{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T17:18:44Z","timestamp":1778174324317,"version":"3.51.4"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T00:00:00Z","timestamp":1770681600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To evaluate the impact of hydroxychloroquine (HCQ) on pregnancy outcomes and maternal and fetal complications in women with a history of recurrent pregnancy loss (RPL) and autoimmune disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The medical records of pregnant women with a history of RPL and autoimmune disease attending the Shanghai First Maternity and Infant Hospital between January 2017 and December 2019 were retrospectively reviewed. Primary outcomes were gestational week at delivery (term: \u2265 37 weeks; preterm: &amp;lt; 37 weeks). Secondary outcomes were mid-to-late pregnancy loss and maternal and fetal complications, defined in accordance with national and international guidelines.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>103 (20.9%) patients were exposed to HCQ (0.1g twice daily), 389 (79.1%) were not. There were 436 full-term births, 48 preterm births, 5 late-term miscarriages, 2 stillbirths, and 1 fetal malformation-induced abortion. Univariable\/multivariable analyses showed a potential protective trend of HCQ against preterm birth (unadjusted OR 0.86 [95% CI 0.40\u20131.84], p=0.70; Model 1 [adjusted for age, body mass index (BMI), recurrent abortion, antiphospholipid antibodies, undifferentiated connective tissue disease (UCTD)\/Sjogren\u2019s syndrome (SS), serological markers]: OR 0.59 [95% CI 0.19\u20131.84], p=0.37; Model 2 [additional adjustment for low molecular weight heparin (LMWH), intravenous immunoglobulin (IVIG), prednisone, aspirin]: OR 0.41 [95% CI 0.11\u20131.51], p=0.18). Fetal weight (HCQ: 3215.46\u00a0\u00b1\u00a0459.21g vs. non-HCQ: 3226.96\u00a0\u00b1\u00a0500.01g, p=0.84) and maternal-fetal complications showed no differences. Subgroup analysis stratified by autoimmune diagnosis (antiphospholipid syndrome [APS], UCTD, SS) revealed no heterogeneity (APS: OR 0.78 [95% CI 0.28, 2.22], p = 0.64; UCTD: OR 0.52 [95% CI 0.15, 1.81], p = 0.30; SS: OR 1.03 [95% CI 0.12, 8.87], p = 0.98).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study showed that in women with a history of RPL and autoimmune disease, HCQ use was not statistically significantly associated with adverse pregnancy outcomes or maternal-fetal complications. A potential protective trend against preterm birth was observed, but this association did not reach statistical significance.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1756063","type":"journal-article","created":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T07:05:35Z","timestamp":1770707135000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Hydroxychloroquine therapy for women with both recurrent pregnancy loss and autoimmune disease: association with pregnancy outcomes and maternal-fetal complications"],"prefix":"10.3389","volume":"17","author":[{"given":"Mengyang","family":"Du","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruixiu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Na","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liying","family":"Peng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shihua","family":"Bao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,10]]},"reference":[{"key":"B1","article-title":"Recurrent Pregnancy Loss","volume-title":"StatPearls","author":"Boedeker","year":"2025"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3390\/jcm12124074","article-title":"Recurrent pregnancy loss etiology, risk factors, diagnosis, and management. Fresh look into a full box","volume":"12","author":"Turesheva","year":"2023","journal-title":"J Clin Med"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbih.2024.100868","article-title":"Recurrent Pregnancy Loss: Immunological aetiologies and associations with mental health","volume":"41","author":"Laijawala","year":"2024","journal-title":"Brain Behav Immun Health"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1097\/cm9.0000000000001691","article-title":"Systemic autoimmune diseases and recurrent pregnancy loss: research progress in diagnosis and treatment","volume":"134","author":"Gao","year":"2021","journal-title":"Chin Med J (Engl)"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinsp.2022.100140","article-title":"A meta-analysis of the effect of Sj\u00f6gren's syndrome on adverse pregnancy outcomes","volume":"77","author":"Geng","year":"2022","journal-title":"Clinics (Sao Paulo)"},{"key":"B6","doi-asserted-by":"publisher","first-page":"e36873","DOI":"10.1097\/md.0000000000036873","article-title":"Causal association between rheumatoid arthritis and pregnancy loss and intrauterine growth retardation: A bidirectional two-sample Mendelian randomization study","volume":"103","author":"Guo","year":"2024","journal-title":"Med (Baltimore)"},{"key":"B7","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1186\/s13075-022-02783-0","article-title":"Systemic sclerosis and pregnancy outcomes: a retrospective study from a single center","volume":"24","author":"Barilaro","year":"2022","journal-title":"Arthritis Res Ther"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2019.10.002","article-title":"Immunologic and rheumatologic causes and treatment of recurrent pregnancy loss: what is the evidence","volume":"112","author":"Odendaal","year":"2019","journal-title":"Fertil Steril"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/s0049-3848(19)30366-4","article-title":"Managing antiphospholipid syndrome in pregnancy","volume":"181","author":"Schreiber","year":"2019","journal-title":"Thromb Res"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1136\/rmdopen-2024-004091","article-title":"Management of pregnancy in autoimmune rheumatic diseases: maternal disease course, gestational and neonatal outcomes and use of medications in the prospectiveItalian P-RHEUM.it study","volume":"10","author":"Andreoli","year":"2024","journal-title":"RMD Open"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3238\/arztebl.m2021.0353","article-title":"Pregnancy and autoimmune disease","volume":"119","author":"Merz","year":"2022","journal-title":"Dtsch Arztebl Int"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2019.101322","article-title":"Autoimmune diseases and pregnancy","volume":"33","author":"Tincani","year":"2019","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbspin.2021.105143","article-title":"Hydroxychloroquine in systemic and autoimmune diseases: Where are we now","volume":"88","author":"Dima","year":"2021","journal-title":"Joint Bone Spine"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1111\/nep.13991","article-title":"The efficacy and safety of hydroxychloroquine in pregnant patients with IgA nephropathy: A retrospective cohort study","volume":"27","author":"Tang","year":"2022","journal-title":"Nephrol (Carlton)"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deae146","article-title":"Hydroxychloroquine in recurrent pregnancy loss: data from a French prospective multicenter registry","volume":"39","author":"Dernoncourt","year":"2024","journal-title":"Hum Reprod"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10020179","article-title":"Women with a history of recurrent pregnancy loss are a high-risk population for adverse obstetrical outcome: A retrospective cohort study","volume":"10","author":"Rasmark Roepke","year":"2021","journal-title":"J Clin Med"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1007\/s00296-023-05457-5","article-title":"The effects of hydroxychloroquine and its promising use in refractory obstetric antiphospholipid syndrome","volume":"44","author":"Fierro","year":"2024","journal-title":"Rheumatol Int"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.17459","article-title":"Protection by hydroxychloroquine prevents placental injury in obstetric antiphospholipid syndrome","volume":"26","author":"Liu","year":"2022","journal-title":"J Cell Mol Med"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1186\/1546-0096-7-9","article-title":"Systematic review of hydroxychloroquine use in pregnant patients with autoimmune diseases","volume":"7","author":"Sperber","year":"2009","journal-title":"Pediatr Rheumatol Online J"},{"key":"B20","doi-asserted-by":"publisher","first-page":"e001239","DOI":"10.1136\/lupus-2024-001239","article-title":"Effect of hydroxychloroquine on pregnancy outcome in patients with SLE: a systematic review and meta-analysis","volume":"11","author":"Zhu","year":"2024","journal-title":"Lupus Sci Med"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keac372","article-title":"Outcomes of children born to mothers with systemic lupus erythematosus exposed to hydroxychloroquine or azathioprine","volume":"62","author":"Reynolds","year":"2023","journal-title":"Rheumatol (Oxford)"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2020.09.007","article-title":"Hydroxychloroquine early in pregnancy and risk of birth defects","volume":"224","author":"Huybrechts","year":"2021","journal-title":"Am J Obstet Gynecol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keae168","article-title":"Hydroxychloroquine in lupus or rheumatoid arthritis pregnancy and risk of major congenital malformations: a population-based cohort study","volume":"64","author":"Nguyen","year":"2025","journal-title":"Rheumatol (Oxford)"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1002\/art.11304","article-title":"Safety of hydroxychloroquine in pregnant patients with connective tissue diseases: a study of one hundred thirty-three cases compared with a control group","volume":"48","author":"Costedoat-Chalumeau","year":"2003","journal-title":"Arthritis Rheum"},{"key":"B25","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1186\/s12884-025-07471-w","article-title":"Antiphospholipid syndrome in pregnancy: a comprehensive literature review","volume":"25","author":"Murvai","year":"2025","journal-title":"BMC Pregnancy Childbirth"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.2147\/ijwh.S503677","article-title":"Elevated homocysteine levels and endothelial dysfunction in unexplained recurrent spontaneous abortion","volume":"17","author":"Qi","year":"2025","journal-title":"Int J Womens Health"},{"key":"B27","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.nutres.2021.05.002","article-title":"Hyperhomocysteinemia and low vitamin B12 are associated with the risk of early pregnancy loss: A clinical study and meta-analyses","volume":"91","author":"Bala","year":"2021","journal-title":"Nutr Res"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1111\/aji.12402","article-title":"Autoantibodies to factor XII and kininogen-dependent antiphosphatidylethanolamine antibodies in patients with recurrent pregnancy loss augment platelet aggregation","volume":"74","author":"Sato","year":"2015","journal-title":"Am J Reprod Immunol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.jogc.2025.103167","article-title":"Guideline no. 464: recurrent pregnancy loss","volume":"47","author":"Motan","year":"2025","journal-title":"J Obstet Gynaecol Can"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keu236","article-title":"Impaired endothelial function in patients with undifferentiated connective tissue disease: a follow-up study","volume":"53","author":"Laczik","year":"2014","journal-title":"Rheumatol (Oxford)"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1007\/s13224-019-01212-8","article-title":"Systemic lupus erythematosus and pregnancy: A brief review","volume":"69","author":"Dalal","year":"2019","journal-title":"J Obstet Gynaecol India"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-019-04670-7","article-title":"Characteristics of pregnancy complications and treatment in obstetric antiphospholipid syndrome in China","volume":"38","author":"Zhou","year":"2019","journal-title":"Clin Rheumatol"},{"key":"B33","doi-asserted-by":"publisher","first-page":"e13931","DOI":"10.1111\/aji.13931","article-title":"Clinical features between primary obstetric antiphospholipid syndrome and non-criteria obstetric antiphospholipid syndrome and risk factors of adverse pregnancy outcomes: A retrospective study of 1006 cases","volume":"92","author":"Liu","year":"2024","journal-title":"Am J Reprod Immunol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3390\/jcm13123454","article-title":"Modern management of pregnancy in systemic lupus erythematosus: from prenatal counseling to postpartum support","volume":"13","author":"Gamba","year":"2024","journal-title":"J Clin Med"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12872","article-title":"Reproductive outcomes following hydroxychloroquine use for autoimmune diseases: a systematic review and meta-analysis","volume":"81","author":"Kaplan","year":"2016","journal-title":"Br J Clin Pharmacol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2004.11.009","article-title":"Safety of hydroxychloroquine in pregnant patients with connective tissue diseases. Review of the literature","volume":"4","author":"Costedoat-Chalumeau","year":"2005","journal-title":"Autoimmun Rev"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.31486\/toj.20.0013","article-title":"Systemic lupus erythematosus: perinatal outcomes in patients treated with and without hydroxychloroquine","volume":"20","author":"Baalbaki","year":"2020","journal-title":"Ochsner J"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1136\/lupus-2021-000651","article-title":"Hydroxychloroquine in the pregnancies of women with lupus: a meta-analysis of individual participant data","volume":"9","author":"Clowse","year":"2022","journal-title":"Lupus Sci Med"},{"key":"B39","doi-asserted-by":"publisher","first-page":"e13761","DOI":"10.1111\/aji.13761","article-title":"Does adding hydroxychloroquine to empiric treatment improve the live birth rate in refractory obstetrical antiphospholipid syndrome? A systematic review","volume":"90","author":"Hooper","year":"2023","journal-title":"Am J Reprod Immunol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1080\/01443615.2022.2141615","article-title":"The effect of hydroxychloroquine on pregnancy outcomes in patients with unexplained recurrent pregnancy loss: a placebo-controlled study \"pilot study","volume":"42","author":"Moini","year":"2022","journal-title":"J Obstet Gynaecol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1136\/lupus-2025-001654","article-title":"Risk of preterm delivery and early pregnancy hydroxychloroquine use from a Californian lupus cohort","volume":"12","author":"Rector","year":"2025","journal-title":"Lupus Sci Med"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.722511","article-title":"Chloroquine and hydroxychloroquine use during pregnancy and the risk of adverse pregnancy outcomes using real-world evidence","volume":"12","author":"B\u00e9rard","year":"2021","journal-title":"Front Pharmacol"},{"key":"B43","doi-asserted-by":"publisher","first-page":"29","DOI":"10.63032\/SEDD2624","article-title":"Pregnancy outcomes in connective tissue diseases: a 30-year study of 465 cases from a single-center Spanish registry with insights on hydroxychloroquine use","volume":"4","author":"Sieiro Santos","year":"2025","journal-title":"ARP Rheumatol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keaa592","article-title":"Fetal safety of chloroquine and hydroxychloroquine use during pregnancy: a nationwide cohort study","volume":"60","author":"Andersson","year":"2021","journal-title":"Rheumatol (Oxford)"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1632388","article-title":"Effect of additional treatments combined with conventional therapies in pregnant patients with high-risk antiphospholipid syndrome: A multicentre study","volume":"118","author":"Ruffatti","year":"2018","journal-title":"Thromb Haemost"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1756063\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T07:05:37Z","timestamp":1770707137000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1756063\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,10]]},"references-count":45,"alternative-id":["10.3389\/fimmu.2026.1756063"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1756063","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,10]]},"article-number":"1756063"}}