Surfactant use in late preterm infants: a survey among Belgian neonatologists.

Specific recommendations on surfactant administration in late preterm (LPT) infants with pulmonary disease are lacking. We performed an online-based, nationwide survey amongst all (n = 102) Belgian neonatologists to identify the use of surfactant in LPT infants suffering from several respiratory pathologies. The survey used clearly defined clinical cases and resulted in a 86% response rate. Neonatologists adhere to the 200 mg/kg initial surfactant dosing scheme. Surfactant is widely used in respiratory distress syndrome (70.1%), but there is less unanimity on its use in meconium aspiration syndrome (58.0%), transient tachypnoea of the newborn (30.6%), congenital pneumonia (27.2%) and congenital diaphragmatic hernia (8.6%). Respondents adhere to the European guideline of a timely referral to a newborn intensive care unit (non-invasive ventilation and FiO2 > 0.30 at 12 h of age), in order to minimise the risk of deterioration.Conclusion: We demonstrate a wide variety in the use of surfactant within LPT infants. The majority of Belgian neonatologists therefore urge for an investment in multi-centre trials on surfactant administration in LPT infants, in order to create an evidence-based practice as well as to reduce the strain on health care budgets.Trial registration: https://clinicaltrials.gov What is Known: • Any late preterm (LPT) infant with respiratory distress needs a timely referral to a neonatal intensive care unit in case of non-invasive ventilation and FiO2 > 0.30 at 12 h of life, in order to minimise the risk of acute deterioration as well as chronic lung disease. • Any modest increase in morbidity in the sizeable group of LPT infants exerts a significant strain on health care budgets. What is New: • We report the attitudes and opinions of Belgian neonatologists about the use of surfactant in LPT infants suffering from several respiratory diseases. • Our survey demonstrates a significant variability in practice between neonatologists during treatment of respiratory pathologies in LPT infants. This highlights an urgent need for univocal therapeutic lines.

Congenital glucose-galactose malabsorption: a novel deletion within the SLC5A1 gene.

Glucose-galactose malabsorption (GGM) is an autosomal recessive disease caused by mutations in the Na(+)/glucose cotransporter gene SLC5A1 (OMIM 182380, phenotype number 606824). Patients with GGM present with neonatal onset of severe life-threatening diarrhoea and dehydration. We describe a 5-day-old girl with the typical clinical course of GGM. Our clinical diagnosis was confirmed by an abnormal chromatography of the stool and normal small bowel biopsies. Mutation analysis revealed a novel, homozygous deletion within exon 10 of the SLC5A1 gene, i.e. c.1107_1109 del AGT.

Validation of the continuous glucose monitoring sensor in preterm infants.

OBJECTIVE: Recent studies have highlighted the need for improved methods of monitoring glucose control in intensive care to reduce hyperglycaemia, without increasing the risk of hypoglycaemia. Continuous glucose monitoring is increasingly used in children with diabetes, but there are little data regarding its use in the preterm infant, particularly at extremes of glucose levels and over prolonged periods. This study aimed to assess the accuracy of the continuous glucose monitoring sensor (CGMS) across the glucose profile, and to determine whether there was any deterioration over a 7 day period. DESIGN: Prospectively collected CGMS data from the NIRTURE Trial was compared with the data obtained simultaneously using point of care glucose monitors. SETTING: An international multicentre randomised controlled trial. PATIENTS: One hundred and eighty-eight very low birth weight control infants. OUTCOME MEASURES: Optimal accuracy, performance goals (American Diabetes Association consensus), Bland Altman, Error Grid analyses and accuracy. RESULTS: The mean (SD) duration of CGMS recordings was 156.18 (29) h (6.5 days), with a total of 5207 paired glucose levels. CGMS data correlated well with point of care devices (r=0.94), with minimal bias. It met the Clarke Error Grid and Consensus Grid criteria for clinical significance. Accuracy of single readings to detect set thresholds of hypoglycaemia, or hyperglycaemia was poor. There was no deterioration over time from insertion. CONCLUSIONS: CGMS can provide information on trends in glucose control, and guidance on the need for blood glucose assessment. This highlights the potential use of CGMS in optimising glucose control in preterm infants.

Therapeutic hypothermia in neonatal asphyxia.

Hypoxic ischemic encephalopathy is a serious condition affecting newborn infants which can result in death and disability. There is now strong clinical evidence that moderate post-asphyxial total body cooling or hypothermia in full term neonates results in long-term neuroprotection, allowing us to proclaim this innovative therapy as "standard of care." The treatment is a time-critical emergency and should be started within 6 hours after the insult. Such -requires optimal collaboration among local hospitals, transport teams and the closest neonatal intensive care unit. The technique is only safe when applied according to published clinical trial protocols, and with admission of these patients to a neonatal intensive care unit. Future studies should be aimed at optimizing the onset, duration, and depth of hypothermia. Combination of hypothermia and drugs may further improve neuroprotection in asphyxiated full term neonates.

Perinatal inflammation and infection.

We here review the relation between feto-maternal and neonatal inflammatory/infective processes (e.g. chronic lung disease and necrotising enterocolitis) and their interaction with genetic and environmental factors. We also investigate the available evidence suggesting a link between perinatal inflammatory responses and neonatal (neuro)morbidity. Currently there does not appear to exist a silver bullet capable to prevent an impaired neurodevelopmental outcome in the event of a fetal and/or neonatal inflammatory response. A clear need thus exists for more epidemiology studies, using advanced techniques for laboratory research and neuro-imaging, with sufficiently long periods of follow-up. It is hoped that these studies will identify pre and postnatal inflammatory risk profiles, this through clarification of the relationship between inflammation markers and their expression in the fetal and neonatal circulation over time. Although such research will be complex, only then we may become successful in the development of new anti-inflammatory interventions in the newborn.

Fetal and neonatal inflammatory response and adverse outcome.

This article will define the concept of fetal/neonatal inflammatory response, and examine the complex interaction between inflammation and neurotoxicity. There appear to be important interactions between infection/inflammation and hypoxia-ischaemia leading to cytokine release and subsequent brain injury. This article will also define adverse outcome and summarize the complexities inherent to neurodevelopmental assessment. Finally, this article will investigate the currently available evidence suggesting a link between inflammatory response and adverse neurodevelopmental outcome, and focus on those variables that need further study: timing and nature of the infectious/inflammatory process; established and new anti-insult strategies; morbidity in organs other than the brain; genetic influences; and environmental factors.

Cerebral perfusion in infants and neonates: preliminary results obtained using dynamic susceptibility contrast enhanced magnetic resonance imaging.

BACKGROUND: Previous studies have used the dynamic susceptibility contrast enhanced (DSCE) magnetic resonance (MR) imaging technique to measure cerebral perfusion in adults. OBJECTIVE: To assess the feasibility of the technique in a heterogeneous cohort of sick human infants and identify cerebral perfusion abnormalities. METHODS: Perfusion measurements were made by characterising the changing concentration of an injected bolus of contrast agent using a series of MR images acquired during the first pass of the contrast bolus. Qualitative values of relative cerebral blood flow (rCBF) were then calculated from these data on a pixel by pixel basis to generate parametric maps of perfusion. RESULTS: Images of perfusion were successfully calculated from 12 out of 27 neonates and infants, all with established cerebral pathology. Normal vascular anatomical structures such as the circle of Willis were identified within all calculated images. Values of rCBF were generally larger in grey matter than in white matter. In several patients, perfusion abnormalities resulted in structural abnormalities which were detected in conventional MR imaging at follow up. The acquisition of perfusion data was most difficult when the least mature brains were examined because of motion artefacts and a smaller head size with a lower level of rCBF than adults. CONCLUSIONS: This preliminary study shows that: (a) maps of rCBF can be acquired from neonates and infants; (b) characterisation of the bolus passage becomes progressively easier as the brain matures; (c) early abnormalities in cerebral perfusion may have negative prognostic implications; (d) the main difficulty when using the DSCE technique to study neonates relates to image artefacts resulting from bulk head motion.

Magnetic resonance imaging of the infant brain: anatomical characteristics and clinical significance of punctate lesions.

OBJECTIVE: To describe the magnetic resonance imaging (MRI) characteristics of punctate brain lesions in neonates (number, appearance, distribution, and association with other brain abnormalities) and to relate them to neurodevelopmental outcome. METHODS: A retrospective analysis was performed of 110 MRI brain scans from 92 infants admitted in 1998 to the neonatal intensive care unit. Results of routine neurodevelopmental follow up (1998-2001) in those infants with punctate brain lesions were analysed. RESULTS: Punctate lesions were observed in 15/50 preterm and 2/42 term infants. In the preterm group, the number of lesions was < 3 in 20%, 3-10 in 27%, and > 10 in 53%. In 14/15 the lesions were linearly organised and located in the centrum semiovale. Other brain abnormalities were absent or minor--that is, "isolated" punctate lesions--in 8/15 and major in 7/15. In the term group, punctate lesions were organised in clusters and no other brain abnormalities were observed. Isolated punctate lesions were observed in 10/17 infants, and a normal neurodevelopmental outcome was seen in 9/10 (mean follow up 29.5 months). One infant showed a slight delay in language development. In the infants with associated brain lesions (7/17, mean follow up 27.5 months), outcome was normal in only two subjects. CONCLUSIONS: Punctate lesions are predominantly seen in preterm infants, are usually linearly organised, and border the lateral ventricles. Isolated punctate lesions may imply a good prognosis, because most of these subjects have a normal neurodevelopmental outcome so far.

The neural substrate of orientation short-term memory and resistance to distractor items.

We used Positron Emission Tomography to map the neural substrate of human short-term memory for orientation, defined as retaining a single orientation in memory over a long delay, by comparing a successive discrimination task with a 6-s delay to the same task with a brief 0.3 s delay and to an identification control task. Short-term memory engaged the superior parietal lobe bilaterally, the middle occipital gyrus bilaterally and the left dorsolateral prefrontal cortex. In addition, we studied the resistance to a distractor item by comparing the successive discrimination task with long delay, with and without an intervening distractor stimulus. This manipulative process engaged left ventral premotor cortex and left dorsolateral prefrontal cortex. The activation of left dorsolateral prefrontal cortex is interpreted as reflecting co-ordination between task components. These results, combined with those of two previous studies using an identical reduction strategy, underscore the functional heterogeneity in the prefrontal cortex during short-term and working memory.

The neural substrate of orientation working memory.

We have used positron emission tomography (PET) to identify the neural substrate of two major cognitive components of working memory (WM), maintenance and manipulation of a single elementary visual attribute, i.e., the orientation of a grating presented in central vision. This approach allowed us to equate difficulty across tasks and prevented subjects from using verbal strategies or vestibular cues. Maintenance of orientations involved a distributed fronto-parietal network, that is, left and right lateral superior frontal sulcus (SFSl), bilateral ventrolateral prefrontal cortex (VLPFC), bilateral precuneus, and right superior parietal lobe (SPL). A more medial superior frontal sulcus region (SFSm) was identified as being instrumental in the manipulative operation of updating orientations retained in the WM. Functional connectivity analysis revealed that orientation WM relies on a coordinated interaction between frontal and parietal regions. In general, the current findings confirm the distinction between maintenance and manipulative processes, highlight the functional heterogeneity in the prefrontal cortex (PFC), and suggest a more dynamic view of WM as a process requiring the coordinated interaction of anatomically distinct brain areas.

Cerebral maturation in premature infants: quantitative assessment using MR imaging.

BACKGROUND AND PURPOSE: The assessment of whether brain development is at an appropriate level for age has become an integral part of clinical MR reporting, although few studies have quantitatively defined the developmental changes occurring in premature infants. We have developed a simple scoring system to assess four parameters of cerebral maturation--myelination, cortical folding, glial cell migration, and germinal matrix distribution--to determine the total maturation score (TMS). The aim of this study was to validate this scoring system in a large population of preterm infants across a range of gestational ages. METHODS: A retrospective analysis was conducted of MR images acquired over a 3-year period with an identical imaging protocol. Infants born more than 14 days before the imaging examination and those with a clinical or radiologic history suggestive of neuroabnormality were excluded from the study. The TMS was derived by consensus. Interobserver agreement was evaluated by using the Bland-Altman plot. RESULTS: Images from 134 infants (23-41 weeks' gestational age) were evaluated. The TMS was significantly related to the postmenstrual age of the infant, with the mean TMS for each age group increasing with advancing postmenstrual age. Interobserver agreement was found to be high (mean difference in score = 0.07, SD = 0.56). CONCLUSION: This scoring system provides a standardized method for assessing cerebral maturation in the premature infant. The TMS is easy to calculate from standard MR images, is reproducible, and can help detect changes occurring within a postnatal age of a few weeks.

Post-resuscitative management of the asphyxiated term and preterm infant.

Up until the recent past, the treatment for perinatal asphyxia included only supportive measures. Babies were resuscitated and then observed for signs of multi-organ system dysfunction. Apart from standard supportive management, a new arsenal of potential neuroprotective strategies have emerged over the past years, in order to decrease the severity of brain injury following asphyxia. Today, several neuroprotective therapies are being evaluated in human infants.

Magnetic resonance and cranial ultrasound characteristics of periventricular white matter abnormalities in newborn infants.

OBJECTIVE: To characterize the range of abnormalities within the periventricular white matter (PVWM) in a cohort of newborns using magnetic resonance (MR) brain imaging and to compare the focal MR abnormalities with the cranial ultrasound (CUS) findings. METHODS: Retrospective study of MR brain and CUS findings of infants born in the 18-month period 1998-1999. PVWM abnormalities were identified by MR and focal lesions were characterized by size, number and distribution using a grading scale. Correspondence with CUS findings was assessed. RESULTS: 175 MR examinations corresponding to n = 105 preterm infants, (median GA 28, range 23-36 weeks) and n = 25 term infants (median GA 39, range 37-42 weeks) were analysed for PVWM abnormalities. In the preterm group, MR demonstrated a normal PVWM in n = 76, focal areas of altered signal intensity (SI) in PVWM in n = 26 and venous infarction in n = 3. In the term group, MR demonstrated a normal PVWM in n = 15, focal areas of altered SI in PVWM in n = 4, oedematous PVWM in n = 2 and a middle cerebral artery infarction in n = 4. All infants with normal MR had normal CUS findings. A focal PVWM SI abnormality detectable on MR corresponded with an abnormality on CUS in only n = 10/30. CONCLUSIONS: MR appears considerably more sensitive than CUS in demonstrating the existence and extent of focal PVWM lesions in newborn infants. Satisfactory correspondence between the two imaging investigations is obtained only for cystic PVWM lesions.

Separate neural correlates for the mnemonic components of successive discrimination and working memory tasks.

We have used positron emission tomography to map the mnemonic components of two tasks at the extremes of the visual short-term/ working memory spectrum. The successive discrimination task requires only storage of a single item for very short time (ultra-short- term memory), while the 2back task requires both maintenance (i.e. storage and rehearsal) and manipulation of several items (working memory). We tested whether or not the storage component, common to the two tasks, engaged the same cerebral regions. To remove unnecessary confounds, we reduced the cues available to the subjects to a single elementary attribute, the orientation of a grating presented in central vision. This prevented subjects from using verbal strategies or vestibular cues and allowed equating of difficulty among tasks. Ultra-short-term memory for orientation engaged a large expanse of occipito-temporal cortex with a rate-dependent antero-posterior gradient: a fast trial rate engaged posterior regions, a slow trial rate anterior regions. On the other hand, working memory for orientation involved the left inferior parietal cortex, left dorsolateral prefrontal cortex and a left superior frontal sulcus region, and to a lesser degree the symmetrical right superior frontal region and a left superior parietal region. Direct comparison of the two orientation memory networks confirmed their functional segregation. We conclude that at least the storage of orientation information engages distinct regions depending on whether or not short-term memory/working memory involves rehearsal and/or manipulative processes.

Regional brain activity during shape recognition impaired by a scopolamine challenge to encoding.

In the present positron emission tomography (PET) study, we examine the effect of a scopolamine-induced challenge to encoding upon the pattern of regional cerebral blood flow during recognition of a list of abstract visual shapes 3 days after encoding of these shapes. This study was conducted to test hypotheses concerning the fusiform and thalamic contributions to object recognition arising from a previous imaging study of impaired recognition. In that study, we demonstrated that activity in the fusiform cortex and the thalamus during shape recognition was modulated by memory challenges. These memory challenges included, on one hand, impaired storage as a consequence of diazepam administration during encoding, and, on the other hand, impaired retrieval caused by a perceptual challenge. Activation in the fusiform cortex decreased during impaired recognition, irrespective of the type of challenge. In contrast, thalamic activation increased only when the recognition deficit resulted from impaired memory storage. Based on these results, we hypothesized that fusiform activation during recognition reflects the matching of an incoming stimulus with a stored one, whereas thalamic activation reflects retrieval attempts. These hypotheses would receive considerable support if scopolamine, which also impairs memory storage, induced similar modulations of fusiform and thalamic activation. In the present study, we observed that a scopolamine challenge to encoding does indeed modulate the activity in the very same regions that were previously modulated by a diazepam challenge. Hence, a similar memory deficit, although primarily effected through different neurochemical pathways, was paralleled by a similar modulation of activity in the same set of nodes in the shape recognition network. In the fusiform cortex, scopolamine decreased recognition-related activity, as did the sensory challenge of retrieval. Furthermore, covariate analysis demonstrated that the level of fusiform activity linearly correlates with behavioural performance. In the thalamus, activation increased following impaired encoding. This is in accordance with the idea that enhanced thalamic activity reflects increased effort expended in retrieval. In addition, in the intraparietal sulcus, differential activation also increased following impaired memory storage, possibly reflecting enhanced visuospatial attention in an effort to compensate for impaired performance.

Tethered cord syndrome in occult spinal dysraphism: timing and outcome of surgical release.

OBJECTIVE: To investigate the influence of neurosurgical intervention on the appearance of upper motor neuron (UMN) signs in newborns diagnosed with occult spinal dysraphism and tethered cord (TC) during the first month of life. METHODS: A prospective study (1990 to 1996) of 22 consecutive newborns with occult spinal dysraphism monitored for the appearance of UMN signs. Untethering was performed when neurologic or urodynamic investigation indicated the presence of UMN dysfunction. RESULTS: Of 22 patients, 10 remained free of UMN symptoms during follow-up (mean, 67+/-22 months). Untethering was performed in 12 of 22 patients because of the presence of UMN symptoms. In 7 of these 12 patients, there was a documented asymptomatic period of 13+/-11 months before the onset of UMN symptoms. Untethering at a mean age of 18+/-17 months restored normal neurologic and urinary function in all patients (mean postoperative follow-up, 25+/-16 months). Of the 12 children, 5 presented with UMN signs at birth. In these children, untethering was performed at a mean age of 9+/-5 months. In two of these five patients, UMN symptoms did not resolve after surgery, and ongoing conservative bladder treatment was required (mean follow-up, 37+/-14 months). In none of the 12 operated children did signs of retethering occur. CONCLUSIONS: A significant number (10/22) of children born with occult spinal dysraphism and TC did not develop UMN symptoms during follow-up; neurosurgical correction after the appearance of an UMN sign restored normal neurologic and urinary function in all children; and untethering in children presenting at birth with UMN symptoms resulted in poorer outcome.