大口 昭英

Small extracellular vesicles (small EVs) play pivotal roles in intercellular communication and pregnancy maintenance, but their clinical significance in preeclampsia (PE) remains unclear. We obtained plasma samples from non-pregnant women, healthy pregnant women, and patients with early-onset (EoPE) and late-onset PE (LoPE). Small EVs were isolated using ultracentrifugation and validated using transmission electron microscopy and nanoparticle tracking analysis; in addition, Western blotting was performed to identify suitable surface markers for plasma-derived small EVs. In our analysis, we consistently detected cluster of differentiation 9 (CD9), whereas classical markers such as cluster of differentiation 63 (CD63) and tumor susceptibility gene 101 (TSG101) were absent. In a prospective, nested case–control study, we analyzed first-trimester samples by using a CD9-based ELISA for small-EV quantification. The number of small EVs did not significantly differ between non-pregnant and healthy pregnant women regardless of the gestational age. However, EVs were significantly elevated in both EoPE (3.5-fold) and LoPE (1.5-fold) compared with matched controls. First-trimester EV levels did not show differences between women who later developed PE and normal controls. These findings indicate that CD9 is a promising marker for plasma-derived small EVs and that an elevated number of small EVs is associated with established PE but has limited predictive value in early pregnancy. Further studies are required to elucidate the cellular origin and clinical implications of small EVs in PE.

We aimed to investigate the effects of serum sFlt-1/PlGF ratio levels in women with suspected or confirmed early-onset preeclampsia and super-imposed preeclampsia (PE/SPE) on composite and individual adverse maternal and fetal outcomes, stratified by gestational age at blood sampling (<34, 34-36, and ≥37 weeks). We also evaluated whether serum sFlt-1/PlGF ratio levels influenced the time interval from blood sampling to delivery. This prospective cohort study assessed serum levels of sFlt-1, PlGF, and the sFlt-1/PlGF ratio in women with suspected or confirmed PE/SPE admitted to a tertiary maternal-fetal-neonatal center between 2012 and 2023. Finally, 241 women were analyzed. An elevated sFlt-1/PlGF ratio at <34 weeks of gestation, but not at 34-36 or ≥37 weeks, was significantly associated with composite adverse maternal and fetal outcomes in women with suspected or confirmed PE/SPE. An sFlt-1/PlGF ratio of 400 was identified as the optimal cut-off level for predicting composite adverse maternal and fetal outcomes at <34 weeks. Among women with suspected or confirmed early-onset PE/SPE, HELLP syndrome alone was significantly associated with an sFlt-1/PlGF ratio ≥400. Additionally, the sFlt-1/PlGF ratio was significantly higher in women with HELLP syndrome, abnormal umbilical artery Doppler findings, or non-reassuring fetal status (NRFS) requiring immediate delivery, compared with those without these conditions. Furthermore, the interval from blood sampling to delivery significantly shortened with increasing sFlt-1/PlGF ratio. In conclusion, elevated sFlt-1/PlGF ratios were significantly associated with HELLP syndrome, abnormal umbilical artery Doppler findings, and NRFS requiring immediate delivery in women with suspected or confirmed early-onset PE/SPE. The sFlt-1/PlGF ratio at <34 weeks of gestation, but not at 34-36 or ≥37 weeks, was associated with composite adverse maternal and fetal outcomes in women with suspected or confirmed preeclampsia and super-imposed preeclampsia (PE/SPE). In women with suspected or confirmed early-onset PE/SPE, the sFlt-1/PlGF ratio was significantly higher not only in those with HELLP syndrome, but also in those with abnormal umbilical artery Doppler findings and non-reassuring fetal status (NRFS) requiring immediate delivery. Among women with suspected or confirmed early-onset PE/SPE, time to delivery from blood sampling decreased with increasing sFlt-1/PlGF ratio.

AIM: To describe how decreased fetal movement (DFM) was managed in patients with fetomaternal hemorrhage (FMH) and to evaluate the diagnostic limitations of this condition in real-world settings. METHODS: This retrospective cohort study included individuals who developed FMH with cerebral palsy from the Japanese nationwide cerebral palsy registry between 2009 and 2022. We investigated whether patients experienced DFM or were prenatally diagnosed with FMH. Furthermore, we assessed how DFM was managed. RESULTS: This study included 57 patients who developed FMH with cerebral palsy, and none were prenatally diagnosed with FMH. DFM was present in 43/57 (75.4%) patients. A sinusoidal pattern was observed in 29/57 (50.9%) patients, and elevated middle cerebral artery peak systolic velocity (MCA-PSV) was detected in 6/10 (60.0%) patients who underwent this test. Of the 43 patients with DFM, 42 (97.7%) sought medical care for this symptom; however, only 12 (27.9%) underwent examinations on the same day as the onset of DFM, and 9 (20.9%) were admitted on that same day. Furthermore, 6/43 (14.0%) were instructed to stay home after telephone consultation or medical examination for this symptom. In five of the 43 patients (11.6%) who experienced DFM, the initial non-stress test was reactive. However, all these patients eventually developed either a non-reactive or non-reassuring fetal status. CONCLUSIONS: DFM was prevalent among pregnancies complicated by FMH; however, it was often inadequately managed, resulting in diagnostic delays. Furthermore, fetal heart rate monitoring and MCA-PSV evaluations had diagnostic limitations. To facilitate early treatment, clinicians need to promptly assess preceding DFM while recognizing the limitations of existing tests.

Systemic lupus erythematosus (SLE) may be exacerbated at any stage of pregnancy, complicating maternal and fetal outcomes. Additionally, pregnancies with SLE have a higher risk of preeclampsia (PE), requiring careful differentiation between SLE flare and PE when symptoms such as proteinuria emerge. We herein describe a 36-year-old pregnant woman with SLE who developed severe proteinuria (13 g/day) at 30 weeks of gestation without hypertension or thrombocytopenia. No abnormal urinary segments were observed. The differential diagnosis between SLE flare and the preliminary sign of PE was challenging. The soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF) ratio was utilized for diagnostic clarification. A normal sFlt-1/PlGF ratio at 29+4 weeks of gestation suggested SLE flare rather than the preliminary sign of PE. Intensified immunosuppressive therapy with increased prednisolone (30 mg/day) attenuated proteinuria, allowing for late-term pregnancy. At 37+4 weeks of gestation, the patient developed late-onset PE with a hypertensive crisis, necessitating emergency cesarean delivery. The infant was delivered safely without complications. Postpartum recovery was uneventful, with stable maternal renal function. This case underscores the importance of angiogenic markers in distinguishing SLE flare from PE. An elevated sFlt-1/PlGF ratio is typically associated with PE, but not SLE flare, aiding in a differential diagnosis and guiding treatment strategies.