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In utero exposure to Azathioprine in autoimmune disease. Where do we stand?

• アブストラクト	Azathioprine (AZA), an oral immunosuppressant, is safe during pregnancy. Some reports suggested different impairments in the offspring of mothers with autoimmune diseases (AI) exposed in utero to AZA. These observations are available from retrospective studies or case reports. However, data with respect to the long-term safety in the antenatally exposed child are still lacking. The aim of this study is to summarize the current knowledge in this field and to focus on the need for a prospective study on this population. We performed a PubMed search using several search terms. The actual data show that although the risk of congenital anomalies in offspring, as well as the infertility risk, are similar to those found in general population, there is a higher incidence of prematurity, of lower weight at birth and an intra-uterine delay of development. There is also an increased risk of materno- fetal infections, especially cytomegalovirus infection. Some authors raise the interrogations about neurocognitive impairment. Even though the adverse outcomes might well be a consequence of maternal illness and disease activity, interest has been raised about a contribution of this drug. However, the interferences between the external agent (in utero exposure to AZA), with the host (child genetic susceptibility, immune system anomalies, emotional status), environment (public health, social context, availability of health care), economic, social, and behavioral conditions, cultural patterns, are complex and represent confounding factors. In conclusion, it is necessary to perform studies on the medium and long-term outcome of children born by mothers with autoimmune diseases, treated with AZA, in order to show the safety of AZA exposure. Only large-scale population studies with long-term follow-up will allow to formally conclude in this field. TAKE HOME MESSAGES.
  ジャーナル名	Autoimmunity reviews
  投稿日	2020/4/3
  投稿者	Belizna, Cristina; Meroni, Pier Luigi; Shoenfeld, Yehuda; Devreese, Katrien; Alijotas-Reig, Jaume; Esteve-Valverde, Enrique; Chighizola, Cecilia; Pregnolato, Francesca; Cohen, Hannah; Fassot, Celine; Mattera, Patrick Martin; Peretti, Pascale; Levy, Alexandre; Bernard, Laurence; Saiet, Mathilde; Lagarce, Laurence; Briet, Marie; Riviere, Marianne; Pellier, Isabelle; Gascoin, Geraldine; Rakotonjanahary, Jose; Borghi, Maria Orietta; Stojanovich, Ljudmila; Djokovic, Aleksandra; Stanisavljevic, Natasa; Bromley, Rebecca; Elefant-Amoura, Elisabeth; Bahi Buisson, Nadia; Pindi Sala, Taylor; Kelchtermans, Hilde; Makatsariya, Alexander; Bidsatze, Viktoria; Khizroeva, Jamilya; Latino, Jose Omar; Udry, Sebastian; Henrion, Daniel; Loufrani, Laurent; Guihot, Anne Laure; Muchardt, Christian; Hasan, Milena; Ungeheuer, Marie Noelle; Voswinkel, Jan; Damian, Laura; Pabinger, Ingrid; Gebhart, Johanna; Lopez Pedrera, Rosario; Cohen Tervaert, Jan Willem; Tincani, Angela; Andreoli, Laura
  組織名	Vascular and Coagulation Department, University Hospital Angers, Angers, France;;MITOVASC institute and CARFI facility, University of Angers, UMR CNRS 6015,;INSERM U1083, Angers, France; Internal Medicine Department, Clinique de l'Anjou,;Angers, France; UMR CNRS 6015, Angers, France; INSERM U1083, Angers, France.;Electronic address: cristina.belizna@wanadoo.fr.;Clinical Immunology and Rheumatology Research Department Auxologico Institute,;Milan, Italy.;The Zabludowicz Center for Autoimmune Diseases, Affiliated to Sackler Faculty of;Medicine, Tel-Aviv University, Israel; I.M. Sechenow First Moscow State Medical;University, Moscow, Russia.;Coagulation Laboratory, Department of Clinical Biology, Immunology and;Microbiology, Ghent University Hospital, Ghent, Belgium.;Systemic Autoimmune Disease Unit, Department of Internal Medicine, Vall d'Hebron;University Hospital, Barcelona, Spain; Department of Medicine, Universitat;Autonoma, Barcelona, Spain.;Internal Medicine Althaia Healthcare Network of Manresa, Barcelona, Spain.;Haematology Department, University College Hospital, London, UK.;Internal Medicine Department, Clinique de l'Anjou, Angers, France.;Faculty of Human and Social Sciences, Laboratory of Research in Psychopathology,;3 place Andre Leroy, 49008 Angers, France.;Departement of Pharmacovigilance, University Hospital Angers, Angers, France.;French Lupus and Other Autoimmune Disease Patients Association, AFL+, Cuvry,;France.;Department of Pediatrics, University Hospital Angers, Angers, France.;Department of Neonatology, University Hospital Angers, Angers, France.;Scientific Research Department, Internal Medicine-Rheumatology Bezhanijska Kosa,;University Medical Center, Belgrade University, Serbia.;Manchester University Hospitals NHS Trust, Manchester, UK; Division of Evolution;and Genomic Science, School of Biological Sciences, University of Manchester,;Manchester Academic Health Science Centre, Manchester, UK.;Genetical and Medical Embriology, CRAT Reference Center on Teratogenic Agents,;Paris Est - Hopital d'Enfants Armand-Trousseau, 26 avenue du Docteur Arnold;Netter, 75571 Paris, France.;Neurology & Neurodevelopmental disorders Department Necker Enfants Malades;University Hospital, APHP, Paris 149 Rue de Sevres, 75015 Paris; INSERM U1163,;Hopital Necker Enfants Malades, 149 rue de Sevres, 75015 Paris, France; INSERM;U1163, Hopital Necker Enfants Malades, 149 rue de Sevres, 75015 Paris, France.;EA 7334, Patient Centered Outcomes Research, University Paris Diderot, Paris,;Synapse Research Institute, Maastricht, the Netherlands; Cardiovascular Research;Institute Maastricht, Maastricht University Medical Center, Maastricht, the;Netherlands.;Department of Obstetrics and Gynecology, I.M. Sechenow First Moscow State Medical;Autoimmune and thrombophilic disorders Department, Hospital Carlos G. Durand,;Buenos Aires, Argentina.;Unit of Epigenetic Regulation, Department of Developmental and Stem Cell Biology,;UMR3738 CNRS, Institut Pasteur, Paris, France.;Cytometry and Biomarkers Unit of Technology and Service, Center for Translational;Science, Institut Pasteur, 28, Rue Doct Roux, 75015 Paris, France.;Clinical Investigation and Acces to Bioresources Department, Institut Pasteur,;28, Rue Doct Roux, 75015 Paris, France.;Department of Internal Medicine I, Saarland Medical School, University of;Saarland, Homburg, Saarland, Germany.;Department of Rheumatology, County Emergency Hospital Cluj-Napoca, Cluj-Napoca,;Romania.;Department of Medicine, Division of Hematology and Haemostasis, University;Hospital of Vienna, Austria.;Institute Maimonides of Biomedical Investigations, University Hospital Reina;Sofia, Cordoba, Spain.;Department of Medicine, Division of Rheumatology, University of Alberta,;Edmonton, AB, Canada.;Rheumatology and Clinical Immunology Unit, University of Brescia, Brescia, Italy;;I.M. Sechenow First Moscow State Medical University, Moscow, Russia.;Rheumatology and Clinical Immunology Unit, University of Brescia, Brescia, Italy.
  Pubmed リンク	https://www.ncbi.nlm.nih.gov/pubmed/32240856/

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