Secondary prevention of early-onset sepsis: A less invasive Italian approach for managing neonates at risk

Strategies to prevent early-onset sepsis (EOS) have led to a substantial decline in many countries. However, one of the most controversial topics in neonatology is the management of asymptomatic full-term and late preterm neonates at risk for EOS, and guidelines lack substantial consensus regarding this issue. A strategy for managing neonates, entirely based on serial physical examinations, has been developed in two Italian regions. This strategy seems safe, while reducing laboratory tests and unnecessary antibiotics. In the current commentary we provide area-based data concerning the prevention of EOS in 2 northern Italian regions, and we detail the results of their strategy for managing healthy-appearing newborns at risk for EOS

Longitudinal Growth and Body Composition of Twins versus Singletons in the First Month of Life

Background. Although twin gestation is well recognized to be associated with impaired fetal and postnatal growth, specific data about body composition of twins in the first month of life are scarce. Objective. The aim of this study was to compare the body composition of twins, evaluated with air-displacement plethysmography, to that of singletons of similar gestational age and adequacy of growth, during the first month of life. We tested the hypothesis that the quality of growth would be similar. Methods. Anthropometric and air-displacement plethysmography measurements were performed in 18 pairs of twins and in 36 singleton neonates, longitudinally, from birth to the 30th day of life. Each twin was matched to a singleton infant of similar gestational age and birth weight z-score. Results. With regard to anthropometric measures, the only difference was a lower weight in twins versus singletons on the 15th day of life. With regard to body composition, we did not find any difference between groups at any time point. Fat mass increased significantly from day 1 to day 30 in both twins and singletons. Conclusion. In terms of body composition, twins do not differ from singletons of similar gestational age and weight, either at birth or in early postnatal life

Parental Stress, Depression, and Participation in Care Before and During the COVID-19 Pandemic: A Prospective Observational Study in an Italian Neonatal Intensive Care Unit.

Background: Recent studies reported, during the COVID-19 pandemic, increased mental distress among the general population and among women around the childbirth period. COVID-19 pandemic may undermine the vulnerable well-being of parents in Neonatal Intensive Care Units (NICUs). Objective: Our study aimed to explore whether parental stress, depression, and participation in care in an Italian NICU changed significantly over three periods: pre-pandemic (T0), low (T1), and high COVID-19 incidence (T2). Methods: Enrolled parents were assessed with the Parental Stressor Scale in the NICU (PSS:NICU), Edinburgh Postnatal Depression Scale (EPDS), and Index of Parental Participation (IPP). Stress was the study primary outcome. A sample of 108 parents, 34 for each time period, was estimated to be adequate to detect a difference in PSS:NICU stress occurrence level score (SOL) of 1.25 points between time periods. To estimate score differences among the three study periods a non-parametric analysis was performed. Correlation among scores was assessed with Spearman rank coefficient. Results: Overall, 152 parents were included in the study (62 in T0, 56 in T1, and 34 in T2). No significant differences in the median PSS:NICU, EPDS, and IPP scores were observed over the three periods, except for a slight increase in the PSS:NICU parental role sub-score in T2 (T0 3.3 [2.3-4.1] vs. T2 3.9 [3.1-4.3]; p = 0.038). In particular, the question regarding the separation from the infant resulted the most stressful aspect during T2 (T0 4.0 [4.0-5.0] vs. T2 5.0 [4.0-5.0], p = 0.008). The correlation between participation and stress scores (r = 0.19-022), and between participation and depression scores (r = 0.27) were weak, while among depression and stress, a moderate positive correlation was found (r = 0.45-0.48). Conclusions: This study suggests that parental stress and depression may be contained during the COVID-19 pandemic, while participation may be ensured

Secondary prevention of early-onset sepsis: A less invasive Italian approach for managing neonates at risk

Strategies to prevent early-onset sepsis (EOS) have led to a substantial decline in many countries. However, one of the most controversial topics in neonatology is the management of asymptomatic full-term and late preterm neonates at risk for EOS, and guidelines lack substantial consensus regarding this issue. A strategy for managing neonates, entirely based on serial physical examinations, has been developed in two Italian regions. This strategy seems safe, while reducing laboratory tests and unnecessary antibiotics. In the current commentary we provide area-based data concerning the prevention of EOS in 2 northern Italian regions, and we detail the results of their strategy for managing healthy-appearing newborns at risk for EOS

Late-term fetuses with reduced umbilical vein blood flow volume: An under-recognized population at increased risk of growth restriction

Objectives: To investigate the umbilical vein and uterine arteries blood flow volume (UV-Q, UtA-Q) in late-term pregnancies.& nbsp;Study design: This was a prospective observational cohort study of singleton pregnancies > 40 + 0 weeks in which UV-Q and UtA-Q, both absolute and normalized for estimated fetal weight (EFW) values, were evaluated in relation to AC drop of > 20 percentiles from 20 weeks to term, Doppler signs of fetal cerebral blood flow redistribution and composite adverse perinatal outcome. The presence of neonatal hypoglycaemia and the need of formula milk supplementation were also examined.& nbsp;Results: The study population comprised 200 women. Fetuses with AC drop (n = 34) had a significantly lower UV-Q and UV-Q/EFW than fetuses without AC drop (n = 166): median UV-Q 184 ml/min (IQR 143-225) vs 233 ml/min (IQR 181-277), p = 0.0006; median UV-Q/EFW 55 ml/min/kg (IQR 42-66) vs 63 ml/min/kg (IQR 48-74), p = 0.03. Fetuses with cerebral blood flow redistribution (n = 48) had a significantly lower UV-Q and UV-Q/EFW than those without (n = 134): median UV-Q 210 ml/min (IQR 155-263) vs 236 ml/min (IQR 184-278), p = 0.04; median UV-Q/EFV 58 ml/min/kg (IQR 45-70) vs 65 ml/min/kg (IQR 50-76), p = 0.04. There was a significant moderate correlation between middle cerebral artery pulsatility index (MCA-PI) and UV -Q and UV-Q/EFW (Spearman Rho-0.20 and-0.20; p = 0.008 and p = 0.006).& nbsp;Conclusions: The umbilical vein blood flow volume might have a potential role to identify fetuses with stunted growth in late-term pregnancies

Exploiting natural polysaccharides to enhance in vitro bio-constructs of primary neurons and progenitor cells

Current strategies in Central Nervous System (CNS) repair focus on the engineering of artificial scaffolds for guiding and promoting neuronal tissue regrowth. Ideally, one should combine such synthetic structures with stem cell therapies, encapsulating progenitor cells and instructing their differentiation and growth. We used developments in the design, synthesis, and characterization of polysaccharide-based bioactive polymeric materials for testing the ideal composite supporting neuronal network growth, synapse formation and stem cell differentiation into neurons and motor neurons. Moreover, we investigated the feasibility of combining these approaches with engineered mesenchymal stem cells able to release neurotrophic factors. We show here that composite bio-constructs made of Chitlac, a Chitosan derivative, favor hippocampal neuronal growth, synapse formation and the differentiation of progenitors into the proper neuronal lineage, that can be improved by local and continuous delivery of neurotrophins. Statement of Significance In our work, we characterized polysaccharide-based bioactive platforms as biocompatible materials for nerve tissue engineering. We show that Chitlac-thick substrates are able to promote neuronal growth, differentiation, maturation and formation of active synapses. These observations support this new material as a promising candidate for the development of complex bio-constructs promoting central nervous system regeneration. Our novel findings sustain the exploitation of polysaccharide-based scaffolds able to favour neuronal network reconstruction. Our study shows that Chitlac-thick may be an ideal candidate for the design of biomaterial scaffolds enriched with stem cell therapies as an innovative approach for central nervous system repair

EPG5-related Vici syndrome: a paradigm of neurodevelopmental disorders with defective autophagy

Vici syndrome is a progressive neurodevelopmental multisystem disorder due to recessive mutations in the key autophagy gene EPG5. We report genetic, clinical, neuroradiological, and neuropathological features of 50 children from 30 families, as well as the neuronal phenotype of EPG5 knock-down in Drosophila melanogaster. We identified 39 different EPG5 mutations, most of them truncating and predicted to result in reduced EPG5 protein. Most mutations were private, but three recurrent mutations (p.Met2242Cysfs*5, p.Arg417*, and p.Gln336Arg) indicated possible founder effects. Presentation was mainly neonatal, with marked hypotonia and feeding difficulties. In addition to the five principal features (callosal agenesis, cataracts, hypopigmentation, cardiomyopathy, and immune dysfunction), we identified three equally consistent features (profound developmental delay, progressive microcephaly, and failure to thrive). The manifestation of all eight of these features has a specificity of 97%, and a sensitivity of 89% for the presence of an EPG5 mutation and will allow informed decisions about genetic testing. Clinical progression was relentless and many children died in infancy. Survival analysis demonstrated a median survival time of 24 months (95% confidence interval 0–49 months), with only a 10th of patients surviving to 5 years of age. Survival outcomes were significantly better in patients with compound heterozygous mutations (P = 0.046), as well as in patients with the recurrent p.Gln336Arg mutation. Acquired microcephaly and regression of skills in long-term survivors suggests a neurodegenerative component superimposed on the principal neurodevelopmental defect. Two-thirds of patients had a severe seizure disorder, placing EPG5 within the rapidly expanding group of genes associated with early-onset epileptic encephalopathies. Consistent neuroradiological features comprised structural abnormalities, in particular callosal agenesis and pontine hypoplasia, delayed myelination and, less frequently, thalamic signal intensity changes evolving over time. Typical muscle biopsy features included fibre size variability, central/internal nuclei, abnormal glycogen storage, presence of autophagic vacuoles and secondary mitochondrial abnormalities. Nerve biopsy performed in one case revealed subtotal absence of myelinated axons. Post-mortem examinations in three patients confirmed neurodevelopmental and neurodegenerative features and multisystem involvement. Finally, downregulation of epg5 (CG14299) in Drosophila resulted in autophagic abnormalities and progressive neurodegeneration. We conclude that EPG5-related Vici syndrome defines a novel group of neurodevelopmental disorders that should be considered in patients with suggestive features in whom mitochondrial, glycogen, or lysosomal storage disorders have been excluded. Neurological progression over time indicates an intriguing link between neurodevelopment and neurodegeneration, also supported by neurodegenerative features in epg5-deficient Drosophila, and recent implication of other autophagy regulators in late-onset neurodegenerative disease

The Italian arm of the PREPARE study: an international project to evaluate and license a maternal vaccine against group B streptococcus.

BACKGROUND: Group B streptococcus (GBS) is a leading cause of sepsis, pneumonia and meningitis in infants, with long term neurodevelopmental sequelae. GBS may be associated with poor pregnancy outcomes, including spontaneous abortion, stillbirth and preterm birth. Intrapartum antibiotic prophylaxis (IAP) is currently the only way to prevent early-onset disease (presenting at 0 to 6 days of life), although it has no impact on the disease presenting over 6 days of life and its implementation is challenging in resource poor countries. A maternal vaccine against GBS could reduce all GBS manifestations as well as improve pregnancy outcomes, even in low-income countries. MAIN BODY: The term "PREPARE" designates an international project aimed at developing a maternal vaccination platform to test vaccines against neonatal GBS infections by maternal immunization. It is a non-profit, multi-center, interventional and experimental study (promoted by the St George University of London. [UK]) with the aim of developing a maternal vaccination platform, determining pregnancy outcomes, and defining the extent of GBS infections in children and mothers in Africa. PREPARE also aims to estimate the protective serocorrelates against the main GBS serotypes that cause diseases in Europe and Africa and to conduct two trials on candidate GBS vaccines. PREPARE consists of 6 work packages. In four European countries (Italy, UK, Netherlands, France) the recruitment of cases and controls will start in 2020 and will end in 2022. The Italian PREPARE network includes 41 centers. The Italian network aims to collect: GBS isolates from infants with invasive disease, maternal and neonatal sera (cases); cord sera and GBS strains from colonized mothers whose infants do not develop GBS infection (controls). SHORT CONCLUSION: PREPARE will contribute information on protective serocorrelates against the main GBS serotypes that cause diseases in Europe and Africa. The vaccine that will be tested by the PREPARE study could be an effective strategy to prevent GBS disease

Integrating health care practices with the promotion of breastfeeding

Although breastfeeding is the normative standards for infant nutrition, exclusive breastfeeding rates at hospital discharge in the general population of newborns are still suboptimal. Besides many other psychological, social, economical, cultural factors, breastfeeding success is also significantly influenced by maternity practices that have the potential to foster or otherwise to hinder breastfeeding physiology during postpartum hospital stay. On their part, health professionals need to improve their knowledge on lactation, to acquire better skills to manage breastfeeding problems and to commit themselves to prepare evidence based clinical protocols that support breastfeeding and the use of human milk. At the Institute for Maternal and Child Health in Trieste (Italy), we have developed two surveillance protocols related to situations that commonly challenge health professionals to give their qualified advice to the breastfeeding dyad. Particularly, we have documented the feasibility of a protocol on the management of skin to skin contact between mother and his/her newborn infant. This protocol is applied in the delivery room in the context of the prevention of sudden unexpected postnatal collapse. The second protocol refers to the management of early neonatal weight loss. Finally, we believe that combining an effective promotion of breastfeeding with good clinical practice is appropriated and safe and we recognize that both the competence and the attitude of staff have an essential role in the success of the initiation of breastfeeding.   Proceedings of the 10th International Workshop on Neonatology · Cagliari (Italy) · October 22nd-25th, 2014 · The last ten years, the next ten years in Neonatology Guest Editors: Vassilios Fanos, Michele Mussap, Gavino Faa, Apostolos Papageorgio