Search Results (87)

Late-preterm (34^0/7–36^6/7 weeks) and early-term (37^0/7–38^6/7 weeks) newborns were, up until recently, erroneously categorized as low-risk and were conflated with full-term (39^0/7–40^6/7 weeks) deliveries. However, emerging evidence refuted this notion and demonstrated that late-preterm and, to a lesser extent, early-term newborns have a significantly higher risk of experiencing various neonatal morbidities, including respiratory distress syndrome, transient tachypnea of the newborn, pneumonia, jaundice, hypoglycemia, and breastfeeding difficulties, compared to their full-term counterparts—reflecting their relative physiologic and developmental immaturity. Recent evidence also unravels the lingering adverse effects of late-preterm and early-term delivery up until mid-adulthood, with the increased susceptibility of these newborns to neurodevelopmental delays, behavioral and neuropsychiatric problems, and adult chronic diseases. Moreover, apart from increased neonatal and infant mortality rates, these newborns continue to encounter a heightened risk of mortality even up to mid-adulthood. As the full spectrum of the complications these newborns face is gradually being unveiled, this review presents and discusses the current knowledge base, identifies gaps in the literature, and highlights future research implications. Full article

Background: Duchenne muscular dystrophy (DMD), which affects 1 in 3500 to 5000 newborn boys worldwide, is characterized by progressive skeletal muscle weakness and degeneration. The reduced muscle regeneration capacity presented by patients is associated with increased fibrosis. Satellite cells (SCs) are skeletal muscle stem cells that play an important role in adult muscle maintenance and regeneration. The absence or mutation of dystrophin in DMD is hypothesized to impair SC asymmetric division, leading to cell cycle arrest. Methods: To overcome the limited availability of biopsies from DMD patients, we used our 3D skeletal muscle organoid (SMO) system, which delivers a stable population of myogenic progenitors (MPs) in dormant, activated, and committed stages, to perform SMO cultures using three DMD patient-derived iPSC lines. Results: The results of scRNA-seq analysis of three DMD SMO cultures versus two healthy, non-isogenic, SMO cultures indicate reduced MP populations with constant activation and differentiation, trending toward embryonic and immature myotubes. Mapping our data onto the human myogenic reference atlas, together with primary SC scRNA-seq data, indicated a more immature developmental stage of DMD organoid-derived MPs. DMD fibro-adipogenic progenitors (FAPs) appear to be activated in SMOs. Conclusions: Our organoid system provides a promising model for studying muscular dystrophies in vitro, especially in the case of early developmental onset, and a methodology for overcoming the bottleneck of limited patient material for skeletal muscle disease modeling. Full article

Background: Adolescents with a chronological age of less than 15 years or a gynecological age of less than 2 years may have a higher probability of complications because they are more likely to conceive within 1 to 2 years of menarche and, therefore, are still growing and maturing. This could impair their ability to adapt to the physiological demands of pregnancy. Objective: To evaluate the relationship between chronological age and gynecological age with low birth weight and small for gestational age among adolescent mothers in Mexico City. Methods: A retrospective cohort design of adolescent mother–child dyads was conducted. The study followed 1242 adolescents under 19 years of age and their children, collecting data on physical, socioeconomic, and clinical characteristics, including hemoglobin levels. Low birth weight was assessed using the Intergrowth-21st project standards and categorized as above or below 2500 g. The mothers were grouped by chronological age (<15 years and ≥15 years) and gynecological age (<3 years and ≥3 years). Adjusted odds ratios were calculated using binary logistic regression models. The outcome variables were low birth weight and small for gestational age. The independent variables included gynecological age, chronological age, age at menarche, hemoglobin concentration, and gestational weight gain, among others. All independent variables were converted to dummy variables for analysis. Calculations were adjusted for the following variables: marital status, maternal education, occupation, educational lag, family structure, socioeconomic level, pre-pregnancy body mass index, and initiation of prenatal care. Results: The average age of the participants was 15.7 ± 1 years. The frequency of small for gestational age and low birth weight was 20% and 15.3%, respectively. Factors associated with small for gestational age included gynecological age < 3 years [aOR = 2.462, CI 95%; 1.081–5.605 (p = 0.032)], hemoglobin < 11.5 g/dL [aOR = 2.164, CI 95%; 1.08–605 (p = 0.019)], insufficient gestational weight gain [aOR = 1.858, CI 95%; 1.059–3.260 (p = 0.031)], preterm birth [aOR = 1.689, CI 95%; 1.133–2.519 p = 0.01], and living more than 50 km from the care center [aOR = 2.256, CI 95%; 1.263–4.031 (p = 0.006)]. An early age of menarche [aOR = 0.367, CI 95%; 0.182–0.744 (p = 0.005)] showed a protective effect against small for gestational age. Factors associated with low birth weight included gynecological age < 3 years [aOR = 3.799, CI 95%; 1.458–9.725 (p = 0.006)], maternal age < 15 years [aOR = 5.740, CI 95%; 1.343–26.369 (p = 0.019)], preterm birth [aOR = 54.401, CI 95%; 33.887–87.335, p = 0.001], living more than 50 km from the care center [aOR = 1.930, CI 95%; 1.053–3.536 (p = 0.033)], and early age of menarche [aOR = 0.382, CI 95%; 0.173–0.841 (p = 0.017), which demonstrated a protective effect, respectively. Conclusions: The study concludes that biological immaturity, particularly early gynecological age, significantly contributes to adverse birth outcomes during adolescent pregnancies. Interestingly, early menarche appeared to have a protective effect, whereas chronological age was not a significant predictor of small for gestational age. Chronological age has an even greater impact: women younger than 15 years are 5.7 times more likely to have low birth weight infants. However, chronological age did not increase the likelihood of having an SGA newborn. Full article

Background: Neonatal influenza is a rare condition. Young infants have immature immune defenses and are unable to receive direct vaccination; this can result in significant illness. Maternal anti-influenza immunization during pregnancy provides passive antibodies to the newborn via transplacental transfer, significantly decreasing the incidence and severity of influenza in early infancy. Nevertheless, the vaccination coverage during pregnancy remains low in many regions, leaving certain neonates without adequate protection. Methods: We present three cases of laboratory-confirmed influenza infection in neonates admitted to the “Sf. Ioan” Clinical Emergency Pediatric Hospital in Galați and conduct a literature review. The clinical presentation, co-infections, timing of antiviral therapy, laboratory findings, maternal vaccination status, and outcomes (including the hospitalization duration and recovery) were systematically analyzed for each case. Results: All three neonates were full-term and previously healthy, born to mothers who had not received influenza vaccinations during their pregnancies. They presented at ages ranging from 2 to 4 weeks with fever, respiratory symptoms including a cough, nasal congestion, and respiratory distress, as well as feeding difficulties. One case involved a co-infection with Bordetella pertussis, which manifested as a severe paroxysmal cough, cyanosis, and apnea. Laboratory findings in the cases with influenza alone indicated leukopenia accompanied by normal C-reactive protein levels. In the co-infection case, leukocytosis, lymphocytosis, and thrombocytosis were observed. All the infants received oseltamivir treatment within 48 h of the symptom onset; the case with pertussis co-infection also received azithromycin. Each infant required supplemental oxygen, but none necessitated mechanical ventilation. Clinical improvement was observed in all cases, with hospitalization ranging from 6 to 7 days and complete recovery without complications. Conclusions: Neonatal influenza may result in considerable morbidity, particularly in infants born to unvaccinated mothers. Positive outcomes, however, have been correlated with early diagnosis and antiviral treatment. Pertussis co-infection may exacerbate clinical progression, underscoring the importance of maternal immunization against both influenza and pertussis. In this case series, we aim to present three cases of laboratory-confirmed influenza in neonates born to mothers who were not immunized against influenza during pregnancy. These cases highlight the clinical presentations of neonatal influenza, underscore the risks associated with pertussis co-infection, and reinforce the importance of maternal influenza and Tdap vaccination for preventing severe outcomes in newborns. Full article

Background: Respiratory support required by preterm infants involves contact between their immature skin and ventilation devices, which can lead to skin breakdown. Methods: A prospective observational study including newborns with a nasal injury related to respiratory support, born at gestational age < 33 weeks, from May 2020 to January 2022, in the neonatal intensive care unit of Strasbourg. Injuries were recorded using a validated scale at inclusion and 3, 7 and 28 days. Sequelae were evaluated at discharge and 4, 9 and 12 months post-menstrual age. Results: In total, 64/276 newborns (23%) had a nasal injury. Most of the injuries were stage 2 (34/64, 53%) and stage 1 (25/64, 39%). The interface most frequently associated with injury was continuous positive airway pressure (53/64, 83%). Favorable evolution was associated with the injury site (p < 0.01) and the type of respiratory support needed when collecting at the 28th day (p = 0.04). At discharge, 34/58 infants (59%) had sequelae. The presence of a scar was associated with the maximum injury severity (p < 0.001) and total duration of respiratory support (p = 0.02). At 12 months, 31/47 infants (66%) had esthetic sequelae. Conclusions: Nasal injuries related to respiratory support in preterm infants were frequent, and more than half of the injuries resulted in medium-term sequelae. Full article

Objective: The development of a normal sleep–wake rhythm in the first weeks of life depends on the physiological sensory needs of the newborn as well as the environment surrounding them. This includes, for example, avoiding pain, exposure to bright light at night and high noise levels. In high-risk newborns, this process can be influenced by immaturity of the central and peripheral nervous systems, therapeutic strategies and the work organization of an intensive care unit. Methods: This study used a narrative review to examine the literature on the interrelationship of sensory modalities on sleep–wake behavior in the context of neonatal intensive care. The current Cochrane reviews on cycled lighting’s effect on premature infants’ circadian rhythm development and noise or sound management in the neonatal intensive care unit, as well as the World Health Organization (WHO) global position paper on kangaroo mother care, were included. Results: An extensive body of literature relates to fetal and neonatal development of the five sensory modalities: touch, taste, smell, hearing and sight. In contrast, there is a lack of evidence regarding the choice of optimal lighting and suitable measures for noise reduction. Since 2023, the WHO has recommended that, from the moment of birth, every “small and sick” newborn should remain in skin-to-skin contact (SSC) with their mother. Developmental support pursues a multimodal approach with the goal of fostering early parent–child bonding, including the child’s needs and environmental conditions. Discussion: The implementation of early SSC and attention to the sleep–wake cycle require systemic changes in both the obstetric and neonatal settings to ensure seamless perinatal management and subsequent neonatal intensive care. Since there is a lack of evidence on the optimal sensory environment, well-designed, well-conducted and fully reported randomized controlled trials are needed that analyze short-term effects and long-term neurodevelopmental outcomes. Full article

Physiological oxidative stress plays a pivotal role in supporting proper growth and development. While moderate oxidative stress is essential for activating key metabolic pathways and maintaining normal cellular signaling, excessive production of reactive oxygen species (ROSs) can overwhelm the immature antioxidant systems of newborns, potentially leading to cellular damage and impaired physiological function. This vulnerability is particularly pronounced in the central nervous system, where limited detoxification capacity exacerbates the risk of oxidative damage, following hypoxic–ischemic events. Antioxidants agents—such as melatonin, erythropoietin, allopurinol, N-acetylcisteine, selenium, iminobiotin, taurine, and acetyl-L-carnitine—have demonstrated significant neuroprotective effects in preclinical experimental studies, reducing markers of oxidative injury and improving neurological outcomes. These neuroprotective agents have also been evaluated in clinical trials, demonstrating antioxidant effects. A major issue lies in the complexity of neurological damage, which is not associated with a single pathological pathway. Additionally, the inability of these agents to reach effective concentrations within the central nervous system, along with inconsistencies across clinical trials in terms of dosage and administration methods, hinders the ability to obtain robust results. Future efforts should therefore focus on the development of delivery systems capable of crossing the blood–brain barrier and on establishing standardized clinical trial protocols and study designs. This educational review aims to provide a comprehensive overview of emerging protective strategies, including antioxidant bioactive agents and nutritional interventions. It also explores the underlying mechanisms of oxidative stress and its impact on neonatal brain injury. Full article

Diarrhea in piglets causes intestinal inflammation and epithelial damage. Weaned piglets fed with Bacillus subtilis (B.S) have enhanced intestinal mucosal immunity and reduces diarrhea in piglets. However, the immune system of newborn piglets is immature, and B.S cannot effectively activate the intestinal mucosal reaction when given directly. This research explored the impact of the maternal supplementation of B.S-Dia during the final 35 days of gestation on piglet intestinal development and mucosal immunity. The results demonstrated that B.S-Dia administration significantly increased the body weight, jejunal villus height, and crypt depth in the piglets. In addition, B.S-Dia also significantly increased the proliferative activity of intestinal epithelial cells, as evidenced by proliferating cell nuclear antigen (PCNA) staining and the elevated mRNA expression of the proliferation-related gene (c-Myc). Furthermore, B.S-Dia supplementation also reinforced the intestinal mucosal barrier by increasing goblet cell numbers and upregulating the mRNA expression of antimicrobial peptides, such as Muc2 and Lyz-1. Finally, elevated levels of IL-4 and IFN-γ, along with an increased abundance of CD3⁺ T cells, revealed that the intestinal mucosal immunity of piglets was improved after B.S-Dia administration. Our study indicates that feeding B.S-Dia to sow spromotes intestinal development and improves intestinal mucosal immunity in piglets. Full article

Background: Vitamin D is essential for neonatal health, with maternal vitamin D status crucial in fetal development and neonatal outcomes. During pregnancy, vitamin D is transferred to the fetus via the placenta, forming an initial reserve. Postnatally, neonates rely on maternal levels and supplementation due to limited sunlight exposure and immature skin synthesis. Objectives: This review evaluates neonatal vitamin D deficiency’s causes and clinical consequences, emphasizing its impact on newborn and infant health. Results: Maternal vitamin D levels strongly correlate with neonatal 25(OH)D concentrations, influencing birth weight, bone development, and overall health. Supplementation during pregnancy reduces the risk of severe deficiencies and rickets, particularly in exclusively breastfed infants who require daily supplementation of 400 IU. Formula-fed infants typically meet requirements through fortified formulas. Preterm infants are at a higher risk of complications like osteopenia and rickets, with mixed evidence on the effectiveness of higher supplementation doses. Vitamin D is critical in skeletal development, immune function, and protection against respiratory infections such as bronchiolitis and pneumonia. Deficiency is associated with respiratory distress syndrome (RDS), atopic dermatitis, and impaired bone mineralization due to reduced placental calcium transport. Conclusions: Vitamin D deficiency during pregnancy and infancy has significant clinical implications, including impaired skeletal and immune development. Maternal and neonatal supplementations are critical to prevent deficiencies, particularly in high-risk groups such as preterm and breastfed infants. Targeted strategies are essential to improve neonatal health outcomes and prevent complications. Full article

Newborns are born with an immature immune system, making them susceptible to infections early in life. Human milk provides essential nutrients and immunological factors that support infant immunity. Maternal vaccination during lactation has the potential to enhance these benefits by triggering an immune response in the mother, potentially extending protection to her child. However, lactating individuals are often excluded from vaccine trials, leading to uncertainties about vaccine safety and efficacy during the postpartum period. This study critically evaluates the effectiveness of vaccines in enhancing the immune-supporting properties of human milk and assesses their safety and efficacy for lactating mothers and their infants. By examining potential benefits alongside safety concerns, we aim to provide a comprehensive understanding of postpartum vaccination’s impact on maternal and infant health. We utilized large-language models (LLMs) to enhance the review process and performed a structured literature search across Ovid/Medline, Embase, and Clarivate Analytics using terms like “breastfeeding”, “postpartum”, and “vaccination”. A three-stage screening process involving human and LLM-assisted evaluation focused on postpartum vaccines and their implications for maternal and infant health. We identified 73 studies covering vaccines against COVID-19, cholera, influenza, pertussis, pneumococcal, rabies, polio, rotavirus, rubella, varicella, typhoid, smallpox, and yellow fever. Most vaccines, such as those for COVID-19 and influenza, appear safe and effective for postpartum use without requiring precautionary measures. However, caution is advised with vaccines such as the yellow fever vaccine, where temporary breastfeeding cessation is recommended. Overall, this review underscores the compatibility of most vaccines with lactation and suggests its benefits for both mother and infant. Full article

Postpartum adaptation causes an increased formation of free radicals (FRs) in the organism, which can lead to development of various FR-mediated diseases (FRMDs) in the newborn. The present study investigates the kinetics of skin and blood carotenoid antioxidants in term and preterm infants and the influence of FRMD. In the first phase, a diffuse reflectance spectroscopy-based scanner was validated for non-invasive measurements of skin carotenoids in term infants (thenar eminence) by correlation with blood carotenoids via reflection spectroscopy. In the second phase, the skin and blood carotenoids of 22 term and 13 preterm infants with and without FRMD were assessed from birth until discharge. It could be shown that the scanner reliably assessed carotenoids in the infants’ skin. The term and preterm infants showed similar kinetics of skin carotenoids, which increased and entered a plateau after 3–4 days. In our cohort, FRMD did not have a significant influence on skin carotenoid concentration. This was due to immature sweat glands and an insufficient excretion of carotenoids. Skin carotenoids seem to be unavailable, suggesting that they may have to be supplemented in infants with FRMD. Blood carotenoid concentrations tended to be lower in preterm infants and infants with FRMD compared to healthy term infants. Full article

Passive maternal-fetal transfer of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies has been demonstrated, whilst the degree of transfer depending on the trimester of infection is lacking. Due to neonates’ immature immune systems, this knowledge could be of interest when investigating the degree of early-life protection against SARS-CoV-2. For perinatal infections such as Rubella and Toxoplasmosis, the timing of infection related to gestational age is crucial for the severity of maternal-fetal outcomes; hence, the trimester of SARS-CoV-2 infection could potentially be crucial. So far, there is no stratification on all three trimesters of SARS-CoV-2 infection in relation to maternal antibody levels in SARS-CoV-2 positive women, and the degree of transfer of SARS-CoV-2 antibodies to the newborn nor on obstetric and neonatal outcomes, which we examined in this study. Eleven departments in Denmark invited women who tested SARS-CoV-2 positive during pregnancy to participate with a blood sample and a cord blood sample at delivery. 459 SARS-CoV-2 positive women and 2567 SARS-CoV-2 negative women were included. A percentage of 87.5%, 95.3%, and 60.3% of newborns of women who tested positive in their first, second, and third trimester, respectively, had a significantly higher immunoglobin G (IgG) antibody level than their mother at delivery, indicating that the fetus is able to concentrate antibody levels or maintain the level of IgG antibodies transferred. None of the examined maternal-fetal outcomes were increased in women infected with SARS-CoV-2. Full article

L-citrulline (L-CIT), a precursor to L-arginine (L-ARG), is a key contributor to the nitric oxide (NO) signaling pathway. Endothelial dysfunction, characterized by deficient nitric oxide synthesis, is implicated in the pathogenesis of various neonatal conditions such as necrotizing enterocolitis (NEC) and bronchopulmonary dysplasia (BPD) associated pulmonary hypertension (PH). This review summarizes the current evidence around the possible role of L-CIT supplementation in the treatment of these conditions. Detoxification of endogenously produced superoxide radicals is inadequate in preterm infants due to immature antioxidants that leads to the production of peroxynitrite, a reactive oxygen-free radical that is cytotoxic and causes damage to organelles and cellular membranes, further disrupting the coupling of endothelial NO synthase enzyme and the generation of high levels of reactive nitrogen and oxygen species. Animal studies in lipopolysaccharide-induced models of chorioamnionitis and hyperoxia- and inflammation-induced BPD-PH in rodent lung models revealed that L-CIT supplementation significantly mitigated structural changes in the pulmonary vasculature, preserved alveolar growth, and increased vascular endothelial growth factor gene expression, highlighting the anti-inflammatory and antioxidant effects of L-CIT supplementation. Similar benefits were noted in newborn piglet models of chronic hypoxia-induced PH and NEC. Pharmacokinetic studies in neonates have shown doses of 100–300 mg/kg/day to be safe and well tolerated. A few studies have shown the beneficial effects of L-CIT supplementation in pulmonary hypertension secondary to congenital heart disease, but evidence of efficacy in the neonatal population is lacking. While L-CIT shows promise in the treatment of various neonatal conditions, adequately powered studies to evaluate the safety and efficacy of L-CIT supplementation post-surgical NEC and BPD ± PH in the extremely preterm population are needed to translate this novel therapy to clinical practice. Full article

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