Chronic Intervillositis of Unknown Etiology (CIUE): Prevalence, patterns and reproductive outcomes at a tertiary referral institution

Simula, Natasha K.; Terry, Jefferson; Kent, Nancy; Robertson, Julie; Purkiss, Susan; Bloomenthal, Dena; Williams, Christina

doi:10.1016/j.placenta.2020.07.032

Cited by 17 publications

(21 citation statements)

References 23 publications

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“…It is their recurrent nature that makes them particularly important for patients and clinicians, despite their relative rarity. VUE affects 5-15% of placentas (9), CHI 0.2% (10), and MPFD 0.5% (11). The underlying disease mechanisms are poorly understood and there are no biomarkers or treatment protocols that can reliably predict or prevent recurrence in a subsequent pregnancy (12,13).…”

Section: Introductionmentioning

confidence: 99%

Chronic Inflammatory Placental Disorders Associated With Recurrent Adverse Pregnancy Outcome

2022

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Chronic inflammatory placental disorders are a group of rare but devastating gestational syndromes associated with adverse pregnancy outcome. This review focuses on three related conditions: villitis of unknown etiology (VUE), chronic histiocytic intervillositis (CHI) and massive perivillous fibrin deposition (MPFD). The hallmark of these disorders is infiltration of the placental architecture by maternal immune cells and disruption of the intervillous space, where gas exchange between the mother and fetus occurs. Currently, they can only be detected through histopathological examination of the placenta after a pregnancy has ended. All three are associated with a significant risk of recurrence in subsequent pregnancies. Villitis of unknown etiology is characterised by a destructive infiltrate of maternal CD8+ T lymphocytes invading into the chorionic villi, combined with activation of fetal villous macrophages. The diagnosis can only be made when an infectious aetiology has been excluded. VUE becomes more common as pregnancy progresses and is frequently seen with normal pregnancy outcome. However, severe early-onset villitis is usually associated with fetal growth restriction and recurrent pregnancy loss. Chronic histiocytic intervillositis is characterised by excessive accumulation of maternal CD68+ histiocytes in the intervillous space. It is associated with a wide spectrum of adverse pregnancy outcomes including high rates of first-trimester miscarriage, severe fetal growth restriction and late intrauterine fetal death. Intervillous histiocytes can also accumulate due to infection, including SARS-CoV-2, although this infection-induced intervillositis does not appear to recur. As with VUE, the diagnosis of CHI requires exclusion of an infectious cause. Women with recurrent CHI and their families are predisposed to autoimmune diseases, suggesting CHI may have an alloimmune pathology. This observation has driven attempts to prevent CHI with a wide range of maternal immunosuppression. Massive perivillous fibrin deposition is diagnosed when >25% of the intervillous space is occupied by fibrin, and is associated with fetal growth restriction and late intrauterine fetal death. Although not an inflammatory disorder per se, MPFD is frequently seen in association with both VUE and CHI. This review summarises current understanding of the prevalence, diagnostic features, clinical consequences, immune pathology and potential prophylaxis against recurrence in these three chronic inflammatory placental syndromes.

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Section: Introductionmentioning

confidence: 99%

Chronic Inflammatory Placental Disorders Associated With Recurrent Adverse Pregnancy Outcome

2022

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“…A study from the Children’s and Women’s Hospital in Vancouver, BC, Canada [ 72 ], reports various empiric treatment in patients with previous diagnosis of CIUE/CHI. One of the options of treatment was HCQ with a dosage ranging between 200 and 400 mg PO daily.…”

Section: Results and Discussion: Hydroxychloroquine In Pregnancymentioning

confidence: 99%

The Potential Benefit of Hydroxychloroquine in Chronic Placental Inflammation of Unknown Etiology Associated with Adverse Pregnancy Outcomes

et al. 2022

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The placenta is the site of connection between maternal and fetal circulation, and the liaison is established early in pregnancy. A large variety of pregnancy complications such as preterm birth, fetal growth restriction, or pregnancy loss have placental expression and can be accompanied in some cases of acute or chronic identifiable placental inflamatory lesions. Chronic placental inflammatory (CPI) lesions include chronic villitis of unknow etiology (CVUE), chronic intervillositis of unknown etiology, CIUE (also described as chronic histiocytic intervillositis, CHI), and chronic deciduits. Hydroxychloroquine (HCQ) has been prescribed with good results during pregnancy to prevent adverse perinatal outcomes in maternal autoimmune conditions. Its success has paved the way to its use in CPI as CIUE/CHI; however, to date, there are no prospective, informatively designed, controlled studies on its value in these setting. This review aims to explore the potential role of HCQ in CPI of unknown etiology. Ideally, properly designed, probably multicentric studies should be undertaken to fully understand HCQ’s role for prevention of adverse pregnancy outcomes after a chronic placental inflammation.

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“…It is known that CHI can exist with or without fibrin deposition and so while it is not necessary for diagnosis, the role of fibrin in severity classification systems is interesting. While in some, fibrin was acknowledged, this was not the case in studies with methods that did not call for fibrin to be noted (19,39). Table 9 illustrates the varying inclusion and exclusion criteria for CHI classification in all the studies included.…”

Section: Discussion Principle Findingsmentioning

confidence: 99%

“…Selection bias was reported in four of the twelve studies due to how participants were selected from a pathology database (15,18,37,39). Furthermore, in other cases, selection bias was detected because of limited search terms comprising only of 'CIUE and chronic intervillositis' in one study and 'intervillositis' in another (15,39).…”

Section: Risk Of Bias Of Included Studiesmentioning

confidence: 99%

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

et al. 2022

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BackgroundChronic 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.ObjectiveThe 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.MethodsA 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.ResultsNo 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).ConclusionsThis 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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Chronic Intervillositis of Unknown Etiology (CIUE): Prevalence, patterns and reproductive outcomes at a tertiary referral institution

Cited by 17 publications

References 23 publications

Chronic Inflammatory Placental Disorders Associated With Recurrent Adverse Pregnancy Outcome

Chronic Inflammatory Placental Disorders Associated With Recurrent Adverse Pregnancy Outcome

The Potential Benefit of Hydroxychloroquine in Chronic Placental Inflammation of Unknown Etiology Associated with Adverse Pregnancy Outcomes

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

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