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Introduction: Peripheral artery disease (PAD) is a common manifestation of atherosclerosis. Despite the effectiveness of endovascular therapy (EVT), patients with PAD often face poor prognoses. This study investigates the relationship between specific inflammatory indices and wound healing in patients with Fontaine stage 4 chronic limb-threatening ischemia (CLTI)., Methods: From June 2021 to January 2024, 168 patients with Fontaine stage 4 CLTI, totaling 185 affected extremities, who underwent successful EVT, were assessed retrospectively. Patients were categorized based on wound healing post-EVT. The Naples prognostic score (NPS), pan-immune inflammation value (PIV), systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI) were calculated. Discrimination and decision curve analyses were used to explore the link between inflammation and wound healing., Results: Wound healing was observed in 142 (76.8%) patients post-EVT. Nonhealing patients exhibited higher indices of NPS, PIV, SII, and SIRI. NPS (aOR = 0.381, 95% CI 0.215-0.675, p = 0.001), PIV (aOR = 0.997, 95% CI 0.996-0.999, p < 0.001), SII (aOR = 0.997, 95% CI 0.996-0.997, p < 0.001), and SIRI (aOR = 0.443, 95% CI 0.313-0.625, p < 0.001) were independently predictive of wound healing. SIRI (AUC = 0.840, 95% CI 0.777-0.904) demonstrated superior predictive ability compared to PIV (AUC = 0.799, 95% CI 0.722-0.876, p dif < 0.001), SII (AUC = 0.788, 95% CI 0.712-0.865, p dif < 0.001), and NPS (AUC = 0.760, 95% CI 0.681-0.838, p dif < 0.001). SIRI also showed higher net reclassification improvement over PIV (68.4%, p dif < 0.001), SII (38.5%, p dif = 0.024), and NPS (29.8%, p dif = 0.079). All inflammatory indices, especially SIRI, provided prognostic value in determining wound healing at high treatment thresholds (> 40%)., Conclusion: In patients with CLTI undergoing EVT, SIRI, SII, PIV, and NPS may help predict the potential for wound healing during in-hospital follow up, with SIRI being the strongest predictor., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Postpartum hemorrhage (PPH) remains a significant complication of pregnancy globally, with uterine atony accounting for the great majority of cases. Second-line hemostatic strategies such as uterine balloon tamponade play a crucial role in managing refractory hemorrhage. Despite its effectiveness, the phenomenon of balloon displacement poses a challenge to PPH management, often leading to treatment failure. Various techniques have been proposed to address this issue, including vaginal packing, cervical cerclage, fixation to the abdominal wall, holding the cervix with ring forceps, and suspending the balloon with cervical sutures. Each method has its advantages and limitations, influencing its suitability in different clinical scenarios. Understanding these techniques may be useful to optimize and improve the management of PPH and maternal outcomes. This review provides a comprehensive summary of these strategies, their mechanisms, and their clinical implications, aiming to guide healthcare providers in choosing the most appropriate approach for individual cases of PPH., (© 2024 International Federation of Gynecology and Obstetrics.)

The global rise in obesity presents serious concerns, particularly due to its association with pregnancy complications such as gestational diabetes, preeclampsia, cesarean delivery, and fetal macrosomia. Maternal obesity also contributes to intergenerational health risks, increasing the likelihood of long-term issues in offspring. Preconception counseling is an essential preventive measure to reduce complications; however, many women miss this opportunity due to unplanned pregnancies. This study explores the impact of pregestational body mass index (BMI) and gestational weight gain (GWG) on pregnancy outcomes, underscoring the importance of routine monitoring of these parameters. Existing studies identify both BMI and GWG as independent risk factors for adverse maternal and neonatal outcomes, with elevated BMI combined with excessive GWG posing an even greater risk. Specifically, a BMI > 30 kg/m 2 doubles the risk of complications such as gestational diabetes, hypertension, and cesarean delivery. Additionally, a review of national and international guidelines highlights a lack of consensus on managing gestational weight gain in women with obesity, particularly regarding antepartum surveillance and timing of delivery. Similarly, no specific guidelines have been established for underweight pregnant women. Additionally, few studies have thoroughly assessed the maternal and fetal risks associated with underweight during pregnancy. Despite this, numerous studies have highlighted an increased risk of preterm birth (PTB) and small-for-gestational-age (SGA) infants. This narrative review emphasizes the need for further research to develop tailored guidelines for managing pregnant women based on pregestational BMI, ultimately improving maternal and neonatal health outcomes.

Background: Up to 25-35% of women receive antibiotics (ABX) during pregnancy, but little is known about the consequences on a key mucosal interface such as the mammary gland, and on the development of the neonatal gut's microbiota and IgA. We hypothesize that prenatal ABX negatively affect the immune functionality of mammary gland, the composition of breast milk microbiota, the development of neonatal fecal microbiota and the abundance of neonatal fecal IgA., Methods: Case-control translational cohort study on women and neonates in the presence or absence (N = 41 + 41 pairs) of exposure to prenatal ABX for at least 7 consecutive days after 32 weeks of gestation., Results: We will evaluate IgA concentration in breast milk and in neonatal feces up to one year after delivery. We will also evaluate clinical parameters, neurodevelopment and the composition of the IgA-coated and uncoated fractions of breast milk and fecal microbiota by means of magnetic-activated cell sorting (MACS) coupled with shotgun metagenomics. Finally, we will measure the concentration of the chemokine CCL28 on maternal serum and breast milk, as a marker of activity of the entero-mammary pathway., Conclusions: Our results might support a data-driven evaluation of breast milk immune function in women exposed to prenatal ABX., Impact: Breast milk IgA and microbiota are critical to determine the positive effects of breastfeeding in infants. This research protocol will investigate breast milk IgA, microbiota, and the IgA + / IgA - fractions of neonatal fecal microbiota upon exposure to prenatal antibiotics. Fecal IgA and microbiota in infants exposed or not exposed to prenatal antibiotics will be analyzed up to 1 year after birth. This research will clarify the impact of prenatal antibiotics on the immune function of breast milk. This, in turn, might support the selective evaluation of breast milk IgA/microbiota in mothers exposed to prenatal antibiotics, or in donor human milk., Competing Interests: Competing interests: The authors declare no competing interests. Consent statement: Written informed consent will be obtained from enrolled women and the fathers of enrolled neonates., (© 2025. The Author(s).)

Introduction: Moderate‑to‑severe tricuspid regurgitation (TR) in the setting of acute heart failure (AHF) has been found to be associated with worse clinical outcomes. Recently, the TRI‑SCORE model was developed to predict clinical outcomes after isolated tricuspid surgery., Objectives: Our aim was to determine whether this score could aid in risk stratification of AHF patients with moderate‑to‑severe TR., Patients and Methods: A total of 233 hospitalized patients with AHF and moderate‑to‑severe TR were included. We calculated the TRI‑SCORE for each patient, including the following parameters: age at least 70 years, New York Heart Association class at least III, right‑sided HF signs, daily furosemide dose at least 125 mg, glomerular filtration rate below 30 ml/min/1.73 m2, elevated total bilirubin concentration, left ventricular ejection fraction below 60%, and moderate-to-severe right ventricular dysfunction. The primary end point was all‑cause mortality during follow‑up., Results: The median (interquartile range [IQR]) age was 74 (65-84) years, 129 patients (55.4%) were women. During median (IQR) follow‑up of 8 (2-21) months, 135 patients (57.9%) reached the primary end point. The patients with the primary end point had a higher median (IQR) TRI‑SCORE value than those without (8 [6-9] vs 6 [4-7]; P <0.001). The multivariable Cox regression analysis showed that a 1‑point increase in the TRI‑SCORE was a significant indicator of all‑cause mortality (hazard ratio, 1.25; 95% CI, 1.14-1.38; P <0.001). The Kaplan-Meier analysis showed early divergence of low (0-3), intermediate (4-5), and high (≥6) TRI‑SCORE curves (log-rank; P <0.001)., Conclusions: The AHF patients with moderate‑to‑severe TR have a poor prognosis during follow‑up. TRI‑SCORE can predict all‑cause mortality in these patients.

Gravitational Field-Flow Fractionation (GrFFF) is an elution-based method designed for the separation of particles ranging from a few micrometers up to approximately 100 μm in diameter. Separation occurs over time, with particles being fractionated based on size and other physico-chemical properties. GrFFF takes advantage of gravitational forces acting perpendicularly to a laminar flow in a thin channel. The fluid exhibits a parabolic velocity profile, with the maximum velocity at the center of the channel and zero velocity at the walls. The exit time of particles depends on their equilibrium position relative to the bottom wall. In hyperlayer mode, larger particles elute faster than smaller ones due to their higher velocities within the channel. This study investigated the effect of adding methylcellulose (MC) to the carrier fluid on the elution behavior - specifically, peak time (t peak ) and resolution (R) - of polystyrene-based (PS) microparticles with sizes of 7, 8, and 10 μm. The results demonstrated that MC not only increases the viscosity of the carrier fluid but also exerts a secondary, predominant effect that improves resolution (R), thereby enhancing the separation of particle populations. This was confirmed by comparing the use of water as the carrier fluid at two different temperatures: 14 °C (high viscosity) and 28 °C (low viscosity). While increasing viscosity by lowering temperature only led to modest reduction in elution time of the fractograms, the addition of MC had a size-dependent effect on the microparticles, significantly improving R without changing other experimental parameters. This suggests the presence of additional phenomena contributing to the improved separation. In conclusion, the addition of MC to the carrier fluid increases the resolving power of GrFFF, enabling the separation of PS microbeads with a size difference of up to 2 μm. This advancement pushes the boundaries of GrFFF and opens up potential new applications. These studies, conducted on PS microbeads, provide a preliminary basis for future work on cells, which have similar density and size. This could pave the way for improved cell separation in diagnostic applications., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Irene Cetin reports financial support was provided by Italian Ministry of Health. Debora Lattuada has patent #WO2014173997A3 issued to Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico di Milano. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Growing evidence demonstrates that maternal nutrition is crucial for the health of the mother-to-be, and early life course of the offspring. However, for most micronutrients, guidelines are inconsistent. This Delphi study aimed to investigate the level of expert consensus on maternal nutrition and micronutrient needs during preconception, pregnancy and lactation., Methods: We conducted a two-round web-based Delphi survey on various topics including general approaches to diet and supplement use, and existing guidelines. For the periods of preconception, pregnancy and lactation, questions focused on the importance and strength of evidence for supplement use with the following micronutrients for low- and high-risk populations: folic acid, choline, iodine, magnesium, calcium, iron, selenium, docosahexaenoic acid (DHA), and vitamins B1, B2, B6, B12, D and K., Results: Thirty-five experts participated in the panel, who were healthcare professionals (HCPs), researchers and joint HCP-researchers with expertise in nutrition, gynaecology and/or obstetrics. Panellists reached consensus on the importance of diet and dietary supplement use during pregnancy and agreed on the lack of clarity and consistency in current guidelines, and the need for education in these areas for HCPs, pregnant people and the general population. For general low-risk populations, there was consensus on the importance of supplement use with iron and vitamin D from preconception through lactation, with folic acid and iodine from preconception through the second and third trimesters, respectively, with DHA from the first trimester through lactation and with calcium during lactation. Panellists agreed that the evidence for supplement use with each of these micronutrients during these phases to improve outcomes and/or foetal development is strong, except for vitamin D (preconception), DHA (first trimester), and iron (both periods). There was also consensus that supplement use advice should be tailored for people following vegan/vegetarian diets, restricted diets due to food intolerances, obesity, polycystic ovary syndrome, diabetes mellitus, and previous nutrition-related pregnancy complications., Conclusion: The findings revealed robust consensus on various aspects of maternal nutrition, including the need for education, the lack of consistency in current guidelines on supplement use, the importance of supplement use across specific phases of pregnancy and the at-risk groups requiring tailored approaches., Competing Interests: Declarations. Ethics approval and consent to participate: The study was reviewed by Pearl Institutional Review Board (2023-0047, https://www.pearlirb.com/ ) and received a Category 2 exemption from full review, in accordance with the US Department of Health and Human Services and Code of Federal Regulations (CFR; 45 CFR 46.104(d)(2)). Participants gave informed consent to participate as part of the survey and could withdraw at any time. Consent for publication: Not applicable. Competing interests: IC has received payments/honoraria unrelated to the present publication from Procter & Gamble (P&G), Bayer and Italfarmaco and has participated on a data safety monitoring board/advisory board for Italfarmaco. RD has received payments/honoraria unrelated to the present publication from P&G and Metagenics and participated on a data safety monitoring board/advisory board for Pfizer and Janssen Pharmaceuticals. RO and SP have received consulting fees and payments/honoraria unrelated to the present publication from P&G. All authors received payment for participation in a steering committee meeting related to the data presented in this manuscript., (© 2024. The Author(s).)

Introduction: Worldwide, approximately 0.5-1 % of women of childbearing age are positive for anti-Ro/SSA antibodies and anti-La/SSB. The presence of these antibodies may be responsible for the appearance of Neonatal Lupus. The pathogenesis of this disease is probably mediated by the binding of these antibodies to fetal myocardiocytes. The typical manifestation is atrioventricular block (AVB), which in most cases is complete (CHB). AVB commonly develops between 16 and 26 weeks of gestation and is cause of severe heart failure. CHB appears to be irreversible, but anecdotal reports suggest that treatment of second-degree AVB can restore sinus rhythm., Objective: The aim of the study is to evaluate the reliability of home monitoraing of fetal heart rate by the use of a hand-held device, extablishing the incidence of fetal AVB in pregnant women positive for anti-Ro/SSA autoantibodies and to evaluate whether early treatment can influence the course of the disease., Methods: Anti-Ro/SAA positive pregnant women are currently recruited from 11 Italian centers in a prospective observational study. Patients are instructed to use a portable doppler between 16 and 34 weeks of gestation and to monitor the fetal heart rate (FHR) every 8 h. In case of FHR anomalies patients will contact the reference center which will guarantee an echocardiogram within 8 h and in case of anomalies, adequate treatment. All patients will undergo check-ups at 20, 26 and 32 weeks of gestation, with the collection of information on the course of the maternal disease, on the use of drugs and on instrumental monitoring progress. After birth, data will be collected on the outcome of pregnancy and the methods of delivery. Newborns will also be evaluated for the possible appearance of clinical signs of Neonatal Lupus., Results: Fetal-Hope is actually enrolling Patients from involved Centers., Conclusions: Fetal-Hope is the first European study assessing the reliability of home monitoring of fetal heart rate using a handheld device, determining the incidence of fetal atrioventricular block (AVB) in pregnant women positive for anti-Ro/SSA autoantibodies and assessing whether early intervention can alter the disease's progression., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The increasing incidence of cancer has necessitated the discovery of novel anticancer compound sources. The presence of taxanes in hazelnut cell cultures has promoted new promising pharmacotherapeutic applications. The antiproliferative properties of hazelnut (Corylus avellana cv. 'Kalınkara') cell culture extracts against different human cancer cell lines (HeLa, MCF-7, MDA-MB-231, A549) with Beas-2B as control were evaluated. The cytotoxicity of C. avellana culture extract (5 µM, 10 µM, and 20 µM) on all cell lines was evaluated with xCELLigence Real Time Cell Analysis System. Mitotic activity (450-655 nm), BrdU activity (450-550 nm) and caspase 3,7 activity (490-520 nm) were analyzed with a spectrophotometer through 24, 48, and 72 hours. Based on the values obtained from the xCELLigence Cell Analysis System, a 10 µM concentration of the culture extract was assigned as the IC50 dose. Culture extracts at 10 µM enhanced the reduction in the proliferation of all cancer cells assayed. The highest decrease in mitotic (59.32%) and BrdU (53.77%) activity was observed in A549 lung cancer cells. However, caspase 3,7 activity (35.08%) was the highest in aggressive MDA-MB-231 breast cancer cells. The culture extracts decreased the viability of A549 cells to a greater extent than that of MCF-7 and MDA-MB-231 breast, and HeLa cervical cancer cells. C. avellana cv. 'Kalınkara' cell culture extracts have potential use in the treatment of lung and, to a lesser extent, breast and cervical cancers.

A significant increase in Parvovirus B 19 (B19V) infections has been reported in the last months in some European countries. This outbreak could be highly detrimental for pregnant women, considering the capacity of the virus to harm the fetus. However, the magnitude and spread of this outbreak is yet unclear. Evidence from other areas is required and there is the need to focus more on the impact on pregnancy. To this aim, pregnant women with B19V infection who were managed in a referral hospital located in Milan, Northern Italy were reviewed. The primary aim was comparing the number of ascertained cases of B19V infection in the period January-July 2024 to the number of cases recorded in the previous 9 years (2015-2023). Overall, the number of B19V infections markedly increased in the first 7 months of 2024. Until 2023, the number of cases per year were below 7, with no cases reported in 2020-2022, while in the period January-July 2024, the number raised to 59 (p < 0.001). Maternal characteristics and fetal outcomes before and after January 2024 did not differ. In conclusion, Italy is also involved in the ongoing outbreak of B19V infection and pregnant women are exposed to this threat. Synopsis: An outbreak of Parvovirus B19 infections is currently ongoing in Italian pregnant women., (© 2024 The Author(s). Journal of Medical Virology published by Wiley Periodicals LLC.)

Background: In Italy, exclusive breastfeeding (EBF) rates at hospital discharge range unsatisfactorily between 20-97%., Methods: In 2023, the Project for Hospital Policy on Breastfeeding (HPB) has been launched to promote breastfeeding in Italian Maternity Hospitals (MHs) as a joint initiative of the Italian Scientific Societies involved in perinatal care together with the National Midwife (FNOPO) and Nurse (FNOPI) Boards and with Vivere Onlus, a family association. The HBP Project has been designed as an uncontrolled before-after study to increase EBF rate at hospital discharge in the population of healthy, term infant with a normal weight at birth following an intervention bundle comprising: 1) Establishment of a local hospital Working Group; 2) Adoption of a hospital policy; 3) Implementation of breastfeeding monitoring; 4) Training for perinatal care professionals; 5) Enhanced implementation of the practices of skin-to-skin contact (SSC) and mother-baby rooming-in; 6) Development/Improvement of perinatal care protocols., Results: We report the pre-intervention assessment of 89 out of the 111 enrolled MHs (80.2%) at the beginning of the Project (Time 1 or T1). Almost all MHs (96.6%) have a multi-professional Breastfeeding Working Group, while a hospital policy on breastfeeding is available only in 48.2%. Moreover, only 56.2% of the 9,777 perinatal health workers have been trained in breastfeeding. Over a 1-month period, SSC has been practiced in the delivery room by 76.9% of 6,304 term healthy newborn infants and rooming-in by 83.4% of 6,735 healthy term newborns of normal weight at birth. Over a 4-month period, 69.1% of 33,367 healthy term newborns of normal birth weight were exclusively breastfed at hospital discharge. Noticeably, EBF rate of MHs ranges from 4% up to 100%, the second quartile being 73%., Conclusion: At T1 of the HPB Project, breastfeeding rates at hospital discharge for healthy, term infants with a normal weight at birth appear to be suboptimal among Italians MHs. Particularly, the range of EBF rates among participating centers is wide, with 50% of the MHs having EBF rate lower than 73%. Therefore, the ongoing HPB Project might represent not only an opportunity to increase the initiation of breastfeeding and to improve quality of health care in the whole study group of MHs, but possibly also to level differences between centers., (© 2024. The Author(s).)

Periodontal disease (PD) during pregnancy may trigger systemic inflammation, increasing the risk of developing cardiometabolic disease (CMD). As a consequence, PD may result in the activation of cellular and molecular pathways, affecting the disease course and pregnancy outcome. Although microRNAs (miRNAs) are considered ideal biomarkers for many diseases, few studies have investigated salivary miRNAs and their role in pregnancy or neonatal outcomes. In this study, we sought to investigate the associations between salivary miRNAs of pregnant women with oral diseases and their effects on neonatal outcomes. Eleven (n = 11) salivary miRNAs from a cohort of pregnant women with oral diseases (n = 32; oral health, H; gingivitis, G; and periodontitis, P) were detected using a previous profiling analysis with an FDR < 0.20 and a fold change (FC) < 0.5 or FC > 2 for the most highly expressed miRNAs. Spearman correlations were performed for 11 salivary microRNAs associated with oral-derived inflammation, which could affect neonatal outcomes during pregnancies at risk for cardiometabolic disease (CMD), defined by the presence of a high pregestational BMI. In addition, ROC curves demonstrated the diagnostic accuracy of the markers used. Upregulation of miR-423-5p expression and a decrease in miR-27b-3p expression were detected in the P-group ( p < 0.05), and ROC analysis revealed the diagnostic accuracy of miR-423-5p for discriminating oral diseases, such as gingivitis versus periodontitis (P vs. G, AUC = 0.78, p < 0.05), and for discriminating it from the healthy oral cavity (P vs. H, AUC = 0.9, p < 0.01). In addition, miR-27b-3p and miR-622 were also able to discriminate the healthy group from the P-group (AUC = 0.8, p < 0.05; AUC = 0.8, p < 0.05). miR-483-5p was able to discriminate between the G-group (AUC = 0.9, p < 0.01) and the P-group (AUC = 0.8, p < 0.05). These data support the role of salivary miRNAs as early biomarkers for neonatal outcomes in pregnant women with periodontal disease at high risk for CMD and suggest that there is cross-talk between salivary miRNAs and subclinical systemic inflammation.

Pregnancies complicated by severe polyhydramnios are associated with a high rate of underlying fetal anomaly. Amnioreduction may be offered to alleviate maternal symptoms. This is a retrospective study of amnioreductions performed on singleton and twin gestations complicated by symptomatic polyhydramnios between 2010 and 2023 at our tertiary referral center. The indications, procedural techniques and pregnancy and neonatal outcomes were retrieved from an archive database and reviewed with the use of the maternal and child medical record chart, the hospital electronic clinical discharge report and telephone recalls. Our study comprised 86 pregnancies, 65 singletons and 21 twin pregnancies. Fetal anomalies were identified in 79% of cases, mainly gastrointestinal obstructive anomalies; 9.3% of cases were idiopathic. The median gestational age at first amnioreduction was 32.5 weeks, and peri-procedural complications were rare (1 case of placental abruption and 2 cases of preterm delivery). The median gestational age at delivery was 36.5 weeks, with a median prolongation of the pregnancy from the time of first drain until birth of 30 days. Preterm labor < 37 weeks occurred in 48.8% of procedures, with 26.7% of patients delivering before 34 weeks and pPROM < 36 weeks recorded in 23.2% of cases. In conclusion, amnioreduction offered to alleviate maternal symptoms is a reasonably safe procedure with a low complication rate. These pregnancies necessitate management in a tertiary referral center because of their need for a multidisciplinary approach both prenatally and postnatally.

During intrauterine life, external stimuli including maternal nutrition, lifestyle, socioeconomic conditions, anxiety, stress, and air pollution can significantly impact fetal development. The human brain structures begin to form in the early weeks of gestation and continue to grow and mature throughout pregnancy. This review aims to assess, based on the latest research, the impact of environmental factors on fetal and neonatal brain development, showing that oxidative stress and inflammation are implied as a common factor for most of the stressors. Environmental insults can induce a maternal inflammatory state and modify nutrient supply to the fetus, possibly through epigenetic mechanisms, leading to significant consequences for brain morphogenesis and neurological outcomes. These risk factors are often synergic and mutually reinforcing. Fetal growth restriction and preterm birth represent paradigms of intrauterine reduced nutrient supply and inflammation, respectively. These mechanisms can lead to an increase in free radicals and, consequently, oxidative stress, with well-known adverse effects on the offspring's neurodevelopment. Therefore, a healthy intrauterine environment is a critical factor in supporting normal fetal brain development. Hence, healthcare professionals and clinicians should implement effective interventions to prevent and reduce modifiable risk factors associated with an increased inflammatory state and decreased nutrient supply during pregnancy.

Background: Maternal cardiovascular adaptations are amplified in twin pregnancies to support the metabolic request of the feto-placental unit. Few studies have evaluated the maternal hemodynamics changes after routine use of laser surgery in the treatment of twin-twin transfusion syndrome., Objective: The aim of our study was to evaluate hemodynamic changes in monochorionic twin pregnancies complicated by twin-twin transfusion syndrome before and after treatment with fetoscopic laser surgery., Study Design: A prospective observational study from 2020 to 2022, included monochorionic twin pregnancies complicated with twin-twin transfusion syndrome undergoing laser surgery between 16 and 26 weeks of gestation. To assess placental function and perfusion, uterine artery pulsatility index, hemoglobin, hematocrit, and soluble fms-like tyrosine kinase-1/placental growth factor ratio sampling prelaser and 24 hours postlaser were measured. Echocardiography by a single cardiologist evaluated maternal hemodynamics at presurgery, 24 hours, and 1 week postlaser. Those data were crosswise compared with cardiovascular indices of uncomplicated monochorionic pregnancies recruited at the same gestational age using nonparametric tests. Moreover, we fitted random-intercept linear regression models to investigate maternal hemodynamic changes according to the amount of amniotic fluid drained during laser surgery., Results: Forty-two twin-twin transfusion syndrome pregnancies with a median gestational age of 19.1 (17.4-20.9) weeks and 15 uncomplicated monochorionic pregnancies at the same gestational age were enrolled. Overall survival rate after laser was 72% with delivery at a median gestational age of 31.5 (27-34) weeks. Significant changes in blood chemistry and placental function were observed in the twin-twin transfusion syndrome group, along with alterations in arterial pressure, heart rate, cardiac output, and ventricular strain, eventually aligning with the uncomplicated group's values by 1 week postlaser. The amount of amniodrainage, with a 1000 ml cut-off, did not significantly impact hemodynamic parameters. Lastly, we detected a percentage of laser surgery complications in agreement with international literature and we did not record any maternal procedure-related problems., Conclusion: Our analysis highlighted that maternal cardiovascular status in monochorionic twin pregnancy complicated by twin-twin transfusion syndrome was more dynamic and; 1 week after fetoscopic laser ablation of placental anastomosis completed by amniodrainage, maternal hemodynamic parameters restored to values similar to uncomplicated monochorionic twin pregnancies., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: Psychiatric disorders burden the peripartum period, often requiring psychopharmacological treatment, including antidepressants. Efficacy and tolerability of antidepressants are influenced by the physiological changes of the peripartum and individual metabolic profiles, which in turn can be modified by pregnancy. The objective of this study is to assess the relationship between antidepressants' pharmacokinetic profiles during pregnancy and individual metabolic profiles, along with the efficacy of the treatment., Methods: In total 87 outpatients with diagnoses of bipolar disorder, major depression, anxiety, obsessive-compulsive disorder and post-traumatic stress disorder who required antidepressant treatment during pregnancy were recruited. Genotyping analysis of hepatic cytochrome P450 (CYPs) individual isoforms was performed. Antidepressants' blood concentrations and psychometric assessments were collected at five time points. Antidepressants' cord blood concentrations were assessed at birth., Results: Sertraline showed greater stability in plasma concentrations and a lower placental penetrance index. Most of the antidepressants' concentrations below the therapeutic range were found in women with an extensive/ultrarapid metabolic profile. Antidepressants mainly metabolized by CYP2C19 were less frequently below the therapeutic range compared with antidepressants metabolized by CYP2D6., Conclusions: Pregnancy modulates cytochrome activity and drugs' pharmacokinetics. Genotyping analysis of CYPs isoforms and therapeutic drug monitoring might be used to guide clinicians in a well-tolerated treatment of psychiatric symptoms in pregnant women., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

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., Competing Interests: The authors declare that they do not have any conflicts of interest., (Copyright © 2024 Vilca, Sarno, Passoni, Antonazzo, Pellegrini, Guida, Cesari and Cetin.)

Introduction: The study of the macroscopic appearance of the placenta may represent a useful tool to understand the pathophysiology of adverse pregnancy outcomes. The aim of this study was to evaluate biometry and morphology of placentas in relation to maternal, neonatal and pregnancy course characteristics., Methods: Clinical and placental data (biometry and macroscopic features of chorionic disk and adnexa) from unselected consecutive singleton pregnancies were recorded at the same Institution. Placental efficiency was approximated as ratio between fetal and placental weight (FPR). The total population was grouped according to the presence of any maternal comorbidity or pregnancy complication (group 1), neonatal complications diagnosed only at birth (2) and absence of any comorbidity (3). Multi-adjusted general linear and logistic regression models were performed to analyze associations between groups and placental biometry and morphology., Results: The study population counted 1008 pregnancies: 576 (57.2 %) classified as group 1, 76 (7.5 %) as group 2 and 356 (35.3 %) uncomplicated controls (group 3). In multivariate models adjusted for confounding factors, no significant differences in placental biometry and macroscopic features were observed among the three groups. Maternal BMI was significantly associated with higher placental and birth weight and lower FPR; moreover FPR was significantly higher in pregnancies carrying males compared to female neonates., Discussion: Maternal comorbidity or pregnancy disease was not associated with significant changes in placental macroscopic biometry and morphology. Conversely, maternal pregestational BMI and fetal sex impact on placental biometry and efficiency, suggesting different intrauterine adaptations in obese mothers and in male and female fetuses., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2023 Università degli Studi di Milano. Published by Elsevier Ltd.. All rights reserved.)

This clinical practice guideline on the supply of the omega-3 docosahexaenoic acid and eicosapentaenoic acid in pregnant women for risk reduction of preterm birth and early preterm birth was developed with support from several medical-scientific organizations, and is based on a review of the available strong evidence from randomized clinical trials and a formal consensus process. We concluded the following. Women of childbearing age should obtain a supply of at least 250 mg/d of docosahexaenoic+eicosapentaenoic acid from diet or supplements, and in pregnancy an additional intake of ≥100 to 200 mg/d of docosahexaenoic acid. Pregnant women with a low docosahexaenoic acid intake and/or low docosahexaenoic acid blood levels have an increased risk of preterm birth and early preterm birth. Thus, they should receive a supply of approximately 600 to 1000 mg/d of docosahexaenoic+eicosapentaenoic acid, or docosahexaenoic acid alone, given that this dosage showed significant reduction of preterm birth and early preterm birth in randomized controlled trials. This additional supply should preferably begin in the second trimester of pregnancy (not later than approximately 20 weeks' gestation) and continue until approximately 37 weeks' gestation or until childbirth if before 37 weeks' gestation. Identification of women with inadequate omega-3 supply is achievable by a set of standardized questions on intake. Docosahexaenoic acid measurement from blood is another option to identify women with low status, but further standardization of laboratory methods and appropriate cutoff values is needed. Information on how to achieve an appropriate intake of docosahexaenoic acid or docosahexaenoic+eicosapentaenoic acid for women of childbearing age and pregnant women should be provided to women and their partners., (Copyright © 2023. Published by Elsevier Inc.)

Maternal nutritional status represents a pivotal predictor of pregnancy outcome. This prospective observational study investigates the associations between maternal characteristics and nutritional habits at term, hemodynamic parameters, and pregnancy outcomes. Healthy women with singleton uncomplicated pregnancies were enrolled at 36-41 gestational weeks. At enrollment, a nutritional score (0-10) was calculated in order to quantify maternal adherence to a healthy diet and lifestyle. Maternal hemodynamic parameters were assessed by using the Ultrasonic Cardiac Output Monitor (USCOM), including cardiac output (CO), systemic vascular resistance (SVR) and Smith-Madigan inotropy index (SMII). Pregnancy outcomes were recorded at delivery. Associations between maternal characteristics and nutritional score, hemodynamic parameters, and pregnancy outcomes were investigated by using multi-adjusted generalized linear models. In total, 143 pregnancies were enrolled. Pregestational body mass index (BMI) was positively associated with SVR, and negatively associated with CO and SMII. Additionally, a positive association was detected between the nutritional score and SMII. Finally, CO was positively associated with birth and placental weight, while RVS showed a negative association with birth and placental weight. This study shows that maternal derangements in nutritional status and habits are associated with a compromised hemodynamic profile at term, with additional impacts on intrauterine growth.

Soft tissue sarcomas accounts for 1-2% of adult malignancies. Undifferentiated pleomorphic sarcoma (UPS) is a rare subtype that lack immunohistochemical markers for a specific definition. About 18% of sarcomas are at a locally advanced stage, often requiring several cycles of chemotherapy and radiotherapy, in addition to surgery. For a young woman, this can mean delaying pregnancies with a high risk of therapy-induced ovarian damage. For this reason, proper counseling on fertility preservation plays a key role. In addition, all women of childbearing age with cancer, should be informed about the importance of planning a pregnancy to improve maternal and neonatal outcomes. We report a rare case of a 40-year-old woman with a UPS who, during CT scan after chemotherapy to decide on surgery, find out she was pregnant. After counseling, the patient decides to go ahead with the pregnancy., Competing Interests: None., (© 2023 The Authors.)

There is currently no worldwide agreement on the real need to administer conjunctival antibiotics to neonates at birth to prevent neonatal conjunctivitis (usually defined as ophthalmia neonatorum) by Chlamydia trachomatis and Neisseria gonorrhoeae . Therefore, there is wide variability in antibiotic administration, conditioned mainly by the social and health context. In Italy, a law enacted in 1940 required doctors and midwives to administer ophthalmic prophylaxis with 2% silver nitrate to all newborns at birth. This law was repealed in 1975 and since then there has been no clear guidance on the use of ophthalmia neonatorum prophylaxis at birth. Since neonatal conjunctivitis caused by C. trachomatis and N. gonorrhoeae is not reported, we carried out a nationwide survey of 1,041,384 neonates across all Italian birth centers to evaluate the incidence of ophthalmia neonatorum and the current practice of prophylaxis. After analyzing the results, we formulated an intersociety position statement on the prevention of ophthalmia neonatorum to update and standardize this prevention strategy in Italy.

Unilateral non-hemorrhagic adrenal infarction (NHAI) is a very uncommon cause of acute abdomen in pregnancy. Diagnosis is highly challenging due to its rarity, heterogeneity of clinical presentation, and inconclusiveness of the initial workup. Timely recognition is pivotal to ensuring optimal outcomes. Here we describe a case of spontaneous unilateral NHAI diagnosed in a singleton pregnant woman at 32 weeks' gestation at our centre and provide the findings of an extensive literature review on the topic. We identified 22 articles describing 31 NHAI cases in 30 obstetric patients: NHAI occurs more frequently on the right side and in the third trimester, and diagnosis is formulated more than 24 h after clinical presentation in 50% of cases; second-level imaging is always necessary to reach a definitive diagnosis and start appropriate treatment. A high degree of clinical suspicion is needed to promptly recognize NHAI in pregnancy, thus allowing appropriate multidisciplinary management and timely treatment initiation. Promotion of knowledge and awareness of NHAI as a potential cause of acute abdomen in pregnancy is mandatory to improve clinical practice and, ultimately, perinatal outcomes.

Objectives: Nausea and vomiting in pregnancy is a common and invalidating condition in early pregnancy. However, no data are available on its prevalence in Italy. This survey aims to evaluate the prevalence and impact of nausea and vomiting during pregnancy on the quality of life of Italian women., Study Design: The survey was performed in three Italian public University Hospitals in two distinct periods: a first interview took place between the 18th and 22nd week of pregnancy, using the Questionnaire for Pregnancy Period (14 questions regarding demographic data and 30 questions about nausea and vomiting in pregnancy, including Pregnancy-Unique Quantification of Emesis questionnaire), and a follow-up interview, by telephone call, took place immediately after giving birth and in any case within 14 days of delivery, using the Questionnaire for Post-Pregnancy (9 questions). Included women were Caucasian, in physiological pregnancy and between the 18th and 22nd week (time of morphological ultrasound), able to communicate adequately with the interviewer, understand the questionnaires and able to provide valid informed consent. Twin pregnancies and women who recurred to medically assisted procreation were excluded. This is an interim report on data collected from 232 of the planned 600 women., Results: Mean age of the recruited subjects was 32.6 ± 4.6 years, with approximately 60% primiparous. The prevalence of nausea and vomiting in pregnancy in the sample examined was 65.5% overall (152 out of 232 subjects). Of these 152 women, 63 (41.4%) experienced only nausea, 6 (3.9%) only vomiting, and 83 (54.6%) reported both. Symptoms were reported to begin at 7.2 ± 2.7 weeks, lasted 10.2 ± 5.6 weeks, and persisted at the time of the interview in 32.2% of cases. Overall, over 50% of the women interviewed experienced a negative impact of nausea and vomiting in pregnancy on social relationships and work activity., Conclusions: A high prevalence of nausea and vomiting in pregnancy, 65.5% overall, was found in this interim analysis. These symptoms appeared capable of negatively influencing women quality of life. Screening procedures should be offered during pregnancy and measures that address nausea and vomiting in pregnancy impact warranted., Competing Interests: Declaration of Competing Interest Serena Tinti, Francesca Praticò, Veronica Bonaldo, Marika Ylenia Rovetto, Marco Liberati,  Mariavittoria Locci, and Irene Cetin declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Dionisio Franco Barattini is employed at Opera CRO, the Contract Research Organization that managed the study. Elena Casolati is a medical consultant for Italfarmaco SpA. Elena Piccolo, and Roberto Piazza are employed at Italfarmaco SpA., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The relationship between proline, its association with oxidative stress, and its connection to schizophrenia is a subject that has not been sufficiently investigated., Objective: The aim of this study is to evaluate the possible effects of atypical and combined (typical and atypical) antipsychotic use on serum prolidase enzyme activity (SPEA) and serum oxidative stress parameters, and to assess the relationship between SPEA and oxidative stress in patients with schizophrenia., Methods: A total of 57 patients with schizophrenia, of which 34 were using atypical (AAPG) and 23 were using combined (typical and atypical) (CAPG) antipsychotic therapy, and 28 healthy volunteers (control group) were included in this case-control study., Results: SPEA levels of AAPG and CAPG were significantly lower than that of control group ( P  = 0.003). The oxidative stress index (OSI) value of AAPG was significantly higher than the other two groups ( P  = 0.001). SPEA (<1860 U/l) and OSI (≥0.54) could discriminate schizophrenia patients with antipsychotic therapy from control groups ( P  = 0.001 and P  = 0.007, respectively). Lower SPEA levels were associated with antipsychotic use ( P  = 0.007)., Conclusion: The SPEA values of patients with schizophrenia on antipsychotics were significantly lower compared to controls. OSI values were significantly higher in atypical antipsychotic recipients compared to those on combined antipsychotics and healthy controls., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Objectives : It is known that inflammatory processes play a role in the pathogenesis of autism spectrum disorder (ASD). It is also reported that immune activation induces the kynurenine pathway (KP), as known as the tryptophan destruction pathway. In our study, we aimed to investigate whether the serum levels of KP products and interleukin (IL)-6 activating indolamine 2-3 dioxygenase (IDO) enzyme are different in healthy developing children and children with ASD. Materials and Methods : Forty-three ASD children aged 2-9 were included in this study. Forty-two healthy developing children, similar to the patient group in terms of age and gender, were selected as the control group. Serum levels of kynurenic acid, kynurenine, quinolinic acid and IL-6 were analyzed using the ELISA method. ASD severity was evaluated with the Autism Behavior Checklist (ABC). Results : The mean age of children with ASD was 42.4 ± 20.5 months, and that of healthy controls was 48.1 ± 15.8 months. While the serum levels of kynurenic acid, kynurenine and interleukin-6 were higher in the group with ASD ( p < 0.05), there was no significant difference ( p > 0.05) in terms of the quinolinic acid level. There was no significant difference between the ABC total and subscale scores of children with ASD and biochemical parameters ( p > 0.05). Conclusions : We conclude that these biomarkers must be measured in all ASD cases. They may be important for the diagnosis of ASD.

Crimean-Congo hemorrhagic fever (CCHF) caused by CCHF virus (CCHFV) is one of the epidemic-prone diseases prioritized by the World Health Organisation as public health emergency with an urgent need for accelerated research. The trajectory of host response against CCHFV is multifarious and remains unknown. Here, we reported the temporal spectrum of pathogenesis following the CCHFV infection using genome-wide blood transcriptomics analysis followed by advanced systems biology analysis, temporal immune-pathogenic alterations, and context-specific progressive and postinfection genome-scale metabolic models (GSMM) on samples collected during the acute (T0), early convalescent (T1), and convalescent-phase (T2). The interplay between the retinoic acid-inducible gene-I-like/nucleotide-binding oligomerization domain-like receptor and tumor necrosis factor signaling governed the trajectory of antiviral immune responses. The rearrangement of intracellular metabolic fluxes toward the amino acid metabolism and metabolic shift toward oxidative phosphorylation and fatty acid oxidation during acute CCHFV infection determine the pathogenicity. The upregulation of the tricarboxylic acid cycle during CCHFV infection, compared to the noninfected healthy control and between the severity groups, indicated an increased energy demand and cellular stress. The upregulation of glycolysis and pyruvate metabolism potentiated energy generation through alternative pathways associated with the severity of the infection. The downregulation of metabolic processes at the convalescent phase identified by blood cell transcriptomics and single-cell type proteomics of five immune cells (CD4 + and CD8 + T cells, CD14 + monocytes, B cells, and NK cells) potentially leads to metabolic rewiring through the recovery due to hyperactivity during the acute phase leading to post-viral fatigue syndrome.

Background: Ophthalmia neonatorum is an acute conjunctivitis that occurs in newborns within the first month of life. The most serious infections are due to Chlamydia trachomatis and Neisseria gonorrhoeae, that may cause permanent damages. The use of ophthalmic prophylaxis varies widely around the world, according to the different health and socio-economic contexts. To date in Italy there is no a clear legislation regarding ophthalmia neonatorum prophylaxis at birth., Methods: We invited all birth centers in Italy to carry out a retrospective survey relating the last three years. We collected data regarding demographics of neonates, drugs used for ophthalmic prophylaxis and results of the screening of pregnant women for Chlamydia trachomatis and Neisseria gonorrhoeae vaginal infections., Results: Among 419 birth centers, 302 (72,1%) responded to the survey. Overall 1041384 neonates, 82,3% of those born in the three years considered, received ophthalmic prophylaxis. Only 4,585 (0,4%) of them received one of the drugs recommended by the WHO. The Centers that participated to the survey reported 12 episodes of Chlamydial conjunctivitis and no Gonococcal infection in the three years. Only 38% of the Centers performed vaginal swabs to pregnant women: 2,6% screened only for Neisseria, 9,6% only for Chlamydia and 25,8% for both germs., Conclusions: The data obtained from the survey showed a low incidence of neonatal conjunctivitis due to either Neisseria gonorrhoeae or Chlamydia trachomatis in Italy. Due to the lack of legislation regulating the prophylaxis of ophthalmia neonatorum in newborns, the Italian Society of Neonatology, the Italian Society of Obstetrics and Gynecology and the Italian Society of Perinatal Medicine have recently issued new recommendations on this topic., (© 2023. Società Italiana di Pediatria.)

Background: Vestibulodynia (VBD) is the most common form of vulvodynia. Because VBD is a pain disorder, transcutaneous electrical nerve stimulation (TENS) can be used as treatment. This study aims to evaluate the effects of two-parameter combinations (frequency and pulse duration) of TENS in reducing pain intensity and dyspareunia in VBD., Methods: A randomized, double-blind, controlled trial was conducted to study the effect of two different electrical stimulation treatment regimens on women with VBD receiving domiciliary TENS. Outcomes were the mean change from baseline at 60 and 120 days of burning/pain and dyspareunia (VAS), Vulvar Pain Functional Questionnaire (V-Q), Female Sexual Functioning Index (FSFI) and vaginal electromyography measurements., Results: A total of 78 subjects, 39 in each group, completed the trial. Patients in Groups 1 and 2 received a mean of 46.9 and 48.4 TENS sessions. By day 120, there was a 38.2% reduction in the burning/pain and a 52.1% reduction in the dyspareunia VAS scores in Group 1, as compared to 21.3% ( p = 0.003) and 23.1% in Group 2 ( p = 0.01), respectively. FSFI, V-Q, and muscle-strength measures also improved but were not statistically significant., Conclusions: Our findings showed the potential of TENS in the treatment of VBD.

Right ventricular outflow tract anomalies (RVOTAs), such as pulmonary stenosis (PS), pulmonary atresia (PA), and pulmonary insufficiency (PI), are typical cardiac anomalies in monochorionic twins, and they are complicated by twin-to-twin transfusion syndrome (TTTS). The aim of this study was to conduct a long-term postnatal cardiological evaluation of prenatal RVOTAs in monochorionic diamniotic twin pregnancies complicated by TTTS and treated with fetoscopic laser surgery (FLS) and to analyze possible prenatal predictors of congenital heart disease (CHD). Prenatal RVOTAs were retrospectively retrieved from all TTTS cases treated with FLS in our unit between 2009 and 2019. Twenty-eight prenatal cases of RVOTAs (16 PI, 10 PS, 2 PA) were observed out of 335 cases of TTTS. Four cases did not reach the postnatal period. CHD was present in 17 of the remaining 24 cases (70.8%), with 10 being severe (58.8%; 10/17); nine cases of PS required balloon valvuloplasty, and one case required biventricular non-compaction cardiomyopathy. The risk of major CHD increased with prenatal evidence of PS and decreased with the gestational age at the time of TTTS and with the prenatal normalization of blood flow across the pulmonary valve. Despite treatment with FLS, the majority of monochorionic diamniotic twin pregnancies complicated by TTTS with prenatal RVOTAs had CHD at long-term follow-up.

Objectives: The authors aimed to assess the characteristics and integration of immunization services into the prenatal care provided by maternity care units (MCUs) in Italy., Methods: A cross-sectional nationwide study using a web-based survey was conducted from June to August 2021. The study population consisted of 342 obstetricians/gynecologists (OB/GYNs), members of the Italian Society of Gynecology and Obstetrics, and heads of MCUs. The main outcome was to assess the performance of several vaccine-related services among the surveyed MCUs., Results: Overall, 112 of 342 MCUs completed the survey, for an overall response rate of 32.7%. Almost all MCUs (96.4%) provided vaccine information, but only 22% had an onsite vaccination clinic. Less than half (43.8%) offered vaccines during prenatal visits and 75% of those sites required women to set up an extra appointment for vaccination. Although 68% MCUs recorded vaccines administered, only 20% of them managed to record vaccines in their own medical records. The institutional-logistic issues were the most voted vaccination barrier (40.2%)., Conclusions: Institutional barriers and lack of certain vaccine-related services offered during prenatal care in Italian MCUs might be responsible for many missed vaccination opportunities. Embedding maternal immunization programs within the current prenatal care services might optimize vaccine coverage., (© 2023 International Federation of Gynecology and Obstetrics.)

COVID-19 infection is associated with increased risk of pregnancy complications, making vaccination during pregnancy critical for mother-neonate dyads. Few data, often with an unrepresentative sample size, are available on SARS-CoV-2 vaccine-induced humoral and cell-mediated response. Here, we evaluated anti-S antibody and interferon-gamma (IFN-γ) production elicited by SARS-CoV-2 immunization in maternal and neonatal plasma. Pregnant women ( n = 230) were prospectively enrolled and classified as unvaccinated ( n = 103) and vaccinated ( n = 127); after serological screening for previous infections, assays were performed on 126 dyads, 15 mothers and 17 newborns. Positive anti-S antibodies were found in most of the vaccinated subjects, regardless of timespan between immunization and delivery (range: 7-391 days). A total of 89 of 92 vaccinated women showed a broad response to COVID-19 immunization and highly effective placental transfer, as attested by anti-S positive rates (maternal = 96.7%, cord = 96.6%). Most of our subjects had indeterminate results in an IGRA assay, preventing a conclusive evaluation of IFN-γ production. Indeed, pregnancy-related hormonal changes may influence T-cell response with an impact on IFN-γ production. Positive pregnancy and perinatal outcomes reinforce the evidence that the anti-SARS-CoV-2 immunization is effective and well-tolerated in pregnant women and also protective for the fetus/neonate, even though it was not possible to define the related IFN-γ production and role.

During female lifetime and pregnancy, inflammation and cellular senescence are implicated in physiological processes, from ovulation and menstruation, to placental homeostasis and delivery. Several lifestyles, nutritional, and environmental insults, as well as long-lasting pregestational inflammatory diseases may lead to detrimental effects in promoting and sustaining a chronic excessive inflammatory response and inflammaging, which finally contribute to the decay of fertility and pregnancy outcome, with a negative effect on placental function, fetal development, and future health risk profile in the offspring. Maladaptation to pregnancy and obstetric disease may in turn increase maternal inflammaging in a feedback loop, speeding up aging processes and outbreak of chronic diseases. Maternal inflammaging may also impact, through transgenerational effects, on future adult health. Hence, efficacious interventions should be implemented by physicians and healthcare professionals involved in prevention activities to reduce the modifiable factors contributing to the inflammaging process in order to improve public health., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Autoimmune rheumatic diseases (ARD) can affect women and men during fertile age, therefore reproductive health is a priority issue in rheumatology. Many topics need to be considered during preconception counselling: fertility, the impact of disease-related factors on pregnancy outcomes, the influence of pregnancy on disease activity, the compatibility of medications with pregnancy and breastfeeding. Risk stratification and individualized treatment approach elaborated by a multidisciplinary team minimize the risk of adverse pregnancy outcomes (APO). Research has been focused on identifying biomarkers that can be predictive of APO. Specifically, preeclampsia and hypertensive disorders of pregnancy tend to develop more frequently in women with ARD. Placental insufficiency can lead to intrauterine growth restriction and small-for-gestational age newborns. Such APO have been shown to be associated with maternal disease activity in different ARD. Therefore, a key message to be addressed to the woman wishing for a pregnancy and to her family is that treatment with compatible drugs is the best way to ensure maternal and fetal wellbeing. An increasing number of medications have entered the management of ARD, but data about their use in pregnancy and lactation are scarce. More information is needed for most biologic drugs and their biosimilars, and for the so-called small molecules, while there is sufficient evidence to recommend the use of TNF inhibitors if needed for keeping maternal disease under control. Other issues related to the reproductive journey have emerged as "unmet needs", such as sexual dysfunction, contraception, medically assisted reproduction techniques, long-term outcome of children, and they will be addressed in this review paper. Collaborative research has been instrumental to reach current knowledge and the future will bring novel insights thanks to pregnancy registries and prospective studies that have been established in several Countries and to their joint efforts in merging data., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Deep learning (DL) methods where interpretability is intrinsically considered as part of the model are required to better understand the relationship of clinical and imaging-based attributes with DL outcomes, thus facilitating their use in the reasoning behind the medical decisions. Latent space representations built with variational autoencoders (VAE) do not ensure individual control of data attributes. Attribute-based methods enforcing attribute disentanglement have been proposed in the literature for classical computer vision tasks in benchmark data. In this paper, we propose a VAE approach, the Attri-VAE, that includes an attribute regularization term to associate clinical and medical imaging attributes with different regularized dimensions in the generated latent space, enabling a better-disentangled interpretation of the attributes. Furthermore, the generated attention maps explained the attribute encoding in the regularized latent space dimensions. Using the Attri-VAE approach we analyzed healthy and myocardial infarction patients with clinical, cardiac morphology, and radiomics attributes. The proposed model provided an excellent trade-off between reconstruction fidelity, disentanglement, and interpretability, outperforming state-of-the-art VAE approaches according to several quantitative metrics. The resulting latent space allowed the generation of realistic synthetic data in the trajectory between two distinct input samples or along a specific attribute dimension to better interpret changes between different cardiac conditions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Ltd.)

Maternal obesity (MO) is expanding worldwide, contributing to the onset of Gestational Diabetes Mellitus (GDM). MO and GDM are associated with adverse maternal and foetal outcomes, with short- and long-term complications. Growing evidence suggests that MO and GDM are characterized by epigenetic alterations contributing to the pathogenesis of metabolic diseases. In this pilot study, plasma microRNAs (miRNAs) of obese pregnant women with/without GDM were profiled at delivery. Nineteen women with spontaneous singleton pregnancies delivering by elective Caesarean section were enrolled: seven normal-weight (NW), six obese without comorbidities (OB/GDM(-)), and six obese with GDM (OB/GDM(+)). miRNA profiling with miRCURY LNA PCR Panel allowed the analysis of the 179 most expressed circulating miRNAs in humans. Data acquisition and statistics (GeneGlobe and SPSS software) and Pathway Enrichment Analysis (PEA) were performed. Data analysis highlighted patterns of significantly differentially expressed miRNAs between groups: OB/GDM(-) vs. NW: n = 4 miRNAs, OB/GDM(+) vs. NW: n = 1, and OB/GDM(+) vs. OB/GDM(-): n = 14. For each comparison, PEA revealed pathways associated with oxidative stress and inflammation, as well as with nutrients and hormones metabolism. Indeed, miRNAs analysis may help to shed light on the complex epigenetic network regulating metabolic pathways in both the mother and the foeto-placental unit. Future investigations are needed to deepen the pregnancy epigenetic landscape in MO and GDM.

Background: Human cytomegalovirus (HCMV) is the leading infectious cause of congenital disabilities. We designed a prospective study to investigate the rate, outcome, and risk factors of congenital CMV (cCMV) infection in neonates born to immune women, and the potential need and effectiveness of hygiene recommendations in this population., Methods: The study was composed of 2 sequential parts: an epidemiology (part 1) and a prevention (part 2) study. Performance of part 2 depended upon a cCMV rate >0.4%. Women enrolled in part 1 did not receive hygiene recommendations. Newborns were screened by HCMV DNA testing in saliva and cCMV was confirmed by urine testing., Results: Saliva swabs were positive for HCMV DNA in 45/9661 newborns and cCMV was confirmed in 18 cases. The rate of cCMV was .19% (95% confidence interval [CI]: .11-.29%), and 3 out of 18 infants with cCMV had symptoms of CMV at birth. Age, nationality, occupation, and contact with children were similar between mothers of infected and noninfected newborns. Twin pregnancy (odds ratio [OR]: 7.2; 95% CI: 1.7-32.2; P = .037) and maternal medical conditions (OR: 3.9; 95% CI: 1.5-10.1; P = .003) appeared associated with cCMV. Given the rate of cCMV was lower than expected, the prevention part of the study was cancelled., Conclusions: Newborns from women with preconception immunity have a low rate of cCMV, which appears to be mostly due to reactivation of the latent virus. Therefore, serological screening in childbearing age would be pivotal to identify HCMV-seropositive women, whose newborns have a low risk of cCMV., Clinical Trials Registration: www.clinicaltrials.gov (NCT03973359)., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Aims: Although adequate clinical management of patients with hypercholesterolemia without a history of known cardiovascular disease is essential for prevention, these subjects are often disregarded. Furthermore, the scientific literature on primary cardiovascular prevention is not as rich as that on secondary prevention; finally, physicians often lack adequate tools for the effective management of subjects in primary prevention and have to face some unsolved relevant issues. This document aims to discuss and review the evidence available on this topic and provide practical guidance., Data Synthesis: Available algorithms and risk charts represent the main tool for the assessment of cardiovascular risk in patients in primary prevention. The accuracy of such an estimate can be substantially improved considering the potential contribution of some additional risk factors (C-reactive protein, lipoprotein(a), family history of cardiovascular disease) and conditions (environmental pollution, sleep quality, socioeconomic status, educational level) whose impact on the cardiovascular risk has been better understood in recent years. The availability of non-invasive procedures to evaluate subclinical atherosclerosis may help to identify subjects needing an earlier intervention. Unveiling the presence of these conditions will improve cardiovascular risk estimation, granting a more appropriate intervention., Conclusions: The accurate assessment of cardiovascular risk in subjects in primary prevention with the use of algorithms and risk charts together with the evaluation of additional factors will allow physicians to approach each patient with personalized strategies, which should translate into an increased adherence to therapy and, as a consequence, a reduced cardiovascular risk., Competing Interests: Declaration of competing interest ALC reports grant(s)/support from Akcea, Amarin, Amgen, Menarini, Mylan, Sanofi, and Sanofi/Regeneron; consultant for Akcea, Amgen, Amarin, Daiichi-Sankyo, Eli Lilly, Esperion, Kowa, Ionis Pharmaceuticals, Menarini, MSD, Mylan, Novartis, Recordati, Regeneron, and Sanofi, outside the submitted work. AFGC reports scientific advice and/or speaking fees from Servier Italia, Fidia Farmaceutici, and Sharper SpA; AC reports scientific advice and/or speaking fees from Servier, DOC, Fidia, Amgen, Sanofi, Daichi Sankyo, AstraZeneca, Novartis; DP reports scientific advice with Merck Serono and Boehringer; GS reports scientific advice and/or speaking fees from Novo Nordisk, Servier, MSD, Sanofi, Daiichi Sankyo, Eli Lilly, Sobi, Vifor Pharma, Amarin, Novartis, Sobi, Teva, and Amgen. Other authors report no conflict of interest related to the topic of this document., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose:  To assess the longitudinal variation of the ratio of umbilical and cerebral artery pulsatility index (UCR) in late preterm fetal growth restriction (FGR)., Materials and Methods:  A prospective European multicenter observational study included women with a singleton pregnancy, 32 + 0 -36 + 6 , at risk of FGR (estimated fetal weight [EFW] or abdominal circumference [AC] < 10 th percentile, abnormal arterial Doppler or fall in AC from 20-week scan of > 40 percentile points). The primary outcome was a composite of abnormal condition at birth or major neonatal morbidity. UCR was categorized as normal (< 0.9) or abnormal (≥ 0.9). UCR was assessed by gestational age at measurement interval to delivery, and by individual linear regression coefficient in women with two or more measurements., Results:  856 women had 2770 measurements; 696 (81 %) had more than one measurement (median 3 (IQR 2-4). At inclusion, 63 (7 %) a UCR ≥ 0.9. These delivered earlier and had a lower birth weight and higher incidence of adverse outcome (30 % vs. 9 %, relative risk 3.2; 95 %CI 2.1-5.0) than women with a normal UCR at inclusion. Repeated measurements after an abnormal UCR at inclusion were abnormal again in 67 % (95 %CI 55-80), but after a normal UCR the chance of finding an abnormal UCR was 6 % (95 %CI 5-7 %). The risk of composite adverse outcome was similar using the first or subsequent UCR values., Conclusion:  An abnormal UCR is likely to be abnormal again at a later measurement, while after a normal UCR the chance of an abnormal UCR is 5-7 % when repeated weekly. Repeated measurements do not predict outcome better than the first measurement, most likely due to the most compromised fetuses being delivered after an abnormal UCR., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Introduction: Monochorionic twins (MC) develop under unique intrauterine conditions and show a high risk of compromise during fetal life. Here we describe umbilical vein blood flow (UVBF) and fetal oxygen and glucose utilization in uncomplicated MC twins and investigate possible differences within twin-pairs according to birth-order., Methods: Prospective single-center study on 48 uncomplicated MC twins enrolled at the time of elective cesarean delivery. Ultrasound measurements of UVBF for Twin 1 and Twin 2 labelled according to birth-order were performed before spinal anesthesia. Umbilical arterial and venous blood samples were collected for each twin after fetal delivery, and fetal oxygen and glucose deliveries and uptakes were computed., Results: All twins were delivered within 2 min from one-another under steady-state conditions at 36.4 weeks of median gestational age (IQR 36.0-37.0). Birthweight and umbilical cord gas analyses were within physiological ranges for all twins. Second-born twins showed significantly lower UVBF, measured before delivery, and lower median birthweight compared to first-borns. Moreover, median values of estimated fetal oxygen and glucose consumption were lower in second compared to first MC twins., Discussion: Uncomplicated MC twins show different birthweight, oxygenation and metabolic rates based on their position in utero, hinting at pre-existing conditions possibly deriving by uneven vascular and metabolic distribution of the two placental territories. The innovative findings of this study emphasize the biological uniqueness of these pregnancies and prompt further physiological studies on MC twins and placenta metabolism., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: We aimed to identify maternal and fetal complications and investigate postnatal and long-term outcomes of fetal hydrothorax (FHT) treated with pleuro-amniotic shunting (shunt)., Methods: Single-center retrospective observational cohort of shunt cases performed from 2000 to 2021. Risk factors for maternal complications, fetal demise, neonatal death (NND), and postnatal outcomes were identified., Results: Out of 88 cases, 70 (79.5%) were complicated by hydrops, with an average gestational age (GA) at diagnosis of 27 weeks (range 16-34). In 16 cases, definitive etiology of FHT was identified; five cases of Noonan syndrome and three cases of monogenic disorders diagnosed by whole-exome sequencing (EPHB4, VEGFR3, RASA1). Shunt was performed at an average GA of 28 weeks (20-34), with a dislodgement in 10 cases (11.4%). Maternal: Complications occurred in three cases; survival rate was 76.1% (67/88). Follow-up data were available for 57/67 (85.1%) children. Incidence of severe neurodevelopmental impairment and pneumopathy (broncho dysplasia, persistent pulmonary hypertension of newborn, and asthma) was 5.3% and 8.8%, respectively. Post-treatment persistence of hydrops, FHT associated with genetic syndromes, and GA at birth were risk factors for fetal demise, NND, and postnatal complications., Conclusion: In truly isolated FHT, whenever indicated, pleuro-amniotic shunting is a safe procedure associated with good survival rate and long-term outcome., (© 2023 S. Karger AG, Basel.)

Maternal sepsis represents a leading cause of mortality and severe morbidity worldwide. In Italy, it is the second cause of direct maternal mortality. Delay in recognition and treatment initiation are the drivers of sepsis-associated adverse outcomes. Between November 2017 and October 2019, the Italian Obstetric Surveillance System coordinated a prospective population-based study on maternal sepsis occurring before or after childbirth from 22 weeks' gestation onward and up to 42 days following the end of pregnancy. A nested 1:2 matched case-control study on postpartum sepsis was also performed. Maternal sepsis was diagnosed for the presence of suspected or confirmed infection alongside signs or symptoms of organ failure. The aim of this study was to assess maternal sepsis incidence and its associated risk factors, management, and perinatal outcomes. Six Italian regions, covering 48.2% of the national births, participated in the project. We identified an incidence rate of 5.5 per 10,000 maternities (95% CI 4.80-6.28). Seventy percent of patients had a low education level and one third were foreigners with a language barrier. Genital, respiratory, and urinary tract infections were the predominant sources of infection; the majority of cases was caused by E. coli and polymicrobial infections. The presence of vascular and indwelling bladder catheters was associated with a nine-fold increased risk of postpartum sepsis. There were no maternal deaths, but one fourth of women experienced a serious adverse event and 28.3% required intensive care; 1.8% of newborns died. Targeted interventions to increase awareness of maternal sepsis and its risk factors and management should be promoted.

Objective: To estimate the incidence, and to investigate risk factors, management, and perinatal outcomes of eclampsia in Italy., Study Design: This is a prospective population-based cohort study enrolling all women admitted for eclampsia between November 2017 and March 2020. Incident cases were reported using electronic and anonymous data collection forms., Main Outcome Measures: Incidence, risk factors, maternal and perinatal morbidity, and mortality., Results: 109 cases were included for an estimated incidence rate of 1.5 (95 % CI 1.2-1.8) per 10.000 births. Risk of developing eclampsia was associated with multiple pregnancies (RR = 4.51; p < 0.001) and with pregnancies achieved with assisted reproductive technologies (RR = 3.03; p < 0.001). Magnesium sulfate was used as prophylaxis in almost 30 % of women with preeclampsia, and to treat an eclamptic fit in 89 % of women. The time interval between the first fit and delivery was 62 min for antepartum and 10 min for intrapartum cases. Around one third of women developed at least one other major complication and one mother died. Severe morbidity affected 13.3 % of the newborns. Two fetal and one neonatal death were reported., Conclusions: Our data revealed low incidence of eclampsia in Italy and prompt administration of antihypertensive drugs and magnesium sulfate to prevent eclampsia and to treat the recurrence of seizures. However, the rate of severe maternal complications is still high: increasing the time interval between fit and delivery seems to be crucial to achieve an effective stabilization of maternal conditions and reduce maternal major complications., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Aim: The use of alcohol affects the central nervous system and plays important roles in various neurological disorders through neurotoxicity resulting from blood-brain barrier (BBB) permeability. The BBB is regulated by tight junction proteins interacting closely with endothelial cells. This study evaluated the serum levels of proteins and spectrin degradation products associated with BBB damage in patients with alcohol use disorder., Methods: This preliminary case-control study was conducted with 30 healthy volunteers and 26 alcohol use disorder patients. The serum levels of spectrin breakdown product 145 (SBDP145), spectrin breakdown product 150 (SBDP150), ubiquitin carboxy-terminal hydrolase L1 (UCHL1), ubiquitin ligase cullin-3 (ULC), occludin and claudin were measured with enzyme-linked immunosorbent assay., Results: There was no significant difference between the levels of SBDP145, SBDP150, UCHL1, ULC, occludin and claudin before and after treatment in patients with alcohol use disorder. SBDP150 levels were significantly lower in patients than controls (P < 0.001). The area under the curve was 0.841 (0.733-0.949) with the 95% confidence interval for SPDP150., Conclusion: A decrease of the serum SBDP150 levels appears to be associated with alcohol use disorder. Future studies might clarify whether diminished serum SBDP150 levels are associated with BBB damage in patients with alcohol use disorder., (© The Author(s) 2022. Medical Council on Alcohol and Oxford University Press. All rights reserved.)

Objectives: It is now well established that in utero vertical SARS-CoV-2 transmission can occur during the late third trimester. However, little is known about other gestational ages. Recently, an increased risk of early miscarriage was reported in pregnant women who were SARS-CoV-2-positive. The objective of the current study was to evaluate the putative SARS-CoV-2 vertical transmission during the first trimester of pregnancy., Design: This is an observational study on pregnant women who were SARS-CoV-2-positive during the first trimester. Fetal and syncytiotrophoblastic specimens were collected by hysterosuction from 17 pregnant women who were SARS-CoV-2-positive and voluntarily terminated the pregnancy between week 8 and 12. We investigated the viral vertical transmission using SARS-CoV-2 RNA detection in the fetus and syncytiotrophoblast by two different techniques., Results: The results suggest that SARS-CoV-2 vertical transmission is indeed possible during the first trimester in asymptomatic women. Although maternal viremia was never detected, roughly 30% of the fetuses and 17% of the syncytiotrophoblasts were found to be SARS-CoV-2-positive., Conclusion: Indeed, SARS-CoV-2 can spread to the fetus through the syncytiotrophoblast. Concerningly, this happens in asymptomatic pregnant women as well. Possible long-term detrimental consequences on fetal development still need to be assessed. This should be taken into consideration in the management of pregnant women by implementing preventive strategies., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: Spontaneous hemoperitoneum in pregnancy is defined as a sudden non-traumatic intraperitoneal bleeding in pregnancy and up to 42 days postpartum. In the present study we aim to estimate the incidence and investigate the risk factors, the management and the outcomes of spontaneous hemoperitoneum in pregnancy in order to improve its clinical identification and reduce avoidable maternal deaths., Material and Methods: This is a prospective population-based cohort study, set in maternity units from nine Italian regions covering 75% of the national births. The study population comprises all women admitted for spontaneous intraperitoneal hemorrhage during pregnancy and up to 42 days postpartum between November 2017 and March 2020. Incident cases were reported by trained clinicians through electronic data collection forms. Descriptive statistics were performed. The main outcome measures included incidence rate of spontaneous hemoperitoneum in pregnancy, association with potential risk factors, clinical management and maternal and perinatal outcomes., Results: Twenty-nine cases met the adopted definition of spontaneous hemoperitoneum in pregnancy with an estimated incidence rate of 0.04 per 1000 births. An increased risk ratio (RR) of this condition was observed in pregnancies conceived by assisted reproductive technology (RR = 6.60, 95% CI 2.52-17.29), in the case of multiple pregnancies (RR = 6.57, 95% CI 1.99-21.69) and maternal age ≥35 years (RR 2.10, 95% CI 1.01-4.35). In 17/29 cases the bleeding site was intra-pelvic (23.5% in the posterior uterine wall and 35.2% in the left hemipelvis). Laparotomy represented the surgical treatment in 27 cases (93%), and most women underwent a cesarean delivery (92.6%). Median blood loss was 1900 mL, one hysterectomy was necessary, and two women died. Twenty-two preterm births were recorded., Conclusions: Spontaneous hemoperitoneum in pregnancy is a rare, life-threatening condition associated with high perinatal morbidity and mortality. Maternal age ≥35 years, multiple pregnancies and assisted reproductive technology were associated to a higher risk of the condition. Two women of 29 died and 70% of births occurred preterm., (© 2022 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)