Methotrexate (Pre-conception only)

Early intrauterine death (< 22 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.
S6697
R18863
Svirsky, 2017 Early missed abortion (< 12 weeks) preconceptional for kinetic reason retrospective cohort unexposed, sick Adjustment: No Exposed group: MTX (monotherapy) MTX more than 3 months before pregnancy MTX treatment for ectopic pregnancy 0.17 [0.05;0.58] C 3/93   22/133 25 93
ref
S10348
R37934
Weber-Schoendorfer (Controls exposed to other treatment, sick), 2014 Spontaneous abortion (fetus weighing <500 gm or <23 weeks of completed gestation) preconceptional for kinetic reason prospective cohort exposed to other treatment, sick excluded Adjustment: Yes Exposed group: MTX (polytherapy or not specified) Indications: Inflammatory diseases Matched MTX less than 3 months before pregnancy 0.80 [0.40;1.40]
excluded (control group)
12/136   44/459 56 136
ref
S10349
R37953
Weber-Schoendorfer (Controls unexposed, disease free), 2014 Spontaneous abortion (fetus weighing <500 gm or <23 weeks of completed gestation) preconceptional for kinetic reason prospective cohort unexposed, disease free Adjustment: Yes Exposed group: MTX (polytherapy or not specified) Indications: Inflammatory diseases Matched MTX less than 3 months before pregnancy 1.30 [0.60;3.00] 12/136   79/1,107 91 136
ref
S7243
R21017
Svirsky, 2009 Abortion (Early missed) preconceptional for kinetic reason retrospective cohort unexposed, sick Adjustment: No Exposed group: MTX (monotherapy) MTX more than 3 months before pregnancy MTX treatment for ectopic pregnancy 0.62 [0.22;1.71] C 6/45   16/80 22 45
ref
Total 3 studies 0.55 [0.18;1.70] 138 274
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 Svirsky, 2017Svirsky, 2017 0.17[0.05; 0.58]259329%ROB confusion: criticalROB selection: criticalROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Weber-Schoendorfer (Controls unexposed, disease free), 2014Weber-Schoendorfer, 2014 1 1.30[0.60; 3.00]9113637%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Svirsky, 2009Svirsky, 2009 0.62[0.22; 1.71]224533%ROB confusion: criticalROB selection: criticalROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Total (3 studies) I2 = 73% 0.55[0.18; 1.70]1382740.05.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, disease free;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 0.55[0.18; 1.70]13827473%NASvirsky, 2017 Weber-Schoendorfer (Controls unexposed, disease free), 2014 Svirsky, 2009 3 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.30[0.58; 2.91]91136 -NAWeber-Schoendorfer (Controls unexposed, disease free), 2014 1 unexposed, sickunexposed, sick 0.34[0.10; 1.20]4713860%NASvirsky, 2017 Svirsky, 2009 2 Tags Adjustment   - No  - No 0.34[0.10; 1.20]4713860%NASvirsky, 2017 Svirsky, 2009 2   - Yes  - Yes 1.30[0.58; 2.91]91136 -NAWeber-Schoendorfer (Controls unexposed, disease free), 2014 1 Exposed group   - MTX (monotherapy)  - MTX (monotherapy) 0.34[0.10; 1.20]4713860%NASvirsky, 2017 Svirsky, 2009 2   - MTX (polytherapy or not specified)  - MTX (polytherapy or not specified) 1.30[0.58; 2.91]91136 -NAWeber-Schoendorfer (Controls unexposed, disease free), 2014 1 Indications   - Inflammatory diseases  - Inflammatory diseases 1.30[0.58; 2.91]91136 -NAWeber-Schoendorfer (Controls unexposed, disease free), 2014 1 MatchedMatched 1.30[0.58; 2.91]91136 -NAWeber-Schoendorfer (Controls unexposed, disease free), 2014 1 MTX less than 3 months before pregnancyMTX less than 3 months before pregnancy 1.30[0.58; 2.91]91136 -NAWeber-Schoendorfer (Controls unexposed, disease free), 2014 1 MTX more than 3 months before pregnancyMTX more than 3 months before pregnancy 0.34[0.10; 1.20]4713860%NASvirsky, 2017 Svirsky, 2009 2 MTX treatment for ectopic pregnancyMTX treatment for ectopic pregnancy 0.34[0.10; 1.20]4713860%NASvirsky, 2017 Svirsky, 2009 2 All studiesAll studies 0.55[0.18; 1.70]13827473%NASvirsky, 2017 Weber-Schoendorfer (Controls unexposed, disease free), 2014 Svirsky, 2009 30.05.01.0

Publication bias and p-hacking diagnosis

funnel plot

Funnel plot not drawn. Less than 3 points.

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

not enought points

p values plot

Funnel plot not drawn. Less than 3 points.

Sub-groups analysis using all included studies

excluded 10348

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.30[0.58; 2.91]91136 -NAWeber-Schoendorfer (Controls unexposed, disease free), 2014 1 unexposed, sick controlsunexposed, sick controls Out of scale0.34[0.10; 1.20]4713860%NASvirsky, 2017 Svirsky, 2009 2 exposed to other treatment, sick controlsexposed to other treatment, sick controls 0.80[0.43; 1.50]56136 -NAWeber-Schoendorfer (Controls exposed to other treatment, sick), 2014 10.510.01.0