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BACKGROUND: Despite major advances in the pharmacologic treatment of hypertension in the nonpregnant population, treatments for hypertension in pregnancy have remained largely unchanged over the years. There is recent evidence that a more adequate control of maternal blood pressure is achieved when the first given antihypertensive drug is able to correct the underlying hemodynamic disorder of the mother besides normalizing the blood pressure values. OBJECTIVE: This study aimed to compare the blood pressure control in women receiving an appropriate or inappropriate antihypertensive therapy following the baseline hemodynamic findings. STUDY DESIGN: This was a prospective multicenter study that included a population of women with de novo diagnosis of hypertensive disorders of pregnancy. A noninvasive assessment of the following maternal parameters was performed on hospital admission via Ultrasound Cardiac Output Monitor before any antihypertensive therapy was given: cardiac output, heart rate, systemic vascular resistance, and stroke volume. The clinician who prescribed the antihypertensive therapy was blinded to the hemodynamic evaluation and used as first-line treatment a vasodilator (nifedipine or alpha methyldopa) or a beta-blocker (labetalol) based on his preferences or on the local protocols. The first-line pharmacologic treatment was retrospectively considered hemodynamically appropriate in either of the following circumstances: (1) women with a hypodynamic profile (defined as low cardiac output [≤5 L/min] and/or high systemic vascular resistance [≥1300 dynes/second/cm2]) who were administered oral nifedipine or alpha methyldopa and (2) women with a hyperdynamic profile (defined as normal or high cardiac output [>5 L/min] and/or low systemic vascular resistances [<1300 dynes/second/cm2]) who were administered oral labetalol. The primary outcome of the study was to compare the occurrence of severe hypertension between women treated with a hemodynamically ap

Objective: Stillbirth is a potentially preventable complication of pregnancy. Identifying women at high risk of stillbirth can guide decisions on the need for closer surveillance and timing of delivery in order to prevent fetal death. Prognostic models have been developed to predict the risk of stillbirth, but none has yet been validated externally. In this study, we externally validated published prediction models for stillbirth using individual participant data (IPD) meta-analysis to assess their predictive performance. Methods: MEDLINE, EMBASE, DH-DATA and AMED databases were searched from inception to December 2020 to identify studies reporting stillbirth prediction models. Studies that developed or updated prediction models for stillbirth for use at any time during pregnancy were included. IPD from cohorts within the International Prediction of Pregnancy Complications (IPPIC) Network were used to validate externally the identified prediction models whose individual variables were available in the IPD. The risk of bias of the models and cohorts was assessed using the Prediction study Risk Of Bias ASsessment Tool (PROBAST). The discriminative performance of the models was evaluated using the C-statistic, and calibration was assessed using calibration plots, calibration slope and calibration-in-the-large. Performance measures were estimated separately in each cohort, as well as summarized across cohorts using random-effects meta-analysis. Clinical utility was assessed using net benefit. Results: Seventeen studies reporting the development of 40 prognostic models for stillbirth were identified. None of the models had been previously validated externally, and the full model equation was reported for only one-fifth (20%, 8/40) of the models. External validation was possible for three of these models, using IPD from 19 cohorts (491 201 pregnant women) within the IPPIC Network database. Based on evaluation of the model development studies, all three models had an overa

Objectives: To analyze soluble Fms-like tyrosine Kinase 1 (sFlt-1) and Placental Growth Factor (PlGF) ratio concentrations in COVID-19 pregnant patients with and without Hypertensive Disorders of Pregnancy (HDP), compared with non COVID-19 pregnant patients with HDP and a control group. Study design: We recruited and obtained a complete follow-up of 19 COVID-19 pregnant patients with HDP and of 24 COVID-19 normotensive pregnant patients. Demographic, clinical and sFlt-1/PlGF ratio findings were compared with a group of 185 non COVID-19 pregnant patients with HDP and 41 non COVID normotensive patients. Findings were based on univariate analysis and on a multivariate adjusted model, and a case by case analysis of COVID-19 pregnant patients with an abnormal sFlt-1/PlGF ratio > 38 at recruitment. Main outcome measures: sFlt-1/PlGF ratio. Results: We confirmed a significant higher prevalence of HDP in women affected by COVID-19 compared to control population. sFlt-1/PlGF ratio was found high in HDP patients, with and without of Sars-Cov2 infection. COVID-19 patients with worse evolution of the disease showed greater rates of obesity and other comorbidities. sFlt/PlGF ratio proved not to be helpful in the differential diagnosis of the severity of this infection. Conclusions: COVID-19 pregnant patients showed a higher prevalence of HDP compared to non COVID-19 controls, as well as higher comorbidity rates. In spite of the possible common endothelial target and damage, between Sars-Cov-2 infection and HDP, the sFlt1/PlGF ratio did not correlate with the severity of this syndrome.

Introduction: Developing techniques for the tagless isolation of homogeneous cell populations in physiological-like conditions is of great interest in medical research. A particular case is Gravitational Field-Flow Fractionation (GrFFF), which can be run avoiding cell fixation, and that was already used to separate viable cells. Cell dimensions have a key role in this process. However, their dimensions under physiological-like conditions are not easily known since the most diffused measurement techniques are performed on fixed cells, and the fixation used to preserve tissues can alter the cell size. This work aims to obtain and compare cell size data under physiological-like conditions and in the presence of a fixative. Methods: We developed a new protocol that allows the analysis of blood cells in different conditions. Then, we applied it to obtain a dataset of human cord blood cell dimensions from 32 subjects, comparing two tubes with anticoagulants (EDTA and Citrate) and two tubes with different preservatives (CellRescue and CellSave). We analyzed a total of 2071 cells by using confocal microscopy via bio-imaging to assess dimensions (cellular and nuclear) and morphology. Results: Cell diameter measured does not differ when using the different anticoagulants, except for the increase reported for monocyte in the presence of citrate. Instead, cell dimensions differ when comparing anticoagulants and cell preservative tubes, with a few exceptions. Cells characterized by high cytoplasm content show a reduction in their size, while morphology appears always preserved. In a subgroup of cells, 3D reconstruction was performed. Cell and nucleus volumes were estimated using different methods (specific 3D tool or reconstruction from 2D projection). Discussion: We found that some cell types benefit from a complete 3D analysis because they contain non-spherical structures (mainly for cells characterized by poly-lobated nucleus). Overall, we showed the effect of the preservativ

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.

The new coronavirus emergency spread to Italy when little was known about the infection’s impact on mothers and newborns. This study aims to describe the extent to which clinical practice has protected childbirth physiology and preserved the mother–child bond during the first wave of the pandemic in Italy. A national population-based prospective cohort study was performed enrolling women with confirmed SARS-CoV-2 infection admitted for childbirth to any Italian hospital from 25 February to 31 July 2020. All cases were prospectively notified, and information on peripartum care (mother–newborn separation, skin-to-skin contact, breastfeeding, and rooming-in) and maternal and perinatal outcomes were collected in a structured form and entered in a web-based secure system. The paper describes a cohort of 525 SARS-CoV-2 positive women who gave birth. At hospital admission, 44.8% of the cohort was asymptomatic. At delivery, 51.9% of the mothers had a birth support person in the delivery room; the average caesarean section rate of 33.7% remained stable compared to the national figure. On average, 39.0% of mothers were separated from their newborns at birth, 26.6% practised skin-to-skin, 72.1% roomed in with their babies, and 79.6% of the infants received their mother’s milk. The infants separated and not separated from their SARS-CoV-2 positive mothers both had good outcomes. At the beginning of the pandemic, childbirth raised awareness and concern due to limited available evidence and led to “better safe than sorry” care choices. An improvement of the peripartum care indicators was observed over time.

Introduction. The study was implemented to provide guidance to decision-makers and clinicians by describing hospital care offered to women who gave birth with confirmed SARS-CoV-2 infection. Materials and methods. National population‐based prospective cohort study involving all women with confirmed SARS-CoV-2 infection who gave birth between February 25 and April 22, 2020 in any Italian hospital. Results. The incidence rate of confirmed SARS-CoV-2 infection in women who gave birth was 2.1 per 1000 maternities at a national level and 6.9/1000 in the Lombardy Region. Overall one third of the women developed a pneumonia and 49.7% assumed at least one drug against SARS-CoV-2 infection. Caesarean rate was 32.9%, no mothers nor newborns died. Six percent of the infants tested positive for SARS-CoV-2 at birth. Conclusions. Clinical features and outcomes of COVID-19 in women who gave birth are similar to those described for the general population, most women developing mild to moderate illness.

Background: Universal testing has been suggested as a useful strategy for a safe exit from the total lockdown, without recurrence of COVID-19 epidemic, delivering women being considered a sentinel population. Further universal testing for pregnant women may be useful in order to define appropriate access to COVID19 areas, dedicated neonatal care, and personal protective equipment. Methods: During the period 10–26 April, all consecutive women admitted for delivery at the Maternity Hospitals of the city of Milan and in six provinces of Lombardy: Brescia, Como, Lecco Monza, Pavia, and Sondrio. areas were tested with nasopharyngeal swabs. Results and conclusion: Out of 1566 women, 49 were tested positive for SARS-Cov-2 (3.1%, 95% Confidence Interval (CI) 2.3–4.0). This value is largely higher than Heath Authorities estimate. Of tested positive women, 22 (44.9%) had symptoms or reported close contacts with positive patients, that is were found at risk by the itemized questionnaire. In conclusion, routine estimate of frequency of positivity among delivering women can be consider a useful methods to monitor positivity at least in females in their fertile ages.

Objective: To report mode of delivery and immediate neonatal outcome in COVID-19 infected women. Design: This is a retrospective study. Setting: Twelve hospitals in northern Italy. Participants: Pregnant women with COVID-19 confirmed infection who delivered. Exposure: COVID 19 infection in pregnancy. Methods: SARS-CoV-2 infected women who were admitted and delivered during the period 1-20 march 2020 were eligible. Data were collected from the clinical records using a standardized questionnaire on maternal general characteristics, any medical or obstetric co-morbidity, course of pregnancy, clinical signs and symptoms, treatment of COVID 19 infection, mode of delivery, neonatal data and breastfeeding. Main Outcome and Measure: Data on mode of delivery and neonatal outcome. Results: 42 women with COVID-19 delivered at the participating centres: 24(57,1%, 95% CI= 41,0-72,3) delivered vaginally. An elective cesarean section was performed in 18/42 (42,9%, 95%CI 27,7-59,0) cases: in 8 cases the indication was unrelated to COVID-19 infection. Pneumonia was diagnosed in 19/42(45,2%, 95%CI 29,8-61,3) cases: of these 7/19(36,8%,95CI 16,3-61,6) required oxygen support and 4/19(21,1%,95%CI=6,1-45,6) were admitted to a critical care unit. Two women with COVID-19 breastfed without a mask because infection was diagnosed in the post-partum period: their new-borns tested positive for SARS-Cov-2 infection. In one case a new-born had a positive test after a vaginal operative delivery. Conclusions: Although post-partum infection cannot be excluded with 100% certainty, these findings suggest that vaginal delivery is associated with a low risk of intrapartum SARS-Cov-2 transmission to the new-born.

Objectives: To verify whether the use of the temporal criterion of 32 weeks' gestation is effective in identifying maternal hemodynamic differences between early- and late-onset fetal growth restriction (FGR), and to test the statistical performance of a classificatory algorithm for FGR. Materials and methods: A prospective multicenter study conducted at three centers over 17 months. Singleton pregnant women with a diagnosis of FGR based on the international Delphi survey consensus at ≥ 20 weeks of gestation were included. FGR was classified as early-onset if diagnosed <32 weeks' gestation and as late-onset if ≥32 weeks. Hemodynamic assessment was performed by USCOM-1A at the time of FGR diagnosis. Comparisons between early- and late-onset FGR among the entire study cohort, FGR associated with hypertensive disorders of pregnancy (HDP-FGR), and isolated FGR (i-FGR) were performed. In addition, HDP-FGR cases were compared to i-FGR, regardless of the temporal cut-off of 32 weeks' gestation. Finally, a classificatory analysis based on the Random Forest model was performed to identify significant variables with the ability to differentiate FGR phenotypes. Results: During the study period, 146 pregnant women fulfilled the inclusion criteria. In 44 cases, FGR was not confirmed at birth, thus limiting the final study population to 102 patients. In 49 (48.1%) women, FGR was associated to HDP. Fifty-nine (57.8%) cases were classified as early-onset. Comparison of the maternal hemodynamics between early- and late-onset FGR did not show any difference. Similarly, non-significant findings were observed in sensitivity analyses performed for HDP-FGR and for i-FGR. In turn, comparison between pregnant women with FGR and hypertension and women with i-FGR, independently of the gestational age at FGR diagnosis, revealed substantial differences, with the former showing higher vascular peripheral resistances and lower cardiac output, among other significant parameters. The classifica

BACKGROUND: Women's memories of their childbirth experience tend to remain unchanged over time. This experience can be influenced by obstetric factors as well as by sociodemographic and psychological variables.OBJECTIVE: To examine whether women's perceived childbirth experience changes over time; to identify the predictors (obstetric, sociodemographic, and psychological variables) of this experience immediately after delivery and after 3 months.METHODS: This prospective longitudinal study comprised two hundred and twenty-one Italian women who completed a self-report questionnaire at two assessment points: immediately (1-3 days) after birth (Time 1) and 3 months postpartum (Time 2). At Time 1, the questionnaire included some questions on sociodemographic, psychological, and obstetric information, and the Wijma Delivery Experience Questionnaire (WDEQ(B); at Time 2 women compiled again the WDEQ(B).RESULTS: Repeated measures ANOVA revealed that the childbirth experience did not change from Time 1 to Time 2. However, predictors of this experience were different between Time 1 and Time 2: at Time 1, the childbirth experience (WDEQ(B)_t1) was significantly predicted nly by type of cesarean section; at Time 2, the childbirth experience (WDEQ(B)_t2) was significantly predicted by WDEQ(B)_ t1, history of psychological disorders, and type of conception.DISCUSSIONS: Our findings enhance the understanding of the main predictors of a woman's childbirth experience. Identifying areas of vulnerability is important for clinical practice, as well as for developing maternal health policies to improve women's birth experiences, postpartum well-being, and the baby's development

Introduction: Postpartum depression is commonly experienced by mothers worldwide and is associated with anxiety disorders, parenting stress, and other forms of distress, which may lead to a complex illness condition. Several studies have investigated the risk factors for this disorder, including biological and socio-demographic variables, medical and obstetric factors, and psychological and relational dimensions. The present study aimed to describe the psychological status of mothers up to 12 months postpartum, and to investigate the predictors of depressive symptoms at 12 months postpartum, considering obstetric factors along with psychological and relational variables. Methods: A sample of 137 women completed a questionnaire composed of a sheet on anamnestic and obstetric information and the following scales: Wijma Delivery Experience Questionnaire; State-Trait Anxiety Inventory; Edinburgh Postnatal Depression Scale; Parenting Stress Index (Short Form); Dyadic Adjustment Scale; and Multidimensional Scale of Perceived Social Support. Data were collected at four assessment times: 2–3 days, 3 months, 6 months, and 12 months postpartum. Results: Findings showed that the highest percentage of women with clinically significant symptoms of anxiety (state and trait) and depression was found at 12 months postpartum, which indicated that this was the most critical time. The quality of childbirth experience and trait anxiety at three months postpartum emerged as significant predictors of postpartum depression at 12 months. Conclusion: Our findings highlight the importance of providing stable programs (such as educational programs) to mothers in the first year postpartum. Furthermore, because the quality of the childbirth experience is one of the most important predictors of PPD at 12 months postpartum, effort should be made by healthcare professionals to guarantee a positive experience to all women to reduce possible negative long-term consequences of this experience.

Objective: To evaluate the performance of third-trimester ultrasound for the diagnosis of clinically significant placenta accreta spectrum disorder (PAS) in women with low-lying placenta or placenta previa. Methods: This was a prospective multicenter study of pregnant women aged ≥ 18 years who were diagnosed with low-lying placenta (< 20 mm from the internal cervical os) or placenta previa (covering the internal cervical os) on ultrasound at ≥ 26 + 0 weeks' gestation, between October 2014 and January 2019. Ultrasound suspicion of PAS was raised in the presence of at least one of these signs on grayscale ultrasound: (1) obliteration of the hypoechogenic space between the uterus and the placenta; (2) interruption of the hyperechogenic interface between the uterine serosa and the bladder wall; (3) abnormal placental lacunae. Histopathological examinations were performed according to a predefined protocol, with pathologists blinded to the ultrasound findings. To assess the ability of ultrasound to detect clinically significant PAS, a composite outcome comprising the need for active management at delivery and histopathological confirmation of PAS was considered the reference standard. PAS was considered to be clinically significant if, in addition to histological confirmation, at least one of these procedures was carried out after delivery: use of hemostatic intrauterine balloon, compressive uterine suture, peripartum hysterectomy, uterine/hypogastric artery ligation or uterine artery embolization. The diagnostic performance of each ultrasound sign for clinically significant PAS was evaluated in all women and in the subgroup who had at least one previous Cesarean section and anterior placenta. Post-test probability was assessed using Fagan nomograms. Results: A total of 568 women underwent transabdominal and transvaginal ultrasound examinations during the study period. Of these, 95 delivered in local hospitals, and placental pathology according to the study protocol w