TNF-alpha inhibitors

Table   Graphic  
individual studies
OutcomeTE95% CIn casesn exposedkPub. 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 131.57[1.16; 2.14]206971low 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 91.67[1.08; 2.58]64680not evaluable Congenital heart defects Cooper, 2014 19.39[0.38; 233.76]156not evaluable Digestive system anomalies Cooper, 2014 13.09[0.19; 50.25]256not evaluable Limb defects Cooper, 2014 13.07[0.06; 156.65]-56not evaluable Nervous system anomalies Cooper, 2014 13.07[0.06; 156.65]-56not evaluable Oro-facial clefts 0----- Respiratory system anomalies 0----- Chromosomal abnormalities Weber-Schoendorfer, 2015 11.80[0.48; 6.69]15421not evaluable Genital anomalies Cooper, 2014 19.39[0.38; 233.76]156not evaluable Urinary malformations Cooper, 2014 10.61[0.03; 12.84]256not 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 11.27[0.70; 2.30]82419not 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 181.38[1.16; 1.64]1,4552,329low 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 81.72[0.83; 3.58]21311not 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 71.86[0.66; 5.25]291752not evaluable Macrosomia (> 4000g) Agosti, 2015 De Lorenzo (Controls unexposed, sick), 2020 22.97[0.24; 36.82]136not evaluable Maternal consequences Caesarean Zbinden (rheumatoid arthritis), 2018 Duricova, 2019 22.56[0.15; 42.43]59100not evaluable Gestational diabetes Vinet (Controls unexposed, sick), 2018 Drechsel, 2020 21.15[0.88; 1.49]573394not evaluable Maternal consequences (as a whole) Hoxha, 2017 Luu, 2018 Zbinden (rheumatoid arthritis), 2018 31.66[1.40; 1.95]41,125not evaluable Preeclampsia Fu - Etanercept, 2019 Drechsel, 2020 20.53[0.03; 9.33]11109not evaluable Maternal infections Desai, 2017 Luu, 2018 21.42[1.24; 1.63]191,849not 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 70.90[0.77; 1.04]961,064not evaluable Neonatal death (< 28 days of life) Verstappen, 2011 Drechsel, 2020 24.47[0.37; 54.48]164not evaluable Neonatal medical care 0----- Jaundice / Icterus Agosti, 2015 11.00[0.06; 16.97]224not evaluable Neonatal disorders (as a whole) Cooper, 2014 11.80[0.51; 6.40]1156not evaluable Infant health status Agosti, 2015 11.84[0.39; 8.77]824not 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 80.99[0.66; 1.48]8201,417not 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 61.43[0.68; 3.03]491,042not 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 61.65[1.03; 2.65]5091,172not evaluable Intrauterine deaths (as a whole or unspecified) Komoto, 2016 Hoxha, 2017 21.57[0.03; 83.21]948not evaluable Ectopic pregnancy Diav-Citrin (Controls unexposed, disease free), 2014 Drechsel, 2020 212.76[1.31; 124.74]2104not evaluable Therapeutic terminations of pregnancy 0----- Neuro-developmental disorders Neuro-developmental disorders (as a whole) Agosti, 2015 Duricova, 2019 20.83[0.29; 2.40]1596not evaluable ASD (Autism spectrum disorder): Diagnosis Duricova, 2019 10.96[0.06; 15.62]272not evaluable ASD (Autism spectrum disorder): Diagnosis/Risk Duricova, 2019 10.96[0.06; 15.62]272not evaluable0.0100.01.0