Presence of metabolic syndrome markers in very low birth weight ex-premature infants during early adolescence.

OBJECTIVES: 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.

Premature newborns with intraventricular hemorrhage do not have vasospasm pattern by cranial Doppler ultrasound: A pilot study.

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.

Efficacy of bowel ultrasound to diagnose necrotizing enterocolitis in extremely low birthweight infants.

BACKGROUND: Bowel ultrasound (US) is one of the methods used to enhance diagnostic accuracy of necrotizing enterocolitis (NEC) and its associated complications in premature newborns. AIM: To explore the diagnostic accuracy of BUS in extremely low birth weight (ELBW) infants with NEC. METHODS: 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). RESULTS: The specific BUS 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). CONCLUSIONS: BUS 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.

A Review of the Use of Extracellular Vesicles in the Treatment of Neonatal Diseases: Current State and Problems with Translation to the Clinic.

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.

Uma travessia no contexto da prematuridade: da uti-neonatal até a casa / Un camino en el contexto de la prematuridad: de la uci neonatal al hogar / A path in the context of prematurity: from neonatal icu to home

RESUMO. Este estudo retrata, através de relatos e observações clínicas, o caminho percorrido por uma mãe para tornar-se suporte, porto ou casa, para seus bebês gêmeos, durante a internação em UTI neonatal e logo após a alta hospitalar. A investigação, que teve como base a abordagem psicanalítica de Donald Winnicott, emergiu de um recorte da pesquisa de mestrado da autora principal. A pesquisa ocorreu em dois momentos: I) acompanhamento da mãe e bebês durante a internação do recém-nascido na UTI-neonatal de um hospital geral de Porto Alegre durante um mês e nove dias com frequência semanal e II) acompanhamento após a alta através de visitas domiciliares. A segunda etapa teve início após uma semana da alta hospitalar e ocorreu durante um mês e 19 dias com frequência quinzenal. Para a coleta dos dados foram utilizados diários clínicos como um dispositivo na escuta das singularidades observadas em cada atendimento. Observou-se que a experiência de internação representou vivências de (des) continuidade para os bebês e mãe. O processo da travessia para casa representou uma inflexão importante em relação à sustentação corporal (e psíquica) dos bebês pela mãe. Destacamos ainda que o acompanhamento psicológico demonstrou ter sido importante para sustentar essa mãe ao longo da travessia e ajudá-la a se tornar 'casa' para seus recém-nascidos.

RESUMEN. Este estudio retrata, a través de informes y observaciones clínicas, el camino recorrido por una madre para convertirse en apoyo, puerto u hogar para sus bebés gemelos durante el ingreso a la UCI Neonatal y poco después del alta hospitalaria. La investigación se basó en el enfoque psicoanalítico de Donald Winnicott y se desarrolló en dos momentos: I) Seguimiento de la madre y los bebés durante la hospitalización en la UCI Neonatal de un hospital general de Porto Alegre durante un mes y nueve días con frecuencia semanal y II) Seguimiento tras el alta a domicilio. La segunda etapa se inició luego de una semana del alta hospitalaria y se desarrolló durante un mes y diecinueve días con una frecuencia quincenal. Para la recogida de datos se utilizaron diarios clínicos como dispositivo para escuchar las singularidades observadas en cada servicio. Se observó que la experiencia de hospitalización representó experiencias de (dis) continuidad para los bebés y la madre. El proceso de ir a casa representó una inflexión importante en relación al apoyo corporal (y psíquico) de los bebés por parte de la madre. También destacamos que la asistencia psicológica resultó ser importante para apoyar a esta madre durante todo el camino y ayudarla a convertirse en un 'hogar' para sus recién nacidos.

ABSTRACT. This study portrayed, through reports and clinical observations, the path taken by a mother to become support, harbor, or home, for her twin babies during admission to the Neonatal ICU and shortly after hospital discharge. Such investigation, based on Donald Winnicott's psychoanalytical approach, arose as a part of the first author's master's research. The research took place in two moments: I) Weekly follow-up of the mother and babies during the newborn's admission to the Neonatal ICU of a general hospital in Porto Alegre, state of Rio Grande do Sul, for one month and nine days, and II) Follow-up after discharge through home visits. The second stage started one week after hospital discharge and occurred for one month and nineteen days, with a fortnightly frequency. For data collection, clinical diaries were used as a device to listen to the singularities observed in each service. The hospitalization represented experiences of (dis) continuity for the babies and the mother. The journey process to home was an important inflection about the bodily (and psychic) support of babies by the mother. Psychological care proved essential to support this mother throughout the journey and help her become a 'home' for her newborns.

Retinopathy of Prematurity Screening of Preterm Infants With Icteric Vitreous.

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.

Early Postnatal Expression of Tgfß-1 and Fgf-2 Correlates With Regenerative Functions of Unrestricted Somatic Stem Cell Infusion After Rabbit GMH-IVH.

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 TGFß1, 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 TGFß1 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.

Pulmonary hemorrhage and associated risk factors among newborns admitted to a tertiary level neonatal unit in Botswana.

Introduction: 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. Methods and materials: 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. Result: 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. Conclusion: 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.

Did the change of the vaccination schedule effect pneumococcal conjugate vaccination compliance and adherence of premature and mature born infants in Germany? Answers from a claims database analysis.

BACKGROUND: In August 2015, the German Standing Committee on Vaccination (STIKO) changed the pneumococcal conjugate vaccination (PCV) schedule for mature infants from a 3+1 to a 2+1scheme. For premature infants, the 3+1schedule remained unchanged. Aim was to assess vaccination rates, completeness, and timeliness for PCV stratified by premature and mature infants before and after the recommendation change based on real-world data. METHODS: Retrospective claims data analyses were conducted using a comprehensive research database. The study population consisted of all mature and premature infants born in 2013, 2016, or 2018 with an individual follow-up of 24 months using ICD-10-GM codes P07.2 and P07.3 for premature infants. Hexavalent (HEXA) combination vaccination with a consistent 3+1recommendation for premature and mature infants was analyzed as a reference. RESULTS: After follow-up of 24 months, rates of premature and mature infants receiving ≥1PCV and HEXA vaccination steadily increased since the change of STIKO's recommendation. However, in 2018 (2016/2013), only 47 % (41 %/65 %) of premature but 74 % (72 %/68 %) of mature infants obtained the recommended 3+1 respectively 2+1 PCV doses. At the same age, a consistent increase in complete HEXA vaccination with 3+1 doses was observed over time in premature (2013/2016/2018: 66 %/68 %/70 %) and mature (2013/2016/2018: 69 %/72 %/73 %) infants. Timeliness of PCV and HEXA booster administration remained stable with âˆ¼50 % of all premature and mature infants receiving the booster according to recommended timelines. CONCLUSION: There is no proven evidence that the reduced PCV schedule for mature infants induced a higher acceptance of vaccination. The rate of unvaccinated infants remained at a considerable level and vaccinations were often delayed. Although the STIKO still recommends a 3+1 PCV schedule for premature infants in Germany, less than half of children showed a completed vaccination series. To protect these vulnerable groups, efforts are needed to increase adherence to the STIKO recommendation especially for premature infants.

Risk factors associated with vitamin D deficiency in preterm neonates: a single-center step-wise regression analysis.

BACKGROUND: Vitamin D deficiency is particularly concerning in pregnant women, leading to various health-related issues in mothers and their babies, especially those born prematurely, including neonatal skeletal and respiratory disorders. In addition, there have been several reports indicating the presence of multiple impactful factors in the development of vitamin D deficiency. Therefore, we aimed to evaluate the vitamin D level in very preterm and moderately preterm newborns and investigate its association with presumed influential factors. METHODS: This cross-sectional descriptive study was performed on 54 mothers and their preterm neonates with gestational ages less than 34 weeks at delivery (i.e., very preterm and moderately preterm). After the serum vitamin D levels were determined from samples obtained in the first 24 h after birth, the babies were divided into two groups based on the presence or absence of deficiency. The relationship between several factors and the neonatal serum vitamin D level was investigated separately and in a linear step-wise regression model. RESULTS: The differences between the groups regarding maternal age, gestational age, neonate's gender, birth weight, and delivery method with neonatal vitamin D levels were not statistically significant. However, maternal vitamin D levels strongly correlated with neonatal vitamin D levels (P-value < 0.001, r = 0.636). The regression model also yielded a strong predictive capability (P-value < 0.001, Adjusted R2 = 0.606), with the maternal vitamin D level demonstrating a significant impact. CONCLUSIONS: Low vitamin D levels in pregnant mothers correlate with deficient levels in their preterm neonates. Therefore, as vitamin D deficiency significantly affects both the mother's and newborn's health, it is recommended that healthcare providers provide comprehensive plans for vitamin D supplementation during pregnancy.

Effect of Musical Stimulation on Placental Programming and Neurodevelopment Outcome of Preterm Infants: A Systematic Review.

BACKGROUND: The fetal environment is modulated by the placenta, which integrates and transduces information from the maternal environment to the fetal developmental program and adapts rapidly to changes through epigenetic mechanisms that respond to internal (hereditary) and external (environmental and social) signals. Consequently, the fetus corrects the trajectory of own development. During the last trimester of gestation, plasticity shapes the fetal brain, and prematurity can alter the typical developmental trajectories. In this period, prevention through activity-inducing (e.g., music stimulation) interventions are currently tested. The purpose of this review is to describe the potentialities of music exposure on fetus, and on preterm newborns in the Neonatal Intensive Care Unit evaluating its influence on neurobehavioral development. METHODS: Databases were searched from 2010 to 2022 for studies investigating mechanisms of placental epigenetic regulation and effects of music exposure on the fetus and pre-term neonates. RESULTS: In this case, 28 selected papers were distributed into three research lines: studies on placental epigenetic regulation (13 papers), experimental studies of music stimulation on fetus or newborns (6 papers), and clinical studies on premature babies (9 papers). Placental epigenetic changes of the genes involved in the cortisol and serotonin response resulted associated with different neurobehavioral phenotypes in newborns. Prenatal music stimulation had positive effects on fetus, newborn, and pregnant mother while post-natal exposure affected the neurodevelopment of the preterm infants and parental interaction. CONCLUSIONS: The results testify the relevance of environmental stimuli for brain development during the pre- and perinatal periods and the beneficial effects of musical stimulation that can handle the fetal programming and the main neurobehavioral disorders.

Shh activation restores interneurons and cognitive function in newborns with intraventricular haemorrhage.

Premature infants with germinal matrix haemorrhage-intraventricular haemorrhage (GMH-IVH) suffer from neurobehavioural deficits as they enter childhood and adolescence. Yet the underlying mechanisms remain unclear. Impaired development and function of interneurons contribute to neuropsychiatric disorders. Therefore, we hypothesized that the occurrence of IVH would reduce interneuron neurogenesis in the medial ganglionic eminence and diminish the population of parvalbumin+ and somatostatin+ cortical interneurons. Because Sonic Hedgehog promotes the production of cortical interneurons, we also postulated that the activation of Sonic Hedgehog signalling might restore neurogenesis, cortical interneuron population, and neurobehavioural function in premature newborns with IVH. These hypotheses were tested in a preterm rabbit model of IVH and autopsy samples from human preterm infants. We compared premature newborns with and without IVH for intraneuronal progenitors, cortical interneurons, transcription factors regulating neurogenesis, single-cell transcriptome of medial ganglionic eminence and neurobehavioural functions. We treated premature rabbit kits with adenovirus expressing Sonic Hedgehog (Ad-Shh) or green fluorescence protein gene to determine the effect of Sonic Hedgehog activation on the interneuron production, cortical interneuron population and neurobehaviour. We discovered that IVH reduced the number of Nkx2.1+ and Dlx2+ progenitors in the medial ganglionic eminence of both humans and rabbits by attenuating their proliferation and inducing apoptosis. Moreover, IVH decreased the population of parvalbumin+ and somatostatin+ neurons in the frontal cortex of both preterm infants and kits relative to controls. Sonic Hedgehog expression and the downstream transcription factors, including Nkx2.1, Mash1, Lhx6 and Sox6, were also reduced in kits with IVH. Consistent with these findings, single-cell transcriptomic analyses of medial ganglionic eminence identified a distinct subpopulation of cells exhibiting perturbation in genes regulating neurogenesis, ciliogenesis, mitochondrial function and MAPK signalling in rabbits with IVH. More importantly, restoration of Sonic Hedgehog level by Ad-Shh treatment ameliorated neurogenesis, cortical interneuron population and neurobehavioural function in kits with IVH. Additionally, Sonic Hedgehog activation alleviated IVH-induced inflammation and several transcriptomic changes in the medial ganglionic eminence. Taken together, IVH reduced intraneuronal production and cortical interneuron population by downregulating Sonic Hedgehog signalling in both preterm rabbits and humans. Notably, activation of Sonic Hedgehog signalling restored interneuron neurogenesis, cortical interneurons and cognitive function in rabbit kits with IVH. These findings highlight disruption in cortical interneurons in IVH and identify a novel therapeutic strategy to restore cortical interneurons and cognitive function in infants with IVH. These studies can accelerate the development of new therapies to enhance the neurodevelopmental outcome of survivors with IVH.

Assessment of Indicators of Left Ventricular Performance Obtained by Tissue Doppler Imaging in Prematurely Born Neonates.

Introduction: Tissue Doppler imaging techniques (pulsed-wave TDI (pwTDI) and color-coded TDI (cTDI)) allow for the assessment of myocardial performance during the cardiac cycle. The application of such techniques in neonatology is sporadic and poorly studied. Objective: The objective of the present study was to determine average values of pwTDI indicators of left ventricular performance (maximum systolic velocity of the mitral annulus (s'), maximum velocity in early diastole (e') and maximum velocity in late diastole (a')) and to examine their dynamics in prematurely born newborns in the first week of life. Methods: Prematurely born newborns of postnatal age up to 7 days were divided by gestational age into Group1 (<28 weeks) and Group 2 (≥28 weeks). Standard pwTDI parameters (s', e' and a') were measured, compared between the groups and correlated with gestational and postnatal age, as well as application of respiratory support. Results: Fifty subjects were included (Group 1: 24; Group 2: 26). Average values of parameters s', e' and a' were: Group 1: 4.06 ± 0.78 cm/s, 3.71 ± 0.40 cm/s and 3.98 ± 1.06 cm/s, respectively; Group 2: 4.18 ± 1.22 cm/s, 4.68 ± 1.04 cm/s and 4.12 ± 0.94 cm/s, respectively. Values of parameter e' differed significantly between groups (p = 0.001) and strongly correlated with gestational age (p = 0, Pearson's R = 0.88). There was no significant difference between groups for parameters s' and a' (p = 0.42 and 0.31, respectively). The values of s', e' and a' did not differ between patients with an without respiratory support. Conclusion: Parameter e' depends on gestational age, whereas parameters s' and a' are independent of gestational age. pwTDI indicators do not change during the first week of life, nor are all robust to hemodynamic circumstances caused by invasive/non-invasive respiratory support.

The First Experience of Application the Umbilical Cord-Derived Human Autologous Mesenchymal Stromal Cells for the Rehabilitation Therapy of Premature Infants with Extremely Low Body Weight and Hypoxic-Ischemic Encephalopathy.

Two clinical cases of the use of cell therapy with umbilical cord-derived autologous mesenchymal stromal cells in the rehabilitation therapy of extremely premature newborns (27-28 weeks gestation, body weights 900 and 870 g, respectively) with hypoxic-ischemic encephalopathy are described. The girls were born by caesarean section; the 1-min Apgar score was 6 points. After resuscitation including artificial ventilation, stabilization of the condition was achieved against the background of the development of hypoxic-ischemic encephalopathy. Rehabilitation therapy included administration of umbilical cord-derived mesenchymal stromal cells harvested at birth. The cells were injected in a dose of 1.6-7 million/kg body weight at the age of 3, 6, 12 months (the first patient) and 3, 6, 9, 15 months (the second patient). Psychoneurological developmental delay was scored using the Hellbrügge scale. Cell therapy induced no significant adverse reactions and improved the psychomotor development of children.

Possibilities of Influencing Procedural Pain Associated with Premature Newborn Retinopathy Screening with Oral Clonidine.

BACKGROUND: The aim of our study was to compare the analgesic/sedative effects of various fundus-related procedural pain management strategies on the risk of retinopathy in premature infants. METHOD: This was a prospective comparative study involving a total of 94 neonates randomized to three groups meeting the criteria for at-risk neonates. Ophthalmologic screening was performed to evaluate the outcome of three procedural pain management strategies. The intensity of pain over time during and after the screening examination was evaluated. At the same time, we also looked at the occurrence of vegetative symptoms and their influence by the chosen medication. Pain response was observed in all 94 neonates enrolled in the study. In group A, no pain treatment was given. Group B had a local anesthetic oxybuprocaine hydrochloride 0.4% introduced into both eyes immediately prior to the examination. Group C received oral clonidine. The study was conducted as a pilot project and aimed to clarify the problem so that a project with a higher proband representation could take place in the future. Consequently, we performed quantitative analysis of complete pain and vegetative functions, followed by a qualitative analysis of their internal components. RESULTS: In our study, we identified the most considerable effects for all three groups, including NIPS (Neonatal Infant Pain Scale) responses immediately during and after the examination. The influence of vegetative functions is of a longer-term nature and increased values can be clearly demonstrated even six hours after the examination. CONCLUSION: The current results identify and quantify differences among all three methods of pain treatment on the level of single variables. Their internal structures, however, can be analysed only qualitatively because of the small size of the analysed sample.

Effects of Fish Oil (SMOFlipid®) and Olive Oil Lipid (ClinOleic®) on Neonatal Morbidities in Preterm Infants.

Objective: Total parenteral nutrition (TPN) is very important for providing optimal nutrition during the critical developmental period of preterm newborns. Thus, there is a need to optimize TPN solutions to reduce morbidities. This study aimed to examine the effects of olive oil (ClinOleic®) and fish oil (SMOFlipid®) therapies on the frequencies of neonatal morbidities. Methods: Premature newborns hospitalized in the neonatal intensive care unit and receiving TPN for at least 14 days were included in the study. Newborns who were hospitalized and received olive oil-based lipid (ClinOleic®) were included in the olive oil group, and those who received omega-3 containing multi-lipid (SMOFlipid®) were included in the SMOFlipid group. Results: This study enrolled a total of 222 very-low-birth-weight premature newborns. The breastfeeding rate in the olive oil group was significantly lower than that in the SMOFlipid group (p<0.05). The rate of necrotizing entercolitis (NEC) in the olive oil group was significantly higher than that in the SMOFlipid group (p<0.05). The rate of bronchopulmonary dysplasia (BPD) in the SMOFlipid group was lower than that in the olive oil group (p<0.05). Conclusions: The rates of BPD and NEC were lower in the fish oil group. In this situation, fish oil therapy may provide protection against the development of BPD and NEC. Prospective studies are needed to determine whether this is caused by lipid therapy or an effect of breast milk.

Association Analysis of the Cerebral Fractional Tissue Oxygen Extraction (cFTOE) and the Cerebral Oxygen Saturation (crSaO2) with Perinatal Factors in Preterm Neonates: A Single Centre Study.

(1) Background: Near-infrared spectroscopy (NIRS) is a non-invasive, easily performed method of monitoring brain oxygenation. The regional cerebral oxygen saturation (crSaO2) and the cerebral fractional tissue oxygen extraction (cFTOE) evaluated by NIRS provide more accurate information on brain oxygenation than the blood oxygen saturation. We investigated the effect of perinatal factors on cerebral oxygenation of preterm newborns. (2) Methods: We conducted a longitudinal study with 48 preterm newborns <34 weeks of gestation who underwent NIRS registration during the first 72 h of life. crSaO2 was measured and cFTOE was calculated foreach patient. (3) Results: One-way ANOVA showed no significant main effect of IVH severity on crSaO2 and cFTOE (p > 0.05); there was a tendency toward statistical significance concerning the difference between the means of crSaO2 (p = 0.083) and cFTOE (p = 0.098). Patients with intraventricular haemorrhage (IVH) had a lower mean of crSaO2 and a higher mean of cFTOE (59.67 ± 10.37% vs. 64.92 ± 10.16% for crSaO2; 0.37 ± 0.11 vs. 0.32 ± 0.11 for cFTOE) compared to those with no IVH. Significantly lower values of crSaO2 and higher values of cFTOE were found in neonates receiving inotropic treatment (p < 0.0001). Episodes of apnoea also proved to influence the cerebral oxygen saturation of the study group (p = 0.0026). No significant association between the maternal hypertension treatment and the cerebral oxygenation of preterms was found. (4) Conclusions: This study showed a decreased cerebral oxygen saturation of preterms with IVH, inotrope support and apnoea episodes.

Stability of glutathione added as a supplement to parenteral nutrition.

BACKGROUND: Most very premature newborns (<32 weeks of gestation) receive parenteral nutrition (PN) that is inherently contaminated with peroxides. Oxidative stress induced by PN is associated with bronchopulmonary dysplasia, a main pathological complication in these infants who have weak antioxidant capacity to detoxify peroxides because of their glutathione deficiency. In animals, glutathione supplementation of PN prevented oxidative stress and alveolar loss (the main characteristic of bronchopulmonary dysplasia). Of its two forms-oxidized glutathione (GSSG) and reduced glutathione (GSH)-GSSG was used because of its better stability. However, a 30% loss of GSSG in PN is observed. The potentially high therapeutic benefits of GSSG supplementation on the health of very premature infants make the study of its stability highly important. METHODS: GSSG was incubated in combination with the following components of PN: dextrose, multivitamins, Primene, and Travasol, and with cysteine, cystine, and peroxides, for 24 h. Total glutathione in these solutions was measured 0-24 h after the addition of GSSG. RESULTS: The combination of cysteine and multivitamins caused the maximum loss of glutathione. The stability of GSSG was not affected by multivitamins. The cysteine was responsible for ∼20% of the loss of GSSG; in the presence of multivitamins, the loss reached >70%. Removing the cysteine prevented the degradation of glutathione. CONCLUSION: GSSG reacts with cysteine to form cysteine-glutathione mixed disulfide, another suitable glutathione substrate for preterm neonates. The study confirms that GSSG added to PN can potentially provide a precursor to de novo synthesis of glutathione in vivo.

Impact of Oropharyngeal Administration of Colostrum in Preterm Newborns' Oral Microbiome.

The initial colonization of the human microbiota is of paramount importance. In this context, the oropharyngeal administration of colostrum is a safe, viable, and well-tolerated practice even by the smallest preterm infants. Therefore, this study evaluated the effects of oropharyngeal administration of colostrum on the establishment of preterm infants' oral microbiota. A longitudinal observational study was carried out with 20 premature neonates, divided into two groups: one receiving the protocol (Oropharyngeal Administration of Colostrum; OAC) and the other one receiving Standard Caare (SC). Saliva samples were collected from the newborns weekly during the study period (from the day of birth until the 21st day of life) for analysis of oral microbiota through 16S rRNA gene sequencing. We observed that the colonization of the oral microbiota of preterm newborns preseanted a higher relative abundance of Staphylococcus on the 7th day of life, mainly in the OAC group. Additionally, an increased abundance of Bifidobacterium and Bacteroides was observed in the OAC group at the first week of life. Regarding alpha and beta diversity, time was a key factor in the oral modulation of both groups, showing how dynamic this environment is in early life.

Vaccination rates and adherence in premature infants before and after pneumococcal conjugate vaccine schedule change for term infants - A claims database analysis in Germany.

BACKGROUND: In 2015, the German Standing Committee on Vaccination (STIKO) changed the pneumococcal conjugate vaccination (PCV) schedule for mature infants from a 3+1scheme (2, 3, 4, and 11-14 months of age) to a 2+1scheme (2, 4, and 11-14 months of age). For premature infants, the 3+1scheme remained. The aim of this study was to assess vaccination rates, completeness, and timeliness for PCV in premature infants before and after the modified recommendation. METHODS: A retrospective claims data analysis using the "Institut für angewandte Gesundheitsforschung Berlin" Research Database was conducted. Premature infants born in 2013 and 2016 with an individual follow-up of 24 months were included. Hexavalent combination (HEXA) vaccination with a consistent 3+1recommendation for mature and premature infants was analyzed as reference vaccination. RESULTS: After 24 months, the PCV rate for at least one dose remained stable in premature newborns of 2016 compared to 2013, while the HEXA vaccination rate increased slightly. However, a significant decrease of a completed PCV schedule (4 doses) in premature infants was noted, whereas the completeness of HEXA vaccination did not change. The timeliness of PCV in premature newborns increased for the first and the booster PCV, while the timeliness of HEXA immunization did not change from 2013 to 2016. CONCLUSION: Although STIKO still recommends a 3+1PCV schedule for premature infants in Germany, premature infants were vaccinated according to the changed recommendations for mature born infants. A substantial share of premature infants remained unvaccinated, and their vaccinations were often delayed.