Why might cord blood be a better source of platelets for transfusion to neonates?

Thrombocytopenia (defined as a platelet count <150×109/L) is a common condition in preterm neonates and may occur in 18-35% of all infants admitted to the Neonatal Intensive Care Unit (NICU). Neonatal platelet functionality in terms of reactivity is often described as reduced compared to adults, even in healthy, term neonates. However, this platelet "hyporeactivity" does not correspond to a global functional impairment of the normal delicately balanced neonatal hemostatic system. The extent to which neonatal thrombocytopenia and platelet hyporeactivity contribute to the bleeding risk in preterm neonates remains unknown. Prophylactic platelet transfusions are often administered to them to reduce the risk of bleeding. However, recent literature indicates that adopting a higher platelet transfusion threshold than a lower one results in significantly higher death rates or major bleeding and can be harmful. Although the mechanism by which this occurs is not entirely clear, a mismatch between adult transfused platelets and the neonatal hemostatic system, as well as volume overload, are speculated to be potentially involved. Therefore, future research should consider novel transfusion products that may be more suitable for premature neonates. Blood products derived from umbilical cord blood (UCB) are promising, as they might perfectly match neonatal blood features. Here, we discuss the current knowledge about UCB-derived products, focusing on UCB-derived platelet concentrates and their potential for future clinical application. We will discuss how they may overcome the potential risks of transfusing adult-derived platelets to premature infants while maintaining efficacy.

Human Bone Marrow-Derived Mesenchymal Stromal Cells Reduce the Severity of Experimental Necrotizing Enterocolitis in a Concentration-Dependent Manner.

Necrotizing enterocolitis (NEC) is a devastating gut disease in preterm neonates. In NEC animal models, mesenchymal stromal cells (MSCs) administration has reduced the incidence and severity of NEC. We developed and characterized a novel mouse model of NEC to evaluate the effect of human bone marrow-derived MSCs (hBM-MSCs) in tissue regeneration and epithelial gut repair. NEC was induced in C57BL/6 mouse pups at postnatal days (PND) 3-6 by (A) gavage feeding term infant formula, (B) hypoxia/hypothermia, and (C) lipopolysaccharide. Intraperitoneal injections of PBS or two hBM-MSCs doses (0.5 × 106 or 1 × 106) were given on PND2. At PND 6, we harvested intestine samples from all groups. The NEC group showed an incidence of NEC of 50% compared with controls (p < 0.001). Severity of bowel damage was reduced by hBM-MSCs compared to the PBS-treated NEC group in a concentration-dependent manner, with hBM-MSCs (1 × 106) inducing a NEC incidence reduction of up to 0% (p < 0.001). We showed that hBM-MSCs enhanced intestinal cell survival, preserving intestinal barrier integrity and decreasing mucosal inflammation and apoptosis. In conclusion, we established a novel NEC animal model and demonstrated that hBM-MSCs administration reduced the NEC incidence and severity in a concentration-dependent manner, enhancing intestinal barrier integrity.

Viscoelastic coagulation testing in Neonatal Intensive Care Units: advantages and pitfalls in clinical practice.

The expression "developmental hemostasis" indicates the age-related physiological changes occurring during the maturational process of the hemostatic system. Despite the quantitative and qualitative alterations, the neonatal hemostatic system is competent and well-balanced. Conventional coagulation tests do not provide reliable information as they only explore the procoagulants during the neonatal period. In contrast, viscoelastic coagulation tests (VCTs), such as viscoelastic coagulation monitoring (VCM), thromboelastography (TEG or ClotPro), and rotational thromboelastometry (ROTEM), are point-of-care assays that provide a quick, dynamic and global view of the hemostatic process, allowing prompt and individualized therapeutic intervention when necessary. Their use in neonatal care is on the increase and they could help monitor patients at risk of hemostatic derangement. In addition, they are crucial for anticoagulation monitoring during extracorporeal membrane oxygenation. Moreover, implementing VCT-based monitoring could optimize blood product use.

Endothelial dysfunction in preterm infants: The hidden legacy of uteroplacental pathologies.

Millions of infants are born prematurely every year worldwide. Prematurity, particularly at lower gestational ages, is associated with high mortality and morbidity and is a significant global health burden. Pregnancy complications and preterm birth syndrome strongly impact neonatal clinical phenotypes and outcomes. The vascular endothelium is a pivotal regulator of fetal growth and development. In recent years, the key role of uteroplacental pathologies impairing endothelial homeostasis is emerging. Conditions leading to very and extremely preterm birth can be classified into two main pathophysiological patterns or endotypes: infection/inflammation and dysfunctional placentation. The first is frequently related to chorioamnionitis, whereas the second is commonly associated with hypertensive disorders of pregnancy and fetal growth restriction. The nature, timing, and extent of prenatal noxa may alter fetal and neonatal endothelial phenotype and functions. Changes in the luminal surface, oxidative stress, growth factors imbalance, and dysregulation of permeability and vascular tone are the leading causes of endothelial dysfunction in preterm infants. However, the available evidence regarding endothelial physiology and damage is limited in neonates compared to adults. Herein, we discuss the current knowledge on endothelial dysfunction in the infectious/inflammatory and dysfunctional placentation endotypes of prematurity, summarizing their molecular features, available biomarkers, and clinical impact. Furthermore, knowledge gaps, shadows, and future research perspectives are highlighted.

Veno-Arterial Extracorporeal Membrane Oxygenation (ECMO) Impairs Bradykinin-Induced Relaxation in Neonatal Porcine Coronary Arteries.

Extracorporeal membrane oxygenation (ECMO) is a lifesaving support for respiratory and cardiovascular failure. However, ECMO induces a systemic inflammatory response syndrome that can lead to various complications, including endothelial dysfunction in the cerebral circulation. We aimed to investigate whether ECMO-associated endothelial dysfunction also affected coronary circulation. Ten-day-old piglets were randomized to undergo either 8 h of veno-arterial ECMO (n = 5) or no treatment (Control, n = 5). Hearts were harvested and coronary arteries were dissected and mounted as 3 mm rings in organ baths for isometric force measurement. Following precontraction with the thromboxane prostanoid (TP) receptor agonist U46619, concentration−response curves to the endothelium-dependent vasodilator bradykinin (BK) and the nitric oxide (NO) donor (endothelium-independent vasodilator) sodium nitroprusside (SNP) were performed. Relaxation to BK was studied in the absence or presence of the NO synthase inhibitor Nω-nitro-L-arginine methyl ester HCl (L-NAME). U46619-induced contraction and SNP-induced relaxation were similar in control and ECMO coronary arteries. However, BK-induced relaxation was significantly impaired in the ECMO group (30.4 ± 2.2% vs. 59.2 ± 2.1%; p < 0.0001). When L-NAME was present, no differences in BK-mediated relaxation were observed between the control and ECMO groups. Taken together, our data suggest that ECMO exposure impairs endothelium-derived NO-mediated coronary relaxation. However, there is a NO-independent component in BK-induced relaxation that remains unaffected by ECMO. In addition, the smooth muscle cell response to exogenous NO is not altered by ECMO exposure.

Hemostasis in neonatal ECMO.

Extracorporeal membrane oxygenation (ECMO) is a life-saving support for cardio-respiratory function. Over the last 50 years, the extracorporeal field has faced huge technological progress. However, despite the improvements in technique and materials, coagulation problems are still the main contributor to morbidity and mortality of ECMO patients. Indeed, the incidence and survival rates of the main hemorrhagic and thrombotic complications in neonatal respiratory ECMO are relevant. The main culprit is related to the intrinsic nature of ECMO: the contact phase activation. The exposure of the human blood to the non-endothelial surface triggers a systemic inflammatory response syndrome, which chronically activates the thrombin generation and ultimately leads to coagulative derangements. Pre-existing illness-related hemostatic dysfunction and the peculiarity of the neonatal clotting balance further complicate the picture. Systemic anticoagulation is the management's mainstay, aiming to prevent thrombosis within the circuit and bleeding complications in the patient. Although other agents (i.e., direct thrombin inhibitors) have been recently introduced, unfractionated heparin (UFH) is the standard of care worldwide. Currently, there are multiple tests exploring ECMO-induced coagulopathy. A combination of the parameters mentioned above and the evaluation of the patient's underlying clinical context should be used to provide a goal-directed antithrombotic strategy. However, the ideal algorithm for monitoring anticoagulation is currently unknown, resulting in a large inter-institutional diagnostic variability. In this review, we face the features of the available monitoring tests and approaches, mainly focusing on the role of point-of-care (POC) viscoelastic assays in neonatal ECMO. Current gaps in knowledge and areas that warrant further study will also be addressed.

Proinflammatory Endothelial Phenotype in Very Preterm Infants: A Pilot Study.

Very preterm infants are exposed to prenatal inflammatory processes and early postnatal hemodynamic and respiratory complications, but limited data are available about the endothelial effect of these conditions. The present pilot study investigates the perinatal endothelial phenotype in very preterm infants (VPIs) and explores its predictive value on neonatal mortality and hemodynamic and respiratory complications. Angiopoietin 1 (Ang-1), Ang-2, E-selectin, vascular adhesion molecule 1 (VCAM-1), tissue factor (TF), and endothelin 1 (ET-1) concentrations were tested in first (T1), 3rd (T2), and 7-10th (T3) day of life in 20 VPIs using Luminex technology and compared with 14 healthy full-term infants (FTIs). Compared to FTIs, VPIs had lower Ang-1 at T1 and T2; higher Ang-2 at T1, T2, and T3; higher Ang-2/Ang-1 ratio at T1, T2, and T3; lower E-selectin at T1, T2, and T3; higher VCAM-1 at T1; higher TF at T2. No differences in concentrations were found in neonatal deaths. VPIs with hemodynamic or respiratory complications had higher Ang-2 at T3. Perinatal low Ang-1 and high Ang-2 associated with high VCAM-1 and TF in VPIs suggest a proinflammatory endothelial phenotype, resulting from the synergy of a pathological prenatal inheritance and a premature extrauterine transition.

Hemostatic Evaluation With Viscoelastic Coagulation Monitor: A Nicu Experience.

Background: Viscoelastic coagulation tests provide valuable information in neonatal intensive care units (NICUs), but the lack of reference intervals still limits their decision-making power according to gestational age. The aim of the present study is to evaluate the hemostasis of a cohort of full-term (FT) and late-preterm (LP) infants using the viscoelastic coagulation monitor (VCM®) system, a new portable device that uses untreated whole blood. Methods: An observational study was performed to identify non-coagulopathic FT and LP infants admitted to III° level NICU (January 2020 to December 2021) with a VCM test in the first 72 h of life. Results: Forty-five patients were enrolled, 26 FT and 19 LP. No statistical differences in hemostatic parameters were observed between FT and LP nor between stable and unstable neonates. Clotting time (CT) was positive correlated with PT (p = 0.032), not with aPTT (p = 0.185). From linear regression, platelet resulted associated with: clot formation time (CTF, p = 0.003), alpha angle (Alpha, p = 0.010), amplitude at 10 (A10, p = 0.001), amplitude at 20 min (A20, p < 0.001), maximum clot firmness (MCF, p < 0.001); and fibrinogen was associated with: A10 (p = 0.008), A20 (p = 0.015) and MCF (p = 0.024). Compared to the adult reference population, neonates showed shorter CT (mean (SD): 5.3 (1.4) vs. 7.0 (0.9) min, p < 0.001), CFT (2.4 (0.7) vs. 2.8 (0.6) minutes, p < 0.001) and higher Alpha (60.8 (6.3) vs. 55 (5)°, p < 0.001). In addition, the neonatal cohort showed an early transient difference in amplitude and fibrinolysis, as follows: A10 (28.0 (5.0) vs. 26 (4) VCM units, p =0.004), A20 (34.8 (5.0) vs. 33 (4) VCM units, p =0.012), and LI30 (99.8 (0.5) vs. 99 (1)%, p <0.001). Conclusions: The viscoelastic profile of FT and LP infants assessed with VCM showed a hemostatic competence characterized by accelerated coagulation and clot formation time, in line with other viscoelastic techniques. VCM system provides promising applications in the NICU setting.

Optimizing fresh-frozen plasma transfusion in surgical neonates through thromboelastography: a quality improvement study.

Fresh frozen plasma (FFP) is largely misused in the neonatal setting. The aim of the study is to evaluate the impact of a Thromboelastography (TEG)-based Quality Improvement (QI) project on perioperative FFP use and neonatal outcomes. Retrospective pre-post implementation study in a level-III NICU including all neonates undergoing major non-cardiac surgery before (01-12/2017) and after (01-12/2019) the intervention. In 2018, the intervention included the following: (1) Training on TEG, (2) Implementation of TEG, and (3) Algorithm for TEG-directed FFP administration in surgical neonates. We compared pre- vs post-intervention patient characteristics, hemostasis, and clinical management. Linear and logistic regression models were used to evaluate the impact of the project on main outcomes. We analyzed 139 neonates (pre-intervention: 72/post-intervention: 67) with a mean (± SD) gestational age (GA) 34.9 (± 5) weeks and birthweight 2265 (± 980) grams which were exposed to 184 surgical procedures (pre-intervention: 91/post-intervention: 93). Baseline characteristics were similar between periods. In 2019, prothrombin time (PT) was longer (14.3 vs 13.2 s; p < 0.05) and fibrinogen was lower (229 vs 265 mg/dl; p < 0.05), if compared to 2017. In 2019, the intraoperative exposure to FFP decreased (31% vs 60%, p < 0.001), while the pre-operative FFP use did not change. The reduction of intraoperative FFP did not impact on mortality and morbidity. Intraoperative FFP use was lower in the post-intervention even after controlling for GA, American Society of Anesthesiologists score, PT, and fibrinogen (Odds ratio: 0.167; 95% CI: 0.070, 0.371).   Conclusion: The TEG-based QI project for the management of FFP during neonatal surgery reduced intraoperative FFP exposure. What is Known: • PT and aPTT are poor predictors of bleeding risk in acquired neonatal coagulopathy, leading to likely unnecessary fresh frozen plasma (FFP) transfusion in the Neonatal Intensive Care Setting.  • As neonatal hemostasis is a delicate balance between the concomitant reduction of pro- and anti-coagulants drivers, thromboelastography (TEG) is a promising alternative for coagulation monitoring. What is New: • The implementation of TEG, training, and shared protocols contributed to reduced intraoperative FFP use, which was not associated with increased mortality or bleeding events. • These findings inform future research showing that there is clinical equipoise to allow for larger studies to confirm the use of TEG in NICUs and to identify TEG cut-offs for transfusion practice.

Red blood cell transfusions in preterm newborns and neurodevelopmental outcomes at 2 and 5 years of age.

BACKGROUND: Red blood cell (RBC) transfusion is often considered a life-saving measure in preterm neonates. However, it has been associated with detrimental effects on short-term morbidities and, recently, on brain development. The aim of the present study was to evaluate the association between RBC and long-term neurodevelopmental outcome in a cohort of preterm infants. MATERIALS AND METHODS: This retrospective cohort study was carried out in the period 2007-2013. Preterm infants with a gestational age (GA) ≤ 32 weeks and birthweight (BW) <1,500 g were included. Infants underwent Griffiths assessment at 24±6 months corrected age (CA) and at 5±1 years of age. We used a multivariate regression model to assess the association of RBC transfusions and long-term neurodevelopment after controlling for GA, being small for GA, major neonatal morbidities, and socio-economic status. We also evaluated the impact of early RBC administration (within the first 28 days of life) compared to those performed after the first month of life. RESULTS: We enrolled 644 preterm infants, among whom 54.3% were transfused during their stay in the neonatal intensive care unit (NICU). In infants with a longitudinal follow-up evaluation (n=360), each RBC transfusion was independently associated with a reduction in the Griffiths General Quotient (GQ) by -0.96 (p=0.002) at 24 months CA. Early RBC administration had the biggest impact, especially in children without brain lesions, where the reduction in Griffiths GQ for each additional transfusion was -2.12 (p=0.001) at 24 months CA and -1.31 (p=0.006) at 5 years of age, respectively. DISCUSSION: In preterm infants, RBC transfusions are associated with long-term neurodevelopmental outcome, with a cumulative effect. Early RBC administration is associated with a greater reduction in Griffiths scores. The impact of RBC transfusion on neurodevelopment is greater at 24 months CA, but persists, although to a lesser degree, at 5 years of age.

Selective Bronchial Occlusion for Treatment of a Bronchopleural Fistula in an Extremely Preterm Infant.

Neonatal pulmonary air leak commonly occurs as a complication of mechanical ventilation in infants with underlying hyaline membrane disease. They can commonly be managed conservatively or with the application of a chest drain, but some severe cases pose a significant challenge in finding an alternative therapeutic solution. Selective bronchial occlusion represents an unconventional rescue therapy for treating bronchopleural fistula resistant to the standard therapy. A 27-week gestation preterm infant ventilated for respiratory distress syndrome developed tension right-sided pneumothorax. Conventional modalities of treatment were tried and were unsuccessful. Intermittent selective bronchial occlusion with a Fogarty's catheter and high-frequency oscillatory ventilation resulted in considerable improvement in the infant's clinical condition and radiographic findings.

Individualized Bleeding Risk Assessment through Thromboelastography: A Case Report of May-Hegglin Anomaly in Preterm Twin Neonates.

May-Hegglin anomaly (MHA) is a rare autosomal dominant disorder in the spectrum of myosin heavy chain-related disorders (MYH9-RD), characterized by congenital macrothrombocytopenia and white blood cell inclusions. MHA carries a potential risk of hemorrhagic complications. Bleeding diathesis is usually mild, but sporadic, life-threatening events have been reported. Data regarding the clinical course and outcomes of neonatal MYH9-RD are limited, and specific guidelines on platelet transfusion in asymptomatic patients are lacking. We present monochorionic twins born preterm at 32 weeks of gestation to an MHA mother; both presented with severe thrombocytopenia at birth. Peripheral blood smear demonstrated the presence of macrothrombocytes, and immunofluorescence confirmed the diagnosis of MHA. Close clinical monitoring excluded bleeding complications, and serial hemostatic assessments through a viscoelastic system demonstrated functionally normal primary hemostasis in both patients. Therefore, prophylactic platelet transfusions were avoided. Whole DNA sequencing confirmed the pathogenetic variant of MHA of maternal origin in both twins. Thromboelastography allowed real-time bedside bleeding risk assessment and supported individualized transfusion management in preterm newborns at risk of hemostatic impairment. This report suggests that dynamic and appropriate clotting monitoring may contribute to the more rational use of platelets' transfusions while preserving patients with hemorrhagic complications and potential transfusion-related side effects.

Severe Presentation of Congenital Hemolytic Anemias in the Neonatal Age: Diagnostic and Therapeutic Issues.

Congenital hemolytic anemias (CHAs) are a group of diseases characterized by premature destruction of erythrocytes as a consequence of intrinsic red blood cells abnormalities. Suggestive features of CHAs are anemia and hemolysis, with high reticulocyte count, unconjugated hyperbilirubinemia, increased lactate dehydrogenase (LDH), and reduced haptoglobin. The peripheral blood smear can help the differential diagnosis. In this review, we discuss the clinical management of severe CHAs presenting early on in the neonatal period. Appropriate knowledge and a high index of suspicion are crucial for a timely differential diagnosis and management. Here, we provide an overview of the most common conditions, such as glucose-6-phosphate dehydrogenase deficiency, pyruvate kinase deficiency, and hereditary spherocytosis. Although rare, congenital dyserythropoietic anemias are included as they may be suspected in early life, while hemoglobinopathies will not be discussed, as they usually manifest at a later age, when fetal hemoglobin (HbF) is replaced by the adult form (HbA).

Thrombin Generation in Preterm Newborns With Intestinal Failure-Associated Liver Disease.

Background and Aim: Intestinal failure-associated liver disease (IFALD) affects one-fifth of neonates receiving parenteral nutrition (PN) for more than 2 weeks. We aimed to define the effect of IFALD on hemostasis of preterm infants. Methods: This is an ancillary analysis of a prospective study aimed at defining coagulation in preterm infants. We included neonates exposed to PN (at least 14 days), in full-enteral feeding. We compared thrombin generation in the presence of thrombomodulin, defined as endogenous thrombin potential-ETP, PT, aPTT between infants with IFALD vs. those without (controls), at birth, and after 30 days. IFALD was defined as conjugated bilirubin ≥1 mg/dl. Results: We enrolled 92 preterm infants (32 IFALD; 60 controls). Cholestatic patients had a lower birthweight, longer exposure to PN, and longer hospitalization. Infants with IFALD showed longer median PT (12.8-vs.-12 sec; p = 0.02) and aPTT (39.2-vs.-36.5 sec; p = 0.04) than controls, with no difference in ETP. Conclusions: Despite prolonged PTs and aPTTs infants with IFALD had similar ETP than those without.

Iron Homeostasis Disruption and Oxidative Stress in Preterm Newborns.

Iron is an essential micronutrient for early development, being involved in several cellular processes and playing a significant role in neurodevelopment. Prematurity may impact on iron homeostasis in different ways. On the one hand, more than half of preterm infants develop iron deficiency (ID)/ID anemia (IDA), due to the shorter duration of pregnancy, early postnatal growth, insufficient erythropoiesis, and phlebotomy losses. On the other hand, the sickest patients are exposed to erythrocytes transfusions, increasing the risk of iron overload under conditions of impaired antioxidant capacity. Prevention of iron shortage through placental transfusion, blood-sparing practices for laboratory assessments, and iron supplementation is the first frontier in the management of anemia in preterm infants. The American Academy of Pediatrics recommends the administration of 2 mg/kg/day of oral elemental iron to human milk-fed preterm infants from one month of age to prevent ID. To date, there is no consensus on the type of iron preparations, dosages, or starting time of administration to meet optimal cost-efficacy and safety measures. We will identify the main determinants of iron homeostasis in premature infants, elaborate on iron-mediated redox unbalance, and highlight areas for further research to tailor the management of iron metabolism.

Thromboelastographic profiles of healthy very low birthweight infants serially during their first month.

OBJECTIVE: We determined thromboelastographic (TEG) profiles of healthy very low birthweight infants (VLBWIs) of the day of birth and at set intervals during their first month. DESIGN: Prospective observational study with blinded clinical and laboratory follow-up. SETTING: Level III neonatal intensive care unit (June 2015 to June 2018). PATIENTS: Consecutive qualifying VLBWIs were enrolled at birth and followed up for 30 days. INTERVENTIONS AND MAIN OUTCOMES MEASURES: Laboratory (citrated-native TEG, prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, blood count) and clinical variables were retrieved at birth, 3rd-5th, 10th and 30th day of life. Blood samples temporally related to events with a potential hemostatic impact (sepsis, bleeding, platelets/plasma transfusions, ibuprofen/indomethacin administration) were excluded from analysis. RESULTS: We enrolled 201 VLBWIs and 72 full-term neonates. Sixty-seven of the healthy VLBWIs completed the 30-day follow-up. 541 TEG traces were analysed.On day 1, the median (minimum-maximum) TEG values were as follows: reaction time (R), 8.2 min (1-21.8); kinetics (K), 2.8 min (0.8-16); α angle, 51° (14.2-80.6); maximum amplitude (MA), 54.9 mm (23.9-76.8). PT and APTT were 15.9 s (11.7-51.2) and 59 s (37.8-97.5), respectively. The above parameters suggest minor hypocoagulability compared with term infants. On day 30, the median (minimum-maximum) R was 5 (1-16.9), K 1 (0.8-4.1), α 74.7 (41.1-86.7) and MA 70.2 (35.8-79.7). PT and APTT were 12.1 (10.4-16.6) and 38.8 (29.6-51.4), respectively. Those parameters are consistent with a relatively hypercoagulable phenotype, compared with term infants. CONCLUSIONS: Healthy VLBWIs have a prolonged PT and APTT, but their TEG profiles suggest a relatively balanced hemostatic system, with slight hypocoagulability initially (compared with term neonates), gradually evolving to a somewhat more procoagulant phenotype over the first month.

Delayed Cord Clamping Increased the Need for Phototherapy Treatment in Infants With AB0 Alloimmunization Born by Cesarean Section: A Retrospective Study.

Objective: To compare the effect of Delayed Cord Clamping (DCC) to Immediate Cord Clamping (ICC) on phototherapy treatment in a cohort of cesarean-delivered newborns with AB0-alloimmunization. Study Design: In a retrospective cohort study neonates with Gestational Age (GA) ≥ 35 weeks and diagnosed with AB0-alloimmunization before implementation of DCC (ICC group) were compared with neonates born after implementation (DCC group). The primary outcome was the need for phototherapy. Secondary outcomes included hospital stay, readmission rate, need for extra intravenous fluids, maximum bilirubin concentration, and hours of life at bilirubin peak. We used regression models to adjust for weight loss, type of feeding, birth weight, and gestational age. Results: In total 336 neonates were included, of which 192 neonates in the ICC group and 144 in the DCC group. There were no differences in basic characteristics between the two groups except for birth weight (ICC 3193 ± 468 g vs. DCC 3053 ± 446 g, p = 0.01) and GA (ICC 38.2 ± 1 weeks of GA, vs. DCC 37.9 ± 1 weeks of GA; p = 0.01). When adjusted for confounding factors, after implementation of DCC, significantly more infants with AB0 alloimmunization needed phototherapy (22.4% vs. 36.8%, RR 1.61 CI: 1.15-2.28; p = 0.006; Number Needed to Harm 7), needed to stay longer in hospital (20.3% vs. 30.5%, RR 1.53 CI: 1.05-2.23; p = 0.03). The maximum bilirubin was higher (11.4 ± 4.0 mg/dl vs. 12.9 ± 3.5 mg/dl, p < 0.001) and occurred later [74 (67-92) hours vs. 84 (70-103) hours; p = 0.04]. There was no difference in the need for intravenous fluids (1.6% vs. 4.9%; not significant) and readmissions (1.6% vs. 3.5%; not significant). Conclusion: Infants with AB0 alloimmunization needed more often phototherapy and were admitted longer after implementation of DCC policy. Further studies are needed to see whether the benefit of DCC outweighs the increased morbidity, admission days, and related hospital costs.

The Italian version of the Zarit Burden interview: a validation study.

BACKGROUND: Caregiving experiences in dementia may have adverse effects on the caregiver's own physical and mental health. The Zarit Burden Interview (ZBI) is the most widely used instrument for assessing family carer burden and the purpose of the present study was to evaluate the psychometric properties of the Italian version of the ZBI (I-ZBI). METHODS: I-ZBI was administered to a non-randomized sample of 273 caregivers related to consecutively attending outpatients with a previously established primary diagnosis of dementia, according to DSM-IV criteria. Measurements used for the construct validity of the instrument were the General Health Questionnaire (GHQ-12), Hospital Anxiety and Depression Scale (HADS) and the Symptom Checklist-90-Revised (SCL-90-R). Validity and reliability were evaluated, as well as the factor structure of the instrument. RESULTS: Most caregivers were children (65%), female (72%) and living with the patient (53%), with quite a high level of burden. The I-ZBI demonstrates good reliability with high internal consistency (α = 0.90) and split-half correlation of 0.78, and good concurrent validity with other assessment tools. A five-factor solution was obtained for the I-ZBI and the original bi-factorial structure of the ZBI was not confirmed. CONCLUSIONS: The Italian version of the Zarit Burden Interview is valid, reliable and useful for use in clinical contexts and in future studies that could lead to a better understanding of carer burden in dementia. Clarifying the factorial structure of the ZBI would help to further the understanding of the large body of research using it and would also help to advance the understanding of subjective burden.