Increased levels of serum IL-33 is associated with adverse maternal outcomes in placenta previa accreta.

PURPOSE: IL-33 is associated with invasion, proliferation, and metastasis of various cancers. The trophoblastic cells of placenta previa accreta (PPA) invade into the myometrium in a similar way to the invasion of cancers. We studied the role of IL-33 in PPA and also aimed to investigate its relation with adverse maternal outcome in this placental disorder. METHODS: A total of 87 pregnant patients were enrolled in this prospective case-control study [27 with PPA, 30 with placenta previa totalis (PPT; nonadherent placenta previa), and 30 controls]. IL-33 and IL-6 levels were studied in maternal serum at late preterm gestation weeks. Multiple logistic regression analyses analyzed the risk factors which are associated with PPA and adverse maternal outcomes. Adjusted odds ratios and 95% confidence intervals were also calculated. Enzyme-linked immunosorbent assay (ELISA) method was used to determine maternal serum IL-33 and IL-6 levels. RESULTS: Serum IL-33 levels were significantly higher in PPA patients when compared with both nonadherent PPT and the control groups (p = .011, p = .010). Serum IL-6 and neutrophil/lymphocyte ratio levels were significantly higher than the control group's (p = .045, p = .028). IL-33 levels and history of previous cesarean section were found to be significantly associated with PPA (OR: 1.039, 95% CI: 1.004-1.075; p = .030 and OR: 0.067, 95% CI: 0.014-0.309, p = .001, respectively). Serum IL-33 levels were positively correlated with previous cesarean section history in PPA. Increased maternal serum IL-33 levels were found to be independently associated with a cesarean hysterectomy and massive transfusion in PPA patients (OR: 1.098, 95% CI: 0.998-1.207; p = .049 and OR: 1.162 95% CI: 1.010-1.337; p = .036). CONCLUSION: Increased levels of maternal serum IL-33 and history of previous cesarean section were found to be significantly associated with PPA, and also increased maternal serum IL-33 levels were related to cesarean hysterectomy and massive blood transfusion in PPA. We suggest that IL-33 may have a role in abnormal placental invasion.

Dynamic Thiol/Disulfide Homeostasis in Predicting Adverse Neonatal Outcomes in Fetal Growth Restriction.

Aim: The main aim of this study was to investigate thiol/disulfide homeostasis associated with fetal growth restriction (FGR) and to evaluate whether alterations are predictive for adverse neonatal outcomes. Methods: 273 pregnant women (77 with FGR and 196 with normal fetal growth) were enrolled in this prospective case-control study. Results: Native thiol and total thiol were decreased in FGR compared to the control group (p < .001; p < .001). Decreased levels of maternal serum native and total thiol were significantly associated with adverse neonatal outcomes in FGR (OR: 0.983, 95% CI 0.976-0.991, p < .001; OR: 0.983, 95% CI 0.976-0.991, p < .001). Decreased maternal serum total thiol levels were the only significantly associated risk factor with adverse neonatal outcomes in FGR (OR: 0.981, 95% CI 0.963-1.000, p = .046). Conclusion: The decrease in the antioxidants of thiol/disulfide mechanism may be related to the development of both FGR and adverse neonatal outcome in FGR.

Impact of Gestational Diabetes Mellitus and Maternal Obesity on Cord Blood Dynamic Thiol/Disulfide Homeostasis.

AIM: Our aim in this study was to investigate the effect of maternal obesity and gestational diabetes mellitus (GDM) on cord blood dynamic thiol/disulfide homeostasis. METHODS: A prospective case-control study was carried out in 125 pregnant women (27 GDM, 30 obese, 68 controls). Cord blood samples were collected from all participants and native thiol-disulfide exchanges were examined with automated method enabling the measurement of both sides of thiol-disulfide balance. RESULTS: Disulfide amounts, disulfide/native thiol and disulfide/total thiol ratios were increased (p < 0.001), while native thiol/total thiol was decreased in the cord blood of babies born to an obese or diabetic mother (p < 0.001). Moreover, increased disulfide amounts, disulfide/native thiol, disulfide/totalthiol ratios and decreased native/total thiol were found to be significantly associated with adverse outcomes in GDM. CONCLUSION: The current study suggests that the offsprings born to obese or diabetic mothers are exposed to increased oxidative stress.

ADAMTS4 and Oxidative/Antioxidative Status in Preterm Premature Rupture of Membranes.

AIM: To determine the function of a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS4), total oxidant status (TOS), total antioxidant status (TAS), and aryl esterase (ARES) in preterm premature rupture of membranes (PPROM) and to investigate the association with premature rupture of membranes (PROMs). MATERIAL AND METHODS: 58 pregnant women were included in this prospective study which comprised 29 PPROM patients as the study group and 29 patients, having healthy amniotic membranes, as the control group. ADAMTS4, TAS, TOS, and ARES levels were studied in the amniotic membrane homogenates of the patients. RESULTS: ADAMTS4, TAS TOS, and ARES levels of amniotic membrane lysates were significantly different between PPROM and control groups (p < 0.001, p < 0.001, p = 0.008 and p = 0.002, respectively). Increased amniotic membrane ADAMTS4 (OR: 1.051 95% CI 1.006-1.098, p = 0.024) and TOS (OR: 12.777 95% CI 1.595-102.323, p = 0.016) were found to be significantly associated with the increased risk of PPROM. CONCLUSION: ADAMTS4, TOS, and ARES levels were higher and TAS level was lower in PPROM patients than the normal healthy control group which had healthy amniotic membranes at term. As a result, ADAMTS4 may have a role in the pathogenesis by causing increased oxidative and inflammatory environment in PPROM.

Role of ADAMTS5 in Unexplained Fetal Growth Restriction (FGR).

AIM: We aim to determine the role of serum and placental A disintegrin and metalloproteinase with thrombospondin motif 5 (ADAMTS5) in fetal growth restriction (FGR). MATERIAL AND METHODS: 43 pregnancies suffering FGR and 45 healthy ones were homogenized for their body mass indices, ages, and gestational weeks. Expression of ADAMTS5 in placental samples was determined by immunohistochemical methods and concurrent maternal serum ADAMTS5 levels were determined with enzyme-linked immunosorbent assay. RESULTS: Expression of ADAMTS5 was higher in FGR group than the healthy control in placenta. Both the cytoplasmic staining pattern of the syncytiotrophoblasts and staining of the decidual plate were shown in the FGR group; but not in the control group. A negative correlation between serum ADAMTS5 levels and birth weight in FGR group was observed. CONCLUSION: Increased ADAMTS5 levels were observed in placental insufficiency cases. This study demonstrates that ADAMTS5 may be a sensitive indicator of placental insufficiency which has variable factors in etiology. Additional work is needed to delineate the mechanism of its involvement.