TNF-alpha inhibitors

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.
S4995
R13082		 Drechsel, 2020 Stillbirth 1st trimester prospective cohort unexposed, sick Adjustment: No 1.36 [0.05;34.56] C 0/21   1/85 1 21
ref
S4098
R8757		 Carman - Etanercept (Controls unexposed, disease free), 2017 Stillbirth during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed, disease free excluded Adjustment: No 0.55 [0.13;2.39] C
excluded (control group) 		2/337   18/1,685 20 337
ref
S4099
R8773		 Carman - Etanercept (Controls unexposed, sick), 2017 Stillbirth during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed, sick Adjustment: No 0.68 [0.16;2.87] C 2/337   25/2,861 27 337
ref
S2888
R4117		 Weber-Schoendorfer, 2015 Stillbirth 1st trimester prospective cohort unexposed, disease free Adjustment: No 2.22 [0.70;7.04] C 5/495   7/1,532 12 495
ref
S4074
R8625		 Cooper, 2014 Fetal death 1st trimester retrospective cohort (claims database) unexposed, sick Adjustment: No 0.33 [0.02;6.29] C 0/56   4/171 4 56
ref
S2897
R4078		 Diav-Citrin (Controls exposed to other treatments), 2014 Stillbirth (beyond 20 completed weeks) 1st trimester prospective cohort exposed to other treatment, sick excluded Adjustment: No 1.04 [0.06;16.85] C
excluded (control group) 		1/83   1/86 2 83
ref
S2893
R4062		 Diav-Citrin (Controls unexposed, disease free), 2014 Stillbirth (beyond 20 completed weeks) 1st trimester prospective cohort unexposed, disease free Adjustment: No 12.53 [0.51;310.51] C 1/83   0/341 1 83
ref
S3037
R4569		 Seirafi, 2014 Deaths in utero 3 months (or more) before pregnancy or during pregnancy excluded retrospective cohort unexposed, sick Adjustment: No before conception and/or during pregnancy 1.50 [0.13;16.74] C
excluded (exposition period) 		2/133   1/99 3 133
ref
S2916
R4128		 Verstappen, 2011 Intrauterine death (NOS) early pregnancy prospective cohort unexposed, sick Adjustment: No 1.40 [0.19;10.26] C 2/50   2/69 4 50
ref
Total 6 studies 1.43 [0.68;3.03] 49 1,042
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 Drechsel, 2020Drechsel, 2020 1.36[0.05; 34.56]1215%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Carman - Etanercept (Controls unexposed, sick), 2017Carman - Etanercept, 2017 1 0.68[0.16; 2.87]2733727%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Weber-Schoendorfer, 2015Weber-Schoendorfer, 2015 2.22[0.70; 7.04]1249542%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Cooper, 2014Cooper, 2014 0.33[0.02; 6.29]4566%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Diav-Citrin (Controls unexposed, disease free), 2014Diav-Citrin, 2014 2 12.53[0.51; 310.51]1835%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Verstappen, 2011Verstappen, 2011 1.40[0.19; 10.26]45014%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (6 studies) I2 = 0% 1.43[0.68; 3.03]491,0420.250.01.0ROB: 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;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.43[0.68; 3.03]491,0420%NADrechsel, 2020 Carman - Etanercept (Controls unexposed, sick), 2017 Weber-Schoendorfer, 2015 Cooper, 2014 Diav-Citrin (Controls unexposed, disease free), 2014 Verstappen, 2011 6 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 2.71[0.92; 8.01]135780%NAWeber-Schoendorfer, 2015 Diav-Citrin (Controls unexposed, disease free), 2014 2 unexposed, sickunexposed, sick 0.81[0.29; 2.26]364640%NADrechsel, 2020 Carman - Etanercept (Controls unexposed, sick), 2017 Cooper, 2014 Verstappen, 2011 4 Tags Adjustment   - No  - No 1.43[0.68; 3.03]491,0420%NADrechsel, 2020 Carman - Etanercept (Controls unexposed, sick), 2017 Weber-Schoendorfer, 2015 Cooper, 2014 Diav-Citrin (Controls unexposed, disease free), 2014 Verstappen, 2011 6 All studiesAll studies 1.43[0.68; 3.03]491,0420%NADrechsel, 2020 Carman - Etanercept (Controls unexposed, sick), 2017 Weber-Schoendorfer, 2015 Cooper, 2014 Diav-Citrin (Controls unexposed, disease free), 2014 Verstappen, 2011 60.150.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-3.94.21.9820.000Drechsel, 2020Carman - Etanercept (Controls unexposed, sick), 2017Weber-Schoendorfer, 2015Cooper, 2014Diav-Citrin (Controls unexposed, disease free), 2014Verstappen, 2011

Asymetry test p-value = 0.9862 (by Egger's regression)

slope=0.3433 (1.0178); intercept=0.0201 (1.0903); t=0.0184; p=0.9862

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 2897, 4098

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.66[0.42; 6.53]3391549%NACarman - Etanercept (Controls unexposed, disease free), 2017 Weber-Schoendorfer, 2015 Diav-Citrin (Controls unexposed, disease free), 2014 3 unexposed, sick controlsunexposed, sick controls 0.81[0.29; 2.26]364640%NADrechsel, 2020 Carman - Etanercept (Controls unexposed, sick), 2017 Cooper, 2014 Verstappen, 2011 4 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.04[0.06; 16.85]283 -NADiav-Citrin (Controls exposed to other treatments), 2014 10.510.01.0