A national survey on current practice of ultrasound in labor ward.

OBJECTIVES: Use of ultrasonography has been suggested as an accurate adjunct to clinical evaluation of fetal position and station during labor. There are no available reports concerning its actual use in delivery wards. The aim of this survey was to evaluate the current practice regarding the use of ultrasonography during labor. METHODS: A questionnaire was sent to members of the Italian Society of Ultrasound in Obstetrics and Gynecology employed in delivery wards. The qFeuestionnaire was made up of 22 questions evaluating participant characteristics and the current use of ultrasound in labor in their hospital of employment. The answers were grouped according to participant characteristics. RESULTS: A total of 200 participants replied. Ultrasound was considered useful before an operative vaginal delivery by 59.6 % of respondents, while 51.8 and 52.5 % considered it useful in the management of prolonged first and second stages of labor, respectively. The major indication for ultrasound use during labor was the assessment of fetal occiput position. The major difficulties in its application were the perceived lack of training and the complexity of the ultrasound equipment use. Participants that reported fewer difficulties were those employed in hospitals with a higher number of deliveries or having delivery units with more years of experience using ultrasound in labor, or those who had attended specific training courses. CONCLUSIONS: The results indicate that, despite the reported evidence of a higher accuracy of ultrasound compared to clinical evaluation in assessing fetal position and station, its use is still limited, even amongst maternal-fetal medicine practitioners specialized in ultrasonography.

Risk of stillbirth in singleton fetuses with advancing gestational age at term: A 10-year experience of late third trimester prenatal screenings of 50,000 deliveries in a referral center in northern Italy.

BACKGROUND: The risk of intrauterine death (IUD) at term varies from less than one to up to three cases per 1,000 ongoing pregnancies. The cause of death is often largely undefined. Protocols and criteria to prevent and define the rates and causes of stillbirth are the subjects of important scientific and clinical debates. We examined the gestational age and rate of stillbirth at term in a 10-year period at our maternity hub to evaluate the possible favorable impact of a surveillance protocol on maternal and fetal well-being and growth. METHODS AND FINDINGS: Our cohort included all women with singleton pregnancies resulting in early term to late term birth at our maternity hub between 2010 and 2020, with the exclusion of fetal anomalies. As per our protocol for monitoring term pregnancies, all women underwent near term to early term maternal and fetal well-being and growth surveillance. If risk factors were identified, outpatient monitoring was initiated and early- or full-term induction was indicated. Labor was induced at late term (41+0-41+4 weeks of gestation), if it did not occur spontaneously. We retrospectively collected, verified, and analyzed all cases of stillbirth at term. The incidence of stillbirth at each week of gestation, was calculated by dividing the number of stillbirths observed that week by the number of women with ongoing pregnancies in that same week. The overall rate of stillbirth per 1000 was also calculated for the entire cohort. Fetal and maternal variables were analyzed to assess the possible causes of death. RESULTS: A total of 57,561 women were included in our study, of which 28 cases of stillbirth (overall rate, 0.48 per 1000 ongoing pregnancies; 95% CI: 0.30-0.70) were identified. The incidence of stillbirth in the ongoing pregnancies measured at 37, 38, 39, 40, and 41 weeks of gestation was 0.16, 0.30, 0.11, 0.29, and 0.0 per 1000, respectively. Only three cases occurred after 40+0 weeks of gestation. Six patients had an undetected small for gestational age fetus. The identified causes included placental conditions (n = 8), umbilical cord conditions (n = 7), and chorioamnionitis (n = 4). Furthermore, the cases of stillbirth included one undetected fetal abnormality (n = 1). The cause of fetal death remained unknown in eight cases. CONCLUSIONS: In a referral center with an active universal screening protocol for maternal and fetal prenatal surveillance at near and early term, the rate of stillbirth was 0.48 per 1000 in singleton pregnancies at term in a large, unselected population. The highest incidence of stillbirth was observed at 38 weeks of gestation. The vast majority of stillbirth cases occurred before 39 weeks of gestation and 6 of 28 cases were SGA, and the median percentile of the remaining case was the 35th.

The cumulative incidence of neonatal metabolic acidemia after terminal bradycardia in the 2nd stage of labor: a survival-based model.

PURPOSE: The aim of the study was to estimate by a survival analysis model the hazard function (HF) for neonatal metabolic acidemia (MA) throughout the 2nd stage of labor (2STG) at the time of occurrence of a terminal bradycardia ≥ 10 min requiring expedited delivery, and the cumulative incidence function (CIF) for MA according with the duration of bradycardia stratified in 10-12 min and > 12 min. METHODS: Singleton pregnancies experiencing terminal fetal bradycardia requiring expedited delivery in the 2STG at 38 + 0-41 + 3 weeks and delivering in the year 2019, were identified. The presence of MA (pH < 7 and/or BE ≤ - 12 mmol/L) was determined based on the acid-base status in the umbilical artery cord blood. Survival analysis was used to assess the hazard function (HF) and the cumulative incidence function (CIF) for MA occurring after terminal fetal bradycardia, at the 2STG. RESULTS: Out of a non-consecutive population of 12,331 pregnancies, there were 52 cases that fit the inclusion criteria. Twenty-four (46.2%) of those develop MA. Abnormal quantitative pH values and the HF for MA correlated with the duration of 2STG at the time of bradycardia onset, but not with bradycardia duration. After 60 min of duration of 2STG, the HF (or instantaneous rate of failure) increased dramatically (from 1.2 to 20 about at 120 min). At paired duration of 2STG, a higher CIF was observed for the terminal bradycardia > 12 min. CONCLUSION: Forty-six percent of term fetuses with terminal bradycardia had MA at birth. Despite the low sensitivity and a non-significant association with quantitative pH values, the duration of terminal bradycardia in the 2STG is associated with a higher CIF for MA.

Epigenetics Beyond Fetal Growth Restriction: A Comprehensive Overview.

Fetal growth restriction is a pathological condition occurring when the fetus does not reach the genetically determined growth potential. The etiology of fetal growth restriction is expected to be multifactorial and include fetal, maternal, and placental factors, the latter being the most frequent cause of isolated fetal growth restriction. Severe fetal growth restriction has been related to both an increased risk of perinatal morbidity and mortality, and also a greater susceptibility to developing diseases (especially cardio-metabolic and neurological disorders) later in life. In the last decade, emerging evidence has supported the hypothesis of the Developmental Origin of Health and Disease, which states that individual developmental 'programming' takes place via a delicate fine tuning of fetal genetic and epigenetic marks in response to a large variety of 'stressor' exposures during pregnancy. As the placenta is the maternal-fetal interface, it has a crucial role in fetal programming, such that any perturbation altering placental function interferes with both in-utero fetal growth and also with the adult life phenotype. Several epigenetic mechanisms have been highlighted in modulating the dynamic placental epigenome, including alterations in DNA methylation status, post-translational modification of histones, and non-coding RNAs. This review aims to provide a comprehensive and critical overview of the available literature on the epigenetic background of fetal growth restriction. A targeted research strategy was performed using PubMed, MEDLINE, Embase, and The Cochrane Library up to January 2022. A detailed and fully referenced synthesis of available literature following the Scale for the Assessment of Narrative Review Articles guidelines is provided. A variety of epigenetic marks predominantly interfering with placental development, function, and metabolism were found to be potentially associated with fetal growth restriction. Available evidence on the role of environmental exposures in shaping the placental epigenome and the fetal phenotype were also critically discussed. Because of the highly dynamic crosstalk between epigenetic mechanisms and the extra level of complexity in interpreting the final placental transcriptome, a full comprehension of these phenomenon is still lacking and advances in multi-omics approaches are urgently needed. Elucidating the role of epigenetics in the developmental origins of health and disease represents a new challenge for the coming years, with the goal of providing early interventions and prevention strategies and, hopefully, new treatment opportunities.

Meningioma during pregnancy: what can influence the management? A case series and review of the literature.

Purpose: Meningioma is a benign tumor, more frequent in female population. During pregnancy, distinguishing a meningioma from other common conditions presenting with similar symptoms (headache, vomiting, visual impairment) is challenging. Moreover, the management must consider not only maternal but also fetal health. The rarity of the condition does not allow to define the features to which look in order to stratify the risk for the need of surgery during pregnancy. We reported three cases of meningioma in pregnant women treated at our department and reviewed those previously reported in the literature. The aim of this review is to evaluate which factors are more determinant in such management.Methods: Electronic databases were searched from year 2000 until June 2020, to identify clinical studies on management of meningioma diagnosed during pregnancy. The primary outcome was surgical timing. Secondary outcomes were delivery methods, maternal and neonatal outcomes.Results: Surgery after pregnancy is more frequently performed in PR + tumor (p-value 0.038) and with HA (p-value 0.0445), as well as in meningioma diagnosed during the third trimester, compared to those diagnosed before (p-value 0.0012). Surgery during pregnancy was more frequent in patients with visual loss (p-value 0.006). No significant differences were found in surgical management, according to age, WHO grade, tumor location, lesion diameter and ER positivity. Delivery method is independent from both hormonal receptor status and main symptoms, but women who had neurosurgery during pregnancy delivered more frequently with spontaneous vaginal delivery (p-value <0.01).Conclusion: The decision regarding surgical timing of meningioma diagnosed during pregnancy depends on PR + and impending symptoms as visual loss or headache. It seems that timing of neurosurgery does not affect the delivery method. A multidisciplinary approach is always useful to perform a rapid and appropriate diagnosis and to better evaluate pros and cons of surgery during pregnancy and following management both for maternal and fetal wellness.

Management of gestational diabetes in women with a concurrent severe acute respiratory syndrome coronavirus 2 infection, experience of a single center in Northern Italy.

OBJECTIVE: In this study we describe the management of women with gestational diabetes (GD) and an ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The aim of the study is to evaluate whether coronavirus disease 2019 (COVID-19) can further complicate pregnancies, and if the protocol we usually use for GD pregnancies is also applicable to patients who have contracted a SARS-CoV-2 infection. METHODS: This is a retrospective study analyzing all pregnant women with GD and concomitant COVID-19 admitted to our institution for antenatal care between March 1 and April 30, 2020. RESULTS: Among pregnant women with GD and a concomitant SARS-CoV-2 infection, the mean age was 32.9 (SD 5.6) years. Two patients (33%) were of white racial origin and four (67%) were of non-white racial origin. All patients were diagnosed with COVID-19 during the third trimester of pregnancy. Two women were asymptomatic and four were symptomatic. Only two (33.3%) women received treatment with insulin. None of the patients required intensive care or mechanical ventilation. No complications were found among the neonates. CONCLUSION: COVID-19 was not found to worsen the prognosis of patients with GD or of their offspring. Glycemic monitoring, diet therapy, and insulin, when needed, are sufficient for good metabolic control and favorable maternal and fetal outcomes.

Use of Negative Pressure Wound Therapy Systems after Radical Vulvectomy for Advanced Vulvar Cancer.

A retrospective cohort study was performed to evaluate the efficacy of negative pressure wound therapy in improving vulvectomy healing. Women who underwent radical vulvectomy with complete inguinofemoral lymphadenectomy for advanced vulvar cancer were divided into two groups according to immediate postoperative care: patients treated with negative pressure wound therapy using the device applied on the site of the wound (including vulva and inguinal region), and patients receiving conventional care. 18 patients were included in the study. 7 (38.9%) women were treated with negative pressure wound therapy immediately after the surgery and were included in the intervention group, and 11 (61.1%) patients were included in the control group. Women who received negative pressure wound therapy had significantly lower length of stay in the hospital (14.2 ± 4.7 versus 17.1 ± 6.1 days, mean difference -6.90 days, 95% confidence interval -11.91 to -1.89), and significantly lower length for wound healing (-31.90 days, 95% confidence interval -43.48 to -20.32). In conclusion, the utilization of the negative wound pressure therapy may contribute to reduce hospitalization after radical vulvectomy for vulvar cancer. Large and well-designed randomized trials with cost effectiveness analyses are needed to confirm these findings.

Circulating Nucleic Acids in Maternal Plasma and Serum in Pregnancy Complications: Are They Really Useful in Clinical Practice? A Systematic Review.

OBJECTIVE: A systematic review was carried out to summarize the available evidence to assess whether circulating nucleic acids in maternal plasma and serum (CNAPS) have the potential to serve as extra and independent markers for the prediction and/or progression monitoring of the most common and severe complications of pregnancy, including preeclampsia, intrauterine growth restriction, preterm delivery, morbidly adherent placenta, gestational diabetes, antiphospholipid syndrome, threatened abortion, intrahepatic cholestasis of pregnancy, and hyperemesis gravidarum. METHOD: A comprehensive literature search of the MEDLINE (PubMed), EMBASE, and ISI Web of Knowledge databases was conducted to identify relevant studies that included amounts of CNAPS in the abovementioned pregnancy complications. RESULTS: Eighty-three studies met the eligibility criteria. The vast majority of studies were conducted on the quantity of total circulating cell free DNA (cfDNA) and cell free fetal DNA (cffDNA), and some were conducted on messenger RNA (mRNA) species. A few studies have instead evaluated the cell free DNA fetal fraction (cfDNAff), but only in a limited number of pregnancy complications. Despite the growing interest and the abundance of the papers available, little information is available for other new CNAPS, including microRNA (miRNA), long noncoding RNA (lncRNA), mitochondrial DNA (mtDNA), and circular RNA. CONCLUSION: Due to the heterogeneity of the populations enrolled, the scarcity of the studies that adjusted the CNAPS values for possible confounding factors, and the difficulty in interpreting the published data, no conclusion regarding the statistical robustness and clinical relevance of the data can be made at present. If assayed at the third trimester, the CNAPS have, however, shown better performance, and could be used in populations already at risk of developing complications as suggested by the presence of other clinical features. Other CNAPS, including miRNA, are under investigation, especially for the screening of gestational diabetes mellitus, but no data about their clinical utility are available. Circulating DNA (cfDNA, cffDNA, and cfDNAff) and mRNA have not been properly evaluated yet, especially in patients asymptomatic early in pregnancy but who developed complications later, perhaps because of the high cost of these techniques and the availability of other predictors of pregnancy complications (biochemical, biophysical, and ultrasound markers). Therefore, from the analysis of the data, the positive predictive value is not available. As regards the new CNAPS, including miRNA, there are still no sufficient data to understand if they can be promising markers for pregnancy complications monitoring and screening, since CNAPS are statistically weak and expensive. It is reasonable to currently conclude that the use of the CNAPS in clinical practice is not recommended.

Aspirin for Evidence-Based Preeclampsia Prevention trial: influence of compliance on beneficial effect of aspirin in prevention of preterm preeclampsia.

BACKGROUND: The Aspirin for Evidence-Based Preeclampsia Prevention trial was a multicenter study in women with singleton pregnancies. Screening was carried out at 11-13 weeks' gestation with an algorithm that combines maternal factors and biomarkers (mean arterial pressure, uterine artery pulsatility index, and maternal serum pregnancy-associated plasma protein A and placental growth factor). Those with an estimated risk for preterm preeclampsia of >1 in 100 were invited to participate in a double-blind trial of aspirin (150 mg/d) vs placebo from 11-14 until 36 weeks' gestation. Preterm preeclampsia with delivery at <37 weeks' gestation, which was the primary outcome, occurred in 1.6% (13/798) participants in the aspirin group, as compared with 4.3% (35/822) in the placebo group (odds ratio in the aspirin group, 0.38; 95% confidence interval, 0.20 to 0.74). OBJECTIVE: We sought to examine the influence of compliance on the beneficial effect of aspirin in prevention of preterm preeclampsia in the Aspirin for Evidence-Based Preeclampsia Prevention trial. STUDY DESIGN: This was a secondary analysis of data from the trial. The proportion of prescribed tablets taken was used as an overall measure of compliance. Logistic regression analysis was used to estimate the effect of aspirin on the incidence of preterm preeclampsia according to compliance of <90% and ≥90%, after adjustment for the estimated risk of preterm preeclampsia at screening and the participating center. The choice of cut-off of 90% was based on an exploratory analysis of the treatment effect. Logistic regression analysis was used to investigate predictors of compliance ≥90% among maternal characteristics and medical history. RESULTS: Preterm preeclampsia occurred in 5/555 (0.9%) participants in the aspirin group with compliance ≥90%, in 8/243 (3.3%) of participants in the aspirin group with compliance <90%, in 22/588 (3.7%) of participants in the placebo group with compliance ≥90%, and in 13/234 (5.6%) of participants in the placebo group with compliance <90%. The odds ratio in the aspirin group for preterm preeclampsia was 0.24 (95% confidence interval, 0.09-0.65) for compliance ≥90% and 0.59 (95% confidence interval, 0.23-1.53) for compliance <90%. Compliance was positively associated with family history of preeclampsia and negatively associated with smoking, maternal age <25 years, Afro-Caribbean and South Asian racial origin, and history of preeclampsia in a previous pregnancy. CONCLUSION: The beneficial effect of aspirin in the prevention of preterm preeclampsia appears to depend on compliance.

Preoperative treatment of uterine leiomyomas: clinical findings and expression of transforming growth factor-beta3 and connective tissue growth factor.

OBJECTIVE: To evaluate the clinical features and the expression of transforming growth factor-beta3 (TGF-beta3) and connective tissue growth factor (CTGF) in myometrium and uterine leiomyomas after preoperative treatment with gonadotropin-releasing hormone-analogs (GnRH-a) and tibolone. METHODS: Twenty-three patients received 3.75 mg leuprolide acetate depot for 4 months. Twenty-two patients received the same therapy plus 2.5 mg tibolone daily. Patients underwent uterine surgery after therapy. Twenty-two untreated patients underwent surgery directly. Hematologic tests, bone mineral density (BMD) measurement, and ultrasonographic evaluation of uterine volume were performed before and after treatment. Menorrhagia and pelvic pain were evaluated with a visual analog scale. Hot flushes were recorded in daily diaries. Immunohistochemical expression of TGF-beta3 and CTGF in myometrium and myoma samples was evaluated semiquantitatively. RESULTS: After therapy, hemoglobin and iron levels similarly increased in both groups. BMD significantly decreased only in the GnRH-a group. Uterine volume similarly decreased in both groups. No patient had menorrhagia or pelvic pain at the end of therapy. The number of hot flushes increased after the first month in the GnRH-a group; in the GnRH-a plus tibolone group, it remained constant and was lower. In untreated cases, TGF-beta3 and CTGF smooth muscle cell immunoexpression was lower in myometrium than in leiomyomas. After medical treatment, growth factor immunoexpression remained unchanged in myometrial samples and was reduced in leiomyomas. Endothelial cells showed strong immunopositivity, both in untreated and in treated cases. CONCLUSION: This study focuses on the effects of GnRH-a and tibolone on TGF-beta3 and CTGF expression in myometrium and myomas and supports the hypothesis of a pathogenetic role of these growth factors in uterine fibromatosis.