Patient’s characteristics. The study included 40 women. Their demographic, clinical, and serological variables are summarized in Table 1. Their mean age at the index preeclampsia episode was 30.5 years ± 4.6 SD, and it occurred during their first pregnancy in 21 women (52.5%). Overall, 14 women (35%) had at least one thrombotic event before the index episode, with a median time of 7.5 years (IQR 3–12) between the thrombotic and obstetric events. Nine women (22.5%) had had obstetric manifestations of APS before the index episode.
APS was diagnosed before the index episode of preeclampsia in 12 women (30%), with a median follow up of 5 years (IQR 3–12) 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. Before the index episode of preeclampsia, 19 women (47.5%) had had a total of 45 pregnancies that resulted in 11 live births (24.4%, including two premature births with IUGR associated with HELLP syndrome in one and non-severe preeclampsia in another), 13 miscarriages (28.9%), 11 IUFD (24.4%), and 10 elective abortions (22.2%). Finally, three women (15.8%) had two consecutive miscarriages before the index preeclampsia episode, but none had a history of three consecutive miscarriages.
Description of the index pregnancy with severe preeclampsia. For various reasons (known APS, positive aPL, previous obstetric complications), 23 (57.5%) women were receiving a treatment during the index preeclampsia episode: 4 by LDA, 4 by LMWH and 15 by both LDA and LMWH. Seven patients were also under treatment with hydroxychloroquine (HCQ), eight with glucocorticoids and three with immunosuppressive drugs. The other 17 women (42.5%) were not receiving any treatment at the onset of the preeclampsia episode.
The median gestational age at the index episode was 25.5 weeks' gestation (IQR 23–29). Maternal complications occurred in 21 women (52.5%), including HELLP syndrome in 18 (45%), eclampsia in 6 (15%), placental abruption in 3 (7.5%), and/or catastrophic APS (CAPS) in 3 (7.5%). Foetal complications were observed in all index pregnancies and included 11 IUFD (27.5%) and 29 preterm live births, 15 of whom (born at a median term of 24 weeks) died before day 28. The 14 premature surviving children were born at a median term of 31 weeks (IQR 27–33), 2 (14.3%) with IUGR.
Doppler ultrasound examinations at or after 22 weeks' gestation were available for 38 women and reported as abnormal in 17 (44.7%). Abnormalities included bilateral uterine artery proto-diastolic notches (n = 10) or a unilateral notch (n = 5) and/or reverse or absent end-diastolic umbilical flow (n = 2).
Subsequent pregnancies. After a median follow-up of 3.5 years (IQR 2–6) after the index preeclampsia episode, 26 (65%) women had at least one new pregnancy, with a total of 37 new pregnancies. Treatment was LDA in 37 pregnancies (100%), LMWH in 33 (89.2%), and HCQ in 16 (43.2%). The overall outcomes were live births in 33 pregnancies (89.2%), IUFD in 3 (8.1%), and one miscarriage (2.7%). No woman had 3 consecutive miscarriages. Of the 33 live births, 20 (60.6%) were uncomplicated, while 13 had at least one complication including preeclampsia (n = 8), IUGR (n = 5), HELLP syndrome (n = 4) and/or preterm delivery (n = 4). No eclampsia, CAPS, or placental abruptions were observed.
Thrombotic events. By the end of the follow-up after the index preeclampsia episode (median 3.5 years, IQR 2–6), 16 women (40%) had had at least one thrombotic event. The first thrombosis occurred before or at the time of the index episode, except in two who had their first thrombosis, one after delivery and the other 12 years afterwards. The sites of thromboses were venous in 12 women, arterial in 6, and microthrombotic in 4. Four women experienced CAPS, 3 simultaneously with preeclampsia and one before the index case.
Associated autoimmune diseases. At the end of follow-up after the index preeclampsia episode (median 3.5 years, IQR 2–6), 12 women had been diagnosed with SLE (30%), 9 (22.5%) before the index episode, 2 (5%) during that episode, and 1 (2.5%) 4 years after it. The live birth rate did not differ between women with SLE and APS and those with primary APS at the time of the index pregnancy (P = 0.60).