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

Preterm (< 37 weeks)

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.
S18083
R76136		 Leite (Phenobarbital) (Epilepsy), 2024 Premature Delivery <37weeks during pregnancy (anytime or not specified) retrospective cohort unexposed, disease free Adjustment: No 0.60 [0.24;1.48] -/70   98/492 - 70
ref
S9551
R33734		 Coste (Phenobarbital) (Controls exposed to Lamotrigine, sick), 2020 Gestational age at birth (< 37 WA) during pregnancy (anytime or not specified) retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No Controls: mixed indications 0.95 [0.38;2.39] C
excluded (control group) 		5/84   175/2,813 180 84
ref
S9552
R33752		 Coste (Phenobarbital) (Controls unexposed, NOS), 2020 Gestational age at birth (< 37 WA) during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No 1.12 [0.45;2.77] C 5/84   91,255/1,710,441 91,260 84
ref
S9546
R33721		 Kilic (Phenobarbital or Primidone) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014 Preterm (< 37 weeks) during pregnancy (anytime or not specified) population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No 1.21 [0.65;2.25] C
excluded (control group) 		13/116   83/880 96 116
ref
S9547
R33724		 Kilic (Phenobarbital or Primidone) (Controls unexposed NOS) (Mixed indications), 2014 Preterm (< 37 weeks) during pregnancy (anytime or not specified) population based cohort retrospective unexposed (general population or NOS) excluded Adjustment: No 2.39 [1.34;4.25] C
excluded (control group) 		13/116   33,974/676,834 33,987 116
ref
S9548
R33727		 Kilic (Phenobarbital or Primidone) (Controls unexposed, sick) (Mixed indications), 2014 Preterm (< 37 weeks) during pregnancy (anytime or not specified) population based cohort retrospective unexposed, sick Adjustment: No Controls: epilepsy indication 1.62 [0.90;2.91] C 13/116   383/5,296 396 116
ref
S9491
R33448		 Endo (Phenobarbital) (Controls unexposed, disease free), 2004 Preterm delivery (< week 37) throughout pregnancy retrospective cohort unexposed, disease free excluded Adjustment: No 0.59 [0.07;4.70] C
excluded (control group) 		1/10   104/656 105 10
ref
S9492
R33463		 Endo (Phenobarbital) (Controls unexposed, sick), 2004 Preterm delivery (< week 37) throughout pregnancy retrospective cohort unexposed, sick Adjustment: No 0.18 [0.00;12.84] C 1/10   0/1 1 10
ref
S9590
R33959		 Koch (Phenobarbital or Primidone), 1996 Prematurity (< 37 weeks) during pregnancy (anytime or not specified) prospective cohort unexposed (general population or NOS) Adjustment: No Matched 18.29 [1.90;176.35] C 4/18   1/65 5 18
ref
S9564
R33830		 Van der Pol (Phenobarbital) (Controls unexposed, disease free), 1991 Gestational age (≤ 37 wk) throughout pregnancy prospective cohort unexposed, disease free excluded Adjustment: No Matched 1.16 [0.12;11.40] C
excluded (control group) 		1/12   4/55 5 12
ref
S9565
R33855		 Van der Pol (Phenobarbital) (Controls unexposed, sick), 1991 Gestational age (≤ 37 wk) throughout pregnancy prospective cohort unexposed, sick Adjustment: No 0.91 [0.07;11.19] C 1/12   2/22 3 12
ref
Total 6 studies 1.27 [0.62;2.59] 91,665 310
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 Leite (Phenobarbital) (Epilepsy), 2024Leite, 2024 1 0.60[0.24; 1.48]-7025%ROB confusion: criticalROB selection: unclearROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: critical Coste (Phenobarbital) (Controls unexposed, NOS), 2020Coste, 2020 2 1.12[0.45; 2.77]91,2608425%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Kilic (Phenobarbital or Primidone) (Controls unexposed, sick) (Mixed indications), 2014Kilic, 2014 3 1.62[0.90; 2.91]39611633%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Endo (Phenobarbital) (Controls unexposed, sick), 2004Endo, 2004 4 0.18[0.00; 12.84]1103%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Koch (Phenobarbital or Primidone), 1996Koch, 1996 5 18.29[1.90; 176.35]5188%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Van der Pol (Phenobarbital) (Controls unexposed, sick), 1991Van der Pol, 1991 6 0.91[0.07; 11.19]3127%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Total (6 studies) I2 = 48% 1.27[0.62; 2.59]91,6653100.050.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Phenobarbital) (Epilepsy; 2: Phenobarbital) (Controls unexposed, NOS; 3: Phenobarbital or Primidone) (Controls unexposed, sick) (Mixed indications; 4: Phenobarbital) (Controls unexposed, sick; 5: Phenobarbital or Primidone; 6: Phenobarbital) (Controls unexposed, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.27[0.62; 2.59]91,66531048%NALeite (Phenobarbital) (Epilepsy), 2024 Coste (Phenobarbital) (Controls unexposed, NOS), 2020 Kilic (Phenobarbital or Primidone) (Controls unexposed, sick) (Mixed indications), 2014 Endo (Phenobarbital) (Controls unexposed, sick), 2004 Koch (Phenobarbital or Primidone), 1996 Van der Pol (Phenobarbital) (Controls unexposed, sick), 1991 6 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.55[0.40; 5.97]91,26517274%NALeite (Phenobarbital) (Epilepsy), 2024 Coste (Phenobarbital) (Controls unexposed, NOS), 2020 Koch (Phenobarbital or Primidone), 1996 3 unexposed, sickunexposed, sick 1.51[0.86; 2.66]4001380%NAKilic (Phenobarbital or Primidone) (Controls unexposed, sick) (Mixed indications), 2014 Endo (Phenobarbital) (Controls unexposed, sick), 2004 Van der Pol (Phenobarbital) (Controls unexposed, sick), 1991 3 Tags Adjustment   - No  - No 1.27[0.62; 2.59]91,66531048%NALeite (Phenobarbital) (Epilepsy), 2024 Coste (Phenobarbital) (Controls unexposed, NOS), 2020 Kilic (Phenobarbital or Primidone) (Controls unexposed, sick) (Mixed indications), 2014 Endo (Phenobarbital) (Controls unexposed, sick), 2004 Koch (Phenobarbital or Primidone), 1996 Van der Pol (Phenobarbital) (Controls unexposed, sick), 1991 6 Controls   - epilepsy indication  - epilepsy indication 1.62[0.90; 2.91]396116 -NAKilic (Phenobarbital or Primidone) (Controls unexposed, sick) (Mixed indications), 2014 1 MatchedMatched 18.29[1.90; 176.35]518 -NAKoch (Phenobarbital or Primidone), 1996 1 All studiesAll studies 1.27[0.62; 2.59]91,66531048%NALeite (Phenobarbital) (Epilepsy), 2024 Coste (Phenobarbital) (Controls unexposed, NOS), 2020 Kilic (Phenobarbital or Primidone) (Controls unexposed, sick) (Mixed indications), 2014 Endo (Phenobarbital) (Controls unexposed, sick), 2004 Koch (Phenobarbital or Primidone), 1996 Van der Pol (Phenobarbital) (Controls unexposed, sick), 1991 60.050.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-5.15.42.6250.000Leite (Phenobarbital) (Epilepsy), 2024Coste (Phenobarbital) (Controls unexposed, NOS), 2020Kilic (Phenobarbital or Primidone) (Controls unexposed, sick) (Mixed indications), 2014Endo (Phenobarbital) (Controls unexposed, sick), 2004Koch (Phenobarbital or Primidone), 1996Van der Pol (Phenobarbital) (Controls unexposed, sick), 1991

Asymetry test p-value = 0.9783 (by Egger's regression)

slope=0.2252 (0.6211); intercept=0.0346 (1.1917); t=0.0290; p=0.9783

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 9564, 9491, 9546, 9547, 9551

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.44[0.67; 3.11]125,45131059%NALeite (Phenobarbital) (Epilepsy), 2024 Coste (Phenobarbital) (Controls unexposed, NOS), 2020 Kilic (Phenobarbital or Primidone) (Controls unexposed NOS) (Mixed indications), 2014 Endo (Phenobarbital) (Controls unexposed, disease free), 2004 Koch (Phenobarbital or Primidone), 1996 Van der Pol (Phenobarbital) (Controls unexposed, disease free), 1991 6 unexposed, sick controlsunexposed, sick controls 1.51[0.86; 2.66]4001380%NAKilic (Phenobarbital or Primidone) (Controls unexposed, sick) (Mixed indications), 2014 Endo (Phenobarbital) (Controls unexposed, sick), 2004 Van der Pol (Phenobarbital) (Controls unexposed, sick), 1991 3 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.12[0.67; 1.88]2762000%NACoste (Phenobarbital) (Controls exposed to Lamotrigine, sick), 2020 Kilic (Phenobarbital or Primidone) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014 20.510.01.0