Sonographic Cortical Development and Anomalies in the Fetus: A Systematic Review and Meta-Analysis.

The aim of this systematic review is to report the normal cortical development of different fetal cerebral fissures on ultrasound, describe associated anomalies in fetuses with cortical malformations, and evaluate the quality of published charts of cortical fissures. The inclusion criteria were studies reporting development, anomalies, and reference charts of fetal cortical structures on ultrasound. The outcomes observed were the timing of the appearance of different cortical fissures according to different gestational age windows, associated central nervous system (CNS) and extra-CNS anomalies detected at ultrasound in fetuses with cortical malformation, and rate of fetuses with isolated anomaly. Furthermore, we performed a critical evaluation of the published reference charts for cortical development on ultrasound. Random-effect meta-analyses of proportions were used to combine the data. Twenty-seven studies (6875 fetuses) were included. Sylvian fissure was visualized on ultrasound in 97.69% (95% CI 92.0-100) of cases at 18-19, 98.17% (95% CI 94.8-99.8) at 20-21, 98.94% (95% CI 97.0-99.9) at 22-23, and in all cases from 24 weeks of gestation. Parieto-occipital fissure was visualized in 81.56% (95% CI 48.4-99.3) of cases at 18-19, 96.59% (95% CI 83.2-99.8) at 20-21, 96.85% (95% CI 88.8-100) at 22-23, and in all cases from 24 weeks of gestation, while the corresponding figures for calcarine fissure were 37.27% (95% CI 0.5-89.6), 80.42% (95% CI 50.2-98.2), 89.18% (95% CI 74.0-98.2), and 96.02% (95% CI 96.9-100). Malformations of cortical development were diagnosed as an isolated finding at ultrasound in 6.21% (95% CI 2.9-10.9) of cases, while they were associated with additional CNS anomalies in 93.79% (95% CI 89.1-97.2) of cases. These findings highlight the need for large studies specifically looking at the timing of the appearance of the different brain sulci. Standardized algorithms for prenatal assessment of fetuses at high risk of malformations of cortical development are also warranted.

Adherence to physical activity among pregnant women in Southern Italy: results of a cross-sectional survey.

PROBLEM: Knowledge about physical activity in pregnancy is limited compared to general population and several approaches have been used to evaluate duration and intensity of physical activity during pregnancy. BACKGROUND: Although physical activity can contribute to maternal and fetal well-being, more than half of women stopped their physical activity because of pregnancy. AIM: To evaluate the adherence to physical activity of low-risk pregnant women by adapting an Italian version of the PPAQ. METHODS: PPAQ was administered to women with singleton uneventful pregnancies between May and December 2022. The intensity of physical activity was calculated using activity's metabolic equivalent (MET). FINDINGS: Respondents spent 8.5 hours/week during the third trimester in all the types of activities included in the questionnaire, and the majority of METs were spent in household/caregiving activities (91.7 METs-h/week). Only 2,6 % of women reported they spent at least 150 minutes per week in moderate-intensity sport/exercise activity. One-hundred-forty-one women (37.2 %) reported they have been counselled by a midwife or an obstetrician regarding the importance of physical activity in pregnancy and 164 participants (43.3 %) declared that have been advised in favour of bed rest at least once in the current pregnancy. DISCUSSION: Our results showed that a very small percentage was regularly involved in sport/exercise activities. CONCLUSION: The engagement in physical activity of pregnant women during the third trimester is still very low and specific policies to improve exercise in pregnancy should be warrantied.

Controlled ovarian stimulation leads to cardiovascular changes in patients undergoing in vitro fertilization.

OBJECTIVE: To study hemodynamic changes along controlled ovarian stimulation in women undergoing in vitro fertilization. STUDY DESIGN: Prospective observational cohort study conducted at Mother and Child Department of University Hospital Federico II, in Naples, Italy, between April 2021 and July 2022. Sixty-eight infertile patients undergoing controlled ovarian stimulation with gonadotropin, antagonist protocol and a fresh embryo transfer were included. Haemodynamic assessment was carried out using UltraSonic Cardiac Output Monitor at baseline (T1), estradiol peak (T2), fresh embryo-transfer day (T3). To evaluate relationships between quantitative variables and groups a Student T test for independent data was assessed. One-way analysis of variance (ANOVA) was used to determine the differences between the means of three time points (T1, T2 and T3) for quantitative variables. A mixed-model analysis of variance (ANOVA) was used to determine the differences between groups, among time points (T1, T2 and T3). RESULTS: Sixty-eight patients were included. Significant differences over the three time points have been observed for CO (f = 3.78 l/min; p = 0.025), SVI (f = 3.56 ml/m2;p = 0.013), and RSVI (f = 4.84 dscm-5 m2; p = 0.009). No significant differences in trends have been found between beta hCG positive and beta hCG negative groups. There were no significant differences in maternal hemodynamic parameters at time-point T3 between patients treated with hCG 10,000 UI and with Triptorelin. Patients considered at increased risk of hyperstimulation reported a significant increase in SVI at baseline (26.9 ± 9.0 mL/m2 vs 21.9 ± 7.0 mL/m2; p = 0.010). CONCLUSION: According to the results of our study, during controlled ovarian stimulation with antagonist protocol, patients undergo significant changes in maternal cardiovascular parameters over a very short period.

Unveiling therapeutic potentials and exploring maternal-fetal health benefits of metformin in pregnancy: A scoping review.

This scoping review synthesizes evidence on metformin's use during pregnancy, encompassing diverse conditions like gestational diabetes, type 1 and type 2 diabetes, polycystic ovary syndrome (PCOS), and obesity. Metformin demonstrates comparable efficacy to insulin in gestational diabetes, positive outcomes in type 2 diabetes pregnancies, and potential benefits in reducing complications. The review highlights nuances in its effects across conditions, indicating advantages such as reduced risk of macrosomia and cesarean section in gestational diabetes. However, its prophylactic role in preventing gestational diabetes and associated complications remains inconclusive. In obese pregnant women, mixed results are observed, with potential benefits in reducing pre-eclampsia risk. Metformin shows promise in preventing preterm birth and late miscarriage in PCOS pregnancies. Categorizing patient subgroups is crucial for identifying advantages, especially in gestational diabetes and type 2 diabetes. Challenges arise from study heterogeneity, necessitating standardized indications for dosage, timing, and postpartum follow ups. Efforts to identify patient characteristics influencing metformin efficacy are crucial for tailored therapy. Although metformin emerges as a viable option in complicated pregnancies, comprehensive research, standardized protocols, and subgroup identification efforts will enhance clinical utility, ensuring evidence-based therapies and optimal maternal and fetal outcomes. Bridging existing knowledge gaps remains imperative for advancing metformin's role in pregnancy management.

Maternal Reassurance, Satisfaction, and Anxiety after First-Trimester Screening for Aneuploidies: Comparison between Contingent Screening and Universal Cell-Free DNA Testing.

BACKGROUND: This study aims to evaluate maternal reassurance, satisfaction, and anxiety after two different strategies for the first-trimester screening for aneuploidies. METHODS: Patients between 11 + 3 and 13 + 6 weeks of gestation attending the first-trimester screening at Department of Mother and Child, University Hospital Federico II, Naples, Italy have been recruited and randomly allocated to contingent screening or universal cell-free fetal DNA testing (cffDNA). Questionnaires to measure reassurance, satisfaction, and anxiety have been filled twice: (Q1) after randomization and (Q2) after receiving results. Anxiety was measured by an Italian-version short form of the state scale of the Spielberger State-Trait Anxiety Inventory (STAI); child-related anxiety was measured by the 11-item Pregnancy-Related Anxiety Questionnaire-Revised Regardless of Parity (PRAQ-R2 scale); fear of bearing a physically or mentally handicapped child was measured considering only four items (item 4, 9, 10, and 11) of the PRAQ-R2 scale. RESULTS: 431 patients were recruited: 205 (49%) were randomized in the contingent screening arm, 226 (51%) in the cfDNA arm. Maternal reassurance, satisfaction, and anxiety were not different in the two groups. CONCLUSION: A contingent screening for aneuploidies in the first trimester seems able to ensure the same maternal reassurance and satisfaction as a cfDNA analysis in the low-risk population and to not affect maternal anxiety.

Randomized trial of screening for preterm birth in low-risk women - the preterm birth screening study.

BACKGROUND: Preterm birth is a major cause of perinatal morbidity and mortality. It is unclear whether the introduction of a universal transvaginal ultrasound cervical length screening program in women at low risk for preterm delivery is associated with a reduction in the frequency of preterm birth. OBJECTIVE: To test the hypothesis that the introduction of a midtrimester universal transvaginal ultrasound cervical length screening program in asymptomatic singleton pregnancies without prior preterm delivery would reduce the rate of preterm birth at <37 weeks of gestation. STUDY DESIGN: This study was a multicenter nonblinded randomized trial of screening of asymptomatic singleton pregnancies without prior spontaneous preterm birth, who were randomized to either cervical length screening program (ie, intervention group) or no screening (ie, control group). Participants were randomized at the time of their routine anatomy scan between 18 0/7 and 23 6/7 weeks of gestation. Women randomized in the screening group received cervical length measurement. Those who were found to have cervical length ≤25 mm were offered 200 mg vaginal progesterone daily along with cervical pessary. The primary outcome was preterm birth at <37 weeks. The risk of primary outcome was quantified by the relative risk with 95% confidence interval, and was based on the intention-to-screen principle. RESULTS: A total of 1334 asymptomatic women with singleton pregnancies and without prior preterm birth, were included in the trial. Out of the 675 women randomized in the transvaginal ultrasound cervical length screening group, 13 (1.9%) were found to have transvaginal ultrasound cervical length ≤25 mm during the screening. Preterm birth at <37 weeks of gestation occurred in 48 women in the transvaginal ultrasound cervical length screening group (7.5%), and 54 women in the control group (8.7%) (relative risk, 0.86; 95% confidence interval, 0.59-1.25). Women randomized in the transvaginal ultrasound cervical length screening group had no significant differences in the incidence of preterm birth at less than 34, 32, 30, 28, and 24 weeks of gestation. CONCLUSION: The introduction of a universal transvaginal ultrasound cervical length screening program at 18 0/6 to 23 6/7 weeks of gestation in singleton pregnancies without prior spontaneous preterm birth, with treatment for those with cervical length ≤25 mm, did not result in significant lower incidence of preterm delivery than the incidence without the screening program.

Impact of the COVID-19 Pandemic on Prenatal Care Utilization Among Italian and Immigrant Pregnant Women: A Multicenter Survey.

Objectives: To compare the utilization of prenatal services between immigrant and Italian women during the COVID-19 pandemic. Methods: A cross-sectional survey was conducted at 3 maternity care centers in Italy. Results: We included 1,312 women, 1,198 (91.3%) were Italian and 114 (8.7%) were immigrants. A significantly higher proportion of Italians underwent 8 or more prenatal care visits (64.4% vs. 54.4%, p = 0.03) and more immigrants than Italians attended their appointments at hospital settings (45% vs. 18%, p < 0.001). Regarding prenatal course, Italians were more likely than immigrants to attend a non-hospital setting or an online class (49.6% and 30.2% vs. 34.9% and 11.6%, p = 0.008). A higher influenza vaccine uptake among immigrants compared with Italians was observed (39.5% vs. 19.8%, p < 0.001). Among women not receiving certain prenatal services, immigrants were more likely to state COVID-19 pandemic was the main reason for non-compliance. Conclusion: Immigrant pregnant women were more likely to receive prenatal services at a hospital setting than their Italian counterparts. Among women who did not comply with prenatal services, immigrants were more likely to cite the pandemic as their main reason.

Semaphorin 3A Increases in the Plasma of Women with Diminished Ovarian Reserve Who Respond Better to Controlled Ovarian Stimulation.

Semaphorin 3A (SEMA3A) plays a crucial role in the development, differentiation, and plasticity of specific types of neurons that secrete Gonadotropin-Releasing Hormone (GnRH) and regulates the acquisition and maintenance of reproductive competence in humans and mice. Its insufficient expression has been linked to reproductive disorders in humans, which are characterized by reduced or failed sexual competence. Various mutations, polymorphisms, and alternatively spliced variants of SEMA3A have been associated with infertility. One of the common causes of infertility in women of reproductive age is diminished ovarian reserve (DOR), characterized by a reduced ovarian follicular pool. Despite its clinical significance, there are no universally accepted diagnostic criteria or therapeutic interventions for DOR. In this study, we analyzed the SEMA3A plasma levels in 77 women and investigated their potential role in influencing fertility in patients with DOR. The results revealed that the SEMA3A levels were significantly higher in patients with DOR than in healthy volunteers. Furthermore, the SEMA3A levels were increased in patients who underwent fertility treatment and had positive Beta-Human Chorionic Gonadotropin (ßHCG) values (ß+) after controlled ovarian stimulation (COS) compared to those who had negative ßHCG values (ß-). These findings may serve as the basis for future investigations into the diagnosis of infertility and emphasize new possibilities for the SEMA3A-related treatment of sexual hormonal dysfunction that leads to infertility.

Brain flexibility increases during the peri-ovulatory phase as compared to early follicular phase of the menstrual cycle.

The brain operates in a flexible dynamic regime, generating complex patterns of activity (i.e. neuronal avalanches). This study aimed at describing how brain dynamics change according to menstrual cycle (MC) phases. Brain activation patterns were estimated from resting-state magnetoencephalography (MEG) scans, acquired from women at early follicular (T1), peri-ovulatory (T2) and mid-luteal (T3) phases of the MC. We investigated the functional repertoire (number of brain configurations based on fast high-amplitude bursts of the brain signals) and the region-specific influence on large-scale dynamics across the MC. Finally, we assessed the relationship between sex hormones and changes in brain dynamics. A significantly larger number of visited configurations in T2 as compared to T1 was specifically observed in the beta frequency band. No relationship between changes in brain dynamics and sex hormones was evident. Finally, we showed that the left posterior cingulate gyrus and the right insula were recruited more often in the functional repertoire during T2 as compared to T1, while the right pallidum was more often part of the functional repertoires during T1 as compared to T2. In summary, we showed hormone-independent increased flexibility of the brain dynamics during the ovulatory phase. Moreover, we demonstrated that several specific brain regions play a key role in determining this change.

Is there a lesser value type of violence? Older people abuse: "The silence of the lambs".

The World Health Organization (WHO) describes gender violence as a real global health problem with a major impact not only on the victims' physical and mental health, but also on the economics of the National Health System. Gender-based violence has been also extended to all types of subjects defined as fragile: children, elderly, women, men and disabled people. Older people abuse, more frequent in women, is a far less socially debated issue, with many forms: physical, sexual, psychological, abandonment, neglect, economic-financial, pharmaceutical, discriminatory, institutional. An electronic literature research was carried out search using the keywords "elderly abuse" on various online sources. The research showed low number of results and little attention to this topic in the scientific literature. The paper highlights how the theme of older people abuse is little reported and not adequately addressed in scientific literature and in real life, being a form of violence certainly underestimated by the public.

Exploring In Vivo Models of Musculoskeletal Frailty: A Comprehensive Systematic Review.

Musculoskeletal frailty-a common and debilitating condition linked to aging and chronic diseases-presents a major public health issue. In vivo models have become a key tool for researchers as they investigate the condition's underlying mechanisms and develop effective interventions. This systematic review examines the current body of research on in vivo models of musculoskeletal frailty, without any time constraints. To achieve this aim, we utilized three electronic databases and incorporated a total of 11 studies. Our investigation delves into varied animal models that simulate specific features of musculoskeletal frailty, including muscle loss, bone density reduction, and functional decline. Furthermore, we examine the translational prospects of these models in augmenting our comprehension of musculoskeletal frailty and streamlining the production of groundbreaking therapeutic approaches. This review provides significant insights and guidance for healthcare researchers and practitioners who aim to combat musculoskeletal frailty, ultimately enhancing the quality of life for older adults and individuals affected by this condition.

In Vitro Models of Cell Senescence: A Systematic Review on Musculoskeletal Tissues and Cells.

Ageing is an irreversible and inevitable biological process and a significant risk factor for the development of various diseases, also affecting the musculoskeletal system, resulting from the accumulation of cell senescence. The aim of this systematic review was to collect the in vitro studies conducted over the past decade in which cell senescence was induced through various methods, with the purpose of evaluating the molecular and cellular mechanisms underlying senescence and to identify treatments capable of delaying senescence. Through three electronic databases, 22 in vitro studies were identified and included in this systematic review. Disc, cartilage, or muscle cells or tissues and mesenchymal stem cells were employed to set-up in vitro models of senescence. The most common technique used to induce cell senescence was the addition to the culture medium of tumor necrosis factor (TNF)α and/or interleukin (IL)1ß, followed by irradiation, compression, hydrogen peroxide (H2O2), microgravity, in vitro expansion up to passage 10, and cells harvested from damaged areas of explants. Few studies evaluated possible treatments to anti-senescence effects. The included studies used in vitro models of senescence in musculoskeletal tissues, providing powerful tools to evaluate age-related changes and pathologies, also contributing to the development of new therapeutic approaches.

A Reverse Shoulder Arthroplasty Implantation With Custom-Made Humerus and Intraoperative GPS Navigation in a Rare Case of Unilateral Hip and Shoulder Dysplasia Associated With a Bone Marrow Mosaic PTEN Truncating Variant: Case Report.

Joint dysplasias always represent a great challenge for prosthetic surgeons. The common altered anatomical landmarks and the subversion of the anatomy of soft tissues surrounding the dysplastic joint are problems that can cause difficulties if approached with standard methods. Together with the resolution of functional issues related to dysplasia, the understanding of the underlying cause is fundamental. DNA analysis is generally performed via blood sampling; however, this might lead to misdiagnosis in case mosaicism is not detected in blood components. The etiology of genetic diseases can be further examined by means of whole exome sequencing and the detection of somatic mosaicism, recognized as a fundamental contributor to genetic diseases themselves. In this study, the clinical case of a patient suffering from a rare unilateral dysplasia localized to the left coxo-femoral and glenohumeral joint and treated at our center for reverse shoulder arthroplasty is reported. By virtue of the glenohumeral anatomical peculiarities, we had to devise a hybrid custom-made and navigated approach by means of a custom-made prosthetic stem and dedicated patient-specific instrumentation, using intraoperative GPS navigation for glenoid prosthesis. In addition, a genetic study was conducted on intraoperatively harvested bone marrow, which proved to be crucial in understanding the epigenetic basis of dysplasia. In fact, the patient resulted negative in blood but positive for a truncating variant of PTEN c.781C > T (p.(Gln261 *)) in 12% of the sequence analyzed in the bone marrow.

Prediction of placenta accreta spectrum in patients with placenta previa using a clinical, US and MRI combined model: A retrospective study with external validation.

PURPOSE: To build and validate a predictive model of placental accreta spectrum (PAS) in patients with placenta previa (PP) combining clinical risk factors (CRF) with US and MRI signs. METHOD: Our retrospective study included patients with PP from two institutions. All patients underwent US and MRI examinations for suspicion of PAS. CRF consisting of maternal age, cesarean section number, smoking and hypertension were retrieved. US and MRI signs suggestive of PAS were evaluated. Logistic regression analysis was performed to identify CRF and/or US and MRI signs associated with PAS considering histology as the reference standard. A nomogram was created using significant CRF and imaging signs at multivariate analysis, and its diagnostic accuracy was measured using the area under the binomial ROC curve (AUC), and the cut-off point was determined by Youden's J statistic. RESULTS: A total of 171 patients were enrolled from two institutions. Independent predictors of PAS included in the nomogram were: 1) smoking and number of previous CS among CRF; 2) loss of the retroplacental clear space at US; 3) intraplacental dark bands, focal interruption of the myometrial border and placental bulging at MRI. A PAS-prediction nomogram was built including these parameters and an optimal cut-off of 14.5 points was identified, showing the highest sensitivity (91%) and specificity (88%) with an AUC value of 0.95 (AUC of 0.80 in the external validation cohort). CONCLUSION: A nomogram-based model combining CRF with US and MRI signs might help to predict PAS in PP patients, with MRI contributing more than US as imaging evaluation.

Ectrodactyly-ectodermal dysplasia-clefting syndrome. Prenatal prospective ultrasound diagnosis.

OBJECTIVE: Prenatal diagnosis of the Ectrodactyly-Ectodermal dysplasia-clefting (EEC) syndrome has been based upon the detection of ectrodactyly, in association with facial clefting and/or positive family history. Our aim is to describe other ultrasonographic features indicating the presuntive diagnosis, regardless of genetic diagnosis, especially in cases of negative family history. MATERIALS AND METHODS: A case report and a review of the literature was assessed. RESULTS: Our case report showed a singleton foetus "lobster claw" deformities of hands and feet. Paternal history revealed bilateral agenesia of two fingers. Through literature, 15 case reports of prenatal diagnosis of EEC syndrome were found, 14 of which were eligible for our systematic review. The 33% of cases (5/15) had a familiar history of EEC, thus, we found one case of consanguinity of parents. Anomalies EEC-related were recognized in the 40% of cases (6/15). An association with genitourinary anomalies was found in 30% (5/15) of them. CONCLUSIONS: A strong suspicion of final diagnosis of EEC may be done in the presence of ectrodactyly, facial clefting and urinary malformation especially in cases of negative family history. More attention should be given to a genetic counseling, especially to understand a possible relation to other genetic syndromes.

Segmentation methods applied to MRI-derived radiomic analysis for the prediction of placenta accreta spectrum in patients with placenta previa.

PURPOSE: To retrospectively evaluate the performance of different manual segmentation methods of placenta MR images for predicting Placenta Accreta Spectrum (PAS) disorders in patients with placenta previa (PP) using a Machine Learning (ML) Radiomics analysis. METHODS: 64 patients (n=41 with PAS and n= 23 without PAS) with PP who underwent MRI examination for suspicion of PAS were retrospectively selected. All MRI examinations were acquired on a 1.5 T using T2-weighted (T2w) sequences on axial, sagittal and coronal planes. Ten different manual segmentation methods were performed on sagittal placental T2-weighted images obtaining five sets of 2D regions of interest (ROIs) and five sets of 3D volumes of interest (VOIs) from each patient. In detail, ROIs and VOIs were positioned on the following areas: placental tissue, retroplacental myometrium, cervix, placenta with underneath myometrium, placenta with underneath myometrium and cervix. For feature stability testing, the same process was repeated on 30 randomly selected placental MRI examinations by two additional radiologists, working independently and blinded to the original segmentation. Radiomic features were extracted from all available ROIs and VOIs. 100 iterations of 5-fold cross-validation with nested feature selection, based on recursive feature elimination, were subsequently run on each ROI/VOI to identify the best-performing method to classify instances correctly. RESULTS: Among the segmentation methods, the best performance in predicting PAS was obtained by the VOIs covering the retroplacental myometrium (Mean validation score: 0.761, standard deviation: 0.116). CONCLUSION: Our preliminary results show that the VOI including the retroplacental myometrium using T2w images seems to be the best method when segmenting images for the development of ML radiomics predictive models to identify PAS in patients with PP.

BDNF and NGF Expression in Preneoplastic Cervical Disease According to HIV Status.

BACKGROUND: Neurotrophins, such as BDNF and NGF, are overexpressed in tumor cells in cervical cancer, and HIV infection is associated with the upregulation of neurotrophin expression. Therefore, we aimed to investigate whether BDNF and NGF are overexpressed in preneoplastic cervical disease from HIV-infected women. METHODS: Women with preneoplastic cervical lesions (cervical intraepithelial neoplasia grade 2 or 3) were prospectively enrolled and grouped according to their HIV status. Samples from Loop Electrosurgical Excision Procedure (LEEP) for suspected cervical cancer were obtained, and immunohistochemistry was performed to evaluate BDNF and NGF expression. RESULTS: We included in our analysis 12 HIV-infected patients who were matched with 23 HIV-negative patients as a control group. Immunohistochemistry analysis showed that BDNF expression was significantly higher in cervical preneoplastic lesions from HIV-positive women than in the lesions from the control group. In particular, BDNF was expressed in 8/12 HIV-positive patients and 7/23 HIV-negative patients (66.7% vs. 30.4%, χ2 = 4.227; p = 0.040). NGF expression was not significantly higher in cervical preneoplastic lesions from HIV-positive women compared with that in the lesions from the control group. In particular, NGF was expressed in 8/12 HIV-positive patients and in 12/23 HIV-negative patients (66.7% vs. 52.2% χ2 = 0.676; p = 0.411). Logistic regression analysis showed that the HIV status is an independent predictor of BDNF expression in pre-invasive preneoplastic cervical disease when considered alone (crude OR 4.6, 95% CI 0.027-20.347; p = 0.046) and when analyzed with other co-factors (adjusted OR 6.786, 95% CI 1.084-42.476; p = 0.041). CONCLUSIONS: In preneoplastic cervical disease, BDNF expression is higher in HIV-infected women than in non-infected controls, and this is independent of the clinical features of the patients and from the presence of the HPV-HR genotype. BDNF can play a key role as a link between the pathways by which HIV and HPV interact to accelerate cervical cancer progression and invasion. These data can be useful to better understand the role of neurotrophins in the cancerogenesis of cervical cancer and the possible therapeutic strategies to improve disease outcomes.

Treatment with valacyclovir during pregnancy for prevention of congenital cytomegalovirus infection: a real-life multicenter Italian observational study.

BACKGROUND: Valacyclovir is the only treatment demonstrated to be effective for the prevention of vertical transmission of cytomegalovirus within a clinical randomized, placebo-controlled trial and has been reimbursed by the Italian National Health System since December 2020. OBJECTIVE: This study reported the results of a real-life Italian multicenter observational study on cytomegalovirus infection in pregnancy evaluating the effect of the introduction of valacyclovir in the clinical practice for the prevention of vertical transmission of cytomegalovirus. STUDY DESIGN: The outcomes of women who received valacyclovir treatment and their fetuses or newborns were compared with those of a retrospective cohort observed between 2010 and 2020 who did not receive the antiviral treatment. The inclusion criterion was the diagnosis of cytomegalovirus primary infection occurring in the periconceptional period or up to 24 weeks of gestation. The primary outcome was the transmission by the time of amniocentesis. The secondary outcomes were termination of pregnancy, transmission at birth, symptomatic infection at birth, and a composite outcome (termination of pregnancy or transmission at birth). RESULTS: A total of 447 pregnant women from 10 centers were enrolled, 205 women treated with valacyclovir (called the valacyclovir group, including 1 twin pregnancy) and 242 women not treated with valacyclovir (called the no-valacyclovir group, including 2 twin pregnancies). Valacyclovir treatment was significantly associated with a reduction of the diagnosis of congenital cytomegalovirus infection by the time of amniocentesis (weighted odds ratio, 0.39; 90% confidence interval, 0.22-0.68; P=.005; relative reduction of 61%), termination of pregnancy (weighted odds ratio, 0.36; 90% confidence interval, 0.17-0.75; P=.0021; relative reduction of 64%), symptomatic congenital cytomegalovirus infection at birth (weighted odds ratio, 0.17; 90% confidence interval, 0.06-0.49; P=.006; relative reduction of 83%). The treatment had no significant effect on the rate of diagnosis of congenital cytomegalovirus infection at birth (weighted odds ratio, 0.85; 90% confidence interval, 0.57-1.26; P=.500), but the composite outcome (termination of pregnancy or diagnosis of congenital cytomegalovirus infection at birth) occurred more frequently in the no-valacyclovir group (weighted odds ratio, 0.62; 90% confidence interval, 0.44-0.88; P=.024). Of note, the only symptomatic newborns with congenital cytomegalovirus infection in the valacyclovir group (n=3) were among those with positive amniocentesis. Moreover, 19 women (9.3%) reported an adverse reaction to valacyclovir treatment, classified as mild in 17 cases and moderate in 2 cases. Lastly, 4 women (1.9%) presented renal toxicity with a slight increase in creatinine level, which was reversible after treatment suspension. CONCLUSION: Our real-life data confirm that valacyclovir significantly reduces the rate of congenital cytomegalovirus diagnosis at the time of amniocentesis with a good tolerability profile and show that the treatment is associated with a reduction of termination of pregnancy and symptomatic congenital cytomegalovirus infection at birth.

A COVID Dilemma: How to Manage Pregnancies in Case of Severe Respiratory Failure?

To date, the impact of the COVID-19 pandemic on the world's health, economics and politics is still heavy, and efforts to mitigate virus transmission have caused remarkable disruption. From the early onset of the pandemic, generated by SARS-CoV-2 spread, the scientific community was aware of its impact on vulnerable individuals, including pregnant women. The purpose of this paper is to highlight scientific pitfalls and ethical dilemmas emerging from management of severe respiratory distress in pregnant women in order to add evidence to this topic through an ethical debate. In the here-presented paper, three cases of severe respiratory syndrome are analyzed. No specific therapeutic protocol was available to guide physicians in a cost-benefit balance, and unequivocal conduct was not a priori suggested from scientific evidence. However, vaccines' advent, viral variants lurking on the horizon and other possible pandemic challenges make it necessary to maximize the experience gained through these difficult years. Antenatal management of pregnancies complicated by COVID-19 infection with severe respiratory failure is still heterogeneous and ethical concerns must be pointed out.