Role of SLC7A11/xCT in Ovarian Cancer.

Ovarian cancer is one of the most dangerous gynecologic cancers worldwide and has a high fatality rate due to diagnosis at an advanced stage of the disease as well as a high recurrence rate due to the occurrence of chemotherapy resistance. In fact, chemoresistance weakens the therapeutic effects, worsening the outcome of this pathology. Solute Carrier Family 7 Member 11 (SLC7A11, also known as xCT) is the functional subunit of the Xc- system, an anionic L-cystine/L-glutamate antiporter expressed on the cell surface. SLC7A11 expression is significantly upregulated in several types of cancers in which it can inhibit ferroptosis and favor cancer cell proliferation, invasion and chemoresistance. SLC7A11 expression is also increased in ovarian cancer tissues, suggesting a possible role of this protein as a therapeutic target. In this review, we provide an overview of the current literature regarding the role of SLC7A11 in ovarian cancer to provide new insights on SLC7A11 modulation and evaluate the potential role of SLC7A11 as a therapeutic target.

Lights and shadows on the use of metformin in pregnancy: from the preconception phase to breastfeeding and beyond.

During pregnancy, the complex hormonal changes lead to a progressive decrease of insulin sensitivity that can drive the onset of gestational diabetes (GDM) or worsen an already-known condition of insulin resistance like type 2 diabetes, polycystic ovarian syndrome (PCOS), and obesity, with complications for the mother and the fetus. Metformin during pregnancy is proving to be safe in a growing number of studies, although it freely crosses the placenta, leading to a fetal level similar to maternal concentration. The aim of this literature review is to analyze the main available evidence on the use of metformin during, throughout, and beyond pregnancy, including fertilization, lactation, and medium-term effects on offspring. Analyzed studies support the safety and efficacy of metformin during pregnancy. In pregnant women with GDM and type 2 diabetes, metformin improves obstetric and perinatal outcomes. There is no evidence that it prevents GDM in women with pregestational insulin resistance or improves lipid profile and risk of GDM in pregnant women with PCOS or obesity. Metformin could have a role in reducing the risk of preeclampsia in pregnant women with severe obesity, the risk of late miscarriages and preterm delivery in women with PCOS, and the risk of ovarian hyperstimulation syndrome, increasing the clinical pregnancy rate in women with PCOS undergoing in vitro fertilization (IVF/FIVET). Offspring of mothers with GDM exposed to metformin have no significant differences in body composition compared with insulin treatment, while it appears to be protective for metabolic and cardiovascular risk.

BDNF and NGF Expression in Preneoplastic Cervical Disease According to HIV Status.

BACKGROUND: Neurotrophins, such as BDNF and NGF, are overexpressed in tumor cells in cervical cancer, and HIV infection is associated with the upregulation of neurotrophin expression. Therefore, we aimed to investigate whether BDNF and NGF are overexpressed in preneoplastic cervical disease from HIV-infected women. METHODS: Women with preneoplastic cervical lesions (cervical intraepithelial neoplasia grade 2 or 3) were prospectively enrolled and grouped according to their HIV status. Samples from Loop Electrosurgical Excision Procedure (LEEP) for suspected cervical cancer were obtained, and immunohistochemistry was performed to evaluate BDNF and NGF expression. RESULTS: We included in our analysis 12 HIV-infected patients who were matched with 23 HIV-negative patients as a control group. Immunohistochemistry analysis showed that BDNF expression was significantly higher in cervical preneoplastic lesions from HIV-positive women than in the lesions from the control group. In particular, BDNF was expressed in 8/12 HIV-positive patients and 7/23 HIV-negative patients (66.7% vs. 30.4%, χ2 = 4.227; p = 0.040). NGF expression was not significantly higher in cervical preneoplastic lesions from HIV-positive women compared with that in the lesions from the control group. In particular, NGF was expressed in 8/12 HIV-positive patients and in 12/23 HIV-negative patients (66.7% vs. 52.2% χ2 = 0.676; p = 0.411). Logistic regression analysis showed that the HIV status is an independent predictor of BDNF expression in pre-invasive preneoplastic cervical disease when considered alone (crude OR 4.6, 95% CI 0.027-20.347; p = 0.046) and when analyzed with other co-factors (adjusted OR 6.786, 95% CI 1.084-42.476; p = 0.041). CONCLUSIONS: In preneoplastic cervical disease, BDNF expression is higher in HIV-infected women than in non-infected controls, and this is independent of the clinical features of the patients and from the presence of the HPV-HR genotype. BDNF can play a key role as a link between the pathways by which HIV and HPV interact to accelerate cervical cancer progression and invasion. These data can be useful to better understand the role of neurotrophins in the cancerogenesis of cervical cancer and the possible therapeutic strategies to improve disease outcomes.

Low Interferon-γ Levels in Cord and Peripheral Blood of Pregnant Women Infected with SARS-CoV-2.

COVID-19 is characterized by the immune system's overreaction resulting in a 'cytokine storm', consisting in a massive release of cytokine into the bloodstream, leading to local and systemic inflammatory response. This clinical picture is further complicated in case of infection of patients with a peculiar immunological status, such as pregnancy. In this paper, we focused on Interferon-γ, which plays a pivotal immunomodulatory role in normal pregnancy and fetal development, as well as in defense against pathogens. In this study, we compared the levels of Interferon-γ and the Interferon autoantibodies of the peripheral and cord blood of pregnant women with confirmed mild COVID-19 and healthy pregnant women. The Interferon-γ was significantly lower both in the peripheral and cord blood of SARS-CoV-2-positive mothers, suggesting that infection can affect the fetal microenvironment even without severe maternal symptoms. In conclusion, further studies are needed to clarify whether lower levels of Interferon-γ due to SARS-CoV-2 infection affect the development or infection susceptibility of infants born to SARS-CoV-2-infected mothers.

Placental diabesity: placental VEGF and CD31 expression according to pregestational BMI and gestational weight gain in women with gestational diabetes.

PURPOSE: The aim of this study is to investigate the placental expression of VEGF and CD31 in pregnancies complicated by gestational diabetes (GDM) and the influence of pregestational BMI and gestational weight gain (GWG) on this expression. METHODS: We prospectively enrolled pregnant women with diagnosis of GDM and healthy controls who delivered in our Center between December 2016 and May 2017. Patients were grouped according to the presence of GDM and we compared pregnancy characteristics, placental VEGF and CD31 expression between the cases and controls. Immunochemistry analysis was performed to assess biomarkers positivity. Positivity of biomarkers was assessed in a dichotomic fashion with positivity set at 5% for VEGF and 1% for CD31. RESULTS: 39 patients matched inclusion criteria, 29 (74.3%) women with GDM and 10 (25.7%) healthy controls. Immunochemistry analysis showed that VEGF was more expressed in placentas from women with GDM compared to controls (21/29, 72.4% vs 2/10, 20%; p = 0.007), and CD31 was more expressed in placentas from women with GDM compared to controls (6/29, 20.7% vs 0/10, 0%; risk difference 0.2). VEGF positivity was associated with the presence of GDM (aOR 22.02, 95% CI 1.13-428.08, p = 0.04), pregestational BMI (aOR 1.53, 1.00-2.34, p = 0.05) and GWG (aOR 1.47, 95% CI 1.03-2.11, p = 0.03). CD31 positivity was associated with the pregestational BMI (aOR 1.47, 95% CI 1.00-2.17, p = 0.05) and with the gestational weight gain (aOR 1.32, 95% CI 1.01-1.72, p = 0.04). CONCLUSION: Pregnancies complicated by GDM are characterized by increased placental expression of VEGF and CD31, and the expression of these markers is also independently associated to maternal increased pregestational BMI and GWG, defining the concept of "placental diabesity".

Third Trimester Myocardial Performance Index in Fetuses from Women with Hyperglycemia in Pregnancy: A Systematic Review and Meta-Analysis.

INTRODUCTION: The myocardial performance index (MPI) has been proposed to evaluate cardiac dysfunction in newborns from diabetic mothers. Although MPI is routinely assessed in newborns, its role in the evaluation of fetuses from women with hyperglycemia in pregnancy (HIP) is still under evaluation. We aimed to evaluate the differences in third trimester fetal MPI in pregnant women with hyperglycemia compared to healthy controls. MATERIALS AND METHODS: Seven electronic databases were searched for all studies assessing women with HIP who underwent evaluation of fetal left MPI during pregnancy compared to a control group. The summary measures were reported as mean differences (MD) in the mean fetal left MPI between women with HIP and healthy controls, with a 95 % confidence interval (CI). A post hoc subgroup analysis based on the type of HIP - pregestational diabetes, GDM, or gestational impaired glucose tolerance (GIGT) - was performed as an additional analysis. RESULTS: 14 studies assessing 1326 fetuses (580 from women with HIP and 746 from controls) were included. Women with HIP had a significantly higher mean left fetal MPI compared to controls (MD 0.08; 95 %CI: 0.05 to 0.11; p < 0.00 001). Subgroup analysis according to the type of HIP concurred with the overall analysis for women with DM (MD 0.07; 95 %CI: 0.01 to 0.13; p = 0.02) and for women with GDM (MD 0.012; 95 %CI: 0.07 to 0.17; p < 0.00 001) but not for women with GIGT (MD -0.01, 95 % CI -0.28 to 0.27; p = 0.96). CONCLUSION: Fetal left MPI is increased in pregnancies with HIP appearing as a potential marker of cardiac dysfunction.

Trends in Caesarean Section Rate According to Robson Group Classification among Pregnant Women with SARS-CoV-2 Infection: A Single-Center Large Cohort Study in Italy.

BACKGROUND: Since there is no available data on temporal trends of caesarean section (CS) rates in pregnant women with COVID-19 through the pandemic, we aimed to analyze the trends in caesarean section rate in a large cohort of pregnant women with COVID-19, according to the Robson Ten Group Classification System of deliveries. METHODS: We prospectively enrolled pregnant women with a diagnosis of COVID-19 who delivered in our center between March 2020 and November 2021. Deliveries were classified, according to the Robson group classification, and according to three time periods: (1) deliveries from March 2020 to December 2020; (2) deliveries from January 2021 to April 2021; (3) deliveries from May 2021 to November 2021. We compared pregnancy characteristics and incidence of caesarean section, according to the Robson category in the total population, and according to the three time periods. RESULTS: We included 457 patients matching the inclusion criteria in our analysis. We found that overall CS rate significantly decreased over time from period 1 to period 3 (152/222, 68.5% vs. 81/134, 60.4% vs. 58/101, 57.4%, χ2 = 4.261, p = 0.039). CS rate significantly decreased over time in Robson category 1 (48/80, 60% vs. 27/47,57.4% vs. 8/24, 33.3%, χ2 = 4.097, p = 0.043) and Robson category 3 (13/42, 31% vs. 6/33, 18.2% vs. 2/22, 9.1%, χ2 = 4.335, p = 0.037). We also found that the incidence of induction of labor significantly increased over time (8/222, 3.6% vs. 12/134, 9% vs. 11/101, 10.9%, χ2 = 7.245, p = 0.027). CONCLUSION: Our data provide an overview of the temporal changes in the management and obstetric outcome of COVID-19 pregnant women through the pandemic, confirming that standards of obstetrical assistance for pregnancies complicated by SARS-CoV-2 infection improved over time.

Bleeding epulis gravidarum: what to evaluate?

INTRODUCTION: Hormonal changes during pregnancy may induce modifications in oral mucosa. Epulis gravidarum (EG) is an oral disease arising during pregnancy, usually regressing after delivery. A case of EG managed at our department is described and those previously reported in literature are reviewed in order to define EG clinical features for stratifying the risk of complications and the need of surgery during pregnancy as well as which factors should be considered more relevant in EG management. EVIDENCE ACQUISITION: Electronic databases (Medline, Embase, Web of Sciences, Scopus and Cochrane Library) were searched from inception of each databases until May 2021 to identify clinical studies on management of EG diagnosed during pregnancy. The aim of this review was to identify factors influencing the need and timing of surgical management. EVIDENCE SYNTHESIS: A woman with a triplet pregnancy suffering from EG, complicated by profuse bleeding, required Caesarean section (CS) given the triplet pregnancy and the impending preterm labor. The surgical removal of EG was not performed because it spontaneously regressed without consequences 40 days after delivery. Review analysis indicated that EG clinical management is dependent on types of symptoms and their severity. Multilinear regression analysis showed that operative management strategy was associated with bone loss on X-ray (t=4.23, P=0.003), while EG surgical treatment during pregnancy was associated with pain (t=-2.91, P=0.03). No significant differences were found in management strategy, according to pain (P=0.12), interference with mastication (P=0.98) and speech (P=0.36). A poor oral hygiene was described in 71% of patients as hypothetical trigger. CONCLUSIONS: EG management strategy depends on bleeding, pain and bone loss on X-ray. A multidisciplinary approach is useful to perform a rapid and appropriate diagnosis and to better evaluate pros and cons of surgery during pregnancy and following management.

Impact of COVID-19 on Breastfeeding among SARS-CoV-2 Infected Pregnant Women: A Single Centre Survey Study.

Background: Although current guidelines recommend that mothers with suspected or confirmed SARS-CoV-2 infection should be encouraged to initiate and continue breastfeeding, up-to-date literature shows conflicting data regarding breastfeeding experiences in infected women. This survey aimed to report on the psychological impact of SARS-CoV-2 infection on breastfeeding practice and medical counselling in a single tertiary center in Southern Italy. Methods: One-hundred breastfeeding women with SARS-CoV-2 infection at delivery were given an anonymous questionnaire regarding breastfeeding and women's perception of the impact of COVID-19 on breastfeeding. Results: 75% of women reported they had difficulty breastfeeding; among them, 66 (66%) declared that separation from their babies after delivery affected their ability to breastfeed. Incidence of reported difficulties in breastfeeding was higher in women who underwent caesarean section compared to women with vaginal delivery (56/65, 86.2% vs. 19/35, 54.3%, χ2 = 12.322, p < 0.001) and in women with a hospital stay of more than 5 days (48/57, 84.2% vs. 23/37, 62.2%, χ2 = 5.902, p = 0.015). Furthermore, the incidence of difficulties in breastfeeding was higher in women who subsequently decided to use exclusively infant formula compared to women who mixed maternal milk with infant formula and women who breastfed exclusively with maternal milk (48/49, 98% vs. 20/25, 80% vs. 7/26, 26.9%, χ2 = 46.160, p < 0.001). Conclusions: Our survey highlights the importance of healthcare support and information on hygiene practices to decrease the perceived stress related to breastfeeding for infected mothers under restrictions, especially in women undergoing cesarean section and with a long hospital stay.

Association between lymphadenopathy after toxoplasmosis seroconversion in pregnancy and risk of congenital infection.

The aim of the study was to describe the pregnancy outcome of a large cohort of women with toxoplasmosis seroconversion in pregnancy and to investigate the relation between maternal lymphadenopathy and risk of congenital toxoplasmosis (CT). This was a retrospective study involving women with confirmed toxoplasmosis seroconversion in pregnancy between 2001 and 2017. Women were clinically evaluated for lymphadenopathy and classified as follows: lymphadenopathy absent (L-) or lymphadenopathy present (L+). The mothers were treated and followed-up according to local protocol, and neonates were monitored at least for 1 year in order to diagnose CT. A total of 218 women (one twin pregnancy) were included in the analysis. Pregnancy outcome was as follows: 149 (68%) of children not infected, 62 (28.3%) infected, 4 (1.8%) first trimester termination of pregnancy, 2 (0.9%) first trimester miscarriages, and 3 (1.4%) stillbirths (of which one already counted in the infected cohort). 13.8% of women were L+ , and they were nearly three times more likely to have a child with CT compared to L- women (aOR, 2.90; 95%CI, 1.28-6.58). Moreover, the result was still statistically significant when the analysis was restricted to 81 children whose mothers were clinically examined and received treatment within 5 weeks from estimated time of infection. In conclusion, there is a positive association between L+ status in pregnant women, and risk of CT also confirmed when restricting the analysis to women with early diagnosis of seroconversion and treatment. This data could be very useful in counselling pregnant women with toxoplasmosis seroconversion and lead to direct a more specific therapeutic and diagnostic protocol.

Continuous Glucose Monitoring in Women with Normal OGTT in Pregnancy.

Continuous glucose monitoring (CGM) might be an effective tool to improve glycemic control in gestational diabetes mellitus (GDM). Few data are available about its utilization as a diagnostic tool to find potential alterations of glycemia in subjects with normal oral glucose tolerance test (OGTT). In this preliminary prospective real-life observational study, we aimed to analyze the glycemic pattern in normal and gestational diabetes mellitus (GDM) women by continuous glucose monitoring (CGM) in order to detect potential differences between the two groups and glycemic alterations despite a normal OGTT. After the screening for GDM, subjects were connected to a CGM system for seven consecutive days. The areas under the curve of the first 60 minutes after each meal and 60 minutes before breakfast were analyzed. Women with normal OGTT that during CGM showed impaired glycemic values (more than 95 fasting or more than 140 one hour after meals or more than 120 two hours after meals) performed one week of self-monitoring of blood glucose (SMBG). After OGTT, 53 women considered normal and 46 affected by GDM were included. CGM parameters did not show any differences between the two groups with impaired glycemic excursions found in both groups. After CGM period, 33 women with normal OGTT showed abnormal glycemic patterns. These 33 women then performed one week of SMBG. After evaluation of one week of SMBG, 21 required diet therapy and 12 required insulin treatment and were followed until the delivery. An increase in gestational weight gain was observed in normal women with normal OGTT but this was not significant. No significant data were found regarding neonatal outcomes in the two groups of women. In conclusion, CGM use in pregnancy might help to detect glycemic fluctuations in women with normal OGTT, improving their treatment and outcomes.

PTH-rP and PTH-R1 Expression in Placentas from Pregnancies Complicated by Gestational Diabetes: New Insights into the Pathophysiology of Hyperglycemia in Pregnancy.

BACKGROUND: this study investigated the expression of parathyroid hormone-related protein (PTH-rP) and PTH/PTH-rP receptor PTH-R1 in placentas from women with gestational DM (GDM), and the relationship between PTH-R1 and PTH-rP expression and pregnancy characteristics. METHODS: we prospectively enrolled 78 pregnant women with GDM, and immunochemistry for PTH-rP and PTH-R1 was performed on placentas. Patients were grouped according to the positivity of PTH-R1 or PTH-rP expression, and pregnancy characteristics were compared between the two groups. RESULTS: PTH-rP and PTH-R1 expression were highest in the extravillous cytotrophoblast and in the decidua. In extravillous cytotrophoblast, PTH-rP expression was higher in women with abnormal at fasting glycemia compared to women with abnormal 60' or 120' glycemia (25/25, 50% vs. 6/28, 21.4%, χ2 = 6.12, p = 0.01), and PTH-R1 expression was higher in women with abnormal oral glucose tolerance test (OGTT) at fasting glycemia compared to women with abnormal 60' or 120' glycemia (37/50, 74% vs. 15/28, 53.6%, χ2 = 3.37, p = 0.06). In syncytiotrophoblast, PTH-rP-positive placentas were characterized by higher incidence of 1 min Apgar score < 7 (2/9, 22.2% vs. 2/69, 2.9%, χ2 = 6.11, p = 0.01) and maternal obesity (4/9, 44.4% vs. 11/69, 16.7%, χ2 = 3.81, p = 0.05). CONCLUSION: placental PTH-rP and PTH-R1 expression is dependent on the type of maternal hyperglycemia, and it is associated with adverse pregnancy outcomes.

Pregnant women's perspectives on severe acute respiratory syndrome coronavirus 2 vaccine.

BACKGROUND: Since coronavirus disease 2019 vaccines have been distributed, a debate has raised on whether pregnant women should get the vaccine. No available data exist so far regarding the safety, efficacy, and toxicology of these vaccines when administered during pregnancy. Most of the Obstetrics and Gynecology societies suggested that pregnant could agree to be vaccinated, after a thorough counseling of risks and benefits with their gynecologists, thus leading to an autonomous decision. OBJECTIVE: This study aimed to evaluate the attitude to coronavirus disease 2019 vaccination in pregnant and breastfeeding women in Italy. STUDY DESIGN: A survey was made at the University of Naples Federico II and the Ospedale Cristo Re, Tor Vergata University of Rome, on pregnant and breastfeeding women asking their perspectives on the available vaccines after reading the recommendations issued by our national Obstetrics, Gynecology, and Neonatology societies. The questionnaire included 12 items finalized to evaluate general features of the women and 6 items specifically correlated to their attitudes toward the severe acute respiratory syndrome coronavirus 2 vaccination. Chi-square or Fisher's exact tests were used to compare group differences of categorical variables and Wilcoxon signed rank or Mann-Whitney U test for continuous variables. The study was approved by the institutional review boards of the University of Naples Federico II (ref. no. 409/2020) and the Ospedale Cristo Re, Tor Vergata University of Rome (ref. #Ost4-2020). RESULTS: Most of the included women did not agree to eventually receive severe acute respiratory syndrome coronavirus 2 vaccine during pregnancy (40 [28.2%] vs 102 [71.8%]). Being pregnant was considered a determinant factor to refuse the vaccine prophylaxis (99 [69.7%] vs 43 [30.3%]; chi-square test=24.187; P<.001), even if a very large percentage declared to be generally in favor of vaccines (128 [90.1%] vs 14 [9.9%]; chi-square test=6.091; P=.014) and most of them confirmed they received or would receive other recommended vaccines during pregnancy (75 [52.8%] vs 67 [47.2%]; chi-square test=10.996; P=.001). CONCLUSION: Urgent data are needed on the safety, efficacy, and toxicology of severe acute respiratory syndrome coronavirus 2 vaccines during pregnancy to modify this trend and to help obstetricians during the counseling. Furthermore, pregnant women should be included in future vaccine development trials to not incur again in such uncertainty.

Histological chorioamnionitis and risk of pulmonary complications in preterm births: a systematic review and Meta-analysis.

Histological chorioamnionitis is associated with significant adverse maternal, perinatal and long-term outcome. We performed a meta-analysis of 30 observational studies in order to clarify the association between Histological chorioamnionitis and pulmonary complications, like respiratory distress syndrome and Bronchopulmonary Dysplasia. Unadjusted data extracted from all studies showed that Histological chorioamnionitis has no effect on development of RDS (RR 0.93, 95% CI 1.08-1.67), while it increased the risk of Bronchopulmonary Dysplasia (RR 1.75, 95% CI 1.37-2.23). However, when we restricted the analysis to the studies that adjust for Gestational Age, in order to exclude the influence of prematurity, we found that HCA reduced the risk of respiratory distress syndrome (RR 0.57, CI 95% 0.35-0.93) and it did not affect the development of Bronchopulmonary Dysplasia (RR 0.99, CI 0.76-1.3). Our results confirmed a possible role of prenatal inflammation on lung maturation. However, further prospective studies with a selected population are needed, in order to clarify the role of Histological chorioamnionitis in neonatal pulmonary complications.

First trimester ultrasound features of X-linked Opitz syndrome and early molecular diagnosis: case report and review of the literature.

X-linked Opitz G/BBB syndrome (XLOS) is a multiple congenital disorder inherited in an X-linked manner. XLOS may be suspected, in prenatal age, on the basis of sonographic findings in the second and/or third trimester of gestation. Pathogenetic variants in MID1 gene have been reported in individuals with XLOS. Prenatal genetic testing is offered for pregnancies at risk, in which the mutation in the family has been identified. To date no cases of prenatal diagnosis, based on first-trimester ultrasound data, have been reported. We present a case of a fetus at 12 gestational weeks with ultrasound multiple anomalies, including increased nuchal translucency, heart defects, cleft lip and palate, enlarged fourth ventricle absence of ductus venosus and family hystory of XLOS. The genetic prenatal test detected the c(0).1286-1G > T mutation of MID1 gene. Data about prenatal ultrasonographic findings consistent with XLOS are limited to second and third trimester. This is the first case reporting ultrasound detectable midline defects suggestive of XLOS as early as the first trimester of gestation. This case also suggests that when multiple anomalies are detected in a fetus with normal chromosomal structure, the possibility of a monogenic disorder must be considered.

Third Trimester Umbilical Artery Doppler in Low-Risk Pregnancies and its Correlation to Estimated Fetal Weight and Birthweight.

PURPOSE: This study investigated the correlation between the umbilical artery (UA) pulsatility index (PI) and the estimated fetal weight percentile and birthweight (BW) percentile, respectively. MATERIALS AND METHODS: We included low-risk pregnancies, in which UA Doppler investigations after 28 weeks were performed. Cases were allocated according to BW percentiles: small for gestational age (SGA) with BW < 10th percentile; appropriate for gestational age (AGA) and large for gestational age (LGA) with BW > 90th percentile. We analyzed differences in the mean UA-PI and UA-PI z-score for gestational age according to the three groups. Linear regression was performed to evaluate any relationship between Doppler indices and BW percentiles. Multiple logistic regression analysis was performed to determine the independent association of UA-PI with LGA babies. In a second step, we considered data on estimated fetal weight (EFW) percentiles and performed the same analysis. RESULTS: We analyzed 14 554 pregnancies from 2004 to 2015. The mean UA-PI and mean UA-PI z-scores in the LGA group were lower than in the AGA and SGA groups (p < 0.001). UA-PI and UA-PI z-scores were linearly related to birthweight percentiles (p < 0.001) and to EFW percentiles (p < 0.001). Logistic regression analysis showed that low UA-PI was independently associated with neonatal LGA (p < 0.001). CONCLUSION: The higher the EFW and BW percentiles, the lower the UA-PI. However, reference ranges for UA Doppler are only based on gestation weeks. Further studies are needed to clarify whether customized reference ranges based on EFW percentiles are more appropriate for the evaluation of fetal wellbeing in the third trimester.

First trimester detection of fetal open spina bifida using BS/BSOB ratio.

BACKGROUND: Despite the well-known second trimester ultrasound signs, current possibilities of in utero surgical repair of open spina bifida require a timely detection of the spine defect. OBJECTIVE: To evaluate the diagnostic accuracy of the ratio between brain stem (BS) diameter and its distance to the occipital bone (BSOB) (BS/BSOB ratio) in the detection of fetuses with open spina bifida at first trimester ultrasound. METHODS: A systematic review and meta-analysis of diagnostic accuracy was performed by searching seven electronic databases from their inception to February 2019 for all studies assessing the association between BS/BSOB ratio and diagnosis of spine bifida. Diagnostic accuracy of BS/BSOB ratio in prenatal diagnosis of spine bifida was assessed as sensitivity, specificity, positive and negative likelihood ratios (LR + and LR-), and area under the curve (AUC) on SROC curves. RESULTS: Four studies, including 17,598 fetuses with 23 cases of open spina bifida, were included in the meta-analysis. BS/BSOB ratio showed pooled sensitivity of 0.70 (95% CI 0.47-0.87; I2 = 78.3%), specificity of 1.00 (95% CI 0.99-1.0; I2 = 99.2%), LR + and LR- of 51.44 (95% CI 9.53-277.64; I2 = 85.5%) and 0.23 (95% CI 0.04-1.17; I2 = 64.8%), respectively, and an AUC of 0.9649. CONCLUSION: First trimester BS/BSOB ratio has a high diagnostic accuracy in detecting fetuses with open spina bifida.

The role of first trimester fetal heart rate in the prediction of gestational diabetes: A multicenter study.

OBJECTIVE: Early pregnancy models for prediction of GDM have been proposed, mostly using anamnestic and biochemical parameters. The aim of our study was to evaluate the strength of association of first trimester fetal heart rate (FHR) in predicting the development of gestational diabetes (GDM). STUDY DESIGN: We considered in our analysis singleton non-diabetic pregnant women who underwent a first trimester screening at 11-14 weeks. Data on maternal age, BMI, cigarette smoking, NT, FHR, CRL, DV-PVI, ß-hCG and PAPP-A were included in the analysis. Multivariate logistic regression analysis was used to estimate the association between maternal characteristics and first-trimester ultrasound measurements and GDM. We evaluated the efficacy of different models for the prediction of GDM. RESULTS: We considered 603 women, of whom 199 (33%) were subsequently diagnosed with GDM. ROC analysis showed that first trimester FHR was highly predictive of GDM (AUC 0.809, 95% CI 0.769-0.849, p < 0.001). At FPR of 20%, first trimester FHR had a detection rate of 65.2% for GDM (positive likelihood ratio: 3.26; negative likelihood ratio: 0.43), which increased to 89.5% at FPR of 40% (positive likelihood ratio: 2.24; negative likelihood ratio: 0.17). When considering as threshold 162 bpm, FHR showed detection rate of 76.9%, specificity of 67.1% and negative predictive value of 85.5% for GDM. CONCLUSION: This is the first study to highlight the potential role of first trimester FHR as early predictor of GDM. In our cohort, a threshold of 162 bpm has shown high detection rate and NPV for GDM.