Search

Importance: A multicenter randomized clinical trial (RCT) showed a lung recruitment maneuver using high-frequency oscillatory ventilation just before surfactant administration (ie, intubate-recruit-surfactant-extubate [IN-REC-SUR-E]) improved the efficacy of treatment compared with the standard intubate-surfactant-extubate (IN-SUR-E) technique without increasing the risk of adverse neonatal outcomes., Objective: To examine follow-up outcomes at corrected postnatal age (cPNA) 2 years of preterm infants previously enrolled in an RCT and treated with IN-REC-SUR-E or IN-SUR-E in 35 tertiary neonatal intensive care units., Design, Setting, and Participants: This was a follow-up study of infants recruited into the primary RCT from 2015 to 2018 at 35 tertiary neonatal intensive care units (NICUs) in Italy. Follow-up examinations included neurodevelopmental, growth, and respiratory outcomes of these children at cPNA 2 years. Participants included spontaneously breathing extremely preterm neonates (24 0/7 to 27 6/7 weeks' gestation) reaching failure criteria for continuous positive airway pressure within the first 24 hours of life. Data were analyzed from April 2023 to January 2024., Intervention: Infants were randomly assigned (1:1) to IN-REC-SUR-E or IN-SUR-E and then followed up., Main Outcomes and Measures: The primary outcome was the occurrence of death after discharge or major disability at cPNA 2 years. Secondary outcomes were neurodevelopmental outcomes (major disability, cerebral palsy, cognitive impairment, visual deficit, or auditory deficit), anthropometric measurements (weight, length, and head circumference), and recurrent respiratory infections and hospitalizations because of respiratory causes at 2y cPNA., Results: A total of 137 extremely preterm infants (median [IQR] gestational age, 26.5 [25.3-27.5] weeks and 75 [54.7%] female), initially enrolled in the original RCT, were followed up at cPNA 2 years, including 64 infants in the IN-SUR-E group and 73 infants in the IN-REC-SUR-E group. There were no significant differences in the occurrence of death after discharge or major disability at cPNA 2 years (IN-SUR-E: 13 children [20.3%] vs IN-REC-SUR-E: 10 children [13.7%]; P = .36). There were no significant differences in incidence of disability, cerebral palsy, or cognitive impairment in the IN-REC-SUR-E group compared with the IN-SUR-E group. There were no significant differences in anthropometric measurements (weight, length, and head circumference) between groups. There were no significant differences in the incidence of recurrent respiratory infections or in hospitalizations because of respiratory causes between groups., Conclusions and Relevance: In this RCT of lung recruitment before surfactant vs standard care there were no significant differences between the 2 groups in death, neurodevelopmental outcomes, anthropometric measurements, or recurrent respiratory infections at the 2-year follow-up. These findings can aid clinicians in decision-making for the best strategy to administer surfactant, considering long-term outcomes.

Ceftazidime/avibactam (CAZ/AVI) is an antibiotic combination approved for the treatment of several infections caused by multi-drug resistant (MDR) Gram-negative bacteria. Neonates admitted to the Neonatal Intensive Care Unit (NICU) are at high risk of developing bacterial infections, and the choice of appropriate antibiotics is crucial. However, the use of antibiotics in neonates carries risks such as antibiotic resistance and disruption of gut microbiota. This study aimed to assess the safety and efficacy of CAZ/AVI in preterm infants admitted to the NICU. Retrospective data from preterm infants with Klebsiella pneumoniae bacteremia who received CAZ/AVI were analyzed. Clinical and microbiological responses, adverse events, and outcomes were evaluated. Eight patients were included in the study, all of whom showed clinical improvement and achieved microbiological cure with CAZ/AVI treatment. No adverse drug reactions were reported. Previous antibiotic therapies failed to improve the neonates' condition, and CAZ/AVI was initiated based on clinical deterioration and epidemiological considerations. The median duration of CAZ/AVI treatment was 14 days, and combination therapy with fosfomycin or amikacin was administered. Previous case reports have also shown positive outcomes with CAZ/AVI in neonates. However, larger trials are needed to further investigate the safety and efficacy of CAZ/AVI in this population.

Rotavirus (RV) is among the most common vaccine-preventable diseases in children under five years of age. Despite the severity of rotavirus pathology in early childhood, rotavirus vaccination for children admitted to the neonatal intensive care unit (NICU), who are often born preterm and with various previous illnesses, is not performed. This multicenter, 3-year project aims to evaluate the safety of RV vaccine administration within the six main neonatal intensive care units of the Sicilian Region to preterm infants. Methods: Monovalent live attenuated anti-RV vaccination (RV1) was administered from April 2018 to December 2019 to preterm infants with gestational age ≥ 28 weeks. Vaccine administrations were performed in both inpatient and outpatient hospital settings as a post-discharge follow-up (NICU setting) starting at 6 weeks of age according to the official immunization schedule. Any adverse events (expected, unexpected, and serious) were monitored from vaccine administration up to 14 days (first assessment) and 28 days (second assessment) after each of the two scheduled vaccine doses. Results : At the end of December 2019, 449 preterm infants were vaccinated with both doses of rotavirus vaccine within the six participating Sicilian NICUs. Mean gestational age in weeks was 33.1 (±3.8 SD) and the first dose of RV vaccine was administered at 55 days (±12.9 SD) on average. The mean weight at the first dose was 3388 (SD ± 903) grams. Only 0.6% and 0.2% of infants reported abdominal colic and fever above 38.5 °C in the 14 days after the first dose, respectively. Overall, 1.9% EAEs were observed at 14 days and 0.4% at 28 days after the first/second dose administration. Conclusions : Data obtained from this study confirm the safety of the monovalent rotavirus vaccine even in preterm infants with gestational age ≥ 28 weeks, presenting an opportunity to improve the vaccination offer both in Sicily and in Italy by protecting the most fragile infants who are more at risk of contracting severe rotavirus gastroenteritis and nosocomial RV infection.

Objectives: The early detection and stratification of asphyxiated infants at higher risk for impaired neurodevelopment is challenging. S100B protein is a well-established biomarker of brain damage, but lacks conclusive validation according to the "gold standard" methodology for hypoxic-ischemic encephalopathy (HIE) prognostication, i.e. brain MRI. The aim of the present study was to investigate the predictive role of urinary S100B concentrations, assessed in a cohort of HIE infants receiving therapeutic hypothermia (TH), compared to brain MRI., Methods: Assessment of urine S100B concentrations was performed by immunoluminometric assay at first void and at 4, 8, 12, 16, 20, 24, 48, 72, 96, 108 and 120-h after birth. Neurologic evaluation, routine laboratory parameters, amplitude-integrated electroencephalography, and cerebral ultrasound were performed according to standard protocols. Brain MRI was performed at 7-10 days of life., Results: Overall, 74 HIE neonates receiving TH were included in the study. S100B correlated, already at first void, with the MRI patterns with higher concentrations in infants with the most severe MRI lesions., Conclusions: High S100B urine levels soon after birth constitute trustable predictors of brain injury as confirmed by MRI. Results support the reliability of S100B in clinical daily practice and open the way to its inclusion in the panel of parameters used for the selection of cases suitable for TH treatment., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

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., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

Background: The importance of lung recruitment before surfactant administration has been shown in animal studies. Well designed trials in preterm infants are absent. We aimed to examine whether the application of a recruitment manoeuvre just before surfactant administration, followed by rapid extubation (intubate-recruit-surfactant-extubate [IN-REC-SUR-E]), decreased the need for mechanical ventilation during the first 72 h of life compared with no recruitment manoeuvre (ie, intubate-surfactant-extubate [IN-SUR-E])., Methods: We did a randomised, unblinded, controlled trial in 35 tertiary neonatal intensive care units in Italy. Spontaneously breathing extremely preterm neonates (24 + 0 to 27 + 6 weeks' gestation) reaching failure criteria for continuous positive airway pressure within the first 24 h of life were randomly assigned (1:1) with a minimisation algorithm to IN-REC-SUR-E or IN-SUR-E using an interactive web-based electronic system, stratified by clinical site and gestational age. The primary outcome was the need for mechanical ventilation in the first 72 h of life. Analyses were done in intention-to-treat and per-protocol populations, with a log-binomial regression model correcting for stratification factors to estimate adjusted relative risk (RR). This study is registered with ClinicalTrials.gov, NCT02482766., Findings: Of 556 infants assessed for eligibility, 218 infants were recruited from Nov 12, 2015, to Sept 23, 2018, and included in the intention-to-treat analysis. The requirement for mechanical ventilation during the first 72 h of life was reduced in the IN-REC-SUR-E group (43 [40%] of 107) compared with the IN-SUR-E group (60 [54%] of 111; adjusted RR 0·75, 95% CI 0·57-0·98; p=0·037), with a number needed to treat of 7·2 (95% CI 3·7-135·0). The addition of the recruitment manoeuvre did not adversely affect the safety outcomes of in-hospital mortality (19 [19%] of 101 in the IN-REC-SUR-E group vs 37 [33%] of 111 in the IN-SUR-E group), pneumothorax (four [4%] of 101 vs seven [6%] of 111), or grade 3 or worse intraventricular haemorrhage (12 [12%] of 101 vs 17 [15%] of 111)., Interpretation: A lung recruitment manoeuvre just before surfactant administration improved the efficacy of surfactant treatment in extremely preterm neonates compared with the standard IN-SUR-E technique, without increasing the risk of adverse neonatal outcomes. The reduced need for mechanical ventilation during the first 72 h of life might facilitate implementation of a non-invasive respiratory support strategy., Funding: None., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Global assessment of antimicrobial agents prescribed to infants in the neonatal intensive care unit (NICU) may inform antimicrobial stewardship efforts., Methods: We conducted a one-day global point prevalence study of all antimicrobials provided to NICU infants. Demographic, clinical, and microbiologic data were obtained including NICU level, census, birth weight, gestational/chronologic age, diagnoses, antimicrobial therapy (reason for use; length of therapy), antimicrobial stewardship program (ASP), and 30-day in-hospital mortality., Findings: On July 1, 2019, 26% of infants (580/2,265; range, 0-100%; median gestational age, 33 weeks; median birth weight, 1800 g) in 84 NICUs (51, high-income; 33, low-to-middle income) from 29 countries (14, high-income; 15, low-to-middle income) in five continents received ≥1 antimicrobial agent (92%, antibacterial; 19%, antifungal; 4%, antiviral). The most common reasons for antibiotic therapy were "rule-out" sepsis (32%) and "culture-negative" sepsis (16%) with ampicillin (40%), gentamicin (35%), amikacin (19%), vancomycin (15%), and meropenem (9%) used most frequently. For definitive treatment of presumed/confirmed infection, vancomycin (26%), amikacin (20%), and meropenem (16%) were the most prescribed agents. Length of therapy for culture-positive and "culture-negative" infections was 12 days (median; IQR, 8-14) and 7 days (median; IQR, 5-10), respectively. Mortality was 6% (42%, infection-related). An NICU ASP was associated with lower rate of antibiotic utilization ( p  = 0·02)., Interpretation: Global NICU antibiotic use was frequent and prolonged regardless of culture results. NICU-specific ASPs were associated with lower antibiotic utilization rates, suggesting the need for their implementation worldwide., Funding: Merck & Co.; The Ohio State University College of Medicine Barnes Medical Student Research Scholarship., Competing Interests: Dr. Pablo J. Sánchez has received research grant support from Merck & Co. during the conduct of the study, and grant from MedImmune, Inc - AstraZeneca, outside of the submitted work. Dr. Pavel Prusakov has received research grant support from Merck & Co. and Pfizer. Dr. Debra A. Goff has received research grant support from Merck & Co. and Pfizer. Dr. Landgrave reports other support from GSK, outside the submitted work. Dr. Kekomäki reports grants and personal fees from Sanofi, grants and personal fees from Merck Sharp & Dome, other support from Pfizer, all outside of the submitted work. Dr. Mesa reports speaker fees from Pfizer and GlaxoSmithKline, outside of the submitted work. Mr. Wozniak received a Barnes Medical Student Research Scholarship grant from The Ohio State University College of Medicine. The other authors have nothing to disclose., (© 2021 The Authors.)

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.

Background: Perinatal asphyxia (PA) is a leading cause of mortality and morbidity in newborns: its prognosis depends both on the severity of the asphyxia and on the immediate resuscitation to restore oxygen supply and blood circulation. Therefore, we investigated whether measurement of S100B, a consolidated marker of brain injury, in salivary fluid of PA newborns may constitute a useful tool for the early detection of asphyxia-related brain injury., Methods: We conducted a cross-sectional study in 292 full-term newborns admitted to our NICUs, of whom 48 suffered PA and 244 healthy controls admitted at our NICUs. Saliva S100B levels measurement longitudinally after birth; routine laboratory variables, neurological patterns, cerebral ultrasound and, magnetic resonance imaging were performed. The primary end-point was the presence of neurological abnormalities at 12-months after birth., Results: S100B salivary levels were significantly (P<0.001) higher in newborns with PA than in normal infants. When asphyxiated infants were subdivided according to a good (Group A; n = 15) or poor (Group B; n = 33) neurological outcome at 12-months, S100B was significantly higher at all monitoring time-points in Group B than in Group A or controls (P<0.001, for all). A cut-off >3.25 MoM S100B achieved a sensitivity of 100% (CI5-95%: 89.3%-100%) and a specificity of 100% (CI5-95%: 98.6%-100%) as a single marker for predicting the occurrence of abnormal neurological outcome (area under the ROC curve: 1.000; CI5-95%: 0.987-1.0)., Conclusions: S100B protein measurement in saliva, soon after birth, is a useful tool to identify which asphyxiated infants are at risk of neurological sequelae.

Objective: Data comparing the effectiveness of high-frequency oscillatory ventilation and of conventional mechanical ventilation in the treatment of respiratory distress syndrome of very low birth weight infants are, to date, still matter of debate. We investigated the effects of first intention high-frequency oscillatory ventilation or conventional mechanical ventilation support on selected primary and secondary outcomes in very low birth weight infants complicated by respiratory distress syndrome in which antenatal glucocorticoid prophylaxis was not performed., Design: Multicenter randomized control trial., Setting: Three tertiary centers of neonatal intensive care units from December 2004 to December 2007., Population: Eighty-eight very low birth weight infants complicated by respiratory distress syndrome, without antenatal glucocorticoids, supported by first intention high-frequency oscillatory ventilation (n = 44) or conventional mechanical ventilation (n = 44)., Interventions: All newborns were monitored by standard monitoring procedure, including routine laboratory variables, neurologic patterns, and ultrasound imaging. Primary outcomes were: the length of ventilatory support, the need of reintubation, and the length of nasal continuous positive airway pressure support in the postextubation period. Secondary outcomes were: the length of stay in neonatal intensive care unit and in hospital, death before discharge, adverse short- and long-term pulmonary and neonatal outcomes, and the need for a second dose of surfactant and of postnatal glucocorticoid treatment., Results: High-frequency oscillatory ventilation infants showed a significant lower duration (p < .001 for all) of ventilator dependency, lower need of reintubation and of duration of nasal continuous positive airway pressure support in the postextubation period. Among secondary outcomes in the high-frequency oscillatory ventilation infants, the need of a second dose of surfactant administration, and the length of stay in the neonatal intensive care unit and in hospital were significantly lower (p < .05 for all)., Conclusions: We found that high-frequency oscillatory ventilation in very low birth weight infants without antenatal glucocorticoid prophylaxis reduced the need of ventilatory support, surfactant therapy, and reintubation, and shortened neonatal intensive care unit and hospital stay, thus reducing unit and hospital costs. These data would support the usefulness of first intention high-frequency oscillatory ventilation strategy in managing in a selected population, such as very low birth weight newborns complicated by severe respiratory distress syndrome not antenatally treated with glucocorticoids.

Cerebral monitoring constitutes an emerging issue in perinatal medicine. Near Infrared Spectroscopy (NIRS) monitors brain oxygenation status in sick infants although data in healthy infants are lacking. The present study investigates whether NIRS parameters change according to gestational age and correlate with S100B protein. We recruited 64 healthy newborns (weeks' gestation: 30-42 wks) in which we performed in the first 6-hours after birth routine clinical, radiological and laboratory variables, cerebral oxygen saturation (rSO2), fractional cerebral tissue oxygen extraction (FTOE) values and S100B urine assessment. rSO2 and FTOE correlated (R=-0.73; R=0.51; P less than 0.01, for both) with gestational age. Highest rSO2 and the lowest FTOE peaks (P less than 0.001) were found at 30-33 wks. From 34 wks onwards, rSO2 progressively decreased and FTOE increased reaching their lower dip/peak (P less than 0.001) at 38-39 weeks. A significant correlation between S100B and NIRS parameters (rSO2: r=0.77; FTOE: r=-0.69; P less than 0.01) has been found. The present study shows that NIRS parameters and S100B protein correlation may be of help in brain function monitoring.

Near Infrared Spectroscopy (NIRS) is an emerging technique for brain oxygenation monitoring in newborns complicated by acute and chronic hypoxia. However, data regarding cerebral oxygenation normal values are still lacking and matter of debate. Therefore, we investigate whether NIRS parameters in healthy preterm/term infants are gestational age and delivery modalities dependent and correlate with standard monitoring parameters. From January to December 2007, 100 healthy newborns with gestational age from 30 to 42 weeks' gestation were evaluated. Routine laboratory variables, daily clinical and neurological evaluation and ultrasound imaging were performed. The regional cerebral oxygen saturation (rSO2) and fractional cerebral tissue oxygen extraction (FTOE) were measured by NIRS in the first 6-hours after birth. Data were recorded by MetaVision ICU X-Edition software and analyzed by SPSS statistical package. rSO2 and FTOE correlated (R=-0.77; R=0.41; P<0.01, for both) with gestational age. Highest rSO2 and the lowest FTOE peaks (P<0.001, for all) were found at 30-33 wks when compared with other monitoring periods. From 34 wks onwards, rSO2 progressively decreased and FTOE increased reaching their lower dip/peak (P<0.001, for all) at 38-39 weeks. rSO2 and FTOE values were significantly different (P<0.05, for both) between preterm and term newborns when corrected for delivery modality. rSO2 correlated (P<0.001 for all) with heart (r=0.63), respiratory (r=-0.58) rate, and with arterial oxygen saturation (r=0.65). In conclusion, in the first 6-hours after birth cerebral oxygenation in healthy newborns is gestational age-dependent and correlated with routine parameters. NIRS reference curve could be particularly useful in sick newborns brain monitoring.

Objective: Cardiac catheterization (CC) is a life-threatening procedure in adult patients. Complicated by idiopathic arterial pulmonary hypertension (IPAH), there is a potential risk of central nervous system (CNS) damage. We measured serum levels of a well-established brain damage marker, namely S100B, collected before, during and after CC in adult patients in whom the nitric oxide (NO) test had been performed., Material and Methods: In 12 adult patients who had undergone CC for IPAH diagnosis, we recorded clinical and standard monitoring procedures (laboratory variables and echocardiographic patterns) and serum concentrations of S100B before (time 0), during (time 1) and after the NO test (time 2) and at 24 h after (time 3) the procedure in samples obtained from the systemic and pulmonary circulation. Patients were subdivided into NO test responders (n=6) and non-responders (n=6). Neurological evaluation was performed at admission and at discharge from hospital., Results: Adult patients subjected to CC showed no overt neurological injury at discharge from hospital. No significant differences (p > 0.05 for all) in S100B serum levels between groups at times 0, 1 and 3 have been shown independently from the sampling site. It was noteworthy that the concentration of protein in the responders group at time 2 was significantly decreased (p < 0.05, for all) compared to the responder group and to baseline values. A significant correlation was found between arterial oxygen partial pressure and individual S100B concentration in the pulmonary and systemic bloodstream in the entire study group (R = -0.66 and R = 0.71, respectively; p < 0.05, for both)., Conclusions: The data suggest that S100B protein assessment, as well as the NO test, may be useful when monitoring possible CNS damage during CC in patients with IPAH, and may also be valuable in relation to brain functions, especially when performed as an emergency procedure in severely hypoxic patients.

Cerebral function monitor (CFM), unlike traditional EEG, allows a long-term evaluation of electric brain activity, without interfering with the nursing of the newborn in the intensive care unit. Our aim was to evaluate the prognostic value of CFM for neurological outcome. We studied 102 newborns (gestational age 34.5 +/- 4.36 weeks; weight 1980 +/- 720 grams) by Multitrace CFM (Lectromed) 5 hours daily in the first week following admission. The patients also underwent cerebral echography, EEG and neurological follow-up to the 24th month. CFM was found to correlate well with the EEG recorded 3 months later. The persistence for at least one week of an I.C. tracing or the normalization of initial tracing have a good prognostic value (positive predictive value 95.23%), a persistently pathologic registration has a negative prognostic value (negative predictive value 85.18%), that even increases if cerebral echographic alterations are demonstrated (98.57%). The association of CFM and ultrasound abnormalities determines a relative risk for neurological motor impairment of 69.14, whereas CFM alone gives a relative risk of 6.4.

In this retrospective study the Authors correlated the hypoxia with the severity of retinopathy of prematurity (ROP) in a population of 683 outborn preterm infants (bw < 2500 g and gestational age < 38 weeks). They excluded all cases with specific pathological conditions. Among neonates with the same gestational age the incidence of ROP was higher (p < .05) in those with hypoxia (pH < 7.25, tcPO2 < 50 mmHg). These data suggest that hypoxia plays a role in the pathogenesis of ROP.

We prospectively determined serum concentrations of soluble intercellular adhesion molecule 1 (sICAM-1) in the first 2 weeks of life in 32 preterm newborns in an attempt to assess whether these concentrations are reliable markers of sepsis in newborns at risk of infection. Ten of the study group were normal and had been hospitalized only for low birth weight. The remaining 22 presented respiratory distress (RDS) and were at even higher risk of infection because they required assisted mechanical ventilation and central venous catheterisation for parenteral feeding and infusion therapy. Sepsis was diagnosed in 11/22 newborns with RDS: in 3 on day 3 and in 8 on day 7. Circulating sICAM-1 concentrations were significantly elevated in neonates with RDS (group II) and associated infection (group III) compared with normal newborns (group I). However, after day 3 of life sICAM-1 values were significantly higher in group III than in group II.

Plasma fibronectic (pFN) is a high molecular weight multifunction glycoprotein, which augments neutrophil and macrofage phagocytosis and acts as a nonspecific opsonin for the reticuloendothelial system. In this study we have determined pFN concentrations in fifty eight preterm infants to discriminate infected from non infected ones. Concentrations of pFN decreased from baselin in babies with early or late onset infections. The changes in pFN concentrations were not found before sepsis, but on day 1. By day 5 pFN concentrations have increased and have been no longer different from controls. We have calculated sensitivity (73.68%), specificity (74.36%), positive (58.35%) and negative (85.29%) predictive values of pFN and of other markers of infections (C-reactive protein--CRP-, Immature/Mature neutrophil ratio--I/M n. ratio-). Adding these tests to pFN, provided equal specificity and positive predictive value, but increased sensitivity (94.73%) and negative predictive value (96.43%). Thus, low concentrations of pFN may be a valuable but not early marker for neonatal infections. The combination of pFN, CRP and I/M n. ratio increase the precision of diagnostic testing.

The Hallermann-Streiff syndrome is a rare affection characterized by beaked nose, dyscephaly, hypotrichosis, cataracts, micrognathia and proportionate short stature. The most severe complication in the syndrome is respiratory embarrassment. Narrow air passage with abnormal glottic closure, prenatal growth deficiency, immunodeficiency and sometimes associated cardiovascular anomalies, can predispose these patients to pulmonary infections. The Authors describe a new-born with Hallermann-Streiff syndrome, who, after a brief period of obstructive apnea successfully treated with CPAP, developed a severe pulmonary infection that caused his death at the age of 61 days.

Doxapram is an analeptic capable of stimulating both central and periferal areas of the respiratory system. During the last few years, intravenous infusion of doxapram has been carried out, with success, for the treatment of idiopathic apnea in preterm infants otherwise unresponsive to methylxantine. Since doxapram has a tendency to precipitate into various solution containing amino acids and calcium gluconate, oral administration has been suggested. The Authors in this study have seen that in 18 preterm infants suffering from idiopathic apnea unresponsive to amynofillina, an oral administration of doxapram at 12 mg/kg/6h resulted in a complete recovery from apnea spells in 66.7% of cases, while 22.2% gave a partial positive response and only 11.1% a negative result. Furthermore the Authors would like to stress that doxapram showed a good tolerance level when administered orally. In fact, no side effects which were previously reported in other publications were presented in the infants studied.

Systemic Candida A. infections are increasing in Neonatal Intensive Care Units. For many years, Amphotericin B, alone or in combination with 5-fluorocytosine, have been used. Recently a search for new and less toxic drugs has been started. In this study we report the case of hepatic candidosis in a preterm newborn. The patient has been treated with itraconazole, an oral antifungal agent with broad spectrum activity. Its tolerance has been good. No severe side effects were observed and biochemical parameters showed no consistent drug induced effects.

Pena-Shokeir syndrome is a rare, often lethal disease, characterized by intrauterine growth retardation and by fetal akinesia or hypokinesia that leads to craniofacial anomalies, limb ankylosis, polyhydramnios and pulmonary hypoplasia. The case that we report had a favourable evolution, although there was at birth a severe respiratory distress. EMG studies revealed deficit of innervation. Contraceptive therapy, wrongly used by the mother in the first period of pregnancy, played, probably, a concomitant role in the pathogenesis of the syndrome.

Systemic Candida Albicans infections in premature newborns are characterized by high morbidity; early diagnosis and immediate treatment are therefore necessary. In this study we report the cases of fourteen newborns admitted to our Newborn Care Unit in a three-year period, in whom candidiasis was diagnosed. The mycetes was isolated from blood, liquor, peritoneal fluid, urine, oesophageal aspirate. Treatment was undertaken immediately with fluconazole, administered through the parenteral route or locally into peritoneal cavum and oesophageal stump. Duration of treatment varied from five to twenty-one days. All cases underwent complete negativization of cultures and no systemic or local side effects.

Retinopathy of prematurity (ROP) is a multifactorial disease where production of free radicals is a pathogenic factor. Bilirubin is regarded today as the most powerful antioxidant substance "in vitro". To test such effect "in vivo" we studied 219 premature infants, admitted to our Neonatal Intensive Case Unit from April 1991 to October 1992, evaluating their serum bilirubin levels from day two to seven and mean bilirubin level of first week for each child. We also calculated the mean rate of daily increase of bilirubin. Our results show that bilirubin parameters considered are higher in neonates which will develop ROP of every stage than in the control ones. These results therefore do not support the concept that bilirubin could have a role in the prevention of ROP.

The authors present a retrospective epidemiological study on retinopathy of prematurity (ROP), performed on 738 newborns with a gestational age of 34 +/- 2.41 weeks and birth weight of 1971 +/- 351 g. They excluded all cases with severe respiratory distress and other pathological conditions. First stage of ROP shows no correlation with gestational age and birth weight, whereas second and third stages of ROP show an inverse correlation with the above mentioned factors, particularly birth weight. Among neonates with the same gestational age, the incidence of ROP is higher in those "small for date". Regarding the pathogenesis of ROP, the authors outline the importance of perinatal hypoxia.

Doxapram is an analeptic of the respiratory system that has been used in the last few years for the treatment of idiopathic apnea spells in infants who show resistance to methylxantine. In this study we have compared the efficacy of aminophylline and doxapram for the prevention of idiopathic apnea spells in two groups of preterm infants comparable for gestational age, birthweight and postnatal age. The two drugs resulted to be effective in preventing the spells of apnea in 66% and 60% of the cases respectively. In the cases in which there was a partial or negative response, the association of the two substances resulted in a noticeable reduction of the apnea spells. The positive effect of the association of aminophylline and doxapram is probably due to the different action mechanism on the stimulation of the respiratory system.