (Phenobarbitone), 2022Thomas a, 2022 3 2.58[0.57; 11.73]-1214%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: criticalROB mesure: lowROB reporting: moderate Coste (Phenobarbital) (Controls unexposed, NOS), 2020Coste, 2020 4 1.50[0.70; 3.20]72,0198427%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Kasradze (Phenobarbital) (Controls unexposed, disease free), 2017Kasradze, 2017 5 10.88[1.25; 94.80]-39%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: criticalROB mesure: lowROB reporting: moderate Total (5 studies) I2 = 58% 1.95[0.94; 4.07]72,4873820.250.01.0ROB: A: confounding, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, sick) (Phenobarbital) (Epilepsy; 2: Phenobarbital; 3: Phenobarbitone; 4: Phenobarbital) (Controls unexposed, NOS; 5: Phenobarbital) (Controls unexposed, disease free;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.95[0.94; 4.07]72,48738258%NAStraub (Controls unexposed, sick) (Phenobarbital) (Epilepsy), 2026 Adams (Phenobarbital), 2022 Thomas a (Phenobarbitone), 2022 Coste (Phenobarbital) (Controls unexposed, NOS), 2020 Kasradze (Phenobarbital) (Controls unexposed, disease free), 2017 5 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 3.08[0.48; 19.98]72,0198765%NACoste (Phenobarbital) (Controls unexposed, NOS), 2020 Kasradze (Phenobarbital) (Controls unexposed, disease free), 2017 2 unexposed, sickunexposed, sick 1.76[0.61; 5.07]46829569%NAStraub (Controls unexposed, sick) (Phenobarbital) (Epilepsy), 2026 Adams (Phenobarbital), 2022 Thomas a (Phenobarbitone), 2022 3 Tags Adjustment   - No  - No 3.58[1.74; 7.37]-490%NAAdams (Phenobarbital), 2022 Thomas a (Phenobarbitone), 2022 Kasradze (Phenobarbital) (Controls unexposed, disease free), 2017 3   - Yes  - Yes 1.07[0.54; 2.11]72,48733335%NAStraub (Controls unexposed, sick) (Phenobarbital) (Epilepsy), 2026 Coste (Phenobarbital) (Controls unexposed, NOS), 2020 2 extrapolated (cont. endpoint)extrapolated (cont. endpoint) 4.27[1.11; 16.37]-1512%NAThomas a (Phenobarbitone), 2022 Kasradze (Phenobarbital) (Controls unexposed, disease free), 2017 2 MatchedMatched 3.95[1.74; 8.97]-370%NAAdams (Phenobarbital), 2022 Kasradze (Phenobarbital) (Controls unexposed, disease free), 2017 2 All studiesAll studies 1.95[0.94; 4.07]72,48738258%NAStraub (Controls unexposed, sick) (Phenobarbital) (Epilepsy), 2026 Adams (Phenobarbital), 2022 Thomas a (Phenobarbitone), 2022 Coste (Phenobarbital) (Controls unexposed, NOS), 2020 Kasradze (Phenobarbital) (Controls unexposed, disease free), 2017 50.250.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-2.93.31.3250.000Straub (Controls unexposed, sick) (Phenobarbital) (Epilepsy), 2026Adams (Phenobarbital), 2022Thomas a (Phenobarbitone), 2022Coste (Phenobarbital) (Controls unexposed, NOS), 2020Kasradze (Phenobarbital) (Controls unexposed, disease free), 2017

Asymetry test p-value = 0.2265 (by Egger's regression)

slope=-0.7666 (0.8956); intercept=2.7277 (1.7980); t=1.5171; p=0.2265

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 9165, 9160, 19383

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 3.08[0.48; 19.98]72,0198765%NACoste (Phenobarbital) (Controls unexposed, NOS), 2020 Kasradze (Phenobarbital) (Controls unexposed, disease free), 2017 2 unexposed, sick controlsunexposed, sick controls 1.76[0.61; 5.07]46829569%NAStraub (Controls unexposed, sick) (Phenobarbital) (Epilepsy), 2026 Adams (Phenobarbital), 2022 Thomas a (Phenobarbitone), 2022 3 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.11[0.69; 1.77]3433360%NAStraub (Controls exposed to LTG) (Phenobarbital) (Epilepsy), 2026 Coste (Phenobarbital) (Controls exposed to Lamotrigine, sick), 2020 Kasradze (Phenobarbital) (Controls exposed to Lamotrigine, sick), 2017 30.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Veroniki b (NMA) (Language delay)Veroniki b (NMA) (Language delay) 1.06[0.22; 5.08]NA-Wwhatever (meta-analysis)Anyduring pregnancy (anytime or not specified)studies TTT-9 metaPregmetaPreg 1.95[0.94; 4.07]58%382----Straub (Controls unexposed, sick) (Phenobarbital) (Epilepsy), 2026 Adams (Phenobarbital), 2022 Thomas a (Phenobarbitone), 2022 Coste (Phenobarbital) (Controls unexposed, NOS), 2020 Kasradze (Phenobarbital) (Controls unexposed, disease free), 2017 50.510.01.0