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Background: Recent studies explored the relationship between early brain function and brain morphology, based on the hypothesis that increased brain activity can positively affect structural brain development and that excitatory neuronal activity stimulates myelination. Objective: To investigate the relationship between maturational features from early and serial aEEGs after premature birth and MRI metrics characterizing structural brain development and injury, measured around 30weeks postmenstrual age (PMA) and at term. Moreover, we aimed to verify whether previously developed maturational EEG features are related with PMA. Design/Methods: One hundred six extremely preterm infants received bedside aEEGs during the first 72h and weekly until week 5. 3T-MRIs were performed at 30weeks PMA and at term. Specific features were extracted to assess EEG maturation: (1) the spectral content, (2) the continuity [percentage of spontaneous activity transients (SAT%) and the interburst interval (IBI)], and (3) the complexity. Automatic MRI segmentation to assess volumes and MRI score was performed. The relationship between the maturational EEG features and MRI measures was investigated. Results: Both SAT% and EEG complexity were correlated with PMA. IBI was inversely associated with PMA. Complexity features had a positive correlation with the cerebellar size at 30weeks, while event-based measures were related to the cerebellar size at term. Cerebellar width, cortical grey matter, and total brain volume at term were inversely correlated with the relative power in the higher frequency bands. Conclusions: The continuity and complexity of the EEG steadily increase with increasing postnatal age. Increasing complexity and event-based features are associated with cerebellar size, a structure with enormous development during preterm life. Brain activity is important for later structural brain development. [ABSTRACT FROM AUTHOR]

Objective: Early experience of pain and stress in the neonatal intensive care unit is known to have an effect on the neurodevelopment of the infant. However, an automated method to quantify the procedural pain or perinatal stress in premature patients does not exist. Approach: In the current study, EEG and ECG data were collected for more than 3 hours from 136 patients in order to quantify stress exposure. Specifically, features extracted from the EEG and heart-rate variability in both quiet and non-quiet sleep segments were used to develop a subspace linear-discriminant analysis stress classifier. Main results: The main novelty of the study lies in the absence of intrusive methods or pain elicitation protocols to develop the stress classifier. Three main findings can be reported. First, we developed different stress classifiers for the different age groups and stress intensities, obtaining an area under the curve in the range [0.78-0.93] for non-quiet sleep and [0.77-0.96] for quiet sleep. Second, a dysmature EEG was found in patients under stress. Third, an enhanced cortical connectivity and increased brain–heart communication was correlated with a higher stress load, while the autonomic activity did not seem to be associated to stress exposure. Significance: The results shed a light on the pain and stress processing in preterm neonates, suggesting that software tools to investigate dysmature EEG might be helpful to assess stress load in premature patients. These results could be the foundation to assess the impact of stress on infants' development and to tune preventive care. [ABSTRACT FROM AUTHOR]

Aim: Perinatal asphyxia is one of the most frequent causes of neonatal morbidity and mortality worldwide, and 96% of the burden of neonatal encephalopathy occurs in low-income countries. This study investigated the feasibility of providing neuroprotective treatment for neonatal encephalopathy in low-income countries.Methods: Neonates with a gestational age of at least 36 weeks, with signs of perinatal asphyxia, were included in this 2015 observational study in three hospitals in Kinshasa, capital of the Democratic Republic of Congo. Their characteristics were described, including the time to admission and Thompson score on admission.Results: We found that 42 of 134 patients (31.3%) reached the hospital within six hours of birth with a Thompson score of at least seven on admission. Another 15 patients (11.2%) had a five-minute Apgar score of up to five, without a Thompson score, and were eligible for treatment. Of the 57 (42.5%) eligible patients, 31 were discharged (54.4%), 25 died (43.9%) and one (1.8%) remained in hospital at the end of the study.Conclusion: Interventional studies are feasible and necessary, especially in countries where the burden of neonatal encephalopathy is largest. A Thompson score of 7-15 might be a useful entry criterion for neuroprotective treatment in low-income countries. [ABSTRACT FROM AUTHOR]

Brain injuries remain a significant problem for preterm infants, despite extensive physiological monitoring. Near infrared spectroscopy ( NIRS) monitoring in the neonatal intensive care unit has to date remained limited to research activities. Conclusion This review highlights the increasing clinical application of NIRS in delivery suites and neonatal units. Four randomised controlled trials incorporating NIRS monitoring suggest that the future may indeed be brighter for this technology in the care of very preterm infants. [ABSTRACT FROM AUTHOR]

Background Itch is an unpleasant feeling that leads to scratching. It is a common, but understudied, problem in patients with epidermolysis bullosa ( EB). Objectives We measured the prevalence and characteristics of itch in the three major forms of EB: generalized EB simplex ( EBS), junctional EB ( JEB) and dystrophic EB ( DEB). Methods Forty patients with EB were recruited from two tertiary care centres and one patient organization. The sample included 19 patients with EBS, seven with JEB and 14 with DEB. Patients completed the Leuven Itch Scale ( LIS), a multidimensional self-report instrument that quantifies the frequency, duration, severity, distress, consequences and surface area of itch. This instrument has good clinimetric properties. Results Itch occurred in 85% of the patients, with substantial differences across the subtypes ( EBS 74%, JEB 100%, DEB 93%). Itch, in all its dimensions, was most pronounced in patients with JEB and DEB, and less prominent in patients with EBS. The scores were significantly different for itch frequency, severity, distress and surface area, and the overall itch scores were comparable with those of atopic dermatitis. Itch mainly occurred in a hot environment (65%) and when sweating (62%). The most prevalent consequences were difficulty in falling asleep (88%) and lesions from scratching (85%). Differences between the three major subtypes were also observed in terms of circumstances, consequences and sensory characteristics. Conclusions As expected, itch is common among patients with EB. All aspects of itch measured by the LIS were more severe in JEB and DEB than in EBS. [ABSTRACT FROM AUTHOR]

Background: Extremely preterm babies (delivered at <28 completed weeks of gestation) are frequently diagnosed with hypotension and treated with inotropic and pressor drugs in the immediate postnatal period. Dopamine is the most commonly used first-line drug. Babies who are treated for hypotension more frequently sustain brain injury, have long-term disability or die compared to those who are not. Despite the widespread use of drugs to treat hypotension in such infants, evidence for efficacy is lacking, and the effect of these agents on long-term outcomes is unknown. Hypothesis: In extremely preterm babies, restricting the use of dopamine when mean blood pressure (BP) values fall below a nominal threshold and using clinical criteria to determine escalation of support ('restricted' approach) will result in improved neonatal and longer-term developmental outcomes. Research Plan: In an international multi-centre randomised trial, 830 infants born at <28 weeks of gestation, and within 72 h of birth, will be allocated to 1 of 2 alternative treatment options (dopamine vs. restricted approach) to determine the better strategy for the management of BP, using a conventional threshold to commence treatment. The first co-primary outcome of survival without brain injury will be determined at 36 weeks' postmenstrual age and the second co-primary outcome (survival without neurodevelopmental disability) will be assessed at 2 years of age, corrected for prematurity. Discussion: It is essential that appropriately designed trials be performed to define the most appropriate management strategies for managing low BP in extremely preterm babies. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Cefazolin (CFZ) is highly and saturably bound to human serum albumin (HSA) in adults. We aim to describe CFZ protein binding and its covariates in neonates. In neonates to whom intravenous CFZ (50 mg/kg) was administered prior to a surgical procedure, total and unbound CFZ plasma concentrations (mg/l) were determined at 0.5, 2, 4 and 8 h after CFZ administration. Linear and multiple regression analyses were used to document covariates of unbound CFZ fraction. The Wilcoxon signed-rank test was used for the paired analysis of unbound CFZ fractions. In 40 patients with a median weight of 2,767 (range 830-4,200) g and a postmenstrual age (PMA) of 39 (25-45) weeks, 131 samples were collected. The median unbound CFZ fraction was 0.39 (0.10-0.73). Linear regression of unbound CFZ fraction versus unbound CFZ plasma concentration ( R = 0.39) had a slope significantly different from zero ( p < 0.001). In a multiple regression analysis, albuminaemia, total CFZ concentration, indirect bilirubinaemia and PMA resulted in an R value of 0.496. The median unbound CFZ fraction at the peak concentration (0.46, range 0.28-0.69) was significantly higher compared to the trough level (0.36, range 0.17-0.73) ( p < 0.001). The between- and within-patient saturability of CFZ plasma protein binding were documented in neonates. The median unbound CFZ fraction in neonates is higher than in adults and depends partly on albuminaemia, total CFZ concentration, indirect bilirubinaemia and PMA. Integration of CFZ protein binding in future pharmacokinetic/pharmacodynamic research is warranted in order to optimise neonatal CFZ dosing. We recommend protein binding assessment in the neonatal pharmacokinetic evaluation of highly protein-bound or clinically relevant drugs. [ABSTRACT FROM AUTHOR]

Aim: Surgical patent ductus arteriosus (PDA) ligation is considered after failure or contraindication of medical treatment. Till now ligation of the PDA has been associated with low morbidity and mortality although recently concerns have been raised about the possible association of ductal clipping and neurodevelopmental abnormalities later in life. By means of near-infrared spectroscopy (NIRS), we analysed the changes in the cerebral tissue oxygenation index (TOI) and fractional tissue oxygen extraction (FTOE) at the time of clipping as well as after clipping. Method: Ten preterm infants with a symptomatic PDA who underwent surgical ligation were continuously monitored for heart rate (HR), mean arterial blood pressure (MABP), peripheral oxygen saturation (SaO2) and TOI from 1 h before up to 1 h after clipping. FTOE and haemoglobin difference (HbD) were calculated. Changes in parameters at 5 min after ligation represent the effect of the clipping itself whereas changes up to 1 h-post-clipping represent the post-clipping effect. Results: At the exact time of clipping, over the entire group, we found a significant increase in TOI of 2.9% (p = 0.037), in HbD of 12.5 μmol/l (p = 0.047) and in HR of 6.5 bpm (p = 0.012). FTOE significantly decreased by 0.02% (p = 0.013). One hour post-clipping, the cerebral and peripheral parameters were not significantly different from the control values before clipping. Conclusion: The ductal clipping in se has no negative effect on the cerebral oxygenation. [ABSTRACT FROM AUTHOR]

The tissue oxygenation index (TOI), measured by spatially resolved spectroscopy (SRS), reflects the ratio between oxygenated and deoxygenated tissue hemoglobin. We investigated whether liver TOI is a noninvasive parameter for early detection of intestinal ischemia. In seven adult New Zealand rabbits the superior mesenteric artery (SMA) and vein were exposed by laparotomy. The SRS probe was attached at the skin above the liver to calculate the TOI. The bowel (SbO2) and peripheral (SpO2) oxygen saturation were continuously measured. The SMA was occluded, creating small bowel ischemia for 90 minutes. Then reperfusion was started for 1 hour. The median TOI and interquartile range (IQR) of the TOI were calculated. A paired Wilcoxon test was used to evaluate changes in the liver TOI and SpO2 during ischemia and reperfusion. The median TOI was 54.3% (IQR 8) at the start of ischemia, 54.9% (IQR 9) after 30 minutes, 51% (IQR 11) after 60 minutes, and 50.3% (IQR 10) after 90 minutes. The median TOI values were 46.3% (IQR 5) after 30 minutes of reperfusion and 41.2% (IQR 5) after 60 minutes. The decrease in TOI became significant ( p < 0.05) after 90 minutes of ischemia. The SpO2 was stable during the experiment. A significant decrease in liver TOI was seen after 90 minutes of occlusion of the SMA and is likely to be the consequence of bowel ischemia. The further decrease after reperfusion might reflect reperfusion injury. Liver TOI may be a new tool for noninvasive early detection of intestinal ischemia and reperfusion. Further study is needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Objective: To describe severe alarms on home-documented monitoring in infants born prematurely.Methods: In infants born at a post-menstrual age (PMA) less than 35 weeks, a polysomnography was performed before discharge. A heart rate less than 50 beats per minute (bpm) for more than 3 seconds or an apnea lasting for more than 15 seconds with a heart rate less than 60 bpm were defined as abnormal. These babies were given cardiorespiratory home monitoring with memory. Serious alarms on the home monitor were defined as heart rate less than 50 bpm for more than 3 seconds.Results: Of 1058 infants, 96 infants needed cardiorespiratory home monitoring. Sixty-one infants showed alarms at home. The mean post-conceptional age (PCA) when alarms stopped was 46 weeks. Seventeen patients had serious alarms above the PCA of 50 weeks. There was a significant negative correlation (r = -0.46 and p = 0.0002 by Spearman's rank correlation) between the PMA at birth and the PCA at which the last alarm was notedConclusion: Prematurely born infants with an abnormal polysomnography at discharge are at high risk for developing acute events at home. A younger PMA at birth correlates with a higher risk of alarms at a later PCA. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To document pain expression characteristics in former preterm infants in the first year of life in whom systematic evaluation and treatment of pain was provided. METHODS: Data on the Modified Behavioral Pain Scale (MBPS), Visual Analogue Scale (VAS, crying time and heart rate were collected during immunization. The effect of clinical characteristics {postconception and gestational age [PCA], surgery, ventilation, fentanyl, length of stay (LOS)} on bio-behavioral parameters was evaluated. RESULTS: 121 procedures were recorded in 49 infants. GA was 28 (25-32) weeks. PCA was 60 (34-90) weeks. Median MBPS was 8 (2-10), median crying time 44 (0-112) s. Median pre-procedural heart rate was 144 (103-201) and increased to 184 (147-220) afterwards, resulting in a relative increase of 29 (5-99)%. Median VAS score was 7 (1-10). Significant correlations of PCA with pre-procedural heart rate (r=-0.36) and with relative increase in heart rate (r=0.33) were identified. A correlation of LOS on crying time (r=0.37) was observed. CONCLUSIONS: Correlations of PCA with pre-procedural and relative increase in heart rate reflect the maturational decrease in heart rate. LOS had an effect on pain expression, potentially reflecting the impact of cumulative 'minor' procedural pain. [ABSTRACT FROM AUTHOR]

Objective. To develop a safe and accurate method for the administration in the neonatal intensive care unit of several potent medications as a continuous infusion without overloading the infant, especially the very low birth weight (VLBW) infant by diluents. Method. The method designed is based on a weight-adapted solution limiting the diluent administration and allowing for a versatile modulation of dose administration. As this method was initially designed for VLBW infants, the point of departure of this method is a standard maximal fluid load of 0.3 ml/h for each medication, delivered in a low compliant circuit with a high-precision syringe driver. Solutions are made for 24 h, which is a compromise between drug stability and repeated pressure drops in the circuit when changing the syringe and administration set. To translate a prescription into a solution a conversion factor is calculated. In addition to the calculation principle, this conversion factor is given for a number of commonly used drugs in neonatal care. Conclusions. In our experience, the method described adds to the safety and accuracy of continuous drug administration in neonatal care. [ABSTRACT FROM AUTHOR]

: The aim of the study was the evaluation of the effect of methohexital during chest tube removal (CTR) in neonates. : Evaluation was based on the degree of sedation (grades 1–4) and relaxation (grades 1–4) and trends in vital signs heart rate, mean arterial blood pressure (MAP), oxygen saturation at time points (−10, −5, −3, −1, 0, 1, 3, 5, and 10 min) before and after administration of methohexital. A multidimensional pain scale [Leuven Neonatal Pain Scale (LNPS)] was used to evaluate pain expression. Effective sedation and relaxation (grade >2) would enable the physician to perform CTR without difficulties. Paired Wilcoxon was used to compare vital signs and pain expression before and after the procedure. : Twenty-two procedures in 22 infants were recorded. Eleven infants were ventilated and 21 infants were having intravenous analgesics during CTR. Birth weight was 2645 g (range 1235–4500 g). Postnatal age was 6 days (range 1–80 days). Methohexital had no effect on ventilatory weaning, MAP or oxygen saturation. Heart rate increased from 144 (49) to 162 (43) ( P = 0.012) b·min−1. Sedation and relaxation were effective (>grade 2) and lasted for <5 min. No major side effects were documented. Adequate analgesia by LNPS was more difficult to evaluate as clinical pain evaluation was not feasible during full muscular relaxation. : Administration of methohexital for CTR resulted in adequate sedation and relaxation without major side effects in neonates. This approach should be compared with other strategies. [ABSTRACT FROM AUTHOR]

Aim: To describe normal values of the cerebral tissue oxygenation index (TOI) in premature infants. Methods: TOI was measured by spatially resolved spectroscopy in preterm infants on the first 3 days of life. Infants with an abnormal cranial ultrasound were excluded. Other simultaneously measured variables were Pao2, Paco2, pH, mean arterial blood pressure, heart rate, haemoglobin, glycaemia, and peripheral oxygen saturation. Results: Fifteen patients with a median postmenstrual age of 28 weeks were measured. There was a significant increase in median TOl over the first 3 days of life: 57% on day 1, 66.1% on day 2, and 76.1% on day 3. Multiple regression analysis showed no correlation between TOI and postmenstrual age, peripheral oxygen saturation, mean arterial blood pressure, Pao2, Paco2, and haemoglobin concentration. Conclusion: Cerebral TOI increases significantly in the first 3 days of life in premature babies. This increase probably reflects the increase in cerebral blood flow at this time. [ABSTRACT FROM AUTHOR]

The more widely used divalent forms of iron (Fe2+) supplementation often lead to gastrointestinal symptoms in preterm infants although little is known about the use of nonionic trivalent iron preparations (FeIII) in these patients. It is especially under this nonionic form that dietary iron is available. For this reason, a randomized controlled study was undertaken to compare the efficacy and the extent of possible side effects in two groups of preterm infants. In one group, the elemental iron was given in the Fe2+form, while the other group received a nonionic trivalent iron (FeIII) complexed with polysaccharides of low molecular weight. Both groups received 7.5 mg elemental iron daily. Measured parameters in the two study groups did not differ significantly throughout the study period of 14 weeks. Both forms of iron supplementation were well tolerated. However, vomiting, diarrhea, or constipation occurred slightly more often in the group receiving iron supplementation in the Fe2+ form without reaching statistical difference. The authors found a nonionic trivalent polysaccharide-iron complex given as iron supplementation as effective as the generally more favored ferrous sulphate. Since iron therapy is mandatory in the preterm infant, the use of trivalent iron complexes can be considered as a good alternative. [ABSTRACT FROM PUBLISHER]

The effectiveness and safety of a short acting barbiturate, methohexital, was assessed for its use at the time of elective intubation in 18 newborn infants with severe respiratory or cardiac conditions. Evaluation included the speed of action and the degree of relaxation, sedation, and sleep in the first five minutes after administration. All newborn infants were intubated in a fully relaxed and somnolent state. In most infants recovery was completed within five minutes. A slight to moderate oxygen saturation drop was observed during the period of intubation, especially in patients with cyanotic heart disease. The side effects of the drug were twitching and a slight drop in blood pressure. In conclusion, methohexital seems to be a useful drug for short term anaesthesia in neonates, during which, short procedures like elective intubation can be safely performed. [ABSTRACT FROM AUTHOR]

The article focuses on the study about the maturation of 0-demethyl tramadol glucuronidation in a cohort of neonates and young infants. The research shows that 0-demethyl tramadol-glucuronide is the most abundant glucuronidated phase II metabolite. A significant effect of postnatal and postmenstrual age was observed. There is also a significant increase in glucuronidation with increasing postnatal age based on a fast maturation in the first week of postnatal life.

Aim: To investigate the effect of rewarming in preterm infants presenting with hypothermia at admission. Methods: The tissue oxygenation index (TOI), changes in cerebral blood volume (ΔCBV) and changes in intravascular oxygenation (ΔHbD) were measured in eight preterm infants, presenting with a temperature less than 35°C at admission. Results: A significant increase in HbD and TOI was seen in four patients (group A), while a significant increase in CBV and a decrease in HbD was seen in four other patients (group B). Retrospective analysis showed that group A had important signs of peripartal asphyxia. Conclusion: While infants with peripartal asphyxia showed an important increase in oxygenation during rewarming, no significant changes were seen in the non-asphyxiated infants. [ABSTRACT FROM AUTHOR]

Apnoea is a common sign in respiratory syncytial virus (RSV) infections in young infants and can be the first presentation of an acquired RSV infection. We describe polysomnographic recordings of three infants revealing prolonged RSV-related apnoea before RSV infection was diagnosed. The apnoeas were of central origin. The caregivers had not noted any apparent life-threatening events (ALTE) prior to the polysomnography. Cardiorespiratory monitoring after the acute infection did not reveal any further apnoeas. Conclusion: Central, prolonged apnoea can be the first sign of an acquired RSV infection in young infants in the absence of other respiratory symptoms and without any previous observation of apnoea by the caregivers. [ABSTRACT FROM AUTHOR]

Polysomnographic findings were compared with data obtained subsequently from home documented monitoring in order to study the diagnostic value of both techniques. Polysomnography was performed in 1274 infants born prematurely and in 422 patients admitted because of apparent life threatening events (ALTEs). In 72 of the infants, home documented monitoring of the cardiorespiratory pattern, including QRS complexes, was performed. Subsequent documented episodes of heart rate < 50 beats/min were considered as "serious life threatening events". It was confirmed that polysomnographic findings correlated well with subsequent events as registered by home documented monitoring. Especially in the ALTE group where both infants with and without abnormal polysomnography were home monitored, the single polysomnography significantly predicted subsequent life threatening events. Home documented monitoring of the cardiorespiratory pattern has a distinctive advantage over simple cardiorespiratory monitoring as a means to identify and document life threatening events, in addition to its value as a rescue device. [ABSTRACT FROM AUTHOR]

An abstract of the article "Intracranial hemorrhage in the fetal brain: prenatal diagnosis of 19 cases," by B. De Keersmaecker and colleagues is presented.

An abstract of the article "Subependymal cysts in the fetal brain: prenatal diagnosis of 12 cases," by B. De Keersmaecker and colleagues is presented.

Aim: To describe normal values of the cerebral tissue oxygenation index (TOI) in premature infants.Methods: TOI was measured by spatially resolved spectroscopy in preterm infants on the first 3 days of life. Infants with an abnormal cranial ultrasound were excluded. Other simultaneously measured variables were PaO(2), PaCO(2), pH, mean arterial blood pressure, heart rate, haemoglobin, glycaemia, and peripheral oxygen saturation.Results: Fifteen patients with a median postmenstrual age of 28 weeks were measured. There was a significant increase in median TOI over the first 3 days of life: 57% on day 1, 66.1% on day 2, and 76.1% on day 3. Multiple regression analysis showed no correlation between TOI and postmenstrual age, peripheral oxygen saturation, mean arterial blood pressure, PaO(2), PaCO(2), and haemoglobin concentration.Conclusion: Cerebral TOI increases significantly in the first 3 days of life in premature babies. This increase probably reflects the increase in cerebral blood flow at this time. [ABSTRACT FROM AUTHOR]

The effect of prophylactic administration of ibuprofen on the cerebral circulation in preterm babies was measured with near infrared spectroscopy. No significant difference in the change in cerebral blood volume, change in cerebral blood flow, or tissue oxygenation index was found between administration of ibuprofen or placebo. [ABSTRACT FROM AUTHOR]

An abstract of the article "Dural sinus malformation and giant lake with partial thrombosis at mid-gestation" by B. De Keersmaecker and colleagues is presented.

An abstract of the poster presentation "Sonographic evaluation of the developing pericallosal circulation between 11 and 22 weeks of gestation" by B. De Keersmaecker and others, at the 24th World Congress on Ultrasound in Obstetrics and Gynecology in Barcelona, Spain, is presented.

The article discusses the case of a 36-year-old gravida 3, para-2 who delivered a female baby with APGAR score of 1, 2 and 4 after 1, 5 and 10 minutes with arterial blood gas pH of 6.8. When transferred to a tertiary center, haemoglobin was at 4.9 gram per deciliter. The baby developed disseminated intravascular coagulation with profuse bleeding and died seven hours later. Postmortem examination revealed the cause of death as intrauterine thrombosis of the umbilical vein within the venous duct.

An abstract of the article "Outcome of antenatally diagnosed fetal arachnoid cyst," by B. De Keersmaecker and colleagues is presented.

An abstract of the conference paper "Maternal hyperoxygenation test in fetuses with congenital diaphragmatic hernia as a predictor of neonatal outcome," by E. Done and colleagues is presented.