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TNF-alpha inhibitors
Overall results
Study description
Excluded studies
Table
Graphic
auto
during pregnancy (anytime or not specified)
1st trimester
2nd trimester
3rd trimester
2nd and/or 3rd trimester
throughout pregnancy
early pregnancy
days before delivery
late pregnancy
preconception-only
periconceptional
preconceptional for kinetic reason
at least 1st trimester
3 months (or more) before pregnancy or during pregnancy
1st and 2nd trimester
3 months or more before pregnancy or1st trimester
Whatever the period exposition
individual studies
Outcome
TE
95% CI
n cases
n exposed
k
Pub. bias
Congenital malformations
All congenital malformations (majors, minors, majors and minors, or unspecified)
Verstappen, 2011 Cooper, 2014 Diav-Citrin (Controls unexposed, disease free), 2014 Weber-Schoendorfer, 2015 Chambers - Etanercept, 2015 De Lima (Controls unexposed, disease free), 2016 Hoxha, 2017 Chambers - Adalimumab (Controls unexposed, sick, ADA only), 2017 De Lima, 2018 Fu - Etanercept, 2019 De Lorenzo (Controls unexposed, sick), 2020 Drechsel, 2020 Moens (Controls unexposed, sick), 2020
13
1.57
[
1.16
; 2.14]
206
971
low
Major congenital malformations
Cooper, 2014 Diav-Citrin (Controls unexposed, disease free), 2014 Weber-Schoendorfer, 2015 Chambers - Etanercept, 2015 Hoxha, 2017 Chambers - Adalimumab (Controls unexposed, sick, ADA only), 2017 De Lima, 2018 Fu - Etanercept, 2019 Drechsel, 2020
9
1.67
[
1.08
; 2.58]
64
680
not evaluable
Congenital heart defects
Cooper, 2014
1
9.39
[
0.38
; 233.76]
1
56
not evaluable
Digestive system anomalies
Cooper, 2014
1
3.09
[
0.19
; 50.25]
2
56
not evaluable
Limb defects
Cooper, 2014
1
3.07
[
0.06
; 156.65]
-
56
not evaluable
Nervous system anomalies
Cooper, 2014
1
3.07
[
0.06
; 156.65]
-
56
not evaluable
Oro-facial clefts
0
-
-
-
-
-
Respiratory system anomalies
0
-
-
-
-
-
Chromosomal abnormalities
Weber-Schoendorfer, 2015
1
1.80
[
0.48
; 6.69]
15
421
not evaluable
Genital anomalies
Cooper, 2014
1
9.39
[
0.38
; 233.76]
1
56
not evaluable
Urinary malformations
Cooper, 2014
1
0.61
[
0.03
; 12.84]
2
56
not evaluable
Atrial septal defect
0
-
-
-
-
-
Atrioventricular septal defect
0
-
-
-
-
-
Cardiac septal defects
0
-
-
-
-
-
Congenital hydronephrosis
0
-
-
-
-
-
Ear, face and neck anomalies
0
-
-
-
-
-
Eye defects
0
-
-
-
-
-
Eye, ear, face and neck malformations
0
-
-
-
-
-
Hypospadias
0
-
-
-
-
-
Ventricular septal defect
0
-
-
-
-
-
Minor congenital malformations
Weber-Schoendorfer, 2015
1
1.27
[
0.70
; 2.30]
82
419
not evaluable
Growth parameters and prematurity
Preterm (< 37 weeks)
Verstappen, 2011 Cooper, 2014 Diav-Citrin (Controls unexposed, disease free), 2014 Weber-Schoendorfer, 2015 Chambers - Etanercept, 2015 Komoto, 2016 De Lima (Treatment stopped during pregnancy, sick), 2016 Hoxha, 2017 Carman - Etanercept (Controls unexposed, sick), 2017 Chambers - Adalimumab (Controls unexposed, sick, ADA only), 2017 Luu, 2018 Zbinden (rheumatoid arthritis), 2018 De Lima, 2018 Vinet (Controls unexposed, sick), 2018 Duricova, 2019 Moens (Controls unexposed, sick), 2020 De Lorenzo (Controls unexposed, sick), 2020 Drechsel, 2020
18
1.38
[
1.16
; 1.64]
1,455
2,329
low
Small for gestational age (weight)
Agosti, 2015 De Lima (Treatment stopped during pregnancy, sick), 2016 Hoxha, 2017 De Lima, 2018 Zbinden (rheumatoid arthritis), 2018 Moens (Controls unexposed, sick), 2020 De Lorenzo (Controls unexposed, sick), 2020 Drechsel, 2020
8
1.72
[
0.83
; 3.58]
21
311
not evaluable
Low birth weight (< 2500g)
Weber-Schoendorfer, 2015 De Lima (Treatment stopped during pregnancy, sick), 2016 Komoto, 2016 Carman - Etanercept (Controls unexposed, sick), 2017 Chambers - Adalimumab (Controls unexposed, sick, ADA only), 2017 De Lima, 2018 Duricova, 2019
7
1.86
[
0.66
; 5.25]
291
752
not evaluable
Macrosomia (> 4000g)
Agosti, 2015 De Lorenzo (Controls unexposed, sick), 2020
2
2.97
[
0.24
; 36.82]
1
36
not evaluable
Maternal consequences
Caesarean
Zbinden (rheumatoid arthritis), 2018 Duricova, 2019
2
2.56
[
0.15
; 42.43]
59
100
not evaluable
Gestational diabetes
Vinet (Controls unexposed, sick), 2018 Drechsel, 2020
2
1.15
[
0.88
; 1.49]
573
394
not evaluable
Maternal consequences (as a whole)
Hoxha, 2017 Luu, 2018 Zbinden (rheumatoid arthritis), 2018
3
1.66
[
1.40
; 1.95]
4
1,125
not evaluable
Preeclampsia
Fu - Etanercept, 2019 Drechsel, 2020
2
0.53
[
0.03
; 9.33]
11
109
not evaluable
Maternal infections
Desai, 2017 Luu, 2018
2
1.42
[
1.24
; 1.63]
19
1,849
not evaluable
Abruptio placentae (retroplacental hematoma)
0
-
-
-
-
-
Assisted deliveries (forceps, vacuum, ...)
0
-
-
-
-
-
Placenta previa
0
-
-
-
-
-
Neonatal disorders
Neonatal infections
De Lima (Treatment stopped during pregnancy, sick), 2016 Vinet (Controls unexposed, sick), 2018 Luu, 2018 De Lima, 2018 Duricova, 2019 Moens (Controls unexposed, sick), 2020 Drechsel, 2020
7
0.90
[
0.77
; 1.04]
96
1,064
not evaluable
Neonatal death (< 28 days of life)
Verstappen, 2011 Drechsel, 2020
2
4.47
[
0.37
; 54.48]
1
64
not evaluable
Neonatal medical care
0
-
-
-
-
-
Jaundice / Icterus
Agosti, 2015
1
1.00
[
0.06
; 16.97]
2
24
not evaluable
Neonatal disorders (as a whole)
Cooper, 2014
1
1.80
[
0.51
; 6.40]
11
56
not evaluable
Infant health status
Agosti, 2015
1
1.84
[
0.39
; 8.77]
8
24
not evaluable
Low Apgar score (< 7) (at 10 min)
0
-
-
-
-
-
Low Apgar score (< 7) (at 5 min)
0
-
-
-
-
-
Long term consequences
Child/Infant infections (> 1 year)
0
-
-
-
-
-
Intrauterine deaths
Early intrauterine death (< 22 weeks)
Verstappen, 2011 Diav-Citrin (Controls unexposed, disease free), 2014 Chambers - Etanercept, 2015 Weber-Schoendorfer, 2015 Carman - Etanercept (Controls unexposed, sick), 2017 Chambers - Adalimumab (Controls unexposed, sick, ADA only), 2017 Fu - Etanercept, 2019 Drechsel, 2020
8
0.99
[
0.66
; 1.48]
820
1,417
not evaluable
Late intrauterine deaths (> 22 weeks)
Verstappen, 2011 Cooper, 2014 Diav-Citrin (Controls unexposed, disease free), 2014 Weber-Schoendorfer, 2015 Carman - Etanercept (Controls unexposed, sick), 2017 Drechsel, 2020
6
1.43
[
0.68
; 3.03]
49
1,042
not evaluable
Elective/induced termination of pregnancy
Verstappen, 2011 Vinet, 2013 Diav-Citrin (Controls unexposed, disease free), 2014 Weber-Schoendorfer, 2015 Carman - Etanercept (Controls unexposed, sick), 2017 Drechsel, 2020
6
1.65
[
1.03
; 2.65]
509
1,172
not evaluable
Intrauterine deaths (as a whole or unspecified)
Komoto, 2016 Hoxha, 2017
2
1.57
[
0.03
; 83.21]
9
48
not evaluable
Ectopic pregnancy
Diav-Citrin (Controls unexposed, disease free), 2014 Drechsel, 2020
2
12.76
[
1.31
; 124.74]
2
104
not evaluable
Therapeutic terminations of pregnancy
0
-
-
-
-
-
Neuro-developmental disorders
Neuro-developmental disorders (as a whole)
Agosti, 2015 Duricova, 2019
2
0.83
[
0.29
; 2.40]
15
96
not evaluable
ASD (Autism spectrum disorder): Diagnosis
Duricova, 2019
1
0.96
[
0.06
; 15.62]
2
72
not evaluable
ASD (Autism spectrum disorder): Diagnosis/Risk
Duricova, 2019
1
0.96
[
0.06
; 15.62]
2
72
not evaluable
0.0
100.0
1.0