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Background: Synbiotics are a mixture comprising of live microorganisms and substrate(s) selectively utilized by host microorganisms that confers a health benefit on the host. There is an increasing number of studies investigating their role in different diseases and disorders. Aim: The purpose of this article is to provide recommendations for the use of synbiotics in the management of pediatric gastrointestinal disorders. The recommendations are developed by the ESPGHAN Special Interest Group on Gut Microbiota and Modifications. Methods: From existing literature databases, we searched and appraised all systematic reviews and/or meta-analyses, and subsequently published randomized controlled trials (RCTs) that compared the use of synbiotics, in all delivery vehicles and formulations, at any dose, compared to no synbiotics. Synbiotics which are part of infant formula were not assessed. The recommendations were formulated only if at least 2 RCTs that used a well-defined synbiotic were available. Results: Based on the currently available evidence, no recommendation can be formulated in favor or against the use of evaluated synbiotic combination in the treatment of acute gastroenteritis, prevention of necrotizing enterocolitis, Helicobacter pylori infection, inflammatory bowel disease, functional gastrointestinal disorders, and allergy in infants and children. Conclusions: There is a need for more, well- designed RCTs on the role of synbiotics in gastrointestinal disorders with the same outcome measures to enable the inter-studies comparisons.

Antenatal Doppler disturbances are associated with fetal hypoxia and may induce a brain-sparing vascular redistribution at the expense of splanchnic circulation, possibly predisposing to gut complications. We aimed to compare several gastrointestinal outcomes among very-low-birthweight (VLBW) preterm infants with different antenatal Doppler features. VLBW infants born between 2010–2022 were retrospectively included and stratified into the following clusters based on antenatal Doppler characteristics: normal Doppler (controls); absent or reversed end-diastolic flow in the umbilical artery (UA-AREDF) alone or also in the ductus venosus (UA+DV-AREDF); and abnormal Doppler with or without brain-sparing redistribution. The following outcomes were evaluated: time to reach full enteral feeds (FEF), feeding intolerance (FI), necrotizing enterocolitis (NEC), and spontaneous intestinal perforation (SIP). Overall, 570 infants were included. Infants born following UA+DV-AREDF had significantly higher FI, NEC, and SIP rates and achieved FEF later compared to controls. Increased FI prevalence and a longer time to FEF compared to controls were also observed among UA-AREDF infants and in the presence of brain-sparing redistribution, which also increased NEC rates. Antenatal Doppler abnormalities exacerbate the gastrointestinal risks of preterm infants. Detailed knowledge of Doppler features can aid in identifying those at highest risk of intestinal complications who may benefit from tailored enteral feeding management.

Background: Recent evidence supports a role of probiotics in preventing necrotizing enterocolitis (NEC) in preterm infants. Methods: A systematic review and network meta-analysis of randomized controlled trials (RCTs) on the role of probiotics in preventing NEC in preterm infants, focusing on the differential effect of type of feeding, was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A random-effects model was used; a subgroup analysis on exclusively human milk (HM)-fed infants vs. infants receiving formula (alone or with HM) was performed. Results: Fifty-one trials were included (10,664 infants, 29 probiotic interventions); 31 studies (19 different probiotic regimens) were suitable for subgroup analysis according to feeding. In the overall analysis, Lactobacillus acidophilus LB revealed the most promising effect for reducing NEC risk (odds ratio (OR), 0.03; 95% credible intervals (CrIs), 0.00–0.21). The subgroup analysis showed that Bifidobacterium lactis Bb-12/B94 was associated with a reduced risk of NEC stage ≥2 in both feeding type populations, with a discrepancy in the relative effect size in favour of exclusively HM-fed infants (OR 0.04; 95% CrIs B. lactis Bb-12/B94 could reduce NEC risk with a different size effect according to feeding type. Of note, most probiotic strains are evaluated in few trials and relatively small populations, and outcome data according to feeding type are not available for all RCTs. Further trials are needed to confirm the present findings.

During the last decade several paediatric studies have been published with different possible indications for probiotics, leading to a global increase of probiotics’ market. Nevertheless, different study designs, multiple single/combined strains and small sample size still leave many uncertainties regarding their efficacy. In addition, different regulatory and quality control issues make still very difficult the interpretation of the clinical data. The objective of this review is to critically summarise the current evidence on probiotics’ efficacy and safety on a different number of pathologies, including necrotizing enterocolitis, acute infectious diarrhoea, allergic diseases and functional gastrointestinal disorders in order to guide paediatric healthcare professionals on using evidence-based probiotics’ strains. To identify relevant data, literature searches were performed including Medline-PubMed, the Cochrane Library and EMBASE databases. Considering probiotics strain-specific effects, the main focus was on individual probiotic strains and not on probiotics in general.

Zinc is a key element for growth and development. In this narrative review, we focus on the role of dietary zinc in early life (including embryo, fetus and preterm neonate), analyzing consequences of zinc deficiency and adequacy of current recommendations on dietary zinc. We performed a systematic search of articles on the role of zinc in early life. We selected and analyzed 81 studies. Results of this analysis showed that preservation of zinc balance is of critical importance for the avoidance of possible consequences of low zinc levels on pre- and post-natal life. Insufficient quantities of zinc during embryogenesis may influence the final phenotype of all organs. Maternal zinc restriction during pregnancy influences fetal growth, while adequate zinc supplementation during pregnancy may result in a reduction of the risk of preterm birth. Preterm neonates are at particular risk to develop zinc deficiency due to a combination of different factors: (i) low body stores due to reduced time for placental transfer of zinc; (ii) increased endogenous losses; and (iii) marginal intake. Early diagnosis of zinc deficiency, through the measurement of serum zinc concentrations, may be essential to avoid severe prenatal and postnatal consequences in these patients. Typical clinical manifestations of zinc deficiency are growth impairment and dermatitis. Increasing data suggest that moderate zinc deficiency may have significant subclinical effects, increasing the risk of several complications typical of preterm neonates (i.e., necrotizing enterocolitis, chronic lung disease, and retinopathy), and that current recommended intakes should be revised to meet zinc requirements of extremely preterm neonates. Future studies evaluating the adequacy of current recommendations are advocated.

Necrotizing enterocolitis continues to be a devastating disease process for very low birth weight infants in Neonatal Intensive Care Units. The aetiology and pathogenesis of necrotizing enterocolitis are not definitively understood. It is known that necrotizing enterocolitis is secondary to a complex interaction of multiple factors that results in mucosal damage, which leads to intestinal ischemia and necrosis. Advances in neonatal care, including resuscitation and ventilation support technology, have seen increased survival rates among premature neonates and a concomitant detection in the incidence of this intestinal disease. Diagnosis can be difficult, and identifying infants at the onset of disease remains a challenge. Early diagnosis, which relies on imaging findings, and initiation of prompt therapy are essential to limit morbidity and mortality. Moreover, early management is critical and life-saving. This review summarizes what is known on the laboratory and instrumental diagnostic strategies needed to improve neonatal outcomes and, possibily, to prevent the onset of an overt necrotizing enterocolitis.

Preterm infants are often considered too unstable to be fed enterally so they are exposed to complications related to a prolonged enteral fasting. Our study aims to compare feeding tolerance of adequate for gestational age (AGA) versus small for gestational age (SGA) infants and to evaluate which perinatal factors affect feeding tolerance (measured as time to achieve full enteral feeding, FEF). Inborn infants with a gestational age (GA) less than 32 weeks, born from January 2006 to December 2010, were eligible for this study. We enrolled 310 infants. The time to FEF was longer for SGA infants than for AGA, while a longer GA was associated to a reduced time to FEF. A beneficial effect was observed for antenatal steroids, while Apgar score below 7, the administration of inotrops or caffeine, the occurrence of sepsis or NEC and the presence of PDA were associated to a longer time to FEF. When evaluated jointly with a multivariate analysis, GA (p < 0.0001), antenatal steroids prophylaxis (p = 0.002), SGA (p < 0.0001) and occurrence of NEC (p = 0.0002) proved to have independent prognostic impact on the time to FEF. Feeding tolerance is better as GA increases, and worsen in SGA infants. Antenatal betamethasone is effective in reducing the time to FEF in both AGA and SGA.