| Study | Country Study period |
Population source | Exposure definition | Non-exposure definition | Sample size | Rmk |
|---|---|---|---|---|---|---|
| Alami, 2017 |
France 1989 - 2012 |
Women for whom a request had been made by physicians or themselves asking to a French regional pharmacovigilance center to carry out a risk assessment for drug exposure during pregnancy. | Pregnant women who had been exposed to Azathioprine at least during the organogenesis period (from 4 to 12 weeks after last menstrual period (LMP)) and if follow-up data on pregnancy outcome were available. |
unexposed, sick
Pregnant women randomly selected in the same registry who had been exposed at least during the organogenesis period to another drug or immunosuppressant used for the same indication (such as mesalazine, corticosteroids, sulfasalazine, hydroxychloroquine or beta interferon). |
124 / 124 | Mycophenolate not included in the control group. Preterm and LBW not reported because comparison of AZA (at least T3, including T1) versus AZA T1 => not adequate. Control group considered as 'unexposed sick' because co-exposures are in both groups. |
| Angelberger, 2011 |
Austria 1999 - 2007 |
Consecutive pregnant inflammatory bowel disease (IBD) patients, who attended the outpatient clinic during the study period. | Offsprings of inflammatory bowel disease (IBD) patients receiving azathioprine (AZA) during pregnancy and breastfeeding. |
unexposed, sick
Offsprings of inflammatory bowel disease (IBD) patients without any immunosuppressive therapy during pregnancy and breastfeeding. |
15 / 15 | Azathioprine dosage: once a day in the morning (median dose 150 mg/d; range: 100–250 mg/d). |
| Ban (Controls unexposed, disease free), 2014 |
United Kingdom 1990 - 2010 |
All live singleton children born to women aged 15–45 years in the UK during the study period. | Children of women with inflammatory bowel disease (IBD) with a prescription for azathioprine/6-mercaptopurine in the first trimester (between 4 weeks before a woman’s estimated conception date and 12 weeks after). |
unexposed, disease free
Children of women without inflammatory bowel disease (IBD). |
149 / 384811 | |
| Ban (Controls unexposed, sick), 2014 |
United Kingdom 1990 - 2010 |
All live singleton children born to women aged 15–45 years in the UK during the study period. | Children of women with inflammatory bowel disease (IBD) with a prescription for azathioprine/6-mercaptopurine in the first trimester (between 4 weeks before a woman’s estimated conception date and 12 weeks after). |
unexposed, sick
Children of women with inflammatory bowel disease (IBD) without prescription for azathioprine/6-mercaptopurine. |
149 / 1554 | Control group considered as 'unexposed sick' because co-exposures are possible in both groups. Patients with IBD with prescription during 1st trimester of pregnancy for steroids (n=209; 12.3%), 5-aminosalicylates (n=551; 32.4%). |
| Bröms (Crohn’s disease, stable disease), 2014 |
Sweden 2006 - 2010 |
All singleton births of women with Inflammatory Bowel Disease (IBD) in Sweden during the study period. | Infants of women with stable Crohn’s disease (CD) having filled at least 1 prescription of thiopurines (azathioprine or 6-mercaptopurine). (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, disease free
Infants of women without Ulcerative colitis (UC) nor Crohn’s disease (CD). |
-9 / 467057 | Authors provided 4 exposed group (Crohn*2; Ulcerative*2) versus the same comparator => only 1 used: this one with higher exposures (Crohn disease: n=262, no further details according to disease activity) and stable disease to limit impact of illness. |
| 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 hospital. | Pregnancies developed with the Inflammatory bowel disease (IBD) patient on thiopurines (azathioprine or mercaptopurine) alones 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 nflammatory bowel disease patients which did not receive thiopurines nor anti-TNF either during pregnancy or the 3 months before conception. (84% exposed to 5-Aminosalicylates and/or steroids). |
187 / 318 | Exposed population divided in 2 groups: A) thiopurines alone; B) anti-TNF-α drugs (IFX, ADA, and CZB) with or without concomitant thiopurines. Women who had another disease that may affect the course of pregnancy were excluded. |
| Cleary (Controls unexposed, NOS), 2009 |
Sweden 1995 - 2007 |
All births during the study period. | Women who reported taking Azathioprine (AZA) at the first antenatal care visit (defined as early pregnancy). |
unexposed (general population or NOS)
All women with a delivery in the study period who did not report taking azathioprine at the first antenatal care visit. |
476 / 1163554 | For outcomes LBW, preterm and SGA : only singleton infants are counted. For malformations all births are considered. For outcomes other than malformations, numbers vary because of missing values. Indication of AZA use in exposed group is IBD for >60%. |
| Cleary (Controls unexposed, sick), 2009 |
Sweden 1995 - 2007 |
All births during the study period. | Infants of women who reported taking Azathioprine (AZA) at the first antenatal care visit (defined as early pregnancy). |
unexposed, sick
Infants of women with a delivery in the study period who did not report AZA use, but reported medications specifically used in IBD (ATC codes A07EA [corticosteroids acting locally], A07EC02 [mesalazine], A07EC03 [olsalazine], or A07EC04 [balsalazide]); (untreated IBD pregnant women not included). |
481 / 1739 | For outcomes LBW, preterm and SGA : only singleton infants are counted. For malformations all births are considered. For outcomes other than malformations, numbers vary because of missing values. Indication of AZA use in exposed group is IBD for >60%. |
| Coelho (Controls exposed to 5-ASA), 2011 |
France 2004 - 2007 |
Pregnancy within the large cohort of patients with inflammatory bowel disease (CESAME). | Pregnancies in women with inflammatory bowel disease (IBD) exposed to thiopurines alone. |
exposed to other treatment, sick
Pregnancies in women with inflammatory bowel disease (IBD) receiving aminosalicylates alone. |
57 / 67 | No info on deaths inclusion in congenital anomalies. Results based on livebirths. It was not possible to take the full group B as a control group because authors give % and it is not possible to retrieve accurately numerators/denominators. |
| Coelho (Controls unexposed, sick), 2011 |
France 2004 - 2007 |
Pregnancy within the large cohort of patients with inflammatory bowel disease (CESAME). | Pregnancies in women with inflammatory bowel disease (IBD) exposed to thiopurines alone. |
unexposed, sick
Pregnancies in women with inflammatory bowel disease (IBD) not receiving any medication. |
57 / 45 | Deaths are not counted in congenital anomalies (i.e. therapeutic abortion, intrauterine deaths). |
| Colvin, 2010 |
Australia 2002 - 2005 |
All birth events in Western Australia (WA). | Azathioprine dispensed from 14 days after the last menstrual period (LMP) to the end of first trimester or to the end of the pregnancy event. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed (general population or NOS)
All other births (those births to women dispensed a Pharmaceutical Benefits Scheme (PBS) medicine or not). |
29 / 106045 | Category D or X medicines also studied. Total nb of unexposed: 106045=106074-29. Birth defect: structural or functional abnormality. Most minor defects are not recorded in the BDR. Of all cases, about 90% have at least one major birth defect. |
| Dejaco, 2005 |
Austria 2000 - 2003 |
Pregnancies in women affected with Inflammatroy bowel disease (IBD). | Pregnancies in women affected with Inflammatroy bowel disease (IBD) treated with azathioprine, 6-mercaptopurine or thioguanine. |
unexposed, sick
Pregnancies in women affected with Inflammatroy bowel disease (IBD) but without immunosuppressive therapy. |
33 / 35 | |
| Francella, 2003 |
USA Late 1950s - 1997 |
Women from the database of Inflammatory Bowel Disease (IBD) patients from a private practice of one of the authors. All pregnancies occurring after the diagnosis of IBD except those resulting in abortion for social or medical reasons were included. (n=171) | Women with Inflammatory Bowel Disease (IBD) who took 6-mercaptopurine (6-MP) throughout the entire pregnancy. |
unexposed, sick
Women with Inflammatory Bowel Disease (IBD) who took 6-mercaptopurine (6-MP) and stopped the drug prior to conception or patients who had pregnancies prior to treatment with 6-MP (sum of group A and C). |
15 / 132 | Unexposed= pregnancies in female from group A and C=132. All patients had been treated with 6-MP, and none were treated with azathioprine. Infections indexed in neonatal infection because they occurred at 3 and 6 months. |
| Goldstein, 2007 |
Israel, Canada, and Europe (Germany, Finland, the Netherlands and Italy) 2001 - 2004 |
Pregnant women who contacted one of seven teratogen information services to obtain information about the potential risks of drugs during pregnancy. | Pregnant women taking Azathioprine during pregnancy. |
unexposed (general population or NOS)
Pregnant women taking a drug with no teratogenic effect (such as acetaminophen, amoxicillin, prenatal vitamins, or allergy medications) or who were not exposed to drugs. |
189 / 230 | AZA group: 45% (n = 85) took AZA only, 38.6% (n = 73) took AZA together with another potential teratogen (mostly systemic corticosteroids) and 16% (n=30) took AZA with other nonteratogenic treatments. T1: 98%; entire pregnancy: 68%. |
| Howren, 2020 |
Canada 2002 - 2012 |
All births (livebirths and stillbirths) from women with Rheumatic diseases (RD), including rheumatoid arthritis (RA), systemic autoimmune rheumatic diseases (SARDs), and other RD including ankylosing spondylititis (AS), psoriatic arthritis (PsA), and juvenile idiopathic arthritis (JIA). | Pregnancies in women with Rheumatic diseases (RD) with at least one prescription of azathioprine filled during the critical windows of interest (90 days post conception for malformations and from conception to delivery for small-for-gestational-age). |
unexposed, sick
Pregnancies in women with Rheumatic diseases (RD) without filled prescriptions for conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs; e.g. hydroxychloroquine, methotrexate) during aforementioned perinatal windows of interest. |
23 / 6064 | |
| Jolving, 2021 |
Denmark 1995 - 2015 |
All children born alive in Denmark during the study period. | All children born to women who filled at least one prescription with thiopurines (azathioprine (AZA)/mercaptopurine) in a period of up to 3 months prior to conception and/or during pregnancy. |
unexposed (general population or NOS)
All live-born children from the study population, who were not exposed in utero to thiopurines, that is the mothers had no filled prescriptions for thiopurines within 3 months before conception or during pregnancy. |
1047 / 1307731 | For congenital malformations: overlapping with Langagergaard 2007 who used a more appropriate exposure period => Langagergaard 2007 was entered rather than Jolving 2021. |
| Kanis, 2017 |
The Netherlands 2008 - 2016 |
All women with confirmed inflammatory bowel disease (IBD) who visited the IBD preconception outpatient clinic during the study period. | Patients inflammatory bowel disease (IBD) using a thiopurine during conception. |
unexposed, sick
Patients with inflammatory bowel disease (IBD) not using thiopurine during pregnancy. |
146 / 263 | Totally overlapped by Kanis 2021 except for outcomes spontaneous abortions, allergies and eczema, therefore only these outcomes reported here. |
| Kanis, 2021 |
The Netherlands 1999 - 2018 |
In each participating hospital, women diagnosed with inflammatory bowel disease (IBD) and a reported pregnancy or child in their medical chart were identified during an uniform process and were invited per letter. | Women with inflammatory bowel disease (IBD) using a thiopurine during pregnancy (no anti-tumour necrosis factor-α (anti-TNF-α)). |
unexposed, sick
Women with inflammatory bowel disease (IBD) not using a thiopurine nor anti-tumour necrosis factor-α (anti-TNF-α). |
240 / 564 | One mother used methotrexate until pregnancy week 6, all others discontinued 3–6 months prior to conception. Overall, 91% of children exposed to a thiopurine were exposed during the entire pregnancy and only 3 were not exposed during the 1st trimester. |
| 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 thiopurine therapy only (no anti-tumor necrosis factor drugs (anti-TNF)). |
unexposed, sick
Pregnancies in women exposed to neither anti-tumor necrosis factor drugs (anti-TNF) or thiopurine therapy. |
7 / 31 | |
| Koslowsky, 2019 |
Israel 2011 - 2015 |
Pregnant women with a diagnosis of inflammatory bowel diseases (IBD) who had no other known chronic illness and gave birth to healthy newborns. | Women with a diagnosis of inflammatory bowel diseases (IBD) exposed to thiopurines throughout the entire pregnancy. (Patients exposed to steroids or biologics were excluded from the study). |
unexposed, sick
Women with a diagnosis of inflammatory bowel diseases (IBD) and no thiopurine exposure during pregnancy. (Patients exposed to steroids or biologics were excluded from the study). |
21 / 13 | Primary outcome is anemia in neonates. Patients exposed to steroids or biologics were excluded from the study. |
| Langagergaard (Controls unexposed, NOS), 2007 |
Denmark 1996 - 2001 |
All singleton live-born children delivered during the study period. | Children born from women who filled prescriptions for azathioprine or mercaptopurine (AZA/6-MP) in the period from 30 days before conception (i.e. the first day in the last menstruation) until birth. |
unexposed (general population or NOS)
Matched children born from women who did not fill prescriptions for any kind of reimbursable medication during the 3 months prior to conception and the ensuing pregnancy. |
76 / 1274 | The women were classified according to exposure during two gestational stages: (i) the ‘early pregnancy’ group: from 30 days before conception to the end of the first trimester; (ii) The ‘entire pregnancy’ group: during the 1st through the 3rd trimesters. |
| Langagergaard (Controls unexposed, sick), 2007 |
Denmark 1996 - 2001 |
All singleton live-born children born during the study period. | Children born from women who filled prescriptions for azathioprine or mercaptopurine (AZA/6-MP) in the period from 30 days before conception (i.e. the first day in the last menstruation) until birth. |
unexposed, sick
Children born from women who were treated with azathioprine or mercaptopurine before pregnancy (3 months before conception), but not during pregnancy. |
76 / 174 | The women were classified according to exposure during two gestational stages: (i) the ‘early pregnancy’ group: from 30 days before conception to the end of the first trimester; (ii) The ‘entire pregnancy’ group: during the 1st through the 3rd trimesters. |
| Lazzaroni, 2020 |
Italy 1987 - 2014 |
Singleton pregnancy yielding a live birth from two italian centers (Bresicia and Milano) with SLE diagnosis fulfilling the 1997 ACR classification criteria with a singleton live birth pregnancy. Only children of school age (≥6 years of age were included). | Pregnancies in women with Systemic Lupus Erythematosus (SLE) treated with Azathioprine. |
unexposed, sick
Pregnancies in women with Systemic Lupus Erythematosus (SLE) not treated with Azathioprine (NOS). |
27 / 65 | Control group considered as 'unexposed sick' because co-exposures are possible in both groups. Most of the patients were treated with corticosteroids during pregnancy (78.2%), hydroxychloroquine (HCQ) was prescribed in half of the pregnancies (51.1%). |
| Mahadevan, 2021 |
USA 2007 - 2019 |
Singleton pregnancies of inflammatory bowel disease (IBD) pregnant women from the PIANO cohort. | Use of thiopurines (azathioprine or 6-mercaptopurine) (but no biologics: anti-TNF, anti-integrin, anti-IL 12/23) in the 3 months prior to last menstrual period or at any time during pregnancy. |
unexposed, sick
No use of azathioprine nor biologics in the 3 months prior to last menstrual period or any time during pregnancy (includes mesalamine, corticosteroids, and antibiotics). |
242 / 379 | Neurodevelopment outcomes were not extractable because there is no information on dispersion for the control group (only delta? in exposed group and none in unexposed group). |
| Marder, 2013 |
United States of America 2008 - 2010 |
Children born from women with systemic lupus erythematosus (SLE) attending rheumatology outpatient clinics at the University of Michigan, and participants in the Michigan Lupus Cohort (MLC). | Women with systemic lupus erythematosus (SLE) exposed to azathioprine during pregnancy. |
unexposed, sick
Women with systemic lupus erythematosus (SLE) not exposed to of azathioprine during pregnancy (NOS). |
13 / 47 | No Mycophenolate mofetil exposure in infants with Developmental Delay/special educational service utilization. Control group considered as 'unexposed sick' because co-exposures are possible in both groups. |
| Meyer, 2025 |
France 2010 - 2021 |
All births after 22 weeks of pregnancy (livebirths, stillbirths, and pregnancy terminations) between April 1, 2010 and December 31, 2021 in women with inflammatory bowel disease (IBD) aged 15 to 49. | Children exposed in utero to thiopurines (azathioprine, mercaptopurine) during 1st trimester of pregnancy born of women with inflammatory bowel disease (IBD). |
unexposed, sick
Children unexposed in utero to either thiopurines or anti-TNF during 1st trimester of pregnancy born of women with inflammatory bowel disease (IBD). |
5223 / 28827 | Thiopurines were generally azathioprine (95.1% of births exposed to thiopurines) and rarely mercaptopurine (5.0%). When available data excluding exposure to combination therapy was used. |
| Meyer a (Controls exposed to Anti-TNF), 2021 |
France 2010 - 2018 |
All live births during the study period among women aged 15 to 49, diagnosed with inflammatory bowel disease (IBD) before the end of pregnancy. | All children born from women with inflammatory bowel disease (IBD) who were dispensed azathioprine/mercaptopurine (without co-exposure to anti-TNF) during pregnancy or during the previous 2 month. |
exposed to other treatment, sick
All children born from women with inflammatory bowel disease (IBD) who were dispensed anti-TNF monotherapy (infliximab, adalimumab, golimumab, certolizumab) (without co-exposure to thiopurines) during pregnancy or during the previous 2 month. |
3392 / 3399 | If available, use of Sensitivity results 'during pregnancy, narrower def of exposure', rather than '2 months before and/or pregnancy'. Otherwise, primary analysis used because similar results were obtained. Overlapping with Meyer 2021b: infections only. |
| Meyer a (Controls unexposed, sick), 2021 |
France 2010 - 2018 |
All live births during the study period among women aged 15 to 49, diagnosed with inflammatory bowel disease (IBD) before the end of pregnancy. | All children born from women with inflammatory bowel disease (IBD) who were dispensed azathioprine/mercaptopurine (without co-exposure to anti-TNF) during pregnancy or during the previous 2 month. |
unexposed, sick
All children born from women with inflammatory bowel disease (IBD) who were not dispensed or administered at hospital azathioprine/mercaptopurine nor anti-TNF 2 months before or during pregnancy. |
3392 / 18954 | If available, use of Sensitivity results 'during pregnancy, narrower def of exposure', rather than '2 months before and/or pregnancy'. Otherwise, primary analysis used because similar results were obtained. Overlapping with Meyer 2021b: infections only. |
| Meyer b (Controls exposed to Anti-TNF), 2021 |
France 2010 - 2018 |
All pregnancies ending with a live birth or stillbirth in women with with inflammatory bowel disease (IBD) diagnosed before pregnancy end. | All children born from women with inflammatory bowel disease (IBD) who were dispensed azathioprine/mercaptopurine (without co-exposure to anti-TNF) during pregnancy or during the previous 2 month. |
exposed to other treatment, sick
All children born from women with inflammatory bowel disease (IBD) who were dispensed anti-TNF monotherapy (infliximab, adalimumab, golimumab, certolizumab) (without co-exposure to thiopurines) during pregnancy or during the previous 2 month. |
3554 / 3525 | If available, use of Sensitivity results 'during pregnancy, narrower def of exposure', rather than '2 months before and/or pregnancy'. Otherwise, primary analysis used because similar results were obtained. |
| Meyer b (Controls unexposed, sick), 2021 |
France 2010 - 2018 |
All pregnancies ending with a live birth or stillbirth in women with with inflammatory bowel disease (IBD) diagnosed before pregnancy end. | All children born from women with inflammatory bowel disease (IBD) who were dispensed azathioprine/mercaptopurine (without co-exposure to anti-TNF) during pregnancy or during the previous 2 month. |
unexposed, sick
All children born from women with inflammatory bowel disease (IBD) who were not dispensed or administered at hospital azathioprine/mercaptopurine nor anti-TNF 2 months before or during pregnancy. |
3554 / 19811 | If available, use of Sensitivity results 'during pregnancy, narrower def of exposure', rather than '2 months before and/or pregnancy'. Otherwise, primary analysis used because similar results were obtained. |
| Nguyen, 2019 |
International 2005 - 2016 |
Women of child-bearing age (15–45 years inclusive), prospectively enrolled in MSBase with a diagnosis of Relapsing-Remitting Multiple Sclerosis (RRMS). | Pregnancies in Relapsing-Remitting Multiple Sclerosis (RRMS) patients occurring during Azathioprine therapy. (This is a subgroup of exposure among the exposed group considered in the study). |
unexposed, sick
Pregnancies in Relapsing-Remitting Multiple Sclerosis (RRMS) patients not exposed to disease-modifying therapies (DMTs) (pregnancy occurring within a year of DMT discontinuation or without DMT exposure in the prior year). |
4 / 886 | |
| Nguyen_IBD (Controls exposed to TNFi), 2025 |
Sweden 2007 - 2022 |
All singleton pregnancies of individuals with prevalent systemic lupus erythematosus (SLE) or inflammatory bowel disease (IBD). | Inflammatory bowel disease (IBD) pregnancies with at least 1 dispensation of azathiorpine or 6-mercaptopurine (L01BB02) from last menstrual period to one day before delivery or intrahepatic cholestasis of pregnancy (ICP). |
exposed to other treatment, sick
Inflammatory bowel disease (IBD) pregnancies with at least 1 recorded use of tumor necrosis factor inhibitors (TNFi) during pregnancy (infliximab, adalimumab, or golimumab). |
714 / 357 | Pregnancies with dual exposure during pregnancy were excluded to isolate the effect of thiopurines. Median time from the index thiopurine dispensation to ICP diagnosis was 28 and 29 weeks in SLE and IBD, respectively. |
| Nguyen_IBD (Controls unexposed, sick), 2025 |
Sweden 2007 - 2022 |
All singleton pregnancies of individuals with prevalent systemic lupus erythematosus (SLE) or inflammatory bowel disease (IBD). | Inflammatory bowel disease (IBD) pregnancies with at least 1 dispensation of azathiorpine or 6-mercaptopurine (L01BB02) from last menstrual period to one day before delivery or intrahepatic cholestasis of pregnancy (ICP). |
unexposed, sick
Inflammatory bowel disease (IBD) pregnancies without dispensation of azathiorpine or 6-mercaptopurine (L01BB02) from last menstrual period to one day before delivery or intrahepatic cholestasis of pregnancy (ICP). |
1924 / 3848 | Pregnancies with dual exposure during pregnancy were excluded to isolate the effect of thiopurines. Median time from the index thiopurine dispensation to ICP diagnosis was 28 and 29 weeks in SLE and IBD, respectively. |
| Nguyen_SLE (Controls exposed to TNFi), 2025 |
Sweden 2007 - 2022 |
All singleton pregnancies of individuals with prevalent systemic lupus erythematosus (SLE) or inflammatory bowel disease (IBD). | Systemic lupus erythematosus (SLE) pregnancies with at least 1 dispensation of azathiorpine or 6-mercaptopurine (L01BB02) from last menstrual period to one day before delivery or intrahepatic cholestasis of pregnancy (ICP). |
exposed to other treatment, sick
Systemic lupus erythematosus (SLE) pregnancies with at least 1 recorded use of tumor necrosis factor inhibitors (TNFi) during pregnancy (infliximab, adalimumab, or golimumab). |
-9 / -9 | Pregnancies with dual exposure during pregnancy were excluded to isolate the effect of thiopurines. Median time from the index thiopurine dispensation to ICP diagnosis was 28 and 29 weeks in SLE and IBD, respectively. |
| Nguyen_SLE (Controls unexposed, sick), 2025 |
Sweden 2007 - 2022 |
All singleton pregnancies of individuals with prevalent systemic lupus erythematosus (SLE) or inflammatory bowel disease (IBD). | Systemic lupus erythematosus (SLE) pregnancies with at least 1 dispensation of azathiorpine or 6-mercaptopurine (L01BB02) from last menstrual period to one day before delivery or intrahepatic cholestasis of pregnancy (ICP). |
unexposed, sick
Systemic lupus erythematosus (SLE) pregnancies without dispensation of azathiorpine or 6-mercaptopurine (L01BB02) from last menstrual period to one day before delivery or intrahepatic cholestasis of pregnancy (ICP). |
297 / 594 | Pregnancies with dual exposure during pregnancy were excluded to isolate the effect of thiopurines. Median time from the index thiopurine dispensation to ICP diagnosis was 28 and 29 weeks in SLE and IBD, respectively. |
| Norgard, 2020 |
Denmark 1995 - 2015 |
All children live born in Denmark during the study period. | Children exposed in utero to thiopurines (azathioprine/mercaptopurine) in a period of 3 months before conception or during pregnancy. |
unexposed (general population or NOS)
Children who were not exposed in utero for thiopurines in the period of 3 months before conception or during pregnancy. |
1048 / 1309961 | For preterm birth: Overlapping between Langagergaard 2007 and Norgard 2020. Data of Langagergaard 2007 were kept rather than those of Norgard 2020 because this latter use an inappropriate exposition period. |
| Norgard (Controls unexposed, NOS), 2003 |
Denmark 1991 - 2000 |
All singleton pregnancies in the county (live births after the 28th week of gestation, only). | Pregnancies exposed to azathioprine or mercaptopurine (‘early pregnancy’ group: prescriptions from 30 days before conception to the end of the first trimester; or 'entire pregnancy': during the first to the third trimesters). |
unexposed (general population or NOS)
All pregnant women who had not been prescribed any kind of reimbursed medicine from three months before conception to the end of pregnancy. |
10 / 19418 | Overlapping: Only perinatal deaths in results because the study is partially overlap by Langagergaard 2007 for preterm births, LBW and all congenial malformations (larger cohort in Langagergaard 2007). |
| Norgard (Controls unexposed, sick), 2003 |
Danemark 1991-2000 |
All singleton pregnancies in the county (live births after the 28th week of gestation, only). | Pregnancies exposed to azathioprine or mercaptopurine (‘early pregnancy’ group: prescriptions from 30 days before conception to the end of the first trimester; or 'entire pregnancy': during the first to the third trimesters). |
unexposed, sick
Women who used azathioprine or mercaptopurine before pregnancy, but not three months before pregnancy or during pregnancy. |
10 / 30 | Overlapping: Only perinatal deaths in results because the study is partially overlap by Langagergaard 2007 for preterm births, LBW and all congenial malformations (larger cohort in Langagergaard 2007). |
| Reynolds, 2022 |
United Kingdom 2007 - 2011 |
Women who had >=4 criteria for systemic lupus erythematosus (SLE) prior to pregnancy and who regularly attended a rheumatology outpatient department. | Pregnancies in systemic lupus erythematosus (SLE) patients with Azathioprine exposure during pregnancy (continued throughout pregnancy and breastfeeding in almost all cases). |
unexposed, sick
Pregnancies in systemic lupus erythematosus (SLE) patients without Azathioprine exposure during pregnancy. |
86 / 198 | Only live-born children were included. 'As HCQ or AZA were continued throughout pregnancy and breastfeeding in almost all cases, exposure was combined into a single variable for each drug'. |
| Schramm, 2006 |
Germany Not specified. |
Patients with definite Autoimmune Hepatitis (AIH) who have attended the liver clinic or units at the included universities. | Pregnancies in patient with Autoimmune Hepatitis exposed to azathioprine (at anytime during pregnancy). |
unexposed, sick
Pregnancies in patient with Autoimmune Hepatitis not exposed to azathioprine. |
14 / 28 | 14 pregnancies exposed to azathioprine including 10 co-exposed to prednisolone. |
| Selinger (Controls unexposed, disease free), 2023 |
United Kindgom 2014 - 2022 |
All pregnant patients with inflammatory bowel disease (IBD) seen in the Combined Clinic and delivered in Leeds Teaching Hospitals and non-IBD patients from the same geographic area who delivered in Leeds Teaching Hospitals. | Thiopurine-exposed pregnancies in patients with inflammatory bowel disease (IBD), defined as any treatment with thiopurine during pregnancy. |
unexposed, disease free
Non-inflammatory bowel disease (IBD) patients without thiopurine exposure. |
111 / 386 | Thiopurine therapy was delivered dosed at 2–2.5 mg/kg bodyweight for azathioprine and 1–1.5 mg/ kg bodyweight for mercaptopurine. Dose adjustments were made if neutropenia occurred or in case of other side effects. |
| Selinger (Controls unexposed, sick), 2023 |
United Kindgom 2014 - 2022 |
All pregnant patients with inflammatory bowel disease (IBD) seen in the Combined Clinic and delivered in Leeds Teaching Hospitals. | Thiopurine-exposed pregnancies in patients with inflammatory bowel disease (IBD), defined as any treatment with thiopurine during pregnancy. |
unexposed, sick
Inflammatory bowel disease (IBD) patients without thiopurine exposure. |
111 / 275 | Thiopurine therapy was delivered dosed at 2–2.5 mg/kg bodyweight for azathioprine and 1–1.5 mg/ kg bodyweight for mercaptopurine. Dose adjustments were made if neutropenia occurred or in case of other side effects. |
| Shim, 2011 |
Australia 1996 - 2006 |
All women with inflammatory bowel disease (IBD) (Ulcerative Colitis or Crohn's Disease) who were pregnant during the study period. | Births from women with inflammatory bowel disease (IBD) pregnant who reported taking azathioprine/6-mercaptopurine (AZA/6-MP) during their first antenatal visit (i.e. first trimester). |
unexposed, sick
Births from age-matched women with inflammatory bowel disease (IBD) pregnant who were not exposed to azathioprine/6-mercaptopurine (AZA/6-MP) before and during their pregnancy. |
19 / 74 | For LBW: OR provided by authors not reported because aberrant (1.00 (0.99-1.01)). All exposed to AZA/6-MP throughout pregnancy. None of the women in either group were treated with methotrexate, cyclosporine, ciprofloxacin, or biologic therapy. |
| Tennenbaum, 1999 |
France 1989 - 1995 |
Women of child-bearing age (between 16 and 36 years old in 1989) followed for inflammatory bowel disease in three referral centers (Rothschild, Saint-Lazare, Saint-Louis). | Pregnant women with inflammatory bowel disease that continued azathioprine during pregnancy. |
unexposed, sick
Pregnant women with inflammatory bowel disease without any treatment the 6 months before pregnancy. |
12 / 52 | |
| Vestergaard, 2024 |
Denmark 2008 - 2022 |
Every woman with a referral diagnosis of either Crohn’s disease (CD, DK50) or ulcerative colitis (UC, DK51) including all subtypes of inflammatory bowel disease (IBD), who gave birth after the IBD diagnosis. | Pregnant women with inflammatory bowel disease (IBD) who receive treatment with thiopurines monotherapy (i.e without concomitant biologics). |
unexposed, sick
Pregnant women with inflammatory bowel disease (IBD) who did not receive treatment with thiopurines, biologics, or the 2 combined (treated with 5-ASA, corticosteroids, Budesonide or no medical treatment). |
111 / 372 | Concurrent usage of biologics and thiopurines was termed combination treatment. |
| 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 Azathioprine from 3 months prior to pregnancy to delivery (subgroup 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. |
101 / 1360 | 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 Azathioprine from 3 months prior to pregnancy to delivery. (This is a subgroup 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. |
101 / 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. |
| Yeaman (Controls mainly exposed to biologics), 2023 |
Canada 2013 - 2018 |
Pregnant people with inflammatory bowel disease (IBD) recruited from the IBD and Pregnancy Clinic from April 2013 to July 2018. | Pregnant people with inflammatory bowel disease (IBD) with exposure to thiopurines. |
exposed to other treatment, sick
Pregnant people with inflammatory bowel disease (IBD) without exposure to thiopurines (but may have had exposure to biologic IBD treatments including anti-TNF, vedolizumab, and ustekinumab). |
19 / 50 | 27/50 (54%) of the non-thiopurine IBD patients were on biologic monotherapy (infliximab, adalimumab, golimumab, ustekinumab, or vedolizumab) => Mainly exposed to biologics. |
| Yeaman (Controls unexposed, disease free), 2023 |
Canada 2013 - 2018 |
Pregnant people with inflammatory bowel disease (IBD) recruited from the IBD and Pregnancy Clinic from April 2013 to July 2018 and non-IBD people from the adjacent pregnancy clinic at the same center, were recruited between 2015 and 2018. | Pregnant people with inflammatory bowel disease (IBD) with exposure to thiopurines. |
unexposed, disease free
Pregnant people without inflammatory bowel disease (IBD) and with no exposure to thiopurines nor other immunomodulators for any other indication. |
19 / 37 |
| Study | Country Study period |
Case | Control | Sample size | Rmk |
|---|---|---|---|---|---|
| Andreoli, 2022 |
Italy Not specified. |
Children with neurodevelopmental disorders (learning disabilities, attention deficiency and hyperactivity disorder, autism spectrum disorder). | Children without neurodevelopmental disorders (learning disabilities, attention deficiency and hyperactivity disorder, autism spectrum disorder). | 11 / 288 | No overlapping with Lazzaroni 2020, not the same disease ('This paper focuses on the follow-up of children born to patients with RD, as the other themes have already been the subject of a previous paper'). |
| Bröms, 2016 |
Sweden 2006 - 2010 |
Singleton preterm births among women with Inflammatory bowel diseases (IBD). | Randomly selected Inflammatory bowel diseases (IBD) controls who gave birth at a later gestational week than their matched case. | 237 / 239 | For preterm: Overlap with Bröms 2014, which is not specifically designed for this outcome, used general population as control group, did not adjust for previous preterm and separate CD and UC women. => Bröms 2016 used rather than Broms 2014. |
| He, 2022 |
Japan 2013 - 2020 |
Pregnancies with adverse pregnancy outcomes. | Pregnancies without adverse pregnancy outcomes. | 68 / 42 |
-
About
-
Master protocol
-
Browse exposition
-
RSS
-
Made with in Lyon
-
Contact us
-
Privacy policy
-
