Preeclampsia (PE) is a major cause of maternal and perinatal morbidity and mortality. The only fundamental treatment for PE is the termination of pregnancy. Therefore, not only severe maternal complications but also perinatal complications due to immaturity of the infant associated with early delivery are serious issues. The treatment and prevention of preterm onset preeclampsia (POPE) are challenging. In 2017, the ASPRE trial showed that a low oral dose of aspirin administered to POPE high-risk women in early pregnancy reduced POPE by 62%. A prediction algorithm at 11–13 weeks of gestation identifies POPE with 75% sensitivity when the false positive rate is set at 10%. New biomarkers to increase the accuracy of the prediction model for POPE high-risk women in early pregnancy are needed. In this review, we focused on non-coding RNAs (ncRNAs) as potential biomarkers for the prediction of POPE. Highly expressed ncRNAs in the placenta in early pregnancy may play crucial roles in placentation. Furthermore, placenta-specific ncRNAs have been detected in maternal blood. In this review, we summarized ncRNAs that were highly expressed in the primary human placenta in early pregnancy. We also presented highly expressed ncRNAs in the placenta that were associated with or predictive of the development of PE in an expression analysis of maternal blood during the first trimester of pregnancy. These previous studies showed that the chromosome 19 microRNA (miRNA) -derived miRNAs (e.g., miR-517-5p, miR-518b, and miR-520h), the hypoxia-inducible miRNA (miR-210), and long non-coding RNA H19, were not only highly expressed in the early placenta but were also significantly up-regulated in the blood at early gestation in pregnant women who later developed PE. These maternal circulating ncRNAs in early pregnancy are expected to be possible biomarkers for POPE.
Vasohibin-1 (VASH1) is a VEGF-inducible gene of endothelial cells (ECs) that acts as a negative feedback regulator of angiogenesis. To further characterize the function of VASH1, we transfected human VASH1 gene into the mouse EC line MS1, established stable VASH1 expressing clones, and determined gene alteration by cDNA microarray analysis. Among the various angiogenesis-related genes, vascular endothelial growth factor type 1 receptor (VEGFR-1) and its alternative spliced form, soluble VEGFR1 (sVEGFR-1), were found to be the most significantly down-regulated genes. Transient overexpression of VASH1 in human umbilical vein endothelial cells confirmed the down-regulation of VEGFR-1 and sVEGFR-1. sVEGFR-1 is a decoy receptor for VEGF and inhibits angiogenesis. Interestingly, when sVEGFR-1 was overexpressed in ECs, it inhibited the expression of VASH1 in turn. These results suggest that VASH1 and sVEGFR-1, two angiogenesis inhibitors, mutually balance their expressions in ECs.
1 January 2021 in The Tohoku Journal of Experimental Medicine
Subarachnoid hemorrhage is typically present in cerebral aneurysm rupture, whereas acute subdural hematoma without subarachnoid hemorrhage is rare. We herein report a case of cerebral aneurysm rupture during pregnancy resulting in acute subdural hematoma without subarachnoid hemorrhage. A 37-year-old gravida 4 para 3 pregnant woman was admitted for threatened preterm labor at 294/7 weeks of gestation. At 296/7 weeks of gestation (day −14), she developed mild left eye pain, which disappeared within one day. At 316/7 weeks of gestation (day 0), she developed the sudden onset of severe headache and nausea. A neurological examination revealed no abnormal findings, and analgesics ameliorated her headache. At 321/7 weeks of gestation (day 2), after consultations with neurosurgeons, magnetic resonance imaging showed acute subdural hematoma without subarachnoid hemorrhage. Further examinations revealed a cerebral aneurysm. Emergent clipping surgery was performed with the fetus in utero in consideration of the immaturity of the fetus and stable maternal/fetal general conditions. At 356/7 weeks of gestation (day 28), her headache of unknown cause recurred. Considering the maturity of the fetus, the patient underwent cesarean section with good maternal and neonatal outcomes. The absence of subarachnoid hemorrhage does not eliminate cerebral aneurysm rupture.
2 April 2015 in The Journal of Maternal-Fetal & Neonatal Medicine
Objectives. The aims of this study were to clarify the following: (1) how often does prolonged pregnancy >= 34 weeks occur in patients with emergent cerclage without progesterone and (2) the risk factors preventing such pregnancy continuation. Materials and Methods. This retrospective observational study was performed using medical records of patients for whom emergent cerclage had been performed between April 2006 and December 2018 in our institute. Results. Emergent cerclage was performed in 123 patients (median age: 34, interquartile range: 31-36). Primiparous patients numbered 44 (36%). A history of spontaneous preterm birth (SPTB) was present in 30 (24%). The median presurgical cervical length (CL) was 16 (8-21) mm at surgery. Of the 123, 20 (16%) were delivered at 33 + 6 weeks or less (<34 weeks). We conducted logistic regression analysis of the risk factors of SPTBs <34 weeks after cerclage. Three risk factors were identified that increased the risk of SPTB <34 weeks: presurgical CL 0 mm (odds ratio (OR): 5.30; 95% confidence interval (CI): 1.58-17.7), a history of SPTB (OR: 4.65; 95% CI: 1.38-15.7), and the presence of sludge (OR: 4.14; 95% CI: 1.20-14.3). Conclusion. Three risk factors predicted SPTB <34 weeks after emergency cerclage without progesterone administration: unmeasurable CL (CL 0 mm), a history of SPTB, and the presence of sludge on ultrasound. SPTB <34 weeks occurred after emergency cerclage in 16% of patients, being comparable with the recent data with progesterone.