Iron capture through CD71 drives perinatal and tumor-associated Treg expansion.

Beside 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 knock-out neonates. Our findings indicate that CD71-mediated iron absorption is required for Treg perinatal expansion and 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.

Quantitative ultrasonographic examination of cerebral white matter by pixel brightness intensity as marker of middle-term neurodevelopment: a prospective observational study.

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.

The effects of industrial chemicals bonded to plastic materials in newborns: A systematic review.

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.

Oxidative Stress in a Mother Consuming Alcohol during Pregnancy and in Her Newborn: A Case Report.

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.

Analysis of Knowledge, Attitudes and Behaviours of Health Care Workers towards Vaccine-Preventable Diseases and Recommended Vaccinations: An Observational Study in a Teaching Hospital.

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.

Intravenous Lipid Emulsions Affect Respiratory Outcome in Preterm Newborn: A Case-Control Study.

(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.

Morbidity associated with patent ductus arteriosus in preterm newborns: a retrospective case-control study.

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.

New architectural design of delivery room reduces morbidity in preterm neonates: a prospective cohort study.

BACKGROUND: A multidisciplinary committee composed of a panel of experts, including a member of the American Academy of Pediatrics and American Institute of Architects, has suggested that the delivery room (DR) and the neonatal intensive care units (NICU) room should be directly interconnected. We aimed to investigate the impact of the architectural design of the DR and the NICU on neonatal outcome. METHODS: Two cohorts of preterm neonates born at < 32 weeks of gestational age, consecutively observed during 2 years, were compared prospectively before (Cohort 1: "conventional DR") and after architectural renovation of the DR realized in accordance with specific standards (Cohort 2: "new concept of DR"). In Cohort 1, neonates were initially cared for a conventional resuscitation area, situated in the DR, and then transferred to the NICU, located on a separate floor of the same hospital. In Cohort 2 neonates were assisted at birth directly in the NICU room, which was directly connected to the DR via a pass-through door. The primary outcome of the study was morbidity, defined by the proportion of neonates with at least one complication of prematurity (i.e., late-onset sepsis, patent ductus arteriosus, intraventricular hemorrhage, periventricular leukomalacia, bronchopulmonary dysplasia, retinopathy of prematurity and necrotizing enterocolitis). Secondary outcomes were mortality and duration of hospitalization. Statistical analysis was performed using standard methods by SPSS software. RESULTS: We enrolled 106 neonates (56 in Cohort 1 and 50 in Cohort 2). The main clinical and demographic characteristics of the 2 cohorts were similar. Moderate hypothermia (body temperature ≤ 35.9 °C) was more frequent in Cohort 1 (57%) compared with Cohort 2 (24%, p = 0.001). Morbidity was increased in Cohort 1 (73%) compared with Cohort 2 (44%, p = 0.002). No statistically significant differences in mortality and median duration of hospitalization were observed between the 2 cohorts of the study. CONCLUSIONS: If realized according to the proposed architectural standards, renovation of DR and NICU may represent an opportunity to reduce morbidity in preterm neonates.