Gaetano Chirico

Do prebiotics reduce the number of fever episodes in healthy children in their first year of life: a randomised controlled trial

The objective of the present study was to assess the effect of adding specific prebiotics to standard formula feeding on the number of fever episodes in the first year of life. In the present randomised, double-blind, placebo-controlled trial in seven centres in five West European countries, 830 healthy term infants, without a first-degree family history of allergic disease, of mothers who indicated to give only formula feeding were randomised either to receive a standard non-hydrolysed cows milk-based formula to which a mixture of specific oligosaccharides was added (prebiotics group (PG)), or to receive a similar formula without oligosaccharides (control group (CG)). A separate reference group consisted of 300 breast-fed infants. The primary outcome was the number of fever episodes prospectively documented by the parents. There was no difference in the number of fever episodes between the PG (median value 1·19; 25th-75th percentile 0·09-2·34) and CG (1·16; 25th-75th percentile 0·06-2·38). The median number of fever episodes in the separate breast-feeding reference group was 1·24 (25th-75th percentile 0·51-3·45). There was no effect of adding specific prebiotics to standard formula feeding in reducing the number of fever episodes in the present study.

Neonates born from mothers with autoimmune disorders

Systemic autoimmune disorders have a higher prevalence in women, particularly during their childbearing age. A growing interest is being paid to the possible consequences of maternal disease and associated treatment on the fetus and newborn infant. If maternal disease is characterized by the presence of IgG isotype auto-antibodies, these can cross the placenta with possible antibody-mediated damage to the fetus. The risk of gestational complications, including preterm delivery, intrauterine growth retardation and low birth weight is higher in autoimmune diseases rather than in the general population and probably this finding is related to both maternal disorder and immunosuppressive therapy. Recently, results of our studies suggest that the antenatal exposure to immunosuppressive drugs given to mothers during pregnancy to treat autoimmune diseases does not impair significantly the development of immunity in exposed children. Finally, mothers disease and/or treatment could be related to neuropsychological dysfunctions reported in some of their children.

Stem cells and the frontiers of neonatology

The aim of the most recent studies on regenerative medicine was to focus on capability of stem cells deriving not only from haematopoietic system, but also from other organ and tissues, to regenerate damaged tissues. Stem cells derived from foetal annexes such as cord blood, placenta and amniotic fluid can be currently used in the effort to treat prenatally diagnosed genetic diseases. Cells derived from cord blood have been used since 1988 as an alternative source to realize stem cell transplantation. Compared with bone marrow, cord blood has shown the advantages of quick availability, less risk of GHVD, together with higher compatibility rates, and less risk of infections. Mesenchymal stem cells (MSCs) are multi-potent stem cells able to differentiate into different lineages, including osteocytes, chondrocytes, and adipocytes. Because of their trafficking capacity to injured tissues, clinical trials have been started evaluating the use of MSCs in the treatment of metabolic diseases like Hurler syndrome and metachromatic leukodystrophy, or Osteogenesis Imperfecta. MSCs were initially identified in adult bone marrow (BM-MSC), but cells resembling BM-MSCs have also been found in other tissues, both adult (peripheral blood, synovial membrane) and foetal (peripheral blood, liver, spleen, placenta, umbilical cord, and amniotic membrane). BM-MSCs have been widely used in clinical applications, as for cell-based therapy of Osteogenesis Imperfecta and metabolic diseases. In addition, human multi-potent MSCs present in second-trimester amniotic fluids may be a good target for prenatal gene therapy because of their expandability, their ability to differentiate into multiple lineages and their high transduction efficiency.

Diagnostic accuracy and prognostic value of the CD64 index in very low birth weight neonates as a marker of early-onset sepsis

Abstract Objective: To assess the diagnostic and prognostic utility of CD64 expression as a marker of early-onset sepsis (EOS) in very low birth weight (VLBW) neonates. Methods: Neutrophil CD64 expression (CD64 index) was assessed in 129 VLBW neonates within 72 h after birth. The accuracy of the CD64 index in predicting EOS was determined by receiver operating characteristic curve analysis. The relationship between the expression of the CD64 index and neonatal outcomes was evaluated by multivariate analysis. Results: The highest performance of the CD64 index was achieved at 24 h after birth; accuracy, sensitivity, and negative predictive values were 0.85, 0.89, and 0.99, respectively, with a cut-off value of 2.4. The increased expression of CD64 index was significantly associated with subsequent infections (relative risk 1.54; 95% confidence interval 1.02–2.33). Conclusions: The CD64 index could be used as a reliable marker of EOS in VLBW neonates and it is an independent risk factor for late-onset infections.

Cerebral ultrasound abnormalities in infants born to mothers with autoimmune disease

Objectives Cerebral abnormalities detected by cranial ultrasound (cUS) have been reported in infants born to mothers with autoimmune disease. However, the pathogenesis of the infants brain injury remains unclear. The authors aimed to study the possible association between abnormalities on neonatal cUS and perinatal factors related to maternal autoimmune disease. Methods cUS evaluation was carried out at birth in 114 infants born to mothers with autoimmune disease, and repeated up to 8–9 months of life in those showing sonographic abnormalities at the first examination. The authors analysed the relationships among cerebral ultrasound abnormalities and antenatal exposure to maternal drug treatment, placental transfer of auto-antibodies and gestational complications. In addition, infants were investigated for neuromotor development from birth to 24 months of age. Results Cerebral ultrasound abnormalities, including subependymal pseudocyst, lenticulostriate vasculopathy and echogenic periventricular white matter, were detected in 41 of 114 infants (35.9%). No significant associations were found between abnormalities on cUS and the perinatal factors included in the study. No cases of persistent cerebral ultrasound abnormalities or neuromotor delay were observed during the follow-up period. Conclusions A considerable number of cerebral ultrasound abnormalities were observed in a cohort of infants born to mothers with autoimmune disease. However, no perinatal factors were significantly associated with this finding, suggesting the fetal brain impairment had a multi-factorial aetiology. Although no case of neuromotor delay was observed, long term neurological assessment of these babies is recommended in view of the cognitive impairment reported in previous studies.

Central vascular catheters and infections

Newborn infants in critical conditions require a permanent intra-venous line to allow for the administration of fluids, parenteral nutrition and drugs. The use of central venous catheters, however, is associated with an increased risk of infections, leading to prolongation of length of stay and higher hospitalization costs, particularly in extremely preterm infants. Dwell time is a significant factor for complications, with a predicted risk of catheter related infections of about 4 per 1000 catheter-days. To reduce the incidence of complications, several requirements must be met, including adequate staff and resources to provide education, training, and quality improvement programs, within a culture of communication and teamwork. Rigorous reporting schedule on line care and the implementation of unique bundle elements, the use of health care failure mode and effect analysis, the judicious use of antibiotics through an antimicrobial stewardship strategy, the application of specific antifungal prophylaxis are among the most effective interventions, while the addition of heparin to parenteral solution, or the use of antibiotic plus heparin lock therapy are under evaluation. Nursing assistance plays a fundamental role in managing central venous lines and in reducing or preventing the incidence of infection, by the application of several complex professional strategies.

Ventilation strategies for preventing oxidative stress-induced injury in preterm infants with respiratory disease: an update

Reactive oxygen and nitrogen species are produced by several inflammatory and structural cells of the airways. The lungs of preterm newborns are susceptible to oxidative injury induced by both reactive oxygen and nitrogen species. Increased oxidative stress and imbalance in antioxidant enzymes may play a role in the pathogenesis of inflammatory pulmonary diseases. Preterm infants are frequently exposed to high oxygen concentrations, infections or inflammation; they have reduced antioxidant defense and high free iron levels which enhance toxic radical generation. Multiple ventilation strategies have been studied to reduce injury and improve outcomes in preterm infants. Using lung protective strategies, there is the need to reach a compromise between satisfaction of gas exchange and potential toxicities related to over-distension, derecruitment of lung units and high oxygen concentrations. In this review, the authors summarize scientific evidence concerning oxidative stress as it relates to resuscitation in the delivery room and to the strategies of ventilation.

Fresh Frozen Plasma Administration in the Neonatal Intensive Care Unit: Evidence-Based Guidelines.

Neonates receiving fresh frozen plasma (FFP) should do so according to evidence-based guidelines so as to reduce inappropriate use of this life-saving and costly blood product and to minimize associated adverse effects. The consensus-based uses of FFP in neonatology involve neonates with active bleeding and associated coagulopathy. However, because of limited and poor-quality evidence, considerable FFP utilization occurs outside these recommendations. In this review, we describe what we conclude are currently the best practices for the use of FFP in neonates, including interpreting neonatal coagulation tests and strategies for reducing unnecessary FFP transfusions.

Study protocol: safety and efficacy of propranolol 0.2% eye drops in newborns with a precocious stage of retinopathy of prematurity (DROP-ROP-0.2%): a multicenter, open-label, single arm, phase II trial

BackgroundRetinopathy of prematurity (ROP) still represents one of the leading causes of visual impairment in childhood. Systemic propranolol has proven to be effective in reducing ROP progression in preterm newborns, although safety was not sufficiently guaranteed. On the contrary, topical treatment with propranolol eye micro-drops at a concentration of 0.1% had an optimal safety profile in preterm newborns with ROP, but was not sufficiently effective in reducing the disease progression if administered at an advanced stage (during stage 2). The aim of the present protocol is to evaluate the safety and efficacy of propranolol 0.2% eye micro-drops in preterm newborns at a more precocious stage of ROP (stage 1).MethodsA multicenter, open-label, phase II, clinical trial, planned according to the Simon optimal two-stage design, will be performed to analyze the safety and efficacy of propranolol 0.2% eye micro-drops in preterm newborns with stage 1 ROP. Preterm newborns with a gestational age of 23–32xa0weeks, with a stage 1 ROP will receive propranolol 0.2% eye micro-drops treatment until retinal vascularization has been completed, but for no longer than 90xa0days. Hemodynamic and respiratory parameters will be continuously monitored. Blood samplings checking metabolic, renal and liver functions, as well as electrocardiogram and echocardiogram, will be periodically performed to investigate treatment safety. Additionally, propranolol plasma levels will be measured at the steady state, on the 10th day of treatment. To assess the efficacy of topical treatment, the ROP progression from stage 1 ROP to stage 2 or 3 with plus will be evaluated by serial ophthalmologic examinations.DiscussionPropranolol eye micro-drops could represent an ideal strategy in counteracting ROP, because it is definitely safer than oral administration, inexpensive and an easily affordable treatment. Establishing the optimal dosage and treatment schedule is to date a crucial issue.Trial registrationClinicalTrials.gov Identifier NCT02504944, registered on July 19, 2015, updated July 12, 2016. EudraCT Number 2014–005472-29.

Reference intervals of citrated-native whole blood thromboelastography in premature neonates

BACKGROUNDnBleeding due to acquired coagulation disorders is a common complication in premature neonates. In this clinical setting, standard coagulation laboratory tests might be unsuitable to investigate the hemostatic function as they reflect the concentration of pro-coagulant proteins but not of anti-coagulant proteins. Thromboelastography (TEG), providing a more complete assessment of hemostasis, may be able to overcome some of these limitations. Unfortunately, experience on the use of TEG in premature neonates is very limited and, in particular in this population, reference ranges of TEG parameters have not been yet evaluated.nnnAIMSnTo evaluate TEG in preterm neonates, and to assess their reference ranges.nnnMETHODSnOne hundred and eighteen preterm neonates were analyzed for TEG in a retrospective cohort study. Double-sided 95% reference intervals were calculated using a bootstrap method after Box-Cox transformation. TEG parameters were compared between early-preterm and moderate-/late-preterm neonates and between bleeding and non-bleeding preterm neonates.nnnRESULTSnComparing early-preterm with moderate-/late-preterm neonates, TEG parameters were not statistically different, except for fibrinolysis which was significantly higher in early preterm neonates. Platelet count significantly correlated with α angle and MA parameters. Bleeding and non-bleeding neonates had similar TEG values.nnnCONCLUSIONSnThese results reinforce the concept that in stable preterm neonates, in spite of lower concentration of pro- and anti-coagulants proteins, the hemostasis is normally balanced and well functioning.