Le morti in utero: risultati di un progetto pilota di sorveglianza della mortalità perinatale in Italia (SPItOSS).

OBJECTIVES: to describe the results of a pilot population-based perinatal mortality surveillance system, with regards to stillbirths; to study maternal, obstetric, and foetal characteristics, evaluating risk factors and understanding causes. DESIGN: a cross-sectional study was conducted on incident cases of stillbirths collected by the surveillance system from July 2017 to June 2019 in three Italian Regions (Lombardy, Tuscany, and Sicily). SETTING AND PARTICIPANTS: data on stillbirths, resulting from the in-hospital multidisciplinary audits, organised using the Significant Event Audit methodology, were analysed. According to the World Health Organization (WHO) definitions, the project identified stillbirths as foetuses born dead >=28 weeks of gestation. The WHO International Classification of Diseases-Perinatal Mortality was used to categorise the causes of foetal death. MAIN OUTCOMES MEASURES: maternal characteristics, obstetric and foetal findings were investigated. Unadjusted relative risks and 95% confidence intervals were computed with respect to the background population. Finally, causes of death and contributing maternal conditions have been considered. RESULTS: the maternity and neonatal units of the three participating Regions notified 520 stillbirths, of which 435 cases underwent to the multidisciplinary audit (83.7%); 40.0% of cases occurred in the gestational age range between 36 and 39 weeks. The risk of stillbirth was significantly increased in mothers with foreign citizenship (RR: 1.39; 95%CI: 1.13-1.71), multiple pregnancies (RR: 1.59; 95%CI 1.05-2.42), and pregnancies conceived with assisted reproductive technologies (RR: 2.15; 95%CI 1.45-3.19). The rate of congenital malformations was 6.0%. A diagnosis of foetal growth restriction was reported in 10.3% of cases, although the percentage of dead foetuses weighting <10° centile was at least twice in almost all gestational age periods. Post-mortem and placental histological examinations were carried out in more than 70% and more than 90% of cases, respectively. CONCLUSIONS: the implementation of a population-based surveillance system with high participation rate of maternity units and the use of universally accepted definitions could improve the identification of stillbirth avoidable risk factors and potentially modifiable predisposing maternal conditions, highlighting issues of perinatal assistance in need of improvement.

Predicting Time to Delivery in Hypertensive Disorders: Assessing PlGF and sFlt-1 with the Novel Parameter 'Mtp-Multiples of a Normal Term Placenta'.

Background: Imbalanced angiogenesis is characteristic of normal placental maturation but it also signals placental dysfunction, underlying hypertensive disorders during pregnancy. This study aimed to investigate the relationship between angiogenic placental aging, measured by markers placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) using the new index "Multiples of a normal term placenta" (Mtp) and the duration of pregnancy. Methods: A retrospective observational study was conducted, including singleton pregnancies diagnosed or suspected of hypertensive disorders after the 20th gestational week. Mtp measures how far a single dosage of angiogenic marker deviates from the expected value in an uncomplicated full-term pregnancy (Mpt = sFlt-1/sFlt-1 reference value or PIGF/PIGF reference value). We considered the 90th, 95th, and 97.5th centiles for sFlt-1 and the 2.5th, 5th, and 10th centiles for PlGF as references. Results: The categories with longer time to delivery, regardless of gestational age, were: Mtp PlGF 10th c ≥ 2, ≥3 and Mtp sFlt-1 90th c ≤ 0.5 (median days of 9, 11, 15 days, respectively). These two categories Mtp sFlt-1 90th c ≥ 3 and Mtp sFlt-1 97.5th c ≥ 2 allow the identification of women at risk for imminent delivery within 1 day. Women who were deemed at low/medium risk based on the sFlt-1/PIGF ratio appeared to be at high risk when considering the individual values of sFlt-1 and/or PIGF. Conclusions: This new Mtp index for sFlt-1 and PlGF could be employed to assess the degree of placental aging in women with hypertensive disorders. It represents a valid tool for evaluating the risk of imminent birth, irrespective of gestational age, surpassing the current stratification based on the sFlt-1/PIGF ratio.

A vaginal birth is a cost-reduction strategy for women with a low-lying placenta.

BACKGROUND: Alongside health consequences, cesarean delivery (CD) has been associated with increased healthcare resource utilization (HCRU). A CD should be performed in case of placenta previa; in turn, the most appropriate mode of birth in women with a low-lying placenta (LLP) is still controversial. Since no previous data are available on the topic, the aim of this study was to evaluate the HCRU and economic impact on the Italian HC system of vaginal birth (VB) and CD in women with a LLP. METHODS: This retrospective study used patient-level real-world data of a cohort of women with a LLP confirmed at 28-30 weeks. A cost-minimization analysis (CMA) was conducted to compare VB and CD. Since Diagnosis-Related-Group payment may not reflect the actual use of hospital resources, a micro-costing analysis (MCA) was performed to more comprehensively evaluate the economic impact of VB and CD. RESULTS: The study included 86 women with a LLP at the third trimester scan, of which 49 (57%) had a VB and 37 (43%) underwent a CD. The CMA showed an economically marginal difference between VB and CD, especially when considering opportunity costs associated with the resources needed to look after women. However, the MCA identified charges for each VB being about half of those for each CD. CONCLUSIONS: The use of patient-level real-world data allowed to generate basic information to assess the value of available interventions in case of LLP. A VB should be promoted in women with LLP, avoiding further burden on the HC system's limited resources.

Prenatal use of indomethacin for preterm labor and renal function among very low birth weight infants.

BACKGROUND: Indomethacin is administered as a tocolytic agent for threatening preterm labor <28weeks of gestation. Only a few, not conclusive, studies have investigated its nephrotoxicity in very low birth weight (VLBW) infants. We investigated whether indomethacin increases the incidence of acute kidney injury (AKI) among VLBW infants. METHODS: This is a retrospective study including all VLBW infants born at our center between January 1, 2005, and December 31, 2013. Indomethacin was administered to women with preterm labor and intact membranes. Neonatal AKI was defined according to KDIGO classification. Univariate analyses were performed comparing VLBW infants exposed to and not exposed to indomethacin. In the multivariable model, the association of indomethacin and AKI was adjusted for patent ductus arteriosus, use of nephrotoxic medications, birth weight, and gestational age. RESULTS: Five hundred seventy-five VLBW infants were included, 49 (8.5%) of whom were exposed to indomethacin in utero. The univariate analysis showed that infants exposed to indomethacin had lower birth weight, lower gestational age, and higher incidence of AKI than infants not exposed. The multivariable model adjusted for confounding factors confirmed an increased risk of AKI in relation to gestational age at birth <27 weeks, but not to indomethacin. CONCLUSIONS: Our data suggest that extreme prematurity, but not the use of indomethacin, is associated with AKI.

sFlt-1 Levels as a Predicting Tool in Placental Dysfunction Complications in Multiple Pregnancies.

BACKGROUND: several studies have demonstrated that angiogenic markers can improve the clinical management of hypertensive disorders (HDs) and fetal growth restriction (FGR) in singleton pregnancies, but few studies have evaluated the performance of these tests in multiple pregnancies. Our aim was to investigate the role of soluble fms-like tyrosine kinase 1 (sFlt-1) in predicting adverse obstetric outcomes in hospitalized multiple pregnancies with HD (preeclampsia/gestational hypertension/uncontrolled chronic hypertension) and/or FGR in one or more fetuses. METHODS: A retrospective analysis of multiple pregnancies with HD/FGR occurring after the 20th gestational week. Pregnant women were divided into two groups: women with high levels of sFlt-1 and those with low levels of sFlt-1. A value of sFlt-1 greater than or equal to 15,802 pg/mL was considered arbitrarily high, as it is equivalent to two times the 90th percentile expected in an uncomplicated full-term singleton pregnancy based on data from a prospective multicenter study (7901 pg/mL). RESULTS: The cohort included 39 multiple pregnancies. There were no cases of birth <34 weeks, HELLP syndrome, ICU admission, and urgent cesarean sections for HD/FGR complications reported among women with low levels of sFlt-1. CONCLUSIONS: A cut-off value of sFlt-1 ≥ 15,802 pg/mL could represent a valuable tool for predicting adverse obstetric outcomes in multiple pregnancies hospitalized for HD/FGR disorders, regardless of gestational age and chorionicity.

Prevalence and severity of bowel disorders in the third trimester of pregnancy.

BACKGROUND: Bowel-related disorders are common conditions associated with pregnancy and are a cause of significant distress and healthcare burden. However, there is a lack of data in the literature about these disorders. OBJECTIVE: This study aimed to investigate bowel dysfunctions during the third trimester of pregnancy in a large cohort of women using the validated bowel domain of the Italian version of the Pelvic Floor Questionnaire for Pregnant and Postpartum Women. STUDY DESIGN: This was a secondary analysis of a multicenter cross-sectional study conducted in hospitals in Italy and Italian-speaking Switzerland. Women in the third trimester of pregnancy were asked to complete the Italian Pelvic Floor Questionnaire for Pregnant and Postpartum Women. RESULTS: During the study period, 927 pregnant women in the third trimester of pregnancy responded to the questionnaire and were included in the analysis. Overall bowel dysfunctions were reported by 29.6% of patients. Constipation was reported by 66.6% of pregnant women, whereas symptoms of obstructed defecation were reported by 49.9% of patients. In contrast, urgency was reported by 41.1% of patients. Incontinence to flatus and incontinence to stool were reported by 45.1% and 2.8% of patients, respectively. Moreover, age >35 years, familiarity with pelvic floor disorders, nicotine abuse, and pelvic floor contraction inability were identified as independent risk factors for at least 1 bowel symptom. CONCLUSION: Bowel symptoms are extremely common in the third trimester of pregnancy and can greatly affect a patient's quality of life; therefore, bowel symptoms deserve to be investigated and managed properly. The use of validated questionnaires represents a precious tool to investigate functional symptoms that could be very frequent and disabling in this particular period of life for women.

Acute spontaneous non-hemorrhagic adrenal infarction in pregnancy: case-report and literature review.

Unilateral non-hemorrhagic adrenal infarction (NHAI) is a very uncommon cause of acute abdomen in pregnancy. Diagnosis is highly challenging due to its rarity, heterogeneity of clinical presentation, and inconclusiveness of the initial workup. Timely recognition is pivotal to ensuring optimal outcomes. Here we describe a case of spontaneous unilateral NHAI diagnosed in a singleton pregnant woman at 32 weeks' gestation at our centre and provide the findings of an extensive literature review on the topic. We identified 22 articles describing 31 NHAI cases in 30 obstetric patients: NHAI occurs more frequently on the right side and in the third trimester, and diagnosis is formulated more than 24 h after clinical presentation in 50% of cases; second-level imaging is always necessary to reach a definitive diagnosis and start appropriate treatment. A high degree of clinical suspicion is needed to promptly recognize NHAI in pregnancy, thus allowing appropriate multidisciplinary management and timely treatment initiation. Promotion of knowledge and awareness of NHAI as a potential cause of acute abdomen in pregnancy is mandatory to improve clinical practice and, ultimately, perinatal outcomes.

Clinical, ultrasonographic, and functional outcomes after obstetric anal sphincter injury primary repair: A single-center experience.

OBJECTIVE: To present clinical and instrumental sequelae after obstetric anal sphincter injuries (OASIS), evaluating correlations between intrapartum severity of lesions, postpartum symptoms, and sonographic and manometric findings; outcomes during subsequent deliveries were also evaluated. METHODS: This retrospective study evaluated all consecutive women who sustained an OASIS between 2015 and 2020. Postpartum symptoms, anorectal manometry (ARM), and three-dimensional endoanal ultrasonography (3D-EAUS) were analyzed. RESULTS: A total of 107 women underwent OASIS primary repair; 84 (78.5%) of them were asymptomatic after 1 month. The presence and severity of symptoms showed a great correlation with instrumental outcomes in terms of maximum resting pressure, squeeze pressure increment (SPI), circumferential extension of defect for both external anal sphincter (EAS) and internal anal sphincter (IAS), and EAS, IAS and total Starck scores. There was a significant correlation between ARM and 3D-EAUS findings, with the exception of SPI, for which the abnormalities were not predictable based on EAUS results. CONCLUSION: Both ARM and EAUS findings after OASIS are directly related to each other, and associated with symptoms. These instrumental tools may be useful for OASIS assessment and counseling.

Association of intrauterine growth restriction and low birth weight with acute kidney injury in preterm neonates.

BACKGROUND: Preterm birth alters nephrogenesis and reduces the total nephron number. Intrauterine growth restriction (IUGR) seems to worsen nephron loss, but only a few studies have investigated its role in neonatal kidney impairment. We investigated whether IUGR, defined as reduced estimated fetal growth and/or placental flow alterations and low birth weight z-score, increases the risk of developing acute kidney injury (AKI) in very preterm infants. METHODS: We performed a retrospective study including infants born with a birth weight (BW) ≤ 1500 g and/or gestational age (GA) ≤ 32 weeks admitted to our center between January 2016 and December 2021. Neonatal AKI was defined according to the neonatal KDIGO classification based on the decline of urine output and/or creatinine elevation. We used multivariable linear regressions to verify the association between AKI and GA, BW z-score, IUGR definition, and hemodynamically significant patent ductus arteriosus (PDA). RESULTS: We included 282 infants in the analysis, with a median (IQR) GA = 29.4 (27.4, 31.3) weeks, BW = 1150 (870, 1360) g, and BW z-score = - 0.57 (- 1.64, 0.25). AKI was diagnosed in 36 (13%) patients, and 58 (21%) had PDA. AKI was significantly associated with BW z-score (beta (std. error) = - 0.08 (0.03), p = 0.008) and severe IUGR (beta (std. error) = 0.21 (0.08), p = 0.009), after adjusting for GA and PDA. CONCLUSIONS: Our data suggest that low BW z-score and IUGR could represent adjunctive risk factors for kidney impairment in preterm babies. A higher resolution version of the Graphical abstract is available as Supplementary information.

Adverse Childbirth and Perinatal Outcomes Among Healthy, Low-Risk Pregnant Women with Abnormal Total Gestational Weight Gain.

Purpose: Little is known on the potential effects of abnormal gestational weight gain (GWG) among low-risk, healthy pregnant women with no comorbidities or gestational complications. We investigated perinatal outcomes of these pregnancies according to GWG as per the 2009 National Academy of Medicine (NAM) recommendations. Materials and Methods: A retrospective analysis of prospectively collected data of low-risk pregnant women giving birth at term between January 2016 and December 2020. Inclusion criteria were normal pregestational body mass index (pBMI) (18.5-24.9 kg/m2) and no pregestational or gestational complication. Self-reported prepregnancy weight was used to calculate pBMI; GWG was the difference between maternal weight at childbirth and prepregnancy weight. Women were classified according to the 2009 NAM guidelines for GWG: insufficient (iGWG, <11.5 kg), adequate (aGWG, 11.5-16 kg), and excessive (eGWG, >16 kg). Logistic regression analysis with aGWG as referent was performed to independently estimate dose-response associations. Results: During the study period, there were 4,127 (33.1%) births fulfilling the inclusion criteria. Fifty-two percent of women gained outside the recommended range: 33.5% had iGWG and 18.7% had eGWG. iGWG women were 40% more likely to have early-term births and small for gestational age neonates. In turn, eGWG women displayed increased odds of prolonged pregnancy (adjusted odds ratio [aOR] 1.32), cesarean section in labor (aOR 1.50), high-degree perineal tears (aOR 2.04), postpartum hemorrhage ≥1,000 mL (aOR 1.54), and large for gestational age newborns (aOR 1.83). Conclusion: Our data show that abnormal GWG independently associates with heightened risk of adverse outcomes among healthy, low-risk pregnant women with normal pBMI and no comorbidity or gestational complication.

Endometriosis-related spontaneous hemoperitoneum in pregnancy: A case series.

Endometriosis can be associated with adverse pregnancy outcomes. We report six cases of endometriosis-related spontaneous hemoperitoneum diagnosed in pregnant and postpartum women over 13 years. Spontaneous hemoperitoneum in pregnancy mainly occurred in the second half of gestation. All women presented with acute abdominal pain; four of them needed an emergent surgery, two were managed expectantly. The median estimated blood loss was 4250 ml, four women required massive transfusion. Three out of six women had a known history of endometriosis, all of them had histologically confirmed endometriosis after surgery. No maternal or perinatal deaths occurred. In one case, reticence to perform a computed tomography scan led to delayed diagnosis. Since delay can lead to lethal consequences, high levels of suspicion for spontaneous hemoperitoneum should be maintained in cases of severe abdominal pain, even with a woman's negative history of endometriosis. Improved knowledge and regular interdisciplinary meetings are pivotal to ameliorate outcomes.

Women's attitude towards COVID-19 vaccination in pregnancy: A survey study in northern Italy.

OBJECTIVE: To investigate attitudes and risk perceptions towards the coronavirus disease 2019 (COVID-19) vaccine and reasons for hesitancy among pregnant women. METHODS: A prospective survey study was conducted at a University Maternity Department. Participants included any pregnant woman aged 18 years or older, able to understand the Italian language, who accessed the antenatal clinic for a prenatal appointment. The survey comprised questions about sociodemographic characteristics, pregnancy vaccination history, and perception of risk related to the immunization for the woman herself and her infant. RESULTS: A total of 538 women completed the questionnaire, 445 (82.7%) accepted COVID-19 vaccination. Women vaccinated against pertussis were three times more likely to take up the COVID-19 vaccine (odds ratio [OR] 3.19; 95% confidence interval [CI] 1.78-5.72). Having had COVID-19 during pregnancy (OR 0.24; 95% CI 0.11-0.54), and having a high-risk perception towards the immunization for the fetus (OR 0.18; 95% CI 0.09-0.34) were factors associated with vaccine hesitancy. Lack of safety data in pregnancy and the possibility of harm to the fetus were the main concerns. CONCLUSION: A trusting and supportive relationship with the healthcare professional to address fears, and the transmission of evidence-based information, are pivotal to guide women through an informed choice. Understanding the determinants implicated in women's decision making might guide towards effective public health strategies to boost vaccine acceptance.

Prenatal maternal stress during the COVID-19 pandemic and infant regulatory capacity at 3 months: A longitudinal study.

The COVID-19 pandemic is a global traumatic experience for citizens, especially during sensitive time windows of heightened plasticity such as pregnancy and neonatal life. Pandemic-related stress experienced by mothers during pregnancy may act as an early risk factor for infants' regulatory capacity development by altering maternal psychosocial well-being (e.g., increased anxiety, reduced social support) and caregiving environment (e.g., greater parenting stress, impaired mother-infant bonding). The aim of the present longitudinal study was to assess the consequences of pandemic-related prenatal stress on infants' regulatory capacity. A sample of 163 mother-infant dyads was enrolled at eight maternity units in northern Italy. They provided complete data about prenatal stress, perceived social support, postnatal anxiety symptoms, parenting stress, mother-infant bonding, and infants' regulatory capacity at 3 months of age. Women who experienced emotional stress and received partial social support during pregnancy reported higher anxious symptoms. Moreover, maternal postnatal anxiety was indirectly linked to the infants' regulatory capacity at 3 months, mediated by parenting stress and mother-infant bonding. Dedicated preventive interventions should be delivered to mothers and should be focused on protecting the mother-infant dyad from the detrimental effects of pandemic-related stress during the COVID-19 healthcare emergency.

Isolation of single circulating trophoblasts from maternal circulation for noninvasive fetal copy number variant profiling.

OBJECTIVE: To develop a multi-step workflow for the isolation of circulating extravillous trophoblasts (cEVTs) by describing the key steps enabling a semi-automated process, including a proprietary algorithm for fetal cell origin genetic confirmation and copy number variant (CNV) detection. METHODS: Determination of the limit of detection (LoD) for submicroscopic CNV was performed by serial experiments with genomic DNA and single cells from Coriell cell line biobank with known imbalances of different sizes. A pregnancy population of 372 women was prospectively enrolled and blindly analyzed to evaluate the current workflow. RESULTS: An LoD of 800 Kb was demonstrated with Coriell cell lines. This level of resolution was confirmed in the clinical cohort with the identification of a pathogenic CNV of 800 Kb, also detected by chromosomal microarray. The mean number of recovered cEVTs was 3.5 cells per sample with a significant reverse linear trend between gestational age and cEVT recovery rate and number of recovered cEVTs. In twin pregnanices, evaluation of zygosity, fetal sex and copy number profiling was performed in each individual cell. CONCLUSION: Our semi-automated methodology for the isolation and single-cell analysis of cEVTS supports the feasibility of a cell-based noninvasive prenatal test for fetal genomic profiling.

Fibroids-related complications in pregnancy: a twelve-year long experience at a maternal-fetal medicine referral center.

BACKGROUND: Uterine fibroids are the most frequent female benign tumor, which can cause complications during pregnancy, mainly pain. Differential diagnosis may be challenging and a standardized management approach is lacking. We aim to propose an algorithm for the differential diagnosis of pain during pregnancy and for management of fibroid-related pain. METHODS: A retrospective cohort study of all pregnant women admitted to our center for complications related to fibroids between 2008 and 2019. Data regarding clinical examination, laboratory results, imaging parameters, as well as perinatal outcomes, were collected and assessed (Fisher's Exact Test). RESULTS: Twenty-four pregnant patients were admitted for fibroid-related complications. Six patients were admitted more than one times, for a total of 34 admissions. The main cause of hospital admission was pain (N.=33, 94.1%), which was successfully managed with acetaminophen and/or ketoprofen in 91.2%. In two cases, conservative management failed and a surgical approach was undertaken. Most women (N.=20, 90.9%) delivered at term, with a cesarean delivery and post-partum hemorrhage rate of 22.7%. All newborns had normal APGAR score, umbilical artery pH and birth weight. CONCLUSIONS: Pain is the most common complication of fibroids during pregnancy. Accurate differential diagnosis and adequate management are pivotal to ensure good perinatal outcomes.

Prevalence, Outcome, and Prevention of Congenital Cytomegalovirus Infection in Neonates Born to Women With Preconception Immunity (CHILd Study).

BACKGROUND: Human cytomegalovirus (HCMV) is the leading infectious cause of congenital disabilities. We designed a prospective study to investigate the rate, outcome, and risk factors of congenital CMV (cCMV) infection in neonates born to immune women, and the potential need and effectiveness of hygiene recommendations in this population. METHODS: The study was composed of 2 sequential parts: an epidemiology (part 1) and a prevention (part 2) study. Performance of part 2 depended upon a cCMV rate >0.4%. Women enrolled in part 1 did not receive hygiene recommendations. Newborns were screened by HCMV DNA testing in saliva and cCMV was confirmed by urine testing. RESULTS: Saliva swabs were positive for HCMV DNA in 45/9661 newborns and cCMV was confirmed in 18 cases. The rate of cCMV was .19% (95% confidence interval [CI]: .11-.29%), and 3 out of 18 infants with cCMV had symptoms of CMV at birth. Age, nationality, occupation, and contact with children were similar between mothers of infected and noninfected newborns. Twin pregnancy (odds ratio [OR]: 7.2; 95% CI: 1.7-32.2; P = .037) and maternal medical conditions (OR: 3.9; 95% CI: 1.5-10.1; P = .003) appeared associated with cCMV. Given the rate of cCMV was lower than expected, the prevention part of the study was cancelled. CONCLUSIONS: Newborns from women with preconception immunity have a low rate of cCMV, which appears to be mostly due to reactivation of the latent virus. Therefore, serological screening in childbearing age would be pivotal to identify HCMV-seropositive women, whose newborns have a low risk of cCMV. CLINICAL TRIALS REGISTRATION: www.clinicaltrials.gov (NCT03973359).

Midwives' experiences of providing maternity care to women and families during the COVID-19 pandemic in Northern Italy.

PROBLEM: The COVID-19 pandemic has significantly challenged maternity provision internationally. Rapid and radical changes were implemented, with midwives facing anxiety and moral distress if not able to provide optimal and woman-centred care in line with professional values. BACKGROUND: Healthcare professionals' stress and burnout are commonly reported during other global emergencies, which may eventually contribute to reduced quality of care. There is lack of evidence of the challenges faced by midwives in Italy during the COVID-19 pandemic. AIM: To explore midwives' experiences of providing care to women and families during the COVID-19 pandemic. METHODS: Qualitative interpretive phenomenological approach, using semi-structured interviews and thematic analysis. The sample included 15 midwives. Ethical approval was obtained. FINDINGS: Four themes were identified: 1) adjusting to the ever-evolving organisation of care; 2) physical, psychological and relational challenges; 3) support network; 4) deferred sense of awareness. DISCUSSION: Midwives faced professional and personal challenges during the pandemic, displaying feelings of fear, anxiety, uncertainty, discomfort, lack of support and knowledge with potential long-term effects. Adjusting to the continuous, rapid and drastic re-organisation of maternity services was particularly challenging. Factors facilitating a safe, supportive and empowering workplace included support from colleagues and managers, access to appropriate PPE, reliable guidelines, good communication and emotional support. Positive aspects of personal and professional development included communication skills, establishment of trusting relationships, sense of empowerment and teamwork. CONCLUSION: In the context of a pandemic, optimisation of midwives' physical, emotional and psychological wellbeing should be considered. Timely and comprehensive guidelines and appropriate resources should be provided to assist midwives in facilitating family-centred respectful maternity care and preserving childbirth as a bio-psychosocial event.

Gestational Intraplacental Choriocarcinoma in a Term Pregnancy: A Case Report.

Intraplacental choriocarcinoma (IC) is a rare type of gestational choriocarcinoma (GC) occurring within the placenta, and only a small number of cases have been reported so far. Intraplacental choriocarcinoma is usually asymptomatic or may present with aspecific symptoms, including unexplained vaginal bleeding during pregnancy. Early diagnosis and treatment are pivotal for ensuring optimal outcomes. However, intraplacental choriocarcinoma is rarely suspected due to limited knowledge and awareness of the condition. Here, we report the case of a 34-year-old woman diagnosed with intraplacental choriocarcinoma by placental histological examination performed after delivery due to unexplained vaginal bleeding at 29 gestational weeks, requiring hospital admission. Two lines of chemotherapy and surgery were necessary to achieve complete remission. Since unexplained vaginal bleeding during pregnancy can be a clinical manifestation of intraplacental choriocarcinoma, we propose to consider placental histological examination in all pregnancies with this complication.

Imbalanced Angiogenesis in Pregnancies Complicated by SARS-CoV-2 Infection.

COVID-19 and preeclampsia (preE) share the ANG-II mediated endothelial dysfunction, resulting from a significant dysregulation of RAS and an imbalanced proportion of anti-angiogenic and pro-angiogenic soluble plasmatic factors. Of note, an increased incidence of preE has been reported among COVID-19-infected mothers compared to the general pregnant population. The two most promising angiogenic markers are the soluble fms-like tyrosine kinase receptor-1 (sFlt-1), the major antiangiogenic factor, and the placental growth factor (PlGF), a powerful angiogenic factor. Since these markers have proven useful in the prediction, diagnosis, and severity of preE, this study aimed to evaluate their maternal serum levels in pregnancies complicated by SARS-CoV-2 infection and to assess their potential use to guide the management of these women. A retrospective analysis of SARS-CoV-2-positive pregnant women was performed. The serum levels of sFlt-1 and PlGF were collected at the diagnosis of SARS-CoV-2 infection at the hospital, before the beginning of steroid/hydroxychloroquine and/or antithrombotic therapy. The sFlt-1/PlGF ratio was stratified using cut-off values clinically utilized in the diagnosis and prediction of preE (low < 38, intermediate 38−85/110* and high >85/110*, * if before or after the 34th week of gestation). A total of 57 women were included, of whom 20 (35%) had signs and symptoms of COVID-19 at hospital presentation and 37 (65%) were asymptomatic. None were vaccinated. The mean gestational age at diagnosis of SARS-CoV-2 infection was 32 weeks in symptomatic patients and 37 weeks and 5 days in asymptomatic ones (p = 0.089). sFlt-1 serum levels were higher in SARS-CoV-2 positive asymptomatic patients compared to women with COVID-19 related symptoms (4899 ± 4357 pg/mL vs. 3187 ± 2426 pg/mL, p = 0.005). sFlt-1/PlGF at admission was <38 in 18 of the 20 symptomatic women (90%) compared to 22 (59%) of the asymptomatic patients (p = 0.018). Of note, two of the three women admitted to the intensive care unit had a very low ratio (<2). In turn, rates of patients with sFlt-1/PlGF at admission > 85/110 were not significantly different between the two groups: 11% in asymptomatic patients (4/37) vs. none of the symptomatic patients (p = 0.286), and all of them presented a placental dysfunction, like preE (n = 1) and FGR (n = 3). Of note, there were no stillbirths or maternal or neonatal deaths among symptomatic patients; also, no cases of preE, FGR, or small for gestational age neonates were diagnosed. In conclusion, our data suggest that SARS-CoV-2 infection during pregnancy could influence the angiogenic balance. A significant pathological alteration of the sFlt-1/PlGF ratio cannot be identified during the symptomatic phase; however, if left untreated, SARS-CoV-2 infection could potentially trigger placental dysfunction.