Phenytoin (Epilepsy)

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.
S8086
R24719		 Aydin (Phenytoin) (Controls exposed to Lamotrigine, sick), 2020 Preterm delivery (before 37 weeks of gestation) throughout pregnancy retrospective cohort exposed to other treatment, sick excluded Adjustment: No 13.00 [0.10;1680.94] C
excluded (control group) 		0/1   0/7 0 1
ref
S8079
R24658		 Aydin (Phenytoin) (Controls unexposed, sick), 2020 Preterm delivery (before 37 weeks of gestation) throughout pregnancy retrospective cohort unexposed, sick Adjustment: No 7.80 [0.12;487.53] C 0/1   2/22 2 1
ref
S6254
R16660		 Arkilo (Phenytoin), 2015 Premature delivery during pregnancy (anytime or not specified) retrospective cohort exposed to other treatment, sick Adjustment: No 0.65 [0.03;14.95] C 0/5   3/24 3 5
ref
S5922
R15042		 Artama (Phenytoin) (Controls exposed to Lamotrigine, sick), 2013 Preterm birth (<37 gestational weeks) during pregnancy (anytime or not specified) population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No 1.72 [0.34;8.58] C
excluded (control group) 		2/26   8/173 10 26
ref
S305
R14813		 Artama (Phenytoin) (Controls unexposed, disease free), 2013 Preterm birth (<37 gestational weeks) during pregnancy (anytime or not specified) population based cohort retrospective unexposed, disease free excluded Adjustment: Yes 1.85 [0.43;7.88]
excluded (control group) 		2/26   30,027/719,509 30,029 26
ref
S5914
R14946		 Artama (Phenytoin) (Controls unexposed, sick), 2013 Preterm birth (<37 gestational weeks) during pregnancy (anytime or not specified) population based cohort retrospective unexposed, sick Adjustment: Yes 1.52 [0.34;6.76] 2/26   85/1,793 87 26
ref
S6413
R17571		 Pennell (Phenytoin), 2012 Preterm Birth (< 37 weeks GA) during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick Adjustment: No 1.88 [0.57;6.13] C 6/55   6/98 12 55
ref
S7275
R21047		 Koch (Phenytoin), 1996 Prematurity (< 37 weeks) during pregnancy (anytime or not specified) prospective cohort unexposed (general population or NOS) Adjustment: No Matched 11.64 [0.97;139.55] C 2/13   1/65 3 13
ref
Total 5 studies 2.11 [0.93;4.81] 107 100
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 Aydin (Phenytoin) (Controls unexposed, sick), 2020Aydin, 2020 1 7.80[0.12; 487.53]214%ROB confusion: criticalROB selection: criticalROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Arkilo (Phenytoin), 2015Arkilo, 2015 2 0.65[0.03; 14.95]357%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Artama (Phenytoin) (Controls unexposed, sick), 2013Artama, 2013 3 1.52[0.34; 6.76]872630%ROB confusion: moderateROB selection: lowROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Pennell (Phenytoin), 2012Pennell, 2012 4 1.88[0.57; 6.13]125548%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Koch (Phenytoin), 1996Koch, 1996 5 11.64[0.97; 139.55]31311%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (5 studies) I2 = 0% 2.11[0.93; 4.81]1071000.250.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

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

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 2.11[0.93; 4.81]1071000%NAAydin (Phenytoin) (Controls unexposed, sick), 2020 Arkilo (Phenytoin), 2015 Artama (Phenytoin) (Controls unexposed, sick), 2013 Pennell (Phenytoin), 2012 Koch (Phenytoin), 1996 5 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 11.64[0.97; 139.55]313 -NAKoch (Phenytoin), 1996 1 unexposed, sickunexposed, sick 1.84[0.45; 7.49]89270%NAAydin (Phenytoin) (Controls unexposed, sick), 2020 Artama (Phenytoin) (Controls unexposed, sick), 2013 2 exposed to other treatment, sickexposed to other treatment, sick 1.64[0.54; 4.98]15600%NAArkilo (Phenytoin), 2015 Pennell (Phenytoin), 2012 2 Tags Adjustment   - No  - No 2.44[0.91; 6.51]20740%NAAydin (Phenytoin) (Controls unexposed, sick), 2020 Arkilo (Phenytoin), 2015 Pennell (Phenytoin), 2012 Koch (Phenytoin), 1996 4   - Yes  - Yes 1.52[0.34; 6.78]8726 -NAArtama (Phenytoin) (Controls unexposed, sick), 2013 1 MatchedMatched 11.64[0.97; 139.55]313 -NAKoch (Phenytoin), 1996 1 All studiesAll studies 2.11[0.93; 4.81]1071000%NAAydin (Phenytoin) (Controls unexposed, sick), 2020 Arkilo (Phenytoin), 2015 Artama (Phenytoin) (Controls unexposed, sick), 2013 Pennell (Phenytoin), 2012 Koch (Phenytoin), 1996 50.250.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-5.05.72.5320.000Aydin (Phenytoin) (Controls unexposed, sick), 2020Arkilo (Phenytoin), 2015Artama (Phenytoin) (Controls unexposed, sick), 2013Pennell (Phenytoin), 2012Koch (Phenytoin), 1996

Asymetry test p-value = 0.5359 (by Egger's regression)

slope=0.1599 (0.9290); intercept=0.6914 (0.9919); t=0.6970; p=0.5359

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 5922, 305, 8086

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 3.48[0.63; 19.29]30,0323936%NAArtama (Phenytoin) (Controls unexposed, disease free), 2013 Koch (Phenytoin), 1996 2 unexposed, sick controlsunexposed, sick controls 1.84[0.45; 7.49]89270%NAAydin (Phenytoin) (Controls unexposed, sick), 2020 Artama (Phenytoin) (Controls unexposed, sick), 2013 2 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.79[0.73; 4.38]25870%NAAydin (Phenytoin) (Controls exposed to Lamotrigine, sick), 2020 Arkilo (Phenytoin), 2015 Artama (Phenytoin) (Controls exposed to Lamotrigine, sick), 2013 Pennell (Phenytoin), 2012 40.510.01.0