Role of Systemic Immune Inflammatory Index to Predict Intrahepatic Cholestasis of Pregnancy.

BACKGROUND: The goal was to investigate the change of systemic immune inflammation index (SII) in high-risk pregnant women diagnosed with intrahepatic cholestasis of pregnancy (ICP). METHODS: Between May 2018 and April 2020, we retrospectively enrolled 218 pregnant women who were followed in our hospital from the first trimester to delivery. We looked at the sociodemographics, laboratory data, SII values, Apgar ratings, and newborn birth weights of pregnant women with ICP. We also compared SII values in the first (SII 1), second (SII 2), and third trimesters (SII 3) between ICP and the control group. RESULTS: In the ICP group, the neutrophil level increased in the second trimester and decreased in the third trimester. The SII 2 was significantly higher in the severe ICP group, and when the SII values of the subgroups were examined, the SII 2 was significantly higher in the severe ICP group. The SII 2 showed a significant cutoff value for ICP with 92% sensitivity and 96% specificity. Again, a positive but weak correlation was found between SII 2 and SII 3 and FBA. When the neonatal outcomes were evaluated between the groups, gestational age at birth, birth weight and Apgar scores at 1 and 5 minutes were significantly lower in the ICP group. CONCLUSIONS: The relationship between SII and ICP was investigated for the first time in the literature and a significant cutoff value was found with the SII of the 2nd day. This showed that inflammation occupies an important place in the pathophysiology of cholestasis.

Etiology and perinatal outcomes between early and late-onset nonimmune hydrops fetalis

SUMMARY OBJECTIVE: We aimed to compare the etiology and perinatal outcomes of non-immune hydrops fetalis diagnosed early- and late-onset at our hospital. METHODS: The records of the patients who applied to our department were reviewed, and we reached 42 non-immune hydrops fetalis cases retrospectively and examined the medical records. Hydrops diagnosis week, birth week, accompanying anomalies, and perinatal outcomes were compared as ≤12 weeks (early-onset) and >12 weeks (late-onset). RESULTS: The prevalence of non-immune hydrops fetalis was 0.05%, and the median week of diagnosis for hydrops was 18 weeks. Consanguinity (16.7%) was found in seven pregnancies, and the other seven patients (16.7%) had a history of hydrops in previous pregnancies. Anomalies of the skeletal system, central nervous system, and gastrointestinal tract accounted for 66.7% of ≤12 weeks in non-immune hydrops fetalis cases. Cardiac abnormalities were more common (26.7%) in patients at > 12 weeks (p=0.078). A statistically significant difference was found between the distribution of week of birth and week of diagnosis (p=0.029). Notably, 66.7% of patients diagnosed before week 12 and 23.3% of patients diagnosed after week 12 delivered their babies before week 24. Spontaneous intrauterine death occurred before week 12 in 45.5% (n=5) of non-immune hydrops fetalis and after week 12 in 39.1% (n=9) of non-immune hydrops fetalis. Notably, 69.2% (n=9) of the patients who had prenatal invasive testing resulted in normal karyotype. CONCLUSION: In this study, most of the fetuses diagnosed with early-onset non-immune hydrops fetalis were born in the first 24 weeks. Additionally, live birth rates and cardiac anomalies were observed to be higher in late-onset non-immune hydrops fetalis.

Aflibercept suppresses ovarian hyperstimulation syndrome: an experimental study in rats

SUMMARY OBJECTIVE: In this study, we aimed to determine the impact of the antiangiogenic medications, namely, aflibercept and cabergoline in the prevention and treatment of ovarian hyperstimulation syndrome in a rat model. METHODS: A total of 36 female Wistar rats were randomly allocated to one of the five groups, including disease-free and ovarian hyperstimulation syndrome controls: Group no OHSS (control, n=6) received saline only intraperitoneally (i.p.); group just OHSS (ovarian hyperstimulation syndrome only, n=6) received 10 IU pregnant mare serum gonadotropin and 30 IU human chorionic gonadotropin subcutaneously to produce ovarian hyperstimulation syndrome; group cabergoline+OHSS (cabergoline+ovarian hyperstimulation syndrome, n=8) received 100 μg/kg oral cabergoline; group aflibercept (12.5 mg/kg)+OHSS (aflibercept+ovarian hyperstimulation syndrome, n=8) received 12.5 mg/kg i.p. aflibercept; and group aflibercept (25 mg/kg)+OHSS (aflibercept+ovarian hyperstimulation syndrome, n=8) received 25 mg/kg i.p. aflibercept. The groups were compared for ovarian weight, immunohistochemical vascular endothelial growth factor expression, spectrophotometric vascular permeability evaluated with methylene blue solution in peritoneal lavage, and body weight growth. RESULTS: Vascular endothelial growth factor immunoexpression was substantially greater in the just OHSS group (22.00±10.20%) than in the aflibercept (12.5 mg/kg)+OHSS (7.87±6.13%) and aflibercept (25 mg/kg)+OHSS (5.63±4.53%) groups (p=0.008 and p=0.005, respectively). Post-hoc tests indicated that cabergoline, 12.5 mg/kg aflibercept, and 25 mg/kg aflibercept decreased vascular permeability compared to the untreated ovarian hyperstimulation syndrome group (p=0.003, p=0.003, and p=0.001, respectively). JOH group had the heaviest ovaries, whereas aflibercept (25 mg/kg)+OHSS group had the lightest. In terms of body weight gain, cabergoline+OHSS group was substantially greater than the aflibercept (12.5 mg/kg)+OHSS and aflibercept (25 mg/kg)+OHSS groups (p=0.006 and p=0.007, respectively). CONCLUSION: Aflibercept, an antiangiogenic medication, decreased ovarian hyperstimulation syndrome by lowering the vascular permeability and vascular endothelial growth factor expression.

Prediction of maternal near-miss in placenta previa: a retrospective analysis from a tertiary center in Ankara, Turkey.

AIM: To determine risk factors for severe complications during and after cesarean delivery (CD) in placenta previa (PP). METHODS: We reviewed retrospectively collected data from women with PP who underwent CD during a 6-year study period. We identified the complicated group based on the modified WHO near-miss criteria. Complicated and noncomplicated groups were compared considering clinical, laboratory, and sonographic features. RESULTS: Thirty-seven of 256 cases classified as near miss consisting of 14 peripartum hysterectomies, 12 uterine balloon placements, 10 great artery ligations, and four B-lynch suture placement procedures without maternal mortality. Perioperative complications included surgical wound infections (n = 5), bladder injury (n = 4), pelvic abscess (n = 1), and uterine rupture (n = 1). Logistic regression analyses demonstrated following features to be associated with maternal near miss in PP: (1) coexistent abruption (aOR 13.2, 95% CI 5.8-75.3), (2) morbidly adherent placenta (aOR 11.92, 95% CI 3.24-43.82), (3) number of hospitalizations for vaginal bleeding (≥3) (aOR 8.88, 95% CI 3.32-26.69), and (4) transvaginal cervical length (CL) measurement <10th percentile (aOR 5.5, 95% CI 2.1-15.4). CONCLUSION: Short cervical length, recurrent vaginal bleeding, morbidly adherent placenta, and concurrent placental abruption are independent predictors for subsequent severe maternal morbidity in PP cases. Early identification of these risk factors during PP follow-up may improve maternal outcome.

The distribution of angiopoietin-1, angiopoietin-2 and their receptors tie-1 and tie-2 in the very early human placenta.

Angiopoietins are integral to vasculogenesis and angiogenesis, which play crucial roles in the growth and development of the placenta. The current study assessed expression of angiopoietins (Ang-1 and Ang-2) and their receptors (Tie-1 and Tie-2) during development of the early human placenta. First-trimester placental tissues were obtained from women undergoing curettage during normal pregnancies. The use of immunohistochemistry (IHC) showed that Ang-1 was primarily localized to syncytiotrophoblasts where it displayed moderate immunoreactivity, whereas weak immunoreactivity for Ang-1 was observed in endothelial cells and angiogenic cell cords (ACC). Strong immunoreactivity for Ang-2 was also found predominantly in syncytiotrophoblasts with lower immunostaining levels evident in cytotrophoblasts. Moderate immunoreactivity for Ang-2 was observed in endothelial cells, ACC and Hofbauer cells. By contrast, the trophoblastic shell, as well as endothelial cells and ACC exhibited strong staining intensity for Tie-1 with the strongest immunoreactivity for Tie-2 observed in cytotrophoblasts, ACC and endothelial cells. Western blotting of tissue extracts confirmed the IHC results. Previous studies focused on VEGF and its receptors in controlling vasculogenesis and angiogenesis in human placenta. However, the specific localization patterns of angiopoietins and their receptors revealed by the current study emphasize the importance of these molecules in placental vascular development. Functional studies aimed at identifying the molecular mechanisms of actions of these factors and receptors may prove essential in elucidating the pathophysiology of placental disorders such as intrauterine growth restriction and pre-eclampsia.

Hofbauer cells in early human placenta: possible implications in vasculogenesis and angiogenesis.

The stroma of the placental villi contain numerous macrophages, so-called Hofbauer cells which are of mesenchymal origin and are thought to function in many processes. Although there are many studies concerning placental vasculogenesis and angiogenesis, there has been a lack of evidence on the possible roles of Hofbauer cells in these processes. In this study we hypothesized that Hofbauer cell locations and numbers might be correlated with the vascular structures within the placental villi core and therefore may be implicated to play roles in placental vasculogenesis and angiogenesis. Placental tissues were obtained from normal first-trimester pregnancies. Tissues were prepared for light microscopic investigations. Double immunohistochemistry staining with CD31/PECAM1 and CD68 was applied to placental tissues. In placental villous core, majority of the Hofbauer cells were found to be either in close contact with angiogenic cell cords and primitive vascular tubes or located in between them. Moreover, the number of Hofbauer cells and vasculogenic structures were found to be significantly correlated. The findings of this study suggest for the first time that Hofbauer cells might be involved in the processes of vasculogenesis and angiogenesis in the placenta.

Spatial and temporal distribution of Tie-1 and Tie-2 during very early development of the human placenta.

Vasculogenesis in the human placenta comprises differentiation and growth of newly forming blood vessels derived from hemangiogenic stem cells within the mesenchymal core of villi. In a second stage, angiogenesis leads to the expansion and remodeling of the already existing vessels. At present, relatively little is known about the regulatory mechanisms of vasculogenesis and angiogenesis during very early placentation. Using placental villous tissues from days 22 to 48 of pregnancy, we analyzed the spatial and temporal expression of Tie-1 and Tie-2 in parallel to vascular maturation in the human placenta. In immunohistochemistry both receptors, Tie-1 and Tie-2 show a cell and villous type specific expression during this early phase of placental development. Especially, cytotrophoblast and hemangiogenic cell cords in mesenchymal villi and Hofbauer cells in immature intermediate villi have the strongest immunoreactivities. Western blot analysis showed that no significant changes were detected for Tie-1 and Tie-2 as pregnancy advanced. Moreover, phospho-Tie-2 levels did not change significantly in parallel to pregnancy ages. We conclude that both receptors are involved in angiogenesis as well as vascular modulation of early vessels. Due to their spatial distribution we speculate on an additional role in regulation of villous and extravillous trophoblastic behavior.

Sequential expression of VEGF and its receptors in human placental villi during very early pregnancy: differences between placental vasculogenesis and angiogenesis.

Vascularization within the human placenta is the result of the de novo formation of vessels derived from pluripotent precursor cells in the mesenchymal core of the villi. Vascularization of placental villi starts at around day 21 post conception (p.c.) with a four somite embryo. At this stage progenitors of haemangiogenic cells differentiate to form first vessels. These progenitor cells are thought to be directly derived from mesenchymal cells rather than originating from fetal blood cells. We investigated the relation between differentiation of stromal cells towards endothelial cells and vascular structures and the expression pattern of the respective growth factors. Using transmission electron microscopy and immunohistochemistry (for VEGF, Flt-1, Flk-1, CD14, CD34, and CD68) the development of placental vasculogenesis during very early stages of pregnancy (days 22-48 p.c.) was studied. We found that VEGF is strongly expressed in villous cytotrophoblast cells and subsequently in Hofbauer cells while its receptors Flt-1 and Flk-1 are found on vasculogenic and angiogenic precursor cells. The developmental expression and secretion of VEGF suggests its involvement in recruitment, maintenance and formation of first angiogenic cells and vessels. Interactions between VEGF and Flk-1 and Flt-1 may regulate placental vasculogenesis and angiogenesis in a paracrine and autocrine manner. The sequential expression of growth factors in different cell types may point to the fact that placental vasculogenesis and angiogenesis are clearly distinct events.