Methotrexate (Post-conception)

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.
S10694
R39497		 Cooper (Controls exposed to other treatment, sick), 2014 Major congenital malformations 1st trimester retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No Exposed group: MTX (polytherapy or not specified) Indications: Inflammatory diseases 0.86 [0.11;6.73] C
excluded (control group) 		1/23   19/379 20 23
ref
S8721
R29474		 Cooper (Controls unexposed, sick), 2014 Major congenital malformations 1st trimester retrospective cohort (claims database) unexposed, sick Adjustment: Yes Exposed group: MTX (polytherapy or not specified) Indications: Inflammatory diseases 1.96 [0.23;17.00] 1/23   4/171 5 23
ref
S6761
R19214		 Dawson, 2014 Major birth defects 1st trimester case control unexposed (general population or NOS) Adjustment: No Exposed group: MTX (polytherapy or not specified) Indications: Any or not specified 1.83 [0.40;8.36] C 10/12   27,613/37,724 27,623 12
ref
S6775
R19172		 Weber-Schoendorfer (Controls exposed to other treatment, sick), 2014 Major birth defects at least 1st trimester prospective cohort exposed to other treatment, sick excluded Adjustment: Yes Exposed group: MTX (polytherapy or not specified) Indications: Inflammatory diseases Matched 1.80 [0.60;5.70]
excluded (control group) 		7/106   14/393 21 106
ref
S10347
R37912		 Weber-Schoendorfer (Controls unexposed, disease free), 2014 Major birth defects at least 1st trimester prospective cohort unexposed, disease free Adjustment: Yes Exposed group: MTX (polytherapy or not specified) Indications: Inflammatory diseases Matched 3.10 [1.03;9.50] 7/106   29/1,001 36 106
ref
S8745
R29584		 Viktil (Controls exposed to other treatment, sick), 2012 Major malformations 3 months (or more) before pregnancy or during pregnancy population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No Exposed group: MTX (polytherapy or not specified) Indications: Inflammatory diseases 1.85 [0.10;32.87] C
excluded (control group) 		0/8   50/1,453 50 8
ref
S10362
R37984		 Viktil (Controls unexposed NOS), 2012 Major malformations at least 1st trimester population based cohort retrospective unexposed (general population or NOS) Adjustment: No Exposed group: MTX (polytherapy or not specified) Indications: Inflammatory diseases 10.00 [0.41;245.45] C 0/2   5,000/154,976 5,000 2
ref
Total 4 studies 2.70 [1.21;6.02] 32,664 143
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 Cooper (Controls unexposed, sick), 2014Cooper, 2014 1 1.96[0.23; 17.00]52314%ROB confusion: seriousROB selection: criticalROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Dawson, 2014Dawson, 2014 1.83[0.40; 8.36]27,6231228%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Weber-Schoendorfer (Controls unexposed, disease free), 2014Weber-Schoendorfer, 2014 2 3.10[1.03; 9.50]3610652%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Viktil (Controls unexposed NOS), 2012Viktil, 2012 3 10.00[0.41; 245.45]5,00026%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Total (4 studies) I2 = 0% 2.70[1.21; 6.02]32,6641430.520.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, sick; 2: Controls unexposed, disease free; 3: Controls unexposed NOS;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 3.14[1.22; 8.07]5,0411310%NACooper (Controls unexposed, sick), 2014 Weber-Schoendorfer (Controls unexposed, disease free), 2014 Viktil (Controls unexposed NOS), 2012 3 case control studiescase control studies 1.83[0.40; 8.36]27,62312 -NADawson, 2014 1 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 2.85[1.20; 6.75]32,6591200%NADawson, 2014 Weber-Schoendorfer (Controls unexposed, disease free), 2014 Viktil (Controls unexposed NOS), 2012 3 unexposed, sickunexposed, sick 1.96[0.23; 16.85]523 -NACooper (Controls unexposed, sick), 2014 1 Tags Adjustment   - No  - No 2.50[0.63; 9.86]32,623140%NADawson, 2014 Viktil (Controls unexposed NOS), 2012 2   - Yes  - Yes 2.81[1.05; 7.55]411290%NACooper (Controls unexposed, sick), 2014 Weber-Schoendorfer (Controls unexposed, disease free), 2014 2 Exposed group   - MTX (polytherapy or not specified)  - MTX (polytherapy or not specified) 2.70[1.21; 6.02]32,6641430%NACooper (Controls unexposed, sick), 2014 Dawson, 2014 Weber-Schoendorfer (Controls unexposed, disease free), 2014 Viktil (Controls unexposed NOS), 2012 4 Indications   - Any or not specified  - Any or not specified 1.83[0.40; 8.36]27,62312 -NADawson, 2014 1   - Inflammatory diseases  - Inflammatory diseases 3.14[1.22; 8.07]5,0411310%NACooper (Controls unexposed, sick), 2014 Weber-Schoendorfer (Controls unexposed, disease free), 2014 Viktil (Controls unexposed NOS), 2012 3 MatchedMatched 3.10[1.02; 9.41]36106 -NAWeber-Schoendorfer (Controls unexposed, disease free), 2014 1 All studiesAll studies 2.70[1.21; 6.02]32,6641430%NACooper (Controls unexposed, sick), 2014 Dawson, 2014 Weber-Schoendorfer (Controls unexposed, disease free), 2014 Viktil (Controls unexposed NOS), 2012 40.520.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-3.84.81.9600.000Cooper (Controls unexposed, sick), 2014Dawson, 2014Weber-Schoendorfer (Controls unexposed, disease free), 2014Viktil (Controls unexposed NOS), 2012

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

not enought points

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 8745, 10694, 6775

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 2.85[1.20; 6.75]32,6591200%NADawson, 2014 Weber-Schoendorfer (Controls unexposed, disease free), 2014 Viktil (Controls unexposed NOS), 2012 3 unexposed, sick controlsunexposed, sick controls 1.96[0.23; 16.85]523 -NACooper (Controls unexposed, sick), 2014 1 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.52[0.57; 4.08]411290%NACooper (Controls exposed to other treatment, sick), 2014 Weber-Schoendorfer (Controls exposed to other treatment, sick), 2014 20.510.01.0