Impact of Whole Genome Sequencing to investigate transmission of Serratia marcescens in Neonatal Intensive Care Unit.

Newborns admitted to neonatal intensive care units (NICU) are at increased risk of health care-associated infections. Serratia marcescens represent the third most common pathogen in NICU outbreaks. Here we present an outbreak investigation performed using Whole Genome Sequencing (WGS) analyses and the control measures implemented to limit the spread of S. marcescens in the NICU of an Italian hospital. In February 2023 S. marcescens was isolated from six newborns, when in 2022 this pathogen was isolated only from two samples in the same ward. Measures for infection prevention were adopted. Routinary surveillance screening, performed with rectal swabs collected at admission and weekly thereafter, was implemented to search for S. marcescens presence. Environmental samples were collected. All the isolates, obtained from the conjunctival swab of six newborns, from rectal swab of two newborns who did not develop infections, as well as from the aerators of two faucets, were sequenced. WGS analyses showed no correlation between the isolates from newborns and environmental isolates. The implementation of the measures for infection prevention and control had enabled us to successfully control the outbreak within a short period. WGS analyses proved to be crucial in outbreak investigation to limit the spreading of the pathogens.

Why might cord blood be a better source of platelets for transfusion to neonates?

Thrombocytopenia (defined as a platelet count <150×109/L) is a common condition in preterm neonates and may occur in 18-35% of all infants admitted to the Neonatal Intensive Care Unit (NICU). Neonatal platelet functionality in terms of reactivity is often described as reduced compared to adults, even in healthy, term neonates. However, this platelet "hyporeactivity" does not correspond to a global functional impairment of the normal delicately balanced neonatal hemostatic system. The extent to which neonatal thrombocytopenia and platelet hyporeactivity contribute to the bleeding risk in preterm neonates remains unknown. Prophylactic platelet transfusions are often administered to them to reduce the risk of bleeding. However, recent literature indicates that adopting a higher platelet transfusion threshold than a lower one results in significantly higher death rates or major bleeding and can be harmful. Although the mechanism by which this occurs is not entirely clear, a mismatch between adult transfused platelets and the neonatal hemostatic system, as well as volume overload, are speculated to be potentially involved. Therefore, future research should consider novel transfusion products that may be more suitable for premature neonates. Blood products derived from umbilical cord blood (UCB) are promising, as they might perfectly match neonatal blood features. Here, we discuss the current knowledge about UCB-derived products, focusing on UCB-derived platelet concentrates and their potential for future clinical application. We will discuss how they may overcome the potential risks of transfusing adult-derived platelets to premature infants while maintaining efficacy.

Masked or not, I smile to you: Exploring full-term and preterm infants' social smiles to adults wearing a protective facemask.

The early emergence of social smiles is an important milestone of infants' socio-emotional development. Our aim was to assess how the use of protective facemasks by adults affects the display of social smiles in preterm (PT) and full-term (FT) infants at 3 months (corrected age for prematurity). We enrolled 30 FT and 30 PT infants (gestational age ≤ 32 weeks). Infants' social smiles displays were assessed at 2-3-month-age (corrected) across a three-episode (masked mother; unmasked mother; masked adult female stranger) videotaped interactive task. During each episode, the adult was instructed to maintain specific facial expressions (happy-smiling, sad-frowning, neutral-unresponsive) for 15 second windows and then instructed to interact spontaneously for 45 s (of which the first 15 s were coded). FT and PT infants did not differ in the display of social smiles. In both groups, social smiles were mostly exhibited in response to happy/smiling and spontaneously interacting partners. Overall, no effect of wearing a protective facemask emerged. The use of protective facemasks did not result in a lower display of social smiles. The findings suggest that FT and PT might be equally sensitive to their adult interactive partners in terms of social smiles displays at 2-3-month-age.

Fate of melatonin orally administered in preterm newborns: Antioxidant performance and basis for neuroprotection.

Preterm infants cannot counteract excessive reactive oxygen species (ROS) production due to preterm birth, leading to an excess of lipid peroxidation with malondialdehyde (MDA) production, capable of contributing to brain damage. Melatonin (ME), an endogenous brain hormone, and its metabolites, act as a free radical scavenger against ROS. Unfortunately, preterms have an impaired antioxidant system, resulting in the inability to produce and release ME. This prospective, multicenter, parallel groups, randomized, double-blind, placebo-controlled trial aimed to assess: (i) the endogenous production of ME in very preterm infants (gestational age ≤ 29 + 6 WE, 28 infants in the ME and 26 in the placebo group); (ii) the exogenous hormone availability and its metabolization to the main metabolite, 6-OH-ME after 15 days of ME oral treatment; (iii) difference of MDA plasma concentration, as peroxidation marker, after treatment. Blood was collected before the first administration (T1) and after 15 days of administration (T2). ME and 6-OH-ME were detected by liquid chromatography tandem mass spectrometry, MDA was measured by liquid chromatograph with fluorescence detection. ME and 6-OH-ME were not detectable in the placebo group at any study time-point. ME was absent in the active group at T1. In contrast, after oral administration, ME and 6-OH-ME resulted highly detectable and the difference between concentrations T2 versus T1 was statistically significant, as well as the difference between treated and placebo groups at T2. MDA levels seemed stable during the 15 days of treatment in both groups. Nevertheless, a trend in the percentage of neonates with reduced MDA concentration at T2/T1 was 48.1% in the ME group versus 38.5% in the placebo group. We demonstrated that very preterm infants are not able to produce endogenous detectable plasma levels of ME during their first days of life. Still, following ME oral administration, appreciable amounts of ME and 6-OH-ME were available. The trend of MDA reduction in the active group requires further clinical trials to fix the dosage, the length of ME therapy and to identify more appropriate indexes to demonstrate, at biological and clinical levels, the antioxidant activity and consequent neuroprotectant potential of ME in very preterm newborns.

Human inherited CCR2 deficiency underlies progressive polycystic lung disease.

We describe a human lung disease caused by autosomal recessive, complete deficiency of the monocyte chemokine receptor C-C motif chemokine receptor 2 (CCR2). Nine children from five independent kindreds have pulmonary alveolar proteinosis (PAP), progressive polycystic lung disease, and recurrent infections, including bacillus Calmette Guérin (BCG) disease. The CCR2 variants are homozygous in six patients and compound heterozygous in three, and all are loss-of-expression and loss-of-function. They abolish CCR2-agonist chemokine C-C motif ligand 2 (CCL-2)-stimulated Ca2+ signaling in and migration of monocytic cells. All patients have high blood CCL-2 levels, providing a diagnostic test for screening children with unexplained lung or mycobacterial disease. Blood myeloid and lymphoid subsets and interferon (IFN)-γ- and granulocyte-macrophage colony-stimulating factor (GM-CSF)-mediated immunity are unaffected. CCR2-deficient monocytes and alveolar macrophage-like cells have normal gene expression profiles and functions. By contrast, alveolar macrophage counts are about half. Human complete CCR2 deficiency is a genetic etiology of PAP, polycystic lung disease, and recurrent infections caused by impaired CCL2-dependent monocyte migration to the lungs and infected tissues.

Early Postnatal Infection of Neonates Born to Mothers Infected by SARS-CoV-2 Omicron Variant.

OBJECTIVES: To evaluate the rate of postnatal infection during the first month of life in neonates born to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive mothers during the predominant circulation of the omicron (B.1.1.529) variant. METHODS: This prospective, 10-center study enrolled mothers infected by SARS-CoV-2 at delivery and their infants, if both were eligible for rooming-in, between December 2021 and March 2022. Neonates were screened for SARS-CoV-2 RNA at 1 day of life (DOL), 2 to 3 DOL, before discharge, and twice after hospital discharge. Mother-infant dyads were managed under a standardized protocol to minimize the risk of viral transmission. Sequencing data in the study area were obtained from the Italian Coronavirus Disease 2019 Genomic platform. Neonates were included in the final analysis if they were born when the omicron variant represented >90% of isolates. RESULTS: Eighty-two percent (302/366) of mothers had an asymptomatic SARS-CoV-2 infection. Among 368 neonates, 1 was considered infected in utero (0.3%), whereas the postnatal infection rate during virtually exclusive circulation of the omicron variant was 12.1%. Among neonates infected after birth, 48.6% became positive during the follow-up period. Most positive cases at follow-up were detected concurrently with the peak of coronavirus disease 2019 cases in Italy. Ninety-seven percent of the infected neonates were asymptomatic. CONCLUSIONS: The risk of early postnatal infection by the SARS-CoV-2 omicron variant is higher than that reported for previously circulating variants. However, protected rooming-in practice should still be encouraged given the paucity of symptoms in infected neonates.

Anti-Inflammatory and Anti-Allergic Properties of Colostrum from Mothers of Full-Term and Preterm Babies: The Importance of Maternal Lactation in the First Days.

Our narrative review focuses on colostrum components, particularly those that influence the neonatal immune system of newborns. Colostrum is secreted in small volumes by the alveolar cells of the breast during the first two to five days after birth. Colostrum is poor in fat and carbohydrates, with larger protein and bioactive compounds than mature milk. It plays a crucial role in driving neonates' immunity, transferring those immunological factors which help the correct development of the neonatal immune system and support establishing a healthy gut microbiome. The newborn has an innate and adaptive immune system deficiency, with a consequent increase in infection susceptibility. In particular, neonates born prematurely have reduced immunological competencies due to an earlier break in the maternal trans-placenta transfer of bioactive components, such as maternal IgG antibodies. Moreover, during pregnancy, starting from the second trimester, maternal immune cells are conveyed to the fetus and persist in small quantities post-natal, whereby this transfer is known as microchimerism (MMc). Thus, preterm newborns are deficient in this maternal heritage, and have their own immune system under-developed, but colostrum can compensate for the lack. Early breastfeeding, which should be strongly encouraged in mothers of preterm and full-term babies, provides those immunomodulant compounds that can act as a support, allowing the newborn to face immune needs, including fronting infections and establishing tolerance. Moreover, making mothers aware that administering colostrum helps their infants in building a healthy immune system is beneficial to sustain them in the difficult post-partum period.

Variation in delivery room management of preterm infants across Europe: a survey of the Union of European Neonatal and Perinatal Societies.

The aim of the present study, endorsed by the Union of European Neonatal and Perinatal Societies (UENPS) and the Italian Society of Neonatology (SIN), was to analyze the current delivery room (DR) stabilization practices in a large sample of European birth centers that care for preterm infants with gestational age (GA) < 33 weeks. Cross-sectional electronic survey was used in this study. A questionnaire focusing on the current DR practices for infants < 33 weeks' GA, divided in 6 neonatal resuscitation domains, was individually sent to the directors of European neonatal facilities, made available as a web-based link. A comparison was made between hospitals grouped into 5 geographical areas (Eastern Europe (EE), Italy (ITA), Mediterranean countries (MC), Turkey (TUR), and Western Europe (WE)) and between high- and low-volume units across Europe. Two hundred and sixty-two centers from 33 European countries responded to the survey. At the time of the survey, approximately 20,000 very low birth weight (VLBW, < 1500 g) infants were admitted to the participating hospitals, with a median (IQR) of 48 (27-89) infants per center per year. Significant differences between the 5 geographical areas concerned: the volume of neonatal care, ranging from 86 (53-206) admitted VLBW infants per center per year in TUR to 35 (IQR 25-53) in MC; the umbilical cord (UC) management, being the delayed cord clamping performed in < 50% of centers in EE, ITA, and MC, and the cord milking the preferred strategy in TUR; the spotty use of some body temperature control strategies, including thermal mattress mainly employed in WE, and heated humidified gases for ventilation seldom available in MC; and some of the ventilation practices, mainly in regard to the initial FiO2 for < 28 weeks' GA infants, pressures selected for ventilation, and the preferred interface to start ventilation. Specifically, 62.5% of TUR centers indicated the short binasal prongs as the preferred interface, as opposed to the face mask which is widely adopted as first choice in > 80% of the rest of the responding units; the DR surfactant administration, which ranges from 44.4% of the birth centers in MC to 87.5% in WE; and, finally, the ethical issues around the minimal GA limit to provide full resuscitation, ranging from 22 to 25 weeks across Europe. A comparison between high- and low-volume units showed significant differences in the domains of UC management and ventilation practices.    Conclusion: Current DR practice and ethical choices show similarities and divergences across Europe. Some areas of assistance, like UC management and DR ventilation strategies, would benefit of standardization. Clinicians and stakeholders should consider this information when allocating resources and planning European perinatal programs. What is Known: • Delivery room (DR) support of preterm infants has a direct influence on both immediate survival and long-term morbidity. • Resuscitation practices for preterm infants often deviate from the internationally defined algorithms. What is New: • Current DR practice and ethical choices show similarities and divergences across Europe. Some areas of assistance, like UC management and DR ventilation strategies, would benefit of standardization. • Clinicians and stakeholders should consider this information when allocating resources and planning European perinatal programs.

Fulminant echovirus 11 hepatitis in male non-identical twins in northern Italy, April 2023.

Echovirus 11 (E11) has recently been associated with a series of nine neonatal cases of severe hepatitis in France. Here, we present severe hepatitis caused by E11 in a pair of twins. In one of the neonates, the clinical picture evolved to fulminant hepatitis. The E11 genome showed 99% nucleotide identity with E11 strains reported in the cases in France. Rapid genome characterisation using next generation sequencing is essential to identify new and more pathogenetic variants.

Association between the development of bronchopulmonary dysplasia and platelet transfusion: a protocol for a systematic review and meta-analysis.

Background: There is a lack of consensus on the management of thrombocytopenia in preterm infants, and the threshold for prophylactic platelet transfusion varies widely among clinicians and institutions. Reports in animal models suggested that platelets may play a relevant role in lung alveolarization and regeneration. Bronchopulmonary dysplasia (BPD) is a severe respiratory condition with a multifactorial origin that affects infants born at the early stages of lung development. Recent randomized controlled trials on the platelets count threshold for prophylactic transfusions in preterm infants with thrombocytopenia suggest that a higher exposition to platelet transfusion may increase the risk of BPD. Here, we report a protocol for a systematic review, which aims to assist evidence-based clinical practice and clarify if the administration of platelet products may be associated with the incidence of BPD and/or death in preterm infants. Methods: MEDLINE, Embase, Cochrane databases, and sources of gray literature for conference abstracts and trial registrations will be searched with no time or language restrictions. Case-control studies, cohort studies, and nonrandomized or randomized trials that evaluated the risk for BPD and/or death in preterm infants exposed to platelet transfusion will be included. Data from studies that are sufficiently similar will be pooled as appropriate. Data extraction forms will be developed a priori. Observational studies and nonrandomized and randomized clinical trials will be analyzed separately. Odds ratio with 95% confidence interval (CI) for dichotomous outcomes and the mean difference (95% CI) for continuous outcomes will be combined. The expected heterogeneity will be accounted for using a random-effects model. Subgroup analysis will be performed based on a priori-determined covariate of interest. In case of sufficient homogeneity of interventions and outcomes evaluated, results from subgroups of studies will be pooled together in a meta-analysis. Discussion: This systematic review will investigate the association of BPD/death with platelet components administration in preterm infants, and, consequently, it will provide reliable indications for the evidence-based management of premature patients with thrombocytopenia.

Autoantibodies neutralizing type I IFNs underlie West Nile virus encephalitis in ∼40% of patients.

Mosquito-borne West Nile virus (WNV) infection is benign in most individuals but can cause encephalitis in <1% of infected individuals. We show that ∼35% of patients hospitalized for WNV disease (WNVD) in six independent cohorts from the EU and USA carry auto-Abs neutralizing IFN-α and/or -ω. The prevalence of these antibodies is highest in patients with encephalitis (∼40%), and that in individuals with silent WNV infection is as low as that in the general population. The odds ratios for WNVD in individuals with these auto-Abs relative to those without them in the general population range from 19.0 (95% CI 15.0-24.0, P value <10-15) for auto-Abs neutralizing only 100 pg/ml IFN-α and/or IFN-ω to 127.4 (CI 87.1-186.4, P value <10-15) for auto-Abs neutralizing both IFN-α and IFN-ω at a concentration of 10 ng/ml. These antibodies block the protective effect of IFN-α in Vero cells infected with WNV in vitro. Auto-Abs neutralizing IFN-α and/or IFN-ω underlie ∼40% of cases of WNV encephalitis.

Exclusive breastfeeding at 6 months after assisted and spontaneous conceiving: a prospective study in Northern Italy.

Conceiving by assisted infertility treatments may influence breastfeeding duration. In one-year time, to evaluate the goal of 6 months breastfeeding, we recruited 55 consecutive mothers who conceived using assisted treatment compared to 45 mothers conceiving naturally, all giving birth to healthy, full-term, singleton infants, sharing the double-occupancy room. At birth, maternal/neonatal characteristics were obtained by medical records and interviews. Six months after, a telephonic interview was done about the exclusivity of breastfeeding, mood instability, and breastfeeding complications. All the women were supported by the same neonatal-pediatrician team, during the study period. The number of mothers who were exclusively breastfeeding at six months was not statistically different between the two groups, as well as, breastfeeding initiation, BMI, smoking habit, mood instability, co-morbidities. In the assisted group, the women were older, had fewer previous children, upper degree of education, higher rate of cesarean sections, their neonate's birthweight was lower; they reported more breastfeeding complications, but the distribution was not different between groups. The control women had higher number of previously breastfed siblings. Our experience highlights that the mode of conception may not be the defining factor influencing the goal of 6 months lactation. The support of healthcare professional team has a crucial role in maintaining breastfeeding.

Viscoelastic coagulation testing in Neonatal Intensive Care Units: advantages and pitfalls in clinical practice.

The expression "developmental hemostasis" indicates the age-related physiological changes occurring during the maturational process of the hemostatic system. Despite the quantitative and qualitative alterations, the neonatal hemostatic system is competent and well-balanced. Conventional coagulation tests do not provide reliable information as they only explore the procoagulants during the neonatal period. In contrast, viscoelastic coagulation tests (VCTs), such as viscoelastic coagulation monitoring (VCM), thromboelastography (TEG or ClotPro), and rotational thromboelastometry (ROTEM), are point-of-care assays that provide a quick, dynamic and global view of the hemostatic process, allowing prompt and individualized therapeutic intervention when necessary. Their use in neonatal care is on the increase and they could help monitor patients at risk of hemostatic derangement. In addition, they are crucial for anticoagulation monitoring during extracorporeal membrane oxygenation. Moreover, implementing VCT-based monitoring could optimize blood product use.

Survey of transfusion practices in preterm infants in Europe.

BACKGROUND: Preterm infants commonly receive red blood cell (RBC), platelet and fresh frozen plasma (FFP) transfusions. The aim of this Neonatal Transfusion Network survey was to describe current transfusion practices in Europe and to compare our findings to three recent randomised controlled trials to understand how clinical practice relates to the trial data. METHODS: From October to December 2020, we performed an online survey among 597 neonatal intensive care units (NICUs) caring for infants with a gestational age (GA) of <32 weeks in 18 European countries. RESULTS: Responses from 343 NICUs (response rate: 57%) are presented and showed substantial variation in clinical practice. For RBC transfusions, 70% of NICUs transfused at thresholds above the restrictive thresholds tested in the recent trials and 22% below the restrictive thresholds. For platelet transfusions, 57% of NICUs transfused at platelet count thresholds above 25×109/L in non-bleeding infants of GA of <28 weeks, while the 25×109/L threshold was associated with a lower risk of harm in a recent trial. FFP transfusions were administered for coagulopathy without active bleeding in 39% and for hypotension in 25% of NICUs. Transfusion volume, duration and rate varied by factors up to several folds between NICUs. CONCLUSIONS: Transfusion thresholds and aspects of administration vary widely across European NICUs. In general, transfusion thresholds used tend to be more liberal compared with data from recent trials supporting the use of more restrictive thresholds. Further research is needed to identify the barriers and enablers to incorporation of recent trial findings into neonatal transfusion practice.

Surveillance in a Neonatal Intensive Care Unit Allowed the Isolation of a Strain of VIM-Producing Pantoea brenneri.

Here, we describe the isolation of a strain of the genus Pantoea encoding a VIM carbapenemase, the first to our knowledge. The strain, isolated from a rectal swab of a 10-day-old newborn admitted to a neonatal intensive care unit (NICU), was identified through whole-genome sequencing analyses as Pantoea brenneri. The strain harbored the carbapenemases gene blaVIM-1. The prompt application of contact measures and the isolation of the newborn prevented the dissemination of VIM-producing P. brenneri and of the plasmid carrying the VIM-1 gene to other newborns.

BORN study: a multicenter randomized trial investigating cord blood red blood cell transfusions to reduce the severity of retinopathy of prematurity in extremely low gestational age neonates.

BACKGROUND: Extremely low gestational age neonates (ELGANs, i.e., neonates born before 28 weeks of gestation) are at high risk of developing retinopathy of prematurity (ROP), with potential long-life visual impairment. Due to concomitant anemia, ELGANs need repeated red blood cell (RBC) transfusions. These produce a progressive replacement of fetal hemoglobin (HbF) by adult hemoglobin (HbA). Furthermore, a close association exists between low levels of HbF and severe ROP, suggesting that a perturbation of the HbF-mediated oxygen release may derange retinal angiogenesis and promote ROP. METHODS/DESIGN: BORN (umBilical blOod to tRansfuse preterm Neonates) is a multicenter double-blinded randomized controlled trial in ELGANs, to assess the effect of allogeneic cord blood RBC transfusions (CB-RBCs) on severe ROP development. Recruitment, consent, and randomization take place at 10 neonatology intensive care units (NICUs) of 8 Italian tertiary hospitals. ELGANs with gestational age at birth comprised between 24+0 and 27+6 weeks are randomly allocated into two groups: (1) standard RBC transfusions (adult-RBCs) (control arm) and (2) CB-RBCs (intervention arm). In case of transfusion need, enrolled patients receive transfusions according to the allocation arm, unless an ABO/RhD CB-RBC is unavailable. Nine Italian public CB banks cooperate to make available a suitable amount of CB-RBC units for all participating NICUs. The primary outcome is the incidence of severe ROP (stage 3 or higher) at discharge or 40 weeks of postmenstrual age, which occurs first. DISCUSSION: BORN is a groundbreaking trial, pioneering a new transfusion approach dedicated to ELGANs at high risk for severe ROP. In previous non-randomized trials, this transfusion approach was proven feasible and able to prevent the HbF decrease in patients requiring multiple transfusions. Should the BORN trial confirm the efficacy of CB-RBCs in reducing ROP severity, this transfusion strategy would become the preferential blood product to be used in severely preterm neonates. TRIAL REGISTRATION: ClinicalTrials.gov NCT05100212. Registered on October 29, 2021.

LIMIT: LIfestyle and Microbiome InTeraction Early Adiposity Rebound in Children, a Study Protocol.

Childhood obesity is a strong predictor of adult obesity with health and economic consequences for individuals and society. Adiposity rebound (AR) is a rise in the Body Mass Index occurring between 3 and 7 years. Early adiposity rebound (EAR) occurs at a median age of 2 years and predisposes to a later onset of obesity. Since obesity has been associated with intestinal dysbiosis, we hypothesize that EAR could be related to early microbiome changes due to maternal/lifestyle changes and environmental exposures, which can increase the unhealthy consequences of childhood obesity. LIMIT is a prospective cohort study that aims at identifying the longitudinal interplay between infant gut microbiome, infant/maternal lifestyle, and environmental variables, in children with EAR vs. AR. Methods. The study evaluated 272 mother-infant pairs, enrolled at an Italian neonatal unit, at different time points (T0, at delivery; T1, 1 month; T2, 6 months; T3, 12 months; T4, 24 months; T5, 36 months after birth). The variables that were collected include maternal/infant anthropometric measurements, lifestyle habits, maternal environmental endocrine disruptor exposure, as well as infant AR. The LIMIT results will provide the basis for early identification of those maternal and infant modifiable factors on which to act for an effective and personalized prevention of childhood obesity.

Hemostasis in neonatal ECMO.

Extracorporeal membrane oxygenation (ECMO) is a life-saving support for cardio-respiratory function. Over the last 50 years, the extracorporeal field has faced huge technological progress. However, despite the improvements in technique and materials, coagulation problems are still the main contributor to morbidity and mortality of ECMO patients. Indeed, the incidence and survival rates of the main hemorrhagic and thrombotic complications in neonatal respiratory ECMO are relevant. The main culprit is related to the intrinsic nature of ECMO: the contact phase activation. The exposure of the human blood to the non-endothelial surface triggers a systemic inflammatory response syndrome, which chronically activates the thrombin generation and ultimately leads to coagulative derangements. Pre-existing illness-related hemostatic dysfunction and the peculiarity of the neonatal clotting balance further complicate the picture. Systemic anticoagulation is the management's mainstay, aiming to prevent thrombosis within the circuit and bleeding complications in the patient. Although other agents (i.e., direct thrombin inhibitors) have been recently introduced, unfractionated heparin (UFH) is the standard of care worldwide. Currently, there are multiple tests exploring ECMO-induced coagulopathy. A combination of the parameters mentioned above and the evaluation of the patient's underlying clinical context should be used to provide a goal-directed antithrombotic strategy. However, the ideal algorithm for monitoring anticoagulation is currently unknown, resulting in a large inter-institutional diagnostic variability. In this review, we face the features of the available monitoring tests and approaches, mainly focusing on the role of point-of-care (POC) viscoelastic assays in neonatal ECMO. Current gaps in knowledge and areas that warrant further study will also be addressed.

Impact of SARS-CoV-2 infection during pregnancy and persistence of antibody response.

BACKGROUND: Pregnant women may be at an increased risk of developing severe or critical disease associated with the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection causing severities during pregnancy. We performed a prospective study to describe the impact of SARS-CoV-2 infection on pregnancy outcomes and on the newborn, depending on the severity of the disease. The antibody response and persistence of SARS-CoV-2 anti-Spike (S) IgG, IgA and anti-Nu- cleocapsid (NCP) IgG, was investigated. METHODS: A total of 48 pregnant women with SARS-CoV-2 infection were enrolled, and sequential serum samples from 30 of them were collected until one year after infection. Outcomes of pregnan- cy and newborn parameters were evaluated in comparison with 200 uninfected controls. RESULTS: Asymptomatic infection was observed in 31/48 women (64.5%), mild COVID-19 in 12/48 women (25.0%), while 5/48 women (10.5%) developed pneumonia. Women with pneumonia mount- ed significantly higher levels of anti-S IgG, IgA and anti-NCP IgG between 1 and 3 months after onset of infection compared to asymptomatic women. Anti-S IgG persisted in the majority of women from 6 months to at least one year after infection, especially in those with symptomatic infection and pneumonia, while anti-S IgA and anti-NCP IgG declined earlier. Pregnancy complications and new- born parameters were not significantly different from those observed in uninfected controls. CONCLUSION: Anti-SARS-CoV-2 antibody development and persistence was not impaired in pregnant women, while SARS-CoV-2 infection did not cause major pregnancy or newborn complications in asymptomatic or symptomatic women, nor in women with pneumonia receiving prompt clinical care.

SIMPSON-GOLABI-BEHMEL syndrome type 1: How placental immunohistochemistry can rapidly Predict the diagnosis.

INTRODUCTION: Glypican-3 (GPC3) is an oncofetal protein involved in cellular signaling, strongly expressed in the placenta, absent or diminished in postnatal life, but often increased in human malignancies. Germline loss-of-function variants of GPC3 gene are associated with Simpson-Golabi-Behmel syndrome type 1 (SGBS1), a rare recessive X-linked overgrowth disease characterized by typical facial features, congenital abnormalities, and an increased risk of developing childhood cancers. METHODS: A clinical suspicion of SGBS1 was postulated for a newborn with prenatal history of overgrowth and polyhydramnios, presenting with neonatal weight and length >99th percentile, coarse facies, iris and retinal coloboma, supernumerary nipples, and splenomegaly. While waiting for whole-genome sequencing (WGS) results, we investigated placental GPC3 immunohistochemical expression in the proband, in three additional cases of SGBS1, and disorders commonly associated with fetal macrosomia and/or placentomegaly. RESULTS: WGS in the proband identified a likely pathogenic maternally inherited missense variant in GPC3: c.1645A > G, (p.Ile549Val), and GPC3 immunohistochemistry demonstrated full-thickness loss of stain of the placental parenchyma. The same pattern ("null") was also present in the placentas of three additional cases of SGBS1, but not in those of unaffected controls. DISCUSSION: Immunohistochemical expression of GPC3 in the placenta is highly reproducible. Our findings showed that a "null pattern" of staining is predictive of SGBS1 and represents a valuable aid in the differential diagnosis of fetal macrosomias, allowing targeted genetic testing and earlier diagnosis.