Early Brain Activity in Very Preterm Infants of Mothers with Gestational Diabetes Mellitus: A Pilot Study.

INTRODUCTION: Neurological consequences of preterm infants born to mothers with gestational diabetes mellitus (GDM) are unclear. In this pilot study, we investigated the effect of GDM on brain activity in very preterm infants. METHODS: Preterm infants <32 gestational weeks of mothers with GDM compared to gestational age- and sex-matched controls born between 2011 and 2018 were included. Amplitude-integrated electroencephalography (aEEG) was assessed for total maturation and individual component scores according to Burdjalov and colleagues, the dominating visual background, and the presence of sleep-wake cycles per hour in the first 72 h of life and weekly at days 7, 14, 21, and 28. RESULTS: We included 47 infants of mothers with GDM and 94 control infants. Both the aEEG total maturation score and its individual component scores, as well as the percentage of continuous background pattern, increased equally during the first 4 weeks after birth in both groups. GDM-exposed infants showed a slightly but significantly higher number of sleep-wake cycles per hour. CONCLUSION: We found normal maturation of brain activity in the first 4 weeks after birth in very preterm infants born to mothers with GDM, not differing from a very preterm control group. The higher number of sleep-wake cycles per hour in GDM-exposed infants could indicate transiently enhanced maturation. Further studies on brain activity and brain development in very preterm infants of mothers with GDM are needed to validate our results.

Relationship between Brain Function and Microstructural Brain Maturation in Preterm Infants.

INTRODUCTION: Preterm infants are at risk for impairment in brain maturation at term equivalent age (TEA). Diffusion tensor imaging (DTI) is a powerful magnetic resonance imaging (MRI) technique, quantitatively reflecting microstructural brain development of white matter regions with parameters such as fractional anisotropy (FA) and apparent diffusion coefficient (ADC). Amplitude-integrated electroencephalography (aEEG) assesses electrocortical activity and brain function. METHODS: Aim of this study was to investigate a possible correlation between functional and microstructural brain maturation using neonatal aEEG and DTI-MRI at TEA. The study was conducted as a retrospective single-center study in 446 infants born below 32 gestational weeks. Spearman rank's correlation coefficients were calculated between aEEG (total maturation score) and FA/ADC value. To compare aEEG and DTI-MRI to neurodevelopmental outcome at 24 months of corrected age, we performed a multivariate linear regression analysis. RESULTS: Analysis showed an all-time significant correlation between total maturation score and FA/ADC values of the corpus callosum at TEA with the strongest correlation at day 2, day 3, week 3, and week 4. After including perinatal variables in the model, this correlation remained highly significant at day 2 and 3. When comparing the association of aEEG and DTI-MRI to outcome, both the total maturation score at day 2, day 3, and FA/ADC of the splenium of the corpus callosum showed a significant correlation. CONCLUSION: This study indicates that early monitoring of functional brain maturation may predict later assessment of microstructural brain development of corpus callosum in preterm infants with a relation to neurodevelopmental outcome.

Association of aEEG and brain injury severity on MRI at term-equivalent age in preterm infants.

AIM: Measures to detect and monitor brain injury in preterm infants are amplitude-integrated electroencephalography (aEEG) and magnetic resonance imaging (MRI). To investigate the association between aEEG and MRI in a large cohort of preterm infants. Five hundred and twenty-three preterm infants were included in the study. METHODS: AEEG was interpreted for the total maturation score (TMS) according to Burdjalov. Cerebral MRI was evaluated using a validated scoring system by Kidokoro. RESULTS: One hundred and forty-six infants (27.9%) showed some form of brain injury, with 111 infants (21.2%) showing mild injury and 35 (6.7%) showing severe injury. TMS were significantly higher in infants without injury compared to severe injury. When comparing infants with isolated intraventricular haemorrhage  to infants without brain injury, TMS were significantly lower. CONCLUSION: Prediction of adverse outcome is an important aspect of neonatal care. The combination of diagnostic measures evaluating brain injury might enhance our abilities in neonatal care to provide accurate information about later outcome. Early aEEG is predictive for the severity of brain injury detected by MRI at term-equivalent age. Whether aEEG is also predictive for neurodevelopmental outcome needs to be further investigated in relation to the various patterns of preterm brain injury.

The Effect of Postnatal Cytomegalovirus Infection on (Micro)structural Cerebral Development in Very Preterm Infants at Term-Equivalent Age.

INTRODUCTION: There are some data indicating a negative impact of postnatal cytomegalovirus (CMV) infection on long-term neurodevelopmental outcome of preterm infants. So far, there is only little knowledge about a cerebral imaging correlate of these neurodevelopmental alterations induced by postnatal CMV infection in preterm infants. The aim of the current study was to investigate the effect of postnatal CMV infection on the incidence of brain injury and on microstructural brain maturation in very preterm infants at term-equivalent age. METHODS: Infants <32 gestational weeks (02/2011-11/2018) received cerebral MRI including axial diffusion-weighted images at term-equivalent age. All infants were screened for CMV infection using urine/saliva samples, and infection was regarded as acquired postnatal if a sample became positive >5 postnatal days. We compared brain injury as well as fractional anisotropy and apparent diffusion coefficient in 14 defined cerebral regions between infants with and without postnatal CMV infection. RESULTS: 401 infants were eligible, of whom 18 (4.5%) infants had a postnatal CMV infection. There were no significant differences in rates of brain injury or in microstructural brain development between both groups. This applied equally to the subgroup of infants <28 gestational weeks. CONCLUSION: Although infants with postnatal CMV infection were born more immature and more frequently suffered from complications related to immaturity, we neither observed a higher rate of preterm brain injury nor disadvantageous alterations in microstructural brain maturation at term-equivalent age.

Microstructural Brain Development and Neurodevelopmental Outcome of Very Preterm Infants of Mothers with Gestational Diabetes Mellitus.

INTRODUCTION: There are data linking gestational diabetes mellitus (GDM) with adverse neurodevelopmental outcome in the offspring. We investigated the effect of GDM on microstructural brain development and neurodevelopmental outcome of very preterm infants. MATERIALS AND METHODS: Preterm infants <32 gestational weeks of mothers with GDM obtained cerebral magnetic resonance imaging (MRI) including diffusion-tensor imaging at term-equivalent age. For every infant, two gestational age-, sex-, and MRI scanner type-matched controls were included. Brain injury was assessed and fractional anisotropy (FA) and apparent diffusion coefficient (ADC) measured in 14 defined cerebral regions. Neurodevelopmental outcome was quantified at the corrected age of 24 months using the Bayley Scales of Infant Development. RESULTS: We included 47 infants of mothers with GDM and 94 controls. There were no differences in neonatal morbidity between the groups, nor in any type of brain injury. The GDM group showed significantly higher FA values in the centrum semiovale, the posterior limb of the internal capsule and the pons bilaterally, in the corpus callosum and the right occipital white matter, as well as lower ADC values in the right centrum semiovale, the right occipital white matter and the corpus callosum. Neurodevelopmental outcome did not differ between the groups. CONCLUSION: We found no impairment of brain development in GDM-exposed infants compared to matched controls, but differences in white matter microstructure in specific regions indicating an enhanced maturation. However, neurodevelopmental outcome was equal in both groups. Further studies are needed to better understand brain maturation in preterm infants exposed to GDM.

Prophylactic low-dose paracetamol for ductal closure and neurodevelopmental outcome in very preterm infants.

AIM: To investigate the direct effect of prophylactic low-dose paracetamol administration for ductal closure on neurodevelopmental outcome in very preterm infants who did not receive ibuprofen or surgical ligation for treatment of a patent ductus arteriosus. METHODS: Infants < 32 gestational weeks born 10/2014-12/2018 received prophylactic paracetamol (paracetamol group, n = 216); infants born 02/2011-09/2014 did not receive prophylactic paracetamol (control group, n = 129). Psychomotor (PDI) and mental (MDI) outcome were assessed using Bayley Scales of Infant Development at 12 and 24 months corrected age. RESULTS: Our analyses showed significant differences in PDI and MDI at age 12 months (B = 7.8 (95% CI 3.90-11.63), p < 0.001 and B = 4.2 (95% CI 0.81-7.63), p = 0.016). At age 12 months, the rate of psychomotor delay was lower in the paracetamol group (OR 2.22, 95% CI 1.28-3.94, p = 0.004). There was no significant difference between the rates of mental delay at any time-point. All group differences remained significant after adjustment for potential confounders (PDI 12 months B = 7.8 (95% CI 3.77-11.34), p < 0.001, MDI 12 months B = 4.3 (95% CI 0.79-7.45), p = 0.013, PDI < 85 12 months OR 2.65 (95% CI 1.44-4.87), p = 0.002). CONCLUSION: We found no impairment of psychomotor and mental outcome at age 12 and 24 months in very preterm infants after prophylactic low-dose paracetamol administration.

Pituitary Stalk Interruption Syndrome - Clinical Presentation and Management of a Potentially Life-threatening Disease in Newborns.

Pituitary stalk interruption syndrome (PSIS) is a rare congenital disease resulting in hypopituitarism of variable degree. Serious courses, due to severe combined pituitary insufficiency, are even rarer and associated with a very early manifestation immediately after birth. First clinical signs are elusive and lead to delayed diagnosis and treatment, often resulting in life-threatening complications. Objective of the current report is to point out early leading symptoms and key issues of neonatal manifested PSIS to increase the awareness, improve the clinical management and thereby enable an early diagnosis and treatment to prevent further complications. This report presents and compares the clinical course and management of two male newborns with manifested PSIS. Early leading symptoms were the same in both patients, including recurrent hypoglycaemia, hyponatraemia, jaundice, cholestasis, sucking weakness and genital abnormalities. Patient 1 developed an infection-induced adrenal crisis, persistent substitution-dependent thrombocytopenia and convulsions due to severe hypoglycaemia in delayed PSIS diagnosis. In patient 2, due to recognised above-mentioned symptoms, endocrine testing and a subsequent cerebral magnetic resonance imaging were performed early and he was diagnosed and treated before major complications occurred. Genetic testing was performed in both patients. GLI2 gene mutation (NM_005270.5:c.2537del; p.(Pro846Argfs*66)) heterozygous was detected in patient 1. No mutation was found in patient 2. Conclusively, the early diagnosis of neonatal PSIS is indispensable in the treatment and prevention of the possible severe clinical manifestation of this orphan disease. Therefore, increased awareness for early leading symptoms and proper clinical management are crucial.

Prophylactic Low-Dose Paracetamol Administration for Ductal Closure and Amplitude-Integrated Electroencephalography in Preterm Infants.

Introduction: Prophylactic low-dose paracetamol administration is used to induce closure of the ductus arteriosus in preterm infants. In our recent study we found no impairment on microstructural maturation processes in the brain of preterm infants at term-equivalent age following prophylactic low-dose paracetamol administration. We now assessed amplitude-integrated electroencephalography (aEEG) signals in preterm infants with and without exposure to prophylactic low-dose paracetamol administration. Methods: Infants <32 gestational weeks born between 10/2014 and 12/2018 received prophylactic paracetamol (10 mg/kg intravenously every 8 h until echocardiography after at least 72 h) and form the paracetamol group; infants born between 02/2011 and 09/2014 formed the control group. Four single parameters (continuity, cyclicity, amplitude of lower border, bandwidth span) together with their sum (Burdjalov total score) and presence of sleep-wake cycles were compared between the groups. Results: Included in the study were 338 infants. Two-hundred and seventeen infants received prophylactic paracetamol and 121 formed the control group. The paracetamol group showed a significantly higher number of sleep-wake cycles per hour and a significantly higher total scores compared to the control group (p < 0.05). Conclusion: Paracetamol exposure has been regarded critically with respect to safety in preterm infants in recent years. We found no impairment on amplitude-integrated electroencephalography signals in preterm infants receiving low-dose prophylactic paracetamol compared to controls. Growing awareness and greater availability of data may encourage the clinicians to administer prophylactic paracetamol for ductal closure in preterm infants. The clinical relevance of our findings has to be evaluated in long-term follow up studies on neurodevelopmental outcome.

Prophylactic Low-Dose Paracetamol Administration for Ductal Closure and Microstructural Brain Development in Preterm Infants.

INTRODUCTION: Prophylactic low-dose paracetamol administration is used to induce closure of the ductus arteriosus. Effects on the neurological outcome in preterm infants remain unknown. We compared microstructural brain development in very preterm infants with and without exposure to prophylactic paracetamol by using MR-based diffusion tensor imaging. MATERIALS AND METHODS: Infants aged <32 gestational weeks born between October 2014 and December 2018 received prophylactic paracetamol (10 mg/kg intravenously every 8 h until echocardiography after at least 72 h) and form the paracetamol group; infants born between February 2011 and September 2014 form the control group. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) at term-equivalent age were measured in 14 defined cerebral regions and compared between the groups. RESULTS: Included in the study were 340 infants, of whom 217 received prophylactic paracetamol, and 123 formed the control group. The paracetamol group showed significantly higher FA values and lower ADC values in the splenium of the corpus callosum, as well as higher FA values in the pons bilaterally, the left middle cerebellar peduncle, the right occipital white matter, and the right posterior limb of the internal capsule (p ≤ 0.02). CONCLUSION: The perceived safety of prenatal paracetamol exposure has been questioned in recent years. We found no impairment on microstructural maturation processes in the brain of preterm infants at term-equivalent age following early paracetamol administration. The clinical relevance of these imaging findings has to be determined in long-term follow-up studies on neurodevelopmental outcome.

Amplitude-integrated electroencephalography signals in preterm infants with cerebral hemorrhage.

OBJECTIVE: To evaluate whether preterm infants with cerebral hemorrhage show alterations of aEEG signals in the first four weeks of life. STUDY DESIGN: Preterm infants (n = 536) born before 32 completed weeks of pregnancy at Innsbruck Medical University Hospital were included in the study. AEEG recordings were evaluated for the Burdjalov score and cerebral hemorrhage was diagnosed by cerebral ultrasound. RESULTS: Eighty preterm infants with cerebral hemorrhage (median gestational age 28.9 weeks, median birth weight 1157 g) and 456 preterm infants without cerebral hemorrhage (median gestational age 30.0 weeks, median birth weight 1300 g) were investigated. Burdjalov total scores were significantly lower in infants with cerebral hemorrhage. Infants with mild cerebral hemorrhage showed higher Burdjalov total scores compared to infants with severe cerebral hemorrhage in the first days of life. A Burdjalov total score of seven or more was predictive for no development of a cerebral hemorrhage, with a highest area under the curve (0.613) at postnatal day three. CONCLUSION: Preterm infants with cerebral hemorrhage show alterations in aEEG signals in the newborn period. In future aEEG could be used as a supplemental method to monitor preterm infants at risk for cerebral hemorrhage. The use of aEEG in early life could reduce the number of ultrasound examinations and limit cumulative stress and discomfort in preterm infants.

Supratentorial Brain Metrics Predict Neurodevelopmental Outcome in Very Preterm Infants without Brain Injury at Age 2 Years.

INTRODUCTION: Very preterm infants are at risk for adverse neurodevelopmental outcome. To better identify children without brain injury at risk for developmental sequelae, we assessed predictive values of supratentorial brain metrics in relation to outcome. METHODS: Very preterm infants underwent magnetic resonance imaging (MRI) at term-equivalent age. Infants with any grade of supra- or infratentorial brain injury according to Kidokoro et al. [Pediatrics 2014;134:e444-53] were excluded. Supratentorial brain metrics (biparietal width, extracerebral space, interhemispheric distance) were measured and categorised using existing cut-off values. The Psychomotor Developmental Index (PDI) and Mental Developmental Index (MDI) were assessed using the Bayley Scales of Infant Development, second and third edition, at 2 years of age. Developmental delay was defined as a score <85. Positive and negative predictive values for developmental delay were calculated. RESULTS: A total of 237 very preterm infants were enrolled. Of all infants, 59 (21.2%) showed developmental delay. Infants with z-scores less than -0.5 for biparietal width had significantly lower PDI (p = 0.039) and MDI (p = 0.042) than infants with normal z-scores. Enlargement of extracerebral spaces was also related to lower PDI (p = 0.047) and MDI (p = 0.036). Negative predictive value was highest when all brain metrics were within the normal range (PDI <85: 96.6%, MDI <85: 90.0%). Combining the biparietal width and the interhemispheric distance showed highest positive predictive values for developmental delay (MDI or PDI <85: 58.3%). DISCUSSION: Supratentorial brain metrics are predictive for neurodevelopmental outcome in infants with ostensibly normal MRI. A combination of supratentorial brain metrics is most meaningful for identifying infants at risk for long-term sequelae.

Reduced Cerebellar Size at Term-Equivalent Age Is Related to a 17% Lower Mental Developmental Index in Very Preterm Infants without Brain Injury.

INTRODUCTION: Cerebellar injury is increasingly recognized as a relevant complication of premature birth. However, the prevalence of reduced cerebellar growth and its consequences for neurodevelopmental outcome in preterm infants without overt brain injury remain to be defined in detail. The aim of this study was to assess the transcerebellar diameter (TCD) at term-equivalent age (TEA) in very preterm infants without brain injury and to evaluate whether TCD is related to neurodevelopmental outcome in this population. METHODS: Very preterm infants underwent magnetic resonance imaging at TEA. Infants with any grade of supra- or infratentorial brain injury were excluded. TCD was measured and categorized using existing cut-off values as normal TCD and mild or severe TCD reduction. Psychomotor Developmental index (PDI) and Mental Developmental index (MDI) were assessed using Bayley Scales of Infant Development II and III at a corrected age of 2 years. RESULTS: A total of 166 infants with a mean gestational age of 29.9 ± 1.8 weeks and a mean birth weight of 1,317 ± 393 g were included. Mean TCD of girls was significantly lower compared to the mean TCD of boys (p = 0.004). TCD reduction was present in 8 infants (4.8%). Infants with a mild TCD reduction achieved lower mean MDI than infants with normal TCD (p = 0.021). DISCUSSION: We found that reduced TCD was associated with a 17% lower mean MDI at a corrected age of 2 years. Thus, TCD at TEA may be used as an imaging marker for adverse cognitive outcome in the apparently low-risk group of preterm infants without brain injury.

Early preterm infants with abnormal psychomotor neurodevelopmental outcome at age two show alterations in amplitude-integrated electroencephalography signals.

INTRODUCTION: Recent studies showed that neurodevelopment in preterm infants can be predicted by using amplitude-integrated electroencephalography (aEEG)-derived parameters. In our previous study we demonstrated that aEEG could be useful in predicting neurodevelopmental outcome in very preterm infants at the corrected age of 2 years. AIM: The aim of this study was to further evaluate aEEG for predicting neurodevelopmental outcome at the at the corrected age of 2 years in preterm infants. METHODS: Between July 2010 and June 2016 440 very preterm infants were eligible for the study at Innsbruck Medical University Hospital. The aEEG was evaluated for the Burdjalov score in 306 preterm infants (mean gestational age 29.5 weeks; range: 24.1-31.9 weeks). At the corrected age of 2 years outcome was assessed by the Bayley Scales of Infant and Toddler Development. RESULTS: The cohort was divided into three subgroups: 248 infants with normal outcome, 40 infants with delayed outcome and 18 infants with abnormal outcome. Burdjalov scores were lower in infants with delayed outcome than in infants with normal outcome and even lower in infants with abnormal outcome. Post-hoc analysis showed significant differences between normal and delayed psychomotor outcome at 18-24 h (5 (3;6) versus 3 (3;5), p = .024), 30-36 h (6 (4;8) versus 4 (4;6), p = .033), 42-48 h (7 (5;8.5) versus 4 (4;7), p = .003), 54-60 h (7 (6;9) versus 5 (4;7), p = .003), 66-72 h (8 (6;9) versus 6.5 (4.25;7.75), p = .027) and week one (8 (7;10) versus 6.5 (5;8), p = .021). Additionally, when comparing normal to abnormal outcome, a significant difference was found at week four (12 (9;12) versus 8 (7;10), p = .024). The Burdjalov score was only predictive for a delayed psychomotor outcome, presenting the highest area under the curve (0.690) at week two of life. CONCLUSION: We observed differences in aEEG signals and neurodevelopmental outcome at the corrected age of 2 years, especially for psychomotor outcome. The predictive value of the Burdjalov score regarding neurodevelopmental outcome at the corrected age of 2 years in preterm infants was low.

Short-, Mid-, and Long-Term Effect of Granulocyte Colony-Stimulating Factor/Stem Cell Factor and Fms-Related Tyrosine Kinase 3 Ligand Evaluated in an In Vivo Model of Hypoxic-Hyperoxic Ischemic Neonatal Brain Injury.

Hematopoietic growth factors are considered to bear neuroprotective potential. We have previously shown that delayed treatment with granulocyte colony-stimulating factor (G-CSF)/stem cell factor (SCF) and Fms-related tyrosine kinase 3 ligand (FL) ameliorates excitotoxic neonatal brain injury. The effect of these substances in combined-stressor neonatal brain injury models more closely mimicking clinical conditions has not been investigated. The aim of this study was to assess the short-, mid-, and long-term neuroprotective potential of G-CSF/SCF and FL in a neonatal model of hypoxic-hyperoxic ischemic brain injury. Five-day-old (P5) CD-1 mice were subjected to unilateral common carotid artery ligation and subsequent alternating periods of hypoxia and hyperoxia for 65 minutes. Sixty hours after injury, pups were randomly assigned to intraperitoneal treatment with (i) G-CSF (200 µg/kg)/SCF (50 µg/kg), (ii) FL (100 µg/kg), or (iii) vehicle every 24 hours for three or five consecutive days. Histopathological and functional outcomes were evaluated on P10, P18, and P90. Baseline outcome parameters were established in sham-treated and healthy control animals. Gross brain injury did not significantly differ between treatment groups at any time point. On P10, caspase-3 activation and caspase-independent apoptosis were similar between treatment groups; cell proliferation and the number of BrdU-positive vessels did not differ on P18 or P90. Neurobehavioral assessment did not reveal significant differences between treatment groups in accelerod performance, open field behavior, or novel object recognition capacity on P90. Turning behavior was more frequently observed in G-CSF/SCF- and FL-treated animals. No sex-specific differences were detected in any outcome parameter evaluated. In hypoxic-hyperoxic ischemic neonatal brain injury, G-CSF/SCF and FL treatment does not convey neuroprotection. Prior to potential clinical use, meticulous assessment of these hematopoietic growth factors is mandated.

Amplitude-integrated electroencephalography shows alterations in children born preterm displaying poor literacy precursor skills.

AIM: To assess whether amplitude-integrated electroencephalography (aEEG) alterations in the newborn period are associated with poor precursor skills of literacy at five years of age in children born preterm. METHODS: Between October 2007 and September 2011 248 preterm infants were eligible for the study at Innsbruck Medical University Hospital. aEEG was analysed for dominating background activity, calculation of the percentage of continuous activity, the Burdjalov scoring system, the minimum, mean and maximum amplitude. At the age of five years, we evaluated preterm born children by the Bielefelder screening (BISC) to assess for early diagnosis of reading problems and weak spelling and classified them as normal performers (n = 64) or poor performers (n = 20). Completion of testing was not possible for one infant. RESULTS: The minimum amplitude was significantly lower in the poor BISC performance group as compared to the normal BISC performance group at postnatal week two. The percentage of continuous background activity was significantly higher in infants with normal BISC performance than in infants with poor BISC performance at postnatal week three. CONCLUSION: Children with poor developed precursor skills of literacy showed alterations in aEEG signals. The aEEG could be useful in further diagnosing preterm infants at risk for developmental complications.

The Cerebellar-Cerebral Microstructure Is Disrupted at Multiple Sites in Very Preterm Infants with Cerebellar Haemorrhage.

BACKGROUND: Recent advances in magnetic resonance imaging (MRI) techniques have prompted reconsideration of the anatomical correlates of adverse outcomes in preterm infants. The importance of the contribution made by the cerebellum is now increasingly appreciated. The effect of cerebellar haemorrhage (CBH) on the microstructure of the cerebellar-cerebral circuit is largely unexplored. OBJECTIVES: To investigate the effect of CBH on the microstructure of cerebellar-cerebral connections in preterm infants aged <32 gestational weeks. METHODS: Infants underwent diffusion tensor MRI at term-equivalent age. MRI was evaluated for CBH and additional supratentorial brain injury using a validated scoring system. Region of interest-based measures of brain microstructure (fractional anisotropy [FA] and apparent diffusion coefficient) were quantified in 5 vulnerable regions (the centrum semiovale, posterior limb of the internal capsule, corpus callosum, and superior and middle cerebellar peduncles). Group differences between infants with CBH and infants without CBH were assessed. RESULTS: There were 267 infants included in the study. Infants with CBH (isolated and combined) had significantly lower FA values in all regions investigated. Infants with isolated CBH showed lower FA in the middle and superior cerebellar peduncles and in the posterior limb of the internal capsule. CONCLUSIONS: This study provides evidence that CBH causes alterations in localised and remote WM pathways in the developing brain. The disruption of the cerebellar-cerebral microstructure at multiple sites adds further support for the concept of developmental diaschisis, which is propagated as an explanation for the consequences of early cerebellar injury on cognitive and affective domains.

Routine Magnetic Resonance Imaging at Term-Equivalent Age Detects Brain Injury in 25% of a Contemporary Cohort of Very Preterm Infants.

INTRODUCTION: In recent years, significant investigation has been undertaken by means of magnetic resonance imaging (MRI) in an attempt to identify preterm infants at risk for adverse outcome. The primary objective is to provide a comprehensive characterization of cerebral injury detected by conventional MRI at term-equivalent age in an unselected, consecutive, contemporary cohort of preterm infants born <32 gestational weeks. Secondly, this study aims to identify risk factors for the different injury types in this population. METHODS: Data for all preterm infants born <32 gestational weeks and admitted to Innsbruck Medical University Hospital were prospectively collected (October 2010 to December 2015). Cerebral MRI was evaluated retrospectively using a validated scoring system that incorporates intraventricular haemorrhage (IVH), white matter disease (WMD) and cerebellar haemorrhage (CBH). RESULTS: 300 infants were included in the study. MRI showed 24.7% of all infants to have some form of brain injury. The most common injury type was IVH (16.0%). WMD and CBH were seen in 10.0% and 8.0%. The prevalence of common neonatal risk factors was greater within the group of infants with CBH. In particular indicators for respiratory disease were observed more often: longer ventilation duration, more frequent need for supplemental oxygen at day 28, higher rates of hydrocortisone treatment. Catecholamine treatment was the only neonatal risk factor that was overrepresented in infants with WMD. DISCUSSION: Cerebral MRI at term-equivalent age, as addition to cranial ultrasound, detected brain injury in 25% of preterm survivors. The diagnosis of IVH was already made by neonatal ultrasound in most cases. In contrast, only a minority of the CBH and none of the non-cystic WMD have been detected prior to MRI. Decreasing gestational age and neonatal complications involved with immaturity have been identified as risk factors for CBH, whereas WMD was found in relatively mature infants with circulatory disturbances.

Amplitude-integrated electroencephalography can predict neurodevelopmental outcome at 12 months of corrected age in very preterm infants.

AIM: It is difficult to find diagnostic tools than can reliably predict neurodevelopmental outcomes in very preterm infants in clinical practice. This study evaluated whether amplitude-integrated electroencephalography predicted neurodevelopmental outcome in preterm infants when they reached 12 months of corrected age. METHODS: Between October 2007 and December 2013, we studied 232 preterm infants (51% male) at Innsbruck Medical University Hospital, Austria. Their mean birthweight was 1264 g, and their mean gestational age was 29.5 weeks. Amplitude-integrated electroencephalography was evaluated using the Burdjalov score, and outcomes were assessed using the Bayley Scales of Infant Development - Second Edition. RESULTS: The cohort was divided into three subgroups: 154 infants with normal outcomes, 53 infants with moderate delays and 25 infants with severe delays. The amplitude-integrated electroencephalography Burdjalov scores were lower in infants with moderate delays than in infants with normal outcomes and even lower in infants with severe delays. The highest area under the curve (0.776) for the Burdjalov score was at 18-24 hours of life. CONCLUSION: Our study confirmed the predictive value of amplitude-integrated electroencephalography and showed that this needed to be carried out early in life to provide reliable information on neurodevelopmental outcomes in very preterm infants.

Case report of a central venous access device-associated thrombosis with aortic embolism in a preterm infant.

BACKGROUND: Thrombosis in neonates is commonly a central venous access device (CVAD) associated complication. Furthermore, a patent foramen ovale (PFO) is frequently seen in preterm infants. Even though a coincidence of both is not unusual, detaching of the thrombus and organisation of an aortic embolism has not been described until now. Treatment recommendations of CVAD-associated thrombosis in neonates do not consider frequently seen complications of preterm infants e.g. intraventricular haemorrhage. This is the first case of a very preterm infant with pre-existing intraventricular haemorrhage, who developed a CVAD-associated thrombosis and thromboembolic complications. CASE PRESENTATION: The authors report on a very preterm girl with a pre-existing intraventricular haemorrhage and a CVAD-associated thrombus that, after removal of the CVAD, led to assumed pulmonary embolism and to an extended aortic embolism with consequent cerebral stroke. The girl was treated with unfractionated heparin (UFH) for about 50 days. During the further in-hospital stay the girl developed a mild bronchopulmonary dysplasia. Follow-up revealed clinical signs of cerebral palsy. CONCLUSION: Even though preterm infants are often diagnosed with a PFO which constitutes the risk for paradoxical embolism, such complications do not occur frequently due to the physiological heart pressure proportion. Nevertheless, it is important to monitor vital parameters and cerebral perfusion after removing a CVAD with confirmed associated thrombosis, because thromboembolic complications are possible. If practicable, patients with a confirmed CVAD-associated thrombosis should be anticoagulated before removing the CVAD. However, in our patient it was rational to remove the CVAD without prior anticoagulation due to the pre-existing intraventricular haemorrhage. There are various treatment recommendations for thrombosis or embolism in infants. However, there are no clear recommendations in very preterm infants with a high risk of cerebral bleeding respectively a pre-existing intraventricular haemorrhage. We decided to treat our patient with unfractionated heparin until the affected vessels were recanalised. Finally, it remains a case-by-case decision how to treat CVAD-associated thrombosis and consequent embolism depending on the patient's medical history.