Chronic Inflammatory Conditions in Pregnancy

Chronic inflammatory conditions of pregnancy encompass a spectrum of placental lesions driven by persistent immune cell infiltration and dysregulated maternal–fetal tolerance. These syndromes include chronic histiocytic intervillositis, characterised by maternal macrophages accumulating in the intervillous space; villitis of unknown aetiology, in which maternal T lymphocytes invade the chorionic villi; and massive perivillous fibrin deposition, marked by extensive fibrin occupying the intervillous region. Although relatively rare, each condition carries a high risk of adverse outcomes such as fetal growth restriction, preterm birth, miscarriage and stillbirth. Recurrence rates are notable, particularly in subsequent gestations, underscoring the need for early recognition and intervention. Pathogenesis is thought to involve alloimmune and autoimmune mechanisms, with emerging evidence of antibody and complement activation at the maternal–fetal interface. Diagnosis currently relies on postpartum histopathological examination, highlighting an urgent requirement for antenatal biomarkers and targeted therapies to improve maternal and neonatal health worldwide.

Research from Nature Portfolio

Recent studies have revealed a pronounced upregulation of HLA-Class II molecules on syncytiotrophoblast in cases of chronic histiocytic intervillositis, suggesting that altered antigen presentation may drive macrophage recruitment and complement activation at the maternal–fetal boundary. Although anti-HLA antibodies were not significantly elevated in maternal sera, the degree of HLA-Class II expression correlated closely with lesion severity and C4d deposition, implicating local immune dysregulation in pathogenesis. In parallel, a large retrospective analysis of over one hundred pregnancies affected by chronic intervillositis documented substantial rates of miscarriage, stillbirth and fetal growth restriction, with nearly half of women experiencing recurrence in subsequent gestations. These findings underscore both the clinical burden of this condition and the critical need for standardised diagnostic criteria and effective prophylactic strategies.

Chronic Inflammatory Conditions in Pregnancy publication trend

The graph below shows the total number of articles in chronic inflammatory conditions in pregnancy across all publications each year (not limited to Nature Index journals).

Technical terms

Chronic histiocytic intervillositis (CHI): A placental lesion defined by maternal macrophage infiltration of the intervillous space leading to impaired exchange and adverse outcomes.

Villitis of unknown aetiology (VUE): Maternal T-lymphocyte invasion of chorionic villi in the absence of infection, associated with growth restriction and recurrence.

Massive perivillous fibrin deposition (MPFD): Extensive accumulation of fibrin within the intervillous compartment that disrupts maternal–fetal gas and nutrient transfer.

HLA-Class II: Antigen-presenting molecules normally expressed on immune cells, whose upregulation on trophoblast may trigger maternal immune activation.

References

1. Virtual crossmatching reveals upregulation of placental HLA-Class II in chronic histiocytic intervillositis. Scientific Reports (2024).
2. Adverse perinatal outcomes of chronic intervillositis of unknown etiology: an observational retrospective study of 122 cases. Scientific Reports (2020).
3. Chronic Inflammatory Placental Disorders Associated With Recurrent Adverse Pregnancy Outcome. Frontiers in Immunology (2022).
4. Immunomodulatory Therapy Reduces the Severity of Placental Lesions in Chronic Histiocytic Intervillositis. Frontiers in Medicine (2021).