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BackgroundMetabolic Acidosis (MA) is a disturbance of the acid-base balance that can occur in preterm and critically ill term neonates due to different etiologies. Intravenous sodium bicarbonate (SB) has been traditionally used to correct such unbalance, despite the lack of evidence about its safety and efficacy. In literature, reported undesirable effects of treatment with SB in neonates include worsening of intracellular acidosis, impairment of myocardial function, cerebral blood flow fluctuations and intracranial hemorrhage. A national survey was conducted by the Neonatal Pharmacotherapy Study Group of the Italian Society of Neonatology with the aim to assess and describe attitudes and practices concerning the use of SB, particularly for the treatment of MA in Italian NICUs.MethodsA questionnaire regarding treatment of MA and SB prescription habits was sent to the directors of 120 Italian NICUs from June 2017 to March 2018.ResultsThe survey response rate was 97.5% (117/120 centers). Findings showed that in 55% of the surveyed NICUs (64/117 units) it is common practice to correct MA with intravenous SB. On the other hand, the remaining 45% of the units try to solve the metabolic disturbances adopting different approaches (improving perfusion, adjusting ventilation parameters or increasing blood volume). Moreover, to prevent the occurrence of MA, 37.6% of the NICUs (44/117) include buffer salts (lactate, acetate or both) in parenteral nutrition prescriptions. SB is also used as a treatment for other conditions, mainly pathologies with bicarbonate loss and tubular acidosis (respectively in 53.8 and 32.5% of the NICUs).ConclusionThis survey showed how SB is a commonly used treatment for MA in more than half of Italian NICUs, with indications and prescription criteria that significantly vary across centers. Based on current knowledge, it is reasonable to suggest that the management of neonatal MA should be firstly directed to identify the underlying disorders. Thus, the use of SB should be reserved only for selected cases, also considering the severity of SB adverse effects and the lack of evidence about its efficacy. Guidance for the management of MA is required to harmonize practices and reduce the use of potentially inappropriate and unsafe treatments.

Background Despite regionalization of perinatal care provides for the “in utero” transfer of high-risk pregnancies, there will always be a number of neonates who undergo acute inter-facility transport. The presence of a well-organized Neonatal Emergency Transport Service (NETS) can prevent and reduce risks of transportation, especially for very preterm infants, and is therefore mandatory for any program of regionalization of perinatal care. Italian National Health System is highly decentralized and Regions are autonomous to structure, plan and delivery their regional health services. Consequently, organization models and resources available vary widely and significant regional differences in access and quality of health services have been reported in the past years. A national survey was conducted in 2015 by the neonatal transport study group of the Italian Society of Neonatology with the aim to describe neonatal transfer practices and to assess the Neonatal Emergency Transport Services (NETS) status in the 20 Italian regions. Methods A questionnaire regarding neonatal transfer practices and NETS activity for the previous year (2014) was sent to the 44 NETS operating in the 20 Italian regions. Demographic data were obtained from the Italian National Statistical Institute (ISTAT). Results The overall survey response rate was 100%. In 2014, only 12 (60%) of the 20 Italian regions were fully covered by NETS, 3 (15%) regions were partially covered, while neonatal transport was not available in 5 (25%) regions. Overall, in 2014, the 44 NETS operating in Italy transported a total of 6387 infants, including 522 (8.17%) having a gestational age

QUBIC, the Q & U Bolometric Interferometer for Cosmology, is a novel ground-based instrument that aims to measure the extremely faint B-mode polarisation anisotropy of the cosmic microwave background at intermediate angular scales (multipoles of = 30 − 200). Primordial B-modes are a key prediction of Inflation as they can only be produced by gravitational waves in the very early universe. To achieve this goal, QUBIC will use bolometric interferometry, a technique that combines the sensitivity of an imager with the immunity to systematic effects of an interferometer. It will directly observe the sky through an array of back-to-back entry horns whose beams will be superimposed using a cooled quasioptical beam combiner. Images of the resulting interference fringes will be formed on two focal planes, each tiled with transition-edge sensors, cooled down to 320 mK. A dichroic filter placed between the optical combiner and the focal planes will select two frequency bands (centred at 150 GHz and 220 GHz), one frequency per focal plane. Polarization modulation will be achieved using a cold stepped half-wave plate (HWP) and polariser in front of the sky-facing horns. The full QUBIC instrument is described elsewhere1,2,3,4; in this paper we will concentrate in particular on simulations of the optical combiner (an off-axis Gregorian imager) and the feedhorn array. We model the optical performance of both the QUBIC full module and a scaled-down technological demonstrator which will be used to validate the full instrument design. Optical modelling is carried out using full vector physical optics with a combination of commercial and in-house software. In the high-frequency channel we must be careful to consider the higher-order modes that can be transmitted by the horn array. The instrument window function is used as a measure of performance and we investigate the effect of, for example, alignment and manufacturing tolerances, truncation by optical components and off-axis aberrations. We also report on laboratory tests carried on the QUBIC technological demonstrator in advance of deployment to the observing site in Argentina.

International audience; QUBIC (the Q and U Bolometric Interferometer for Cosmology) is a ground-based experiment which seeks to improve the current constraints on the amplitude of primordial gravitational waves. It exploits the unique technique, among Cosmic Microwave Background experiments, of bolometric interferometry, combining together the sensitivity of bolometric detectors with the control of systematic effects typical of interferometers. QUBIC will perform sky observations in polarization, in two frequency bands centered at 150 and 220 GHz, with two kilo-pixel focal plane arrays of NbSi Transition-Edge Sensors (TES) cooled down to 350 mK. A subset of the QUBIC instrument, the so called QUBIC Technological Demonstrator (TD), with a reduced number of detectors with respect to the full instrument, will be deployed and commissioned before the end of 2018. The voltage-biased TES are read out with Time Domain Multiplexing and an unprecedented multiplexing (MUX) factor equal to 128. This MUX factor is reached with two-stage multiplexing: a traditional one exploiting Superconducting QUantum Interference Devices (SQUIDs) at 1K and a novel SiGe Application-Specific Integrated Circuit (ASIC) at 60 K. The former provides a MUX factor of 32, while the latter provides a further 4. Each TES array is composed of 256 detectors and read out with four modules of 32 SQUIDs and two ASICs. A custom software synchronizes and manages the readout and detector operation, while the TES are sampled at 780 Hz (100kHz/128 MUX rate). In this work we present the experimental characterization of the QUBIC TES arrays and their multiplexing readout chain, including time constant, critical temperature, and noise properties.

QUBIC, the Q & U Bolometric Interferometer for Cosmology, is a novel ground-based instrument that has been designed to measure the extremely faint B-mode polarisation anisotropy of the cosmic microwave background at intermediate angular scales (multipoles of 𝑙 = 30 − 200). Primordial B-modes are a key prediction of Inflation as they can only be produced by gravitational waves in the very early universe. To achieve this goal, QUBIC will use bolometric interferometry, a technique that combines the sensitivity of an imager with the systematic error control of an interferometer. It will directly observe the sky through an array of 400 back-to-back entry horns whose signals will be superimposed using a quasi-optical beam combiner. The resulting interference fringes will be imaged at 150 and 220 GHz on two focal planes, each tiled with NbSi Transition Edge Sensors, cooled to 320 mK and read out with time-domain multiplexing. A dichroic filter placed between the optical combiner and the focal planes will select the two frequency bands. A very large receiver cryostat will cool the optical and detector stages to 40 K, 4 K, 1 K and 320 mK using two pulse tube coolers, a novel 4He sorption cooler and a double-stage 3He/4He sorption cooler. Polarisation modulation and selection will be achieved using a cold stepped half-wave plate (HWP) and polariser, respectively, in front of the sky-facing horns. A key feature of QUBIC’s ability to control systematic effects is its ‘self-calibration’ mode where fringe patterns from individual equivalent baselines can be compared. When observing, however, all the horns will be open simultaneously and we will recover a synthetic image of the sky in the I, Q and U Stokes’ parameters. The synthesised beam pattern has a central peak of approximately 0.5 degrees in width, with secondary peaks further out that are damped by the 13-degree primary beam of the horns. This is Module 1 of QUBIC which will be installed in Argentina, near the city of San Antonio de los Cobres, at the Alto Chorrillos site (4869 m a.s.l.), Salta Province. Simulations have shown that this first module could constrain the tensor-to-scalar ratio down to σ(r) = 0.01 after a two-year survey. We aim to add further modules in the future to increase the angular sensitivity and resolution of the instrument. The QUBIC project is proceeding through a sequence of steps. After an initial successful characterisation of the detection chain, a technological demonstrator is being assembled to validate the full instrument design and to test it electrically, thermally and optically. The technical demonstrator is a scaled-down version of Module 1 in terms of the number of detectors, input horns and pulse tubes and a reduction in the diameter of the combiner mirrors and filters, but is otherwise similar. The demonstrator will be upgraded to the full module in 2019. In this paper we give an overview of the QUBIC project and instrument.

Aim: To analyse antibiotic prescriptions in a cohort of extremely low birth weight neonates admitted to Italian level III Neonatal intensive Care Units. Methods: An online questionnaire was used to collect detailed information for each newborn. Antibiotic prescriptions were classified about their license status and compared with British National Formulary for Children (BNFC) and with a practical guide prepared by the Italian Society of Neonatology (ISN). Results: During the study period (May-July 2014) among 93 neonates admitted to 30 Italian Neonatal intensive Care Units, 56 (60%) received at least an antibiotic (92 prescriptions in total). Ampicillin, gentamicin and vancomycin were the antibiotics most commonly used for the prevention/treatment of bacterial infections. 56/92 antibiotic prescriptions (61%) resulted off-label mainly as regards dosing frequency, while 13 prescriptions (14%) regarded antibiotics used in absence of specific indication for newborns (meropenem, imipenem, piperacillin/tazobactam, clindamycin, clarithromycin). 50/56 neonates (89.3%) received at least one off-label antibiotic prescription. Differences have been observed in dosing regimens between current study and recommendations contained in BNFC, while prescriptions adhered more frequently to ISN indications. Conclusions: Our results confirm the high prevalence of off-label antibiotic use in ELBW neonates and underline a better adherence to indications based on clinical practice.

International audience; Remnant radiation from the early universe, known as the Cosmic Microwave Background (CMB), has been redshifted and cooled, and today has a blackbody spectrum peaking at millimetre wavelengths. The QUBIC (Q&U Bolometric Interferometer for Cosmology) instrument is designed to map the very faint polaristion structure in the CMB. QUBIC is based on the novel concept of bolometric interferometry in conjunction with synthetic imaging. It will have a large array of input feedhorns, which creates a large number of interferometric baselines. The beam from each feedhorn is passed through an optical combiner, with an off-axis compensated Gregorian design, to allow the generation of the synthetic image. The optical-combiner will operate in two frequency bands (150 and 220 GHz with 25% and 18.2 % bandwidth respectively) while cryogenically cooled TES bolometers provide the sensitivity required at the image plane. The QUBIC Technical Demonstrator (TD), a proof of technology instrument that contains 64 input feed-horns, is currently being built and will be installed in the Alto Chorrillos region of Argentina. The plan is then for the full QUBIC instrument (400 feed-horns) to be deployed in Argentina and obtain cosmologically significant results. In this paper we will examine the output of the manufactered feed-horns in comparison to the nominal design. We will show the results of optical modelling that has been performed in anticipation of alignment and calibration of the TD in Paris, in particular testing the validity of real laboratory environments. We show the output of large calibrator sources (50 ° full width haf max Gaussian beams) and the importance of accurate mirror definitions when modelling large beams. Finally we describe the tolerance on errors of the position and orientation of mirrors in the optical combiner.

International audience; QUBIC, the QU Bolometric Interferometer for Cosmology, is a novel forthcoming instrument to measure the B-mode polarization anisotropy of the Cosmic Microwave Background. The detection of the B-mode signal will be extremely challenging; QUBIC has been designed to address this with a novel approach, namely bolometric interferometry. The receiver cryostat is exceptionally large and cools complex optical and detector stages to 40 K, 4 K, 1 K and 350 mK using two pulse tube coolers, a novel 4He sorption cooler and a double-stage 3He/4He sorption cooler. We discuss the thermal and mechanical design of the cryostat, modelling and thermal analysis, and laboratory cryogenic testing.

(1)H-NMR spectroscopy coupled with multivariate statistical analysis was used for the first time to compare the urinary NMR metabolic profiles of neonates with intrauterine growth retardation (IUGR) and large for gestational age (LGA). For the sake of comparison, infants who were adequate for gestational age (AGA) were also analyzed. Pattern recognition methods, including Principal Component Analyses (PCA), Partial Least Squares Discriminant Analysis (PLS-DA) and Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA), were used to analyze NMR data. Clear differences among the metabolic profiles of AGA, IUGR and LGA were observed. The main metabolites responsible for these differentiations were identified as myo-inositol, creatinine, creatine, citrate, urea and glycine. In particular, among these, myo-inositol may be a potential biomarker of an altered glucose metabolism during fetal development both in IUGR and LGA. This study highlights the applicability of NMR-based metabolomics for improving the understanding of the relations among nutrition, integrated metabolism and health in neonatology.

Background: Women in many countries are advised to use folic acid supplements before and early during pregnancy to reduce the risk of neural tube defects in their infants. This study aimed to update the prevalence and to identify possible determinants of preconception folic acid supplement use in Italian women. Methods: The study was based on cross-sectional data from seven maternity clinics located in six Italian regions from January to June, 2012. Data on maternal characteristics and supplement use were collected for 2,189 women using a self-administered questionnaire. Results: Preconception folic acid use was reported by 23.5 % (n = 515) of the participants. Of these, 479 (93 %) women had taken folic acid supplements on a daily basis as recommended by the health authorities. Women who both had intended their pregnancy and had requested a preconception health visit to a doctor/gynecologist were substantially more likely than the reference group to initiate folic acid supplementation before their pregnancy (48.6 versus 4.8 %). Preconception folic acid use was also associated with higher maternal age, higher education, marriage/cohabitation, lower parity, infertility treatments, and chronic disease. Conclusions: Data from seven maternity clinics located in six Italian regions indicate that preconception folic acid supplement use in many Italian women is low. Women who do not plan their pregnancy or do not request a preconception health visit to their doctor have among the lowest prevalence of preconception folic acid use. Improving folate status in these and other supplemental non-users may have important disease preventive effects. publishedVersion

In this study, a gas-chromatography mass spectrometry (GC-MS) metabolomics study was applied to examine urine metabolite profiles of different classes of neonates under different nutrition regimens. The study population included 35 neonates, exclusively either breastfed or formula milk fed, in a seven-day timeframe. Urine samples were collected from intrauterine growth restriction (IUGR), large for gestational age (LGA), and appropriate gestational age (AGA) neonates. At birth, IUGR and LGA neonates showed similarities in their urine metabolite profiles that differed from AGA. When neonates started milk feeding, their metabolite excretion profile was strongly characterized by the different diet regimens. After three days of formula milk nutrition, urine had higher levels of glucose, galactose, glycine and myo-inositol, while up-regulated aconitic acid, aminomalonic acid and adipic acid were found in breast milk fed neonates. At seven days, neonates fed with formula milk shared higher levels of pseudouridine with IUGR and LGA at birth. Breastfed neonates shared up-regulated pyroglutamic acid, citric acid, and homoserine, with AGA at birth. The role of most important metabolites is herein discussed.

The use of medicines among newborns admitted to intensive care units is characterized by a high prevalence of off-label/unlicensed use and a wide variability in the absence of international guidelines. A prospective cross-sectional study was organized with the aim to analyse drug prescriptions among all 107 Italian level III neonatal intensive care units. An online questionnaire was used to collect detailed information for each newborn, and a classification was made about the license status of all prescriptions. In addition, prescriptions were analysed taking into account a practical guide prepared by the Italian Society of Neonatology (ISN). The 1-day survey (May–July 2014) regarded 220 newborn infants admitted to 36/107 Italian neonatal intensive care units: 191 prematures and 29 born at term. In total, 720 prescriptions (corresponding to 79 different drugs) were analysed: 191 (26.5 %) followed the terms of the product license, 529 (73.5 %) were off-label or unlicensed: 193/220 newborns (87.7 %) received at least one off-label/unlicensed prescription. Antiinfectives were the most common medicine used, followed by respiratory drugs and antianaemics; in an off-label manner, the most common was cardiovascular and central nervous system (CNS) drugs, gastrointestinals and antiinfectives. The most common categories of off-label use were age (34.4 %) and dosing frequency (20.6 %). Compared to ISN practical guide, prescriptions adhered more frequently to indications (100 % for ampicillin/sulbactam, >80 % for ampicillin, fluconazole, fentanyl, ranitidine and vancomicin). Our results confirm the high prevalence of off-label/unlicensed drug use in the neonatal population and underline a better adherence to indications based on clinical practice, suggesting the need to update information contained in the data sheets of medicines.

Apnoea, desaturations and bradycardias are common problems in preterm infants which can be treated with nasal continuous positive airway pressure (NCPAP) and nasal intermittent positive pressure ventilation (NIPPV). It is unclear whether synchronised NIPPV (SNIPPV) would be even more effective.To assess the effects of flow-SNIPPV, NIPPV and NCPAP on the rate of desaturations and bradycardias in preterm infants and, secondarily, to evaluate their influence on pattern of breathing and gas exchange.Nineteen infants (mean gestational age at study 30 weeks, 9 boys) with apnoeic spells were enrolled in a randomised controlled trial with a cross-over design. They received flow-SNIPPV, NIPPV and NCPAP for 4 h each. All modes were provided by a nasal conventional ventilator able to provide synchronisation by a pneumotachograph. The primary outcome was the event rate of desaturations (≤80% arterial oxygen saturation) and bradycardias (≤80 bpm) per hour, obtained from cardiorespiratory recordings. The incidence of central apnoeas (≥10 s) as well as baseline heart rate, FiO2, SpO2, transcutaneous blood gases and respiratory rate were also evaluated.The median event rate per hour during flow-SNIPPV, NIPPV and NCPAP was 2.9, 6.1 and 5.9, respectively (p0.001 and 0.009, compared with flow-SNIPPV). Central apnoeas per hour were 2.4, 6.3 and 5.4, respectively (p=0.001, for both compared with flow-SNIPPV), while no differences in any other parameter studied were recorded.Flow-SNIPPV seems more effective than NIPPV and NCPAP in reducing the incidence of desaturations, bradycardias and central apnoea episodes in preterm infants.

Background: Neonatal onset hypopituitarism is a life-threatening, potentially treatable endocrine disease. A possible cause is congenital absence of the anterior pituitary gland, a condition very rarely reported in the literature. Methods: A series of 5 cases of children with pituitary aplasia referred to the Centre of Paediatric Endocrinology ‘Rina Balducci’, Tor Vergata University, Rome, is presented. Results: Major clinical features in our patients were respiratory distress on the first day of life, in spite of uneventful pregnancy, labour and delivery, metabolic acidosis, non-cholestatic jaundice, hypotonia, severe hypoglycaemia, hypogenitalism, and midline defects. Diagnosis was established by endocrine tests during hypoglycaemia and hypothalamic-pituitary MRI scan. Symptoms disappeared soon after replacement therapy was started. Conclusion: We stress the importance of performing baseline endocrine tests as soon as possible during hypoglycaemia and MRI of the brain aimed at visualizing the hypothalamic-pituitary area in neonates with hypogenitalism and severe unexplained hypoglycaemia, so that the irreversible neurological and developmental consequences of panhypopituitarism can be prevented by adequate replacement therapy.

The etiology of congenital idiopathic talipes equinovarus deformity is unclear. Studies on populations, families, and twins have suggested a genetic component. However, the mode of inheritance does not fit classic patterns. The intrauterine posture and environmental and developmental causative factors have also been associated with the deformity. Neurologic, muscular, bony, connective tissue, and vascular structures can be affected. We present the case of monochorionic triplets with bilateral congenital idiopathic talipes equinovarus deformities. To the best of our knowledge, such a presentation has not been previously described and supports a genetic etiology of congenital idiopathic talipes equinovarus deformity.

Extrauterine growth retardation (EUGR) seriously affects premature newborns and is related to the impairment of growth during childhood. There are very limited data available concerning the growth outcome of EUGR children. Our aim was to assess the growth outcome in a cohort of children born before 34 weeks of gestation with severe EUGR. This was a retrospective multicenter study, performed in outpatient endocrinology clinic. A total of 103 premature children with weight and/or length below −2 standard deviation score (SDS) of “intrauterine” growth expectation at the time of discharge from hospital (within 42 weeks of postmenstrual age) were included in the study. The study participants underwent a thorough anthropometric assessment at a mean age of 3.9 years ± 1.7 SD. Of the EUGR children, 12.6 % showed a height below −2 SDS and 7.7 % even below −2.5 SDS. Growth impairment was more common in males than in females (17 vs. 8 %). The prevalence of subnormal weight (below −2 SDS) was 13.6 %, being higher in males than in females (17 vs. 10 %). BMI values below −2 SDS were found in 18.4 % of our study population (22.7 % in males and 12 % in females). The 19.6 % of EUGR children did not catch up in head circumference during early childhood. Length at term was the major predictor of height in childhood (P

Objectives To compare breastfeeding rates at discharge for very preterm infants between European regions and neonatal units, and to identify characteristics associated with breast feeding using multilevel models. Methods Population-based cohort of 3006 very preterm births (2231 weeks of gestation) discharged home from neonatal units in eight European regions in 2003. Results Breastfeeding rates varied from 19% in Burgundy to 70% in Lazio, and were correlated with national rates in the entire newborn population. Women were more likely to breast feed if they were older, primiparous and European; more premature, smaller and multiple babies or those with bronchopulmonary dysplasia were breast fed less. Variations across regions and neonatal units remained statistically significant after adjusting for maternal, infant and unit characteristics. Conclusion It is possible to achieve high breastfeeding rates for very preterm infants, but rates varied widely across regions and neonatal units throughout Europe.

Objective: To investigate trigeminal small-fibre function in patients with diabetes mellitus. Methods: In 52 diabetic patients we studied the trigeminal laser evoked potentials after stimulation of the skin bordering the lower lip. In the 21 patients with the severest peripheral nerve damage we also studied the electrically evoked corneal reflex, Both responses are mediated by small myelinated afferents. Results: Laser evoked potentials had a longer mean latency and lower amplitude in diabetic patients than in normal subjects (P < 0.005). The abnormality frequency of the laser evoked potentials correlated with the severity of polyneuropathy (P < 0.005). In contrast, the corneal reflex was normal. Conclusion: Dysfunction of small afferents of the mandibular nerve is frequent in patients with diabetic polyneuropathy, We speculate that the primary cause could be segmental demyelination. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.

Objective : To verify whether laser evoked potentials are useful in assessing the function of small afferent fibers and to compare dysfunction of large and small afferent fibers in patients with diabetic polyneuropathy. Methods : The brain potentials evoked by CO 2 laser stimulation of the hand and foot were studied in diabetic patients ( n =45) with various degrees of peripheral nerve damage. Laser evoked potentials (which assess the function of small myelinated afferents) were also compared with ulnar and sural nerve sensory action potentials (which assess the function of large myelinated afferents) by scoring the abnormalities of the two neurophysiological tests with similar criteria. Results : Laser evoked potentials were often absent; the mean latency was normal and mean amplitude decreased, as expected in axonopathies. Although clinical examination showed more frequent impairment of vibratory than pinprick sensation, laser evoked potentials and sensory action potentials yielded similar abnormality scores and showed a strong intra-individual correlation. Conclusions : Laser evoked potentials, possibly better than standard clinical examination for assessing the abnormalities of small-diameter afferents, indicate that diabetic polyneuropathy induces large- and small-afferent dysfunction in parallel.

Idiopathic focal hand dystonia (FHD) arises from abnormal plasticity in the primary motor cortex (M1) possibly reflecting abnormal sensori-motor integration processes. In this transcranial magnetic stimulation (TMS) study in FHD, we evaluated changes in motor evoked potentials (MEPs) after intermittent theta burst stimulation (iTBS) and paired associative stimulation (PAS), techniques that elicit different forms of experimentally-induced long-term potentiation (LTP)-like plasticity in M1. We also examined behaviorally-induced LTP-like plasticity as reflected by early motor learning of a simple motor task. We studied 14 patients with FHD and 14 healthy subjects. MEPs were recorded before and after iTBS and PAS at the 25 ms interstimulus interval (PAS25) in separate sessions. Subjects did a simple motor task entailing repetitive index finger abductions. To measure early motor learning we tested practice-related improvement in peak velocity and peak acceleration. In FHD patients iTBS failed to elicit the expected MEP changes and PAS25 induced abnormally increased MEPs in target and non-target muscles. In the experiment testing early motor learning, patients lacked the expected practice-related changes in kinematic variables. In FHD, the degree of early motor learning correlated with patients' clinical features. We conclude that experimentally-induced (iTBS and PAS) and behaviorally-induced LTP-like plasticity are both altered in FHD.

Aim. To evaluate whether synchronized-NIPPV (SNIPPV) used after the INSURE procedure can reduce mechanical ventilation (MV) need in preterm infants with RDS more effectively than NCPAP and to compare the clinical course and the incidence of short-term outcomes of infants managed with SNIPPV or NCPAP.Methods. Chart data of inborn infants 2need >0.4, respiratory acidosis, or intractable apnoea that occurred within 72 hours of surfactant administration.Results. Eleven out of 31 (35.5%) infants in the NCPAP group and 2 out of 33 (6.1%) infants in the SNIPPV group failed the INSURE approach and underwent MV (). Fewer infants in the INSURE/SNIPPV group needed a second dose of surfactant, a high caffeine maintenance dose, and pharmacological treatment for PDA. Differences in O2dependency at 28 days and 36 weeks of postmenstrual age were at the limit of significance in favor of SNIPPV treated infants.Conclusions. SNIPPV use after INSURE technique in our NICU reduced MV need and favorably affected short-term morbidities of our premature infants.

BACKGROUND Abnormal complete blood count (CBC) and high plasma C-reactive protein (CRP) are associated with neonatal infections and could be helpful in the diagnosis of neonatal sepsis and to monitor the antibiotic treatment. OBJECTIVES The aim of this work is to evaluate and compare the performance of a bedside analyzer for blood count and C-reactive protein (CRP) with a conventional analyzer in a neonatal population. METHODS 150 capillary or venous blood samples of term and preterm newborns were processed on an ABX-MicrosCRP200 analyzer and on a SysmexXE2100 (conventional hematology analyzer) for CBC, leukocyte differential, reticulocytes, and nucleated red blood cells (NRBC); high-sensitivity CRP (hs-CRP) was performed on a ModularPE. The differences between complete blood count and CRP were regressed against their means and assessed by means of intra-class-correlation. RESULTS The intra-class-correlation for white blood cell (WBC) was 0.98, for hemoglobin 0.97, for hematocrit 0.96, for mean corpuscular volume 0.95, and for platelet 0.98. ABX-MicrosCRP200 overestimated the WBC (+1.27 x 10(3)/microL; p < 0.001), hematocrit (+1.80%; p < 0.001), and platelet (+13.55 x 10(3)/microL; p < 0.001). The intra-class-correlation for CRP was high (0.97), without systematic difference between the two values (p = 0.64). CONCLUSIONS The agreement between the two methods was high for both tests. However, the SD of the difference for WBC and platelet could be clinically important in leukopenic or thrombocytopenic newborns.

Neonatal transfer is necessary when a newborn baby needs care that cannot be provided in the referral centre. Since it represents an additional risk factor for a critically ill neonate [1, 2], it should be performed, when possible, by a well-organized neonatal transport service.

As the vitamin K content of human milk is low and the newborn infant's stores of vitamin K are small, vitamin K deficiency with hemorrhage in the newborn is a worldwide problem. Proteins Induced by Vitamin K Absence (PIVKA-II) are the inactive under-γ-carboxylated forms of vitamin K-dependent clotting factors and they could be useful in predicting subclinical vitamin K deficiency (VKD).To demonstrate that PIVKA-II are earlier markers of subclinical VKD than Prothrombin time (PT) in exclusively breast-fed newborns.A prospective, controlled, randomized study, including 53 term newborns receiving vitamin K prophylaxis (0.5 mg i.m.) at birth, was performed. At 30 days newborns were divided into three groups (G) receiving respectively: 25 μg/die of vitamin K (G I), 12 μg/die (G II) or placebo (G III). PIVKA-II and PT were measured on 30th and 90th days of life.G III and GII showed a significant increase in PIVKA-II from 30 to 90 days of life respectively from 2.6 to 4.7 (p = 0.001) and from 2.3 to 3.5 (p0.001). No significant changes were found in GI. PT showed no significant changes among groups.PT is a less sensitive marker than PIVKA II. Oral supplementation with 25 μg/die avoids an increase of PIVKA-II. Despite increased PIVKA-II do not mean an impending occurrence of bleeding, they highlight a subclinical VKD and its relative risk.

We examined the motor performance of Parkinson's disease patients and normal subjects during nonrepetitive and repetitive sequential tasks. Parkinson's disease patients took longer than normal subjects to complete the nonrepetitive task, the sequential drawing of a pentagon. In patients, movement times lengthened as the sequence neared completion. The amount of lengthening was similar in nonrepetitive and repetitive tasks (sequential alternating drawing of each side of the pentagon). In parkinsonian patients the slowing at the end of the sequential tasks does not appear to be influenced by whether the sequential task involves nonrepetitive or repetitive movements.

Mechanical ventilation is often required by very preterm infants with respiratory failure, even if invasive respiratory support is related to lung injury and adverse neurologic outcomes. The exposure to mechanical ventilation should be therefore limited. Optimal extubation however remains challenging, as approximately 30% of intubated preterm infants fails attempted extubation due to poor respiratory drive, atelectasis, residual pulmonary function abnormalities or intercurrent illness. This review outlines the advantages of different weaning strategies that should be considered by neonatologists for current use to reduce unsuccessful extubation.

Background: A considerable local variability in the rate of bronchopulmonary dysplasia (BPD) has been recorded previously. Objectives: The objectives of the present study were to describe regional differences in the rate of BPD in very preterm neonates from a European population-based cohort and to further delineate risk factors. Methods: 4,185 survivors to 36 weeks’ postmenstrual age of 4,984 live-born infants born at 24+0–31+6 weeks’ gestation in 2003 (the MOSAIC cohort) in 10 European regions were enrolled using predefined structured questionnaires. Results: Overall median gestational age of preterms without BPD was 30 weeks (range 23–31), median birth weight 1,320 g (range 490–3,150) compared with 27 weeks (23–31) and 900 g (370–2,460) in those with BPD. The region-specific crude rate of BPD ranged from 10.2% (Italian region) to 24.8% (UK Northern region). Maternal hypertension, immaturity, male gender, small for gestational age, Apgar Conclusion: A wide variability of BPD between European regions may be explained by different local practices; the strongest association however was with degree of immaturity.

Aims: To evaluate to which extent pregnancies of very short duration ( Methods: Area-based study in the 57 maternity units of the Lazio Region (Italy), years 2003–2004, including: 1012 live births (gestational age 22–31 weeks), 261 fetal losses (22–31 weeks) and 209 induced abortions (22–25 weeks). Variables associated with access to a level III unit were evaluated through multivariable logistic regression models. Results: 83.7% of all pregnancies Conclusions: Regionalization of perinatal care in Lazio is not satisfactory. Concentration of high-risk deliveries in level III centers is good, but in utero transfer is insufficient. This study can help to define the effectiveness of different organizational systems on access to locally available perinatal facilities and to optimize general organizational patterns of perinatal care.

Evoked by electrical stimulation of the mental nerve, the masseter inhibitory reflex consists of an early and a late silent period (SP1 and SP2), which interrupt the voluntary electromyographic (EMG) activity in the masseter muscle. We recorded the masseter inhibitory reflex and measured its latency, depth of suppression, duration and recovery cycle to paired stimuli, in patients with Huntington's chorea, Parkinson's disease, dystonia, or unilateral masticatory spasm. In patients with Huntington's chorea the reflex data and recovery cycle were normal. In patients with Parkinson's disease or dystonia, although the reflex data were normal, SP2 recovered far more rapidly than it did in control subjects. This is possibly due to hypoactivity of an inhibitory control of the polysynaptic chain of ponto-medullary interneurons that mediate SP2. In patients with unilateral masticatory spasm, both SP1 and SP2 were absent. Suppression is probably absent because this involuntary movement originates at a point along the peripheral course of the nerve.

Sensory complaints in the area of the mandible and mouth often escape notice or remain undiagnosed. Using electromyographic recording of the trigeminal reflexes and motor responses, we sought trigeminal dysfunction in 50 patients with peripheral neuropathy, and tried to gain pathophysiological information on the mechanisms provoking trigeminal damage. Trigeminal reflex recordings (early and late blink reflex after supraorbital stimulation, early and late masseter inhibitory reflex after mental stimulation, and jaw jerk) disclosed abnormalities caused by sensory trigeminal neuropathy in 8 out of 15 patients with chronic inflammatory demyelinating polyneuropathy (CIDP), 13 out of 23 patients with severe diabetic polyneuropathy, and in none of 12 patients with mild diabetic polyneuropathy. Six patients had abnormal motor responses in facial or masseter muscles. The response affected most frequently was the masseter early inhibitory reflex (also called first silent period, SP1) after mental nerve stimulation, its latency being strongly delayed. We found these long delays not only in patients with CIDP, but also in diabetic patients with severe polyneuropathy. We conclude that peripheral polyneuropathies often cause subclinical damage to the trigeminal nerve, especially to its mandibular branch. We believe that the nerve fibers running along the alveolar-mandibular pathway are more exposed to damage because of their cramped anatomical route in the mandibular canal and below the internal pterygoid muscle and fascia.

The excitatory and inhibitory interneuronal pathways in the brainstem are tested by examining the blink reflex and the masseter inhibitory reflex, respectively. We studied the R2 component of the blink reflex and the SP2 component of the masseter inhibitory reflex and their recovery cycle in 56 patients with various forms of dystonia. In patients with cranial, cervical, and generalized dystonia, but not in patients with extracranial segmental dystonia, the recovery cycle of both reflexes was enhanced. The recovery cycle of R2 and SP2 can demonstrate subclinical changes in excitability of brainstem interneurons. The degree of enhancement of the recovery cycles did not correlate, however, with the severity of clinical facial muscle impairment. In addition, the recovery cycles correlated positively with each other, showing that excitatory as well as inhibitory interneuronal pathways in the brainstem are perturbed in dystonia. Study of the trigemino-facial and trigemino-trigeminal reflexes provides an objective tool for assessing functional abnormalities in dystonia.

15 infants weighing 501 to 1000 g, less than 4 h of age, who had received one dose of surfactant and required ventilation with mean airway pressure >4–6 cm H2O and FiO2 >0.25, and had an anticipated duration of ventilation greater than 48 h. Newborns were stratified by birth weight and prenatal steroid status, and then randomized to either HFOV or SIMV with tidal volume monitoring. Ventilator management for patients in both study arms was strictly governed by protocols that included optimizing lung inflation and blood gases, weaning strategies and extubation criteria.

Background: premature infants born near-term may develop severe idiopathic respiratory distress requiring mechanical ventilation (MV). Aim: 1) to ascertain whether, in moderately premature infants with severe respiratory distress, a single dose of surfactant given by rapid intubation and extubation may reduce the entity of the disease and thus avoid MV; 2) to investigate whether infections or pulmonary hypertension may be associated with failure of surfactant treatment. Population: neonates weighing >=1500g at birth (35–37 weeks GA) and presenting with idiopathic respiratory distress requiring an FiO2>=0.70 or an FiO2>=0.6 (Silverman score >=7) to maintain an SaO2 of 90–95%. Infants were treated with oxygen and NCPAP or NSIPPV (Giulia, Ginevri) if necessary. Before surfactant was administered, a bronchoalveolar lavage was obtained for microbiological studies and echocardiography was used to evaluate pulmonary arterial pressures. Results: 18 infants (mean BW 2808g, 2230–3530, 13/18 born by C/S) received surfactant (Curosurf, 100 mg/kg) at an average age of 19h (1–54). The majority of chest radiographs showed retained lung fluid while, in a few cases, granular opacification with air bronchogram or widespread opacification of both lungs was seen. There was a marked and sustained decrease in FiO2 in those infants in whom surfactant treatment succeeded (FiO2 preINSURE: 0.68±0.10; FiO2 postINSURE at 3h 0.30±0.06; at 6h 0.29±0.06; at 12h 0.29±0.07; at 24h 0.26±0.05; ANOVA p

Latash & Anson's explanation of bradykinesia in patients with Parkinson's disease and cocontraction in dystonic patients is intriguing. However, the proposed adaptive changes in the central nervous system do not fit well with both clinical and experimental evidence of motor impairment in these patients. In particular, we question the explanation of: (1) the role of postural reactions and spatial accuracy in bradykinesia, (2) certain abnormalities during the execution of sequential and simultaneous movements, (3) the sudden changes in mobility (ON and OFF) of Parkinsonian patients, and (4) the meaning of reflex circuitry changes in dystonia.

We compared simultaneous measurement of aortic, direct (Dir) and of indirect (Ind) systolic (S), mean (M) and diastolic (D) arterial pressure (AP) determined by an automatic oscillometric instrument (DINAMAP) in neonates with birthweight of 1000-3680 g. DINAMAP measurements were performed with cuffs of increasing width and length, recommended by the manufacturer for increasing arm circumference, and with a Standard sized cuff (2.5 X 15 cm), previously considered as suitable for neonates of any body size. In addition, we compared simultaneous measurements of Dir SAP and of Ind SAP determined by a Doppler technique and the Standard cuff. In DINAMAP SAP measurements with the Standard cuff, a statistically significant correlation between arm circumference and delta Ind-Dir SAP values (i.e. the difference between simultaneous Ind and Dir SAP measurements) was found. In DINAMAP MAP measurements with the cuff recommended for arm circumference, a statistically significant difference of the mean delta Ind-Dir MAP values was observed in infants whose arm was or was not completely encircled by the bladder of the cuff. In SAP as well as in MAP DINAMAP determinations, the overall error of measurement with the Standard cuff was smaller than with the recommended cuff. The Doppler method was found considerably more accurate than the DINAMAP method for the determination of SAP. In spite of these limitations, the DINAMAP method with the Standard cuff was considered to be reasonably accurate for the clinical determination of SAP and MAP, provided that several consecutive measurements are performed and averaged in order to minimize the error of measurement. When considering DAP measurements the error was so unacceptably high that the DINAMAP method cannot be recommended for clinical use. The need for a careful consideration of the cuff characteristics when evaluating new methods for the indirect measurement of AP in the neonate is emphasized.

Mechanical or electrical stimulations in the area of the mouth evoke two phases of inhibition in the masseter muscle (early and late inhibitory reflex, also called masseter silent periods). The question whether the afferents of the human masseter inhibitory reflex are nociceptive or non-nociceptive has not yet been settled. We showed that an innocuous stimulus, such as a fine jet of saline directed to the lips of healthy humans, evokes an early and a late masseter inhibitory reflex, similar to those following electrical stimulation. We measured the efferent and afferent delay of the masseter early inhibitory reflex in patients submitted to intracranial stimulation of the motor and sensory trigeminal root, and found that the reflex afferents belong to the intermediately-fast conducting fibre group.

The corneal reflex evoked by electrical stimulation of the corneal mucosa and the blink reflex evoked by electrical stimulation of the supraorbital nerve were recorded in 8 normal subjects. Habituation to repetitive stimulation and the recovery cycle to double shock were studied. The corneal reflex habituated significantly to repetitive stimulations at a rate of 0.2–1 Hz but was more resistant than the late component of the blink reflex (R2). There was a clear dissociation between the recovery of the corneal reflex and that of R2; the corneal reflex was again less affected by the preceding impulse. These results suggest that the corneal reflex is relayed through fewer intramedullary synapses than R2.

Recent advances in perinatal care have brought improvement in the survival rate of very low birth weight (VLBW) and asphyxiated newborn infants over the last decades. Nevertheless the incidence of major neuro-developmental abnormalities in these patients has remained relatively high.

Summary A method is described which facilitates the location of the tip of an umbilical venous catheter in the inferior vena cava near the right atrium by means of internal e!ectrocardio-scopy using standard umbilical catheters and cardiomonitoring equipment. Entering the atria was chiefly indicated by tall and peaked P waves. On withdrawal of the catheter, small and peaked P waves were elicited at a radiological position of the catheter tip between 0.5 cm above and 1.0 cm below the diaphragm, presumably corresponding to the inferior vena cava near the atrial inlet. The latter location was obtained in 38 (67%) out of 57 newborns undergoing the procedure. The present method is simple and accurate, and it is considered superior to methods used so far for the same purpose. The need for safety precautions against electrical hazards has been stressed.

An apparatus was deviced allowing to shift from CPAP breathing by nasal prongs to nasal IPPV upon activation of the alarm of bradycardia (HR 20 sec (0-13% vs 43-62%); higher minimum HR (m 68-75/min vs 53-58/min). In the remaining 2 infants no significant differences were observed.