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Besides suppressing immune responses, regulatory T cells (Tregs) maintain tissue homeostasis and control systemic metabolism. Whether iron is involved in Treg-mediated tolerance is completely unknown. Here, we showed that the transferrin receptor CD71 was upregulated on activated Tregs infiltrating human liver cancer. Mice with a Treg-restricted CD71 deficiency spontaneously developed a scurfy-like disease, caused by impaired perinatal Treg expansion. CD71-null Tregs displayed decreased proliferation and tissue-Treg signature loss. In perinatal life, CD71 deficiency in Tregs triggered hepatic iron overload response, characterized by increased hepcidin transcription and iron accumulation in macrophages. Lower bacterial diversity, and reduction of beneficial species, were detected in the fecal microbiota of CD71 conditional knockout neonates. Our findings indicate that CD71-mediated iron absorption is required for Treg perinatal expansion and is related to systemic iron homeostasis and bacterial gut colonization. Therefore, we hypothesize that Tregs establish nutritional tolerance through competition for iron during bacterial colonization after birth.
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Antígenos CD , Hierro , Receptores de Transferrina , Linfocitos T Reguladores , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/metabolismo , Receptores de Transferrina/metabolismo , Animales , Hierro/metabolismo , Ratones , Humanos , Antígenos CD/metabolismo , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Ratones Noqueados , Femenino , Microbioma Gastrointestinal/inmunología , Masculino , Hígado/metabolismo , Hígado/inmunología , HomeostasisRESUMEN
Non-cystic white matter (WM) injury has become prevalent among preterm newborns and is associated with long-term neurodevelopmental impairment. Magnetic resonance is the gold-standard for diagnosis; however, cranial ultrasound (CUS) is more easily available but limited by subjective interpretation of images. To overcome this problem, we enrolled in a prospective observational study, patients with gestational age at birth < 32 weeks with normal CUS scans or grade 1 WM injury. Patients underwent CUS examinations at 0-7 days of life (T0), 14-35 days of life (T1), 370/7-416/7 weeks' postmenstrual age (T2), and 420/7-520/7 weeks' postmenstrual age (T3). The echogenicity of parieto-occipital periventricular WM relative to that of homolateral choroid plexus (RECP) was calculated on parasagittal scans by means of pixel brightness intensity and its relationship with Bayley-III assessment at 12 months' corrected age was evaluated. We demonstrated that: (1) Left RECP values at T1 negatively correlated with cognitive composite scores; (2) Right RECP values at T2 and T3 negatively correlated with language composite scores; (3) Left RECP values at T1 and T2 negatively correlated with motor composite scores. Thus, this technique may be used as screening method to early identify patients at risk of neurodevelopmental issues and promptly initiate preventive and therapeutic interventions.
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Lesiones Encefálicas , Sustancia Blanca , Recién Nacido , Humanos , Lactante , Recien Nacido Prematuro , Sustancia Blanca/diagnóstico por imagen , Ultrasonografía , Edad Gestacional , Imagen por Resonancia Magnética/métodos , Lesiones Encefálicas/patología , Encéfalo/diagnóstico por imagen , Encéfalo/patologíaRESUMEN
BACKGROUND: Phthalates are a family of industrial chemicals noncovalently bonded to plastic materials to enhance flexibility and durability. These compounds are extensively used in a variety of consumer products and even in many medical devices. Newborns present a higher susceptibility to phthalates. OBJECTIVE: To assess the short- and long-term health consequences of exposure to phthalates during the neonatal period. METHODS: Systematic review in accordance with the PRISMA statements. Eligible articles in English language were searched in MEDLINE, Scopus, ISI Web of Science, and Ovid databases using the following terms: "phthalate", "newborn", and "neonate". Unpublished data were searched in ClinicalTrials.gov website. All in vivo studies of any design published before May 16th, 2023 and fulfilling the following criteria were included: 1) investigations in which preterm and/or term newborns underwent one or more measurement of concentrations of phthalates on biological samples taken during the neonatal period; 2) studies in which quantitative measurement of phthalates was related to any kind of health outcome. Subgroup analysis was conducted by type of outcome. The quality assessment was performed according to the criteria from the "NIH Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies". RESULTS: 11,895 records were identified; finally, 5 articles were included for review. A mixture of phthalates was associated with improved performance on the NNNS summary scales of Attention, Handling, and Non-optimal reflexes before NICU discharge. At 2 months' corrected age, some phthalates were positively associated with problem-solving and gross motor abilities; increased levels of mono (2-ethylhexyl) phthalate, mono (2-ethyl-5-carboxypentyl) phthalate, and sum of di (2-ethylhexyl) phthalate (DEHP) metabolites (∑3DEHP and ∑4DEHP) were associated with worse fine motor performance. Furthermore, DEHP was associated with transient alteration of gut microbiota and increased IgM production after vaccine. A linear positive association between a mixture of phthalates and slope of the first growth spurt was even reported in preterm newborns. No relationship emerged between phthalates and bronchopulmonary dysplasia. Three studies out of 5 had fair quality. CONCLUSION: Given some methodological issues and the paucity of related studies, further investigations of flawless quality aimed at clarifying the relationship between early exposure to phthalates and health outcomes are needed.
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Dietilhexil Ftalato , Recién Nacido , Humanos , Estudios Transversales , Bases de Datos FactualesRESUMEN
(1) Background: An increased protein intake via parenteral nutrition (PN) in early life is associated with an improvement of the nitrogen balance in preterm newborns. However, the role of energy intake on amino acid (AA) utilization provided by PN remains to be defined. We investigated the effects of energy intake on blood AA levels and profiles. (2) Methods: Quasi-experimental study including preterm very low birth weight newborns who received an energy enhanced PN (Cohort A) or an energy standard PN (Cohort B), with a similar protein amount in the first week of life. Blood AA levels were measured between three and seven days of life (T0) and at fifteen days of life (T1) and compared between the two study cohorts. (3) Results: AA levels of 40 newborns from each group were analyzed. No difference was found for total essential and non-essential blood AA concentration at T0 between the two study cohorts. At T1, we found a significantly higher blood concentration of leucine, isoleucine and proline, and a significantly lower concentration of tyrosine in Cohort B. However, multivariate analysis did not confirm this result. (4) Conclusions: An enhanced PN protocol in terms of energy but not of protein did not influence AA levels and profiles. Considering the high risk of side effects, we suggest exercising caution when administering high energy intake via PN in the first week of life.
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Aminoácidos , Recien Nacido Prematuro , Recién Nacido , Humanos , Aminoácidos/metabolismo , Nutrición Parenteral , Leucina , Ingestión de EnergíaRESUMEN
BACKGROUND: Despite multifactorial pathogenesis, dysregulation of inflammatory immune response may play a crucial role in necrotizing enterocolitis (NEC). Regulatory T cells (Tregs) are involved in immune tolerance early in life. We aimed to investigate the predicting role of Tregs in developing NEC in neonates at high risk. METHODS: We studied six newborns with a diagnosis of NEC (cases) in comparison with 52 controls (without NEC). We further classified controls as neonates with feeding intolerance (FI) and neonates without it (FeedTol). The rate of female and male neonates (sex defined as a biological attribute) was similar. We analyzed the blood frequency of Tregs (not overall numbers) at three time points: 0-3 (T0), 7-10 (T1), and 27-30 (T2) days after birth by flow cytometry. Neonates' sex was defined based on the inspection of external genitalia at birth. RESULTS: We observed, at T0, a significantly lower frequency of Tregs in NEC cases (p < 0.001) compared with both FI (p < 0.01) and FeedTol controls (p < 0.01). Multivariate analysis reported that the occurrence of NEC was independently influenced by Treg frequency at birth (ß 2.98; p = 0.039). CONCLUSION: Tregs frequency and features in the peripheral blood of preterm neonates, early in life, may contribute to identifying neonates at high risk of developing NEC. IMPACT: Regulatory T cells may play a pivotal role in regulating the immune response in early life. Reduction of Tregs in early life could predispose preterm newborns to necrotizing enterocolitis. Early markers of necrotizing enterocolitis are still lacking. We demonstrated a predicting role of assessment of regulatory T cells in the diagnosis of this gastrointestinal emergency. Early identification of newborns at high risk of necrotizing enterocolitis through measurement of regulatory T cells may guide clinicians in the management of preterm newborns in order to reduce the development of this severe condition.
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Enterocolitis Necrotizante , Enfermedades Fetales , Enfermedades del Recién Nacido , Recién Nacido , Masculino , Humanos , Femenino , Enterocolitis Necrotizante/diagnóstico , Enterocolitis Necrotizante/epidemiología , Recien Nacido Prematuro , Linfocitos T ReguladoresRESUMEN
Fetal alcohol spectrum disorder (FASD) is a set of conditions resulting from prenatal alcohol exposure (PAE). FASD is estimated to affect between 2% and 5% of people in the United States and Western Europe. The exact teratogenic mechanism of alcohol on fetal development is still unclear. Ethanol (EtOH) contributes to the malfunctioning of the neurological system in children exposed in utero by decreasing glutathione peroxidase action, with an increase in the production of reactive oxygen species (ROS), which causes oxidative stress. We report a case of a mother with declared alcohol abuse and cigarette smoking during pregnancy. By analyzing the ethyl glucuronide (EtG, a metabolite of alcohol) and the nicotine/cotinine in the mother's hair and meconium, we confirmed the alcohol and smoking abuse magnitude. We also found that the mother during pregnancy was a cocaine abuser. As a result, her newborn was diagnosed with fetal alcohol syndrome (FAS). At the time of the delivery, the mother, but not the newborn, had an elevation in oxidative stress. However, the infant, a few days later, displayed marked potentiation in oxidative stress. The clinical complexity of the events involving the infant was presented and discussed, underlining also the importance that for cases of FASD, it is crucial to have more intensive hospital monitoring and controls during the initial days.
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Hyperglycemia (HG) is an independent risk factor of mortality and morbidity in very low birth weight newborns (VLBW). Achievement of high nutritional intakes in the first days of life (DoL) by parenteral nutrition (PN) increases the risk of HG. We aim to assess if a delayed achievement of the PN macronutrient target dose could reduce the occurrence of HG in VLBW. We enrolled 353 VLBW neonates in a randomized controlled clinical trial comparing two PN protocols that differed in the timing of energy and amino acid target dose achievement: (1) early target dose achievement (energy within 4-5 DoL; amino acids within 3-4 DoL) vs. (2) late target dose achievement (energy within 10-12 DoL; amino acids within 5-7 DoL). The primary outcome was the occurrence of HG during the first week of life. An additional endpoint was long-term body growth. We observed a significant difference in the rate of HG between the two groups (30.7% vs. 12.2%, p = 0.003). Significant differences were observed in terms of body growth at 12 months of life between the two groups (weight Z-Score: -0.86 vs. 0.22, p = 0.025; length: -1.29 vs. 0.55, p < 0.001). Delayed achievement of energy and amino acid intake may be useful to reduce the risk of HG along with an increase of growth parameters in VLBW neonates.
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Hiperglucemia , Nutrición Parenteral , Recién Nacido , Humanos , Nutrición Parenteral/métodos , Recién Nacido de muy Bajo Peso , Aminoácidos , NutrientesRESUMEN
Background: Preterm birth and subsequent NICU admission can be a traumatic experience for parents who may subsequently develop post-traumatic stress (PTS) disorder (PTSD). Given that developmental issues are common among children of parents with PTSD, interventions for prevention and treatment are essential. Objective: To assess the most effective non-pharmacological interventions to prevent and/or treat PTS symptoms in parents of preterm newborns. Methods: Systematic review performed in accordance with the PRISMA statements. Eligible articles in English language were searched in MEDLINE, Scopus, and ISI Web of Science databases using the following medical subject headings and terms: "stress disorder, post-traumatic," "parents," "mothers," "fathers," "infant, newborn," "intensive care units, neonatal," and "premature birth." The terms "preterm birth" and "preterm delivery" were also used. Unpublished data were searched in ClinicalTrials.gov website. All intervention studies published until September 9th, 2022 and including parents of newborns with gestational age at birth (GAb) <37 weeks which underwent ≥1 non-pharmaceutical interventions for prevention and/or treatment of PTS symptoms related to preterm birth were included. Subgroup analyses were conducted by type of intervention. The quality assessment was performed according to the criteria from the RoB-2 and the "NIH Quality Assessment Tool for Before-After studies." Results: Sixteen thousand six hundred twenty-eight records were identified; finally, 15 articles (1,009 mothers, 44 fathers of infants with GAb ≤ 366/7 weeks) were included for review. A good standard of NICU care (effective as sole intervention: 2/3 studies) and education about PTSD (effective in association with other interventions: 7/8 studies) could be offered to all parents of preterm newborns. The 6-session Treatment Manual is a complex intervention which revealed itself to be effective in one study with low risk of bias. However, the effectiveness of interventions still remains to be definitively established. Interventions could start within 4 weeks after birth and last 2-4 weeks. Conclusion: There is a wide range of interventions targeting PTS symptoms after preterm birth. However, further studies of good quality are needed to better define the effectiveness of each intervention.
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Background: Recommended vaccinations are the cheapest and most effective measure to reduce the risk of transmission and related complications, especially in high-risk healthcare settings. This study aimed to evaluate the knowledge, attitudes and behaviours of HCWs in relation to national recommendations. Methods: A transversal study was conducted through administration of a questionnaire by personal interview. The following care units were involved: Paediatric, Neonatal, Cardiac Surgery and General Intensive Care Units and Infectious Diseases Unit. Results: The study sample comprised 308 HCWs. Half the sample were aware of the vaccination recommendations, with occupation and age found to be predictive factors (OR = 9.38, 95%CI: 2.07−42.41; OR = 0.36, 95%CI: 0.22−0.60). A higher percentage defined the diseases as a risk for their patients' health, although this perception was lower in the over-40 age group. In several cases, there were statistically significant differences between the care units (p < 0.001). Around three-quarters of the sample agreed that vaccination should be mandatory; willingness to undergo a future booster vaccination was statistically correlated with the variables of age and care unit (p < 0.001, p = 0.03). Conclusion: The protection of health in the workplace can be achieved through some strategic actions, such as the implementation of educational strategies, and protocols for the monitoring of immunocompetence and the improvement of vaccination.
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Background: Preterm birth and admission to the neonatal intensive care unit (NICU) could induce post-traumatic stress disorder (PTSD). PTSD is an important factor to focus on, as it is associated with parental mental health difficulties and with changes in caregiving quality such as increased intrusiveness, reduced sensitivity, and increased attachment insecurity for the child. Aims: We aimed to study the main risk factors, in the early life of newborns, and preventive measures for PTSD in parents of neonates hospitalized in the NICU. Methods: We included parents of preterm newborns, consecutively admitted to the NICU of the University La Sapienza of Rome. The presence of PTSD following preterm birth and NICU admission was assessed using the Clinician-administered PTSD scale (CAPS) at enrollment and at 28-30 days following NICU admission or the moment of discharge. We also evaluated the Family Environment Scale which measures the social environment of all types of families; the Parental Stressor Scale which measures parental anxiety and stress; the Spielberger State-Trait Anxiety Inventory consisting of two parts measuring the State (response to present situation) and Trait (pre-disposition to be anxious) anxieties separately, and the Beck Depression Inventory Second Edition assessing depressive symptoms. Results: We found, in a multivariate analysis, that the gestational age of newborns admitted to NICU significantly (ß = 2.678; p = 0.040) influences the occurrence of PTSD. We found that the cases showed significantly (ß = 2.443; p = 0.020) more pathological Parental Stressor Scale sights and sounds scores compared to controls. The early Kangaroo-Care (KC) significantly (ß = -2.619; p = 0.015) reduces the occurrence of PTSD. Conclusion: Post-traumatic stress disorder in parents of preterm newborns is a pathological condition that should be properly managed, in the very first days after birth. The NICU environment represents a main risk factor for PTSD, whereas KC has been demonstrated to have a protective role in the occurrence of PTSD.
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Introduction: Parenteral nutrition (PN) may have detrimental effects on neurodevelopment in preterm newborns. Moreover, enteral nutrition (EN) seems to be protective. To understand the mechanisms of how neurological development can be influenced by the route of administration of nutritional intake, we investigated the relationship between the serum levels of the nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) and nutritional intake received in early life by preterm newborns. Materials and methods: Specimens of blood were obtained at 28 days of life (DOL) for NGF/BDNF determination in neonates <32 weeks of gestation and/or with birth weight <1,500 g, consecutively observed in the neonatal intensive care unit. We analyzed the relation between amino acid content and energy intake and NGF/BDNF measurements at 28 DOL. PN protein intake was referred to as the total amounts of amino acid intake received daily. Results: We enrolled 20 newborns (gestational age 30.45 ± 1.76 weeks, birth weight 1,340 ± 352.63 g). Serum NGF value at 28 DOL was positively correlated with enteral protein and energy intake (r = 0.767; r = 0.746, p < 0.001), whereas, negatively correlated with parenteral amino acid and energy intake (r = -0.652, p < 0.001; r = -0.466, p < 0.05). Similar significant correlations were described between BDNF level at 28 DOL and enteral energy intake (r = 0.493, p < 0.05). Multivariate regression analysis showed that NGF level at 28 DOL depends on enteral protein and energy intake administrated in the 1st week of life. Conclusion: Neurotrophin values varied according to the route of nutrition administration in preterm newborns. NGF/BDNF serum levels are influenced positively and negatively by EN and PN, respectively.
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Evidences demonstrated that timing of weaning influences long-term growth in full term infants. However, studies on preterm infants are still lacking, and the international guidelines are focused only on healthy full-term newborn, without consensus for preterms. We aimed at evaluating, in a cohort study, the consequences of different timing of weaning on auxological outcomes up to 12 months of corrected age in a population of neonates born with gestational age < 32 weeks or birth weight < 1500 g. We divided the enrolled neonates in two cohorts according to the timing of weaning: (i) Early Weaning: introduction of complementary food before 6 months of corrected age; (ii) Late Weaning: complementary food introduced after 6 months of corrected age. Growth parameters (weight, length, body mass index, and ponderal index) were measured at 12 months of life. The two groups were statistically comparable for baseline clinical characteristics, and differences on growth parameters were not reported between the two study groups. These results were confirmed in linear and binary logistic regression multivariate models. Timing of weaning is not related to growth of preterm newborns in the first 12 months of corrected age. Studies are needed to reach consensus for the appropriate nutritional approach for preterm babies after discharge.
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(1) Background: The tolerance of preterm newborns for the high nutritional intakes given by parenteral nutrition (PN) is still debated because of the risk of metabolic complications. Despite enteral nutrition (EN) being the preferred route of nutrition, an exclusive enteral feeding is not always possible, as in preterm newborns, the gut is immature and less tolerant of EN. We aimed to study the impact of a minimal enteral feeding (MEF) on the possible early metabolic complications of PN in a cohort of preterms with gestational age at birth GA ≤ 29 + 6/7 weeks of postmenstrual age. (2) Methods: We divided the study sample in two cohorts: 1) Late-Feeding (cohort 1), newborns who received MEF starting from the 8th day of age, and (2) Early-Feeding (cohort 2), newborns who received MEF, consisting of the administration of at least 4-5 mL/kg/day by the enteral route, in the first 7 days of age. The primary outcome of the study was the rate of at least one metabolic complication, including hyperglycemia, hypertriglyceridemia, or metabolic acidosis. (3) Results: We enrolled 80 newborns (Late-Feeding cohort 51 vs. Early-Feeding cohort 29). The rate of all metabolic complications was statistically higher in the Late-Feeding cohort compared to the Early-Feeding cohort. Binary logistic regression analysis showed that late administration of MEF negatively influenced the rate of all metabolic complications. (4) Conclusions: Early minimal administration of EN is associated with less frequent PN-related metabolic side effects and a higher rate of survival in critically ill newborns.
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Nutrición Enteral/métodos , Enfermedades del Prematuro/terapia , Recien Nacido Prematuro/metabolismo , Enfermedades Metabólicas/etiología , Nutrición Parenteral/efectos adversos , Acidosis , Enfermedad Crítica/terapia , Femenino , Edad Gestacional , Humanos , Hiperglucemia , Hipertrigliceridemia , Recién Nacido , Modelos Logísticos , Masculino , Estudios Prospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
(1) Background: Preterm birth exposes the infant to the known risk factors for atopic diseases. We aimed to study the neonatal risk factors and to describe the clinical manifestations of atopy, including the march of symptoms, in a cohort of preschool children born preterm. (2) Methods: We enrolled neonates with gestational age < 32 weeks or birth weight < 1500 g. We classified patients in cases and controls according to the presence of at least one atopic manifestation. (3) Results: We observed 72 cases and 93 controls. Multivariate models showed that the administration of more than one cycle of antibiotics (B 0.902, p = 0.026) and gestational diabetes (B 1.207, p = 0.035) influence the risk of atopy in babies born preterm. In addition, risk of atopic dermatitis was influenced by gestational age < 29 weeks (B -1.710, p = 0.025) and gestational diabetes (B 1.275, p = 0.027). The risk of wheeze was associated with familiarity for asthma (B 1.392, p = 0.022) and the administration of more than one cycle of antibiotics (B 0.969, p = 0.025). We observed a significant reduction in the rate of atopic manifestation after 2 years of life (33.9% vs. 23.8%, p < 0.05). (4) Conclusions: Modifiable (gestational diabetes, antibiotics use) and unmodifiable (familiarity for asthma) conditions influence the risk of atopy in babies born preterm. Extreme prematurity reduces the risk of atopic dermatitis. Preterm babies showed a peculiar atopic march.
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Current guidelines for preterm newborns recommend high energy nutrition soon after birth in order to limit growth retardation. However, long-term effects of this nutritional approach are still debated, and it has been demonstrated that cerebral growth depends on protein intake in early life. A negative impact of early high energy intake by parenteral nutrition (PN) has been reported for patients in critically ill conditions, observed in intensive care unit. We aimed at evaluating the impact of energy intake on cerebral growth in preterm neonates early in life. We included preterm newborns with gestational age < 32 weeks or birth weight (BW) < 1500 g. Measurement of cerebral structures was performed by cranial Ultrasonography (cUS) between 3 and 7 days of life (DOL, T0) and at 28 DOL (T1). We evaluated the relation between energy intake and cerebral growth in the first 28 DOL. We observed in 109 preterm newborns a significant (p < 0.05) negative correlation between energy intake received by PN and right caudate head growth (r = - 0.243*) and a positive correlation between total energy intake and transverse cerebellum diameter (r = 0.254*). Multivariate analysis showed that energy intake administered by enteral nutrition (EN), independently increased growth of left caudate head (ß = 0.227*) and height cerebellar vermis (ß = 0.415*), while PN independently affected growth of both right and left caudate head (ß = - 0.164* and ß = - 0.228*, respectively) and cerebellum transverse diameter (ß = - 0.849*). The route of energy administration may exert different effects on cerebral growth in early life. High energy intake administered through EN seems to be positively correlated to cerebral growth; conversely, PN energy intake results in a poorer cerebral growth evaluated with cUS.
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Encéfalo/diagnóstico por imagen , Ingestión de Energía , Nutrición Enteral/métodos , Recien Nacido Prematuro/fisiología , Encéfalo/crecimiento & desarrollo , Femenino , Humanos , Recién Nacido , Recien Nacido Prematuro/crecimiento & desarrollo , Masculino , UltrasonografíaRESUMEN
Introduction: An early diagnosis of necrotizing enterocolitis (NEC), a major gastrointestinal emergency in preterm newborns, is crucial to improve diagnostic approach and prognosis. We evaluated whether fecal high-mobility group box protein 1 (HMGB1) may early identify preterms at risk of developing NEC. Materials and Methods: A case-control study including neonates admitted at the Neonatal Intensive Care Unit (NICU) of the Sapienza University Hospital "Umberto I" in Rome, from July 2015 to December 2016. Stool samples obtained from cases (preterm newborns with NEC) and controls (newborns without NEC) were collected at the enrolment (T0) and within 7-14 days after the first sample collection (T1). HMGB1, extracted and measured with western blot, was reported as densitometry units (DUS). Results: HMGB1 levels in 30 cases (n = 28-Bell stage 1, n = 2 Bell stage 2) were higher [T0: 21,462 DUS (95% CI, 16,370-26,553 DUS)-T1: 17,533 DUS (95% CI, 13,052-22,014 DUS)] than in 30 preterm controls [T0: 9,446 DUS (95% CI, 6,147-12,746 DUS)-T1: 9,261 DUS (95% CI, 5,126-13,396 DUS), p < 0.001). Preterm newborns showed significant higher levels of HMGB1 (15,690 DUS (95% CI, 11,929-19,451 DUS)] in comparison with 30 full-term neonates with birth weight >2,500 g [6,599 DUS (95% CI, 3,141-10,058 DUS), p = 0.003]. Multivariate analysis showed that the risk of NEC was significantly (p = 0.012) related to the HMGB1 fecal levels at T0. Conclusions: We suggest fecal HMGB1 as a reliable marker of early NEC in preterm neonates. This study supports further investigation on the role of fecal HMGB1 assessment in managing preterm newborns at risk of NEC. Further studies are advocated to evaluate diagnostic accuracy of this marker in more severe forms of the disease.
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OBJECTIVES: Preterm births are at higher risk for neurodevelopment (NDV) disabilities. To limit long-term consequences, guidelines recommend aggressive parenteral nutrition (PN) soon after birth. The aim of this study was to examine the effects of energy-enhanced PN in the first week of life on long-term NDV in preterm neonates. METHODS: We compared two cohorts of newborns (group A: energy-enhanced PN and group B: energy-standard PN) with different energy intake in the first 7 d of life (DoL) given by PN with the same protein amount, to study the influences of an energy-enhanced PN on NDV at 24 mo of life evaluated with the Bayley Scale of Infant Development-III edition. RESULTS: We analyzed 51 newborns (A: n = 24 versus B: n = 27). The two cohorts were similar in baseline characteristics (gestational age group A 29 wk, 95% confidence interval [CI], 28-30 wk versus group B 29 wk, 95% CI, 28-30 wk; birth weight A: 1214 g, 95% CI, 1062-1365 g versus B 1215 g, 95% CI, 1068-1363 g; boys A 62.5% versus B 55.6%). Infants in cohort B showed significantly (P < 0.05) better gross motor, total scaled, and total composite motor scores (A: 8 (1) versus B 9 (2); A 17 (4) versus B 19 (5); A 91 (12) versus B 97 (15); respectively). Cohort A showed a higher percentage of infants with delayed socioemotional competence (A 30.4% versus B 7.7%, P < 0.05). No differences were found in growth parameters at 24 mo of life. Linear regression analysis showed that socioemotional competence and motor score were negatively associated with energy intake of the first 7 DoL given by PN. CONCLUSIONS: A more aggressive PN strategy results in lower motor score and socioemotional competence performance at 24 mo of life. More caution might be advocated for an energy-enhanced PN protocol, particularly in neonates with lower birth weight, for long-term NDV in preterm neonates.
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Recien Nacido Prematuro , Nutrición Parenteral , Peso al Nacer , Niño , Estudios de Cohortes , Humanos , Lactante , Recién Nacido , Masculino , Nutrición Parenteral TotalRESUMEN
(1) Background: Hypertriglyceridemia (HiTG) is a metabolic complication of intravenous lipid emulsions (ILEs) infusion. We aimed to evaluate the influence of HiTG on the respiratory outcome of preterm babies; (2) Methods: We enrolled, in a case-control study, newborns with gestational age <32 weeks or birth weight <1500 g, over a 3-year period. They were divided into cases and controls; cases were defined by the detection of HiTG defined as serum triglycerides (TG) value >150 mg/dL; (3) Results: We enrolled 40 cases and 105 controls. Cases had an increased incidence of bronchopulmonary dysplasia (30.0% vs. 14.3%, p < 0.05) and longer duration of invasive mechanical ventilation (7 days, 95% CI 4-10 days vs. 4 days, 95% CI 1-7 days, p < 0.01) compared to controls. Multivariate analysis confirmed that HiTG independently influenced the duration of invasive mechanical ventilation, also in the subgroups with gestational age ≤28 + 6/7 weeks or birth weight ≤1000 g; (4) Conclusion: Newborns with HiTG related to ILEs had a longer duration of invasive mechanical ventilation. Temporary suspension or reduction in ILEs in the case of HiTG is associated with an improvement of respiratory outcome.
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Emulsiones Grasas Intravenosas/efectos adversos , Recien Nacido Prematuro/fisiología , Respiración , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Hipertrigliceridemia , Recién Nacido , Modelos Logísticos , Nutrición Parenteral , Embarazo , Respiración ArtificialRESUMEN
INTRODUCTION: Association between persistency of a patent ductus arteriosus (PDA) and morbidity in preterm newborns is still controversial. We aimed to investigate the relation between PDA and morbidity in a large retrospective study. METHODS: A case-control study including neonates consecutively admitted to the Neonatal Intensive Care Unit (NICU), with gestational age (GA) < 32 weeks or body birth weight (BW) < 1500 g, over a 5-year period. Newborns were divided into Cases and Controls, according with the presence or absence of a hemodynamically significant PDA (hs-PDA). RESULTS: We enrolled 85 Cases and 193 Controls. Subjects with hs-PDA had significantly (p < 0.001) lower GA (26.7 w, 95%CI 27.1-28.0 vs. 30.1 w, 95%CI 29.7-30.4), BW (1024 g, 95% CI 952-1097 vs. 1310 g 95%CI 1263-1358) and an increased morbidity (60.0% vs. 18.7%). In a sub-group of extremely preterm newborns (GA ≤ 28 weeks and BW ≤ 1000 g), the rate of bronchopulmonary dysplasia (BPD) was significantly increased in Cases (31.7%) compared with Controls (5.9%, p = 0.033). Multivariate analysis showed that morbidity significantly depended on hs-PDA, GA and BW, and that, in extremely preterms, the hs-PDA represented an independent risk factor for BPD. CONCLUSIONS: Occurrence of the main morbidities of prematurity depended by hs-PDA, in association with GA, BW, and use of prenatal steroids. In extremely premature babies, hs-PDA is a risk factor for BPD, one of the most important morbidity of prematurity, independently by other confounding variables.