Methotrexate (Pre-conception only)

Major congenital malformations

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
R18867
Svirsky, 2017 Serious birth malformation 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 1.19 [0.07;19.35] C 1/89   1/106 2 89
ref
S10346
R37888
Dawson, 2014 Major birth defects preconceptional for kinetic reason case control unexposed (general population or NOS) Adjustment: No Exposed group: MTX (polytherapy or not specified) Indications: Any or not specified MTX less than 3 months before pregnancy 0.92 [0.18;4.72] C 5/7   27,618/37,729 27,623 7
ref
S10348
R37940
Weber-Schoendorfer (Controls exposed to other treatment, sick), 2014 Major birth defects 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 1.10 [0.30;4.20]
excluded (control group)
4/114   14/393 18 114
ref
S10349
R37959
Weber-Schoendorfer (Controls unexposed, disease free), 2014 Major birth defects 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 1.60 [0.40;7.30] 4/114   29/1,001 33 114
ref
Total 3 studies 1.24 [0.45;3.42] 27,658 210
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 1.19[0.07; 19.35]28913%ROB confusion: criticalROB selection: criticalROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Dawson, 2014Dawson, 2014 0.92[0.18; 4.72]27,623738%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Weber-Schoendorfer (Controls unexposed, disease free), 2014Weber-Schoendorfer, 2014 1 1.60[0.40; 7.30]3311449%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Total (3 studies) I2 = 0% 1.24[0.45; 3.42]27,6582100.25.01.0ROB: 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 1.50[0.41; 5.45]352030%NASvirsky, 2017 Weber-Schoendorfer (Controls unexposed, disease free), 2014 2 case control studiescase control studies 0.92[0.18; 4.72]27,6237 -NADawson, 2014 1 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.25[0.42; 3.71]27,6561210%NADawson, 2014 Weber-Schoendorfer (Controls unexposed, disease free), 2014 2 unexposed, sickunexposed, sick 1.19[0.07; 19.35]289 -NASvirsky, 2017 1 Tags Adjustment   - No  - No 0.98[0.24; 4.03]27,625960%NASvirsky, 2017 Dawson, 2014 2   - Yes  - Yes 1.60[0.37; 6.84]33114 -NAWeber-Schoendorfer (Controls unexposed, disease free), 2014 1 Exposed group   - MTX (monotherapy)  - MTX (monotherapy) 1.19[0.07; 19.35]289 -NASvirsky, 2017 1   - MTX (polytherapy or not specified)  - MTX (polytherapy or not specified) 1.25[0.42; 3.71]27,6561210%NADawson, 2014 Weber-Schoendorfer (Controls unexposed, disease free), 2014 2 Indications   - Any or not specified  - Any or not specified 0.92[0.18; 4.72]27,6237 -NADawson, 2014 1   - Inflammatory diseases  - Inflammatory diseases 1.60[0.37; 6.84]33114 -NAWeber-Schoendorfer (Controls unexposed, disease free), 2014 1 MatchedMatched 1.60[0.37; 6.84]33114 -NAWeber-Schoendorfer (Controls unexposed, disease free), 2014 1 MTX less than 3 months before pregnancyMTX less than 3 months before pregnancy 1.25[0.42; 3.71]27,6561210%NADawson, 2014 Weber-Schoendorfer (Controls unexposed, disease free), 2014 2 MTX more than 3 months before pregnancyMTX more than 3 months before pregnancy 1.19[0.07; 19.35]289 -NASvirsky, 2017 1 MTX treatment for ectopic pregnancyMTX treatment for ectopic pregnancy 1.19[0.07; 19.35]289 -NASvirsky, 2017 1 All studiesAll studies 1.24[0.45; 3.42]27,6582100%NASvirsky, 2017 Dawson, 2014 Weber-Schoendorfer (Controls unexposed, disease free), 2014 30.25.01.0

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) 1.25[0.42; 3.71]27,6561210%NADawson, 2014 Weber-Schoendorfer (Controls unexposed, disease free), 2014 2 unexposed, sick controlsunexposed, sick controls 1.19[0.07; 19.35]289 -NASvirsky, 2017 1 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.10[0.29; 4.12]18114 -NAWeber-Schoendorfer (Controls exposed to other treatment, sick), 2014 10.510.01.0