Defective Leukocyte ß2 Integrin Expression and Reactive Oxygen Species Production in Neonates.

Neonates are highly susceptible to bacterial infections, which represent a major source of mortality and morbidity in this age category. It is recognized that ß2 integrins play a critical role in innate immunity by mediating leukocyte vascular adhesion, transmigration and bacterial phagocytosis. Therefore, we aimed to assess if the impaired immune functions seen in newborns may derive, in part, from a transient insufficient ß2 integrin expression. In the present study we measured baseline lymphocyte function-associated antigen-1 (LFA-1 or CD11a/CD18), macrophage-1 antigen (MAC-1 or CD11b/CD18) and leukocyte integrin p150-95 (CD11c/CD18) expression on cord blood, and on the third day of life in a cohort of 35 healthy neonates, compared with a control group of 12 healthy adults. For any of the three ß2 integrins, the expression on polymorphonuclear cells was significantly lower on cord blood than in adults and increased from birth to day 3. We also compared superoxide radical (SR) production in these neonates with 28 non-smoking adults. SR production in response to integrin stimulation by Zymosan was significantly lower at birth than in adults, and it decreased further in the third day of life. These findings suggest that innate immune impairment in newborns may be, in part, accounted for by a lower ß2 integrin expression on phagocytes in the neonatal period, but also by a functional impairment of free radical production.

Pain in Mucopolysaccharidoses: Analysis of the Problem and Possible Treatments.

Mucopolysaccharidosis (MPS) are a group of lysosomal storage disorders that are caused by the deficiency of enzymes involving in the catabolism of glycosaminoglycan (GAGs). GAGs incompletely degraded accumulate in many sites, damaging tissues and cells, leading to a variety of clinical manifestations. Many of these manifestations are painful, but few data are available in the literature concerning the prevalence, etiology, and pathogenesis of pain in children with MPS. This review, through the analysis of the data available the in literature, underscores the relevant prevalence of pain in MPSs' children, provides the instruments to discern the etiopathogenesis of the disease and of pain, illustrates the available molecules for the management of pain and the possible advantages of non-pharmacological pain therapy in MPSs' patients.

Rights of the Dying Child: The Nurses' Perception.

AIM: The Charter of the Rights of the Dying Child was formulated as a professional guide for caring the child in the final stages. The study examines the nurses' degree of agreement with the Charter's principles and their perception of the implementation of those principles in hospital. MATERIALS AND METHODS: A multicenter, cross-sectional study to observe the nurses' positions about the 10 rights outlined in the Charter, using an online questionnaire in 5 pediatric hospitals in northern Italy. RESULTS: A total of 119 nurses (44.9%) completed the questionnaire. The majority (range: 86.6-100%) expressed their agreement with the Charter's principles (Likert ≥4). Lower ratings were reported in Charter's principles implementation items (range: 42.9-89.1%). Being older and working in a smaller hospital lead the nurses to overlook the child's right to be informed and to be given the opportunity to make decisions about his/her own life and death (p = 0.02, p < 0.01). Postgraduate training induced greater awareness of the dying child (p = 0.01). CONCLUSIONS: This study highlights the value of the Charter of the Rights of the Dying Child as a reference guideline for nurses working in pediatric hospitals. Better training is important to improve the nurse's communication skills and the pediatric palliative care should be offered to all families that have a child with incurable disease mostly in the end of life.

The rights of the dying child and the duties of healthcare providers: the "Trieste Charter".

PURPOSE: The death of a child is a devastating and tragic event for all those involved. This charter aims to help healthcare workers and people assisting terminally ill children to recognize some important rights of the child, with some related suggestions. We consider it important to have a trace of this process, based on the skillfulness of long-lasting experts. METHODS: In September 2012, a group of professionals working with children affected by incurable illness in Italy launched a project to formulate the charter. Trieste is the city where the group of professionals first met to start the project. The first step was a detailed literature search on the topic, the second step was an extensive discussion among the professionals (writing committee) to prepare a first draft; later (third step) the draft was revised by 38 experts in different areas, including patient and family representatives, and lastly (fourth step) the final version of the charter was prepared. RESULTS: We developed a document containing 10 rights and corresponding duties that could be applied to any clinical situation or circumstances and used as a guide by professionals and families caring for children in the terminal stages of an illness. CONCLUSIONS: The Trieste Charter proposes fundamental rights for children who are approaching the end of their lives. The charter will have achieved its purpose when every person caring for a dying child is capable of staying near the child until the last moments of his or her life, prepared to accept his or her death, ensuring both respect and dignity.

Barriers to the development of pediatric palliative care in Italy.

INTRODUCTION: In recent years the emergence of new types of patient, clinical situations, technological frontiers and "health" objectives have changed considerably the needs of ill children, this also concerns pediatric palliative care (PPC). In Italy, despite the introduction of legislation (Law 38/2010) stipulating the right of children and families to access appropriate services for pain control and pediatric palliative care, the availability of these services is still limited. AIM: The aim of this study is to highlight, through a review of the existing data and published literature, the critical issues that obstacle the planning and development of PPC services in Italy. RESULTS: Four main areas identified were: socio-cultural setting; types of patients and nature of diseases requiring PPC; training for PPC providers; regulatory and political issues. CONCLUSIONS: This type of analysis can provide the rational for advancing proposals and developing supportive, corrective and implementation strategies.

Communication with parents in neonatal intensive care.

The psycho-relational problems in Neonatal Intensive Care Units (NICU) are complex and multifaceted and have only recently been properly addressed. Some specific factors make communication in NICU particularly problematic; the baby's clinical condition, the emotional and working conditions of the medical staff, the emotional state of the parents and the setting of the NICU and the interaction of multiple professional figures with the parents. The purpose of communication in NICUs is not only to inform parents of their child's clinical condition; the medical and nursing staff must also educate and guide parents so that they can actively participate in caring for their child and become true "partners" with the medical team in the decision-making process. Furthermore, the staff must also use their communication skills to understand and contain the anxieties and emotions of parents, supporting and comforting them through the most critical moments of their child's illness and possibly even bereavement. Given the number and complexity of the interpersonal exchanges that take place in the NICU, the risk of misunderstanding, misinterpretation and conflict is high. One could say that the interpersonal aspect is an area where the risk of iatrogenesis is elevated. It is recognized that poor staff-family interactions not only reflect negatively on the baby's care and are a source of distress and discontent for the parents, but are also a major cause of medico-legal litigation and increase the incidence of "burnout". Therefore, specific training of the staff in communication is essential if the optimal results, obtained through modern technology, are not to be invalidated.

Awareness, understanding and attitudes of Italians regarding palliative care.

There are numerous difficulties encountered in the diffusion of palliative care (PC) in developed countries. A correct and widespread awareness of PC among the general public represents an important factor for its enhanced diffusion and use. The aim of this study is to verify the level of awareness of PC among Italians and their perception of the needs of patients with incurable illness. A random sample of 1897 adult subjects, aged 18 to 74 years, representative of the Italian population, was interviewed after stratification by gender, age (6 strata), education (3 levels), geographic area of residency (4 areas) and town of residency (4 dimensions). 59.4% of those interviewed had heard of PC, but only 23.5% of them believed that they had an adequate or precise idea of what PC is; 27% of them did not know or had a mistaken idea about the nature of PC. The most accepted perception was that PC alleviates pain and improves quality-of-life. The principal concerns attributed to incurable patients were: fear of suffering and of death, and the principal needs were perceived as: relief from pain and physical suffering. The primary needs of the family were identified in: medical and nursing care at home, followed by: care provided by volunteers and psychological support. The most appropriate care-setting for these patients was indicated as their home, possibly with the support of professional carers. In the case of children, the main concern indicated was that of being "separated" from family, friends, home and toys. Only 45.2% of interviewees thought that they knew a person who had experienced PC. In conclusion, the awareness of the Italian population of PC is scarce and often incorrect. In order to achieve a greater diffusion and better use of PC in our country, this awareness needs to be improved by appropriate intervention.

Ethical issues in neonatal intensive care.

Recent progress in neonatal care have significantly improved the prognosis and chances of survival of critically ill or extremely preterm neonates and have modified the limits of viability. However, in some circumstances, when the child's death can only be briefly postponed at the price of severe suffering, or when survival is associated with severe disabilities and an intolerable life for the child and his/her parents, the application of the full armamentarium of modern neonatal intensive care may not be appropriate. In such circumstances the limitation of intensive treatments (withholding or withdrawing) and shift towards palliative care, can represent a more humane and reasonable alternative. This article examines and discusses the ethical principles underlying such difficult decisions, the most frequent situations in which these decisions may be considered, the role of parents in the decisional process, and the opinions and behaviours of neonatologists of several European neonatal intensive units as reported by the EURONIC study.

A polymorphism in the macrophage migration inhibitory factor promoter is associated with bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is a common adverse outcome of prematurity, causing severe morbidity and mortality. The cytokine macrophage migration inhibitory factor (MIF) has been recently shown to favor murine fetal lung development. In this prospective study, we evaluate the expression of MIF in the lung and in the serum of preterm infants (n = 50) and investigate whether the -173 G/C MIF promoter polymorphism is associated with the risk of BPD (n = 103). MIF was highly expressed in lung tissue from preterm infants. Serum MIF levels were measured by ELISA at d 1 after birth. MIF levels were increased [median (interquartile range), 71.01 (44.9-162.3) ng/mL], particularly in those infants with RDS [110.4 (59.4-239.2) ng/mL] compared with healthy adults [2.4 (1.2-5.0) ng/mL], (p < 0.001). The MIF -173*C allele, which predisposes to higher MIF production, was associated with a lower incidence of BPD (OR, 0.2; 95% CI, 0.04-0.93), independently from mechanical ventilation and oxygen exposure (p = 0.03). In conclusion, these data show that MIF expression is increased in lung and serum of preterm infants and suggest that the high producing MIF -173*C allele may be a protective factor for BPD.

Ethical problems in the care of high risk neonates.

Recent progress in neonatal care has greatly improved the prognosis and the probabilities of survival in very sick or very preterm neonates and has modified the concept and limits of the so called viability. However, in some circumstances, when the death of the baby can only be postponed temporarily, at the price of severe suffering, or when survival is associated with severe disabilities and an intolerable life for the child and the family, then it might not be appropriate to utilize all the armamentarium of neonatal intensive care. In such circumstances, limitation of intensive treatments (withholding or withdrawal) generally invasive and painful, could represent a more human and reasonable alternative. The ethical principles underlying those decisions, the most frequent situations occurring in practice, the role of parents in the decision-making process, and the opinions and behavior of neonatologists from many European intensive care units will be examined and discussed.

Role of mannose-binding lectin in nosocomial sepsis in critically ill neonates.

We investigated the association of mannose-binding lectin (MBL) serum levels with nosocomial sepsis (NS), their changes overtime during infection, their relation with pathogens, with the MBL2 genotype and their relationship with mortality. In a prospective observational study, we included 365 critically ill neonates: 261 had no infection and 104 had at least 1 septic event. The median MBL serum concentration was significantly lower in infected than in noninfected neonates (p < 0.001). Low MBL levels on admission increased the risk of infection, independently from gestational age and invasive procedures. The median peak MBL level during infection was higher than the median level on admission (p < 0.001) and was correlated with it (r(2) = 0.83, p < 0.001). Moreover, MBL levels on admission were not associated with death (OR = 0.80, 95% CI = 0.56-1.14, p = 0.21). Similarly, no association was found between MBL peak levels during infection and death among infected neonates (OR = 1.10, 95% CI = 0.78-1.57, p = 0.57). In 127 neonates (42 infected) genotyped for exon-1 and -221 promoter MBL2 variants, we did not find significant difference in the frequencies of MBL2 genotypes between infected and noninfected neonates. Moreover, no association was found between MBL2 genotypes and death.

Determinants of nosocomial infection in 6 neonatal intensive care units: an Italian multicenter prospective cohort study.

BACKGROUND: Nosocomial infections are still a major cause of morbidity and mortality among neonates admitted to neonatal intensive care units (NICUs). OBJECTIVE: To describe the epidemiology of nosocomial infections in NICUs and to assess the risk of nosocomial infection related to the therapeutic procedures performed and to the clinical characteristics of the neonates at birth and at admission to the NICU, taking into account the time between the exposure and the onset of infection. DESIGN: A multicenter, prospective cohort study. PATIENTS AND SETTING: A total of 1,692 neonates admitted to 6 NICUs in Italy were observed and monitored for the development of nosocomial infection during their hospital stay. METHODS: Data were collected on the clinical characteristics of the neonates admitted to the NICUs, their therapeutic interventions and treatments, their infections, and their mortality rate. The cumulative probability of having at least 1 infection and the cumulative probability of having at least 1 infection or dying were estimated. The hazard ratio (HR) for the first infection and the HR for the first infection or death were also estimated. RESULTS: A total of 255 episodes of nosocomial infection were diagnosed in 217 neonates, yielding an incidence density of 6.9 episodes per 1,000 patient-days. The risk factors related to nosocomial infection in very-low-birth-weight neonates were receipt of continuous positive airway pressure (HR, 3.8 [95% confidence interval {CI}, 1.7-8.1]), a Clinical Risk Index for Babies score of 4 or greater (HR, 2.2 [95% CI, 1.4-3.4]), and a gestational age of less than 28 weeks (HR, 2.1 [95% CI, 1.2-3.8]). Among heavier neonates, the risk factors for nosocomial infection were receipt of parenteral nutrition (HR, 8.1 [95% CI, 3.2-20.5]) and presence of malformations (HR, 2.3 [95% CI, 1.5-3.5]). CONCLUSIONS: Patterns of risk factors for nosocomial infection differ between very-low-birth-weight neonates and heavier neonates. Therapeutic procedures appear to be strong determinants of nosocomial infection in both groups of neonates, after controlling for clinical characteristics.

Developmental evaluation at age 4: Validity of an Italian parental questionnaire.

AIM: To validate an Italian parental questionnaire designed to evaluate the neuropsychological and behavioural developmental status of 4-year-olds and identify children in need of further evaluation. METHODS: The questionnaire (Questionario per la valutazione dello Sviluppo di bambini a 4 anni - Genitori (QS4-G) ) consisted of 93 questions divided into 10 areas: language, visual-motor abilities, memory/attention, fine and gross motor and self-help abilities, lateralisation, social skills, stress, sleep, alimentation and evacuation. It was distributed to 263 parents of 4-year-olds: 94 healthy preterm (gestational age <33 weeks and/or <1500 g, without major neurosensory damage); 44 children with developmental disorders and 125 children with typical development. Cognitive and neuropsychological evaluations were performed using standardised tests. RESULTS: The internal consistency of the areas was adequate (Cronbach's alpha: 0.69-0.79). The correlation coefficients (r=|0.30|-|0.68|) with standardised tests (Griffiths, Vineland and neuropsychological tests) indicated a good concurrent validity. The receiver operating characteristic curve, for predicting a Griffiths Quotient less than 81, showed an area under the curve of 0.90 and a high diagnostic and discriminatory capacity (sensitivity of 0.88 and specificity of 0.84) for the optimal cut-off (value 48.4). CONCLUSION: The QS4-G seems to be a valid tool for identifying 4-year-old children at risk for low or borderline cognitive development and/or problematic behaviour who need a complete assessment. It can describe individual neuropsychological profiles. QS4-G is not a diagnostic tool. It is useful for outcome studies in preterm children and in other pathologies. It could also be useful for preschooler prevention programmes.

Ethical problems with neonatal screening.

The availability of novel technologies, such as tandem-mass-spectrometry (MS/MS) and DNA analysis, has expanded tremendously the number of genetic conditions that can be diagnosed through neonatal screening programs at birth, including conditions that cannot be treated nor prevented, or that will become manifest only later in life, or that identify individuals that are only at an increased risk of multifactorial conditions. This has increased the number and complexity of ethical problems related to newborn screening programs, creating considerable confusion and generating controversies and ethical concerns. The experience so far gained indicates that, besides the incomplete knowledge of many aspects of the conditions to be identified, the majority of screening programs do not pay sufficient attention to the problems of communication, information and counselling of the parents. Therefore, communication must be substantially improved if we wish to increase the efficiency of such programs and avoid possible unwanted side effects. Furthermore, ethical issues should receive more attention and consideration for a better and more complete understanding of the overall impact of neonatal screening programs. This more extensive and ethically correct approach should allow us to find an optimal equilibrium between the potential benefits and the possible damages deriving from neonatal screening programs.

Access to level III perinatal care for pregnancies of very short duration (<32 weeks).

AIMS: To evaluate to which extent pregnancies of very short duration (<32 weeks' gestation) are concentrated in level III centers. METHODS: Area-based study in the 57 maternity units of the Lazio Region (Italy), years 2003-2004, including: 1012 live births (gestational age 22-31 weeks), 261 fetal losses (22-31 weeks) and 209 induced abortions (22-25 weeks). Variables associated with access to a level III unit were evaluated through multivariable logistic regression models. RESULTS: 83.7% of all pregnancies <32 weeks (88.8% of live births, 71.6% of fetal losses and 75.1% of induced abortions) were admitted to a level III perinatal center; 23.4% of live newborns, delivered in a level III hospital, were subsequently transferred to a same level facility. The probability that a fetal loss was not treated in a level III perinatal unit was higher for women without pregnancy complication, with lower education level, and living outside the metropolitan area. CONCLUSIONS: Regionalization of perinatal care in Lazio is not satisfactory. Concentration of high-risk deliveries in level III centers is good, but in utero transfer is insufficient. This study can help to define the effectiveness of different organizational systems on access to locally available perinatal facilities and to optimize general organizational patterns of perinatal care.

Lung volumes and distribution of ventilation in survivors to congenital diaphragmatic hernia (CDH) during infancy.

UNLABELLED: The assessment of lung volumes, particularly functional residual capacity (FRC), is crucial for understanding lung development during infancy in CDH patients. AIM: To evaluate changes in lung function during infancy in subjects with CDH treated with a "gentle ventilation" technique and delayed surgery strategy in the neonatal period. METHODS: 13 CDH infants were studied twice and compared with a population of 28 healthy infants (HI). Tidal-Volume (Vt), respiratory rate (RR) and time to peak expiratory flow/expiratory time ratio (tPTEF/Te) were measured with an ultrasonic flow meter; Compliance (Crs) and Resistance (Rrs) of the respiratory system were studied with the single occlusion technique; FRC and Lung Clearance Index (LCI), were assessed with the sulfur hexafluoride (SF6) wash-in/wash-out technique. The differences between the first (T1) and second (T2) measurement in the CDH group were assessed by the Student's t-test for paired values. For each set of measurement (T1 and T2) the values were compared with HI by Student's t-test. RESULTS: Mean age at test was 7.5 +/- 5.2 months for HI, 4.5 +/- 2.5 at T1 and 11.9 +/- 4.5 months at T2 for CDH infants. At T1 there were no significant differences between CDH infants and HI in Vt, Crs, and FRC, while tPTEF/te ratio was lower and RR, Rrs, and LCI were higher in CDH patients than in HI. At T2 Vt, Crs, and FRC remained normal in CDH patients as well as RR that, at this time was not different between CDH and healthy infants; tPTEF/te remained below and Rrs and LCI remained above normal ranges, indicating a persistent impairment in lower airways patency. CONCLUSIONS: Lung function in infants with severe CDH is characterized by a persistent impairment in airways patency and significant inhomogeneity of ventilation, suggesting a peripheral bronchial obstruction even if the other lung function tests are within normal ranges.

Low serum levels of mannose binding lectin are a risk factor for neonatal sepsis.

Mannose binding lectin (MBL) is a soluble pattern recognition receptor of innate immunity that binds a wide range of pathogens and exerts opsonic effects. We investigated the association between serum MBL levels and development of sepsis in infants admitted to neonatal intensive care units (NICUs). Serum MBL levels on admission were measured by enzyme-linked immunosorbent assay (ELISA) in 206 neonates consecutively admitted to an NICU of whom 138 did not develop hospital-acquired sepsis and 68 did. Of these 68, 40 had confirmed sepsis with positive blood cultures, 19 clinically suspected sepsis, with negative blood cultures, and nine had clinically suspected sepsis with blood culture yielding coagulase-negative staphylococci (CoNS). Serum MBL levels on admission were significantly lower in infants with sepsis [0.45 microg/mL; interquartile range (IQR) 0.09-1.68], particularly in those with confirmed sepsis (0.17 microg/mL; IQR 0.05-0.96), compared with infants without sepsis (1.45 microg/mL; IQR 0.43-3.52), and infants with CoNS-positive blood culture (1.70 microg/mL: IQR 0.85-3.60). After adjusting for duration of exposure gestational age (GA) and birth weight (BW), the association of low MBL levels with development of sepsis was maintained [odds ratio (OR) = 0.52; 95% confidence interval (CI): 0.36-0.75]. The measurement of serum MBL levels on admission in NICU may help to identify neonates at higher risk of developing sepsis.