Early-Stage Breast Cancer Detection in Breast Milk.

Breast cancer occurring during pregnancy (PrBC) and postpartum (PPBC) is usually diagnosed at more advanced stages compared with other breast cancer, worsening its prognosis. PPBC is particularly aggressive, with increased metastatic risk and mortality. Thus, effective screening methods to detect early PrBC and PPBC are needed. We report for the first time that cell-free tumor DNA (ctDNA) is present in breast milk (BM) collected from patients with breast cancer. Analysis of ctDNA from BM detects tumor variants in 87% of the cases by droplet digital PCR, while variants remain undetected in 92% of matched plasma samples. Retrospective next-generation sequencing analysis in BM ctDNA recapitulates tumor variants, with an overall clinical sensitivity of 71.4% and specificity of 100%. In two cases, ctDNA was detectable in BM collected 18 and 6 months prior to standard diagnosis. Our results open up the potential use of BM as a new source for liquid biopsy for PPBC detection. SIGNIFICANCE: For the first time, we show that BM obtained from patients with breast cancer carries ctDNA, surpassing plasma-based liquid biopsy for detection and molecular profiling of early-stage breast cancer, even prior to diagnosis by image. See related commentary by Cunningham and Turner, p. 2125. This article is featured in Selected Articles from This Issue, p. 2109.

Confirmation of preeclampsia-like syndrome induced by severe COVID-19: an observational study.

BACKGROUND: Since the outbreak of the COVID-19 pandemic, some studies have reported an increased preeclampsia incidence in pregnant women with SARS-CoV-2 infection. Several explanations for this association have been proposed, including a preeclampsia-like syndrome induced by severe COVID-19. This syndrome was described in a small case series and has not been confirmed in larger studies, and its effect on perinatal outcomes has not been studied. OBJECTIVE: This study aimed to confirm the preeclampsia-like syndrome because of COVID-19 and to investigate its implications on pregnancy outcomes and prognosis. STUDY DESIGN: This was a prospective, observational study conducted in a tertiary referral hospital. The inclusion criteria were pregnant women admitted to the intensive care unit for severe pneumonia because of COVID-19. They were classified into 3 groups based on clinical and laboratory findings: preeclampsia, preeclampsia-like syndrome, and women without preeclampsia features. The 3 cohorts were analyzed and compared at 3 different times: before, during, and after severe pneumonia. The main outcomes were incidence of adverse perinatal outcomes and signs and symptoms of PE, such as hypertension, proteinuria, thrombocytopenia, elevated liver enzymes, and increased angiogenic factors (soluble fms-like tyrosine kinase 1-to-placental growth factor ratio). RESULTS: A total of 106 women were admitted to the intensive care unit because of severe pneumonia, and 68 women were included in the study. Of those, 53 (50.0%) did not meet the diagnostic criteria for preeclampsia and remained pregnant after pneumonia (non-preeclampsia); 7 (6.6%) met the diagnostic criteria for preeclampsia, had abnormal (>38) soluble fms-like tyrosine kinase 1-to-placental growth factor ratio (preeclampsia), and delivered during severe pneumonia, and 8 (7.5%) met the diagnostic criteria for preeclampsia, had normal (≤38) soluble fms-like tyrosine kinase 1-to-placental growth factor ratio (preeclampsia like), and did not deliver during pneumonia. Despite not having delivered, most preeclampsia-related features improved after severe pneumonia in women with preeclampsia-like syndrome. Women with preeclampsia had significantly poorer outcomes than women with preeclampsia-like syndrome or without preeclampsia. CONCLUSION: More than 50% of women with severe COVID-19 and diagnostic criteria for preeclampsia may not be preeclampsia but a preeclampsia-like syndrome, which may affect up to 7.5% of women with severe COVID-19. Preeclampsia-like syndrome might have similar perinatal outcomes to those of normotensive women with severe pneumonia because of COVID-19. For these reasons, preeclampsia-like syndrome should be excluded by using soluble fms-like tyrosine kinase 1-to-placental growth factor ratio in future research and before making clinical decisions.

[Twin gestation with complete hydatidiform mole and a coexisting live fetus: A case report and review of the literature]. / Embarazo gemelar con mola hidatiforme completa y feto vivo asociado: reporte de un caso y revisión bibliográfica.

Twin pregnancies with complete hydatidiform mole and coexisting live fetus are very rare, with only about 300 reported cases. This type of pregnancy is considered a high obstetric risk due to the possibility of severe maternal-fetal complications. Although the clinical and ultrasound findings can be highly suggestive of this type of pregnancy, the definitive diagnosis is usually reached by histopathological examination. The differential diagnosis usually includes partial hydatidiform mole and hydropic pregnancies, which can present similar findings in specimens from the first trimester of pregnancy and thus it is important to interpret correctly the differentiating features. The use of immunohistochemistry for p57 can prove very useful, although some cases show an aberrant expression. We present a case of a twin pregnancy with complete hydatidiform mole associated with a live fetus, with magnetic resonance imaging and ultrasound for radiopathological correlation. We discuss the differential diagnosis and the utility of p57 immunohistochemistry.

Shared risk factors for COVID-19 and preeclampsia in the first trimester: An observational study.

INTRODUCTION: The association between preeclampsia and coronavirus disease 2019 (COVID-19) is under study. Previous publications have hypothesized the existence of shared risk factors for both conditions or a deficient trophoblastic invasion as possible explanations for this association. The primary aim of this study was to examine baseline risk factors measured in the first-trimester combined screening for preeclampsia in pregnant women with COVID-19 compared with the general population. A secondary aim of this study was to compare risk factors among patients with mild and severe COVID-19. MATERIAL AND METHODS: This was an observational retrospective study conducted at Vall d'Hebron Hospital Campus (Catalonia, Spain). Study patients were 231 pregnant women undergoing the first-trimester screening for preeclampsia and positive for severe acute respiratory syndrome coronavirus 2 between February 2020 and September 2021. The reference cohort were 13 033 women of the general population from six centers across Catalonia from May 2019 to June 2021. Based on the need for hospitalization, patients were classified in two groups: mild and severe COVID-19. First-trimester screening for preeclampsia included maternal history, mean arterial blood pressure, mean uterine artery pulsatility index (UtAPI), placental growth factor (PlGF), and pregnancy-associated plasma protein-A (PAPP-A). RESULTS: The proportion of cases at high risk for preeclampsia was significantly higher among the COVID-19 group compared with the general population (19.0% and 13.2%, respectively; p = 0.012). When analyzing risk factors for preeclampsia individually, women with COVID-19 had higher median body mass index (25.2 vs 24.5, p = 0.041), higher UtAPI multiple of the median (MoM) (1.08 vs 1.00, p < 0.001), higher incidence of chronic hypertension (2.8% vs 0.9%, p = 0.015), and there were fewer smokers (5.7% vs 11.6%, p = 0.007). The MoMs of PlGF and PAPP-A did not differ significantly between both groups (0.96 vs 0.97, p = 0.760 and 1.00 vs 1.01, p = 0.432; respectively). CONCLUSIONS: In patients with COVID-19, there was a higher proportion of women at high risk for preeclampsia at the first-trimester screening than in the general population, mainly because of maternal risk factors, rather than placental signs of a deficient trophoblastic invasion.

Congenital infection of SARS-CoV-2 in live-born neonates: a population-based descriptive study.

OBJECTIVE: To evaluate the evidence of mother-to-child transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: This is a descriptive, multicentre, observational study in nine tertiary care hospitals throughout Spain. The study population was women with coronavirus disease 2019 during pregnancy. Mother-to-child transmission was defined as positive real-time RT-PCR of SARS-CoV-2 in amniotic fluid, cord blood, placenta or neonatal nasopharyngeal swabs taken immediately after birth. RESULTS: We included 43 women with singleton pregnancies and one with a twin pregnancy, as a result we obtained 45 samples of placenta, amniotic fluid and umbilical cord blood. The median gestational age at diagnosis was 34.7 weeks (range 14-41.3 weeks). The median interval between positive RT-PCR and delivery was 21.5 days (range 0-141 days). Fourteen women (31.8%, 95% CI 18.6%-47.6%) were positive at the time of delivery. There was one singleton pregnancy with SARS-CoV-2 RT-PCR positive in the placenta, amniotic fluid and umbilical cord blood (2.2%, 95% CI 0.1%-11.8%). Nasopharyngeal aspiration was performed on 38 neonates at birth, all of which were negative (0%, 95% CI 0%-9.3%). In 11 neonates the nasopharyngeal aspiration was repeated at 24-48 hours, and one returned positive (9.1%, 95% CI 0.2%-41.3%). CONCLUSIONS: The presence of SARS-CoV-2 in placenta, amniotic fluid and cord blood shows that mother-to-child transmission is possible but uncommon.

Diffuse trophoblast damage is the hallmark of SARS-CoV-2-associated fetal demise.

Placental pathology in SARS-CoV-2-infected pregnancies seems rather unspecific. However, the identification of the placental lesions due to SARS-CoV-2 infection would be a significant advance in order to improve the management of these pregnancies and to identify the mechanisms involved in a possible vertical transmission. The pathological findings in placentas delivered from 198 SARS-CoV-2-positive pregnant women were investigated for the presence of lesions associated with placental SARS-CoV-2 infection. SARS-CoV-2 infection was investigated in placental tissues through immunohistochemistry, and positive cases were further confirmed by in situ hybridization. SARS-CoV-2 infection was also investigated by RT-PCR in 33 cases, including all the immunohistochemically positive cases. Nine cases were SARS-CoV-2-positive by immunohistochemistry, in situ hybridization, and RT-PCR. These placentas showed lesions characterized by villous trophoblast necrosis with intervillous space collapse and variable amounts of mixed intervillous inflammatory infiltrate and perivillous fibrinoid deposition. Such lesions ranged from focal to massively widespread in five cases, resulting in intrauterine fetal death. Two of the stillborn fetuses showed some evidence of SARS-CoV-2 positivity. The remaining 189 placentas did not show similar lesions. The strong association between trophoblastic damage and placenta SARS-CoV-2 infection suggests that this lesion is a specific marker of SARS-CoV-2 infection in placenta. Diffuse trophoblastic damage, massively affecting chorionic villous tissue, can result in fetal death associated with COVID-19 disease.

Gestation and COVID-19: clinical and microbiological observational study (Gesta-COVID19).

BACKGROUND: The Coronavirus Disease 2019 (COVID-19) is a novel disease which has been having a worldwide affect since December 2019. Evidence regarding the effects of SARS-CoV-2 during pregnancy is conflicting. The presence of SARS-CoV-2 has been demonstrated in biological samples during pregnancy (placenta, umbilical cord or amniotic fluid); however, maternal and fetal effects of the virus are not well known. METHODS: Descriptive, multicentre, longitudinal, observational study in eight tertiary care hospitals throughout Spain, that are referral centres for pregnant women with COVID-19. All pregnant women with positive SARS-CoV-2 real-time reverse transcriptase polymerase chain reaction during their pregnancy or 14 days preconception and newborns born to mothers infected with SARS-CoV-2 will be included. They will continue to be followed up until 4 weeks after delivery. The aim of the study is to investigate both the effect of COVID-19 on the pregnancy, and the effect of the pregnancy status with the evolution of the SARS-CoV-2 disease. Other samples (faeces, urine, serum, amniotic fluid, cord and peripheral blood, placenta and breastmilk) will be collected in order to analyse whether or not there is a risk of vertical transmission and to describe the behaviour of the virus in other fluids. Neonates will be followed until 6 months after delivery to establish the rate of neonatal transmission. We aim to include 150 pregnant women and their babies. Ethics approval will be obtained from all the participating centres. DISCUSSION: There is little information known about COVID-19 and its unknown effects on pregnancy. This study will collect a large number of samples in pregnant women which will allow us to demonstrate the behaviour of the virus in pregnancy and postpartum in a representative cohort of the Spanish population.

Prediction of preterm birth and adverse perinatal outcomes after cervical pessary placement in singleton pregnancies with short cervical length.

OBJECTIVES: To identify ultrasound-assessed cervical characteristics, modified after pessary placement, which could be predictive of spontaneous preterm birth (sPTB) at < 34 weeks of gestation (WG) or severe adverse perinatal outcomes (APO). STUDY DESIGN: This prospective observational study conducted at Vall d'Hebron Universitary Hospital assessed multiple cervical characteristics in women with short cervical length (CL). All participants were examined by transvaginal ultrasound before and immediately after a cervical pessary was placed. Cervical assessment included CL, uterocervical angles (UCA), and cervical consistency indexes (cervical consistency index (CCI) and cervical length consistency index (CLCI)). Pregnancy outcomes were recorded to determine the capacity of these variables for predicting sPTB at < 34 WG and severe APO. RESULTS: Thirty-one women with short CL, 17 (54.8%) with asymptomatic midtrimester short CL, and 14 (45.2%) after arrested threatened preterm labor were enrolled. After pessary placement, transvaginal ultrasound detected four participants in whom the pessary was not correctly placed around the cervix (12.9%); additionally, significant changes were observed in most cervical baseline characteristics, with CL, anterior UCA (A-UCA), CLCI, and intersegmentary angle (ISA) being predictive of sPTB at <34 WG and severe APO. Receiver operator curves were calculated to compare the predictive capacity of these variables, with CL and A-UCA after pessary placement being the best predictive parameters with an area under the curve of 0.88 and 0.87, respectively. CONCLUSIONS: Transvaginal ultrasound after pessary placement detects incorrect pessary placement after pessary insertion and during follow-up. APO and sPTB can be predicted by measuring CL, A-UCA, CLCI, and ISA immediately after pessary placement, being CL and A-UCA more accurate and easier to be measured. Our results help to better identify women in whom the pessary is more likely to fail. Further research is required to assess the effectiveness of applying alternative, sequential or additional treatments to reduce prematurity and our results could be considered when designing such studies.

Impact of simulation-based teamwork training on COVID-19 distress in healthcare professionals.

CONTEXT: Non-technical skills such as leadership, communication, or situation awareness should lead to effective teamwork in a crisis. This study aimed to analyse the role of these skills in the emotional response of health professionals to the COVID-19 pandemic. METHODS: Before the COVID-19 outbreak, 48 doctors and 48 nurses participated in a simulation-based teamwork training program based on teaching non-technical skills through simulation. In May 2020, this group of professionals from a COVID-19 referral hospital was invited to participate in a survey exploring stress, anxiety, and depression, using the PSS-14 (Perceived Stress Scale) and the HADS (Hospital Anxiety and Depression Scale) measures. A control group that did not receive the training was included. We conducted a logistic regression to assess whether having attended a simulation-based teamwork training program modified the probability of presenting psychological distress (PSS-14 > 18 or HADS> 12). RESULTS: A total of 141 healthcare professionals were included, 77 in the intervention group and 64 in the control group. Based on the PSS-14, 70.1% of the intervention group and 75% of the control group (p = 0.342) had symptoms of stress. Having contact with COVID-19 patients [OR 4.16(1.64-10.52)]; having minors in charge [OR 2.75 (1.15-6.53)]; working as a doctor [0.39(0.16-0.95)], and being a woman [OR 2.94(1.09-7.91)] were related with PSS14 symptoms. Based on the HADS, 54.6% of the intervention group and 42.2% of the control group (p = 0.346) had symptoms of anxiety or depression. Having contact with COVID-19 patients [OR 2.17(1.05-4.48)] and having minors in charge [OR 2.14(1.06-4.32)] were related to HADS symptoms. Healthcare professionals who attended COVID-19 patients showed higher levels of anxiety and depression [OR 2.56(1.03-6.36) (p = 0.043)]. CONCLUSION: Healthcare professionals trained in non-technical skills through simulation tended towards higher levels of anxiety and depression and fewer levels of stress, during the COVID-19 pandemic.

Fetal Transient Skin Edema in Two Pregnant Women With Coronavirus Disease 2019 (COVID-19).

BACKGROUND: The risk of vertical transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains unknown. Positive reverse-transcription polymerase chain reaction (RT-PCR) test results for SARS-CoV-2 infection in neonates and placental tissue have been reported, and immunoglobulin M antibodies have been detected in neonates born to mothers with infection. CASES: The first case is a woman at 22 3/7 weeks of gestation with coronavirus disease 2019 (COVID-19) who was admitted to the intensive care unit. In the second case, the patient remained at home with mild symptoms, starting at 20 weeks of gestation. In both cases, fetal skin edema was observed on ultrasound examination while maternal SARS-COV-2 RT-PCR test results were positive and resolved when maternal SARS-COV-2 RT-PCR test results became negative. The RT-PCR test result for SARS-CoV-2 in amniotic fluid was negative in both cases. The two pregnancies are ongoing and uneventful. CONCLUSION: Transient fetal skin edema noted in these two patients with COVID-19 in the second trimester may represent results of fetal infection or altered fetal physiology due to maternal disease or may be unrelated to the maternal illness.