Phenobarbital (Epilepsy)

Microcephaly / Small head circumference for gestational age

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.
S5865
R14586
Holmes (Phenobarbital) (Controls unexposed, disease free), 2001 Microcephaly at birth (Head circumference more than 2 SD below the mean value for the same race, sex and gestational age) during pregnancy (anytime or not specified) retrospective cohort unexposed, disease free excluded Adjustment: No 3.18 [0.82;12.31] C
excluded (control group)
3/62   8/508 11 62
ref
S5866
R14594
Holmes (Phenobarbital) (Controls unexposed, sick), 2001 Microcephaly at birth (Head circumference more than 2 SD below the mean value for the same race, sex and gestational age) during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: No 2.39 [0.39;14.73] C 3/62   2/96 5 62
ref
S6436
R17692
Battino (Phenobarbital), 1999 Small head circumferences (at birth < 10th percentile) throughout pregnancy prospective cohort unexposed, sick Adjustment: No 1.88 [0.50;7.07] C 14/81   3/30 17 81
ref
S6779
R19143
Díaz-Romero (Phenobarbital), 1999 Head circumference <2 SD at birth (measured by a physician and correlated with sex and with gestational age) during pregnancy (anytime or not specified) cohort unexposed, sick Adjustment: No 5.00 [0.07;366.35] C 0/2   0/8 0 2
ref
S6930
R19484
Dravet (Phenobarbital), 1992 Isolated microcephaly at birth (head circumference >2 SD lower than those given in the reference tables adjusted for gestational age at birth) 1st trimester prospective cohort unexposed, sick Adjustment: No 3.55 [0.42;29.89] C 12/56   1/14 13 56
ref
S6953
R19667
Kelly (Phenobarbital), 1984 Microcephaly at unknown age (head circumference < 5th centile) during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No 3.64 [0.30;44.78] C 2/13   1/21 3 13
ref
Total 5 studies 2.50 [1.04;5.99] 38 214
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 Holmes (Phenobarbital) (Controls unexposed, sick), 2001Holmes, 2001 1 2.39[0.39; 14.73]56223%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Battino (Phenobarbital), 1999Battino, 1999 2 1.88[0.50; 7.07]178144%ROB confusion: criticalROB selection: lowROB classification: lowROB missing: moderateROB mesure: moderateROB reporting: moderate Díaz-Romero (Phenobarbital), 1999Díaz-Romero, 1999 3 5.00[0.07; 366.35]024%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Dravet (Phenobarbital), 1992Dravet, 1992 4 3.55[0.42; 29.89]135617%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Kelly (Phenobarbital), 1984Kelly, 1984 5 3.64[0.30; 44.78]31312%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (5 studies) I2 = 0% 2.50[1.04; 5.99]382140.510.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

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

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 2.50[1.04; 5.99]382140%NAHolmes (Phenobarbital) (Controls unexposed, sick), 2001 Battino (Phenobarbital), 1999 Díaz-Romero (Phenobarbital), 1999 Dravet (Phenobarbital), 1992 Kelly (Phenobarbital), 1984 5 case control studiescase control studies 0 Type of controls unexposed, sickunexposed, sick 2.50[1.04; 5.99]382140%NAHolmes (Phenobarbital) (Controls unexposed, sick), 2001 Battino (Phenobarbital), 1999 Díaz-Romero (Phenobarbital), 1999 Dravet (Phenobarbital), 1992 Kelly (Phenobarbital), 1984 5 Tags Adjustment   - No  - No 2.50[1.04; 5.99]382140%NAHolmes (Phenobarbital) (Controls unexposed, sick), 2001 Battino (Phenobarbital), 1999 Díaz-Romero (Phenobarbital), 1999 Dravet (Phenobarbital), 1992 Kelly (Phenobarbital), 1984 5 All studiesAll studies 2.50[1.04; 5.99]382140%NAHolmes (Phenobarbital) (Controls unexposed, sick), 2001 Battino (Phenobarbital), 1999 Díaz-Romero (Phenobarbital), 1999 Dravet (Phenobarbital), 1992 Kelly (Phenobarbital), 1984 50.510.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-5.26.12.6290.000Holmes (Phenobarbital) (Controls unexposed, sick), 2001Battino (Phenobarbital), 1999Díaz-Romero (Phenobarbital), 1999Dravet (Phenobarbital), 1992Kelly (Phenobarbital), 1984

Asymetry test p-value = 0.0342 (by Egger's regression)

slope=0.1415 (0.2219); intercept=0.8226 (0.2222); t=3.7018; p=0.0342

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 5865

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 3.18[0.82; 12.31]1162 -NAHolmes (Phenobarbital) (Controls unexposed, disease free), 2001 1 unexposed, sick controlsunexposed, sick controls 2.50[1.04; 5.99]382140%NAHolmes (Phenobarbital) (Controls unexposed, sick), 2001 Battino (Phenobarbital), 1999 Díaz-Romero (Phenobarbital), 1999 Dravet (Phenobarbital), 1992 Kelly (Phenobarbital), 1984 50.510.01.0