Emerging biomarkers for improving pregnancy planning in multiple sclerosis.

Background: Patient disability, relapse rate, and age are used for family planning in multiple sclerosis (MS). However, the need for more accurate biomarkers is widely recognized. We aimed to explore the influence of age on neurofilament light chain (sNfL), which reflects acute inflammation; glial fibrillary acidic protein (GFAP), associated with disability progression independent of relapses; and anti-Müllerian hormone (AMH), reflecting ovarian reserve, to provide a tailored family planning strategy. Methods: This case-control study included 95 MS patients and 61 healthy control women (HCW). sNfL and GFAP levels were measured using a sensitive single-molecule array assay. AMH levels were measured by the automated Elecsys® Anti-Müllerian Hormone Assay. Results: We observed no significant differences in AMH values between MS patients and the control group within any of the age-matched categories. Age exhibited a negative correlation with AMH values in both groups, as expected. Nevertheless, our findings suggest a slight tendency toward reduced ovarian reserve in MS patients (rho MS patients = -0.67, p < 0.0001; rho HCW = -0.43, p = 0.0006). Interestingly, among the 76 MS participants under 40 years old, we identified ten individuals (13.1%) with AMH levels below 0.7 ng/ml, indicative of a low ovarian reserve, and an additional six individuals (7.8%) with AMH levels between 0.7 ng/ml and 0.9 ng/ml, suggesting a potential risk of premature ovarian failure. Conversely, sNfL and GFAP levels in the MS group exhibited high variability but showed no significant association with age intervals. Conclusion: We found no significant differences in AMH, sNfL or GFAP values between MS patients and the control group within any of the age-matched categories. The assessment of AMH, sNFL and GFAP levels at MS onset facilitates personalized therapeutic and family planning strategies for childbearing-age women.

Workshop for Basic Gynaecological Examinations: Improving Medical Student Learning through Clinical Simulation.

INTRODUCTION: This study was designed to evaluate whether the Workshop on Basic Principles for Clinical Gynaecological Exploration, offered to medical students, improves theoretical-practical knowledge, safety, confidence, global satisfaction and the achievement of the proposed objectives in the area of gynaecological clinical examinations. MATERIALS AND METHODS: This was a quasi-experimental pre-post-learning study carried out at the Gynaecology and Obstetrics department of Gregorio Marañón Hospital in Madrid (Spain). The volunteer participants were 4th-year students earning a degree in Medicine during the 2020-2021 and 2021-2022 academic years. The study period was divided into the following stages: pre-workshop, intra-workshop and 2 weeks post-workshop. In the pre-workshop stage, students completed a brief online course to prepare for the workshop. The effectiveness of the workshop was evaluated through multiple-choice tests and self-administered questionnaires to assess self-assurance, self-confidence, self-satisfaction and the achievement of the objectives. RESULTS: Of the 277 students invited in both academic years, 256 attended the workshop (92.4%), with a total participation in the different stages of the study greater than 70%. A total of 82.5% of the students in the 2020-2021 academic year and 80.6% of students in the 2021-2022 academic year did not have any type of experience performing gynaecological clinical examinations. Between the pre-workshop and 2 weeks post-workshop stages, there was significant improvement in theoretical-practical knowledge (improvement mean = 1.38 and 1.21 in 2020-2021 and 2021-2022 academic years, respectively). The security and confidence of the students prior to the workshop were low (average scores less than 5 points) in both academic years. However, post-workshop scores for satisfaction and the achievement of objectives were high in the two academic years; all the values approached or exceeded 8 points. CONCLUSIONS: Our students, after outstanding participation, evaluated the BPCGE, and improved their theoretical and practical knowledge, as well as their skills in a gynaecological clinical examination. Moreover, in their view, after the workshop, they felt very satisfied, far outreaching the proposed aims. In addition, excellent results were maintained over time, year after year.

SARS-CoV2 Infection During Pregnancy Causes Persistent Immune Abnormalities in Women Without Affecting the Newborns.

SARS-CoV2 infection in pregnancy and exposed newborns is poorly known. We performed a longitudinal analysis of immune system and determined soluble cytokine levels in pregnant women infected with SARS-CoV2 and in their newborns. Women with confirmed SARS-CoV2 infection and their exposed uninfected newborns were recruited from Hospital General Universitario Gregorio Marañón. Peripheral blood mononuclear cells (PBMCs), cord cells and plasma were collected at birth and 6 months later. Immunophenotyping of natural killer (NK), monocytes and CD4/CD8 T-cells were studied in cryopreserved PBMCs and cord cells by multiparametric flow cytometry. Up to 4 soluble pro/anti-inflammatory cytokines were assessed in plasma/cord plasma by ELISA assay. SARS-CoV2-infected mothers and their newborns were compared to matched healthy non-SARS-CoV2-infected mothers and their newborns. The TNFα and IL-10 levels of infected mothers were higher at baseline than those of healthy controls. Infected mothers showed increased NK cells activation and reduced expression of maturation markers that reverted after 6 months. They also had high levels of Central Memory and low Effector Memory CD4-T cell subsets. Additionally, the increased CD4- and CD8-T cell activation (CD154 and CD38) and exhaustion (TIM3/TIGIT) levels at baseline compared to controls remained elevated after 6 months. Regarding Treg cells, the levels were lower at infected mothers at baseline but reverted after 6 months. No newborn was infected at birth. The lower levels of monocytes, NK and CD4-T cells observed at SARS-CoV2-exposed newborns compared to unexposed controls significantly increased 6 months later. In conclusion, SARS-CoV2 infection during pregnancy shows differences in immunological components that could lead newborns to future clinical implications after birth. However, SARS-CoV2 exposed 6-months-old newborns showed no immune misbalance, whereas the infected mothers maintain increased activation and exhaustion levels in T-cells after 6 months.

Influence of the Human Development Index on the Maternal-Perinatal Morbidity and Mortality of Pregnant Women with SARS-CoV-2 Infection: Importance for Personalized Medical Care.

Coronavirus disease-19 (COVID-19) is perhaps the most worrisome pandemic in the 21st century, having entailed devastating consequences for the whole society during the last year. Different studies have displayed an existing association between pregnancy and COVID-19 severity due to the various physiological changes that occur during gestation. Recent data identified maternal country of origin as an important determinant of COVID-19 presentation in pregnant women. However, the explanation of this fact remains to be fully elucidated. Therefore, the purpose of this work is to analyze the possible relationship between Human Development Index (HDI) of maternal country of origin with the morbimortality of pregnant women and their newborns. Here, we conducted a multicentric, ambispective, observational case-control study (1:1 ratio) and compare with the HDI of each country (group 1-very high HDI, group 2-high HDI, group 3-medium HDI, and group 4-low HDI). In total, 1347 pregnant women with confirmed SARV-CoV-2 infection (cases) were enrolled, and each was paired with one control to give a total number of 2694 participants from 81 tertiary care centers. Among the women with SARS-CoV-2 infection, more cases were produced of perinatal mortality, overall maternal morbidity, COVID-19 maternal morbidity, C-sections, hypertensive maternal morbidity, and perinatal morbidity. Our results described an inverse association between HDI and maternofetal morbidity and mortality. Moreover, the countries with an HDI lower than 1 showed higher rates of patients with maternal COVID-19-related morbidity (6.0% vs. 2.4%, p < 0.001), a need for oxygen therapy (4.7% vs. 1.8%, p < 0.001), and maternal ICU admission (2.6% vs. 1.0%, p = 0.007). Compared to other risk factors such as overweight, obesity, preexisting and obstetric comorbidities, HDI emerged as an independent risk factor explaining much of the increased maternal-perinatal morbidity and mortality detected in our group of cases. Further research is needed to establish to confirm the real impact of this factor and its components on pregnancy outcomes.

Comparing Infection Profiles of Expectant Mothers with COVID-19 and Impacts on Maternal and Perinatal Outcomes between the First Two Waves of the Pandemic.

During 2020, Coronavirus Disease-19 (COVID-19) incidence fluctuated in two clear waves across the spring and autumn periods. This study was designed to compare the maternal and perinatal clinical outcomes in obstetrics patients with COVID-19 between the two waves of infection in Spain. We conducted an observational, analytical, ambispective cohort study with longitudinal follow-up of mothers with confirmed SARV-CoV-2 infection from different hospitals in our country between March-November 2020. We recruited 1295 pregnant women with SARS-CoV2 infection from 78 hospitals, 846 (65.3%) of whom were diagnosed during the first wave and 449 (34.7%) during the second wave. Our results show that patients developing COVID-19 during the first wave had more symptoms at triage, early in pregnancy with greater rates of COVID-19-related maternal morbidity; caesarean section and preterm birth in the first wave. We register two cases of maternal mortality and only during the first wave. Maternal morbidity events showed a strong link to perinatal mortality events in the first wave compared to the second wave, in which maternal morbidity was more associated with pneumonia. Likewise, maternal morbidity showed a strong correlation with perinatal morbidity events in both waves. We describe the differences between the patients' profiles and management between the two waves and related to maternal and perinatal outcomes. Differences were also observed in the management of pregnant women with COVID-19. Thus, there were fewer caesarean sections, and maternal and perinatal morbidity events were reduced in the second wave, while the impacts of respiratory symptoms and their severity, including a greater need for maternal treatment, were greater in this last period. Identifying the impact that changes in the profile as well as in the treatment have on maternal-perinatal morbidity and mortality will help improve the well-being of our patients and their newborns.

Identification and characterization of endometrial carcinoma with tumor markers HE4 and CA125 in serum and endometrial tissue samples

Objective: Diagnosis of endometrial cancer (EC) is made by biopsy sampling with pathological analysis, but it is extremely important to make an accurate diagnosis in order to plan the specific treatment. We hypothesized that human epididymis protein 4 (HE4) in endometrial tissue and in serum could be beneficial for a more precise diagnosis. Material and Methods: This prospective study compared patients with EC against non- EC, matched through several variables. The inclusion criteria were: females older than 18 years who accepted to participate; who had never undergone surgery for other oncological pathologies (ovarian, colon, cervical carcinoma or uterine sarcoma); none of them had received preoperative chemo- or radio-therapy; and no participant had any severe renal or liver pathology. All had pre-surgery blood sampling and then underwent hysterectomy. Histopathological assessment of endometrial samples was made by a pathologist who compared normal histopathological staining with HE4-antibody staining. Results: In total there were 34 cases and 35 controls recruited. There was poor correlation between tissue HE4 in patients with and without carcinoma. However, serum HE4 was significant for the diagnosis of endometrial carcinoma (median EC: 123.1 U, median NE: 64.67 U, p=0.002), although the carbohydrate antigen 125 level was not significant (p=0.208). Conclusion: The findings concerning the utility of HE4 contrast with earlier reports. However, the conclusions for serum measurements are positive and suggest that the tumor marker HE4 seems to be able to diagnose EC.

SARS-COV-2 infection in pregnant women and newborns in a Spanish cohort (GESNEO-COVID) during the first wave.

BACKGROUND: Knowledge about SARS-CoV-2 infection in pregnancy and newborns is scarce. The objective of this study is to analyse clinical and epidemiological characteristics of a cohort of women infected with SARS-CoV-2 during pregnancy and their newborns exposed to SARS-CoV-2 during gestation. METHODS: Multicentric observational study of Spanish hospitals from the GESNEO-COVD cohort, participants in RECLIP (Spanish Network of Paediatric Clinical Assays). Women with confirmed SARS-CoV-2 infection by PCR and/or serology during pregnancy, diagnosed and delivering during the period 15/03/2020-31/07/2020 were included. Epidemiological, clinical, and analytical data was collected. RESULTS: A total of 105 pregnant women with a median of 34.1 years old (IQR: 28.8-37.1) and 107 newborns were included. Globally, almost 65% of pregnant women had some COVID-19 symptoms and more than 43% were treated for SARS-COV-2. Overall, 30.8% of pregnant women had pneumonia and 5 (4.8%) women were admitted to the intensive care unit needing invasive mechanical ventilation. There was a rate of 36.2% of caesarean sections, which was associated with pneumonia during pregnancy (OR: 4.203, CI 95%: 1.473-11.995) and lower gestational age at delivery (OR: 0.724, CI 95%: 0.578-0.906). The prevalence of preterm birth was 20.6% and prematurity was associated with pneumonia during gestation (OR: 6.970, CI95%: 2.340-22.750) and having a positive SARS-CoV-2 PCR at delivery (OR: 6.520, CI95%: 1.840-31.790). All nasopharyngeal PCR in newborns were negative at birth and one positivized at 15 days of life. Two newborns died, one due to causes related to prematurity and another of unexpected sudden death during early skin-to-skin contact after delivery. CONCLUSIONS: Although vertical transmission has not been reported in this cohort, the prognosis of newborns could be worsened by SARS-CoV-2 infection during pregnancy as COVID-19 pneumonia increased the risk of caesarean section deliveries and preterm births.

The Profile of the Obstetric Patients with SARS-CoV-2 Infection According to Country of Origin of the Publication: A Systematic Review of the Literature.

SARS-CoV-2 is the novel member of coronavirus responsible for the worldwide pandemic COVID-19, affecting all types of people. In this context, established research identified pregnant women as a susceptible group of SARS-CoV-2 infection, although there is still limited data regarding the real impact of COVID-19 in this group. With that purpose, we conducted a systematic review describing the maternal-fetal results of pregnant women infected by SARS-CoV-2, in aim to analyze the profile of the obstetric patients according to the country of origin of the publication. A total of 38 articles were included in this systematic review with 2670 patients from 7 countries, with 20 works published from China (52.6%). We reported significative differences according to the median maternal age, with Spain as the country with the highest age (34.6 years); The percentage of tabaquism; proportion of symptomatic patients in the triage; type of radiological exam (China and France conduct CT scans on all their patients in comparison to the use of chest X-Ray in the rest of the countries studied); percentages of C-sections (83.9% in China; 35.9% Spain, p < 0.001); maternal mortality rate, proportion of patients who need treatments, the use of antivirals, antibiotics, and anticoagulants as well as measurements of the newborns. Perinatal results are favorable in the majority of countries, with very low rates of vertical transmission in the majority of works. The studies collected in this review showed moderate to high index of quality. The different works describe the affectation during the first wave of the pandemic, where the pregnant woman with SARS-CoV-2 infection is generally symptomatic during the third trimester of gestation along with other factors associated with worse prognosis of the disease, such as higher age, body mass index, and further comorbidities developed during pregnancy. In the obstetric patient, proportion of C-sections are elevated together with prematurity, increasing maternal perinatal morbimortality. Differences found between countries could be based on the proper profile of the patient in each region, the period of the pandemic directly affecting how it was managed, and the variations regarding in situ medical attention.

Maternal and Perinatal Outcomes in Patients with Suspected COVID-19 and Their Relationship with a Negative RT-PCR Result.

This study was designed to examine maternal-perinatal outcomes in pregnant women with suspected coronavirus disease 2019 (COVID-19) according to the result of a real-time reverse transcription polymerase chain reaction (RT-PCR) test and to investigate possible variables that could be useful for predicting a negative RT-PCR result. Participants of this retrospective cohort study were obstetrics patients with suspected COVID-19 who underwent an RT-PCR test in a tertiary hospital in Madrid, Spain. Maternal-perinatal features were analysed according to the results of this test. Clinical, radiological and analytical characteristics that could be associated with a negative result were also explored. In a final subgroup analysis, patients were included if they had pneumonia and a negative test result for the virus. Out of the 111 obstetric patients with suspected COVID-19 that were enrolled, 38.7% returned a negative result. In this RT-PCR-negative group, we recorded lower rates of pneumonia (21.4% vs. 45.6%, p = 0.009), severe or critical clinical features (4.7% vs. 11.8% and 0.0% vs. 5.9%, p = 0.02, respectively), lower lactate dehydrogenase (LDH) levels (168 UI/L vs. 224.5 UI/L, p = 0.003), a greater need for maternal treatment (60.3% vs 24.4%, p < 0.001), a reduced need for oxygen therapy (2.4% vs 28.8%, p < 0.001) and a lower rate of intensive care unit admission (0.0% vs. 3.7%, p = 0.046) than the RT-PCR-positive group. While no differences were found in other variables, the monocyte count was higher (946.2/µL vs. 518.8/µL, p = 0.022) in this group. The predictive model for a negative test result included the monocyte count, LDH level and no need for oxygen therapy. This model was able to identify 73.5% of patients with a negative RT-PCR result. Only 11% of the patients with pneumonia testing negative for the virus had IgG antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The proportion of pregnant women with suspected COVID-19 and a negative RT-PCR result was nearly 39%. In these patients, the symptoms were mild and the systemic severity of the disease was lower. The monocyte count, LDH level and no need for oxygen therapy were the factors that were more related to a negative test result in this group. These variables could be used to guide the management of patients with suspected COVID-19, mainly while waiting for RT-PCR results or in settings where this test is not available.

Risk factors associated with adverse fetal outcomes in pregnancies affected by Coronavirus disease 2019 (COVID-19): a secondary analysis of the WAPM study on COVID-19.

Objectives To evaluate the strength of association between maternal and pregnancy characteristics and the risk of adverse perinatal outcomes in pregnancies with laboratory confirmed COVID-19. Methods Secondary analysis of a multinational, cohort study on all consecutive pregnant women with laboratory-confirmed COVID-19 from February 1, 2020 to April 30, 2020 from 73 centers from 22 different countries. A confirmed case of COVID-19 was defined as a positive result on real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay of nasal and pharyngeal swab specimens. The primary outcome was a composite adverse fetal outcome, defined as the presence of either abortion (pregnancy loss before 22 weeks of gestations), stillbirth (intrauterine fetal death after 22 weeks of gestation), neonatal death (death of a live-born infant within the first 28 days of life), and perinatal death (either stillbirth or neonatal death). Logistic regression analysis was performed to evaluate parameters independently associated with the primary outcome. Logistic regression was reported as odds ratio (OR) with 95% confidence interval (CI). Results Mean gestational age at diagnosis was 30.6±9.5 weeks, with 8.0% of women being diagnosed in the first, 22.2% in the second and 69.8% in the third trimester of pregnancy. There were six miscarriage (2.3%), six intrauterine device (IUD) (2.3) and 5 (2.0%) neonatal deaths, with an overall rate of perinatal death of 4.2% (11/265), thus resulting into 17 cases experiencing and 226 not experiencing composite adverse fetal outcome. Neither stillbirths nor neonatal deaths had congenital anomalies found at antenatal or postnatal evaluation. Furthermore, none of the cases experiencing IUD had signs of impending demise at arterial or venous Doppler. Neonatal deaths were all considered as prematurity-related adverse events. Of the 250 live-born neonates, one (0.4%) was found positive at RT-PCR pharyngeal swabs performed after delivery. The mother was tested positive during the third trimester of pregnancy. The newborn was asymptomatic and had negative RT-PCR test after 14 days of life. At logistic regression analysis, gestational age at diagnosis (OR: 0.85, 95% CI 0.8-0.9 per week increase; p<0.001), birthweight (OR: 1.17, 95% CI 1.09-1.12.7 per 100 g decrease; p=0.012) and maternal ventilatory support, including either need for oxygen or CPAP (OR: 4.12, 95% CI 2.3-7.9; p=0.001) were independently associated with composite adverse fetal outcome. Conclusions Early gestational age at infection, maternal ventilatory supports and low birthweight are the main determinants of adverse perinatal outcomes in fetuses with maternal COVID-19 infection. Conversely, the risk of vertical transmission seems negligible.