Intrauterine fetal death (IUFD) may be an early sign of antiphospholipid syndrome (APS) in pregnant women, according to study data published in Arthritis Research & Therapy.

Investigators retrospectively analyzed the medical history and clinical data of women at 4 French hospitals (n=65). Participating women had an APS diagnosis and IUFD at or after 10 weeks of gestation during the data collection period from 2000 to 2016. Clinical data included antibody testing for lupus anticoagulant, anticardiolipin antibodies (aCL), and anti-ß2 glycoprotein-1 antibodies (anti-ß2GP1). In addition, researchers captured treatment received during pregnancy, including low-dose aspirin and low-molecular-weight heparin before 12 weeks gestation.

The median age at initial IUFD was 29 years (interquartile range [IRQ], 26 to 33 years) and 38 (58%) participants were primigravida. The index IUFD was the first APS clinical manifestation in 48 women (74%). Lupus anticoagulant, aCL, and anti-ß2GP1 positivity was observed in 72%, 71%, and 51% of women, respectively. In the study, 15 women (23%) were positive for 2 types of antibodies and 35% had a triple-positive antibody profile. 

The median gestational age at loss of pregnancy was 24 weeks (IQR, 18 to 27 weeks). Due to known APS or a history of thrombosis or miscarriage, 16 women (25%) had been treated with low-dose aspirin, prophylactic low-molecular-weight heparin, or a combination of both during the study course. In addition, 5 women received treatment with hydroxychloroquine or corticosteroids and the remaining 49 women had not received treatment during pregnancy. 

Maternal obstetric complications were observed in 16 cases (25%), including preeclampsia (n=12), hemolysis, elevated liver enzymes, and low platelet syndrome (n = 6), and placental abruption (n=5). Of the 50 women for whom ultrasound data was available, half had a small-for-gestational age fetus. During the mean follow-up period of 4 years (IQR, 2 to 9 years), 28 women (43%) had at least 1 thrombosis and 29% were diagnosed with systemic lupus erythematosus. Including women with pre-IUFD and post-IUFD pregnancies, 54 (83%) had at least 1 live birth. Only 1 woman experienced 3 consecutive early miscarriages.

This report provides in-depth clinical data on patients with IUFD and APS. According to these data, IUFD was identified as the “inaugural event of APS,” in that it was the first manifestation of APS in 74% of women who experienced fetal deaths. Among the other indicators of APS, preeclampsia and thromboses were common in this cohort, while the “3 consecutive early miscarriages” criterion for APS was met only once.

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These data highlight the necessity of new interventions to improve obstetric outcome in this specific population of women.

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Belhocine M, Coutte L, Silva NM, et al. Intrauterine fetal deaths related to antiphospholipid syndrome: a descriptive study of 65 women [published online November 6, 2018]. Arthritis Res Ther. doi:10.1186/s13075-018-1745-2