Placental growth factor as a predictive marker of preeclampsia - PREBIO study - PREeclampsia BIOchemical study.

INTRODUCTION: To evaluate the clinical utility of placental growth factor (PlGF) for the prediction of preeclampsia (PE). MATERIALS AND METHODS: This prospective cohort study included women divided into three groups: (1) pregnancies without preconceptional risk of developing PE; (2) pregnancies with a preconceptional and/or current risk of developing PE; (3) PE-complicated pregnancies (control group). Blood samples were collected every 4-5 weeks or during hospitalization from early second trimester until delivery in the group 1 and 2, at the diagnosis of PE in the group 3. Plasma levels of PlGF were measured using The Triage PlGF test (Alere) and considered pathological under the 5th centile for gestational age. Sensitivity (Sn), specificity (Sp), positive and negative predictive value (PPV, NPV) were calculated. RESULTS: In group 1, 30% of women (3/10) had pathological test but none of them developed PE (Sp 70%, NPV 100%). In group 2 (n = 75), none of the patients with normal test developed PE (0/24), while 39% of women with PlGF < 5th centile (20/51) developed PE (Sn 100%, Sp 44%, PPV 39%, NPV 100%). In group 3 (n = 11) all women except one had a pathological PlGF test (Sn 90%, PPV 100%). CONCLUSIONS: Our data support recent studies which identify PlGF as a biochemical marker not only of PE, but also of placental dysfunction. In fact, it is useful for ruling out PE in women at risk because of the high Sn and high NPV: a normal PlGF is related with a positive pregnancy outcome. Therefore, the measurement of this biomarker would simplify PE clinical management and would reduce costs.

Mode of birth in women with low-lying placenta: protocol for a prospective multicentre 1:3 matched case-control study in Italy (the MODEL-PLACENTA study).

INTRODUCTION: The term placenta praevia defines a placenta that lies over the internal os, whereas the term low-lying placenta identifies a placenta that is partially implanted in the lower uterine segment with the inferior placental edge located at 1-20 mm from the internal cervical os (internal-os-distance). The most appropriate mode of birth in women with low-lying placenta is still controversial, with the majority of them undergoing caesarean section. The current project aims to evaluate the rate of vaginal birth and caesarean section in labour due to bleeding by offering a trial of labour to all women with an internal-os-distance >5 mm as assessed by transvaginal sonography in the late third trimester. METHODS AND ANALYSIS: The MODEL-PLACENTA is a prospective, multicentre, 1:3 matched case-control study involving 17 Maternity Units across Lombardy and Emilia-Romagna regions, Italy. The study includes women with a placenta located in the lower uterine segment at the second trimester scan. Women with a normally located placenta will be enrolled as controls. A sample size of 30 women with an internal-os-distance >5 mm at the late third trimester scan is needed at each participating Unit. Since the incidence of low-lying placenta decreases from 2% in the second trimester to 0.4% at the end of pregnancy, 150 women should be recruited at each centre at the second trimester scan. A vaginal birth rate ≥60% in women with an internal-os-distance >5 mm will be considered appropriate to start routinely admitting to labour these women. ETHICS AND DISSEMINATION: Ethical approval for the study was given by the Brianza Ethics Committee (No 3157, 2019). Written informed consent will be obtained from study participants. Results will be disseminated by publication in peer-reviewed journals and presentation in international conferences. TRIAL REGISTRATION NUMBER: NCT04827433 (pre-results stage).

Analysis of SARS-CoV-2 vertical transmission during pregnancy.

The impact of SARS-CoV-2 infection during gestation remains unclear. Here, we analyse the viral genome on maternal and newborns nasopharyngeal swabs, vaginal swabs, maternal and umbilical cord plasma, placenta and umbilical cord biopsies, amniotic fluids and milk from 31 mothers with SARS-CoV-2 infection. In addition, we also test specific anti-SARS-CoV-2 antibodies and expression of genes involved in inflammatory responses in placentas, and in maternal and umbilical cord plasma. We detect SARS-CoV-2 genome in one umbilical cord blood and in two at-term placentas, in one vaginal mucosa and in one milk specimen. Furthermore, we report the presence of specific anti-SARS-CoV-2 IgM and IgG antibodies in one umbilical cord blood and in one milk specimen. Finally, in the three documented cases of vertical transmission, SARS-CoV-2 infection was accompanied by a strong inflammatory response. Together, these data support the hypothesis that in utero SARS-CoV-2 vertical transmission, while low, is possible. These results might help defining proper obstetric management of COVID-19 pregnant women, or putative indications for mode and timing of delivery.

Performance of an extended triage questionnaire to detect suspected cases of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in obstetric patients: Experience from two large teaching hospitals in Lombardy, Northern Italy.

OBJECTIVES: 1. To assess the performance of an extended questionnaire in identifying cases of SARS-CoV-2 infection among obstetric patients. 2. To evaluate the rate of infection among healthcare workers involved in women's care. STUDY DESIGN: A prospective cohort study of obstetric patients admitted to MBBM Foundation and Buzzi Hospital (Lombardy, Northern Italy) from March 16th to May 22nd, 2020. Women were screened on admission by a questionnaire investigating major and minor symptoms of infection and high-risk contacts in the last 14 days. SARS-CoV-2 assessment was performed by RT-PCR on nasopharyngeal swabs. Till April 7th, a targeted SARS-CoV-2 testing triggered by a positive questionnaire was used; from April 8th, a universal testing approach was implemented. RESULTS: There were 1,177 women screened by the questionnaire, which yielded a positive result in 130 (11.0%) cases. SARS-CoV-2 RT-PCR was performed in 865 (73.5%) patients, identifying 51 (5.9%) infections. During the first period, there were 29 infected mothers, 4 (13.8%) of whom had a negative questionnaire. After universal testing implementation, there were 22 (3%, 95% CI 1.94% - 4.04%) infected mothers, 13 (59.1%) of whom had a negative questionnaire; rate of infection among asymptomatic women was 1.9%. Six of the 17 SARS-CoV-2-positive women with a negative questionnaire reported symptoms more than 14 but within 30 days before admission. Isolated olfactory or taste disorders were identified in 15.7% of infected patients. Rate of infection among healthcare workers was 5.8%. CONCLUSIONS: An exhaustive triage questionnaire can effectively discriminate women at low risk of SARS-CoV-2 infection in the context of a targeted and a universal viral testing approach. In 15.7% of infected women, correct classification as a suspected case of infection was due to investigation of olfactory and taste disorders. Extension of the assessed time-frame to 30 days may be worth considering to increase the questionnaire's performance.

A case of endometrial glassy cell carcinoma: a rare entity which necessitates of better understanding.

Endometrial glassy cell carcinoma (EGCC) is a rare neoplasm, accounting for 0.5% of the carcinomas in the endometrium, composed of cells with granular eosinophilic or amphophilic cytoplasm, giving it a ground glass appearance. Till date, only 14 cases of this carcinoma have been reported. In this report, we have described a case of EGCC to help define standard diagnostic criteria and better understand the course, ideal treatment, and accurate prognosis of this disease. We report a case of a 64-year-old woman diagnosed with EGCC after an abnormal pap smear. She underwent a hysteroscopy, which led to the histological diagnosis. Laparotomic total hysterectomy and bilateral salpingo-oophorectomy were performed with pelvic lymphadenectomy and peritoneal and omental biopsies. Final pathological examination confirmed the initial diagnosis. Pelvic nodes removed during surgery and peritoneal and omental biopsies were negative for tumor cells. Treatment was considered appropriate and the patient did not require additional therapies. She was subsequently assigned to clinical follow-up and is alive, with no evidence of the disease.

Neonatal hypoxia of the second twin after vaginal delivery of the first twin: what matters?

Objective: Optimal management of twin deliveries is controversial. We aimed to assess potential risk factors correlated to the development of hypoxia in the second twin after vaginal delivery of the first twin. Study design: This is a retrospective observational study including diamniotic twin pregnancies delivering at our Institution at 35 weeks of gestational age or more, weighing ≥1800 g. Hypoxia was defined as at least one of the following: Apgar score <5 at 10 minute, neonatal resuscitation for >10 minutes, neonatal acidosis (pH ≤7 and/or BE ≥12 mmol/L). Results: A number of 275 diamniotic twin pregnancies met the inclusion criteria and were divided within the following groups: (1) second twin not developing neonatal hypoxia (n = 265); and (2) second twin developing neonatal hypoxia (n = 10). The rate of second twins with neonatal hypoxia during the study period was 3.6% (10/275). Abnormal cardiotocography during the intertwin delivery interval, defined as ACOG category III, was significantly correlated to second twin hypoxia. Of interest, there was no significant difference in the intertwin delivery interval between the study groups. In addition, breech presentation of the second twin did not show to be a risk factor for neonatal hypoxia. None of the second twins developing neonatal hypoxia was reported to have encephalopathy (follow up of at least 24 months). At multivariate analysis, only abnormal cardiotocography was an independent risk factor for second twin hypoxia (OR 17.8, 95% CI 4.1-77.2). Conclusions: In our study, neonatal hypoxia was significantly correlated to abnormal cardiotocography, while intertwin delivery interval was not correlated to the development of this adverse neonatal outcome.

What is the effect of intertwin delivery interval on the outcome of the second twin delivered vaginally?

Objective: Optimal management of twin deliveries is controversial. We aimed to assess if intertwin delivery interval, after vaginal delivery of the first twin, may have an influence on adverse neonatal outcomes of the second twin Study design: This is a retrospective observational study including diamniotic twin pregnancies with vaginal delivery of the first twin, between January 2000 and July 2017. Inclusion criteria were diamniotic pregnancies and vaginal delivery of the first twin. We excluded higher twin order, monoamniotic pregnancies, cesarean delivery of the first twin and patients with missing data. Results: A number of 400 diamniotic twin pregnancies met the inclusion criteria and were divided, considering intertwin delivery interval into (1) ≤30 minutes (n = 365); and (2) >30 minutes (n = 35). Considering the two study groups, maternal and first twin characteristics and outcomes were similar. Second twin reported higher incidence of cesarean section and vacuum delivery, but similar incidence of neonatal adverse outcomes, in case of intertwin interval >30 minutes. At multivariate analysis, a difference between second and first twin weight ≥25% was correlated to neonatal adverse outcome, while we did not found this correlation with a cut-off of 30 minutes. Conclusions: In our study, growth discrepancy between twins was significantly correlated to adverse neonatal outcomes, while intertwin delivery time was not an influencing factor. So, in line with this result, in our clinical practice, we do not use a fixed time in which both twins should be delivered, neither in monochorionic nor in dichorionic pregnancies, when fetal wellbeing was demonstrated during labor.