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Meta-Analysis
. 2022 Jul 22:13:945543.
doi: 10.3389/fendo.2022.945543. eCollection 2022.

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

Laurel Moar  1 , Chloe Simela  1 , Surabhi Nanda  1   2 , Andreas Marnerides  3 , Mudher Al-Adnani  3 , Catherine Nelson-Piercy  1   2 , Kypros H Nicolaides  1   4 , Panicos Shangaris  1   2   5
Affiliations
Meta-Analysis

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

Laurel Moar et al. Front Endocrinol (Lausanne). .

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.

Keywords: CHI; intervillositis; recurrent miscarriage; small gestation age (SGA); stillbirth.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Study selection process of the systematic review and meta-analysis into outcomes of pregnancies affected by CHI.
Figure 2
Figure 2
Forest plot summarising odds of live birth rates in treated vs untreated pregnancies.
Figure 3
Figure 3
Forest plot summarising risk ratios of pregnancy loss in low/moderate vs severe CHI.
See this image and copyright information in PMC

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