Interferon beta (IFN-beta)

All congenital malformations (majors, minors, majors and minors, 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.
S3728
R8027		 Portaccio, 2018 Malformations (minor and major) early pregnancy prospective cohort unexposed, sick Adjustment: No 1.08 [0.22;5.33] C 2/76   7/288 9 76
ref
S3716
R11318		 Thiel (control unexposed, sick), 2016 Major congenital anomalies early pregnancy prospective cohort unexposed, sick Adjustment: Yes 0.72 [0.29;1.80] 7/227   10/181 17 227
ref
S3627
R7397		 Lu (control exposed to Glatiramer), 2012 Congenital anomalies (major and minor) during pregnancy (anytime or not specified) retrospective cohort exposed to other treatment, sick excluded Adjustment: No 0.38 [0.01;21.58] C
excluded (control group) 		0/15   0/6 0 15
ref
S3629
R7403		 Lu (control unexposed, sick), 2012 Congenital anomalies during pregnancy (anytime or not specified) excluded retrospective cohort unexposed, sick Adjustment: No 0.52 [0.03;9.05] C
excluded (exposition period) 		0/15   24/397 24 15
ref
S3618
R7375		 Finkelsztejn (control exposed to Glatiramer), 2011 Neonatal malformations early pregnancy retrospective cohort exposed to other treatment, sick excluded Adjustment: No 1.47 [0.07;31.84] C
excluded (control group) 		2/69   0/20 2 69
ref
S3619
R7377		 Finkelsztejn (control unexposed, sick), 2011 Neonatal malformations early pregnancy retrospective cohort unexposed, sick Adjustment: No 3.20 [0.15;68.20] C 2/69   0/43 2 69
ref
S3735
R11317		 Colvin - IFN beta1b, 2010 Birth defects 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No 3.40 [0.40;28.00] 1/7   4,994/106,045 4,995 7
ref
S3613
R7361		 Weber-Schoendorfer (control exposed to Glatiramer), 2009 Birth defects (all) at least 1st trimester prospective cohort exposed to other treatment, sick excluded Adjustment: No 0.71 [0.11;4.51] C
excluded (control group) 		3/54   2/26 5 54
ref
S3614
R7365		 Weber-Schoendorfer (control unexposed, disease free), 2009 Birth defects (all) at least 1st trimester prospective cohort unexposed, disease free excluded Adjustment: No 0.90 [0.17;2.88]
excluded (control group) 		3/54   86/1,408 89 54
ref
S3615
R7369		 Weber-Schoendorfer (control unexposed, sick), 2009 Birth defects (all) at least 1st trimester prospective cohort unexposed, sick Adjustment: No 0.61 [0.14;2.69] C 3/54   5/57 8 54
ref
S3723
R11315		 Boskovic (control unexposed, disease free), 2005 Major malformations 1st trimester prospective cohort unexposed, disease free excluded Adjustment: No 1.81 [0.15;21.60] C
excluded (control group) 		2/23   1/20 3 23
ref
S3724
R11316		 Boskovic (control unexposed, sick), 2005 Major malformations 1st trimester prospective cohort unexposed, sick Adjustment: No 1.90 [0.16;22.69] C 2/23   1/21 3 23
ref
Total 6 studies 0.97 [0.52;1.81] 5,034 456
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 Portaccio, 2018Portaccio, 2018 1.08[0.22; 5.33]97616%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Thiel (control unexposed, sick), 2016Thiel, 2016 1 0.72[0.29; 1.80]1722747%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Finkelsztejn (control unexposed, sick), 2011Finkelsztejn, 2011 2 3.20[0.15; 68.20]2694%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Colvin - IFN beta1b, 2010Colvin - IFN beta1b, 2010 3.40[0.40; 28.00]4,99579%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Weber-Schoendorfer (control unexposed, sick), 2009Weber-Schoendorfer, 2009 3 0.61[0.14; 2.69]85418%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Boskovic (control unexposed, sick), 2005Boskovic, 2005 4 1.90[0.16; 22.69]3236%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (6 studies) I2 = 0% 0.97[0.52; 1.81]5,0344560.210.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: control unexposed, sick; 2: control unexposed, sick; 3: control unexposed, sick; 4: control unexposed, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 0.97[0.52; 1.81]5,0344560%NAPortaccio, 2018 Thiel (control unexposed, sick), 2016 Finkelsztejn (control unexposed, sick), 2011 Colvin - IFN beta1b, 2010 Weber-Schoendorfer (control unexposed, sick), 2009 Boskovic (control unexposed, sick), 2005 6 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 3.40[0.41; 28.45]4,9957 -NAColvin - IFN beta1b, 2010 1 unexposed, sickunexposed, sick 0.86[0.44; 1.65]394490%NAPortaccio, 2018 Thiel (control unexposed, sick), 2016 Finkelsztejn (control unexposed, sick), 2011 Weber-Schoendorfer (control unexposed, sick), 2009 Boskovic (control unexposed, sick), 2005 5 Tags Adjustment   - No  - No 1.26[0.53; 2.99]5,0172290%NAPortaccio, 2018 Finkelsztejn (control unexposed, sick), 2011 Colvin - IFN beta1b, 2010 Weber-Schoendorfer (control unexposed, sick), 2009 Boskovic (control unexposed, sick), 2005 5   - Yes  - Yes 0.72[0.29; 1.79]17227 -NAThiel (control unexposed, sick), 2016 1 All studiesAll studies 0.97[0.52; 1.81]5,0344560%NAPortaccio, 2018 Thiel (control unexposed, sick), 2016 Finkelsztejn (control unexposed, sick), 2011 Colvin - IFN beta1b, 2010 Weber-Schoendorfer (control unexposed, sick), 2009 Boskovic (control unexposed, sick), 2005 60.210.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-3.73.61.8740.000Portaccio, 2018Thiel (control unexposed, sick), 2016Finkelsztejn (control unexposed, sick), 2011Colvin - IFN beta1b, 2010Weber-Schoendorfer (control unexposed, sick), 2009Boskovic (control unexposed, sick), 2005

Asymetry test p-value = 0.0412 (by Egger's regression)

slope=-1.1282 (0.4000); intercept=1.5145 (0.5102); t=2.9683; p=0.0412

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 3723, 3613, 3614, 3618, 3627

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.43[0.49; 4.14]5,087840%NAColvin - IFN beta1b, 2010 Weber-Schoendorfer (control unexposed, disease free), 2009 Boskovic (control unexposed, disease free), 2005 3 unexposed, sick controlsunexposed, sick controls 0.86[0.44; 1.65]394490%NAPortaccio, 2018 Thiel (control unexposed, sick), 2016 Finkelsztejn (control unexposed, sick), 2011 Weber-Schoendorfer (control unexposed, sick), 2009 Boskovic (control unexposed, sick), 2005 5 exposed to other treatment, sick controlsexposed to other treatment, sick controls 0.86[0.18; 4.20]71230%NAFinkelsztejn (control exposed to Glatiramer), 2011 Weber-Schoendorfer (control exposed to Glatiramer), 2009 20.510.01.0