Metabolomics applications in children: A right way to go

Metabolomics is a new science based on the study of the metabolome, representing the set of all the metabolites of a biological organism, which are the final products of its gene expression. Metabolomics appears to be a promising tool in perinatal studies, such as hypoxic–ischemic encephalopathy (HIE), intrauterine growth restriction (IUGR), congenital infections, genetic diseases, neonatal nutrition

Mediterranean Diet in Developmental Age: A Narrative Review of Current Evidences and Research Gaps

Numerous studies in recent decades have shown that Mediterranean diet (MD) can reduce the risk of developing obesity in pediatric patients. The current narrative review summarizes recent evidence regarding the impact of MD across the different stages of child development, starting from fetal development, analyzing breastfeeding and weaning, through childhood up to adolescence, highlighting the gaps in knowledge for each age group. A literature search covering evidence published between 1 January 2000 and 1 March 2022 and concerning children only was conducted using multiple keywords and standardized terminology in PubMed database. A lack of scientific evidence about MD adherence concerns the age group undergoing weaning, thus between 6 months and one year of life. In the other age groups, adherence to MD and its beneficial effects in terms of obesity prevention has been extensively investigated, however, there are still few studies that correlate this dietary style with the incidence of non-communicable diseases. Furthermore, research on multi-intervention strategy should be implemented, especially regarding the role of education of children and families in taking up this healthy dietary style

Vegetarian and vegan weaning of the infant: How common and how evidence-based? a population-based survey and narrative review

Background: Vegetarian and vegan weaning have increasing popularity among parents and families. However, if not correctly managed, they may lead to wrong feeding regimens, causing severe nutritional deficiencies requiring specific nutritional support or even the need for hospitalization. Aim: To assess the prevalence of vegetarian and vegan weaning among Italian families and to provide an up-to-date narrative review of supporting evidence. Materials and methods: We investigated 360 Italian families using a 40-item questionnaire. The narrative review was conducted searching scientific databases for articles reporting on vegetarian and vegan weaning. Results: 8.6% of mothers follow an alternative feeding regimen and 9.2% of infants were weaned according to a vegetarian or vegan diet. The breastfeeding duration was longer in vegetarian/vegan infants (15.8 vs. 9.7 months; p < 0.0001). Almost half of parents (45.2%) claim that their pediatrician was unable to provide sufficient information and adequate indications regarding unconventional weaning and 77.4% of parents reported the pediatrician’s resistance towards alternative weaning methods. Nine studies were suitable for the review process. The vast majority of authors agree on the fact that vegetarian and vegan weaning may cause severe nutritional deficiencies, whose detrimental effects are particularly significant in the early stages of life. Discussion and conclusion: Our results show that alternative weaning methods are followed by a significant number of families; in half of the cases, the family pediatrician was not perceived as an appropriate guide in this delicate process. To date, consistent findings to support both the safety and feasibility of alternative weaning methods are still lacking. Since the risk of nutritional deficiencies in the early stages of life is high, pediatricians have a pivotal role in guiding parents and advising them on the most appropriate and complete diet regimen during childhood. Efforts should be made to enhance nutritional understanding among pediatricians as an unsupervised vegetarian or vegan diet can cause severe nutritional deficiencies with possible detrimental long-term effects

Invasive fungal infections in Neonatal Intensive Care Units of Southern Italy: a multicentre regional active surveillance (AURORA Project)

Introduction. During the past years invasive fungal infections (IFIs) have become an increasingly important problem in infants hospitalized in the Neonatal Intensive Care Unit (NICU). Candida species is the third most-common agent of late-onset infections in critically ill neonates, with an estimated incidence of 2.6-10% in very low birth weight and 5.5-20% in extremely low birth weight infants. The aim of this observational study is to evaluate the epidemiology of IFIs among infants admitted to NICUs of one Italian region by a multicenter surveillance (Aurora Project). Methods. The IFIs surveillance was carried out prospectively in Apulia (Southern Italy) between February 2007 and August 2008. This report focuses on the results from 6 enrolled NICUs. Results. Twenty-one neonates developed IFIs: the overall incidence was 1.3% and crude mortality was 23.8%. Infants weighing ? 1500g (4.3%) showed a significantly higher incidence than those ? 2500g (0.2%). C.parapsilosis (61.9%) was the most frequent isolated species. The main potential risk factors were having a central venous catheter placed, length of stay in NICU > 7 days and total parenteral nutrition for > 5 days. The (1,3)-Ã-D glucan (BDG), mannan antigens and anti-Candida antibodies? evaluation was performed in 7 neonates. All neonates were positive to the BDG; the mannan antigen result was positive in 5 newborns, the anti-mannan antibodies were always negative. All isolates were amphotericin B and fluconazole-susceptible. Discussion. This first prospective study on neonatal fungal infection in one Italian region gives evidence of a preponderance of non-albicans Candida spp and indicates potential utility of BDG as an adjunct diagnostic test

COVID-19 Infection in Pregnancy: Obstetrical Risk Factors and Neonatal Outcomes—A Monocentric, Single-Cohort Study

The effects of coronavirus disease 2019 caused by severe acute respiratory syndrome coronavirus 2 on pregnant women and neonates are mainly unknown, since limited data are available in the literature. We conducted a monocentric and cross-sectional study enrolling 122 un-vaccinated pregnant women with COVID-19 infection tested by RT-PCR nasopharyngeal swab. Only 4.1% of the patients had severe COVID-19 symptoms together with major respiratory symptoms and intensive care unit admission, whereas 35.25% of women had comorbidities and two-thirds of them were overweight or obese. COVID-19 was detected mainly in the third trimester (98.36%) and multiparous women (59.02%). The mode of delivery was influenced by mild–severe COVID-19 symptoms, with a higher number of urgent or emergent cesarean sections than spontaneous or operative vaginal births. Preterm births were associated with high BMI, mode of delivery (higher among cesarean sections), nulliparity, and severe COVID-19 symptoms. In cases of severe COVID-19 symptoms, there was a higher rate of respiratory distress syndrome among newborns. In the end, only the presence of a severe COVID-19 infection worsened the obstetrical and neonatal outcomes, with higher rates of urgent or emergent cesarean section, preterm births, and neonatal respiratory distress syndrome

An autoregressive model based on the generalized hyperbolic distribution

We define a nonlinear autoregressive time series model based on the generalized hyperbolic distribution in an attempt to model time series with non-Gaussian features such as skewness and heavy tails. We show that the resulting process has a simple condition for stationarity and it is also ergodic. An empirical example with a forecasting experiment is presented to illustrate the features of the proposed model.Peer reviewe

Longitudinal Multi-Omics Study of a Mother-Infant Dyad from Breastfeeding to Weaning: An Individualized Approach to Understand the Interactions Among Diet, Fecal Metabolome and Microbiota Composition

The development of the human gut microbiota is characterized by a dynamic sequence of events from birth to adulthood, which make the gut microbiota unique for everyone. Its composition and metabolism may play a critical role in the intestinal homeostasis and health. We propose a study on a single mother-infant dyad to follow the dynamics of an infant fecal microbiota and metabolome changes in relation to breast milk composition during the lactation period and evaluate the changes induced by introduction of complementary food during the weaning period. Nuclear Magnetic Resonance (NMR)-based metabolomics was performed on breast milk and, together with 16S RNA targeted-metagenomics analysis, also on infant stool samples of a mother-infant dyad collected over a period running from the exclusive breastfeeding diet to weaning. Breast milk samples and neonatal stool samples were collected from the 4th to the 10th month of life. Both specimens were collected from day 103 to day 175, while from day 219–268 only stool samples were examined. An exploratory and a predictive analysis were carried out by means of Common component and specific weight analysis and multi-block partial least squares discriminant analysis, respectively. Stools collected during breastfeeding and during a mixed fruit/breastfeeding diet were characterized by high levels of fucosyl-oligosaccharides and glycolysis intermediates, including succinate and formate. The transition to a semi-solid food diet was characterized by several changes in fecal parameters: increase in short-chain fatty acids (SCFAs) levels, including acetate, propionate and butyrate, dissapearance of HMOs and the shift in the community composition, mainly occurring within the Firmicutes phylum. The variations in the fecal metabolome reflected the infant’s diet transition, while the composition of the microbiota followed a more complex and still unstable behavior

A Possible Outbreak by Serratia Marcescens: Genetic Relatedness between Clinical and Environmental Strains

Serratia marcescens (SM) is a Gram-negative bacterium that is frequently found in the environment. Since 1913, when its pathogenicity was first demonstrated, the number of infections caused by SM has increased. There is ample evidence that SM causes nosocomial infections in immunocompromised or critically ill patients admitted to the intensive care units (ICUs), but also in newborns admitted to neonatal ICUs (NICUs). In this study, we evaluated the possible genetic correlation by PFGE between clinical and environmental SM strains from NICU and ICU and compared the genetic profile of clinical strains with strains isolated from patients admitted to other wards of the same hospital. We found distinct clonally related groups of SM strains circulating among different wards of a large university hospital. In particular, the clonal relationship between clinical and environmental strains in NICU and ICU 1 was highlighted. The identification of clonal relationships between clinical and environmental strains in the wards allowed identification of the epidemic and rapid implementation of adequate measures to stop the spread of SM

Less is more: Antibiotics at the beginning of life

Antibiotic exposure at the beginning of life can lead to increased antimicrobial resistance and perturbations of the developing microbiome. Early-life microbiome disruption increases the risks of developing chronic diseases later in life. Fear of missing evolving neonatal sepsis is the key driver for antibiotic overtreatment early in life. Bias (a systemic deviation towards overtreatment) and noise (a random scatter) affect the decision-making process. In this perspective, we advocate for a factual approach quantifying the burden of treatment in relation to the burden of disease balancing antimicrobial stewardship and effective sepsis management

Is Lactoferrin More Effective in Reducing Late-Onset Sepsis in Preterm Neonates Fed Formula Than in Those Receiving Mother's Own Milk? Secondary Analyses of Two Multicenter Randomized Controlled Trials

Background: Lactoferrin is the major antimicrobial protein in human milk. In our randomized controlled trial (RCT) of bovine lactoferrin (BLF) supplementation in preterm neonates, BLF reduced late-onset sepsis (LOS). Mother's own milk (MM) contains higher concentrations of lactoferrin than donor milk or formula, but whether BLF is more effective in infants who receive formula or donor milk is uncertain. Aim: To evaluate the incidence of LOS in preterm infants fed MM and in those fed formula and/or donor milk. Study Design: This is a (A) post hoc subgroup analysis, in our RCT of BLF, of its effects in preterm infants fed MM, with or without formula, versus those fed formula and/or donor milk (no-MM) and (B) post hoc meta-analysis, in our RCT of BLF and in the ELFIN (Enteral Lactoferrin in Neonates) RCT, of the effect of BLF in subgroups not exclusively fed MM. Results (A) Of 472 infants in our RCT, 168 were randomized to placebo and 304 were randomized to BLF. Among MM infants, LOS occurred in 22/133 (16.5%) infants randomized to placebo and in 14/250 (5.6%) randomized to BLF (relative risk or risk ratio (RR): 0.34; relative risk reduction (RRR): 0.66; 95% confidence interval (95% CI) for RR: 0.18-0.64; p < 0.0008). Among no-MM infants, LOS occurred in 7/35 (20.0%) randomized to placebo and in 2/54 (3.7%) randomized to BLF (RR: 0.19; RRR: 0.81; 95% CI for RR: 0.16-0.96; p = 0.026). In multivariable logistic regression analysis, there was no interaction between BLF treatment effect and type of feeding (p = 0.628). (B) In 1,891 infants not exclusively fed MM in our RCT of BLF and in the ELFIN RCT, BLF reduced the RR of LOS by 18% (RR: 0.82; 95% CI: 0.71-0.96; p = 0.01). Conclusion: Adequately powered studies should address the hypothesis that BLF is more effective in infants fed formula or donor milk than those fed MM. Such studies should evaluate whether a specific threshold of total lactoferrin intake can be identified to protect such patients from LOS