Guglielmo Salvatori

Effect of Breast and Formula Feeding on Gut Microbiota Shaping in Newborns

The gastrointestinal microbiota is a complex and dynamic ecosystem consisting of several hundreds of different microbes, mainly bacteria (1011–12 bacteria/g of colonic content, forming 60% of total fecal mass; Eckburg et al., 2005; O’Hara and Shanahan, 2006). Total number of bacteria exceeds 10 times the number of human cells, and the collection of microbial genome (microbiome) contains 100 times more genes than the human genome (Vael and Desager, 2009). Gut microbiota influence the growth and differentiation of gut epithelial cells, and play pivotal nutritive, metabolic, immunological, and protective functions (O’Hara and Shanahan, 2006). Its deregulation is involved in the pathogenesis of immunological, cardiovascular, and metabolic diseases (Hammer, 2011; Maslowski and MacKay, 2011; Harris et al., 2012). The investigation on microbiota composition started in 1900 (Tissier, 1900) and has been performed by culturing methods since the recent advent of DNA sequence-based methods, that, thanks to their ability to identify a large number of species that cannot be cultivated, have allowed a more complete and rapid assessment of the gastrointestinal ecosystem (Palmer et al., 2007; Adlerberth and Wold, 2009). On the basis of 16S ribosomial – RNA encoding gene, more than 7000 distinct phylotypes have been detected in the human distal gut (Vael and Desager, 2009), with high inter-individual and age variability, but belonging to a limited number of broad taxonomic divisions (mainly the anaerobes Bacteroides, Eubacterium, Clostridium; Hayashi et al., 2002; Eckburg et al., 2005; Zoetendal et al., 2008). In a very recent study, Arumugam et al. (2011), by combining fecal metagenomes of individuals from different countries, identified three different enterotypes (with the prevalence of Bacteroides, Prevotella, and Ruminococcus species, respectively) that are not nation or continent specific, and showed that intestinal microbiota variation is stratified, not continuous, indicating further the existence of a limited number of well-balanced host-microbial symbiotic states. These enterotypes do not seem to differ in functional richness and apparently do not correlate with nationality, gender, age, or body mass index; at the same time, they seem to characterize and be quite stable in individuals, so that they can be restored after perturbations. Gut microbiota composition and concentration physiologically varies throughout the gastrointestinal tract (increasing gradient from the stomach to the colon and characteristic gut-compartment distribution of microflora) and life stages, progressing from the newborn sterility to the extremely variable and dense colonization of adult gut, under the influence of various internal host-related and external factors (Mackie et al., 1999; Palmer et al., 2007).

Breastfeeding promotion in neonatal intensive care unit: impact of a new program toward a BFHI for high‐risk infants

Aim: The study evaluates a breastfeeding promotion program in an Italian neonatal intensive care unit (NICU) over a period of time.

Multicentre consensus recommendations for skin care in inherited epidermolysis bullosa

BackgroundInherited epidermolysis bullosa (EB) comprises a highly heterogeneous group of rare diseases characterized by fragility and blistering of skin and mucous membranes. Clinical features combined with immunofluorescence antigen mapping and/or electron microscopy examination of a skin biopsy allow to define the EB type and subtype. Molecular diagnosis is nowadays feasible in all EB subtypes and required for prenatal diagnosis. The extent of skin and mucosal lesions varies greatly depending on EB subtype and patient age. In the more severe EB subtypes lifelong generalized blistering, chronic ulcerations and scarring sequelae lead to multiorgan involvement, major morbidity and life-threatening complications. In the absence of a cure, patient management remains based on preventive measures, together with symptomatic treatment of cutaneous and extracutaneous manifestations and complications. The rarity and complexity of EB challenge its appropriate care. Thus, the aim of the present study has been to generate multicentre, multidisciplinary recommendations on global skin care addressed to physicians, nurses and other health professionals dealing with EB, both in centres of expertise and primary care setting.MethodsAlmost no controlled trials for EB treatment have been performed to date. For this reason, recommendations were prepared by a multidisciplinary team of experts from different European EB centres based on available literature and expert opinion. They have been subsequently revised by a panel of external experts, using an online-modified Delphi method to generate consensus.ResultsRecommendations are reported according to the age of the patients. The major topics treated comprise the multidisciplinary approach to EB patients, global skin care including wound care, management of itching and pain, and early diagnosis of squamous cell carcinoma. Aspects of therapeutic patient education, care of disease burden and continuity of care are also developed.ConclusionThe recommendations are expected to be useful for daily global care of EB patients, in particular in the community setting. An optimal management of patients is also a prerequisite to allow them to benefit from the specific molecular and cell-based treatments currently under development.

Phylogenetic and Metabolic Tracking of Gut Microbiota during Perinatal Development

The colonization and development of gut microbiota immediately after birth is highly variable and depends on several factors, such as delivery mode and modality of feeding during the first months of life. A cohort of 31 mother and neonate pairs, including 25 at-term caesarean (CS) and 6 vaginally (V) delivered neonates (DNs), were included in this study and 121 meconium/faecal samples were collected at days 1 through 30 following birth. Operational taxonomic units (OTUs) were assessed in 69 stool samples by phylogenetic microarray HITChip and inter- and intra-individual distributions were established by inter-OTUs correlation matrices and OTUs co-occurrence or co-exclusion networks. 1H-NMR metabolites were determined in 70 stool samples, PCA analysis was performed on 55 CS DNs samples, and metabolome/OTUs co-correlations were assessed in 45 CS samples, providing an integrated map of the early microbiota OTUs-metabolome. A microbiota “core” of OTUs was identified that was independent of delivery mode and lactation stage, suggesting highly specialized communities that act as seminal colonizers of microbial networks. Correlations among OTUs, metabolites, and OTUs-metabolites revealed metabolic profiles associated with early microbial ecological dynamics, maturation of milk components, and host physiology.

Pharmacological research in neonatology

In neonatalogy unit 40 to 80% of the drugs are used as off-label or unlicensed, particularly in Neonatal Intensive Care Unit (NICU), where it has been described that in a single patient up to 60 parenteral drugs can be administered. The course of a drug inside the organism can be defined in 4 different phases: absorption, distribution, metabolism, elimination; for each of these phases the newborn infant has different characteristics than child and adult. In the last years much more attention has been put in pharmacological research specific for the neonatal age and a good trial design should take into account the following points: (1) to define the pediatric disease in terms of natural history, prevalence, severity, treatment and impact of the new drug; (2) to avoid the “try and error” method based on the adult dose corrected for weight or age; (3) to use adapted methodologies (pharmacokinetics); (4) to avoid small clinical trials (limited number of patients), the use of Randomized Controlled Trials rather than observational studies; (5) to consider ethics providing clear information and reducing pain and stress to the baby and its family.

A Sensitive and Effective Proteomic Approach to Identify She-Donkey's and Goat's Milk Adulterations by MALDI-TOF MS Fingerprinting

She-donkey’s milk (DM) and goat’s milk (GM) are commonly used in newborn and infant feeding because they are less allergenic than other milk types. It is, therefore, mandatory to avoid adulteration and contamination by other milk allergens, developing fast and efficient analytical methods to assess the authenticity of these precious nutrients. In this experimental work, a sensitive and robust matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) profiling was designed to assess the genuineness of DM and GM milks. This workflow allows the identification of DM and GM adulteration at levels of 0.5%, thus, representing a sensitive tool for milk adulteration analysis, if compared with other laborious and time-consuming analytical procedures.

WTX R353X mutation in a family with osteopathia striata and cranial sclerosis (OS-CS): case report and literature review of the disease clinical, genetic and radiological features

Osteopathia striata with cranial sclerosis (OS-CS) or Horan-Beighton syndrome is a rare X-linked dominant inherited bone dysplasia, characterized by longitudinal striations of long bones and cranial sclerosis. Patients can be asymptomatic or present with typical facial dysmorphism, sensory defects, internal organs anomalies, growth and mental retardation, depending on the severity of the disease. WTX gene (Xq11) has been recently identified as the disease causing gene. Aim of this article is to present the case of a 6 year old girl initially evaluated for bilateral hearing loss. Patient’s head CT scan pointed out sclerosis of skull base and mastoid cells, and abnormal middle-ear ossification. Clinical examination of the patient and her mother were suspicious for OS-CS. The diagnosis was confirmed by X-rays examination showing typical longitudinal striation. Genetic analysis allowed the identification of maternally transmitted heterozygous nonsense c.1057C>T (p.R353X) WTX gene mutation. We also provide a systematic review of currently available knowledge about clinical, radiologic and genetic features typical of the OS-CS.

Docosahexaenoic Acid Supplementation during Pregnancy: A Potential Tool to Prevent Membrane Rupture and Preterm Labor

Polyunsaturated fatty acids (PUFAs) are required to maintain the fluidity, permeability and integrity of cell membranes. Maternal dietary supplementation with ω-3 PUFAs during pregnancy has beneficial effects, including increased gestational length and reduced risk of pregnancy complications. Significant amounts of ω-3 docosahexaenoic acid (DHA) are transferred from maternal to fetal blood, hence ensuring high levels of DHA in the placenta and fetal bloodstream and tissues. Fetal DHA demand increases exponentially with gestational age, especially in the third trimester, due to fetal development. According to the World Health Organization (WHO) and the Food and Agriculture Organization of the United Nations (FAO), a daily intake of DHA is recommended during pregnancy. Omega-3 PUFAs are involved in several anti-inflammatory, pro-resolving and anti-oxidative pathways. Several placental disorders, such as intrauterine growth restriction, premature rupture of membranes (PROM) and preterm-PROM (pPROM), are associated with placental inflammation and oxidative stress. This pilot study reports on a preliminary evaluation of the significance of the daily DHA administration on PROM and pPROM events in healthy pregnant women. Further extensive clinical trials will be necessary to fully elucidate the correlation between DHA administration during pregnancy and PROM/pPROM occurrence, which is related in turn to gestational duration and overall fetal health.

Radiological contrast media in the breastfeeding woman: a position paper of the Italian Society of Radiology (SIRM), the Italian Society of Paediatrics (SIP), the Italian Society of Neonatology (SIN) and the Task Force on Breastfeeding, Ministry of Health, Italy

ObjectivesBreastfeeding is a well-recognised investment in the health of the mother-infant dyad. Nevertheless, many professionals still advise breastfeeding mothers to temporarily discontinue breastfeeding after contrast media imaging. Therefore, we performed this review to provide health professionals with basic knowledge and skills for appropriate use of contrast media.MethodsA joint working group of the Italian Society of Radiology (SIRM), Italian Society of Paediatrics (SIP), Italian Society of Neonatology (SIN) and Task Force on Breastfeeding, Ministry of Health, Italy prepared a review of the relevant medical literature on the safety profile of contrast media for the nursing infant/child.ResultsBreastfeeding is safe for the nursing infant of any post-conceptional age after administration of the majority of radiological contrast media to the mother; only gadolinium-based agents considered at high risk of nephrogenic systemic fibrosis (gadopentetate dimeglumine, gadodiamide, gadoversetamide) should be avoided in the breastfeeding woman as a precaution; there is no need to temporarily discontinue breastfeeding or to express and discard breast milk following the administration of contrast media assessed as compatible with breastfeeding.ConclusionsBreastfeeding women should receive unambiguous professional advice and clear encouragement to continue breastfeeding after imaging with the compatible contrast media.Key Points:• Breastfeeding is a well-known investment in the health of the mother-infant dyad.• Breastfeeding is safe after administration of contrast media to the mother.• There is no need to temporarily discontinue breastfeeding following administration of contrast media.

Teaching NeuroImages: Acute necrotizing encephalopathy during novel influenza A (H1N1) virus infection

Since the outbreak of novel influenza A (H1N1) in 2009, various neurologic complications have been cited.1 A 2-month-old girl died of a rapidly progressive encephalopathy after influenza infection. MRI, performed after 12 hours from the onset of symptoms, showed bilateral and symmetric lesions including the thalamus, the cortical–subcortical regions of the occipital and parietal lobes, and brainstem tegmentum …