Improved neonatal outcomes in pregnancies with coexisting gestational diabetes and preeclampsia in normal birthweight neonates- insights from a retrospective cohort study.

INTRODUCTION: We aimed to assess neonatal and maternal outcomes in appropriate-for-gestational-weight (AGA) neonates of mothers with both gestational diabetes mellitus (GDM) and preeclampsia (PET). METHODS: Medical records of women diagnosed with GDM or PET were reviewed. Women with AGA neonates were divided into three groups- GDM, PET, and GDM + PET and maternal neonatal and placental outcomes were compared. The primary outcome was a composite of adverse neonatal outcomes, including intensive care unit admission (NICU), neurological morbidity, hypoglycemia, ventilation, respiratory distress syndrome (RDS), phototherapy, sepsis, blood transfusion, and neonatal death. Post-hoc analysis was performed to determine between-group significance. RESULTS: Composite adverse neonatal outcomes are significantly lower in women with multiple morbidities compared to women with confined PET (p = 0.015), and a similar trend is observed when comparing neonatal outcomes between women with GDM to those with GDM + PET, yet these results are underpowered (18.9 % vs. 12.8 % respectively, p = 0.243). Placentas of women with GDM + PET were larger, with a lower rate of placentas below the 10th percentile as compared to placentas of women with isolated PET (p < 0.001), but with similar rates of MVM lesions. DISCUSSION: While maternal and placental outcomes in patients of the GDM + PET group resemble the characteristics of the PET group, surprisingly, the neonatal outcomes in this group are significantly better compared to isolated morbidities. The paradoxical benefit attributed to the coexistence of GDM + PET may be explained by a balance of the opposing trends characterizing these morbidities-the reduced blood and nutrient supply characterizing PET vs. chronic overflow and abundance typical of GDM. CLINICAL TRIAL REGISTRATION: approval of local ethics committee WOMC-19-0152.

The effect of concomitant histologic chorioamnionitis in pregnancies complicated by fetal growth restriction.

INTRODUCTION: We aimed to investigate the effect of placental histologic chorioamnionitis (HC) on neonatal outcomes in pregnancies complicated by fetal growth restriction (FGR). METHODS: - The computerized medical files of all pregnancies diagnosed with FGR (birthweight <10th percentile) at 24-42 weeks of gestation between 2008 and 2019 were reviewed. Maternal and neonatal outcomes were compared between FGR with and without evidence of placental HC. Placental lesions were classified according to "Amsterdam" criteria. Composite adverse neonatal outcome-included any of the following complications: neurological morbidity, neonatal respiratory assistance, RDS, NEC, sepsis, blood transfusion, phototherapy, hypoglycemia, or neonatal death. Composite severe adverse neonatal outcome included any of the following complications - neurological morbidity, blood transfusion, NEC, sepsis, RDS, neonatal death. RESULTS: - Compared to FGR without HC (n = 446), FGR with HC (n = 57) was characterized by more advanced gestational age at delivery 39.2 (38.3-39.9) vs. 38.2 (36.9-39.2), weeks respectively, p < 0.001), higher rate of nulliparity (73.7% vs. 45.1%, p < 0.001), less vascular lesions of MVM (1.8% vs.11.2%, p = 0.02), higher rate of Apgar scores at 5 min <7 (10.5% vs. 2%, p = 0.004), increased neonatal death (7.0% vs. 0.9%, p = 0.007), higher rates of both composite adverse neonatal outcome (31.1% vs. 17.3% p = 0.02), and composite severe adverse neonatal outcome (16.3% vs. 8.2% p = 0.04). By multivariate regression analysis HC was found to be independently associated with composite adverse neonatal outcome (aOR = 1.21, 95% CI 1.08-2.38) and with severe composite adverse neonatal outcome (aOR = 1.39, 95% CI 1.16-3.76). CONCLUSIONS: Pregnancies complicated by FGR with concomitant HC were associated with higher rates of adverse neonatal outcomes.

Reduced fetal movements is twin pregnancies and the association with adverse neonatal outcomes.

OBJECTIVE: Reduced fetal movements (RFM) is an obstetric complaint known to be associated with adverse neonatal outcomes and should serve as an alarming sign in obstetric triage. Whether this assumption holds for twin pregnancies, is still an obstetric enigma, and this complaint is sometimes overlooked in twins. We, therefore, aimed to study neonatal outcomes in twin pregnancies complicated by RFM. We hypothesised that in twin pregnancy, maternal ability to perceive RFM will be limited, and therefore, will not be associated with adverse neonatal outcome. STUDY DESIGN: Included were all dichorionic twin pregnancies between 2009-2019 who presented to our obstetric triage at a gestational age >34 weeks with an isolated complaint of RFM and delivered during the subsequent two weeks (RFM group). The control group included patients with twin pregnancies (matched for gestational age and maternal age) who presented for routine assessment and reported regular fetal movements throughout pregnancy (no RFM group). Data regarding pregnancy, delivery, and neonatal outcomes were compared between the groups. The primary outcome was a composite of adverse neonatal outcomes, which included one or more of the following: neonatal hypoglycemia, respiratory morbidity, cerebral morbidity, phototherapy, neonatal sepsis, blood transfusions, necrotizing enterocolitis, or neonatal death. Multivariable regression analysis was used to identify independent associations with adverse neonatal outcomes. RESULTS: Maternal demographics and gestational age at delivery did not differ between the RFM group (n = 83 pregnancies and 166 neonates) and the no RFM group (n = 83 pregnancies and 166 neonates). Neonatal birthweights, as well as the rate of birthweights <10th centile, did not differ between the groups. There were 2 cases of fetal demise diagnosed at triage in the RFM group. The rate of the primary outcome, as well as NICU admissions, were significantly higher in the RFM group compared to the no RFM group (29.5 % vs. 19.2 %, p = 0.01 and 32.5 % vs. 19.2 %, p = 0.001). In multivariable analysis RFM (aOR = 1.18, 95 % CI = 1.06-2.73), and GA at delivery (aOR = 0.88, 95 % CI = 0.67-0.97) were associated with adverse neonatal outcome-independent from background confounders. CONCLUSION: Patients presented to obstetric triage with twin pregnancies and isolated RFM had higher rates of adverse neonatal outcomes and NICU admissions compared to twin pregnancies without RFM.

Reduced fetal movements at term in singleton low risk pregnancies-Is there an association with placental histopathological findings?

INTRODUCTION: Maternal perception of fetal movements has long been considered an indicator of fetal well-being. A sudden decrease in the number of fetal movements is suggestive of fetal compromise. We aimed to determine whether the maternal perception of reduced fetal movements (RFM) is associated with placental pathological lesions in a low-risk term population. MATERIAL AND METHODS: Our study was a case-control study that was performed in a single university center. Placental histopathology, maternal demographics, labor characteristics, and neonatal outcomes of term, singleton pregnancies with maternal perception of RFM during the 2 weeks prior to delivery were collected. To isolate the effect of RFM on placental pathology, we excluded cases complicated by preterm birth, hypertensive disorders, diabetes mellitus, small-for-gestational-age and congenital/genetic anomalies. We compared pregnancy outcomes and placental pathology between the RFM group and a control group matched for gestational age and mode of delivery. Placental lesions were classified according to the "Amsterdam" criteria. Composite adverse neonatal outcome was defined as one or more of the following: sepsis, transfusion, hypoglycemia, phototherapy, respiratory morbidity, cerebral morbidity, necrotizing enterocolitis and fetal/neonatal death. Multivariable regression analysis was performed to identify independent associations with adverse neonatal outcome. RESULTS: We included patients who gave birth from January 2008 until May 2019. The study group included 203 term pregnancies with RFM during the 2 weeks prior to delivery, which was matched with 203 controls. The RFM group was characterized by a higher rate of placental weight <10th percentile (22.6% vs. 3.9%, P < .001), a higher rate of maternal vascular malperfusion lesions (30.5% vs. 18.7%, P = .007) and lesions of maternal inflammatory response (43.3% vs. 29.5%, P = .005). At delivery, the RFM group had higher rates of cesarean delivery due to non-reassuring fetal heart rate monitoring (P = .01), 5-minute Apgar score ≤7 (P = .03), neonatal intensive care unit admissions (P < .001) and composite adverse neonatal outcomes (P = .007). Using multivariable analysis, RFM (adjusted odds ratio [aOR] 1.7, 95% confidence interval [CI] 1.1-4.8), and placental maternal vascular malperfusion lesions (aOR 1.2, 95% CI 1.0-2.9) were independently associated with adverse neonatal outcome. CONCLUSIONS: After excluding important placental-related morbidities, RFM was associated with a higher rate of placental weight <10th percentile and placental maternal vascular malperfusion lesions vs. controls. This study suggests a placental involvement in the association between RFM at term and adverse pregnancy outcomes.

Does midwife experience affect the rate of severe perineal tears?

BACKGROUND: Our aim was to study whether midwife experience affects the rate of severe perineal tears (3rd and 4th degree). METHODS: A retrospective cohort study of all women with term vertex singleton pregnancies, who underwent normal vaginal deliveries, in a single tertiary hospital, between 2011 and 2015, was performed. Exclusion criteria were instrumental deliveries and stillbirth. All midwives used a "hands on" technique for protecting the perineum. The midwife experience at each delivery was calculated as the time interval between her first delivery and current delivery. A comparison was performed between deliveries in which midwife experience was less than 2 years (inexperienced), between 2 and 10 years (moderately experienced), and more than 10 years (highly experienced). A multivariate regression analysis was performed to assess the association between midwife experience and the incidence of severe perineal tears, after controlling for confounders. RESULTS: Overall, 15 146 deliveries were included. Severe perineal tears were diagnosed in 51 (0.33%) deliveries. Women delivered by inexperienced midwives had a higher rate of severe perineal tears compared with women delivered by highly experienced midwives (0.5% vs 0.2%, respectively, P=.024). On multivariate regression analysis, midwife experience was independently associated with a lower rate of severe perineal tears, after controlling for confounding factors. Each additional year of experience was associated with a 4.7% decrease in the risk of severe perineal tears (adjusted OR 0.95 [95% CI 0.91-0.99, P=.03). CONCLUSION: More experienced midwives had a lower rate of severe perineal tears, and may be preferred for managing deliveries of women at high risk for such tears.

Green tea extracts interfere with the stress-protective activity of PrP and the formation of PrP.

A hallmark in prion diseases is the conformational transition of the cellular prion protein (PrP(C)) into a pathogenic conformation, designated scrapie prion protein (PrP(Sc)), which is the essential constituent of infectious prions. Here, we show that epigallocatechin gallate (EGCG) and gallocatechin gallate, the main polyphenols in green tea, induce the transition of mature PrP(C) into a detergent-insoluble conformation distinct from PrP(Sc). The PrP conformer induced by EGCG was rapidly internalized from the plasma membrane and degraded in lysosomal compartments. Isothermal titration calorimetry studies revealed that EGCG directly interacts with PrP leading to the destabilizing of the native conformation and the formation of random coil structures. This activity was dependent on the gallate side chain and the three hydroxyl groups of the trihydroxyphenyl side chain. In scrapie-infected cells EGCG treatment was beneficial; formation of PrP(Sc) ceased. However, in uninfected cells EGCG interfered with the stress-protective activity of PrP(C). As a consequence, EGCG-treated cells showed enhanced vulnerability to stress conditions. Our study emphasizes the important role of PrP(C) to protect cells from stress and indicate efficient intracellular pathways to degrade non-native conformations of PrP(C).