Ventilatory Support, Extubation, and Cerebral Perfusion Changes in Pre-Term Neonates: A Near Infrared Spectroscopy Study.

Early extubation is considered to be beneficial for pre-term neonates. On the other hand, premature extubation can cause lung derecruitment, compromised gas exchange, and need for reintubation, which may be associated with severe brain injury caused by sudden cerebral blood flow changes. We used near infrared spectroscopy (NIRS) to investigate changes in cerebral oxygenation (rScO2) and fractional tissue oxygen extraction (+) after extubation in pre-term infants. This is a single-center retrospective study of NIRS data at extubation time of all consecutive pre-term neonates born at our institution over a 1-year period. Comparison between subgroups was performed. Nineteen patients were included; average gestational age (GA) was 29.4 weeks. No significant change was noted in rScO2 and cFTOE after extubation in the whole population. GA and germinal matrix hemorrhage (GMH)-intraventricular hemorrhage (IVH) showed a significant change in rScO2 and cFTOE after extubation. A significant increase in cFTOE was noted in patients with previous GMH-IVH (+0.040; p = 0.05). To conclude, extubation per se was not associated with significant change in cerebral oxygenation and perfusion. Patients with a diagnosed GMH-IVH showed an increase in cFTOE, suggesting perturbation in cerebral perfusion suggesting further understanding during this challenging phenomenon. Larger studies are required to corroborate our findings.

Early Extra-Uterine Growth Restriction in Very-Low-Birth-Weight Neonates with Normal or Mildly Abnormal Brain MRI: Effects on a 2-3-Year Neurodevelopmental Outcome.

Extra-uterine growth restriction (EUGR) is a common complication and a known risk factor for impaired development in very-low-birth-weight (VLBW) neonates. We report a population of 288 patients with no or with low-grade MRI lesions scanned at a term equivalent age (TEA) born between 2012 and 2018. Griffiths Mental Development Scale II (GMDS II) at 2 and 3 years, preterm complications and weight growth were retrospectively analyzed. EUGR was defined for weight z-score ˂ 10 percentile at TEA, 6 and 12 months of correct age or as z-score decreased by 1-point standard deviation (SDS) from birth to TEA and from TEA to 6 months. Multivariate analysis showed that a higher weight z-score at 6 months is protective for the global developmental quotient (DQ) at 2 years (OR 0.74; CI 95% 0.59-0.93; p = 0.01). EUGR at 6 months was associated with worse locomotor, personal/social, language and performance DQ at 2 years and worse language and practical reasoning DQ at 3 years. In conclusion, a worse weight z-score at 6 months of age seems to be an independent risk factor for significantly reduced GMDS in many areas. These results suggest that we should invest more into post-discharge nutrition, optimizing family nutritional education.

Neurodevelopmental consequences of preterm punctate white matter lesions: a systematic review.

OBJECTIVES: To evaluate punctate white matter lesion (PWML) influence in preterm infants on the long-term neurodevelopmental outcome (NDO). METHODS: PubMed and EMBASE were searched from January 1, 2000, to May 31, 2021. Studies were included in which PWML in preterm infants on MRI around term-equivalent age (TEA) and NDO at ≥12 months were reported. Study and patient characteristics and NDO on motor, cognitive, and behavioral domains were extracted. The quality of studies was assessed using the Cochrane-approved Quality in Prognosis Studies tool. RESULTS: This analysis included nine studies with a total of 1655 patients. Mean incidence of isolated PWML was 22.1%. All studies showed a relationship between PWML and motor delay. Two studies found a significant correlation between cognitive and behavioral outcomes and PWML. Number and PWML location are related to severity and impairment types. LIMITATIONS: PWML were not always separately described from generalized WMI, only studies with imaging around TEA were included, and studies were heterogenic in design and quality. CONCLUSIONS: PWML is common in preterm infants and predictive of adverse NDO, in particular on motor outcomes and less on cognitive and behavioral outcomes. The type and severity of impairments are related to the number and location of PMWL. IMPACT: PWML is common in preterm infants and seems predictive of adverse NDO. DWI and SWI MRI sequences are informative because the different patterns suggest a difference in the underlying pathology. The type and severity of impairments are related to the number and location of PMWL. Our review can inform clinicians and parents about the NDO of preterm infants with a diagnosis of PWML. Prospective neuroimaging case-control cohort studies are recommended.

Adenosine Blood Level: A Biomarker of White Matter Damage in Very Low Birth Weight Infants.

BACKGROUND: Very low birth weight infants are at risk of developing periventricular white matter lesions. We previously reported high blood adenosine levels in premature infants and infants with low birth weight. We asked whether blood adenosine levels could be related to the vulnerability of the maturing white matter to develop lesions. The present study aims at finding a biomarker for the early detection of brain white matter lesions that can profoundly influence the neurodevelopmental outcome, whose pathophysiology is still unclear. METHODS: Dried blood spots were prospectively collected for the newborn screening program and adenosine concentration measurements. Fifty-six newborns who tested four times for blood adenosine concentration (at days 3, 15, 30, and 40 post-birth) were included in the program. All infants underwent brain MRI at term equivalent age. Neurodevelopmental outcomes were studied with Griffiths Mental Development Scales (GMDS) at 12 ± 2 months corrected age. RESULTS: Blood adenosine concentration increased over time from a median of 0.75 µM at Day 3 to 1.46 µM at Day 40. Adenosine blood concentration >1.58 µM at Day 15 was significantly associated with brain white matter lesions at MRI (OR (95 % CI) of 50.0 (3.6-688.3), p-value < 0.001). A moderate negative correlation between adenosine at 15 days of life and GMDS at 12 ± 2 months corrected age was found. CONCLUSION: These findings suggest a potential role for blood adenosine concentration as a biomarker of creberal white matter lesions in very low birth weight infants.

External ventricular drainage for posthemorrhagic ventricular dilatation in preterm infants: insights on efficacy and failure.

OBJECTIVE: The objective of this study was to describe the clinical and neuroradiological characteristics of a cohort of preterm infants who had undergone external ventricular drain insertion as a temporary measure to treat posthemorrhagic ventricular dilatation. In addition, the authors investigated the factors predicting permanent shunt dependency. METHODS: The authors retrospectively reviewed the medical records of a cohort of preterm infants who had undergone external ventricular drain insertion at Gaslini Children's Hospital (Genoa, Italy) between March 2012 and February 2018. They also analyzed clinical characteristics and magnetic resonance imaging data, including diffusion- and susceptibility-weighted imaging studies, which were obtained before both catheter insertion and removal. RESULTS: Twenty-eight infants were included in the study. The mean gestational age was 28.2 ± 2.7 weeks, and the mean birth weight was 1209 ± 476 g. A permanent ventriculoperitoneal shunt was inserted in 15/28 (53.6%) infants because of the failure of external ventricular drainage as a temporary treatment option. Compared with the shunt-free group, the shunt-dependent group had a significantly lower gestational age (29.3 ± 2.3 vs 27.2 ± 2.7 weeks, p = 0.035) and tended toward a lower birth weight (p = 0.056). None of the clinical and neuroradiological characteristics significantly differed between the shunt-free and shunt-dependent groups at the time of catheter insertion. As expected, ventricular parameters as well as the intraventricular extension of intracerebral hemorrhage, as assessed using the intraventricular hemorrhage score, were reportedly higher in the shunt-dependent group than in the shunt-free group before catheter removal. CONCLUSIONS: External ventricular drainage is a reliable first-line treatment for posthemorrhagic hydrocephalus. However, predicting its efficacy as a unique treatment remains challenging. A lower gestational age is associated with a higher risk of posthemorrhagic hydrocephalus progression, suggesting that the more undeveloped the mechanisms for the clearance of blood degradation products, the greater the risk of requiring permanent cerebrospinal fluid diversion, although sophisticated MRI investigations are currently unable to corroborate this hypothesis.

Nosological Differences in the Nature of Punctate White Matter Lesions in Preterm Infants.

Background: The pathogenesis of punctuate white matter lesions (PWMLs), a mild form of white matter damage observed in preterm infants, is still a matter of debate. Susceptibility-weighted imaging (SWI) allows to differentiate PWMLs based on the presence (SWI+) or absence (SWI-) of hemosiderin, but little is known about the significance of this distinction. This retrospective study aimed to compare neuroradiological and clinical characteristics of SWI+ and SWI- PWMLs. Materials and Methods: MR images of all VLBW infants scanned consecutively at term-equivalent age between April 2012 and May 2018 were retrospectively reviewed, and infants with PWMLs defined as small areas of high T1 and/or low T2 signal in the periventricular white matter were selected and included in the study. Each lesion was analyzed separately and characterized by localization, organization pattern, and distance from the lateral ventricle. Clinical data were retrieved from the department database. Results: A total of 517 PWMLs were registered in 81 patients, with 93 lesions (18%) visible on SWI (SWI+), revealing the presence of hemosiderin deposits. On univariate analysis, compared to SWI- PWML, SWI+ lesions were closer to the ventricle wall, more frequently organized in linear pattern and associated with lower birth weight, lower gestational age, lower admission temperature, need for intubation, bronchopulmonary dysplasia, retinopathy of prematurity, and presence of GMH-IVH. On multivariate analysis, closer distance to the ventricle wall on axial scan and lower birth weight were associated with visibility of PMWLs on SWI (p = 0.003 and p = 0.0001, respectively). Conclusions: Our results suggest a nosological difference between SWI+ and SWI- PWMLs. Other prospective studies are warranted to corroborate these observations.

Neonatal Hypoglycemia and Brain Vulnerability.

Neonatal hypoglycemia is a common condition. A transient reduction in blood glucose values is part of a transitional metabolic adaptation following birth, which resolves within the first 48 to 72 h of life. In addition, several factors may interfere with glucose homeostasis, especially in case of limited metabolic stores or increased energy expenditure. Although the effect of mild transient asymptomatic hypoglycemia on brain development remains unclear, a correlation between severe and prolonged hypoglycemia and cerebral damage has been proven. A selective vulnerability of some brain regions to hypoglycemia including the second and the third superficial layers of the cerebral cortex, the dentate gyrus, the subiculum, the CA1 regions in the hippocampus, and the caudate-putamen nuclei has been observed. Several mechanisms contribute to neuronal damage during hypoglycemia. Neuronal depolarization induced by hypoglycemia leads to an elevated release of glutamate and aspartate, thus promoting excitotoxicity, and to an increased release of zinc to the extracellular space, causing the extensive activation of poly ADP-ribose polymerase-1 which promotes neuronal death. In this review we discuss the cerebral glucose homeostasis, the mechanisms of brain injury following neonatal hypoglycemia and the possible treatment strategies to reduce its occurrence.

Post-haemorrhagic hydrocephalus management: Delayed neonatal transport negatively affects outcome.

BACKGROUND: Post-haemorrhagic ventricular dilatation (PHVD) still represents an important cause of brain injury in premature infants. Intervention for PHVD is recommended once Ventricular Index (VI) crosses the 97th percentile + 4 mm line according to Levene. OBJECTIVES: We aimed to compare PHVD severity, timing of intervention, and outcome between outborn infants transferred to a level IV NICU in order to be treated for PHVD and a control population of inborn infants. METHODS: Preterm infants with PHVD requiring treatment were divided into: outborn infants (transferred to our NICU in order to be treated for PHVD) and inborn infants (PHVD diagnosed at our NICU). Age at intervention, difference between VI and the 97th percentile according to postmenstrual age (VI-p97), permanent shunt rate, and developmental delay rate were compared between the two groups. Neurodevelopmental outcome was assessed using the Vineland Adaptive Behavior Scales II (VABS-II), a parental questionnaire investigating four domains of adaptive behaviour and overall adaptive functioning. Developmental delay was defined as a score <70 (-2 SD or less). RESULTS: Twelve outborn and 15 inborn infants were included. Age at intervention (31.6 vs 17.4 days) and VI-p97 (left 10.0 vs 5.1 mm, right 7.7 vs 5.1 mm) were significantly higher among outborn infants. A permanent shunt was inserted in 66.7% of outborn and in 40.0% of inborn infants (p = 0.18). After excluding subjects with parenchymal lesions, a significantly higher rate of developmental delay was observed at 5 years in outborn patients compared to inborn patients (66.7% of outborn vs 18.2% of inborn patients with VABS-II composite score <70, p = 0.04). CONCLUSIONS: Outborn infants reached a significantly more severe ventricular dilatation than inborn infants, largely exceeding the recommended cutoff for intervention. Our follow-up data showed a trend towards a higher rate of permanent shunt and developmental delay in outborn than in inborn patients. Infants requiring treatment should be timely transported to centres with adequate expertise in PHVD management.

Randomized Control Trial of Postnatal rhIGF-1/rhIGFBP-3 Replacement in Preterm Infants: Post-hoc Analysis of Its Effect on Brain Injury.

Background: Postnatal insulin-like growth factor-1 (IGF-1) replacement with recombinant human (rh)IGF-1 and IGF binding protein-3 (rhIGF-1/rhIGFBP-3) is being studied as a potential treatment to reduce comorbidities of prematurity. We have recently reported on a phase II, multicenter, randomized, controlled trial comparing postnatal rhIGF-1/rhIGFBP-3 replacement with standard of care (SOC) in extremely preterm infants (NCT01096784). Maximum severity of retinopathy of prematurity was the primary endpoint of the trial and presence of GMH-IVH/PHI one of the pre-specified secondary endpoints. Infants therefore received serial cranial ultrasound scans (CUS) between birth and term age. In this post-hoc analysis we present a detailed analysis of the CUS data of this trial and evaluate the effect of postnatal rhIGF-1/rhIGFBP-3 replacement on the incidence of different kinds of brain injury in extremely preterm infants. Methods: This report is an exploratory post-hoc analysis of a phase II trial in which infants <28 weeks gestational age were randomly allocated to rhIGF-1/rhIGFBP-3 or SOC. Serial cranial ultrasounds were performed between birth and term-equivalent age. Presence of germinal matrix hemorrhage and intraventricular hemorrhage (GMH-IVH), periventricular hemorrhagic infarction (PHI), post-hemorrhagic ventricular dilatation, and white matter injury (WMI) were scored by two independent masked readers. Results: The analysis included 117 infants; 58 received rhIGF-1/rhIGFBP-3 and 59 received SOC. A trend toward less grade II-III GMH-IVH and PHI was observed in treated infants vs. SOC. A subanalysis of infants without evidence of GMH-IVH at study entry (n = 104) showed reduced progression to GMH-IVH in treated infants (25.0% [13/52] vs. 40.4% [21/52]; not significant). No effects of rhIGF-1/rhIGFBP-3 on WMI were observed. Conclusion: The potential protective effect of rhIGF-1/rhIGFBP-3 on the occurrence of GMH-IVH/PHI appeared most pronounced in infants with no evidence of GMH-IVH at treatment start.

Placental Pathology Findings and the Risk of Intraventricular and Cerebellar Hemorrhage in Preterm Neonates.

Placental pathology as a predisposing factor to intraventricular hemorrhage remains a matter of debate, and its contribution to cerebellar hemorrhage development is still largely unexplored. Our study aimed to assess placental and perinatal risk factors for intraventricular and cerebellar hemorrhages in preterm infants. This retrospective cohort study included very low-birth weight infants born at the Gaslini Children's Hospital between January 2012 and October 2016 who underwent brain magnetic resonance with susceptibility-weighted imaging at term-equivalent age and whose placenta was analyzed according to the Amsterdam Placental Workshop Group Consensus Statement. Of the 286 neonates included, 68 (23.8%) had intraventricular hemorrhage (all grades) and 48 (16.8%) had a cerebellar hemorrhage (all grades). After correction for gestational age, chorioamnionitis involving the maternal side of the placenta was found to be an independent risk factor for developing intraventricular hemorrhage, whereas there was no association between maternal and fetal inflammatory response and cerebellar hemorrhage. Among perinatal factors, we found that intraventricular hemorrhage was significantly associated with cerebellar hemorrhage (odds ratio [OR], 8.14), mechanical ventilation within the first 72 h (OR, 2.67), and patent ductus arteriosus requiring treatment (OR, 2.6), whereas cesarean section emerged as a protective factor (OR, 0.26). Inotropic support within 72 h after birth (OR, 5.24) and intraventricular hemorrhage (OR, 6.38) were independent risk factors for cerebellar hemorrhage, whereas higher gestational age was a protective factor (OR, 0.76). Assessing placental pathology may help in understanding mechanisms leading to intraventricular hemorrhage, although its possible role in predicting cerebellar bleeding needs further evaluation.

Bivalirudin anticoagulation to overcome heparin resistance in a neonate with cerebral sinovenus thrombosis.

: Anticoagulation in a neonate is a challenge and the availability of anticoagulant options is extremely limited. Here we describe the use of a direct thrombin inhibitor, bivalirudin, in a full-term neonate with symptomatic cerebral sinovenous thrombosis complicated by bilateral thalamic hemorrhagic stroke and intraventricular hemorrhage, who could not be effectively treated with sodium heparin due to heparin resistance (HR) and showed thrombosis regression after start of bivalirudin treatment, without worsening of the hemorrhage. While the use of bivalirudin in neonates has been previously described, the indication of cerebral sinovenous thrombosis and the setting of HR are unique.

Punctate white matter lesions of preterm infants: Risk factor analysis.

AIM: Punctate white matter lesions (PWML) are frequently detected in preterm infants undergoing brain MRI at term equivalent age (TEA). The aims of this study were to assess prevalence of PWML and to identify risk factors for PWML in VLBW infants. METHODS: Brain MRI scans obtained at TEA and clinical charts of a consecutive sample of very low birth weight (VLBW) infants admitted to Gaslini Children's Hospital NICU between 2012 and 2016 were retrospectively analyzed. MRI protocol included Susceptibility Weighted Imaging (SWI) sequence in order to identify hemosiderin depositions as a result of previous microbleeds. PWML were classified according to their number (≤6 lesions and >6 lesions) and signal characteristics (SWI+ lesions and SWI- lesions). Univariate and multivariable analysis were performed in order to identify risk factors for PWML (as a whole) and for each subgroup of PWML. RESULTS: 321 VLBW infants were included. PWML were identified in 61 subjects (19%), 26 of whom (8% of the study population) had more than 6 lesions. Risk factors for PWML (as a whole) were higher birth weight (OR = 1.001; p = 0.04) and absent or incomplete antenatal steroid course (OR = 2.13; p = 0.02). Risk factors for >6 PWML were need for intubation (OR = 11.9; p = 0.003) and higher Apgar score at 5 min (OR = 1.8; p = 0.02). Presence of GMH-IVH was the only identified risk factor for SWI + lesions. CONCLUSIONS: Our results confirm the high prevalence of PWML among VLBW infants. Differentiation between SWI+ and SWI- lesions is crucial as they have different risk factors and may likely represent two different entities.

Brain Volumes and Developmental Outcome in Childhood Following Fetal Growth Restriction Leading to Very Preterm Birth.

Background: Children born very preterm (PT) after fetal growth restriction (FGR) exhibit cognitive impairment at early school age. The relationship between neurodevelopmental impairment and attained regional brain volumes is unknown. Methods: We studied 23 preterm children with FGR (PT-FGR), 24 matched preterm children AGA (PT-AGA), and 27 matched term AGA children (T-AGA) by measuring brain volumes with magnetic resonance imaging at early school age. Cognitive and motor functions were assessed by the Wechsler Intelligence Scales for Children and the ABC-Movement score. Results: The mean (SD) full-scale IQ was 80 (17) in the PT-FGR group and 103 (12) in the PT-AGA group (p < 0.001). The PT-FGR group had lower mean total, gray matter, white matter, thalamic, cerebellar white matter, and hippocampal volumes as compared to the T-AGA group (p = 0.01, 0.04, 0.003, 0.002, 0.001, and 0.009, respectively). Brain volumes did not differ significantly between the PT groups. Reduction of hippocampal volume correlated with degree of growth restriction at birth (r = 0.46, p = 0.05). Neither the full-scale IQ nor the ABC movement score <5th percentile were related to brain volumes. Conclusion: Brain volumes as determined by MRI at early school age were primarily associated with degree of prematurity at birth and less with FGR. Regional brain volumes did not discriminate cognitive and motor function beyond that predicted by gestational age at birth.

Oxidative Stress as a Primary Risk Factor for Brain Damage in Preterm Newborns.

The risk of oxidative stress is high in preterm newborns. Room air exposure of an organism primed to develop in a hypoxic environment, lacking antioxidant defenses, and subjected to hyperoxia, hypoxia, and ischemia challenges the newborn with oxidative stress production. Free radicals can be generated by a multitude of other mechanisms, such as glutamate excitotoxicity, excess free iron, inflammation, and immune reactions. Free radical-induced damage caused by oxidative stress appears to be the major candidate for the pathogenesis of most of the complications of prematurity, brain being especially at risk, with short to long-term consequences. We review the role of free radical oxidative damage to the newborn brain and propose a mechanism of oxidative injury, taking into consideration the particular maturation-dependent vulnerability of the oligodendrocyte precursors. Prompted by our observation of an increase in plasma Adenosine concentrations significantly associated with brain white matter lesions in some premature infants, we discuss a possible bioenergetics hypothesis, correlated to the oxidative challenge of the premature infant. We aim at explaining both the oxidative stress generation and the mechanism promoting the myelination disturbances. Being white matter abnormalities among the most common lesions of prematurity, the use of Adenosine as a biomarker of brain damage appears promising in order to design neuroprotective strategies.

Quantitative susceptibility map analysis in preterm neonates with germinal matrix-intraventricular hemorrhage.

BACKGROUND: Germinal matrix-intraventricular hemorrhage (GMH-IVH) is a common form of intracranial hemorrhage occurring in preterm neonates that may affect normal brain development. Although the primary lesion is easily identified on MRI by the presence of blood products, its exact extent may not be recognizable with conventional sequences. Quantitative susceptibility mapping (QSM) quantify the spatial distribution of magnetic susceptibility within biological tissues, including blood degradation products. PURPOSE/HYPOTHESIS: To evaluate magnetic susceptibility of normal-appearing white (WM) and gray matter regions in preterm neonates with and without GMH-IVH. STUDY TYPE: Retrospective case-control. POPULATION: A total of 127 preterm neonates studied at term equivalent age: 20 had mild GMH-IVH (average gestational age 28.7 ± 2.1 weeks), 15 had severe GMH-IVH (average gestational age 29.3 ± 1.8 weeks), and 92 had normal brain MRI (average gestational age 29.8 ± 1.8 weeks). FIELD STRENGTH/SEQUENCE: QSM at 1.5 Tesla. ASSESSMENT: QSM analysis was performed for each brain hemisphere with a region of interest-based approach including five WM regions (centrum semiovale, frontal, parietal, temporal, and cerebellum), and a subcortical gray matter region (basal ganglia/thalami). STATISTICAL TESTS: Changes in magnetic susceptibility were explored using a one-way analysis of covariance, according to GMH-IVH severity (P < 0.05). RESULTS: In preterm neonates with normal brain MRI, all white and subcortical gray matter regions had negative magnetic susceptibility values (diamagnetic). Neonates with severe GMH-IVH showed higher positive magnetic susceptibility values (i.e. paramagnetic) in the centrum semiovale (0.0019 versus -0.0014 ppm; P < 0.001), temporal WM (0.0011 versus -0.0012 ppm; P = 0.037), and parietal WM (0.0005 versus -0.0001 ppm; P = 0.002) compared with controls. No differences in magnetic susceptibility were observed between neonates with mild GMH-IVH and controls (P = 0.236). DATA CONCLUSION: Paramagnetic susceptibility changes occur in several normal-appearing WM regions of neonates with severe GMH-IVH, likely related to the accumulation of hemosiderin/ferritin iron secondary to diffusion of extracellular hemoglobin from the ventricle into the periventricular WM. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:1199-1207.

Differences in subependymal vein anatomy may predispose preterm infants to GMH-IVH.

BACKGROUND AND PURPOSE: The anatomy of the deep venous system plays an important role in the pathogenesis of brain lesions in the preterm brain as shown by different histological studies. The aims of this study were to compare the subependymal vein anatomy of preterm neonates with germinal matrix haemorrhage-intraventricular haemorrhage (GMH-IVH), as evaluated by susceptibility-weighted imaging (SWI) venography, with a group of age-matched controls with normal brain MRI, and to explore the relationship between the anatomical features of subependymal veins and clinical risk factors for GMH-IVH. METHODS: SWI venographies of 48 neonates with GMH-IVH and 130 neonates with normal brain MRI were retrospectively evaluated. Subependymal vein anatomy was classified into six different patterns: type 1 represented the classic pattern and types 2-6 were considered anatomic variants. A quantitative analysis of the venous curvature index was performed. Variables were analysed by using Mann-Whitney U and χ2 tests, and a multiple logistic regression analysis was performed to evaluate the association between anatomical features, clinical factors and GMH-IVH. RESULTS: A significant difference was noticed among the six anatomical patterns according to the presence of GMH-IVH (χ2=14.242, p=0.014). Anatomic variants were observed with higher frequency in neonates with GMH-IVH than in controls (62.2% and 49.6%, respectively). Neonates with GMH-IVH presented a narrower curvature of the terminal portion of subependymal veins (p<0.05). These anatomical features were significantly associated with GMH-IVH (p<0.05). CONCLUSION: Preterm neonates with GMH-IVH show higher variability of subependymal veins anatomy confirming a potential role as predisposing factor for GMH-IVH.

The effects of mild germinal matrix-intraventricular haemorrhage on the developmental white matter microstructure of preterm neonates: a DTI study.

OBJECTIVES: To evaluate white matter (WM) microstructural changes in preterm neonates (PN) with mild germinal matrix-intraventricular haemorrhage (mGMH-IVH) (grades I and II) and no other associated MRI abnormalities, and correlate them with gestational age (GA) and neurodevelopmental outcome. METHODS: Tract-based spatial-statistics (TBSS) was performed on DTI of 103 patients studied at term-equivalent age, to compare diffusional parameters (fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), axial diffusivity (AD)) between mGMH-IVH neonates (24/103) and controls matched by GA at birth and sex. The relationship between DTI abnormalities, GA and neurodevelopmental outcome assessed with Griffiths' Developmental Scale-Revised:0-2 was explored using TBSS and Spearman-correlation analysis (p < .05). RESULTS: Affected neonates had lower FA, higher RD and MD of the corpus callosum, limbic pathways and cerebellar tracts. Extremely preterm neonates (GA < 29 weeks) presented more severe microstructural impairment (higher RD and MD) in periventricular regions. Neonates of GA ≥ 29 weeks had milder WM alterations (lower FA), also in subcortical WM. DTI abnormalities were associated with poorer locomotor, eye-hand coordination and performance outcomes at 24 months. CONCLUSIONS: WM microstructural changes occur in PN with mGMH-IVH with a GA-dependent selective vulnerability of WM regions, and correlate with adverse neurodevelopmental outcome at 24 months. KEY POINTS: • DTI-TBSS analysis identifies WM microstructural changes in preterm neonates with mGMH-IVH. • Extremely preterm neonates with mGMH-IVH presented more severe impairment of WM microstructure. • Extremely preterm neonates with mGMH-IVH presented microstructural impairment of periventricular WM. • mGMH-IVH affects subcortical WM in preterm neonates with gestational age ≥ 29 weeks. • WM microstructural alterations are related to neurodevelopmental impairments at 24 months.

Incidental findings on routine brain MRI scans in preterm infants.

OBJECTIVE: Many neonatal intensive care units (NICUs) have adopted the practice of performing routine brain MRI in very low birth weight (VLBW) infants at term-equivalent age in order to better evaluate prematurity-related acquired lesions. A number of unexpected brain abnormalities of potential clinical significance can be visualised on routine scans as well. The aim of our study was to describe these incidental findings (IFs) in a VLBW population and to assess their clinical significance. STUDY DESIGN: We retrospectively reviewed a series of brain MRI scans performed in VLBW infants consecutively admitted to our NICU between November 2011 and November 2014. IFs on brain MRI, which were not detected by cranial ultrasound nor suspected clinically, were registered. Clinical significance of IF was assessed in terms of need of further diagnostic or therapeutic interventions. RESULTS: IFs were detected in 28 out of 276 VLBW infants (10.1%). In total, 21 cases (7.6%) required an intervention, which was only diagnostic in 16 cases, and both diagnostic and therapeutic in 5 cases. In the remaining seven cases (2.5%), no further action was considered necessary. CONCLUSIONS: This study suggests that IFs on brain MRI of VLBW infants are not rare. In our population, most of them required a diagnostic or therapeutic intervention. The need and appropriateness of routine MRI scanning in VLBW at term-equivalent age are still subject of debate, and we believe our data can contribute meaningfully to this discussion.

Crossed Pontine Hemiatrophy Associated with Unilateral Cerebellar Hemorrhage in Premature Infants.

Background Cerebellar hemorrhage is a complication of extreme prematurity with a significant impact on the neurodevelopmental outcome. It has been shown that cerebellar hemorrhage is associated with a reduction in the anteroposterior diameter of the pons on the midline sagittal plane at term-equivalent age, suggesting that cerebellar injury may impair overall pons development in premature infants. Objective This study stemmed from an incidental observation of crossed pontine hemiatrophy in a preterm infant with a history of unilateral massive cerebellar bleeding. We aimed to verify the presence of this association in a population of preterm infants. Methods Among all, very preterm infants (GA < 32 weeks) born at our institution over a 6-year period, those with a diagnosis of unilateral massive cerebellar hemorrhage were selected. Magnetic resonance imaging scans of the selected subjects were reviewed. Results Six patients with unilateral massive cerebellar hemorrhage were identified. MRI showed crossed hemiatrophy of the pons in all cases. Conclusion Crossed hemiatrophy of the pons was associated with massive unilateral cerebellar hemorrhage. This finding may reflect retrograde degeneration of pontocerebellar fibers and loss of neurons in contralateral hemipons.

Prenatal MR imaging features of isolated cerebellar haemorrhagic lesions.

OBJECTIVE: Prenatal features of isolated cerebellar haemorrhagic lesions have not been sufficiently characterised. We aimed to better define their MR imaging characteristics, documenting the location, extension, evolution stage and anatomic sequelae, and to better understand cerebellar haemorrhage pathophysiology. MATERIALS AND METHODS: We screened our foetal MR imaging database (3200 cases) for reports of haemorrhagic lesions affecting only the cerebellum (without any supratentorial bleeding or other clastic lesions), defined as one of the following: T2-weighted hypointense or mixed hypo-/hyperintense signal; rim of T2-weighted hypointense signal covering the surface of volume-reduced parenchyma; T1-weighted hyperintense signal; increased DWI signal. RESULTS: Seventeen cases corresponded to the selection criteria. All lesions occurred before the 26th week of gestation, with prevalent origin from the peripheral-caudal portion of the hemispheres and equal frequency of unilateral/bilateral involvement. The caudal vermis appeared affected in 2/3 of cases, not in all cases confirmed postnatally. Lesions evolved towards malformed cerebellar foliation. The aetiology and pathophysiology were unknown, although in a subset of cases intra- and extracranial venous engorgement seemed to play a key role. CONCLUSIONS: Onset from the peripheral and caudal portion of the hemispheres seems characteristic of prenatal cerebellar haemorrhagic lesions. Elective involvement of the peripheral germinal matrix is hypothesised. KEY POINTS: • The cerebellum can be vulnerable to bleeding during foetal development. • Isolated cerebellar haemorrhages can be seen on prenatal MRI. • In our cohort, isolated foetal cerebellar haemorrhages occurred before the 26th gestational week. • Haemorrhagic lesions happening in utero could look like malformations on post-natal MRI. • Venous engorgement could have a role in causing cerebellar haemorrhagic lesions.