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

Small for gestational age (weight)

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.
S16814
R70543
Christensen (Phenobarbital) (All indications) (Controls exposed to LTG), 2024 Small for gestational age (a z-score for birth weight ≤10th percentile for gestational week, sex, and country (including newborns with congenital malformations)) during pregnancy (anytime or not specified) population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No 1.60 [1.07;2.40] C
excluded (control group)
29/183   920/8,756 949 183
ref
S16815
R70547
Christensen (Phenobarbital) (All indications) (Controls unexposed, general population), 2024 Small for gestational age (a z-score for birth weight ≤10th percentile for gestational week, sex, and country (including newborns with congenital malformations)) during pregnancy (anytime or not specified) population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes 1.46 [0.97;2.20] 29/183   446,267/4,467,848 446,296 183
ref
S9551
R33737
Coste (Phenobarbital) (Controls exposed to Lamotrigine, sick), 2020 Small for gestational age (weight) during pregnancy (anytime or not specified) retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No Controls: mixed indications 2.26 [1.31;3.90] C
excluded (control group)
17/84   284/2,813 301 84
ref
S9552
R33755
Coste (Phenobarbital) (Controls unexposed, NOS), 2020 Small for gestational age (weight) during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No 2.34 [1.37;3.98] C 17/84   167,376/1,710,441 167,393 84
ref
S9545
R33718
Hernández-Díaz (Phenobarbital), 2017 Small for gestational age (<10th percentile) throughout pregnancy prospective cohort exposed to other treatment, sick Adjustment: Yes 2.40 [1.60;3.60] -/178   -/1,799 - 178
ref
S9570
R33889
Burja (Phenobarbital or Primidone) (Controls unexposed, disease free), 2006 Small for date (NOS) during pregnancy (anytime or not specified) retrospective cohort (registry) unexposed, disease free excluded Adjustment: No 8.17 [0.49;135.15] C
excluded (control group)
1/2   23/211 24 2
ref
S9568
R33879
Burja (Phenobarbital or Primidone) (Controls unexposed, sick), 2006 Small for date (NOS) during pregnancy (anytime or not specified) retrospective cohort (registry) unexposed, sick Adjustment: No 31.00 [1.02;941.06] C 1/2   1/32 2 2
ref
S9491
R33440
Endo (Phenobarbital) (Controls unexposed, disease free), 2004 Intrauterine growth retardation (NOS) throughout pregnancy retrospective cohort unexposed, disease free excluded Adjustment: No 0.95 [0.05;16.63] C
excluded (control group)
0/10   34/656 34 10
ref
S9492
R33455
Endo (Phenobarbital) (Controls unexposed, sick), 2004 Intrauterine growth retardation (NOS) throughout pregnancy retrospective cohort unexposed, sick Adjustment: No 0.05 [0.00;6.68] C 0/10   0/1 0 10
ref
Total 5 studies 2.03 [1.31;3.14] 613,691 457
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 Christensen (Phenobarbital) (All indications) (Controls unexposed, general population), 2024Christensen, 2024 1 1.46[0.97; 2.20]446,29618334%ROB confusion: seriousROB selection: lowROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Coste (Phenobarbital) (Controls unexposed, NOS), 2020Coste, 2020 2 2.34[1.37; 3.98]167,3938429%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Hernández-Díaz (Phenobarbital), 2017Hernández-Díaz, 2017 3 2.40[1.60; 3.60]-17835%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Burja (Phenobarbital or Primidone) (Controls unexposed, sick), 2006Burja, 2006 4 31.00[1.02; 941.06]222%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Endo (Phenobarbital) (Controls unexposed, sick), 2004Endo, 2004 5 0.05[0.00; 6.68]0101%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (5 studies) I2 = 50% 2.03[1.31; 3.14]613,6914570.0100.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Phenobarbital) (All indications) (Controls unexposed, general population; 2: Phenobarbital) (Controls unexposed, NOS; 3: Phenobarbital; 4: Phenobarbital or Primidone) (Controls unexposed, sick; 5: Phenobarbital) (Controls unexposed, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 2.03[1.31; 3.14]613,69145750%NAChristensen (Phenobarbital) (All indications) (Controls unexposed, general population), 2024 Coste (Phenobarbital) (Controls unexposed, NOS), 2020 Hernández-Díaz (Phenobarbital), 2017 Burja (Phenobarbital or Primidone) (Controls unexposed, sick), 2006 Endo (Phenobarbital) (Controls unexposed, sick), 2004 5 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.79[1.13; 2.83]613,68926747%NAChristensen (Phenobarbital) (All indications) (Controls unexposed, general population), 2024 Coste (Phenobarbital) (Controls unexposed, NOS), 2020 2 unexposed, sickunexposed, sick 1.63[0.00; 827.71]21278%NABurja (Phenobarbital or Primidone) (Controls unexposed, sick), 2006 Endo (Phenobarbital) (Controls unexposed, sick), 2004 2 exposed to other treatment, sickexposed to other treatment, sick 2.40[1.60; 3.60]-178 -NAHernández-Díaz (Phenobarbital), 2017 1 Tags Adjustment   - No  - No 2.42[0.21; 27.21]167,3959656%NACoste (Phenobarbital) (Controls unexposed, NOS), 2020 Burja (Phenobarbital or Primidone) (Controls unexposed, sick), 2006 Endo (Phenobarbital) (Controls unexposed, sick), 2004 3   - Yes  - Yes 1.87[1.15; 3.05]446,29636165%NAChristensen (Phenobarbital) (All indications) (Controls unexposed, general population), 2024 Hernández-Díaz (Phenobarbital), 2017 2 All studiesAll studies 2.03[1.31; 3.14]613,69145750%NAChristensen (Phenobarbital) (All indications) (Controls unexposed, general population), 2024 Coste (Phenobarbital) (Controls unexposed, NOS), 2020 Hernández-Díaz (Phenobarbital), 2017 Burja (Phenobarbital or Primidone) (Controls unexposed, sick), 2006 Endo (Phenobarbital) (Controls unexposed, sick), 2004 50.0100.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-5.86.52.9650.000Christensen (Phenobarbital) (All indications) (Controls unexposed, general population), 2024Coste (Phenobarbital) (Controls unexposed, NOS), 2020Hernández-Díaz (Phenobarbital), 2017Burja (Phenobarbital or Primidone) (Controls unexposed, sick), 2006Endo (Phenobarbital) (Controls unexposed, sick), 2004

Asymetry test p-value = 0.9377 (by Egger's regression)

slope=0.6588 (0.3694); intercept=0.1089 (1.2833); t=0.0848; p=0.9377

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 9491, 9570, 9551, 16814

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.78[1.25; 2.55]613,7472797%NAChristensen (Phenobarbital) (All indications) (Controls unexposed, general population), 2024 Coste (Phenobarbital) (Controls unexposed, NOS), 2020 Burja (Phenobarbital or Primidone) (Controls unexposed, disease free), 2006 Endo (Phenobarbital) (Controls unexposed, disease free), 2004 4 unexposed, sick controlsunexposed, sick controls 1.63[0.00; 827.71]21278%NABurja (Phenobarbital or Primidone) (Controls unexposed, sick), 2006 Endo (Phenobarbital) (Controls unexposed, sick), 2004 2 exposed to other treatment, sick controlsexposed to other treatment, sick controls 2.02[1.56; 2.63]1,2504456%NAChristensen (Phenobarbital) (All indications) (Controls exposed to LTG), 2024 Coste (Phenobarbital) (Controls exposed to Lamotrigine, sick), 2020 Hernández-Díaz (Phenobarbital), 2017 30.510.01.0