Intrauterine fetal deaths related to antiphospholipid syndrome: a descriptive study of 65 women

Abstract

ObjectiveAlthough one of the three obstetric manifestations of antiphospholipid syndrome (APS) is intrauterine fetal death (IUFD), little is known about it in this context. We report the first large series of patients with APS and IUFD.MethodsWe retrospectively analyzed the history and clinical data of women at four French hospitals. All had (1) APS diagnosis (Sydney criteria) and (2) IUFD at or after 10 weeks of gestation (weeks) between 2000 and 2016.ResultsThe study included 65 women. Their median age at the index IUFD was 29 years (IQR 26–33); 38 (58%) were primigravidas. The index IUFD was the first APS clinical manifestation in 48 women (74%). Overall, 35% had a triple-positive antibody profile.IUFD occurred at a median gestational age of 24 weeks (IQR 18–27) and was associated with maternal obstetric complications in 16 women (25%), namely, preeclampsia (n = 12), hemolysis, elevated liver enzymes, and low platelet syndrome (HELLP) (n = 6), and/or placental abruption (n = 5). Half of the 50 women with available data had a small-for-gestational-age fetus.Overall, including during the follow-up period of 4 years (IQR 2–9), 28 women (43%) had at least one thrombosis, and 29% were diagnosed with systemic lupus erythematosus (SLE). Ultimately, 54 women (83%) had at least one live birth. Only one woman had three consecutive early miscarriages.ConclusionIUFD was most often the inaugural sign of APS. Of the APS classification criteria, IUFD, preeclampsia, and thromboses were common in this cohort, while the “3 consecutive early miscarriages” criterion was met only once. With treatment, most of the women successfully had at least one live birth.

Evaluation of the severe preeclampsia classification criterion for antiphospholipid syndrome in a study of 40 patients

“…In the PROMISSE study of 385 SLE patients, LAC was associated with adverse pregnancy outcomes (OR 8.32, 95% CI 3.95-19.26) [12] and it is not surprising that we found a high rate of LAC compared to that observed in unselected APS patients [13]. At the end of the follow-up period, 30% of the women had been diagnosed with SLE, a rate quite similar to other APS series [3,14] where SLE occurred in 29-36% of cases.…”

“…We included both primary APS and APS associated with SLE (de ned according to the SLICC classi cation criteria) [6]. Thirteen women had also been included in our study of IUFD in APS patients, although for 7 of them we considered a different pregnancy [3].…”

“…To our knowledge, no series of APS patients with at least 3 pregnancy losses before the 10th week of gestation is currently available. We recently reported a series of 65 APS patients with foetal deaths [3] in which foetal death was often the inaugural sign of APS and also frequently associated with other APS criteria, in particular, preeclampsia and thromboses, while the "3 consecutive early miscarriages" criterion was met in only one patient [3]. A series of 16 pregnancies complicated by Haemolysis, Elevated Liver Enzymes and Low Platelets (HELLP) syndrome in 15 women with APS, published in 2005, found HELLP syndrome was associated with preeclampsia/eclampsia [4].…”

“…APS was diagnosed before the index episode of preeclampsia in 12 women (30%), with a median follow up of 5 years (IQR[3][4][5][6][7][8][9][10][11][12] between APS diagnosis and this episode, while the remaining 28 (70%) were diagnosed with APS when the preeclampsia occurred. LAC antibodies were positive in 30 women (82.5%), and aPL antibodies triple positive in 21 (52.5%).Previous pregnancies.…”

Non-criteria Manifestations of Antiphospholipid Syndrome: An Overview

“…Placenta-mediated complications, such as abruptio placentae and hematoma and late pre-eclampsia/intrauterine growth restriction (IUGR), have been reported as complications of APS patients in various case reports and cohorts 96,97 . While pre-eclampsia and IUGR before the 34 th week of gestation are included in the revised criteria 1 , those occurring afterward are not.…”