To stratify groups of infants by gestational age and identify the lower limit of normal (LLN) of the cross-sectional area of peripheral muscles as well as diaphragmatic excursion and thickness and parasternal activation during spontaneous respiration in full-term and preterm newborns. A cross-sectional study was conducted at a neonatal unit. Preterm newborns (PTNBs) with gestational age of 28 to 366/7 weeks and full-term newborns (NBs) with gestational age of 37 to 416/7 weeks, clinically and hemodynamically stable, breathing ambient air with no signs of respiratory distress were included. NBs on oxygen therapy, those with known genetic syndromes, malformations of the nervous system and those having undergone surgery were excluded. Ultrasound was performed over the rectus femoris, tibialis anterior, and biceps brachii muscles (cross-sectional area) and diaphragm (thickness and excursion). One hundred twenty NBs were stratified based on gestational age (< 30 weeks [n = 25]; 31 to 35 weeks [n = 51]; 37 to 41 6/7 weeks [n = 44]). Significant differences were found in the cross-sectional area of the rectus femoris muscles and thigh circumference of NBs > 37 weeks compared to the other 2 groups (p < 0.05). Differences were found in diaphragm thickness and excursion between the groups with gestational age > 37 weeks and < 30 weeks. Greater activation of the parasternal muscles was found in the PTNBs. With regard to LLN, significant differences were found between the groups with gestational age > 37 weeks and < 30 weeks for all variables analyzed and between the group with gestational age > 37 weeks and other 2 groups for the cross-sectional area of the rectus femoris, diaphragmatic excursion, and diaphragm contraction velocity. Differences were found among the groups in the size of peripheral muscles as well as diaphragm thickness and excursion. Moreover, greater activation of the parasternal muscle was found in NBs with gestational age < 30 weeks. This study establishes normal values of ultrasound measures for full-term and preterm newborns.

OBJECTIVE: To assess the risk of cognitive impairment among infants born extremely preterm using the INTERGROWTH-21st standards.
METHODS: We analyzed anthropometric data at birth and 36 weeks postmenstrual age (PMA) from infants born extremely preterm (24-26 weeks of gestation) admitted to US neonatal units between 2008 and 2018. To determine INTERGROWTH-21st z-score values that indicate an increased risk of cognitive impairment at 2 years of age (Bayley cognitive score <85), we employed classification and regression trees and redefined growth failure (weight, length, and head circumference z-scores at 36 weeks PMA) and growth faltering (weight, length, and head circumference z-score declines from birth to 36 weeks PMA).
RESULTS: Among 5393 infants with a mean gestational age of 25 weeks, growth failure defined as a weight z-score of -1.8 or below at 36 weeks PMA and growth faltering defined as a weight z-score decline of 1.1 or greater from birth to 36 weeks PMA indicated a higher likelihood of cognitive impairment. A length z-score less than -1 at 36 weeks PMA had the highest sensitivity to detect cognitive impairment at 2 years (80%). A head circumference z-score decline of 2.43 or greater from birth to 36 weeks PMA had the highest specificity (86%). Standard definitions had fair to low sensitivity and specificity for risk detection of cognitive impairment.
CONCLUSIONS: Length and head circumference z-scores had the highest sensitivity and specificity for risk detection of cognitive impairment. Monitoring these growth parameters could guide earlier individualized interventions with potential to reduce cognitive impairment.
BACKGROUND: ClinicalTrials.gov ID Generic Database: NCT00063063.

Multiple randomized controlled trials of hypothermia for moderate or severe neonatal hypoxic-ischemic encephalopathy (HIE) have uniformly demonstrated a reduction in death or disability at early childhood evaluation. These initial trials along with other smaller studies established hypothermia as a standard of care in the neonatal community for moderate or severe HIE. The results of the initial trials have identified gaps in knowledge. This article describes 3 randomized controlled trials of hypothermia (second-generation trials) to address refinement of hypothermia therapy (longer and/or deeper cooling), late initiation of hypothermia (after 6 hours following birth), and use of hypothermia in preterm newborns.

OBJECTIVE: To investigate the association of growth patterns with overweight/obesity and markers of metabolic syndrome in ex-premature adolescents; to assess the relationship between the increase (1 SD) in Z-score weight at term and at 2 years with outcomes in adolescents with or without intrauterine growth restriction; and to evaluate the association between the Cook criteria and overweight/obesity according to body mass index.
METHODS: Cohort, retrospective, analytical study. Population: adolescents born weighting<1,500 g.
RESULTS: One hundred twenty-seven adolescents (11.3 years) were included. There is an association between the 1 SD increase in the percentile (Pc) of weight at 40 weeks and at 2 years in the population with adequate birth weight (PCA) with insulin levels, resistance, and sensitivity at 11 years. Catch-up at 2 years was associated with significantly higher proportion of HDL value<41 (18.75 vs. 5.36 %) OR 4.08 95% CI (1.04-16.05) p=0.031. Overweight/obesity was associated with waist circumference index>0.5, HDL<41, and with blood pressure greater than Pc 90 for sex and height.
CONCLUSIONS: In preterm infants, a 1 SD increase in weight Z score at 40 weeks and 2 years was predictive of metabolic and cardiovascular disorders in adolescence.

Preterm neonates are at risk for neurodevelopmental impairment, especially those with intraventricular hemorrhage (IVH). Cerebral vasospasm (VSP) is a common complication after subarachnoid hemorrhage (SAH) in adult population, but it is unknown if preterm neonates with IVH may develop it. We prospectively enrolled premature newborns < 32 weeks with IVH and without IVH. All patients received serial transcranial sonography through the temporal window of the middle cerebral artery, anterior cerebral artery, posterior cerebral artery, and the internal carotid artery with transcranial Doppler sonography days 2, 4, and 10 of life. Cerebral blood velocities (CBFVs) were measured including median velocity flow (MV), peak systolic velocity (PSV), and maximum end-diastolic velocity (EDV). Resistance index and pulsatility index were calculated. VSP was defined as an increase of 50% in the baseline velocity per day and/or a Lindegaard ratio higher than 3. Fifty subjects were enrolled. None of the patients with IVH showed elevation of MV or a Lindegaard ratio > 3. There were no differences between IVH and without IVH groups regarding resistance index and pulsatility index.    Conclusion: Preterm infants with IVH do not present a pattern of VSP analyzed by Doppler transcranial ultrasound in this pilot study. What is Known: • In adult population with subarachnoid hemorrhage the most treatable cause of cerebral ischemia is due cerebral vasospasm but is unknown if premature newborn may have vasospasm due the extravasation of blood in the context of intraventricular hemorrhage What is New: •In this pilot study we did not find in premature newborn with intraventricular hemorrhage signs of vasoespam measured by transcranial color doppler ultrasound.

UNASSIGNED: Bowel ultrasound (US) is one of the methods used to enhance diagnostic accuracy of necrotizing enterocolitis (NEC) and its associated complications in premature newborns.
UNASSIGNED: To explore the diagnostic accuracy of bowel US in extremely low birth weight (ELBW) infants with NEC.
UNASSIGNED: A single-center retrospective case-control study included 84 extremely low birth weight (ELBW) infants. The infants were divided into three groups: Group 1 -infants with NEC (n = 26); Group 2 -infants with feeding problems (n = 28); Group 3 -control group (n = 30).
UNASSIGNED: The specific bowel US findings in premature newborns with NEC (stage 3) included bowel wall thinning, complex (echogenic) ascites, and pneumoperitoneum, p < 0.05. The diagnostic effectiveness of these sonographic signs was 96.8% (sensitivity 75.0% and specificity 97.6%), p < 0.05. These findings with high specificity were associated with the need for surgical intervention, poor outcomes, or increased mortality. Stage 2 NEC which did not require surgery showed impaired differentiation of the bowel wall layers, absent or decreased bowel peristalsis, pneumatosis intestinalis, portal venous gas, or simple ascites, with a diagnostic accuracy of 82.9% (sensitivity 55.6%, specificity 91.4%, p < 0.05).
UNASSIGNED: Bowel US can be used as an adjunct to abdominal radiography to aid in the diagnosis of infants with suspected NEC by providing more detailed evaluation of the intestine.

Neonatal disorders, particularly those resulting from prematurity, pose a major challenge in health care and have a significant impact on infant mortality and long-term child health. The limitations of current therapeutic strategies emphasize the need for innovative treatments. New cell-free technologies utilizing extracellular vesicles (EVs) offer a compelling opportunity for neonatal therapy by harnessing the inherent regenerative capabilities of EVs. These nanoscale particles, secreted by a variety of organisms including animals, bacteria, fungi and plants, contain a repertoire of bioactive molecules with therapeutic potential. This review aims to provide a comprehensive assessment of the therapeutic effects of EVs and mechanistic insights into EVs from stem cells, biological fluids and non-animal sources, with a focus on common neonatal conditions such as hypoxic-ischemic encephalopathy, respiratory distress syndrome, bronchopulmonary dysplasia and necrotizing enterocolitis. This review summarizes evidence for the therapeutic potential of EVs, analyzes evidence of their mechanisms of action and discusses the challenges associated with the implementation of EV-based therapies in neonatal clinical practice.

Intraventricular hemorrhage (IVH) is a severe complication of preterm birth associated with white matter injury (WMI) and reduced neurogenesis. IVH commonly arises from the germinal matrix, a highly cellular, transient structure, where all precursor cells are born, proliferate, and migrate during brain development. IVH leads to reduced progenitor cell proliferation and maturation and contributes to WMI. Interruption of oligodendrocyte lineage (OL) proliferation and maturation after IVH will prevent myelination. We evaluated whether unrestricted somatic stem cells (USSCs) could recover OL lineage, as USSC release multiple relevant growth factors and cytokines. The effects of USSC infusion at 24 hours after IVH were assessed in the periventricular zone by analysis of OL lineage-specific progression (PDGFR+, OLIG2+, NKX2.2+ with Ki67), and this was correlated with growth factors TGFβ1, FGF2 expression. The early OL cell lineage by immunofluorescence and cell density quantitation showed significant reduction after IVH (P < .05 both PDGFR+, OLIG2+ at day 3); with significant recovery after injection of USSCs (P < .05 both PDGFR+, OLIG2+ at day 3). CSF protein and tissue mRNA levels of TGFβ1 were reduced by IVH and recovered after USSC (P < .05 for all changes). FGF2 showed an increased mRNA after USSC on day3 (P < .05). Cell cyclin genes were unaffected except for the cycle inhibitor P27Kip1 which increased after IVH but returned to normal after USSC on day 3. Our findings demonstrated a plausible mechanism through which USSCs can aid in developmental myelination by recovery of OL proliferation and maturation along with correlative changes in growth factors during brain development.

Purpose: To present 2 cases of premature newborns with hyperbilirubinemia and retinopathy of prematurity (ROP) who could not be examined properly to assess for disease progression because of vitreous opacification in the setting of an icteric vitreous and frail health status. Methods: The cases and their findings were analyzed. Results: Given the sickness of the neonates and examination difficulty, intravitreal bevacizumab was administered in both eyes to prevent disease progression. During subsequent examinations, the patients remained stable until discharge from the neonatal intensive care unit and were followed in the outpatient clinic without complication. Conclusions: The ROP and vitreous opacification in our cases were thought to be caused by hyperbilirubinemia. Because of vitreous opacification, these patients could not be properly examined for ROP. Treatment with an intravitreal antivascular endothelial growth factor injection might be considered to delay disease development until the newborn is healthier and able to be examined.

UNASSIGNED: Pulmonary hemorrhage (PH) is a life-threatening complication seen in very sick newborns with high morbidity and mortality. There is little data on the incidence, risk factors, and ultimate survival of newborns with pulmonary hemorrhage in sub-Saharan countries, where the healthcare provision and facility differ in many ways compared to high-income countries. Hence, this study aimed to determine the incidence, identify the risk factors, and describe the outcome of pulmonary hemorrhage in newborns in a low middle income country setting.
UNASSIGNED: A cohort study with prospective data collection was conducted in a public, tertiary-level hospital in Botswana, the Princess Marina Hospital (PMH). All newborns admitted to the neonatal unit from 1 January 2020 to 31 December 2021 were included in the study. Data were collected using a checklist developed on the RedCap database (https//:ehealth.ub.ac.bw/redcap). The incidence rate of pulmonary hemorrhage was calculated as the number of newborns who had pulmonary hemorrhage per 1,000 newborns in the 2-year period. Group comparisons were made using X2 and Student\'s t-tests. Multivariate logistic regression was used to identify risk factors independently associated with pulmonary hemorrhage.
UNASSIGNED: There were 1,350 newborns enrolled during the study period, of which 729 were male newborns (54%). The mean (SD) birth weight was 2,154(±997.5) g, and the gestational age was 34.3 (±4.7) weeks. In addition, 80% of the newborns were delivered in the same facility. The incidence of pulmonary hemorrhage was 54/1,350 {4% [95% CI (3%-5.2%)]} among the newborns admitted to the unit. The mortality rate in those diagnosed with pulmonary hemorrhage was 29/54 (53.7%). Multivariate logistic regression identified birth weight, anemia, sepsis, shock, disseminated intravascular coagulopathy (DIC), apnea of prematurity, neonatal encephalopathy, intraventricular hemorrhage, mechanical ventilation, and blood transfusion as risk factors independently associated with pulmonary hemorrhage.
UNASSIGNED: This cohort study identified a high incidence and mortality rate of pulmonary hemorrhage in newborns in PMH. Multiple risk factors, such as low birth weight, anemia, blood transfusion, apnea of prematurity, neonatal encephalopathy, intraventricular hemorrhage, sepsis, shock, DIC, and mechanical ventilation, were identified as independently associated risk factors for PH.