TNF-alpha inhibitors

Small for gestational age (weight)

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
R12904
Broms (Controls exposed to other treatments), 2020 Severe small for gestational age (sex-specific weight by gestational age below 2 standard deviations) during pregnancy (anytime or not specified) population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No 1.34 [0.94;1.90]
excluded (control group)
-/-   -/- - -
ref
S4890
R12896
Broms (Controls unexposed, disease free), 2020 Small for gestation age (sex-specific weight by gestational age in the 10th percentile or below 2 standard deviations) 3 months (or more) before pregnancy or during pregnancy excluded population based cohort retrospective unexposed, disease free Adjustment: No 1.52 [1.28;1.81] C
excluded (exposition period)
147/1,027   160,698/1,623,483 160,845 1,027
ref
S4958
R12995
De Lorenzo (Controls unexposed, disease free), 2020 Small for gestational age at least 1st trimester retrospective cohort unexposed, disease free excluded Adjustment: No 3.67 [0.63;21.35] C
excluded (control group)
3/12   3/36 6 12
ref
S4959
R13001
De Lorenzo (Controls unexposed, sick), 2020 Small for gestational age at least 1st trimester retrospective cohort unexposed, sick Adjustment: No 5.00 [0.72;34.73] C 3/12   2/32 5 12
ref
S4995
R13091
Drechsel, 2020 Small for gestational age 1st trimester prospective cohort unexposed, sick Adjustment: No 2.46 [0.21;29.20] C 1/14   2/66 3 14
ref
S4952
R12990
Moens (Controls exposed to Vedolizumab), 2020 Small for gestational age (weight below the 10th percentile with regard to gestational age) at least 1st trimester retrospective cohort exposed to other treatment, sick excluded Adjustment: No 0.39 [0.05;2.81] C
excluded (control group)
2/162   2/64 4 162
ref
S4951
R12985
Moens (Controls unexposed, sick), 2020 Small for gestational age (weight below the 10th percentile with regard to gestational age) at least 1st trimester retrospective cohort unexposed, sick Adjustment: No 0.67 [0.11;4.04] C 2/162   3/163 5 162
ref
S3066
R4658
Chaparro, 2018 Growth retardation (NOS) 3 months (or more) before pregnancy or during pregnancy excluded retrospective cohort unexposed, sick Adjustment: No 1.17 [0.54;2.56] C
excluded (exposition period)
13/388   13/453 26 388
ref
S3123
R4859
De Lima, 2018 Small for gestational age (weight below 2 SD for gestational age according to the Dutch reference chart). at least 1st trimester prospective cohort exposed to other treatment, sick Adjustment: No 0.79 [0.01;43.11] C 0/15   0/12 0 15
ref
S4898
R12942
Zbinden (rheumatoid arthritis), 2018 Small for gestational age (birth weight below the 10th percentile for gestational age). during pregnancy (anytime or not specified) prospective cohort unexposed, disease free Adjustment: Yes 2.60 [0.81;8.37] -/28   -/70 - 28
ref
S4899
R12946
Zbinden b (axial spondyloarthritis), 2018 Small for gestational age (birth weight below the 10th percentile for gestational age). during pregnancy (anytime or not specified) prospective cohort unexposed, disease free excluded Adjustment: Yes 1.30 [0.30;5.60]
excluded (control group)
-/31   -/70 - 31
ref
S3009
R4307
Hoxha, 2017 Small for gestational age (< 10th percentile) 1st trimester prospective cohort unexposed, sick Adjustment: No 2.44 [0.11;55.57] C 2/24   0/11 2 24
ref
S3070
R4685
De Lima (Controls unexposed, disease free), 2016 Small for gestational age (weight below the 10th percentile for gestational age) 1st and 2nd trimester prospective cohort unexposed, disease free excluded Adjustment: No 0.47 [0.17;1.32] C
excluded (control group)
4/83   78/804 82 83
ref
S3071
R4694
De Lima (Treatment stopped during pregnancy, sick), 2016 Small for gestational age (weight below the 10th percentile for gestational age) 1st and 2nd trimester prospective cohort unexposed, sick Adjustment: No 0.16 [0.01;3.15] C 0/32   4/51 4 32
ref
S3069
R4677
Agosti, 2015 Intrauterine growth restriction (NOS) during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: No 1.00 [0.06;16.97] C 1/24   1/24 2 24
ref
S3017
R4516
Schnitzler (Controls unexposed, disease free), 2011 Very small for gestational age < 5% percentile 3 months (or more) before pregnancy or during pregnancy prospective cohort unexposed, disease free excluded Adjustment: No before conception and/or during pregnancy 0.73 [0.13;4.26] C
excluded (control group)
2/32   4/48 6 32
ref
S3018
R4521
Schnitzler (Unexposed control, sick), 2011 Very small for gestational age < 5% percentile 3 months (or more) before pregnancy or during pregnancy excluded prospective cohort unexposed, sick Adjustment: No before conception and/or during pregnancy 0.55 [0.11;2.83] C
excluded (exposition period)
2/32   7/65 9 32
ref
Total 8 studies 1.72 [0.83;3.58] 21 311
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 5.00[0.72; 34.73]51214%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Drechsel, 2020Drechsel, 2020 2.46[0.21; 29.20]3149%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Moens (Controls unexposed, sick), 2020Moens, 2020 2 0.67[0.11; 4.04]516216%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA De Lima, 2018De Lima, 2018 0.79[0.01; 43.11]0153%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Zbinden (rheumatoid arthritis), 2018Zbinden, 2018 3 2.60[0.81; 8.37]-2839%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Hoxha, 2017Hoxha, 2017 2.44[0.11; 55.57]2245%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA De Lima (Treatment stopped during pregnancy, sick), 2016De Lima, 2016 4 0.16[0.01; 3.15]4326%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Agosti, 2015Agosti, 2015 1.00[0.06; 16.97]2247%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (8 studies) I2 = 0% 1.72[0.83; 3.58]213110.010.01.0ROB: 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: rheumatoid arthritis; 4: Treatment stopped during pregnancy, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.72[0.83; 3.58]213110%NADe Lorenzo (Controls unexposed, sick), 2020 Drechsel, 2020 Moens (Controls unexposed, sick), 2020 De Lima, 2018 Zbinden (rheumatoid arthritis), 2018 Hoxha, 2017 De Lima (Treatment stopped during pregnancy, sick), 2016 Agosti, 2015 8 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 2.60[0.81; 8.36]-28 -NAZbinden (rheumatoid arthritis), 2018 1 unexposed, sickunexposed, sick 1.36[0.52; 3.57]212680%NADe Lorenzo (Controls unexposed, sick), 2020 Drechsel, 2020 Moens (Controls unexposed, sick), 2020 Hoxha, 2017 De Lima (Treatment stopped during pregnancy, sick), 2016 Agosti, 2015 6 exposed to other treatment, sickexposed to other treatment, sick 0.79[0.01; 43.11]-15 -NADe Lima, 2018 1 Tags Adjustment   - No  - No 1.32[0.52; 3.38]212830%NADe Lorenzo (Controls unexposed, sick), 2020 Drechsel, 2020 Moens (Controls unexposed, sick), 2020 De Lima, 2018 Hoxha, 2017 De Lima (Treatment stopped during pregnancy, sick), 2016 Agosti, 2015 7   - Yes  - Yes 2.60[0.81; 8.36]-28 -NAZbinden (rheumatoid arthritis), 2018 1 All studiesAll studies 1.72[0.83; 3.58]213110%NADe Lorenzo (Controls unexposed, sick), 2020 Drechsel, 2020 Moens (Controls unexposed, sick), 2020 De Lima, 2018 Zbinden (rheumatoid arthritis), 2018 Hoxha, 2017 De Lima (Treatment stopped during pregnancy, sick), 2016 Agosti, 2015 80.010.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-4.85.32.4460.000De Lorenzo (Controls unexposed, sick), 2020Drechsel, 2020Moens (Controls unexposed, sick), 2020De Lima, 2018Zbinden (rheumatoid arthritis), 2018Hoxha, 2017De Lima (Treatment stopped during pregnancy, sick), 2016Agosti, 2015

Asymetry test p-value = 0.2795 (by Egger's regression)

slope=1.4973 (0.8637); intercept=-0.9741 (0.8195); t=1.1886; p=0.2795

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 3017, 3070, 4899, 4891, 4958, 4952

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.40[0.53; 3.65]8815453%NADe Lorenzo (Controls unexposed, disease free), 2020 Zbinden (rheumatoid arthritis), 2018 Zbinden b (axial spondyloarthritis), 2018 De Lima (Controls unexposed, disease free), 2016 4 unexposed, sick controlsunexposed, sick controls 1.36[0.52; 3.57]212680%NADe Lorenzo (Controls unexposed, sick), 2020 Drechsel, 2020 Moens (Controls unexposed, sick), 2020 Hoxha, 2017 De Lima (Treatment stopped during pregnancy, sick), 2016 Agosti, 2015 6 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.29[0.91; 1.82]41770%NABroms (Controls exposed to other treatments), 2020 Moens (Controls exposed to Vedolizumab), 2020 De Lima, 2018 30.510.01.0