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Immunomodulatory Therapy Reduces the Severity of Placental Lesions in Chronic Histiocytic Intervillositis

Chronic histiocytic intervillositis (CHI) is a rare, but highly recurrent inflammatory placental lesion wherein maternal macrophages infiltrate the intervillous space. Pregnancies with CHI are at high risk of fetal growth restriction, miscarriage or stillbirth. Presently, the diagnosis can only be m...

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Autores principales: Brady, Chloe A., Williams, Charlotte, Batra, Gauri, Church, Elaine, Tower, Clare L., Crocker, Ian P., Heazell, Alexander E. P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8558526/
https://www.ncbi.nlm.nih.gov/pubmed/34733868
http://dx.doi.org/10.3389/fmed.2021.753220
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author Brady, Chloe A.
Williams, Charlotte
Batra, Gauri
Church, Elaine
Tower, Clare L.
Crocker, Ian P.
Heazell, Alexander E. P.
author_facet Brady, Chloe A.
Williams, Charlotte
Batra, Gauri
Church, Elaine
Tower, Clare L.
Crocker, Ian P.
Heazell, Alexander E. P.
author_sort Brady, Chloe A.
collection PubMed
description Chronic histiocytic intervillositis (CHI) is a rare, but highly recurrent inflammatory placental lesion wherein maternal macrophages infiltrate the intervillous space. Pregnancies with CHI are at high risk of fetal growth restriction, miscarriage or stillbirth. Presently, the diagnosis can only be made after histopathological examination of the placenta. Given its proposed immunological etiology, current treatments include aspirin, heparin, and immunomodulatory agents. However, the rationale for these medications is largely based upon small case series and reports as there is a lack of larger studies investigating treatment efficacy. Therefore, this study sought to determine whether inclusion of immunomodulatory medications was effective at reducing the severity of lesions and improving pregnancy outcomes in subsequent pregnancies. Thirty-three women with a history of CHI in at least one pregnancy (index case) were identified retrospectively through medical records. Twenty-eight participants presented with a first subsequent pregnancy and a further 11 with a second subsequent pregnancy at a specialist clinic for pregnancy after loss. Data on maternal demographics, medical history, medication, pregnancy outcome, and placental pathology was collected and compared between pregnancies. Twenty-seven (69%) subsequent pregnancies were treated with at least one or both of prednisolone and hydroxychloroquine. Inclusion of at least one immunomodulatory agent in treatment regimen resulted in an almost 25% increase in overall livebirth rate (61.5 vs. 86.2%). In women treated with immunomodulatory medication a greater proportion of placentas had reduced severity of lesions compared to those treated without (86.7 vs. 33.3%, respectively). A reduction in CHI severity was associated with a 62.3% improvement in livebirth rate compared to those where severity remained unchanged in relation to the index case. These data provide preliminary evidence that the use of immunomodulatory medication in the management of CHI improves histopathological lesions and the chance of livebirth in subsequent pregnancies. Due to CHI's rarity and ethical and feasibility issues, randomized controlled trials in affected women are challenging to conduct. As a result, collaboration between centers is required in future to increase study sample sizes and elucidate the mechanisms of hydroxychloroquine and prednisolone in reducing pathology.
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spelling pubmed-85585262021-11-02 Immunomodulatory Therapy Reduces the Severity of Placental Lesions in Chronic Histiocytic Intervillositis Brady, Chloe A. Williams, Charlotte Batra, Gauri Church, Elaine Tower, Clare L. Crocker, Ian P. Heazell, Alexander E. P. Front Med (Lausanne) Medicine Chronic histiocytic intervillositis (CHI) is a rare, but highly recurrent inflammatory placental lesion wherein maternal macrophages infiltrate the intervillous space. Pregnancies with CHI are at high risk of fetal growth restriction, miscarriage or stillbirth. Presently, the diagnosis can only be made after histopathological examination of the placenta. Given its proposed immunological etiology, current treatments include aspirin, heparin, and immunomodulatory agents. However, the rationale for these medications is largely based upon small case series and reports as there is a lack of larger studies investigating treatment efficacy. Therefore, this study sought to determine whether inclusion of immunomodulatory medications was effective at reducing the severity of lesions and improving pregnancy outcomes in subsequent pregnancies. Thirty-three women with a history of CHI in at least one pregnancy (index case) were identified retrospectively through medical records. Twenty-eight participants presented with a first subsequent pregnancy and a further 11 with a second subsequent pregnancy at a specialist clinic for pregnancy after loss. Data on maternal demographics, medical history, medication, pregnancy outcome, and placental pathology was collected and compared between pregnancies. Twenty-seven (69%) subsequent pregnancies were treated with at least one or both of prednisolone and hydroxychloroquine. Inclusion of at least one immunomodulatory agent in treatment regimen resulted in an almost 25% increase in overall livebirth rate (61.5 vs. 86.2%). In women treated with immunomodulatory medication a greater proportion of placentas had reduced severity of lesions compared to those treated without (86.7 vs. 33.3%, respectively). A reduction in CHI severity was associated with a 62.3% improvement in livebirth rate compared to those where severity remained unchanged in relation to the index case. These data provide preliminary evidence that the use of immunomodulatory medication in the management of CHI improves histopathological lesions and the chance of livebirth in subsequent pregnancies. Due to CHI's rarity and ethical and feasibility issues, randomized controlled trials in affected women are challenging to conduct. As a result, collaboration between centers is required in future to increase study sample sizes and elucidate the mechanisms of hydroxychloroquine and prednisolone in reducing pathology. Frontiers Media S.A. 2021-10-18 /pmc/articles/PMC8558526/ /pubmed/34733868 http://dx.doi.org/10.3389/fmed.2021.753220 Text en Copyright © 2021 Brady, Williams, Batra, Church, Tower, Crocker and Heazell. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Medicine
Brady, Chloe A.
Williams, Charlotte
Batra, Gauri
Church, Elaine
Tower, Clare L.
Crocker, Ian P.
Heazell, Alexander E. P.
Immunomodulatory Therapy Reduces the Severity of Placental Lesions in Chronic Histiocytic Intervillositis
title Immunomodulatory Therapy Reduces the Severity of Placental Lesions in Chronic Histiocytic Intervillositis
title_full Immunomodulatory Therapy Reduces the Severity of Placental Lesions in Chronic Histiocytic Intervillositis
title_fullStr Immunomodulatory Therapy Reduces the Severity of Placental Lesions in Chronic Histiocytic Intervillositis
title_full_unstemmed Immunomodulatory Therapy Reduces the Severity of Placental Lesions in Chronic Histiocytic Intervillositis
title_short Immunomodulatory Therapy Reduces the Severity of Placental Lesions in Chronic Histiocytic Intervillositis
title_sort immunomodulatory therapy reduces the severity of placental lesions in chronic histiocytic intervillositis
topic Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8558526/
https://www.ncbi.nlm.nih.gov/pubmed/34733868
http://dx.doi.org/10.3389/fmed.2021.753220
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