Methotrexate (Pre-conception only)

Late intrauterine deaths (> 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
R18866		 Svirsky, 2017 Late 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 0.28 [0.01;5.95] C 0/93   2/133 2 93
ref
S10348
R37935		 Weber-Schoendorfer (Controls exposed to other treatment, sick), 2014 Stillbirth preconceptional for kinetic reason prospective cohort exposed to other treatment, sick excluded Adjustment: No Exposed group: MTX (polytherapy or not specified) Indications: Inflammatory diseases Matched MTX less than 3 months before pregnancy 1.69 [0.15;18.81] C
excluded (control group) 		1/136   2/459 3 136
ref
S10349
R37954		 Weber-Schoendorfer (Controls unexposed, disease free), 2014 Stillbirth preconceptional for kinetic reason prospective cohort unexposed, disease free Adjustment: No Exposed group: MTX (polytherapy or not specified) Indications: Inflammatory diseases Matched MTX less than 3 months before pregnancy 8.19 [0.51;131.74] C 1/136   1/1,107 2 136
ref
S7243
R21018		 Svirsky, 2009 Abortion (Late 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 1.80 [0.11;29.42] C 1/45   1/80 2 45
ref
Total 3 studies 1.74 [0.27;11.38] 6 274
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 0.28[0.01; 5.95]29330%ROB confusion: criticalROB selection: criticalROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Weber-Schoendorfer (Controls unexposed, disease free), 2014Weber-Schoendorfer, 2014 1 8.19[0.51; 131.74]213635%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Svirsky, 2009Svirsky, 2009 1.80[0.11; 29.42]24535%ROB confusion: criticalROB selection: criticalROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Total (3 studies) I2 = 22% 1.74[0.27; 11.38]62740.220.01.0ROB: 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 1.74[0.27; 11.38]627422%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) 8.19[0.51; 131.74]2136 -NAWeber-Schoendorfer (Controls unexposed, disease free), 2014 1 unexposed, sickunexposed, sick 0.77[0.10; 6.05]41380%NASvirsky, 2017 Svirsky, 2009 2 Tags Adjustment   - No  - No 1.74[0.27; 11.38]627422%NASvirsky, 2017 Weber-Schoendorfer (Controls unexposed, disease free), 2014 Svirsky, 2009 3 Exposed group   - MTX (monotherapy)  - MTX (monotherapy) 0.77[0.10; 6.05]41380%NASvirsky, 2017 Svirsky, 2009 2   - MTX (polytherapy or not specified)  - MTX (polytherapy or not specified) 8.19[0.51; 131.74]2136 -NAWeber-Schoendorfer (Controls unexposed, disease free), 2014 1 Indications   - Inflammatory diseases  - Inflammatory diseases 8.19[0.51; 131.74]2136 -NAWeber-Schoendorfer (Controls unexposed, disease free), 2014 1 MatchedMatched 8.19[0.51; 131.74]2136 -NAWeber-Schoendorfer (Controls unexposed, disease free), 2014 1 MTX less than 3 months before pregnancyMTX less than 3 months before pregnancy 8.19[0.51; 131.74]2136 -NAWeber-Schoendorfer (Controls unexposed, disease free), 2014 1 MTX more than 3 months before pregnancyMTX more than 3 months before pregnancy 0.77[0.10; 6.05]41380%NASvirsky, 2017 Svirsky, 2009 2 MTX treatment for ectopic pregnancyMTX treatment for ectopic pregnancy 0.77[0.10; 6.05]41380%NASvirsky, 2017 Svirsky, 2009 2 All studiesAll studies 1.74[0.27; 11.38]627422%NASvirsky, 2017 Weber-Schoendorfer (Controls unexposed, disease free), 2014 Svirsky, 2009 30.120.01.0

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) 8.19[0.51; 131.74]2136 -NAWeber-Schoendorfer (Controls unexposed, disease free), 2014 1 unexposed, sick controlsunexposed, sick controls 0.77[0.10; 6.05]41380%NASvirsky, 2017 Svirsky, 2009 2 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.69[0.15; 18.81]3136 -NAWeber-Schoendorfer (Controls exposed to other treatment, sick), 2014 10.510.01.0