Prevention of vitamin D deficiency in children. The state of the problem in the world and in Ukraine.

The article presents current data on the prevalence of vitamin D deficiency and criteria for its deficiency in children in different countries. Vitamin D is recognized as one of the most important vitamins involved in many biochemical processes in the body. Its active metabolites play a key role in calcium absorption, bone mineralization and promote phosphate and magnesium metabolism. At the same time, in addition to affecting mineral metabolism, there is a wide range of conditions in which vitamin D also plays a preventive role. Vitamin D has been shown to play a vital role in innate immunity maintenance and is important in prevention of several diseases, including infections, autoimmune diseases, certain forms of cancer, type 1 and 2 diabetes, and cardiovascular diseases. Vitamin D is of particular importance for newborns and young children. This vitamin is involved in important physiological regulatory processes such as bone metabolism, lung development, maturation of the immune system and differentiation of the nervous system. Vitamin D deficiency increases risks of neonatal sepsis, necrotizing enterocolitis, respiratory distress syndrome, and bronchopulmonary dysplasia. Adequate intake of vitamin D and calcium during childhood can reduce the risk of osteoporosis and other diseases associated with vitamin D deficiency in adults. Recently, vitamin D deficiency has shown to be a potential risk factor for COVID-19 propensity. It has been established that to date most scientific pediatric societies have recognized the need to prevent vitamin D deficiency in healthy children of all ages, but data on the dosage of vitamin D in its prophylactic use differ. Most scientific societies recommend an average of 400-600 IU per day of vitamin D for prophylactic purposes. The analysis of published data shows the need to follow a strategy based on an individual approach, taking into account physiological characteristics, individual requirements and lifestyle.Copyright © 2021 University of Tartu Press. All rights reserved.

Special considerations in the premature and ex-premature infant

Advances in neonatal medicine have progressively increased the survival of premature infants. Increased survival has however come at the cost of increased number of infants with prematurity-related complications. This is represented by high rates of respiratory distress syndrome, bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), sepsis, periventricular leukomalacia (PVL), intraventricular haemorrhage (IVH), cerebral palsy, hypoxic ischaemic encephalopathy (HIE) and visual and hearing problems in survivors. In addition to prolonged hospital stay after birth, readmission to hospital in the first year of life is common if chronic lung disease exists. Around 3% of newborns have a congenital physical anomaly with 60% of congenital anomalies affecting the brain or heart and around 1% having multiple anomalies. Individual congenital conditions requiring surgical intervention in the neonatal period are rare. Neonates have a higher perioperative mortality risk largely due to the degree of prior illness, the complexity of their surgeries, and infant physiology. The maintenance of oxygenation and perfusion in the perioperative phase is critical as both affect cerebral perfusion and neurocognitive outcome but the triggers for intervention and the thresholds of physiological parameters during neonatal anaesthesia are not well described. After even minor surgical procedures, ex-premature infants are at higher risk for postoperative complications than infants born at term.Copyright © 2022

Multifaceted involvements of Paneth cells in various diseases within intestine and systemically.

Serving as the guardians of small intestine, Paneth cells (PCs) play an important role in intestinal homeostasis maintenance. Although PCs uniquely exist in intestine under homeostasis, the dysfunction of PCs is involved in various diseases not only in intestine but also in extraintestinal organs, suggesting the systemic importance of PCs. The mechanisms under the participation of PCs in these diseases are multiple as well. The involvements of PCs are mostly characterized by limiting intestinal bacterial translocation in necrotizing enterocolitis, liver disease, acute pancreatitis and graft-vs-host disease. Risk genes in PCs render intestine susceptible to Crohn's disease. In intestinal infection, different pathogens induce varied responses in PCs, and toll-like receptor ligands on bacterial surface trigger the degranulation of PCs. The increased level of bile acid dramatically impairs PCs in obesity. PCs can inhibit virus entry and promote intestinal regeneration to alleviate COVID-19. On the contrary, abundant IL-17A in PCs aggravates multi-organ injury in ischemia/reperfusion. The pro-angiogenic effect of PCs aggravates the severity of portal hypertension. Therapeutic strategies targeting PCs mainly include PC protection, PC-derived inflammatory cytokine elimination, and substituting AMP treatment. In this review, we discuss the influence and importance of Paneth cells in both intestinal and extraintestinal diseases as reported so far, as well as the potential therapeutic strategies targeting PCs.

Neonatal necrotizing enterocolitis due to COVID-19. A case report.

Digestive symptoms have been reported in an important proportion of children with COVID-19, and the clinical expression of critical patients with COVID-19 is thought to result from progressive increase of inflammation and an unusual trend of hypercoagulation. We report a newborn received with abdominal distension, green vomiting and imaging suggestive for enterocolitis. He had a close contact with COVID-19 and the PCR for SARS-CoV-2 came back positive. Despite the supportive measures, his condition deteriorated and a surgery was decided. The surgical exploration found an ischemic bowel. The therapeutic measures were ineffective as the child passed away a few hours after surgery despite the resuscitation treatment performed. The confirmed enterocolitis happening within the period of acute infection by SARS-CoV-2, the NEC was likely a manifestation of COVID-19.

Feasibility and acceptability of a diagnostic randomized clinical trial of bowel ultrasound in infants with suspected necrotizing enterocolitis.

We conducted a pilot diagnostic randomized clinical trial (RCT) to examine the feasibility, acceptability, and preliminary outcomes of adding bowel ultrasound (BUS) to the diagnostic evaluation for necrotizing enterocolitis (NEC). Infants ≤ 32 weeks' gestational age with NEC concern were randomized to undergo abdominal X-ray (AXR) or AXR + BUS. The primary outcome was study feasibility. Secondary outcomes included rates of NEC diagnosis and duration of treatment with bowel rest and antibiotics. A total of 56 infants were enrolled; 16 developed NEC concern and were randomized. Rates of recruitment (56/82 = 68%), retention (16/16 = 100%), and protocol compliance (126/127 = 99%) met pre-specified thresholds for feasibility. No significant differences in rates of NEC diagnosis were found between the two groups. Durations of bowel rest and antibiotic treatment were also similar.   Conclusion: Our study supports the feasibility of conducting a definitive diagnostic RCT to establish safety and efficacy of BUS for NEC.   Clinical trial registration: The study was registered at https://clinicaltrials.gov (NCT03963011). What is Known: • Bowel ultrasound (BUS) is increasingly being utilized as an adjunct to abdominal radiographs in evaluating for necrotizing enterocolitis (NEC). • The impact of BUS on patient outcomes is unknown. What is New: • A diagnostic randomized controlled trial study design to determine safety and effectiveness of adding BUS to NEC evaluation is feasible and acceptable.

DETECTION OF SARS-COV-2 IN STOOL BUT NOT NARES OF NEWBORNS OF MOTHERS WITH COVID-19 DURING PREGNANCY

Purpose of Study To investigate potential evidence of in utero transmission of SARS-CoV-2 in the stool of newborns born to mothers with COVID-19 infection during pregnancy. Methods Used We investigated stool from 1 day to 2 months of age from 14 newborns born at 25-41 weeks whose mothers had COVID-19 during pregnancy. Newborns were admitted at delivery to the NICU or newborn nursery of our urban academic hospital from July 2020 to May 2021. A comparison group of 30 newborns had similar GAs and were born to mothers without COVID-19 during pregnancy. SARS-CoV-2 RNA was quantified with quantitative PCR using primers against SARS-CoV-2 envelope protein and non-structural protein 14 (NSP-14), spike protein with enzyme-linked immunosorbent assay (ELISA), and inflammatory cytokines interleukin- 6 (IL-6) and interferon-g (IFN-γ) elicited by stool homogenates in mouse bone marrow macrophages. This study was IRB approved with parental consent. Summary of Results Despite negative nasal PCRs from all newborns, viral RNAs and spike protein were detected in the stool of 11 out of 14 newborns as early as the first day of life (range 0-2 months, figure 2A and 2B). Stool RNA and spike protein levels increased over time in 2 and 4 newborns, respectively. Stool homogenates from all newborns elicited elevated inflammatory cytokines, IL-6 and IFN-γ, from mouse macrophages (figure 1). Most newborns were clinically well except for one death from gestational autoimmune liver disease and one with necrotizing enterocolitis. Conclusions These novel findings suggest risk of in utero SARS-CoV-2 transmission to the premature and term fetal intestine during gestation despite negative postnatal nasal PCRs. It is unclear if the presence of viral RNA and protein within the gut microbiome represents active virus in newborns with clinical hospital courses typical of their gestational age in 12 out of 14 cases. However, increasing levels of viral RNA and protein over time suggest replication in some infants, and their gut microbiome induced inflammation in mouse models. The presence of SARS-CoV-2 RNA and spike protein in the intestines of newborns may potentially impact development of the gut microbiome and the immune system and should be further investigated. (Figure Presented).

Composition of Human Breast Milk Microbiota and Its Role in Children's Health.

Human milk contains a number of nutritional and bioactive molecules including microorganisms that constitute the so-called "Human Milk Microbiota (HMM)". Recent studies have shown that not only bacterial but also viral, fungal, and archaeal components are present in the HMM. Previous research has established, a "core" microbiome, consisting of Firmicutes (i.e., Streptococcus, Staphylococcus), Proteobacteria (i.e., Serratia, Pseudomonas, Ralstonia, Sphingomonas, Bradyrhizobium), and Actinobacteria (i.e., Propionibacterium, Corynebacterium). This review aims to summarize the main characteristics of HMM and the role it plays in shaping a child's health. We reviewed the most recent literature on the topic (2019-2021), using the PubMed database. The main sources of HMM origin were identified as the retrograde flow and the entero-mammary pathway. Several factors can influence its composition, such as maternal body mass index and diet, use of antibiotics, time and type of delivery, and mode of breastfeeding. The COVID-19 pandemic, by altering the mother-infant dyad and modifying many of our previous habits, has emerged as a new risk factor for the modification of HMM. HMM is an important contributor to gastrointestinal colonization in children and therefore, it is fundamental to avoid any form of perturbation in the HMM that can alter the microbial equilibrium, especially in the first 100 days of life. Microbial dysbiosis can be a trigger point for the development of necrotizing enterocolitis, especially in preterm infants, and for onset of chronic diseases, such as asthma and obesity, later in life.

COVID-19 pandemic in the neonatal intensive care unit: any effect on late-onset sepsis and necrotizing enterocolitis?

The study was aimed at describing potential indirect effects of pandemic-related measures on very-low-birthweight infants in four Italian NICUs. No overall change in late-onset sepsis (LOS) and necrotizing enterocolitis was documented. However, in the NICU where baseline LOS rate was high, a significant reduction in LOS incidence was recorded. Conclusion: COVID-19-related implementation of NICU hygiene policies is likely to reduce the occurrence of LOS in high-risk settings. What is Known: • COVID-19 pandemic has disrupted routine care in Neonatal Intensive Care Units (NICUs), mostly by tightening infection control measures and restricting parental presence in the NICU. • Beyond the described psychological impact of COVID-19 related measures on healthcare workers and NICU families, their consequences in terms of preterm infants' clinical outcomes have not been described in detail yet. What is New: • Strengthened infection-control measures do not seem to have an overall influence on the incidence of necrotising enterocolitis and late-onset sepsis in very-low-birth-weight infants. • However, the implementation of these measures appears to reduce the occurrence of late-onset sepsis in settings where the baseline incidence of the disease is high.

Intravenous Immune Globulin Uses in the Fetus and Neonate: A Review.

Intravenous immune globulin (IVIG) is made after processing plasma from healthy donors. It is composed mainly of pooled immunoglobulin and has clinical evidence-based applications in adult and pediatric populations. Recently, several clinical applications have been proposed for managing conditions in the neonatal population, such as hemolytic disease of the newborn, treatment, and prophylaxis for sepsis in high-risk neonates, enterovirus parvovirus and COVID-19 related neonatal infections, fetal and neonatal immune-induced thrombocytopenia, neonatal hemochromatosis, neonatal Kawasaki disease, and some types of immunodeficiency. The dosing, mechanism of action, effectiveness, side effects, and adverse reactions of IVIG have been relatively well studied in adults but are not well described in the neonatal population. This review aims to provide the most recent evidence and consensus guidelines about the use of IVIG in the fetus and neonate.