Hydroxychloroquine therapy in women with autoimmune recurrent pregnancy loss, refractory to low dose aspirin and heparin: a randomized controlled trial

Abstract

Hydroxychloroquine (HCQ) is a novel medication for women suffering from autoimmune-related recurrent pregnancy loss. Many autoimmune disorders have been related to poor obstetric outcomes; anti-phospholipid syndrome (APS) is the only autoimmune disorder in which pregnancy loss is a diagnostic requirement. The goal of this study is to see how beneficial it is to provide hydroxychloroquine (HCQ) in addition to low-molecular-weight heparin (LMWH) and low-dose aspirin (LDA) to females having a record of autoimmune-related recurrent pregnancy loss and refractoriness to low-dose aspirin and LMWH in previous pregnancies, both during preconception and gestation. Patients and methods. Between January 2019 and January 2021, 120 females with a history of autoimmune recurrent pregnancy loss at Ain Shams University Maternity Hospital were examined. Participants were divided into two classes using computer-based randomization procedures. During preconception and gestation, class A (60 cases) received hydroxychloroquine (HCQ), while class B (60 cases) received a placebo. Also, they received LDA and LMWH. The primary outcome measure in this study was the rate of live births. Secondary outcomes included gestational age at delivery, birth weight, mode of delivery, Apgar score at 5 minutes, neonatal morbidity, rate of neonatal intensive care unit (NICU) admission, and postneonatal mortality rate. Results. The live birth rate was 66% in class A and 42.3 % in class B. So, it was significantly higher in class A than in class B (p-value = 0.016). Additionally, gestational age at delivery was substantially greater in class A than in class B. In terms of live births, C-section was slightly less common in class A than in class B (p-value = 0.015). Notably, the mean birth weight was 2.509 kg in class A and 1.972 kg in class B, indicating that neonatal birth weight was substantially greater in class A than in class B (p-value = 0.003). Finally, NICU admission was significantly less common in class A than in class B (p-value = 0.044). Conclusion. HCQ is a potent, safe, and cost-effective medication used to prevent adverse obstetric outcomes in females with a history of autoimmune-related recurrent pregnancy loss with refractoriness to LDA and LMWH in previous pregnancies. This randomized controlled trial (RCT) provided additional evidence to support previous studies (non-criteria or seronegative APS), in which the diagnosis of APS is made solely based on the medical history, regardless of laboratory findings for antiphospholipid antibodies (aPL). Trial registration: Pan African Clinical Trial registration number is: PACTR2021104858485905. Key words: hydroxychloroquine; anti-phospholipid syndrome; heparin; low dose aspirin; autoimmune recurrent pregnancy loss