Phenytoin (All indications)

Intrauterine deaths (as a whole or unspecified)

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.
S9250
R32090		 Trivedi (Phenytoin) (Controls exposed to Lamotrigine, sick), 2018 Spontaneous fetal loss (both spontaneous abortion before 20 weeks of gestation and stillbirths occurring after 20 weeks of gestation) 1st trimester prospective cohort exposed to other treatment, sick excluded Adjustment: No 0.92 [0.28;3.10] C
excluded (control group) 		10/129   4/48 14 129
ref
S9251
R32091		 Trivedi (Phenytoin) (Controls unexposed, sick), 2018 Spontaneous fetal loss (both spontaneous abortion before 20 weeks of gestation and stillbirths occurring after 20 weeks of gestation) 1st trimester prospective cohort unexposed, sick Adjustment: Yes 5.82 [1.43;23.73] 10/129   5/178 15 129
ref
S9252
R32092		 Vajda (Phenytoin) (Controls exposed to Lamotrigine, sick), 2018 Intrauterine foetal death throughout pregnancy prospective cohort exposed to other treatment, sick excluded Adjustment: No 0.64 [0.08;5.00] C
excluded (control group) 		1/42   14/382 15 42
ref
S9253
R32093		 Vajda (Phenytoin) (Controls unexposed, sick), 2018 Intrauterine foetal death throughout pregnancy prospective cohort unexposed, sick Adjustment: No 4.05 [0.26;63.39] 1/42   1/170 2 42
ref
S9213
R31963		 Miškov (Phenytoin) (Controls exposed to Lamotrigine, sick), 2016 Fetal loss during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick excluded Adjustment: No 7.22 [0.13;411.26] C
excluded (control group) 		0/1   4/37 4 1
ref
S9214
R31967		 Miškov (Phenytoin) (Controls unexposed, disease free), 2016 Fetal loss during pregnancy (anytime or not specified) prospective cohort unexposed, disease free excluded Adjustment: No 255.00 [2.09;31113.60] C
excluded (control group) 		0/1   0/128 0 1
ref
S9215
R31971		 Miškov (Phenytoin) (Controls unexposed, sick), 2016 Fetal loss during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No 7.00 [0.05;953.26] C 0/1   0/4 0 1
ref
S9186
R31765		 Arkilo (Phenytoin), 2015 Unsuccessful pregnancies (miscarriages/stillbirths) during pregnancy (anytime or not specified) retrospective cohort exposed to other treatment, sick Adjustment: No 0.96 [0.04;23.49] C 0/5   2/24 2 5
ref
S9212
R31960		 Meador (Phenytoin), 2006 Fetal death (early and late intrauterine deaths) during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick Adjustment: No 9.11 [0.43;193.31] C 2/56   0/98 2 56
ref
Total 5 studies 4.81 [1.66;13.92] 21 233
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 Trivedi (Phenytoin) (Controls unexposed, sick), 2018Trivedi, 2018 1 5.82[1.43; 23.73]1512957%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Vajda (Phenytoin) (Controls unexposed, sick), 2018Vajda, 2018 2 4.05[0.26; 63.39]24215%ROB confusion: criticalROB selection: moderateROB classification: lowROB missing: lowROB mesure: moderateROB reporting: moderate Miškov (Phenytoin) (Controls unexposed, sick), 2016Miškov, 2016 3 7.00[0.05; 953.26]015%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: criticalROB mesure: moderateROB reporting: moderate Arkilo (Phenytoin), 2015Arkilo, 2015 4 0.96[0.04; 23.49]2511%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Meador (Phenytoin), 2006Meador, 2006 5 9.11[0.43; 193.31]25612%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (5 studies) I2 = 0% 4.81[1.66; 13.92]212330.220.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

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

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 4.81[1.66; 13.92]212330%NATrivedi (Phenytoin) (Controls unexposed, sick), 2018 Vajda (Phenytoin) (Controls unexposed, sick), 2018 Miškov (Phenytoin) (Controls unexposed, sick), 2016 Arkilo (Phenytoin), 2015 Meador (Phenytoin), 2006 5 case control studiescase control studies 0 Type of controls unexposed, sickunexposed, sick 5.48[1.63; 18.43]171720%NATrivedi (Phenytoin) (Controls unexposed, sick), 2018 Vajda (Phenytoin) (Controls unexposed, sick), 2018 Miškov (Phenytoin) (Controls unexposed, sick), 2016 3 exposed to other treatment, sickexposed to other treatment, sick 3.11[0.34; 28.37]4610%NAArkilo (Phenytoin), 2015 Meador (Phenytoin), 2006 2 Tags Adjustment   - No  - No 3.73[0.73; 18.94]61040%NAVajda (Phenytoin) (Controls unexposed, sick), 2018 Miškov (Phenytoin) (Controls unexposed, sick), 2016 Arkilo (Phenytoin), 2015 Meador (Phenytoin), 2006 4   - Yes  - Yes 5.82[1.43; 23.71]15129 -NATrivedi (Phenytoin) (Controls unexposed, sick), 2018 1 All studiesAll studies 4.81[1.66; 13.92]212330%NATrivedi (Phenytoin) (Controls unexposed, sick), 2018 Vajda (Phenytoin) (Controls unexposed, sick), 2018 Miškov (Phenytoin) (Controls unexposed, sick), 2016 Arkilo (Phenytoin), 2015 Meador (Phenytoin), 2006 50.220.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-5.97.53.0090.000Trivedi (Phenytoin) (Controls unexposed, sick), 2018Vajda (Phenytoin) (Controls unexposed, sick), 2018Miškov (Phenytoin) (Controls unexposed, sick), 2016Arkilo (Phenytoin), 2015Meador (Phenytoin), 2006

Asymetry test p-value = 0.6486 (by Egger's regression)

slope=1.9488 (0.8210); intercept=-0.3417 (0.6772); t=0.5046; p=0.6486

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 9213, 9214, 9250, 9252

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) Out of scale255.00[2.09; 31113.60]-1 -NAMiškov (Phenytoin) (Controls unexposed, disease free), 2016 1 unexposed, sick controlsunexposed, sick controls 5.48[1.63; 18.43]171720%NATrivedi (Phenytoin) (Controls unexposed, sick), 2018 Vajda (Phenytoin) (Controls unexposed, sick), 2018 Miškov (Phenytoin) (Controls unexposed, sick), 2016 3 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.18[0.47; 2.95]372330%NATrivedi (Phenytoin) (Controls exposed to Lamotrigine, sick), 2018 Vajda (Phenytoin) (Controls exposed to Lamotrigine, sick), 2018 Miškov (Phenytoin) (Controls exposed to Lamotrigine, sick), 2016 Arkilo (Phenytoin), 2015 Meador (Phenytoin), 2006 50.510.01.0