Should we definitively abandon prophylaxis for patent ductus arteriosus in preterm new-borns?

Although the prophylactic administration of indomethacin in extremely low-birth weight infants reduces the frequency of patent ductus arteriosus and severe intraventricular hemorrhage, it does not appear to provide any long-term benefit in terms of survival without neurosensory and cognitive outcomes. Considering the increased drug-induced reduction in renal, intestinal, and cerebral blood flow, the use of prophylaxis cannot be routinely recommended in preterm neonates. However, a better understanding of the genetic background of each infant may allow for individualized prophylaxis using NSAIDs and metabolomics

group b streptococcal meningitis a description of six case reports

Group B Streptococcus (GBS) is considered the leading bacterial cause of neonatal infections and meningitis is the most serious manifestation. Its clinical manifestations are usually non-specific and its signs and symptoms may be subtle, unspecific, vague, atypical or absent. We report six clinical cases of GBS meningitis with early onset in three infants (first week of life) and late onset (after 1 month of life) in the remaining three. Prenatal GBS screening, performed on four infants, resulted positive only in one case. Cerebral ultrasonography showed high sensitivity in detecting early meningeal involvement confirmed by MRI in all infants. Our study describes the clinical characteristics, antibiotic sensitivity and outcome of the six cases. The results of our analysis emphasize the severity of GBS meningitis and show that cerebrovascular involvement is a common but poorly studied pathologic process in GBS meningitis. In addition, cranial ultrasonography plays an important role in detecting infarctions, cerebritis, hemorrhages or abscesses and in monitoring complications. Neonates with GBS meningitis are prone to adverse outcomes or sequelae. Mortality in GBS meningitis approaches 30% and neurologic sequelae are present in 25% of cases. Int J Clin Pediatr. 2015;4(1):127-136 doi: http://dx.doi.org/10.14740/ijcp179

Once we were bacteria… mitochondria to infinity and beyond

Mitochondria, cytoplasmic organelles originated from endosymbiotic bacteria, can be metaphorically described using “Janus bifrons” image, due to their involvement in life, providing cellular energy and resulting essential even for stem cells, but playing a key role also in cell death. Mitochondria own a maternally inherited genome and are the site of aerobic respiration; they can produce proteins, nucleotides, lipids, steroids and heme and result involved in iron homeostasis. Moreover, mitochondria can generate free radicals, break down waste products and represent the primary source of cellular heat. The size and shape of mitochondria depend on the intracellular metabolic status, from tubular presentation to a blob form in case of irreversible damage. Each mitochondrion carries different sets of DNA; when one set accumulates mutations, it can be replaced by another. It has been widely demonstrated that mitochondrial disorders are involved in many pathologies, including autism, multiple endocrinopathies, diabetes, Alzheimer’s disease, ataxia, Barth’s syndrome, myopathy, and even aging and cancer. Human population is characterized by different mitochondrial DNA haplogroups reflecting the mutations accumulated and useful to characterize genetic diversity. The mitochondrial role also results relevant in pregnancy, providing information about maternal-fetal dyad in physiological and in pathological conditions. Recent evidence suggests that an intriguing bidirectional inter-talk exists between microbiota and mitochondria, influencing cellular homeostasis and metabolism. A recently demonstrated mitochondrial property is the possibility to be transferred from a donor cell to a recipient cell, through a system of tunneling nanotubes. Recently, a promising integrated approach involving omics sophisticate technologies has been applied in mitochondrial pathophysiology. This is still at an early stage, and further studies will clarify such complex genotype-phenotype relationships. In conclusion, mitochondria are not simple energetic organelles but represent dynamic structures communicating with the cell nucleus and even with other cells, influencing metabolism and their targets’ functions. More detailed knowledge of their involvement in disease, even though a combined omics approach, could represent a chance for new therapies

What you have to know about Human Milk Oligosaccharides

Human Milk Oligosaccharides (HMOs), the third most important solid components of BM (the first and the second being lactose and lipids respectively), are a highly variable family of unconjugated glycans related to many pathophysiological short- and long-term effects on infants and, as recently demonstrated, even on the mother. Among their functions are promotion and modulation of gut microbiota, effects on intestinal mucosa and its development, protection against intestinal or extra-intestinal infections, modulation of several immune responses and even extra-intestinal effects, such as brain development, as described in literature. Regarding HMOs composition, it appears that maternal genetic factors play the major role in conferring its high and peculiar inter- and intra-individual variability to BM. HMOs greatly depend on four maternal phenotypes, defined depending on the expression of two specific genes and maternal blood group. The α-1-2-fucosyltransferase (FUT2) gene, expressed in more than 70% of Caucasian women, is codified by the Se gene and allows classification of secretor (Se+) and non-secretor (Se-) mothers. In addition, the α-1-3-4-fucosyltransferase (FUT3) gene indicates positivity or negativity for the Lewis Group (Le+ or Le-). Even other environmental and maternal factors, represented by age, diet, health status, medication and drugs appear to play a role in HMOs composi­tion

Metabolomic Studies in Inborn Errors of Metabolism: Last Years and Future Perspectives

The inborn errors of metabolism (IEMs or Inherited Metabolic Disorders) are a heterogeneous group of diseases caused by a deficit of some specific metabolic pathways. IEMs may present with multiple overlapping symptoms, sometimes difficult delayed diagnosis and postponed therapies. Additionally, many IEMs are not covered in newborn screening and the diagnostic profiling in the metabolic laboratory is indispensable to reach a correct diagnosis. In recent years, Metabolomics helped to obtain a better understanding of pathogenesis and pathophysiology of IEMs, by validating diagnostic biomarkers, discovering new specific metabolic patterns and new IEMs itself. The expansion of Metabolomics in clinical biochemistry and laboratory medicine has brought these approaches in clinical practice as part of newborn screenings, as an exam for differential diagnosis between IEMs, and evaluation of metabolites in follow up as markers of severity or therapies efficacy. Lastly, several research groups are trying to profile metabolomics data in platforms to have a holistic vision of the metabolic, proteomic and genomic pathways of every single patient. In 2018 this team has made a review of literature to understand the value of Metabolomics in IEMs. Our review offers an update on use and perspectives of metabolomics in IEMs, with an overview of the studies available from 2018 to 2022

Multipotent stem cells of mother's milk

In recent years the presence of stem cells (hBSCs: human breastmilkderived stem cells) and epithelial progenitors has been demonstrated in mother’s milk (MM). Stem cells present in samples of fresh MM exhibit a high degree of vitality and this makes possible the performance of cell cultures and to evaluate the differentiation capacity of the hBSCs. The most important datum that expresses the enormous potential of the use of MM stem cells is the presence of a cell population capable of differentiating into the three mesoderm, endoderm and ectoderm lines. The small number of studies and MM samples analyzed and the different sampling methods applied suggest standardization in the collection, analysis and culture of MM in future studies, in consideration of the well-known extreme variability of MM composition, also from the standpoint of cells. The analysis of literature data confirms the uniqueness of MM and its enormous potential

Neonatal congenital central hypoventilation syndrome: Why we should not sleep on it. Literature review of forty-two neonatal onset cases

Congenital Central Hypoventilation Syndrome (CCHS), also referred with the expression "Ondine's Curse" is a rare genetic life-long disease resulting from the mutation of PHOX2B gene on chromosome 4p12.3. CCHS represents an autonomic nervous system disorder; its more fearsome manifestation is central hypoventilation, due to a deficient response of chemoreceptors to hypercapnia and hypoxia. Several associated symptoms can occur, such as pupillary anomalies, arrhythmias, reduced heart rate variability, esophageal dysmotility, structural comorbidities (Hirschprung's Disease or neural crest tumours). CCHS typical onset is during neonatal period, but cases of delayed diagnosis have been reported; moreover, there are both sporadic or familiar cases. In preterm newborns, asphyxia and typical prematurity-related findings may overlap CCHS clinical manifestations and make harder to formulate a correct diagnosis. The early recognition of CCHS allows an appropriate management, useful to reduce immediate and long- term damage

COVID-19 and hepatic damage: what we know? A systematic review

: Since the end of 2019, a new disease outbreak has been spreading worldwide, after starting from Wuhan, China. The viral pathogen responsible for the disease was named as SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2), and for the illness the acronym COVID-19 was coined (COronaVIrus Disease 2019). Viral pathogenesis, epidemiology, and clinics are still somewhat obscure, when occurring during childhood the most. This systematic review aims at evaluating the features of liver involvement and damage in course of COVID-19. An insight into what is known as to COVID-19 and hepatic damage in adulthood as well as paediatric age was given. All the most relevant papers up to 15/10/2020 were identified and discussed. Establishing whether liver damage is due to a direct viral action or host immune system inflammatory reaction or consequence of the administered drugs or secondary to another organ failure (for example the heart) is difficult. What is sure is the fact that liver function should be checked at the time of admission to hospital and during hospitalization. If hepatic markers are altered, a specific therapy to protect liver is needed

New light on white matter damage of the premature brain: a neonatologist's point of view

Periventricular leucomalacia (PVL) is traditionally considered a multifactorial lesion related to three main mechanisms: ischemia, inflammation and excitotoxicity. For years it was believed that hypoperfusion, associated with the peculiar vascular anatomy of the premature brain (border zones), was the conditio sine qua non in the pathogenesis of PVL. More recently this theory has been questioned. Many studies have stressed the importance of the association between inflammation/infection and white matter injury and have supported the multi hit hypothesis according to which several (genetic, hormonal, immune and nutritional) factors may team up in a multi-hit fashion. The emerging concept is that the fetal white cell activation together with the interaction between the innate and adaptive immune system play a main role in white matter damage. Currently there are increasing evidence that PVL is a disease of connectivity. In this article we review the news in the basics of pathogenesis, the incidence, the definition and the diagnosis of PVL. Furthermore, recent follow-up studies and neuroprotective therapies are mentioned.   Proceedings of the International Course on Perinatal Pathology (part of the 10th International Workshop on Neonatology · October 22nd-25th, 2014) · Cagliari (Italy) · October 25th, 2014 · The role of the clinical pathological dialogue in problem solving Guest Editors: Gavino Faa, Vassilios Fanos, Peter Van Eyke