Phenobarbital (Epilepsy)

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.
S7981
R46603		 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
S7809
R46604		 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
S7280
R46601		 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
S7278
R46602		 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
Total 2 studies 7.18 [1.16;44.46] 3,399 87
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 Coste (Phenobarbital) (Controls unexposed, NOS), 2020Coste, 2020 1 3.00[0.40; 21.40]3,3998453%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Kasradze (Phenobarbital) (Controls unexposed, disease free), 2017Kasradze, 2017 2 19.35[2.16; 173.39]-347%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: criticalROB mesure: lowROB reporting: moderate Total (2 studies) I2 = 34% 7.18[1.16; 44.46]3,399870.950.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

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

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 7.18[1.16; 44.46]3,3998734%NACoste (Phenobarbital) (Controls unexposed, NOS), 2020 Kasradze (Phenobarbital) (Controls unexposed, disease free), 2017 2 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 Tags Adjustment   - No  - No 19.35[2.16; 173.37]-3 -NAKasradze (Phenobarbital) (Controls unexposed, disease free), 2017 1   - Yes  - Yes 3.00[0.41; 21.94]3,39984 -NACoste (Phenobarbital) (Controls unexposed, NOS), 2020 1 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 7.18[1.16; 44.46]3,3998734%NACoste (Phenobarbital) (Controls unexposed, NOS), 2020 Kasradze (Phenobarbital) (Controls unexposed, disease free), 2017 20.550.01.0

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 7280, 7981

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 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