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

Cristina Belizna 1 Pier Luigi Meroni 2 Yehuda Shoenfeld 3 Katrien Devreese 4 Jaume Alijotas-Reig 5 Enrique Esteve-Valverde 6 Cecilia Chighizola 2 Francesca Pregnolato 2 Hannah Cohen 7 Celine Fassot 8 Patrick Martin Mattera 9, 10 Pascale Peretti 9, 10 Alexandre Levy 9, 10 Laurence Bernard 9, 10 Mathilde Saiet 9, 10 Laurence Lagarce 11 Marie Briet 11 Marianne Rivière 12 Isabelle Pellier 11 Géraldine Gascoin 11 Jose Rakotonjanahary 11 Maria Orietta Borghi Ljudmila Stojanovich Aleksandra Djokovic Natasa Stanisavljevic Rebecca Bromley Elisabeth Elefant-Amoura Nadia Bahi Buisson Taylor Pindi Sala Hilde Kelchtermans Alexander Makatsariya Viktoria Bidsatze Jamilya Khizroeva Jose Omar Latino Sebastian Udry Daniel Henrion Laurent Loufrani Anne Laure Guihot Christian Muchardt 13, 14 Milena Hasan 15 Marie Noelle Ungeheuer 16 Jan Voswinkel Laura Damian Ingrid Pabinger Johanna Gebhart Rosario Lopez Pedrera Jan Willem Cohen Tervaert Angela Tincani Laura Andreoli 
Abstract : 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
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https://hal.archives-ouvertes.fr/hal-03046085
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Submitted on : Monday, August 22, 2022 - 3:32:38 PM
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Cristina Belizna, Pier Luigi Meroni, Yehuda Shoenfeld, Katrien Devreese, Jaume Alijotas-Reig, et al.. In utero exposure to Azathioprine in autoimmune disease. Where do we stand?. Autoimmunity Reviews, 2020, 19 (9), pp.102525. ⟨10.1016/j.autrev.2020.102525⟩. ⟨hal-03046085⟩

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