Hydroxychloroquine in obstetrics: potential implications of the prophylactic use of hydroxychloroquine for placental insufficiency during pregnancy
1
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
Proper placentation during early pregnancy is a key factor for maintaining a healthy pregnancy. Placental insufficiency leads to critical complications such as preeclampsia, fetal growth restriction, and fetal demise. These complications are often associated with pathological findings of restricted remodeling and obstructive lesions of the myometrial spiral arteries, which have high recurrence rates during subsequent pregnancies. Currently, there are no pharmacological interventions other than aspirin for the prevention of preeclampsia. Hydroxychloroquine (HCQ), a well-known antimalarial drug, reduces inflammatory and thrombotic changes in vessels. For decades, the use of HCQ for autoimmune diseases has resulted in the successful prevention of both arterial and venous thrombotic events and has been extended to the treatment of lupus and antiphospholipid antibody syndrome during pregnancy. HCQ reduces the risk of preeclampsia with lupus by up to 90%. Several recent studies have investigated whether HCQ improves pregnancy outcomes in women with a history of poor outcomes. In addition, in vitro and animal studies have demonstrated the beneficial effects of HCQ in improving endothelial dysfunction and alleviating hypertension and proteinuria. Therefore, we hypothesized that HCQ has the potential to attenuate the vascular inflammatory and thrombogenic pathways associated with placental insufficiency and conducted a multicenter clinical trial on the efficacy of combining aspirin with HCQ for pregnancies at high risk for preeclampsia in Korea. This study summarizes the potential effects of HCQ on pregnancies with placental insufficiency and the implications of HCQ treatment in the field of obstetrics.
Abstract
Proper placentation during early pregnancy is a key factor for maintaining a healthy pregnancy. Placental insufficiency leads to critical complications such as preeclampsia, fetal growth restriction, and fetal demise. These complications are often associated with pathological findings of restricted remodeling and obstructive lesions of the myometrial spiral arteries, which have high recurrence rates during subsequent pregnancies. Currently, there are no pharmacological interventions other than aspirin for the prevention of preeclampsia. Hydroxychloroquine (HCQ), a well-known antimalarial drug, reduces inflammatory and thrombotic changes in vessels. For decades, the use of HCQ for autoimmune diseases has resulted in the successful prevention of both arterial and venous thrombotic events and has been extended to the treatment of lupus and antiphospholipid antibody syndrome during pregnancy. HCQ reduces the risk of preeclampsia with lupus by up to 90%. Several recent studies have investigated whether HCQ improves pregnancy outcomes in women with a history of poor outcomes. In addition, in vitro and animal studies have demonstrated the beneficial effects of HCQ in improving endothelial dysfunction and alleviating hypertension and proteinuria. Therefore, we hypothesized that HCQ has the potential to attenuate the vascular inflammatory and thrombogenic pathways associated with placental insufficiency and conducted a multicenter clinical trial on the efficacy of combining aspirin with HCQ for pregnancies at high risk for preeclampsia in Korea. This study summarizes the potential effects of HCQ on pregnancies with placental insufficiency and the implications of HCQ treatment in the field of obstetrics.
참고문헌 (62)
- Schrezenmeier E, "Mechanisms of action of hydroxychloroquine and chloroquine : implications for rheumatology", Nat Rev Rheumatol, 16, pp.155~166 (2020)
- Sammaritano LR, "2020 American College of Rheumatology guideline for the management of reproductive health in rheumatic and musculoskeletal diseases", Arthritis Rheumatol, 72, pp.529~556 (2020)
- Tang C, "Hydroxychloroquine in lupus : emerging evidence supporting multiple beneficial effects", Intern Med J, 42, pp.968~978 (2012)
- Seo MR, "Hydroxychloroquine treatment during pregnancy in lupus patients is associated with lower risk of preeclampsia", Lupus, 28, pp.722~730 (2019)
- Leroux M, "Impact of hydroxychloroquine on preterm delivery and intrauterine growth restriction in pregnant women with systemic lupus erythematosus : a descriptive cohort study", Lupus, 24, pp.1384~1391 (2015)
- Duan J, "Hydroxychloroquine prophylaxis for preeclampsia, hypertension and prematurity in pregnant patients with systemic lupus erythematosus : a meta-analysis", Lupus, 30, pp.1163~1174 (2021)
- Bermas BL, "Trends in use of hydroxychloroquine during pregnancy in systemic lupus erythematosus patients from 2001 to 2015", Lupus, 27, pp.1012~1017 (2018)
- de Moreuil C, "Hydroxychloroquine may be beneficial in preeclampsia and recurrent miscarriage", Br J Clin Pharmacol, 86, pp.39~49 (2020)
- Brosens I, "The"great obstetrical syndromes"are associated with disorders of deep placentation", Am J Obstet Gynecol, 204, pp.193~201 (2011)
- Robertson WB, "The pathological response of the vessels of the placental bed to hypertensive pregnancy", J Pathol Bacteriol, 93, pp.581~592 (1967)
- Brosens I, "Fetal growth retardation and the arteries of the placental bed", Br J Obstet Gynaecol, 84, pp.656~663 (1977)
- Kadyrov M, "Divergent trophoblast invasion and apoptosis in placental bed spiral arteries from pregnancies complicated by maternal anemia and early-onset preeclampsia", intrauterine growth restriction, 2006, pp.194, 557~563
- De Wolf F, "Fetal growth retardation and the maternal arterial supply of the human placenta in the absence of sustained hypertension", Br J Obstet Gynaecol, 87, pp.678~685 (1980)
- Ball E, "Late sporadic miscarriage is associated with abnormalities in spiral artery transformation and trophoblast invasion", J Pathol, 208, pp.535~542 (2006)
- "Gestational hypertension and preeclampsia: ACOG practice bulletin, number 222", Obstet Gynecol, 135, pp.e237~e260 (2020)
- Ahn TG, "Preeclampsia and aspirin", Obstet Gynecol Sci, 66, pp.120~132 (2023)
- Brouwers L, "Recurrence of pre-eclampsia and the risk of future hypertension and cardiovascular disease : a systematic review and metaanalysis", BJOG, 125, pp.1642~1654 (2018)
- Surapaneni T, "Risk for recurrence of pre-eclampsia in the subsequent pregnancy", J Clin Diagn Res, 7, pp.2889~2891 (2013)
- Elawad T, "Risk factors for pre-eclampsia in clinical practice guidelines : comparison with the evidence", BJOG, 131, pp.46~62 (2024)
- Villar J, "Preeclampsia, gestational hypertension and intrauterine growth restriction, related or independent conditions?", Am J Obstet Gynecol, 194, pp.921~931 (2006)
- Bartsch E, "Clinical risk factors for pre-eclampsia determined in early pregnancy : systematic review and meta-analysis of large cohort studies", BMJ, 353, pp.i1753~ (2016)
- Lamont K, "Risk of recurrent stillbirth : systematic review and meta-analysis", BMJ, 350, pp.h3080~ (2015)
- Butalia S, "Hypertension Canada’s 2018 guidelines for the management of hypertension in pregnancy", Can J Cardiol, 34, pp.526~531 (2018)
- Regitz-Zagrosek V, "2018 ESC guidelines for the management of cardiovascular diseases during pregnancy", Kardiol Pol, 77, pp.245~326 (2019)
- Lowe SA, "SOMANZ guidelines for the management of hypertensive disorders of pregnancy 2014", Aust N Z J Obstet Gynaecol, 55, pp.e1~e29 (2015)
- Brown MA, "Hypertensive disorders of pregnancy : ISSHP classification, diagnosis, and management recommendations for international practice", Hypertension, 72, pp.24~43 (2018)
- Askie LM, "Antiplatelet agents for prevention of pre-eclampsia : a meta-analysis of individual patient data", Lancet, 369, pp.1791~1798 (2007)
- Bujold E, "Prevention of preeclampsia and intrauterine growth restriction with aspirin started in early pregnancy : a meta-analysis", Obstet Gynecol, 116, pp.402~414 (2010)
- Roberge S, "Prevention of perinatal death and adverse perinatal outcome using low-dose aspirin : a meta-analysis", Ultrasound Obstet Gynecol, 41, pp.491~499 (2013)
- Meher S, "Antiplatelet therapy before or after 16 weeks’ gestation for preventing preeclampsia : an individual participant data meta-analysis", Am J Obstet Gynecol, 216, pp.121~128 (2017)
- Roberge S, "The role of aspirin dose on the prevention of preeclampsia and fetal growth restriction : systematic review and meta-analysis", Am J Obstet Gynecol, 216, pp.110~120 (2017)
- Rey E, "Dalteparin for the prevention of recurrence of placental-mediated complications of pregnancy in women without thrombophilia : a pilot randomized controlled trial", J Thromb Haemost, 7, pp.58~64 (2009)
- Groom KM, "Enoxaparin for the prevention of preeclampsia and intrauterine growth restriction in women with a history : a randomized trial", Am J Obstet Gynecol, 216, pp.296~ (2017)
- Oh SY, "Autophagy in the placenta", Obstet Gynecol Sci, 60, pp.241~259 (2017)
- Lotteau V, "Intracellular transport of class II MHC molecules directed by invariant chain", Nature, 348, pp.600~605 (1990)
- Münz C, "Autophagy beyond intracellular MHC class II antigen presentation", Trends Immunol, 37, pp.755~763 (2016)
- Ewald SE, "The ectodomain of toll-like receptor 9is cleaved to generate a functional receptor", Nature, 456, pp.658~662 (2008)
- Steegers EA, "Pre-eclampsia", Lancet, 376, pp.631~644 (2010)
- Jancinová V, "On the inhibitory effect of chloroquine on blood platelet aggregation", Thromb Res, 74, pp.495~504 (1994)
- Bertrand E, "Antiaggregation action of chloroquine", Med Trop(Mars), 50, pp.143~146 (1990)
- Nosál R, "Chloroquine inhibits stimulated platelets at the arachidonic acid pathway", Thromb Res, 77, pp.531~542 (1995)
- Ruiz-Irastorza G, "Effect of antimalarials on thrombosis and survival in patients with systemic lupus erythematosus", Lupus, 15, pp.577~583 (2006)
- Tektonidou MG, "Risk factors for thrombosis and primary thrombosis prevention in patients with systemic lupus erythematosus with or without antiphospholipid antibodies", Arthritis Rheum, 61, pp.29~36 (2009)
- Rahman R, "The effects of hydroxychloroquine on endothelial dysfunction", Pregnancy Hypertens, 6, pp.259~262 (2016)
- Redman CW, "Preeclampsia, biomarkers, syncytiotrophoblast stress, and placental capacity", Am J Obstet Gynecol, 213, pp.S9~ (2015)
- Choi M, "Effect of hydroxychloroquine and chloroquine on syncytial differentiation and autophagy in primary human trophoblasts", Biomed Pharmacother, 149, pp.112916~ (2022)
- Phipps EA, "Preeclampsia : pathogenesis, novel diagnostics and therapies", Nat Rev Nephrol, 15, pp.275~289 (2019)
- Marchetti T, "Hydroxychloroquine restores trophoblast fusion affected by antiphospholipid antibodies", J Thromb Haemost, 12, pp.910~920 (2014)
- Bertolaccini ML, "Complement inhibition by hydroxychloroquine prevents placental and fetal brain abnormalities in antiphospholipid syndrome", J Autoimmun, 75, pp.30~38 (2016)
- Choi M, "Hydroxychloroquine reduces hypertension and soluble fms-like kinase-1 in a Nω-nitro-l-arginine methyl ester-induced preeclampsia rat model", J Hypertens, 40, pp.2459~2468 (2022)
- Smyth A, "A systematic review and meta-analysis of pregnancy outcomes in patients with systemic lupus erythematosus and lupus nephritis", Clin J Am Soc Nephrol, 5, pp.2060~2068 (2010)
- López P, "Epidemiology of systemic lupus erythematosus in a northern Spanish population : gender and age influence on immunological features", Lupus, 12, pp.860~865 (2003)
- Chakravarty EF, "Obstetric hospitalizations in the United States for women with systemic lupus erythematosus and rheumatoid arthritis", Arthritis Rheum, 54, pp.899~907 (2006)
- Borella E, "Predictors of maternal and fetal complications in SLE patients : a prospective study", Immunol Res, 60, pp.170~176 (2014)
- Kaplan YC, "Reproductive outcomes following hydroxychloroquine use for autoimmune diseases : a systematic review and meta-analysis", Br J Clin Pharmacol, 81, pp.835~848 (2016)
- Andersson NW, "Fetal safety of chloroquine and hydroxychloroquine use during pregnancy : a nationwide cohort study", Rheumatology(Oxford), 60, pp.2317~2326 (2021)
- Huybrechts KF, "Hydroxychloroquine early in pregnancy and risk of birth defects", Am J Obstet Gynecol, 224, pp.290~ (2021)
- Sundelin SP, "Different effects of chloroquine and hydroxychloroquine on lysosomal function in cultured retinal pigment epithelial cells", APMIS, 110, pp.481~489 (2002)
- Melles RB, "The risk of toxic retinopathy in patients on long-term hydroxychloroquine therapy", JAMA Ophthalmol, 132, pp.1453~1460 (2014)
- Marshall E, "Prevalence of hydroxychloroquine retinopathy using 2018 Royal College of Ophthalmologists diagnostic criteria", Eye(Lond), 35, pp.343~348 (2021)
- Rosenbaum JT, "American College of Rheumatology, American Academy of Dermatology, Rheumatologic Dermatology Society, and American Academy of Ophthalmology 2020 joint statement on hydroxychloroquine use with respect to retinal toxicity", Arthritis Rheumatol, 73, pp.908~911 (2021)
- Agudelo Higuita NI, "An update on prevention of malaria in travelers", Ther Adv Infect Dis, 8, pp.20499361211040690~ (2021)