Background/Purpose: The antiphospholipid syndrome (APS) is defined by a combination of arterial and/or venous thrombosis, pregnancy morbidity, and persistent antiphospholipid antibodies. There is a real gap in knowledge on intrauterine fetal death (IUFD) in APS patients because there are no large published series. Moreover, heterogeneous gestational ages and varying definitions of APL assays positivity are used in the literature.

Methods: We retrospectively analysed the history and clinical data of women followed in 4 French university hospitals for a diagnosis of APS (Sydney criteria) who experienced an IUFD at or after 10 weeks of gestation (WG) between 2000 and 2016. According to the classification criteria, if the IUFD was otherwise explainable by a fetal or obstetrical complication not related to APS, the patient was excluded. The patients were included when at least 2 positive antibodies were found 12 weeks apart or more and within 5 years of the obstetrical event.

Results: Sixty patients were included. Their mean age at the IUFD was 29 ± 5 years (Table 1). Prior to the IUFD, 10 patients (17%) had a previous live birth, 8 (13%) had an early miscarriage, 5 (8%) an abortion while 37 (62%) were nulligest. APS was already known in 9 patients (15%) and systemic lupus erythematosus (SLE) in 8 patients (13%). There was a high prevalence of triple positive (38%) and double positive (25%) women.

During the index IUFD, treatment consisted of low dose aspirin (LDA) (n=7), low molecular weight heparin (LMWH) (n=3) or a combination of both (n=5). IUFD occurred at a mean gestational age of 22.3 ± 7 WG. It was associated in 16 cases to obstetrical complications, namely preeclampsia (n=12), HELLP syndrome (n=6) and/or placental abruption (n=5). There was no maternal mortality associated. Placental infarctions were found in 25 out of 34 available histologic examinations.

Regarding the following pregnancy, 34 out of the 43 patients (79%) who received a treatment (LDA and/or LMWH started before 12 WG) had a live birth versus 1 out of 9 patients (11%) who did not receive such treatment.

Overall, including the follow up period of 5 years [IQR: 3-10], 26 patients (43%) experienced one or more thrombosis, among which half before the index IUFD, and 28% were diagnosed with SLE. Ultimately, 51 patients had at least one live birth, including 48 after experiencing the IUFD. The median age at last follow-up of the childless women was 33 years old [IQR: 30-45].

Conclusion: The IUFD was mostly inaugural in the APS and unrelated to other obstetrical complications. The strong autoimmune biology, significant occurrence of SLE and thrombosis suggest that these IUFD events happened in patients with a solid APS diagnosis and are not randomly associated with weak autoantibodies. A majority of women succeeded in having at least one live birth when treated.

Table 1. Patients’ characteristics