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

Anca Marina Ciobanu,Ana Maria Scutelnicu,Nicolae Gică,Anca Maria Panaitescu,Alexandra Bouariu,Mihaela Roxana Popescu

doi:10.3390/healthcare10010168

Abstract

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.

Highlights

Considered central to chronic disease development [1], placental phenotype arrangement is thought to determine chronic adult-onset disease
Unbalanced maternal nutrition, periods of chronic hypoxia or increased levels of glucocorticoids or thyroid hormones determine fetal structural alterations such as reduced blood vessel diameter [2], low arterial elastin [3], reduced numbers of nephrons in the kidney [4], reduced number of beta cells in the pancreas [5], and changes in brain structure and function [6] that increase the vulnerability for heart disease, stroke, obesity, and diabetes later in adult life
Hydroxychloroquine is an antimalarial agent firstly described in 1955 that has an anti-inflammatory and immunomodulator effect, showing a complex mechanism of action. It increases intracellular pH within intracellular vacuoles, and it has been demonstrated that it alters various processes such as protein degradation by acidic hydrolases in the lysosome, assembly of macromolecules in the endosomes, and post-translation modification of proteins in the Golgi apparatus [43]

Summary

Introduction

Considered central to chronic disease development [1], placental phenotype arrangement is thought to determine chronic adult-onset disease. Unbalanced maternal nutrition, periods of chronic hypoxia or increased levels of glucocorticoids or thyroid hormones determine fetal structural alterations such as reduced blood vessel diameter [2], low arterial elastin [3], reduced numbers of nephrons in the kidney [4], reduced number of beta cells in the pancreas [5], and changes in brain structure and function [6] that increase the vulnerability for heart disease, stroke, obesity, and diabetes later in adult life. The placenta is the site of connection between maternal and fetal circulation and the liaison is established early in pregnancy, when placentation occurs. Inflammatory placental conditions with acute or chronic onset have specific immunological mechanisms and carry a significant short- and long-term response in fetal development with an increased recurrence rate for subsequent pregnancies. As seen on microscopical preparations, is associated to chorioamnionitis [7].

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