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      Chronic histiocytic intervillositis (CHI): current treatments and perinatal outcomes, a systematic review and a meta-analysis

      systematic-review

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          Abstract

          Background

          Chronic histiocytic intervillositis (CHI) is a rare placental lesion with a high recurrence rate and poor perinatal outcomes. There are currently limited guidelines regarding the diagnosis of this condition in the index pregnancy and treatment where recurrence is suspected.

          Objective

          The primary objective of this systematic review and meta-analysis was to determine the perinatal outcomes of pregnancies affected by chronic histiocytic intervillositis and to what extent they can be improved with treatment. The secondary objective was to assess the relationship between CHI lesion severity and pregnancy loss.

          Methods

          A systematic search of Ovid Embase, Web of Science, Science Direct, PubMed, Ovid Medline, Google Scholar and CINAHL was carried out. Case reports, cohort, case-control and randomised controlled trials (RCT) detailing the perinatal outcomes of CHI pregnancies, both treated and untreated, were included.

          Results

          No RCTs were identified. However, in a review population of 659 pregnancies, with additional 7 in case reports, CHI treatments included aspirin, prednisone, prednisolone, low molecular weight heparin (LMWH), hydroxychloroquine and adalimumab. A descriptive synthesis of data found mixed results for treatments in relation to live birth, miscarriage and fetal growth restriction outcomes. Furthermore, quantitative synthesis of 38 pregnancies revealed a non-significant improvement in live birth rate with CHI targeted treatment (OR 1.79 [95% CI 0.33-9.61] (p=0.50), while meta-analysis of CHI severity in line with pregnancy loss, in a sample of 231 pregnancies, revealed lower odds of pregnancy loss with less severe lesions (OR: 0.17 [0.03-0.80], p=0.03).

          Conclusions

          This systematic review and meta-analysis reinforce notions surrounding the insufficient evidence for CHI treatment. It also strengthens previous hypotheses detailing the positive association between CHI lesion severity and odds of pregnancy loss. Aspirin, LMWH, prednisolone, hydroxychloroquine and adalimumab are candidates with varying levels of weak to moderate evidence supporting their use. Further prospective research is required to obtain robust evidence pertaining to treatment safety and efficacy and optimal drug regimes.

          Systematic Review Registration

          [website], identifier CRD42021237604

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          Most cited references54

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          The PRISMA 2020 statement: an updated guideline for reporting systematic reviews

          Matthew J L Page, Joanne E McKenzie, Patrick Bossuyt … (2025)
          The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement, published in 2009, was designed to help systematic reviewers transparently report why the review was done, what the authors did, and what they found. Over the past decade, advances in systematic review methodology and terminology have necessitated an update to the guideline. The PRISMA 2020 statement replaces the 2009 statement and includes new reporting guidance that reflects advances in methods to identify, select, appraise, and synthesise studies. The structure and presentation of the items have been modified to facilitate implementation. In this article, we present the PRISMA 2020 27-item checklist, an expanded checklist that details reporting recommendations for each item, the PRISMA 2020 abstract checklist, and the revised flow diagrams for original and updated reviews.
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            Sampling and Definitions of Placental Lesions: Amsterdam Placental Workshop Group Consensus Statement.

            T Yee Khong, Eoghan Mooney, Ilana Ariel … (2016)
            -The value of placental examination in investigations of adverse pregnancy outcomes may be compromised by sampling and definition differences between laboratories.
            Article 0 comments Cited 332 times – based on 0 reviews     Review now
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              Assessing the quality of studies in meta-analyses: Advantages and limitations of the Newcastle Ottawa Scale

              Claudio Luchini, Brendon Stubbs, Marco Solmi … (2017)
              Article 0 comments Cited 288 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Journal
                Journal ID (nlm-ta): Front Endocrinol (Lausanne)
                Journal ID (iso-abbrev): Front Endocrinol (Lausanne)
                Journal ID (publisher-id): Front. Endocrinol.
                Title: Frontiers in Endocrinology
                Publisher: Frontiers Media S.A.
                ISSN (Electronic): 1664-2392
                Publication date (Electronic): 22 July 2022
                Publication date Collection: 2022
                Volume: 13
                Electronic Location Identifier: 945543
                Affiliations
                [1] 1 School of Life Course and Population Sciences, King’s College London , London, United Kingdom
                [2] 2 Department of Women and Children, Guy’s and St. Thomas’ NHS Foundation Trust , London, United Kingdom
                [3] 3 Department of Histopathology, St. Thomas Hospital, Westminster Bridge Road , London, United Kingdom
                [4] 4 Harris Birthright Research Centre for Fetal Medicine, King’s College London , London, United Kingdom
                [5] 5 Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King’s College London , London, United Kingdom
                Author notes

                Edited by: Reinaldo Marín, Instituto Venezolano de Investigaciones Científicas (IVIC), Venezuela

                Reviewed by: Chloe A. Brady, The University of Manchester, United Kingdom; Marta Cohen, Sheffield Children’s Hospital, United Kingdom

                *Correspondence: Panicos Shangaris, panicos.shangaris@ 123456kcl.ac.uk

                †These authors share first authorship

                This article was submitted to Developmental Endocrinology, a section of the journal Frontiers in Endocrinology

                Article
                DOI: 10.3389/fendo.2022.945543
                PMC ID: 9355722
                PubMed ID: 35937841
                SO-VID: 60f08a2a-cc27-487a-a75c-b1161cf56f86
                Copyright © Copyright © 2022 Moar, Simela, Nanda, Marnerides, Al-Adnani, Nelson-Piercy, Nicolaides and Shangaris
                License:

                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.

                History
                Date received : 16 May 2022
                Date accepted : 29 June 2022
                Page count
                Figures: 3, Tables: 9, Equations: 0, References: 56, Pages: 17, Words: 8270
                Categories
                Subject: Endocrinology
                Subject: Systematic Review

                ScienceOpen disciplines: Endocrinology & Diabetes
                Keywords: chi,recurrent miscarriage,intervillositis,stillbirth,small gestation age (sga)
                Data availability:
                ScienceOpen disciplines: Endocrinology & Diabetes
                Keywords: chi, recurrent miscarriage, intervillositis, stillbirth, small gestation age (sga)

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