Hemodynamic Assessment of a Large Pulmonary Arteriovenous Malformation in a Neonate: Case Report and Review of Literature.

Herein we report the case of a neonate with a prenatally diagnosed large pulmonary arteriovenous malformation, managed with minimally invasive hemodynamic monitoring in our Neonatal Intensive Care Unit. The combination of Near-Infrared Spectroscopy and Pressure Recording Analytical Method could guide neonatal management of critical cases of vascular anomalies: immediate data are offered to clinicians, from which therapeutic decisions such as timing of surgical resection are made to achieve a positive outcome. We also systemically collected and summarized information on patients' characteristics of previous cases reported in literature to data, and we compared them to our case.

S100B protein, cerebral ultrasound and magnetic resonance imaging patterns in brain injured preterm infants.

OBJECTIVES: The early detection of preterm infants (PI) at risk for intraventricular hemorrhage (IVH) and neurological sequelae still constitutes an unsolved issue. We aimed at validating the role of S100B protein in the early diagnosis and prognosis of IVH in PI by means of cerebral ultrasound (CUS) and magnetic resonance imaging (MRI) today considered standard of care procedures. METHODS: We conducted an observational case-control study in 216 PI of whom 36 with IVH and 180 controls. Standard clinical, laboratory, radiological monitoring procedures and S100B urine measurement were performed at four time-points (first void, 24, 48, 96 h) after birth. Cerebral MRI was performed at 40-42 weeks of corrected gestational age. RESULTS: Elevated (p<0.001, for all) S100B levels were observed in the IVH group at all monitoring time-point particularly at first void when standard monitoring procedures were still silent or unavailable. S100B measured at first void correlated (p<0.001) with the grade of hemorrhage by means of CUS and with the site and extension of neurological lesion (p<0.001, for all) as assessed by MRI. CONCLUSIONS: The present results showing a correlation among S100B and CUS and MRI offer additional support to the inclusion of the protein in clinical daily management of cases at risk for IVH and adverse neurological outcome. The findings open the way to further investigations in PI aimed at validating new neurobiomarkers by means of S100B.

Monitoring the effectiveness of hypothermia in perinatal asphyxia infants by urinary S100B levels.

Background Perinatal asphyxia is a major cause of mortality and morbidity in neonates: The aim of the present study was to investigate, by means of longitudinal assessment of urinary S100B, the effectiveness of hypothermia, in infants complicated by perinatal asphyxia and hypoxic-ischemic encephalopathy. Methods We performed a retrospective case-control study in 108 asphyxiated infants, admitted to nine tertiary departments for neonatal intensive care from January 2004 to July 2017, of whom 54 underwent hypothermia treatment and 54 did not. The concentrations of S100B protein in urine were measured using an immunoluminometric assay at first urination and 4, 8, 12, 16, 20, 24, 48, 72, 96, 108 and 120 h after birth. The results were correlated with the achievement of S100B levels within normal ranges at 72 h from hypothermia treatment. Routine laboratory parameters, longitudinal cerebral function monitoring, cerebral ultrasound and neurologic patterns were assessed according to standard protocols. Results Higher S100B concentrations were found in hypothermia-treated infants in both moderate (up to 12 h) and severe (up to 24 h) hypoxic-ischemic encephalopathy. S100B levels returned to normal ranges starting from 20 h of hypothermia treatment in moderate and from 36 h in severe hypoxic-ischemic encephalopathy. Conclusions The present results offer additional support to the usefulness of longitudinal neuro-biomarkers monitoring in asphyxiated infants treated by hypothermia. The pattern of S100B concentrations during hypothermia supports the need for further investigations aimed at reconsidering the time-window for patient recruitment and treatment, and the optimal duration of the cooling and rewarming phases of the hypothermia procedure.

Functional residual capacity (FRC) and lung clearance index (LCI) in mechanically ventilated infants: application in the newborn with congenital diaphragmatic hernia (CDH).

INTRODUCTION: Functional residual capacity (FRC) and lung clearance index (LCI) are sensitive parameters for early detection of airway disease in infancy. The closed helium dilution method has been applied to assess lung volume and ventilation inhomogeneity (VI) in spontaneously breathing infants. AIMS: The aims of this study were as follows: (1) to assess applicability of the helium gas dilution technique in mechanically ventilated infants with high-risk congenital diaphragmatic hernia (CDH) and to evaluate changes in breathing patterns, lung volume, and VI during the first days of life before and after surgery, and (2) to analyze the possible correlation between changes in lung volume, cerebral hemodynamics, and oxygenation before and after surgical correction of CDH through near-infrared spectroscopy (NIRS) monitoring. METHODS: Lung function tests were performed by multibreath washout traces with an ultrasonic flowmeter and helium gas dilution technique. For all babies, three acceptable FRC and LCI measurements were collected for each test (mean and SD of three measurements were calculated) before surgery (T0), 24 h after surgery (T1) during mechanical ventilation, and within 24 h after extubation in spontaneous breathing (T2). Cerebral and splanchnic hemodynamics were continuously monitored by NIRS during mechanical ventilation to evaluate relationships between changes in lung volume and capillary-venous oxyhemoglobin saturation in tissues. Fraction of inspired oxygen delivered was adjusted to keep oxygen saturation between 90% and 95%. RESULTS: Thirteen CDH infants were studied; median GA = 38 weeks (range 35-41) and median BW = 3000 g (range 1850-3670). FRC and LCI significantly improved after extubation when compared with pre-surgical values. No differences were found in tidal volume (Vt) and NIRS monitoring before and after surgery and after extubation. Neither LCI nor FRC was correlated with NIRS values. CONCLUSIONS: Helium gas dilution technique is an applicable and reliable technique to measure lung volumes and ventilation inhomogeneity also in ventilated infants. NIRS is a non-invasive technique to monitor tissue oxygenation during surgery and mechanical ventilation. In CDH newborns these preliminary data show an improvement in both FRC and LCI after extubation.

Ontogeny and drug metabolism in newborns.

In pediatric age and particularly in newborn infants the drug efficacy and safety are influenced by the growth and development on drug Absorption, Distribution, Metabolism and Excretion (ADME). Thanks to the fast development of pharmacogenomics and pharmacogenetics, the drug therapy promises to be adapted to the genetic profile of the individual, reducing considerably the side effects of drugs and increasing their efficacy. Interindividual variability in drug response is well known in both adults and children. Such a variability is multifactorial considering both intrinsic and extrinsic factors. Drug distribution in the neonate is influenced by a variety of age-dependent factors as a total body water content and distribution variations, role of drug transporters, blood/tissue protein binding, blood and tissue pH and perfusion. The development of enzymes involved in human metabolism were classified in 3 categories: 1) those expressed during the whole or part of the fetal period, but silenced or expressed at low levels within 1-2 years after birth; 2) those expressed at relatively constant levels throughout fetal development, but increased to some extent postnatally; and 3) those whose onset of expression can occur in the third trimester, but substantial increase is noted in the first 1-2 years after birth. Besides this intrinsic aspects influencing pharmacokinetics during the neonatal period there are other important events such as inborn or acquired diseases, environment and finally pharmacogenetics and pharmacogenomics. Thousands of deaths every years are caused by fatal drug reactions; among the potential causes there are not only the severity of the disease being treated, drug interactions, nutritional status, renal and liver functions, but also the inherited differences in drug metabolism and genetic polymorphism. Adverse drug reactions (ADRs) among pediatric patients have been shown to be three times more frequent than in adults. On August 2010 The National Institute of Child Health and Human Development (NICHD) addressed patient safety issues in the NICU, recognizing that to understand and prevent adverse events, systematic research and education in safety issues needed. From all these concepts in terms of ADME, pharmacogenetics (relative to a single gene) and pharmacogenomics (relative to many genes) it is becoming more evident the perspective of the new concept of individualized medicine. The goal of this should be to identify which group of patients responds positively, which patients are nonresponders and who experiences adverse reaction for the same drug and dose. The interindividual variability in response to any drug is mostly dependent on DNA sequence variations across the human genome, the haplotype map (HAPMAP). At present there is still a big distance beween the knowledge in genetic and the practical application to model the drug profile to the genetic/genomic profile of the single patient. In the neonatal period the effects of growth in the pharmacodynamic, processes can help optimizing the dosage of neonatal frequently used medicines, thereby, minimizing their toxicity and increasing their efficacy. It should be useful to create accurate dosage adjustments according to the week of development.

Long term follow-up in high-risk congenital diaphragmatic hernia survivors: patching the diaphragm affects the outcome.

BACKGROUND/PURPOSE: The increased survival rate reached in infants with congenital diaphragmatic hernia (CDH) has shown a concomitant increase in late morbidity. A recent report from CDH Study Group showed that dimension of diaphragmatic defect is the only independent risk factor of mortality. However, the influence of defect size on late morbidity is still controversial. The aim of the study was to evaluate the influence of patch repair (proxy of diaphragmatic defects size) on midterm morbidity. METHODS: All high-risk (prenatal diagnosis and/or respiratory symptoms within 6 hours of life) CDH survivors treated at our institution from 2004 to 2008 were followed up in a multidisciplinary outpatient clinic as part of a longitudinal prospective study. Auxological, gastroesophageal, pulmonary, and orthopedic evaluations were performed at 6, 12, and 24 months of age. Patient outcomes were compared with respect to +/- patch repair. RESULTS: Of 70 survivors, 61 (87%) were enrolled and prospectively evaluated in follow-up. Poorer auxological outcome, increased rate of gastroesophageal reflux, and altered pulmonary function test were observed during follow-up. CONCLUSIONS: Patch repair correlates with higher pulmonary, auxological, and gastroesophageal morbidity without increasing chest wall deformities at long-term follow-up.