PREVENTION OF RECURRENT IDIOPATHIC HYDROPS FETALIS; IS IT RELATED TO THROMBOSIS AND INFLAMMATION?

PV184 / #644 Poster Topic: AS21 - Pregnancy and Reproductive Health Background/Purpose Hydrops Fetalis (HF) involves abnormal fetal fluid accumulation with placental thickening, often due to non-immune causes (85%), with approximately 70% of them are result of cardiovascular, chromosomal, or infectious factors. The remainder are of unknown causes, defined as idiopathic non-immune (i-NIHF). Pathogenesis of HF includes tissue hypoxia, immunological and complement pathways activation, which are usually accompanied by local inflammation. Recurrence of HF suggests that it might be of a heritable origin. Despite advanced in-utero therapy, mortality as high as 50-95% for most non-immune HF cases, especially those with idiopathic type having the worst prognosis. Therefore, prevention is the utmost important approach to preserve fetal vitality and improve pregnancy outcomes. Methods Presenting a case series of women with recurrent miscarriages attributed to i-NIHF that were treated with standard anti-phospholipid syndrome (APS) prophylaxis protocol, which is used for prevention of fetal loss. The therapeutic regimen includes low-dose aspirin (LDA) 100 mg daily, or daily subcutaneous injections of low molecular weight heparin (LMWH), dose of 40-60 mg Enoxaprin (Clexan), or a combination of both. Due to severe history of recurrent fetal loss, and their failure of repeated trials for productive pregnancy and advancing age with time, an addition of corticosteroids (CS) was recommended for all women (prednisone 30 mg daily for 1 st to 20 mg for 2 nd and 10 mg with tapering close to delivery). Results Table 1 summarizes a case series of 5 young females (age; 29-38 years old) with normal thrombophilia tests and no definitive APS diagnosis who had recurrent miscarriages, who were referred to the rheumatology clinic for suspected autoimmunity or APS. They had a total of 23 pregnancies that resulted in only 1 successful birth of a healthy but premature baby. All women had various obstetrical events including recurrent early spontaneous abortions (during the first 10 weeks), intra-uterine fetal death (IUFD) (during 2 nd -3 rd trimester of pregnancy), and a total of 8 episodes of i-NIHF that were identified (ranges between 22-30 weeks). One woman had 3 episodes of i-NIHF, another had 2, and the rest had 1 each. During follow-up, 2 of those cases had some autoimmune features such as arthralgia, mild rash, Raynaud’s phenomenon, and occasional low titers of antinuclear antibodies (ANA), so were treated with Hydroxychloroquine (400 mg/day) and a low dose of prednisone (5 mg/day). All 5 cases received the treatment protocol (LDA, LMWH,CS) given immediately after conception. Following this protocol, a total of 12 pregnancies were uneventful and resulted in the delivery of 11 healthy babies and 1 with mild HF who survived with no further complications. Interestingly, the occurence of i-NIHF was almost entirely prevented by the treatment protocol. Table 1. Outcome of case series of i-NIHF before and after treatment with APS prophylaxis protocol. *mild HF, born, healthy male . w = gestational age in weeks. Conclusions Idiopathic non-immune hydrops fetalis is a serious condition with high mortality rate and limited effective therapy. Therefore, prevention is of crucial importance. It may recur repeatedly and even occur in addition to other pregnancy morbidities. The true mechanism of pathogenesis for this serious condition is still unclear, this study presents a series of cases which may suggest a possible explanation; a combination of intra-uterine inflammatory and micro-thrombotic processes at the level of placenta. In summary, a prophylactic regimen for APS, involving anti-platelets, anti-coagulant and anti-inflammatory therapy during pregnancy, shows promising effects, and promotes the need for further investigation.