TNF-alpha inhibitors

Exposed non-exposed studies (cohort)

Study	Country Study period	Population source	Exposure definition	Non-exposure definition	Sample size	Rmk
Agosti, 2015	Italy Not specified	Not specified	Children who were exposed in utero to anti-TNFalfa agents.	unexposed, sick Non-exposed children born to women with the same disease.	24 / 24	Exposures: 20 exposed to etanercept, 3 to adalimumab, 1 to certolizumab.
Broms (Controls exposed to other treatments), 2020	Denmark, Finland and Sweden 2006 - 2013	All women who gave birth to a singleton infant during the study period.	Women who filled prescriptions for Anti-TNF agent (ETA, IFX, ADA, CZP, or GOL) within 90 days before their LMP until delivery.	exposed to other treatment, sick Women who filled prescriptions for Nonbiologic systemic treatment (mainly azathioprine, corticosteroids, sulfasalazine, anti-malarials, and methotrexate) within 90 days before their LMP until delivery.	1027 / 9393
Broms (Controls unexposed, disease free), 2020	Denmark, Finland and Sweden 2006 - 2013	All women who gave birth to a singleton infant during the study period.	Women who filled prescriptions for Anti-TNF agent (ETA, IFX, ADA, CZP, or GOL) within 90 days before their LMP until delivery.	unexposed, disease free The general population (women without the diseases of interest and without treatment).	1027 / 1623483
Bröms a (Controls unexposed, disease free), 2016	Denmark and Sweden 2004/6 - 2012	Women and their infants up to 1 year of age (among all 15 million residents of Denmark and Sweden).	Women who had filled prescriptions for etanercept, infliximab, adalimumab, certolizumab-pegol, or golimumab within 90 days before and 90 days after their last menstrual period.	unexposed, disease free Women without disease or TNF treatment (ie, the general population).	683 / 1250192	EXPOSURE: ETN (50.4%), INF (22.8%), ADA (23.6%), CER (0.3%), GOL (0.6%), combinations (2.3%).
Bröms a (Controls unexposed, sick), 2016	Denmark and Sweden 2004/6 - 2012	Women and their infants up to 1 year of age (among all 15 million residents of Denmark and Sweden).	Women who had filled prescriptions for etanercept, infliximab, adalimumab, certolizumab-pegol, or golimumab within 90 days before and 90 days after their last menstrual period.	unexposed, sick Women with chronic inflammatory disease but no anti-TNF treatment.	683 / 21549	EXPOSURE: ETN (50.4%), INF (22.8%), ADA (23.6%), CER (0.3%), GOL (0.6%), combinations (2.3%). Controls: Corticosteroids (7.7%); anti-inflammatory treatments (20.8%: AZA, mercaptopurine, cyclosporine, acitretin, mycophenolate...); MTX (0.2%).
Carman - Etanercept (Controls unexposed, disease free), 2017	USA 1995 - 2012	All women with diagnosis or procedure codes suggestive of pregnancy and all mother‐infant pairs enrolled during the study period.	Pregnant women diagnosed with chronic inflammatory arthritis (cIA) or Psoriasis (PsO) treated with etanercept during pregnancy.	unexposed, disease free General population comparator group without chronic inflammatory arthritis (cIA) or Psoriasis (PsO) or TNFi treatment (ETN, adalimumab, certolizumab, golimumab, or infliximab).	337 / 1685	Addition of Chronic Inflammatory Arthritis (n=256) and Psoriasis (n=81) patients and their respective control group (n=1280 and 405).
Carman - Etanercept (Controls unexposed, sick), 2017	USA 1995 - 2012	All women with diagnosis or procedure codes suggestive of pregnancy and all mother‐infant pairs enrolled during the study period.	Pregnant women diagnosed with chronic inflammatory arthritis (cIA) or Psoriasis (PsO) treated with etanercept during pregnancy.	unexposed, sick Pregnant women diagnosed with chronic inflammatory arthritis (cIA) or Psoriasis (PsO) not treated with any TNFi (ETN, adalimumab, certolizumab, golimumab, or infliximab).	337 / 2861	Addition of Chronic Inflammatory Arthritis (n=256) and Psoriasis (n=81) patients and their respective control group (n=1512 and 1349).
Casanova, 2013	Spain Not specified	All women who had become pregnant after the diagnosis of Crohn’s disease (CD) or ulcerative colitis (UC) followed in the IBD Units from 24 Spanish hospitals.	Pregnancies in IBD patients on anti-TNF-α during pregnancy or during the 3 months before conception. (This is a subgroup of exposure among the whole exposed group considered in the study).	exposed to other treatment, sick Pregnancies in IBD patients which did not receive thiopurines or anti-TNF-α drugs either during pregnancy or the 3 months before conception. (84% exposed to 5-Aminosalicylates and/or steroids).	66 / 318	Primary aim: evaluate the safety of thiopurines and anti-TNF-α during conception and pregnancy in IBD patients. Exposed population divided in 2 groups: A) thiopurines alone; B) anti-TNF-α drugs (IFX, ADA, and CZB) with or without concomitant thiopurines.
Chambers - Adalimumab (Controls unexposed, disease free), 2017	USA and Canada 2004 - 2014	Women enrolled in the OTIS Autoimmune Diseases in Pregnancy Project prior to 20 weeks’ gestation.	Pregnant women who had been treated with adalimumab in pregnancy for Rheumatoid arthritis (RA) or Crohn’s Disease (CD).	unexposed, disease free Pregnant women non diseased and unexposed to adalimumab.	257 / 225	Chambers 2017: related to the 2 indications: RA et CD. Chambers 2017 included rather than Burmester 2017 (the latest Short Communication published) because it concerns only RA.
Chambers - Adalimumab (Controls unexposed, sick, ADA only), 2017	USA and Canada 2004 - 2014	Women enrolled in the OTIS Autoimmune Diseases in Pregnancy Project prior to 20 weeks’ gestation.	Pregnant women who had been treated with adalimumab in pregnancy for Rheumatoid arthritis (RA) or Crohn’s Disease (CD).	unexposed, sick Pregnant women disease-matched not treated with adalimumab.	257 / 120	Chambers 2017: related to the 2 indications: RA et CD. Chambers 2017 included rather than Burmester 2017 (the latest Short Communication published) because it concerns only RA.
Chambers - Etanercept, 2015	USA and Canada 2005 - 2012	Women enrolled in the OTIS Autoimmune Diseases in Pregnancy Project.	Pregnancy outcomes in women treated with Etanercept. A total of 344 women received ETA in the first trimester; and 51% used ETA in the third trimester.	unexposed, sick Pregnancy outcomes in disease-matched (DM) women.	370 / 164	There were no significant differences between groups in prenatal or postnatal growth, rates of serious or opportunistic infections, or developmental concerns on the ASQ. No malignancies were reported.
Chaparro, 2018	Multicenter European countries 1999 - 2014	Children born to women diagnosed with IBD.	Children from mothers with IBD treated with anti- TNFα drugs either in monotherapy or in combination with thiopurines at any time during pregnancy or during the 3 months before conception.	unexposed, sick Children from mothers with IBD not treated with anti-TNFα drugs or thiopurines at any time during pregnancy or during the 3 months before conception.	388 / 453	Exposure: Infliximab (n = 223), Adalimumab (n = 164), Certolizumab pegol (n = 1): First trimester : 353 (91%); Second trimester : 345 (89%); Thrid trimester: 148 (38%).
Cooper, 2014	USA 1995 - 2007	Women with inflammatory arthropathies, Systemic lupus erythematosus, and inflammatory bowel disease who filled prescriptions for immunosuppressive or corticosteroids during pregnancy.	Prescription for one of tumor necrosis factor inhibitor (TNFi) (in the absence of methotrexate fetal exposure) during the first trimester of pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed, sick Women with immune-mediated diseases treated with immunosuppressive medications in the 180 days before, but not during, pregnancy.	56 / 171	Births in which the mother received prescriptions during the first trimester for medications thought to be teratogenic (valproic acid, chemotherapy medications, lithium misoprostol, and warfarin) were excluded.
De Lima, 2018	The Netherlands 2014 - 2017	All IBD women who visited the preconception outpatient clinic at the Erasmus University Medical Center Rotterdam.	Children born to mothers with IBD treated with anti-TNF during part of the pregnancy or the entire pregnancy.	exposed to other treatment, sick Children born to mothers with IBD not treated with anti-TNF, but any other IBD medication was permitted.	15 / 12	Women in the study group were treated with anti-TNF alpha during pregnancy, at least until the end of the second trimester. Exposure: IFX (n=8); ADA (n=7)
De Lima (Controls unexposed, disease free), 2016	The Netherlands 2008 - 2014	All women with a confirmed diagnosis of IBD treated with any anti-TNF agent who visited the IBD preconception outpatient clinic were enrolled in the study.	Children born to IBD mothers, exposed to anti-TNF in utero (exposure at least during the 1st trimester and continued during 2nd and/or 3rd trimester).	unexposed, disease free Children born to non-IBD mothers not treated with anti-TNF as recruited from the Generation R cohort.	83 / 804	In part this cohort consists of patients from a previously published cohort (Zelinkova et al., 2013). Exposed group included: Stop group (Anti-TNF stopped after T1 and before 25 GW) and Continue group (anti-TNF not stopped or stopped after 30 GW).
De Lima (Treatment stopped during pregnancy, sick), 2016	The Netherlands 2008 - 2014	All women with a confirmed diagnosis of IBD treated with any anti-TNF agent who visited the IBD preconception outpatient clinic were enrolled in the study.	Children born to IBD mothers exposed to anti-TNF in utero at least during the first trimester and continued at least until GW 30 (continue group).	unexposed, sick Children born to IBD mothers exposed to anti-TNF in utero at least during the first trimester and discontinued before week 25 (stop group).	32 / 51	In part this cohort consists of patients from a previously published cohort (Zelinkova et al., 2013). Exposed group divided by 2: Stop group (Anti-TNF stopped after T1 and before 25 GW) versus continue group (anti-TNF not stopped or stopped after 30 GW).
De Lorenzo (Controls unexposed, disease free), 2020	Italy 2009 - 2017	Mothers who attended the Clinic.	Children born to mothers with autoimmune diseases on Anti-TNF therapy during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed, disease free Children born to healthy mothers.	12 / 36	Exposed group: addition of children exposed in utero to Etanercept, Adalimumab, Infliximad and Certolizumab.
De Lorenzo (Controls unexposed, sick), 2020	Italy 2009 - 2017	Mothers who attended the Clinic.	Children born to mothers with autoimmune diseases on Anti-TNF therapy during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed, sick Children born to mothers with autoimmune diseases not treated with Biologic disease-modifying anti-rheumatic drugs (bDMARDs).	12 / 32	Exposed group: addition of children exposed in utero to Etanercept, Adalimumab, Infliximad and Certolizumab. Unexposed: 13 of 32 neonates were born to mothers under no immunosuppressive, 15 to HCQ, 1 to AZA and 3 to both AZA and HCQ.
Desai, 2017	USA 2000 - 2010	Women with a recorded diagnosis of the systemic inflammatory conditions of interest aged 12 to 55 years with completed pregnancies resulting in liveborn infants and who filled at least one outpatient prescription for an immunosuppressive agent during pregnancy.	Pregnant women treated with TNF inhibitors for rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, or inflammatory bowel disease.	exposed to other treatment, sick Pregnant women treated with non-biologic agents for immunosuppressive drugs for rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, or inflammatory bowel disease.	776 / 816	Two control groups: steroids, non-biologic agents. The control group 'non-biologic agents' was retained because patients should be closer than patients with TNFa inhibitors.
Diav-Citrin (Controls exposed to other treatments), 2014	Israel 2002 - 2011	Pregnant women counseled by the Israeli Teratology Information Service (TIS), Jerusalem.	Pregnant women counseled for TNF-a-antagonists (infliximab, etanercept, or adalimumab) exposure.	exposed to other treatment, sick Pregnant women with similar autoimmune diseases not treated with anti-TNF-a medications during pregnancy (either treated with medications other than anti-TNF-a excluding methotrexate, or untreated during pregnancy).	83 / 86	Analyses were performed for the group of 3 TNF-α inhibitors (35 infliximab-, 25 etanercept-, and 23 adalimumab-exposed pregnan- cies). Indication: various immune mediated disease.
Diav-Citrin (Controls unexposed, disease free), 2014	Israel 2002 - 2011	Pregnant women counseled by the Israeli Teratology Information Service (TIS), Jerusalem.	Pregnant women counseled for TNF-a-antagonists (infliximab, etanercept, or adalimumab) exposure.	unexposed, disease free Pregnant women counseled for non-teratogenic exposure (Pregnancies of women who have chronic diseases were not included in the non-teratogenic-exposed group (unexposed control)).	83 / 341	Analyses were performed for the group of 3 TNF-α inhibitors (35 infliximab-, 25 etanercept-, and 23 adalimumab-exposed pregnan- cies). Indication: various immune mediated disease.
Drechsel, 2020	Not specified 2007 - 2018	Patients with Juvenile idiopathic arthritis (JIA) who were enrolled in BiKeR during childhood and were subsequently transferred to JuMBO, and reported at least one pregnancy in JuMBO.	Pregnancies with maternal TNF inhibitors only exposure.	unexposed, sick Pregnancies unexposed to disease modifying antirheumatic drug (DMARD).	21 / 85	Addition of Etanercept only and other TNFi only. Major congenital anomalies were classified according to the guidelines of the European Surveillance of Congenital Anomalies.
Duricova, 2019	Czech Republic 2007 – 2016	Consecutive children (≥12 months of age) issued from the 2 sources of data	Children (≥12 months of age) born to mothers with IBD (2007–2016) treated with anti-TNF-alpha during pregnancy in 3 centers in the Czech Republic.	unexposed, disease free Unexposed children of non-IBD mothers undergoing mandatory check-ups at general pediatricians’ offices.	72 / 69	Exposure: infliximab or adalimumab.
Fu - Etanercept, 2019	China 2014 - 2017	Refractory recurrent spontaneous abortion patients with innate immune disorders and failure of conventional treatment for RSA (heparin, aspirin, prednisone, cyclosporine A).	Women administered basic treatment (heparin, aspirin, prednisone, cyclosporine) and etanercept (daily s.c. administration at a dosage of 25 mg from the end of menstruation until the occurrence of menstruation or to the end of the 10th week of gestation).	unexposed, sick Women administered basic treatment (heparin, aspirin, prednisone, cyclosporine) and placebo (daily with s.c. saline solution at the same dosage and same time).	95 / 93
Hoxha, 2017	Italy 2008 - 2015	Patients with rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis attending four Rheumatology Units.	Pregnancies in patients which were treated with anti-TNFa agents at conception/ 1st trimester [anti-TNFa therapy was discontinued between 7th-11th weeks of gestations (WG)).	unexposed, sick Pregnancies in women withdrawn anti-TNFa prior to conception [anti-TNFa therapy was discontinued between one to six months prior to conception, following the leaflet recommendations].	24 / 11	Primary analyse concerned AntiTNFa group, which was further categorized into those exposed to ETN (n=17), ADA (n=5) or CZP (n=2) at conception; and 3 paternal exposures (ETN).
Komoto, 2016	Japan 2008 - 2014	Pregnancies in female Japanese Inflammatory Bowel Disease (IBD) patients identified in the 18 collaborating hospitals.	Pregnancies in women exposed to anti-tumor necrosis factor drugs (anti-TNF) therapy only (no thiopurine therapy).	unexposed, sick Pregnancies in women exposed to neither anti-tumor necrosis factor drugs (anti-TNF) or thiopurine therapy.	24 / 31
Langen, 2014	USA 2001 - 2009	All pregnancies complicated by Rheumatoid arthritis (RA) delivered at the institution.	Women with infliximab, adalimumab or etanercept near the time of conception. (Addition of pregnancies exposed to infliximab, adalimumab or etanercept).	exposed to other treatment, sick Women with prednisone only near the time of conception. (This is a subgroup of exposure among the whole exposed group considered in the study).	4 / 15	Addition of pregnancies exposed to infliximab, adalimumab or etanercept (discontinued upon discovery of pregnancy).
Lichtenstein - infliximab, 2018	North America 1999 - 2012	Crohn’s disease (CD) patients.	Pregnancy in CD patients treated with infliximab (at least one infliximab infusion), ≤ 365 days before the pregnancy outcome date.	exposed to other treatment, sick Pregnancy in CD patients treated with non-biologic CD treatments only (such as azathioprine, methotrexate, 6-mercaptopurine, prednisone, and antibiotics or narcotic analgesics).	106 / 106	2 analyses: IFX gestational exposure (≤365 days before the pregnancy outcome date) and IFX pre-gestational exposure (>365 days before the pregnancy outcome date => NOT REPORTED here).
Luu, 2018	France 2011 - 2015	All women with a diagnostic code for inflammatory bowel disease (IBD) and a singleton pregnancy that began between January 1st 2012 and December 31st 2014.	Pregnancies in women with inflammatory bowel disease (IBD) exposed to anti-TNFα.	exposed to other treatment, sick Pregnancies in women with inflammatory bowel disease (IBD) not exposed to anti-TNFα (but treated with other treatments).	1457 / 9818	Exposure: Infliximab or adalimumab accounted for 54.9% and 43.3% of anti-TNFα use and 223 exposed women (15.3%) were concomitantly treated with thiopurines, mainly azathioprine (88.8%).
Moens (Controls exposed to Vedolizumab), 2020	Europe 2009 - 2018	Pregnant women with inflammatory bowel diseases (IBD) treated or not.	Pregnancies exposed to anti‐TNF.	exposed to other treatment, sick Pregnancies exposed to Vedolizumab.	186 / 79	At conception, 84 (45%) were on infliximab (IFX) monotherapy, 101 (54%) on ADM monotherapy and the remaining patient (0.5%) initiated ADM treatment during the first trimester. Three (4%) women initiated VDZ treatment after conception.
Moens (Controls unexposed, sick), 2020	Europe 2009 - 2018	Pregnant women with inflammatory bowel diseases (IBD) treated or not.	Pregnancies exposed to Anti-TNF.	unexposed, sick Pregnancies that were not exposed to biologics nor to immunomodulatory drugs.	186 / 184	At conception, 84 (45%) were on infliximab (IFX) monotherapy, 101 (54%) on ADM monotherapy and the remaining patient (0.5%) initiated ADM treatment during the first trimester.
Schnitzler (Controls unexposed, disease free), 2011	Belgium 1994 - 2007	Pregnant women who delivered at the University Hospital in Leuven.	Pregnant IBD patients treated with IFX or ADA within 3 months prior to conception and/or during pregnancy who delivered at the University Hospital in Leuven.	unexposed, disease free Matched pregnancies of healthy women out of the Flemish population who delivered at the University Hospital in Leuven.	42 / 56	Exposure: 35 pregnancies with IFX; 7 pregnancies with ADA. The first trimester (T1) was defined as the time period from last menstruation until week 13.5, T2 > 13.5 weeks until week 26.5, and T3 > 26.5 weeks until week 40.
Schnitzler (Unexposed control, sick), 2011	Belgium 1994 - 2007	Pregnant women who delivered at the University Hospital in Leuven.	Pregnant IBD patients treated with IFX or ADA within 3 months prior to conception and/or during pregnancy who delivered at the University Hospital in Leuven.	unexposed, sick Pregnancies after diagnosis of IBC but prior to IFX treatment.	42 / 78	Exposure: 35 pregnancies with IFX; 7 pregnancies with ADA. The first trimester (T1) was defined as the time period from last menstruation until week 13.5, T2 > 13.5 weeks until week 26.5, and T3 > 26.5 weeks until week 40.
Seirafi, 2014	France and Belgium 2009 - 2010	Pregnant IBD patients.	Pregnant IBD patients under anti-TNF therapy (IFX, ADA or CTZ) within 3 months prior to conception and/or during pregnancy.	unexposed, sick Pregnant IBD patients not treated with anti-TNF therapy.	133 / 99	Design seems to be a retrospective cohort rather than a case–control study as mentioned by authors. Exposures: IFX (n=86), ADA (n=42) or CTZ (n=5). Anti-TNFs were preventively discontinued before GW 30 in 73% of patients having completed their pregnancy.
Verstappen, 2011	United Kingdom Not specified	Pregnancies in patients with rheumatoid arthritis	Pregnancies in patients treated with one of the three available anti-TNF therapies (adalimumab (ADA), etanercept (ETA) and infliximab (INF)) at time of conception (but no MTX or LEF).	unexposed, sick Pregnancies in patients with active rheumatoid arthritis (RA) exposed to Anti-TNF therapy prior to conception or never exposed to Anti-TNF therapy, but receiving non-biological disease-modifying antirheumatic drugs. Addition of the 2 control groups.	50 / 59	4 groups according to anti-TNF exposure: (1) anti-TNF and to methotrexate and/or leflunomide at conception (n=21); (2) anti-TNF at conception (n=50); (3) anti-TNF prior to conception (n=59); (4) no exposure to anti-TNF (n=10).
Viktil (Controls exposed to other treatments), 2012	Norway 2004 - 2007	Singleton pregnancies in women receiving at least 1 prescription during the study period.	Women with dispensation of Etanercept or Adalimumab from 3 months prior to pregnancy to delivery. (Addition of 2 subgroups of exposure among the whole exposed group considered in the study).	exposed to other treatment, sick Women with dispensation of other anti-rheumatic drugs (Prednisolone, NSAIDs, Sulfasalazine, Hydroxychloroquine, Etanercept, Adalimumab, Methotrexate, Leflunomid, or Anakinra) from 3 months prior to pregnancy to delivery.	40 / 1421	Analysis performed on anti-rheumatic drugs as a whole, no individual analyse for each substance. Raw data (number of exposed pregnancies and malformations) were available in the text and were used for this meta-analysis.
Viktil (Controls unexposed, NOS), 2012	Norway 2004 - 2007	Singleton pregnancies in women receiving at least 1 prescription during the study period.	Women with dispensation of Etanercept or Adalimumab from 3 months prior to pregnancy to delivery. (Addition of 2 subgroups of exposure among the whole exposed group considered in the study).	unexposed (general population or NOS) Singleton pregnancies whose mothers did not received an anti-rheumatic drugs in the period 3 months prior to conception until labour.	40 / 154976	Analysis performed on anti-rheumatic drugs as a whole, no individual analyse for each substance. Raw data (number of exposed pregnancies and malformations) were available in the text and were used for this meta-analysis.
Vinet (Controls unexposed, disease free), 2018	USA 2011 - 2015	The Pregnancies in RA Mothers and matched control group of children born to unaffected mothers.	Children born of rheumatoid arthritis (RA) women with ≥1 filled prescription of TNFi during during the preconception and/or gestational periods.	unexposed, disease free Children born to non-RA mothers without TNFi exposure (i.e., no prescription filled or infusion procedure claim within the preconception and gestational periods).	380 / 14596
Vinet (Controls unexposed, sick), 2018	USA 2011 - 2015	The Pregnancies in RA Mothers and matched control group of children born to unaffected mothers.	Children born of rheumatoid arthritis (RA) women with ≥1 filled prescription of TNFi during during the preconception and/or gestational periods.	unexposed, sick Children born of rheumatoid arthritis (RA) women without TNFi exposure (i.e., no prescription filled or infusion procedure claim within the gestational period and the 12 weeks preceding it).	380 / 2476
Weber-Schoendorfer, 2015	Australia, Finland, France, Italy, The Netherlands, Turkey, Switzerland and the United Kingdom 1998 - 2013	Pregnant women who contact a Teratology information services (TIS), directly or via her health care professional.	Pregnant women who had been exposed to more than one dose of one of the five approved TNF-α inhibitors (ADA, CZP, ETA, GOL and IFX) at any time during the first 12 weeks after the last menstrual period (LMP).	unexposed, disease free Pregnant women identified through spontaneous TIS consultations for other conditions or exposures such as hairdyeing, urinary tract infection, asthma or depression.	495 / 1532	Analyses were performed for the group of 5 TNF-α inhibitors (172 ADA, 7 CZP, 140 ETA, 3 GOL and 168 IFX). Indications: IBD (48,1%) et RA (26,9%).
Zbinden (rheumatoid arthritis), 2018	Switzerland 2000 - 2016	All patients followed at the Centre for Pregnancy in Rheumatic Diseases and pregnancies among employees of the University Hospital of Bern.	Pregnancies in patients with rheumatoid arthritis exposed to Anti-TNF during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed, disease free Pregnancies in healthy women.	28 / 70	In pregnancies of RA patients (n=96 pregnancies), TNFi treatment at any time during pregnancy was used in 29.2%.
Zbinden b (axial spondyloarthritis), 2018	Switzerland 2000 - 2016	All patients followed at the Centre for Pregnancy in Rheumatic Diseases and pregnancies among employees of the University Hospital of Bern.	Pregnancies in patients with in axial spondyloarthritis exposed to Anti-TNF during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed, disease free Pregnancies in healthy women.	31 / 70	Among axSpA patients (n=78 pregnancies), 75.6% were on anti-rheumatic drugs during pregnancy, the most common being TNFi (39.7%).

Case-control studies (cohort)

Study	Country Study period	Case	Control	Sample size	Rmk
Bröms b, 2016	Sweden 2006 - 2010	All women with CD or UC who gave birth to a live-born singleton infant before term.	Randomly selected women with CD or UC who gave birth at a later gestational week than their matched case.	237 / 239	Not the same outcomes than in Bröms(b) 2016 (Swedish AND Danish registers).
Vinet, 2013	Canada 1996 - 2008	Women having an induced abortion based either on 1 procedure code and/or diagnostic code for induced abortion present in the MED-E´CHO hospitalization and/or RAMQ billing databases	Subjects who entered the cohort on the same month and year as the case and who were born within 12 months of the case birthdate	112 / 5855	Primary analysis on MTX. Exposure to anti–tumor necrosis factor (anti-TNF) also investigated.

master protocol