TNF-alpha inhibitors

Preterm (< 37 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.
S4891
R12903		 Broms (Controls exposed to other treatments), 2020 Preterm birth (<37 weeks of gestation) during pregnancy (anytime or not specified) population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No 1.62 [1.29;2.04]
excluded (control group) 		-/-   -/- - -
ref
S4890
R12893		 Broms (Controls unexposed, disease free), 2020 Preterm birth (<37 weeks of gestation) 3 months (or more) before pregnancy or during pregnancy excluded population based cohort retrospective unexposed, disease free Adjustment: No 2.94 [2.44;3.54] C
excluded (exposition period) 		128/1,027   74,981/1,623,489 75,109 1,027
ref
S4958
R12997		 De Lorenzo (Controls unexposed, disease free), 2020 Preterm birth at least 1st trimester retrospective cohort unexposed, disease free excluded Adjustment: No 5.67 [0.82;39.21] C
excluded (control group) 		3/12   2/36 5 12
ref
S4959
R13003		 De Lorenzo (Controls unexposed, sick), 2020 Preterm birth at least 1st trimester retrospective cohort unexposed, sick Adjustment: No 3.22 [0.55;18.85] C 3/12   3/32 6 12
ref
S4995
R13088		 Drechsel, 2020 Preterm delivery (<37 0) 1st trimester prospective cohort unexposed, sick Adjustment: No 1.40 [0.26;7.61] C 2/14   7/66 9 14
ref
S4952
R12989		 Moens (Controls exposed to Vedolizumab), 2020 Premature born children (before 37 weeks of gestation) at least 1st trimester retrospective cohort exposed to other treatment, sick excluded Adjustment: No 0.51 [0.21;1.22] C
excluded (control group) 		14/162   10/64 24 162
ref
S4951
R12984		 Moens (Controls unexposed, sick), 2020 Premature born children (before 37 weeks of gestation) at least 1st trimester retrospective cohort unexposed, sick Adjustment: No 1.19 [0.53;2.66] C 14/162   12/163 26 162
ref
S3072
R4706		 Duricova, 2019 Preterm birth (gestational week < 37) during pregnancy (anytime or not specified) retrospective cohort unexposed, disease free Adjustment: No 3.61 [0.72;18.01] C 7/72   2/69 9 72
ref
S3066
R4666		 Chaparro, 2018 Preterm delivery (before week 37 of gestation) 3 months (or more) before pregnancy or during pregnancy excluded retrospective cohort unexposed, sick Adjustment: No 1.50 [0.93;2.43] C
excluded (exposition period) 		41/388   33/453 74 388
ref
S3123
R4858		 De Lima, 2018 Preterm birth (delivery before 37 weeks of gestation) at least 1st trimester prospective cohort exposed to other treatment, sick Adjustment: No 0.24 [0.01;6.53] C 0/15   1/12 1 15
ref
S4103
R8791		 Lichtenstein - infliximab, 2018 Preterm birth 3 months (or more) before pregnancy or during pregnancy excluded prospective cohort exposed to other treatment, sick Adjustment: No 0.80 [0.21;3.09] C
excluded (exposition period) 		4/81   5/82 9 81
ref
S3093
R4772		 Luu, 2018 Delivery <37WA during pregnancy (anytime or not specified) retrospective cohort (claims database) exposed to other treatment, sick Adjustment: No 1.31 [1.02;1.69] C 83/799   392/4,836 475 799
ref
S3076
R4722		 Vinet (Controls unexposed, disease free), 2018 Preterm birth (NOS) during pregnancy (anytime or not specified) retrospective cohort unexposed, disease free excluded Adjustment: No 1.36 [0.99;1.86] C
excluded (control group) 		45/380   1,313/14,596 1,358 380
ref
S3077
R4725		 Vinet (Controls unexposed, sick), 2018 Preterm birth (NOS) during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: No 1.08 [0.77;1.52] C 45/380   273/2,476 318 380
ref
S4898
R12941		 Zbinden (rheumatoid arthritis), 2018 Preterm delivery (< 37 weeks) during pregnancy (anytime or not specified) prospective cohort unexposed, disease free Adjustment: Yes 0.70 [0.20;2.51] -/28   -/70 - 28
ref
S4899
R12945		 Zbinden b (axial spondyloarthritis), 2018 Preterm delivery (< 37 weeks) during pregnancy (anytime or not specified) prospective cohort unexposed, disease free excluded Adjustment: Yes 4.50 [0.90;22.51]
excluded (control group) 		-/31   -/70 - 31
ref
S4098
R8760		 Carman - Etanercept (Controls unexposed, disease free), 2017 Birth before 37 wk during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed, disease free excluded Adjustment: No 1.70 [1.15;2.51] C
excluded (control group) 		40/217   127/1,081 167 217
ref
S4099
R8775		 Carman - Etanercept (Controls unexposed, sick), 2017 Birth before 37 wk during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed, sick Adjustment: No 1.40 [0.97;2.03] C 40/217   269/1,940 309 217
ref
S4105
R8795		 Chambers - Adalimumab (Controls unexposed, disease free), 2017 Preterm delivery (NOS) at least 1st trimester prospective cohort unexposed, disease free excluded Adjustment: Yes 2.58 [1.20;5.53]
excluded (control group) 		-/-   -/- - -
ref
S4106
R8798		 Chambers - Adalimumab (Controls unexposed, sick, ADA only), 2017 Preterm delivery (NOS) at least 1st trimester prospective cohort unexposed, sick Adjustment: Yes 0.82 [0.50;3.84] -/-   -/- - -
ref
S3009
R4304		 Hoxha, 2017 Premature birth (<37 weeks of gestation) 1st trimester prospective cohort unexposed, sick Adjustment: No 2.44 [0.11;55.57] C 2/24   0/11 2 24
ref
S3023
R5112		 Bröms b, 2016 Preterm birth (delivery before 37 weeks’ of gestation) 3 months or more before pregnancy or1st trimester excluded case control unexposed, sick Adjustment: Yes 4.23 [0.85;21.13]
excluded (exposition period) 		7/9   230/467 237 9
ref
S3070
R4687		 De Lima (Controls unexposed, disease free), 2016 Preterm birth (delivery prior to gestational week 37) 1st and 2nd trimester prospective cohort unexposed, disease free excluded Adjustment: No 2.38 [1.01;5.59] C
excluded (control group) 		7/83   30/804 37 83
ref
S3071
R4696		 De Lima (Treatment stopped during pregnancy, sick), 2016 Preterm birth (delivery prior to gestational week 37) 1st and 2nd trimester prospective cohort unexposed, sick Adjustment: No 1.22 [0.25;5.82] C 3/32   4/51 7 32
ref
S13735
R53498		 Komoto, 2016 Premature birth (<35 weeks) during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: No 0.84 [0.07;10.06] C 1/17   2/29 3 17
ref
S4104
R8794		 Chambers - Etanercept, 2015 Preterm delivery (NOS) at least 1st trimester prospective cohort unexposed, sick Adjustment: Yes 1.60 [0.86;2.98] -/-   -/- - -
ref
S2888
R4118		 Weber-Schoendorfer, 2015 Preterm birth (<37 weeks) 1st trimester prospective cohort unexposed, disease free Adjustment: Yes 1.69 [1.10;2.50] 71/403   123/1,373 194 403
ref
S4074
R8629		 Cooper, 2014 Preterm birth 1st trimester retrospective cohort (claims database) unexposed, sick Adjustment: No 0.81 [0.36;1.82] C 9/56   32/167 41 56
ref
S2897
R4083		 Diav-Citrin (Controls exposed to other treatments), 2014 Preterm 1st trimester prospective cohort exposed to other treatment, sick excluded Adjustment: No 1.76 [0.75;4.17] C
excluded (control group) 		15/66   11/77 26 66
ref
S2893
R4075		 Diav-Citrin (Controls unexposed, disease free), 2014 Preterm 1st trimester prospective cohort unexposed, disease free Adjustment: No 4.08 [1.98;8.38] C 15/66   22/327 37 66
ref
S3037
R4570		 Seirafi, 2014 Preterm delivery (delivery before 37 GW) 3 months (or more) before pregnancy or during pregnancy excluded retrospective cohort unexposed, sick Adjustment: No before conception and/or during pregnancy 1.22 [0.60;2.51] C
excluded (exposition period) 		23/117   15/90 38 117
ref
S3017
R4514		 Schnitzler (Controls unexposed, disease free), 2011 Premature birth (<37 weeks) 3 months (or more) before pregnancy or during pregnancy prospective cohort unexposed, disease free excluded Adjustment: No before conception and/or during pregnancy 5.00 [1.21;20.61] C
excluded (control group) 		8/32   3/48 11 32
ref
S3018
R4519		 Schnitzler (Unexposed control, sick), 2011 Premature birth (<37 weeks) 3 months (or more) before pregnancy or during pregnancy excluded prospective cohort unexposed, sick Adjustment: No before conception and/or during pregnancy 2.38 [0.80;7.06] C
excluded (exposition period) 		8/32   8/65 16 32
ref
S2916
R4130		 Verstappen, 2011 Premature delivery (≤36 weeks) early pregnancy prospective cohort unexposed, sick Adjustment: No 1.53 [0.54;4.39] C 8/32   10/56 18 32
ref
Total 18 studies 1.38 [1.16;1.64] 1,455 2,329
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 De Lorenzo (Controls unexposed, sick), 2020De Lorenzo, 2020 1 3.22[0.55; 18.85]6121%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Drechsel, 2020Drechsel, 2020 1.40[0.26; 7.61]9141%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Moens (Controls unexposed, sick), 2020Moens, 2020 2 1.19[0.53; 2.66]261624%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Duricova, 2019Duricova, 2019 3.61[0.72; 18.01]9721%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA De Lima, 2018De Lima, 2018 0.24[0.01; 6.53]1150%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Luu, 2018Luu, 2018 1.31[1.02; 1.69]47579924%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Vinet (Controls unexposed, sick), 2018Vinet, 2018 3 1.08[0.77; 1.52]31838017%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Zbinden (rheumatoid arthritis), 2018Zbinden, 2018 4 0.70[0.20; 2.51]-282%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Carman - Etanercept (Controls unexposed, sick), 2017Carman - Etanercept, 2017 5 1.40[0.97; 2.03]30921715%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Chambers - Adalimumab (Controls unexposed, sick, ADA only), 2017Chambers - Adalimumab, 2017 6 0.82[0.50; 3.84]--3%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Hoxha, 2017Hoxha, 2017 2.44[0.11; 55.57]2240%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA De Lima (Treatment stopped during pregnancy, sick), 2016De Lima, 2016 7 1.22[0.25; 5.82]7321%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Komoto, 2016Komoto, 2016 0.84[0.07; 10.06]3170%ROB confusion: criticalROB selection: unclearROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Chambers - Etanercept, 2015Chambers - Etanercept, 2015 1.60[0.86; 2.98]--7%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Weber-Schoendorfer, 2015Weber-Schoendorfer, 2015 1.69[1.10; 2.50]19440313%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Cooper, 2014Cooper, 2014 0.81[0.36; 1.82]41564%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Diav-Citrin (Controls unexposed, disease free), 2014Diav-Citrin, 2014 8 4.08[1.98; 8.38]37665%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Verstappen, 2011Verstappen, 2011 1.53[0.54; 4.39]18323%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (18 studies) I2 = 13% 1.38[1.16; 1.64]1,4552,3290.210.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, sick; 2: Controls unexposed, sick; 3: Controls unexposed, sick; 4: rheumatoid arthritis; 5: Controls unexposed, sick; 6: Controls unexposed, sick, ADA only; 7: Treatment stopped during pregnancy, sick; 8: Controls unexposed, disease free;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.38[1.16; 1.64]1,4552,32913%criticalDe Lorenzo (Controls unexposed, sick), 2020 Drechsel, 2020 Moens (Controls unexposed, sick), 2020 Duricova, 2019 De Lima, 2018 Luu, 2018 Vinet (Controls unexposed, sick), 2018 Zbinden (rheumatoid arthritis), 2018 Carman - Etanercept (Controls unexposed, sick), 2017 Chambers - Adalimumab (Controls unexposed, sick, ADA only), 2017 Hoxha, 2017 De Lima (Treatment stopped during pregnancy, sick), 2016 Komoto, 2016 Chambers - Etanercept, 2015 Weber-Schoendorfer, 2015 Cooper, 2014 Diav-Citrin (Controls unexposed, disease free), 2014 Verstappen, 2011 18 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 2.08[1.05; 4.12]24056960%criticalDuricova, 2019 Zbinden (rheumatoid arthritis), 2018 Weber-Schoendorfer, 2015 Diav-Citrin (Controls unexposed, disease free), 2014 4 unexposed, sickunexposed, sick 1.23[1.01; 1.50]7399460%criticalDe Lorenzo (Controls unexposed, sick), 2020 Drechsel, 2020 Moens (Controls unexposed, sick), 2020 Vinet (Controls unexposed, sick), 2018 Carman - Etanercept (Controls unexposed, sick), 2017 Chambers - Adalimumab (Controls unexposed, sick, ADA only), 2017 Hoxha, 2017 De Lima (Treatment stopped during pregnancy, sick), 2016 Komoto, 2016 Chambers - Etanercept, 2015 Cooper, 2014 Verstappen, 2011 12 exposed to other treatment, sickexposed to other treatment, sick 1.29[0.93; 1.80]4768141%criticalDe Lima, 2018 Luu, 2018 2 Tags Adjustment   - No  - No 1.38[1.11; 1.71]1,2611,89820%criticalDe Lorenzo (Controls unexposed, sick), 2020 Drechsel, 2020 Moens (Controls unexposed, sick), 2020 Duricova, 2019 De Lima, 2018 Luu, 2018 Vinet (Controls unexposed, sick), 2018 Carman - Etanercept (Controls unexposed, sick), 2017 Hoxha, 2017 De Lima (Treatment stopped during pregnancy, sick), 2016 Komoto, 2016 Cooper, 2014 Diav-Citrin (Controls unexposed, disease free), 2014 Verstappen, 2011 14   - Yes  - Yes 1.46[1.06; 2.02]1944313%criticalZbinden (rheumatoid arthritis), 2018 Chambers - Adalimumab (Controls unexposed, sick, ADA only), 2017 Chambers - Etanercept, 2015 Weber-Schoendorfer, 2015 4 All studiesAll studies 1.38[1.16; 1.64]1,4552,32913%criticalDe Lorenzo (Controls unexposed, sick), 2020 Drechsel, 2020 Moens (Controls unexposed, sick), 2020 Duricova, 2019 De Lima, 2018 Luu, 2018 Vinet (Controls unexposed, sick), 2018 Zbinden (rheumatoid arthritis), 2018 Carman - Etanercept (Controls unexposed, sick), 2017 Chambers - Adalimumab (Controls unexposed, sick, ADA only), 2017 Hoxha, 2017 De Lima (Treatment stopped during pregnancy, sick), 2016 Komoto, 2016 Chambers - Etanercept, 2015 Weber-Schoendorfer, 2015 Cooper, 2014 Diav-Citrin (Controls unexposed, disease free), 2014 Verstappen, 2011 180.110.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-4.04.32.0190.000De Lorenzo (Controls unexposed, sick), 2020Drechsel, 2020Moens (Controls unexposed, sick), 2020Duricova, 2019De Lima, 2018Luu, 2018Vinet (Controls unexposed, sick), 2018Zbinden (rheumatoid arthritis), 2018Carman - Etanercept (Controls unexposed, sick), 2017Chambers - Adalimumab (Controls unexposed, sick, ADA only), 2017Hoxha, 2017De Lima (Treatment stopped during pregnancy, sick), 2016Komoto, 2016Chambers - Etanercept, 2015Weber-Schoendorfer, 2015Cooper, 2014Diav-Citrin (Controls unexposed, disease free), 2014Verstappen, 2011

Asymetry test p-value = 0.8319 (by Egger's regression)

slope=0.2883 (0.1300); intercept=0.0918 (0.4257); t=0.2157; p=0.8319

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 3017, 2897, 3070, 4098, 4105, 3076, 4899, 4891, 4958, 4952

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.95[1.47; 2.59]1,8071,29239%NADe Lorenzo (Controls unexposed, disease free), 2020 Duricova, 2019 Vinet (Controls unexposed, disease free), 2018 Zbinden (rheumatoid arthritis), 2018 Zbinden b (axial spondyloarthritis), 2018 Carman - Etanercept (Controls unexposed, disease free), 2017 Chambers - Adalimumab (Controls unexposed, disease free), 2017 De Lima (Controls unexposed, disease free), 2016 Weber-Schoendorfer, 2015 Diav-Citrin (Controls unexposed, disease free), 2014 10 unexposed, sick controlsunexposed, sick controls 1.23[1.01; 1.50]7399460%NADe Lorenzo (Controls unexposed, sick), 2020 Drechsel, 2020 Moens (Controls unexposed, sick), 2020 Vinet (Controls unexposed, sick), 2018 Carman - Etanercept (Controls unexposed, sick), 2017 Chambers - Adalimumab (Controls unexposed, sick, ADA only), 2017 Hoxha, 2017 De Lima (Treatment stopped during pregnancy, sick), 2016 Komoto, 2016 Chambers - Etanercept, 2015 Cooper, 2014 Verstappen, 2011 12 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.31[0.96; 1.80]5261,04252%NABroms (Controls exposed to other treatments), 2020 Moens (Controls exposed to Vedolizumab), 2020 De Lima, 2018 Luu, 2018 Diav-Citrin (Controls exposed to other treatments), 2014 50.510.01.0