Neuromuscular maturation in the neonate: Combined electroneurographic and ultrasonographic study.

BACKGROUND: The combined electroneurography and muscle ultrasound examination (ENG-USM) in adult patients showed a correlation between the compound motor action potential (CMAP) and muscular thicknesses (MT). No similar studies exist regarding the neonatal period. AIM: To evaluate the correlations between the maximum compound muscle action potential (CMAP) and maximum muscle thickness (MT) in term and premature newborns versus a group of young adults, as measured by combined electroneurography-ultrasonography (ENG-USM) to assess the stages. STUDY DESIGN: Observational cohort study. SUBJECTS: We studied 36 subjects (14 premature and 11 term infants, and 11 young adults), who underwent ENG-USM of the tibialis anterioris (TA) muscle. OUTCOME MEASURES: We measured: 1) Onset-Peak (O-P) and Peak-to-Peak (P-P) maximum CMAP; 2) maximum MT; and 3) MT at the detected maximum CMAP. RESULTS: The maximum CMAP in term newborns studied was about 1/3 of the mean value measured in the adults; the differences between O-P and P-P values of the term versus premature infants were not significant. We did not find a good correlation between maximum MT and maximum CMAP in the term (r = 0.63) newborns, contrary to what was found in preterms (r = 0.95) and in young adults (r = 0.98). CONCLUSION: Our ENG-USM study shows that in newborns, the site of innervation of the neuromuscular plaque does not correspond to MT since muscle growth is related to the period of development, and depends on the progression of the nerve terminal branches that go to innervate the same muscle.

Methods for analysis of brain connectivity: An IFCN-sponsored review.

The goal of this paper is to examine existing methods to study the "Human Brain Connectome" with a specific focus on the neurophysiological ones. In recent years, a new approach has been developed to evaluate the anatomical and functional organization of the human brain: the aim of this promising multimodality effort is to identify and classify neuronal networks with a number of neurobiologically meaningful and easily computable measures to create its connectome. By defining anatomical and functional connections of brain regions on the same map through an integrated approach, comprising both modern neurophysiological and neuroimaging (i.e. flow/metabolic) brain-mapping techniques, network analysis becomes a powerful tool for exploring structural-functional connectivity mechanisms and for revealing etiological relationships that link connectivity abnormalities to neuropsychiatric disorders. Following a recent IFCN-endorsed meeting, a panel of international experts was selected to produce this current state-of-art document, which covers the available knowledge on anatomical and functional connectivity, including the most commonly used structural and functional MRI, EEG, MEG and non-invasive brain stimulation techniques and measures of local and global brain connectivity.

Abnormal neurological soft signs in babies born to smoking mothers were associated with lower breastfeeding for first three months.

AIM: We examined associations between neurological alterations in infants born to smoking mothers and breastfeeding success at discharge and three months of age. METHODS: This 2016 study compared 35 normal weight infants born to smoking mothers at 37-41 weeks and 35 matched controls born to non-smoking mothers at the Maternity Hospital of Careggi University, Florence, Italy. Neonatal behaviour was evaluated using the neurological soft signs (NSS) component of the Graham-Rosenblith Scale. Breastfeeding variables were measured using the LATCH score that covers: breast latching, audible swallowing, type of nipple, mother's comfort and help they needed to hold their baby to their breast. A questionnaire on excessive crying and feeding was distributed at discharge, and further data were collected during a three-month telephone interview. RESULTS: At discharge, the infants born to smoking mothers had a significantly lower LATCH score and significantly poorer performance on several items of the NSS component than the controls. The LATCH score and number of NSS were inversely proportional. At the three-month follow-up only 57.1% of the smoking group infants were breastfeeding compared with 87.5% of the control infants (p < 0.01). CONCLUSION: Infants with smoking mothers displayed altered neurobehavioural profiles and had a difficult start to breastfeeding.

Gold biosorption by exopolysaccharide producing cyanobacteria and purple nonsulphur bacteria.

AIMS: This study was aimed at investigating the possible exploitation of phototrophic micro-organisms for the removal and the recovery of Au from Au-containing wastewaters deriving from a plating industry. METHODS AND RESULTS: A screening among ten phototrophic micro-organisms was carried out with pure solutions of Au to select the best strain in terms of metal uptake and selectivity. The direct use of the selected micro-organism on the Au-containing industrial wastewater was then carried out with the aim of assessing the potential of its use for the removal and the recovery of the precious metal from industrial wastewaters. CONCLUSIONS: This study showed the good potential of some exopolysaccharide-producing cyanobacteria as biosorbents for the recovery of Au from wastewaters of plating industries but also pointed out the need to design an efficient technology for the recovery of the metal from the biomass. SIGNIFICANCE AND IMPACT OF THE STUDY: The selection of good biosorbents for the recovery of gold from industrial wastewaters may open new perspectives to a green biotechnology so far considered too expensive for the mere treatment of wastewaters containing low valuable metals.

High-dose ibuprofen for patent ductus arteriosus in extremely preterm infants: a randomized controlled study.

Our aim was to assess the hypothesis that a high-dose regimen of ibuprofen is more effective than the standard-dose regimen in closing patent ductus arteriosus (PDA) without increasing adverse effects. Infants of gestational age <29 weeks, with respiratory distress syndrome (RDS) and echocardiographic evidence of significant PDA at 12-24 h of life, were randomized to receive a standard (10-5-5 mg/kg/day) or high-dose (20-10-10 mg/kg/day) course of ibuprofen. We studied 70 infants, 35 of whom received the standard dose of ibuprofen and the other 35 the high dose. Of the infants treated with the standard-dose regimen, 37% had persistent PDA as compared with 14% of those treated with the high-dose regimen (P = 0.03). No differences in the occurrence of adverse effects were observed between the two groups. The high-dose ibuprofen regimen is more effective than the standard-dose regimen in closing PDA in preterm infants <29 weeks of gestation without increasing the adverse effect rate.

Cerebral venous thrombosis treated with enoxaparin in an IUGR neonate with DIC.

BACKGROUND: The case of a term IUGR newborn who presented a cerebral vein thrombosis diagnosed by routine ultrasound brain scan, and confirmed by magnetic resonance imaging and magnetic resonance venography, is reported. A thrombosis of cortical cerebral veins and intracerebral haemorrhage in the right frontal paramedian region was observed. METHODS: Treatment with enoxaparin was started at the initial dose of 0.5 mg/kg subcutaneously every 12 h and then at 1.25 mg/kg per 12 h in order to obtain anti-factor Xa levels between 0.5 and 1.0 U/ml. After hospital discharge, enoxaparin was continued for 2 months with a lower dose (1.8 mg/kg/die). CONCLUSION: Treatment with enoxaparin was effective as demonstrated by a complete "restitutio ad integrum".

Cytokine-induced activation of glial cells in the mouse brain is enhanced at an advanced age.

Numerous neurological diseases which include neuroinflammatory components exhibit an age-related prevalence. The aging process is characterized by an increase of inflammatory mediators both systemically and in the brain, which may prime glial cells. However, little information is available on age-related changes in the glial response of the healthy aging brain to an inflammatory challenge. This problem was here examined using a mixture of the proinflammatory cytokines interferon-gamma and tumor necrosis factor-alpha, which was injected intracerebroventricularly in young (2-3.5 months), middle-aged (10-11 months) and aged (18-21 months) mice. Vehicle (phosphate-buffered saline) was used as control. After a survival of 1 or 2 days (all age groups) or 4 days (young and middle-aged animals), immunohistochemically labeled astrocytes and microglia were investigated both qualitatively and quantitatively. In all age groups, astrocytes were markedly activated in periventricular as well as in deeper brain regions 2 days following cytokine treatment, whereas microglia activation was already evident at 24 h. Interestingly, cytokine-induced activation of both astrocytes and microglia was significantly more marked in the brain of aged animals, in which it included numerous ameboid microglia, than of younger age groups. Moderate astrocytic activation was also seen in the hippocampal CA1 field of vehicle-treated aged mice. FluoroJade B histochemistry and the terminal deoxynucleotidyl transferase-mediated UTP nick-end labeling technique, performed at 2 days after cytokine administration, did not reveal ongoing cell death phenomena in young or aged animals. This indicated that glial cell changes were not secondary to neuronal death. Altogether, the findings demonstrate for the first time enhanced activation of glial cells in the old brain, compared with young and middle-aged subjects, in response to cytokine exposure. Interestingly, the results also suggest that such enhancement does not develop gradually since youth, but appears characterized by relatively late onset.

Role of oxidative stress as physiopathologic factor in the preterm infant.

Oxidative stress usually occurs when the production of damaging free radicals (ROS) and other oxidative molecules exceeds the capacity of the body's antioxidant defenses. This process is supposed to begin after the delivery, but it can even affect the fetus when maternal pregnancy diseases (i.e.: pre-eclampsia, eclampsia, maternal infections) occur and in the case of preterm delivery. Most living organisms have developed well integrated antioxidant defenses to prevent the potential negative role of the ROS, in order to scavenge them and to control their concentration. These mechanisms are deficient in preterm newborn. Many illnesses in preterm infants, including bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), brain injury such as hypoxic/ischemic encephalopathy, and intraventricular hemorrhage (IVH) are thought to be related to the action of ROS. This presumably occurs due to the fact that the antioxidant system of preterm infants is at the same time highly stressed and incompletely developed. Unfortunately, the clinical trials which tried to prevent oxidative stress using antioxidant agents failed their objective and therefore they cannot be considered as an effective therapy. The objective of this review is to clarify the role of oxidative stress in the development of the previous severe diseases in preterm infants, and its possible correlation with hyperbilirubemia.

Effect of blood transfusions on oxidative stress in preterm infants.

OBJECTIVE: To confirm the increase in non-transferrin bound iron (NTBI) after packed red cell (PRC) transfusion and to evaluate the association with increased oxidative stress in preterm infants. METHOD: Twenty healthy preterm infants (gestational age 28.2 (2.2) weeks; birth weight 1047 (230) g), who required blood transfusion for anaemia of prematurity were prospectively studied. Serum concentrations of NTBI, total hydroperoxides (TH), and protein SH groups, and plasma total radical trapping antioxidant capability (TAC) were measured within three hours before and after PRC transfusion. The infants were transfused with 38.6 (23) ml PRCs over 5.8 (1.0) hours, at a mean age of 43.3 (25.1) days. RESULTS: After PRC transfusion, haemoglobin concentration increased from 9.2 (1.1) to 14.6 (1.5) g/l. Mean plasma NTBI concentration after transfusion was significantly higher (0.43 (0.45) v 2.03 (1.31) micromol/l; p = 0.001), while plasma concentrations of TH (212.3 (42.2) v 214.7 (66.3) Carr units/l) and protein SH groups (317.5 (38.8) v 353.8 (57.4) micromol/), and TAC (256.3 (36.1) v 267.1 (42.4) micromol HClO/ml) remained unchanged. CONCLUSION: For three hours after PRC transfusion, plasma NTBI is significantly increased in preterm infants, but this is not associated with significant changes in oxidative stress.

Plasma bilirubin level and oxidative stress in preterm infants.

OBJECTIVE: To assess the hypothesis that changes in plasma total bilirubin levels (Btot) can influence the antioxidant system and oxidative stress in preterm infants. METHODS: Twenty two healthy preterm infants who presented with visible non-haemolytic hyperbilirubinaemia were studied at the mean (SD) age of 3.7 (1.5) days. Btot, plasma total hydroperoxide concentration (TH), plasma protein SH group concentration, and total antioxidant capacity of the plasma (TAC) were measured at study entry and after 24 hours. RESULTS: Btot did not correlate with TH, TAC, or protein SH group concentration, but a significant correlation was found between TH and TAC, TH and protein SH groups, and TAC and protein SH groups, both at study entry and after 24 hours. CONCLUSION: The decrease in plasma bilirubin was contemporary with an increase in plasma antioxidant capacity and decrease in oxidative stress in preterm infants. This may be the result of the pro-oxidant effect of haem oxygenase, mediated by iron release, which may outcompete the antioxidant properties of bilirubin.

Effect of blood transfusions on cerebral haemodynamics in preterm infants.

AIM: To assess the possible cerebral haemodynamic changes occurring in preterm infants after blood transfusions. METHODS: Preterm infants who had undergone blood transfusions were prospectively studied using both near infrared spectroscopy and cerebral Doppler ultrasonography. RESULTS: Fourteen infants (mean gestational age 29.6 wk, SD 2.6; mean birthweight 1,430g, SD 332) were studied at the mean age of 29 (SD 14) d. A significant increase in oxygenated haemoglobin (O2Hb), deoxygenated haemoglobin (HHb), mixed cerebral oxygen saturation (SmO2) and change in cerebral blood volume occurred after transfusion. Between ultrasound parameters, we found a decrease in diastolic velocity and an increase in resistance index. CONCLUSION: Blood transfusions improve cerebral oxygen supply and induce a decrease in cerebral blood volume, probably due to an increase in cerebral vessel resistance.

Haemodynamic changes in the brain after vaginal delivery and caesarean section in healthy term infants.

OBJECTIVE: To investigate whether the mode of delivery may affect neonatal cerebral haemodynamics during the first hour of life. DESIGN: Prospective study. SAMPLE: Healthy infants with gestational age > or =37 weeks and birthweight appropriate for gestational age, born after uncomplicated pregnancy by vaginal delivery or elective caesarean section, two to five hours after the delivery. METHODS: Near infra-red spectroscopy was used to measure changes of oxygenated haemoglobin, deoxygenated haemoglobin, oxidized-reduced cytochrome aa3, and mean cerebral oxygen saturation (mixed cerebral oxygen saturation = oxygenated haemoglobin/total haemoglobin). Changes in cerebral blood volume were calculated. RESULTS: Near infra-red spectroscopy data did not show significant differences between infants born by vaginal delivery or by caesarean section. There was a significant decrease of oxygenated haemoglobin and change of cerebral blood volume values at 120 and 180 minutes in both the groups, while deoxygenated haemoglobin and oxidized-reduced cytochrome aa3 were unchanged. CONCLUSIONS: A decrease of cerebral blood volume occurs after birth and this occurs both in infants born by vaginal delivery and by caesarean section.

Pharmacokinetics of oxatomide in preterm infants.

The pharmacokinetics and tolerability of oxatomide oral suspension were investigated in preterm infants to evaluate the feasibility of planning a further study to assess its antiinflammatory effects and its effectiveness in preventing chronic lung disease (CLD). Following the administration of oxatomide 1 mg/kg, the peak plasma concentration (Cmax), the elimination half-life (t1/2), the volume of distribution (Vd), and the area under the curve (AUC) 0-36 h were measured and the following results were obtained: 42.2 +/- 15 ng/ml at 2 h after oxatomide administration, 41.4 +/- 2.0 h, 37.4 +/- 4.2 l/kg, and 468 +/- 52 ng/ml/h, respectively. Our study, therefore, demonstrated that a dose of 1 mg/kg/day oxatomide was effective in reaching therapeutic plasma levels in preterm infants without inducing adverse effects.

Role of ultrasound evaluation of nuchal translucency in prenatal diagnosis.

BACKGROUND: Nuchal translucency (NT) is the ultrasonographic pattern of the accumulation of subcutaneous fluid (> or = 3 mm) behind the fetal neck. The measurement of NT thickness by ultrasound examination at 11-14 weeks of gestation has been associated with maternal age and to be an effective screening tool for trisomy 21; with an invasive method rate of 5%, about 75% of trisomical pregnancies can be identified. With the association of some biochemical markers like maternal serum free beta-human chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A) to ultrasonography at 11-14 weeks, it is possible to identify about 90% of chromosomal abnormalities. An increase of NT also allows us to identify most other chromosomal abnormalities, a large number of major cardiac defects, skeletal dysplasias, and genetic syndromes. In monochorial twins the discordance in the measurement of NT represents an early sign of twin-to-twin transfusion syndrome (TTTS). METHODS: The objective of our study was to assess the detection of fetal structural defects with an ultrasound scan at 11-14 weeks of gestation. We submitted 3,157 pregnant women to a routine ultrasound examination at 11-14 weeks. The patients were then submitted to ultrasound scan in the second or third trimester of pregnancy. An isolated increased NT thickness was not considered an abnormality, but these patients, nonetheless, were submitted to an early echocardiographic evaluation. Fetal structural abnormalities were classified as major or minor and of early or late onset. RESULTS: A detection rate of 4.3% (135 cases) of abnormalities was found and 22.6% of these (30 cases) were diagnosed by ultrasound scan at 11-14 weeks, including seven cardiac defects associated with increased NT. The antenatal ultrasound detection rate was 73.5%, and 33.2% were diagnosed in the first trimester assessment. A rate of 76.8% of the major defects were diagnosed by the prenatal scan and 35.8% by the scan at 11-14 weeks. Fetal structural defects with the ultrasonography at 11-14 weeks were diagnosed in about 24.3% of the cases, therefore, a second trimester abnormality is important in routine antenatal care to increase the prenatal assessment of fetal anomalies. CONCLUSIONS: As for the introduction of every new technique in routine clinical practice, the operators who perform the ultrasound scan at 11-14 weeks should be submitted to adequate training and to strict quality control.

Paralytic ileus in a mechanically ventilated preterm infant treated with fentanyl.

The administration of fentanyl for sedation of ventilated newborns can induce several side-effects such as hypertension, respiratory muscle rigidity and, as shown in this report, decreased gastrointestinal motility. We report a case of paralytic ileus in a ventilated preterm infant who was given fentanyl in the first 24 hours of life. To our knowledge, the association of paralytic ileus with fentanyl has not been reported previously in full-term or preterm infants. This study indicates that early recognition is required to shorten the delay in diagnosis.

Influence of maternal magnesium sulphate and ritodrine treatment on cerebral blood flow velocity of the preterm newborn.

BACKGROUND: To evaluate the effect of antenatal tocolytic administration of magnesium sulphate and ritodrine on the cerebral blood flow velocity and on the cerebral vascular resistance of preterm newborns in the first hours of life. METHODS: Cerebral blood flow velocity, resistance index and relative vascular resistance were studied in 27 preterm infants (<34 weeks gestation) with antenatal exposure to maternal magnesium sulphate treatment and in 27 preterm infants (<34 weeks gestation) with antenatal exposure to maternal ritodrine treatment. Both antenatal magnesium sulphate or ritodrine were used for tocolysis. Cerebral blood flow was measured, using Doppler ultrasonography, in the anterior cerebral artery, in the left middle cerebral artery and in the right middle cerebral artery. RESULTS: We did not find any significant difference in the blood flow velocity, resistance index or relative vascular resistance in the three cerebral arteries between the two treatment groups. CONCLUSIONS: Our study shows that maternal antenatal administration of magnesium sulphate to delay preterm delivery, compared to antenatal administration of ritodrine, does not induce any significant differences either in cerebral blood flow velocity or in cerebral vascular resistance of preterm infants in the first hours of life.

Liquid ventilation in an infant with persistent interstitial pulmonary emphysema.

We present the case of a full term infant affected by diffuse persistent interstitial pulmonary emphysema (PIPE), who was treated with partial liquid ventilation (PLV) after the failure of conventional management. PIPE is a lethal chronic lung disease of unclear pathogenesis. Clinical history, radiological and histological findings confirmed the diagnosis in our patient. PLV applied for 48 hours resulted in a significant improvement in the infant's respiratory function and was not associated with adverse effects. We concluded that PLV could be effective in prolonging the survival of infants with PIPE; its application represents an effective form of respiratory support in infants with chronic lung disease.

Is breastfeeding really favoring early neonatal jaundice?

OBJECTIVE: The purpose of this study was to evaluate the development of significant hyperbilirubinemia in a large unselected newborn population in a metropolitan area with particular attention to the relationship between type of feeding and incidence of neonatal jaundice in the first week of life. STUDY DESIGN: A population of 2174 infants with gestational age >/=37 weeks was prospectively investigated during the first days of life. Total serum bilirubin determinations were performed on infants with jaundice. The following variables were studied: type of feeding, method of delivery, weight loss after birth in relationship to the type of feeding, and maternal and neonatal risk factors for jaundice. Statistical analyses were performed using the z test for parametric variables and the t test for nonparametric variables. In addition, the multiple logistic regression allows for the estimation of the role of the individual characteristics in the development of hyperbilirubinemia. Data concerning serum bilirubin peak distribution in jaundiced newborns were analyzed using a single and a double Gaussian best fit at least squares. The t test was performed to compare 2 values (high and low) of the serum bilirubin peak in breastfed and supplementary-fed infants with those in bottle-fed infants. RESULTS: The maximal serum bilirubin concentration exceeded 12.9 mg/dL (221 micromol/L) in 112 infants (5.1%). The study demonstrated a statistically significant positive correlation between patients with a total serum bilirubin concentration >12.9 mg/dL (221 micromol/L) and supplementary feeding; oppositely, breastfed neonates did not present a higher frequency of significant hyperbilirubinemia in the first days of life. However, best Gaussian fitting of our data suggests that a small subpopulation of breastfed infants have a higher serum bilirubin peak than do bottle-fed infants. Newborns with significant hyperbilirubinemia underwent a greater weight loss after birth compared with the overall studied population, and infants given mixed feeding lost more weight than breastfed and formula-fed newborns, indicating that formula has been administered in neonates who had a weight loss beyond a predetermined percentage of birth weight. Significant hyperbilirubinemia was also strongly associated with delivery by vacuum extractor, some perinatal complications (cephalohematoma, positive Coombs' test, and blood group systems of A, AB, B, and O [ABO] incompatibility) and Asian origin. Multiple logistic regression analysis shows that supplementary feeding, weight loss percentage, ABO incompatibility, and vacuum extraction significantly increase the risk of jaundice, while only cesarean section decreases the risk. CONCLUSION: The present study confirms the important role of fasting in the pathogenesis of neonatal hyperbilirubinemia, although breastfeeding per se does not seem related to the increased frequency of neonatal jaundice but to the higher bilirubin level in a very small subpopulation of infants with jaundice. In fact, in the breastfed infants, there is a small subpopulation with higher serum bilirubin levels. These infants, when starved and/or dehydrated, could probably be at high risk of bilirubin encephalopathy.