Search Results (74)

Reduced/deficient expression of Protein Kinase C (PKC)ζ in Cord blood (CB) T cells is associated with allergy development in children and a propensity to maintain an immature T-helper (Th)2 cytokine profile. In addition, other PKC isozymes are also low in CBTCs. Since previous studies have reported that cord blood/neonatal monocyte and neutrophil functions are significantly lower than cells from adults, it was of interest to see if the CBTC PKC levels were reflected in CB monocytes and neutrophils. Compared to adult blood, CB expresses low levels of PKCα, β2, ε, θ, μ, ζ and λ/ι in monocytes and PKCα, β2, η, θ, μ, ζ and λ/ι in neutrophils. The T-cell PKCζ levels were positively correlated with levels in CB monocytes but not in neutrophils. However, neither the monocytes nor the neutrophil PKCζ were associated with T-cell development towards a Th1 or Th2 cytokine propensity, based on the production of interferon-gamma and interleukin-4 in response to phytohemagglutinin and phorbol myristate acetate. The results demonstrate that some newborn babies display a deficiency in PKC isozymes in monocytes and neutrophils, as reported for T cells. However, unlike T cells, the PKCζ levels of the phagocytes did not correlate with regulation of development towards a Th1 or Th2 cytokine phenotype. Full article

Numerous genes govern male reproduction, modulating testicular development and spermatogenesis. Our study leveraged RNA-Seq to explore candidate genes and pivotal pathways influencing fecundity in an F1 hybrid of Southdown × Hu sheep testes across four developmental milestones: M0 (0 months old, newborn), M3 (3 months old, sexually immature), M6 (6 months old, sexually mature), and Y1 (1 years old, adult). Histological examination using hematoxylins and eosin staining revealed that the cross-sectional area of the spermatid tubules and the number of supportive cells increased in the other groups, as compared to the M0 group. The cross-sectional area of the vasculature and the number of supporting cells were found to be significantly increased in all other groups in comparison to the M0 group. We conducted GO and KEGG analyses of the differentially expressed genes (DEGs) in the three comparison groups and identified key pathways, including cAMP, MAPK, ECM–receptor interactions, PI3K-Akt, and FOXO signaling, which are closely related to testicular development and spermatogenesis. Notably, alternative splicing (AS) events were markedly elevated in M6 and Y1 stages. Key genes like GATA4, GATA6, SMAD4, SOX9, YAP1, ITGB1 and MAPK1 emerged as significantly enriched in these pathways, potentially orchestrating the transition from immature to mature testes in sheep. These findings offer valuable insights into male reproductive potential and can inform strategies for optimizing animal breeding. Full article

Bilirubin is a product of the metabolism of hemoglobin from red blood cells. Higher levels of bilirubin are a sign that either there is an unusual breaking down rate of red blood cells or the liver is not able to eliminate bilirubin, through bile, into the gastrointestinal tract. For adults, bilirubin is occasionally monitored through urine or invasive blood sampling, whilst all newborns are routinely monitored visually, or non-invasively with transcutaneous measurements (TcBs), due to their biological immaturity to conjugate bilirubin. Neonatal jaundice is a common condition, with higher levels of unconjugated bilirubin concentration having neurotoxic effects. Actual devices used in TcBs are focused on newborn populations, are hand-held, and, in some cases, operate in only two wavelengths, which does not necessarily guarantee reliable results over all skin tones. The same occurs with visual inspections. Based on that, a continuous bilirubin monitoring device for newborns is being developed to overcome visual inspection errors and to reduce invasive procedures. This device, operating optically with a mini-spectrometer in the visible range, is susceptible to patient movements and, consequently, to situations with a lower signal quality for reliable bilirubin concentration estimates on different types of skin. Therefore, as an intermediate development step and, based on skin spectra measurements from adults, this work addresses the device’s placement status prediction as a signal quality indication index. This was implemented by using machine learning (ML), with the best performances being achieved by support vector machine (SVM) models, based on the spectra acquired on the arm and forehead areas. Full article

Mechanisms resulting from the physiological immaturity of the digestive system in children delivered before 32 weeks of gestation and, in particular, different interactions between the microbiome and the body have not been fully elucidated yet. Next-generation sequencing methods demonstrated the presence of bacterial DNA in the placenta and amniotic fluid, which may reflect bacterial populations that initiate intestinal colonization in utero. Numerous studies confirmed the hypothesis stating that intestinal bacteria played an important role in the pathogenesis of necrotizing enterocolitis (NEC) early- and late-onset neonatal sepsis (EONS and LONS). The model and scale of disorders within the intestinal microbiome are the subject of active research in premature infants. Neonatal meconium was primarily used as an indicator defining the environment in utero, as it is formed before birth. Metagenomic results and previous data from microbiological bacterial cultures showed a correlation between the time from birth to sample collection and the detection of bacteria in the neonatal meconium. Therefore, it may be determined that the colonization of the newborn’s intestines is influenced by numerous factors, which may be divided into prenatal, perinatal, and postnatal, with particular emphasis put on the mode of delivery and contact with the parent immediately after birth. Background: The aim of this review was to collect available data on the intrauterine shaping of the fetal microbiota. Methods: On 13 March 2024, the available literature in the PubMed National Library of Medicine search engine was reviewed using the following selected keywords: “placental microbiome”, “intestinal bacteria in newborns and premature infants”, and “intrauterine microbiota”. Results: After reviewing the available articles and abstracts and an in-depth analysis of their content, over 100 articles were selected for detailed elaboration. We focused on the origin of microorganisms shaping the microbiota of newborns. We also described the types of bacteria that made up the intrauterine microbiota and the intestinal microbiota of newborns. Conclusions: The data presented in the review on the microbiome of both term newborns and those with a body weight below 1200 g indicate a possible intrauterine colonization of the fetus depending on the duration of pregnancy. The colonization occurs both via the vaginal and intestinal route (hematogenous route). However, there are differences in the demonstrated representatives of various types of bacteria, phyla Firmicutes and Actinobacteria in particular, taking account of the distribution in their abundance in the individual groups of pregnancy duration. Simultaneously, the distribution of the phyla Actinobacteria and Proteobacteria is consistent. Considering the duration of pregnancy, it may also be concluded that the bacterial flora of vaginal origin dominates in preterm newborns, while the flora of intestinal origin dominates in term newborns. This might explain the role of bacterial and infectious factors in inducing premature birth with the rupture of fetal membranes. Full article

Caffeine is one of the most commonly used drugs in intensive care to stimulate the respiratory control mechanisms of very preterm infants. Respiratory instability, due to the degree of immaturity at birth, results in apnea of prematurity (AOP), hyperoxic, hypoxic, and intermittent hypoxic episodes. Oxidative stress cannot be avoided as a direct reaction and leads to neurological developmental deficits and even a higher prevalence of respiratory diseases in the further development of premature infants. Due to the proven antioxidant effect of caffeine in early use, largely protective effects on clinical outcomes can be observed. This is also impressively observed in experimental studies of caffeine application in oxidative stress-adapted rodent models of damage to the developing brain and lungs. However, caffeine shows undesirable effects outside these oxygen toxicity injury models. This review shows the effects of caffeine in hyperoxic, hypoxic/hypoxic-ischemic, and intermittent hypoxic rodent injury models, but also the negative effects on the rodent organism when caffeine is administered without exogenous oxidative stress. The narrative analysis of caffeine benefits in cerebral and pulmonary preterm infant models supports protective caffeine use but should be given critical consideration when considering caffeine treatment beyond the recommended corrected gestational age. Full article

Microbiota plays a crucial role in intestinal maturation in preterm newborns. The clinical manifestation of the immaturity of the gastro-intestinal tract is called feeding intolerance (FI). This condition may resolve spontaneously or dramatically evolve into necrotizing enterocolitis. One of the most challenging tasks for the neonatologist is to identify those neonates that will develop the disease early in order to adequately provide nutrition to these patients, from the very first hours of life. A close interplay between the maturity of the gastro-intestinal tract and gut microbiota has been described; however, in preterm neonates, this relationship is still undefined. We analyzed the bacterial composition of stool samples, collected early in life, from 30 preterm newborns classified as intolerant or tolerant according to the degree of readiness of the gastro-intestinal tract to receive enteral nutrition. The Pielou evenness index was significantly increased in intolerant compared with tolerant newborns. Data corrected for confounding variables confirmed that the occurrence of gut maturation was independently influenced by Pielou evenness at birth. A lower bacterial diversity very early in life is associated with improved feeding tolerance in preterm newborns. The abundance analysis showed that neonates not ready to receive enteral nutrition for feeding intolerance show, after birth, an increased abundance of Proteobacteria, Lachnospiracae, Enterobacter and Acinetobacter. We can argue that those are the taxa that prevent the establishment of pioneer bacteria. A lower alpha-diversity, in the first days of life, may facilitate the seeding of beneficial pioneer bacteria that, in turn, drive healthy microbial colonization during neonatal life. Full article

Organogenesis occurs in the uterus under low oxygen levels (4%). Preterm birth exposes immature newborns to a hyperoxic environment, which can induce a massive production of reactive oxygen species and potentially affect organ development, leading to diseases such as necrotizing enterocolitis. The β3-adrenoreceptor (β3-AR) has an oxygen-dependent regulatory mechanism, and its activation exerts an antioxidant effect. To test the hypothesis that β3-AR could protect postnatal ileal development from the negative impact of high oxygen levels, Sprague–Dawley rat pups were raised under normoxia (21%) or hyperoxia (85%) for the first 2 weeks after birth and treated or not with BRL37344, a selective β3-AR agonist, at 1, 3, or 6 mg/kg. Hyperoxia alters ileal mucosal morphology, leading to increased cell lipid oxidation byproducts, reduced presence of β3-AR-positive resident cells, decreased junctional protein expression, disrupted brush border, mucin over-production, and impaired vascularization. Treatment with 3 mg/kg of BRL37344 prevented these alterations, although not completely, while the lower 1 mg/kg dose was ineffective, and the higher 6 mg/kg dose was toxic. Our findings indicate the potential of β3-AR agonism as a new therapeutic approach to counteract the hyperoxia-induced ileal alterations and, more generally, the disorders of prematurity related to supra-physiologic oxygen exposure. Full article

The discovery of antimicrobial drugs has led to a significant increase in survival from infections; however, they are very often prescribed and administered, even when their use is not necessary and appropriate. Newborns are particularly exposed to infections due to the poor effectiveness and the immaturity of their immune systems. For this reason, in Neonatal Intensive Care Units (NICUs), the use of antimicrobial drugs is often decisive and life-saving, and it must be started promptly to ensure its effectiveness in consideration of the possible rapid evolution of the infection towards sepsis. Nevertheless, the misuse of antibiotics in the neonatal period leads not only to an increase in the development and wide spreading of antimicrobial resistance (AMR) but it is also associated with various short-term (e.g., alterations of the microbiota) and long-term (e.g., increased risk of allergic disease and obesity) effects. It appears fundamental to use antibiotics only when strictly necessary; specific decision-making algorithms and electronic calculators can help limit the use of unnecessary antibiotic drugs. The aim of this narrative review is to summarize the right balance between the risks and benefits of antimicrobial therapy in NICUs; for this purpose, specific Antimicrobial Stewardship Programs (ASPs) in neonatal care and the creation of a specific antimicrobial stewardship team are requested. Full article

There is a growing interest in the composition of amniotic fluid (AF) in both humans and animals. In addition to its nutritional and protective functions for the foetus, current knowledge demonstrates that AF also serves advanced diagnostic, prognostic, and therapeutic roles. Newborn dogs have an underdeveloped immune system, making them highly susceptible to dangerous pathogens such as canine parvovirus (CPV-2), canine infectious hepatitis virus (CAdV-1), and canine distemper virus (CDV), thus exposing them to a high risk of mortality in the first weeks of life. Immunoglobulins G (IgGs) represent the only antibody isotype capable of crossing the placenta in a small amount and have been detected also in canine AF. The primary aim of this study was to investigate the reliability of AF collected at birth as a marker of passive immunity in canine species. For this purpose, total and specific IgGs against CPV-2, CAdV-1, and CDV were investigated and quantified in both maternal plasma and AF collected at the time of caesarean section. The vaccination status of the bitches was also taken into consideration. Since the immune system can be influenced by gestational age, with preterm infants having immature innate and adaptive immunity, IgG concentrations were correlated with amniotic lecithin, sphingomyelin, cortisol, surfactant protein A, and pentraxin 3 levels. In a previous study from our group on foetal maturity these molecules were measured in the same samples. Finally, correlations between their amniotic content and neonatal outcomes were investigated. This study demonstrates that AF analysis at birth can provide valuable insights into neonatal immunity in puppies, offering a non-invasive method to detect potential early health risks, for improved puppy care and management. Full article

We aimed to analyze the management of the ectopic mediastinal thyroid (EMT) with respect to EMT-related cancer and non-malignant findings related to the pathological report, clinical presentation, imaging traits, endocrine profile, connective tissue to the cervical (eutopic) thyroid gland, biopsy or fine needle aspiration (FNA) results, surgical techniques and post-operatory outcome. This was a comprehensive review based on revising any type of freely PubMed-accessible English, full-length original papers including the keywords “ectopic thyroid” and “mediastinum” from inception until March 2024. We included 89 original articles that specified EMTs data. We classified them into four main groups: (I) studies/case series (n = 10; N = 36 EMT patients); (II) malignant EMTs (N = 22 subjects; except for one newborn with immature teratoma in the EMT, only adults were reported; mean age of 62.94 years; ranges: 34 to 90 years; female to male ratio of 0.9). Histological analysis in adults showed the following: papillary (N = 11/21); follicular variant of the papillary type (N = 2/21); Hürthle cell thyroid follicular malignancy (N = 1/21); poorly differentiated (N = 1/21); anaplastic (N = 2/21); medullary (N = 1/21); lymphoma (N = 2/21); and MALT (mucosa-associated lymphoid tissue) (N = 1/21); (III) benign EMTs with no thyroid anomalies (N = 37 subjects; mean age of 56.32 years; ranges: 30 to 80 years; female to male ratio of 1.8); (IV) benign EMTs with thyroid anomalies (N = 23; female to male ratio of 5.6; average age of 52.1 years). This panel involved clinical/subclinical hypothyroidism (iatrogenic, congenital, thyroiditis-induced, and transitory type upon EMT removal); thyrotoxicosis (including autonomous activity in EMTs that suppressed eutopic gland); autoimmune thyroiditis/Graves’s disease; nodules/multinodular goiter and cancer in eutopic thyroid or prior thyroidectomy (before EMT detection). We propose a 10-item algorithm that might help navigate through the EMT domain. To conclude, across this focused-sample analysis (to our knowledge, the largest of its kind) of EMTs, the EMT clinical index of suspicion remains low; a higher rate of cancer is reported than prior data (18.8%), incident imagery-based detection was found in 10–14% of the EMTs; surgery offered an overall good outcome. A wide range of imagery, biopsy/FNA and surgical procedures is part of an otherwise complex personalized management. Full article

Background: Preterm birth impacts 60% of twin pregnancies, with the subsequent risk of complications in both newborns secondary to the immaturity of organs. This study aims to assess the utility of the sFlt-1/PlGF ratio throughout pregnancy in predicting late preterm birth and adverse perinatal outcomes related to prematurity in twin pregnancies. Methods: This is a prospective cohort study developed at a tertiary hospital. All pregnant women with a twin pregnancy who signed the informed consent were included. The sFlt-1/PlGF ratio was measured at 12, 24, and 32 weeks’ gestation. Results: Seventy patients were included, from which 54.3% suffered late preterm birth. Results revealed a significant difference in sFlt-1/PlGF ratio at week 32 between term and preterm groups, with a one-unit increase associated with a 1.11-fold increase in the probability of preterm birth. The sFlt-1/PlGF ratio at week 32 alone presented considerable predictive capacities (sensitivity of 71%, specificity of 72%, a PPV of 75%, and an NPV of 68%. Similarly, at week 24, a one-unit increase in sFlt-1/PlGF ratio was associated with a 1.24-fold increase in the probability of adverse perinatal events due to prematurity. Combining parity, maternal age, conception method, BMI, and chorionicity, the model yielded better predictive capacities (sensitivity of 82%, specificity of 80%, PPV of 58%, NPV of 93%). Conclusions: The potential of the sFlt-1/PlGF ratio as a predictive tool for preterm birth and adverse perinatal outcomes secondary to prematurity in twin pregnancies is underscored. Full article

Background and Objectives: Respiratory distress syndrome (RDS) in preterm infants commonly occurs due to the immaturity-related deficiency of pulmonary surfactant. Beyond prematurity, various environmental and genetic factors can influence the onset and progression of RDS. This study aimed to analyze three single-nucleotide polymorphisms (SNPs) of the ABCA3 gene to assess the ABCA3 gene as a candidate gene for susceptibility to RDS and overall survival in newborns and to evaluate the utility of MLPA in RDS neonatal patients. Materials and Methods: Three SNPs were chosen and genotyped in a cohort of 304 newborns. Data analysis and statistical tests were employed to examine allele frequencies, haplotypes, and measures of pairwise linkage disequilibrium. Results: There was no observed haplotype association with SNPs rs13332514 (c.1059G>A) and rs170447 (c.1741+33T>C) among newborns, both with and without RDS (p > 0.05). The minor C allele frequency of the ABCA3 rs323043 (c.1755G>C) SNP showed a significant increase in preterm infants with RDS. MLPA results indicated that the predominant findings were normal, revealing no CNVs in the genes ABCA3 and SFTPC that were investigated in our patients. Conclusions: The presence of the variant C allele in the rs323043 (c.1755G>C) SNP may be a risk factor for RDS in premature newborns. Full article

Breastfeeding is particularly important for vulnerable preterm infants as it provides protection from infections and reduces newborn mortality. However, preterm infants are often too immature to breastfeed after birth and may have medical conditions that require admission to the neonatal nursery. The published literature on the development of preterm feeding skills has focused mostly on bottle feeding. In order to better support breastfeeding after preterm birth, there is a need for evidence on the development of breastfeeding skills in preterm infants. The aim of this study was to examine breastfeeding skill development in a group of infants born at 25–33 weeks’ gestation. Infants were assessed during weekly monitored breastfeeds from 33 weeks corrected gestational age (CGA) using the Preterm Infant Breastfeeding Behaviour Scale (PIBBS), and milk transfer was measured. Mothers rated PIBBS items—rooting, areolar grasp, latch to the breast, sucking, longest sucking burst and swallowing—and clinical staff performed test weights. Pearson correlation was used to assess changes in PIBBS scores items over time and associations between total PIBBS score and milk transfer volume. Total PIBBS scores at 33, 34 and 35 weeks’ CGA were compared between groups of infants born at <30/40 and 30–33/40 weeks using Student’s t-test. Our cohort consisted of 60 preterm mother–infant dyads recruited from the neonatal nurseries at King Edward Memorial Hospital between February 2015 and February 2016. A positive trend was found between increasing CGA and higher ratings for six PIBBS items: rooting (R² = 0.08, F (1, 164) = 13.9, p < 0.001), areolar grasp (R² = 0.11, F (1, 164) = 21.0, p < 0.001), latching (R² = 0.14, F (1, 164) = 27.5, p < 0.001), sucking (R² = 0.14, F (1, 164) = 27.1, p < 0.001), longest sucking burst (R² = 0.17, F (1, 164) = 32.3, p < 0.001) and swallowing (R² = 0.14, F (1, 163) = 26.1, p < 0.001). A higher total PIBBS score was associated with a higher milk transfer volume (mL) (R² = 0.214, F (1, 164) = 44.8, p < 0.001). When compared to infants born at 30–33 weeks’ gestation, infants born at 25–29⁺⁶ weeks’ gestation had similar PIBBS scores at 33 weeks’ CGA (9.2 ± 3.6 vs. 9.5 ± 4.1, p = 0.83) and lower scores at 34 weeks’ CGA (9.2 ± 3.4 vs. 11.7 ± 4.3, p = 0.036) and 35 weeks’ CGA (12.3 ± 3.1 vs. 14.9 ± 3.5, p = 0.031). The development of preterm breastfeeding skills advances from 33 weeks CGA with wide inter-individual variation and slower progression observed in those born < 30 weeks’ gestation. Therefore, an individualised approach to anticipatory guidance regarding breastfeeding progression during the neonatal nursery stay is needed. Findings from this study can contribute to the formation of breastfeeding information resources for clinical staff and parents of preterm infants. Full article

Rational drug use in special populations is a clinical problem that doctors and pharma-cists must consider seriously. Neonates are the most physiologically immature and vulnerable to drug dosing. There is a pronounced difference in the anatomical and physiological profiles be-tween neonates and older people, affecting the absorption, distribution, metabolism, and excretion of drugs in vivo, ultimately leading to changes in drug concentration. Thus, dose adjustments in neonates are necessary to achieve adequate therapeutic concentrations and avoid drug toxicity. Over the past few decades, modeling and simulation techniques, especially physiologically based pharmacokinetic (PBPK) modeling, have been increasingly used in pediatric drug development and clinical therapy. This rigorously designed and verified model can effectively compensate for the deficiencies of clinical trials in neonates, provide a valuable reference for clinical research design, and even replace some clinical trials to predict drug plasma concentrations in newborns. This review introduces previous findings regarding age-dependent physiological changes and pathological factors affecting neonatal pharmacokinetics, along with their research means. The application of PBPK modeling in neonatal pharmacokinetic studies of various medications is also reviewed. Based on this, we propose future perspectives on neonatal PBPK modeling and hope for its broader application. Full article

Significant risk of side effects of drug therapy in newborns, especially in premature neonates, is associated with immaturity of a number of enzyme systems and biotransformation mechanisms and pharmacokinetic specificity. We consider the use of thiotriazoline), a drug licensed in Ukraine with proven hepatoprotective and cardioprotective activity and a high safety profile, for premature infants to reduce side effects of antibiotic therapy. The use of thiotriazoline in antibiotic therapy results in an increase in the concentration of eNOS in blood plasma and a decrease in alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase and bilirubin in blood plasma. These results provide experimental support for the use of thiotriazoline to reduce the side effects of azithromycin therapy in newborns. Full article