Neonatal Hypoxic-Ischemic Encephalopathy Spectrum: Severity-Stratified Analysis of Neuroimaging Modalities and Association with Neurodevelopmental Outcomes.

OBJECTIVE: To compare hypoxic-ischemic injury on early cranial ultrasonography (cUS) and post-rewarming brain magnetic resonance imaging (MRI) in newborn infants with hypoxic-ischemic encephalopathy (HIE) and to correlate that neuroimaging with neurodevelopmental outcomes. STUDY DESIGN: This was a retrospective cohort study of infants with mild, moderate, and severe HIE treated with therapeutic hypothermia and evaluated with early cUS and postrewarming MRI. Validated scoring systems were used to compare the severity of brain injury on cUS and MRI. Neurodevelopmental outcomes were assessed at 18 months of age. RESULTS: Among the 149 included infants, abnormal white matter (WM) and deep gray matter (DGM) hyperechogenicity on cUS in the first 48 hours after birth were more common in the severe HIE group than the mild HIE group (81% vs 39% and 50% vs 0%, respectively; P < .001). In infants with a normal cUS, 95% had normal or mildly abnormal brain MRIs. In infants with severely abnormal cUS, none had normal and 83% had severely abnormal brain MRIs. Total abnormality scores on cUS were higher in neonates with near-total brain injury on MRI than in neonates with normal MRI or WM-predominant injury pattern (adjusted P < .001 for both). In the multivariable model, a severely abnormal MRI was the only independent risk factor for adverse outcomes (OR: 19.9, 95% CI: 4.0-98.1; P < .001). CONCLUSION: The present study shows the complementary utility of cUS in the first 48 hours after birth as a predictive tool for the presence of hypoxic-ischemic injury on brain MRI.

Point-of-care brain ultrasound and transcranial doppler or color-coded doppler in critically ill neonates and children.

Point-of-care brain ultrasound and transcranial doppler or color-coded doppler is being increasingly used as an essential diagnostic and monitoring tool at the bedside of critically ill neonates and children. Brain ultrasound has already established as a cornerstone of daily practice in the management of the critically ill newborn for diagnosis and follow-up of the most common brain diseases, considering the easiness to insonate the brain through transfontanellar window. In critically ill children, doppler based techniques are used to assess cerebral hemodynamics in acute brain injury and recommended for screening patients suffering from sickle cell disease at risk for stroke. However, more evidence is needed regarding the accuracy of doppler based techniques for non-invasive estimation of cerebral perfusion pressure and intracranial pressure, as well as regarding the accuracy of brain ultrasound for diagnosis and monitoring of acute brain parenchyma alterations in children. This review is aimed at providing a comprehensive overview for clinicians of the technical, anatomical, and physiological basics for brain ultrasonography and transcranial doppler or color-coded doppler, and of the current status and future perspectives of their clinical applications in critically ill neonates and children. CONCLUSION: In critically ill neonates, brain ultrasound for diagnosis and follow-up of the most common cerebral pathologies of the neonatal period may be considered the standard of care. Data are needed about the possible role of doppler techniques for the assessment of cerebral perfusion and vasoreactivity of the critically ill neonate with open fontanelles. In pediatric critical care, doppler based techniques should be routinely adopted to assess and monitor cerebral hemodynamics. New technologies and more evidence are needed to improve the accuracy of brain ultrasound for the assessment of brain parenchyma of critically ill children with fibrous fontanelles. WHAT IS KNOWN: • In critically ill neonates, brain ultrasound for early diagnosis and follow-up of the most common cerebral and neurovascular pathologies of the neonatal period is a cornerstone of daily practice. In critically ill children, doppler-based techniques are more routinely used to assess cerebral hemodynamics and autoregulation after acute brain injury and to screen patients at risk for vasospasm or stroke (e.g., sickle cell diseases, right-to-left shunts). WHAT IS NEW: • In critically ill neonates, research is currently focusing on the use of novel high frequency probes, even higher than 10 MHz, especially for extremely preterm babies. Furthermore, data are needed about the role of doppler based techniques for the assessment of cerebral perfusion and vasoreactivity of the critically ill neonate with open fontanelles, also integrated with a non-invasive assessment of brain oxygenation. In pediatric critical care, new technologies should be developed to improve the accuracy of brain ultrasound for the assessment of brain parenchyma of critically ill children with fibrous fontanelles. Furthermore, large multicenter studies are needed to clarify role and accuracy of doppler-based techniques to assess cerebral perfusion pressure and its changes after treatment interventions.

Relationship between biparietal diameter/ventricular ratio and neurodevelopmental outcomes in non-handicapped very preterm infants.

PURPOSE: Preterm infants are at high risk for brain damage and long-term neurodevelopmental problems. Cranial ultrasonography is the main neuroimaging technique for very low birth weight infants. Ventricle size and its ratio to brain volume contribute very important information about the central nervous system of preterm babies. We calculated biparietal diameter/ventricular ratio of preterm infants using cranial ultrasonography and evaluate the relationship between this ratio and neurodevelopment. METHODS: Cranial measurements were derived using routine ultrasonographic scanning. Transverse brain length, or biparietal diameter (BPD), was considered a representation of the total brain, ventricular index (VI) and thalamo-occipital distance (TOD) length were used to represent the ventricles, and their ratio was accepted as a measure of the tissue portion of the brain. The ratio of BPD to the sum of left and right VI and TOD values was recorded as BPD/(VI+TOD) ratio. RESULTS: Data from a total of 482 patients were analyzed. The mean gestational age was 27.6 (24-29.6) weeks and the mean birth weight was 1010 (350-1390) g. The mean BPD/(VI+TOD) ratio was 32.90 (± 2.32). At 24 months corrected age, the patients' mean MDI score was 78.64 (± 13.29) and mean PDI score was 79.49 (± 14.31). When patients with and without NDI were compared, there were significant differences between the groups in terms of BPD/(VI+TOD) ratio, MDI, and PDI (p < 0.001, p < 0.001, p < 0.001, respectively). CONCLUSION: The BPD/ventricle ratio can be calculated using two-dimensional measurements in VLBW infants and reduced BPD/ventricle ratio was associated with poor neurodevelopmental outcomes. TRIAL REGISTRATION: NCT02848755.

Periventricular Hemorrhagic Infarction in Very Preterm Infants: Characteristic Sonographic Findings and Association with Neurodevelopmental Outcome at Age 2 Years.

OBJECTIVE: To describe the sonographic characteristics of periventricular hemorrhagic infarction (PVHI) and their association with mortality and neurodevelopmental disability in very preterm infants born in 2008-2013. STUDY DESIGN: Retrospective multicenter observational cohort study. Diagonal PVHI size was measured and severity score assessed. PVHI characteristics were scored and temporal trends were assessed. Neurodevelopmental outcome at 2 years of corrected age was assessed using either the Bayley Scales of Infant and Toddler Development, Third Edition or the Griffiths Mental Development Scales. Multigroup analyses were applied as appropriate. RESULTS: We enrolled 160 infants with median gestational age of 26.6 weeks. PVHI was mostly unilateral (90%), associated with an ipsilateral grade III intraventricular hemorrhage (84%), and located in the parietal lobe (51%). Sixty-four (40%) infants with PVHI died in the neonatal period. Of the survivors assessed at 2 years of corrected age, 65% had normal cognitive and 69% had normal motor outcomes. The cerebral palsy rate was 42%. The composite outcome of death or severe neurodevelopmental disability was observed in 58%, with no trends over the study period (P = .6). Increasing PVHI severity score was associated with death (P < .001). Increasing PVHI size and severity score were negatively associated with gross motor scores (P = .01 and .03, respectively). Trigone involvement was associated with cerebral palsy (41% vs 14%; P = .004). Associated posthemorrhagic ventricular dilation (36%) was an independent risk factor for poorer cognitive and motor outcomes (P < .001 for both). CONCLUSIONS: Increasing PVHI size and severity score were predictive of less optimal gross motor outcome and death in very preterm infants.

Developmental outcomes of very low birthweight infants with non-hemorrhagic ventricular dilatations and the relationships thereof with absolute brain volumes measured via two-dimensional ultrasonography.

PURPOSE: We calculated the brain volumes of preterm infants using two-dimensional cranial ultrasonography and explored the relationships thereof with neurodevelopment. METHODS: Cranial measurements were derived using routine ultrasonographic scanning. The brain was considered to be an ellipsoid and estimated absolute brain volumes (EABVs) were calculated by substracting the volumes of the two lateral ventricles from the total brain volumes. RESULTS: We enrolled preterm infants of mean gestational age 28 ± 2 weeks and mean birthweight 973 ± 187 g. Twenty-one exhibited dilated ventricles; their EABVs were lower than normal (206 ± 11 cm3 vs. 275 ± 17 cm3, p < 0.001). The mental development indices were similar (74 ± 5 vs. 78 ± 14, p = 0.069), but the psychomotor development indices (PDIs) differed significantly (77 ± 7 vs. 86 ± 17, p = 0.001). We found a slight positive correlation between the PDI and EABV (r = + 0.258, p = 0.012). CONCLUSION: The EABV can be calculated using two-dimensional measurements and low EABV found to be associated with poor neurological outcomes. TRIAL REGISTRATION: NCT02848755.

Feasibility and reproducibility of shear wave elastography in pediatric cranial ultrasound.

BACKGROUND: Head ultrasound (US) is commonly used to evaluate the neonatal brain but may be limited by its lack of sensitivity and specificity. Ultrasound shear wave elastography (SWE) might provide additional information to conventional gray-scale imaging. OBJECTIVE: To assess whether SWE of brain parenchyma can be (1) successfully performed at a large academic medical center where US technologists perform the majority of examinations and (2) used to detect intracranial pathology. MATERIALS AND METHODS: Pediatric patients undergoing head ultrasound underwent simultaneous SWE examination. We included normal examinations (n=70) and those with intracranial pathology (n=8) for analysis. We analyzed inter-reader variability and examination success rates and assessed the stiffness of white matter and deep gray nuclei in normal and pathological states across multiple gestational age groups. RESULTS: Average gestational age of the term, pre-term and extreme pre-term groups were 38.4±1.2 weeks, 29.0±3.7 weeks and 28.3±3.1 weeks, respectively. Overall examination success rate was 79.5%. We observed a decrease in the SWE examination time from the first month (5.9±3.7 min) to the second month (4.1±1.7 min; P=0.01). Forty-one repeat examinations were performed on 14 children by different technologists, with an intraclass correlation coefficient (ICC) of 0.91. Mean stiffness in the periventricular white matter was lower than in the deep gray nuclei in all gestational age groups: term group (1.3 m/s vs. 1.5 m/s, P<0.001), pre-term (1.3 m/s vs. 1.4 m/s P=0.12), and extremely preterm group (1.2 m/s vs. 1.4 m/s, P=0.001). Mean stiffness for the deep gray nuclei differed between the term (1.5±0.3 m/s) and pre-term (1.4±0.2 m/s) groups (P<0.01). No significant differences in white matter stiffness were seen in relation to gestational age. Infants with large intraparenchymal hemorrhage had increased white matter stiffness (1.3±0.1 m/s) and deep gray nuclei stiffness (1.6±0.2 m/s) compared to full-term infants with normal head ultrasounds. These differences approached statistical significance with P=0.09 and P=0.06, respectively. CONCLUSION: We demonstrated that SWE performed by pediatric sonography technologists is reproducible. We found differences in stiffness between deep gray nuclei and periventricular white matter across multiple age groups.

Prognostic value of cranial ultrasonography in comparison with magnetic resonance imaging in children with cerebral palsy: a population-based study.

The aim of this population-based study was to evaluate the characteristics of cerebral palsy (CP) in relation to the predominant pattern of the Magnetic Resonance Imaging Classification System (MRICS) that was analogously applied to the neonatal/early infant cranial ultrasound (CUS). The study included children born during the 2004-2007 period from the Croatian part (C28 RCP-HR) of the Surveillance of Cerebral Palsy in Europe (SCPE) CP register. Motor functions, accompanying impairments and brain MRI were evaluated in 227 children, 185 of which also had CUS. Concerning CP types, 56% of children had bilateral spastic, 34% unilateral spastic, 9% dyskinetic and 1% ataxic CP type. Gross Motor Function Classification System (GMFCS) revealed that 62.05% had mild (GMFCS I-III) and 37.85% had severe motor impairment (GMFCS IV-V). CUS showed white matter injury in 60%, gray matter injury in 12%, maldevelopments in 8%, miscellaneous changes in 14%, while 6% were normal; MRI showed significant agreement (κ=0.675, p<0.001). Neuroimaging findings of maldevelopments and predominant gray matter injury were associated with more severe CP, but 7% of children with CP had normal MRI. As we found very good agreement between CUS and MRI findings, CUS is recommended in children at an increased risk of CP if MRI is not available.

Outcome of Preterm Infants with Transient Cystic Periventricular Leukomalacia on Serial Cranial Imaging Up to Term Equivalent Age.

OBJECTIVE: To determine the outcome of preterm infants whose cystic periventricular leukomalacia "disappeared" on serial screening cranial imaging studies. STUDY DESIGN: Infants ≤26 weeks of gestation born between 2002 and 2012 who had cranial imaging studies at least twice, the most abnormal study at <28 days of age and another closest to 36 weeks, were reviewed. The outcome of late death (after 36 weeks postmenstrual age) or neurodevelopmental impairment (NDI) in surviving infants at 18-26 months corrected age was compared between the infants with no cystic periventricular leukomalacia on both studies and cystic periventricular leukomalacia that disappeared (cystic periventricular leukomalacia at <28 days but not at 36 weeks), persisted (cystic periventricular leukomalacia on both studies), or appeared late (cystic periventricular leukomalacia only at 36 weeks). Predictors of NDI were evaluated by logistic regression. RESULTS: Of 7063 eligible infants, 433 (6.1%) had cystic periventricular leukomalacia. Among the 433 infants with cystic periventricular leukomalacia, cystic periventricular leukomalacia disappeared in 76 (18%), persisted in 87 (20%), and 270 (62%) had late cystic periventricular leukomalacia. Loss to follow-up ranged between 3% and 13%. Death or NDI was more common in infants with disappeared cystic periventricular leukomalacia compared with those with no cystic periventricular leukomalacia (38 of 72 [53%] vs 1776 of 6376 [28%]; OR [95% CI] 2.8 [1.8-4.6]). Disappeared, persistent, and late cystic periventricular leukomalacia were all also independently associated with NDI (OR 1.17, 1.21, and 1.16, respectively). CONCLUSIONS: Infants with "disappeared" cystic periventricular leukomalacia are at increased risk of adverse outcome similar to infants with persistent or late cystic periventricular leukomalacia.

The role of certain perinatal features in the early motor repertoire of infants.

BACKGROUND: Lower gestational age negatively affects the neurodevelopmental outcomes of infants. Early motor repertoire is a reliable way to predict neurodevelopmental outcomes. This study aimed to determine the correlation between gestational age and early motor repertoire in infants and also the roles of multiple pregnancies, gender, cranial utrasonography (USG) results, and birth weight in this relationship. METHODS: This study included 139 infants, who were video recorded 9-17 weeks post-term. The recordings were evaluated using the Motor Optimality Score-Revised (MOS-R). Structural equation modeling tool was used for the path analysis of the models. RESULTS: There was a weak positive correlation between gestational age and the MOS-R. In the relationship between gestational age and the MOS-R, multiple pregnancies, gender, and USG outcomes had a moderating effect. While abnormal USG, male gender, and singleton pregnancy increased this correlation to a moderate level, normal USG reduced the strength of the correlation. Female and twin pregnancies were non-significant in the model. Birth weight had a full mediating effect on the relationship between gestational age and the MOS-R. CONCLUSIONS: Infants with younger gestational age or lower birth weight, male infants, and infants with problems on cranial USG may have poorer early motor repertoire.

Cranial ultrasonography in diagnosis of infantile cerebral cavernous malformation.

The case of an infantile cerebral cavernous malformation detected by transfontanelle cranial ultrasonography. Infantile cerebral cavernous malformations tend to cause more major bleeding compared to those in older groups, so early detection and treatment are crucial. Cranial ultrasonography can contribute to the early diagnosis of infantile cerebral cavernous malformations.

Relationships between early postnatal cranial ultrasonography linear measures and neurobehaviour at term-equivalent age in infants born <30 weeks' gestational age.

BACKGROUND: The relationship between early postnatal brain development and neurobehaviour at term-equivalent age (TEA) remains uncertain. AIM: We aimed to explore relationships between early postnatal cranial ultrasonography (cUS) linear measures of brain size and brain growth with neurobehaviour at TEA in infants born <30 weeks' gestational age (GA). STUDY DESIGN: Prospective observational cohort study. SUBJECTS: 137 infants born <30 weeks' GA without major brain injury on neonatal cUS. OUTCOME MEASURES: Neurobehaviour at TEA assessed using the General Movements Assessment (GMA) and Hammersmith Neonatal Neurological Examination (HNNE). RESULTS: The GMA was administered in 115/137 (84%) infants; 80 (70%) presented with abnormal general movements (GMs) (79 poor repertoire, 1 cramped synchronised). The HNNE was assessed in 106/137 (77%) infants; 52 (49%) had a suboptimal total score. With respect to brain size, larger measures of the corpus callosum length (CCL) and right anterior horn width (AHW) at 1-month were related to lower risk of abnormal GMs, and larger measures of the biparietal diameter at 1-week and 2-months were related to lower risk of a suboptimal HNNE. As for brain growth, increases of the CCL and transcerebellar diameter between birth and 1-month, and left and right AHWs between 1- and 2-months, were related to lower risk of abnormal GMs. CONCLUSION: Early postnatal brain size and brain growth were related to neurobehaviour at TEA in infants born <30 weeks' GA. This study provides preliminary evidence for the prognostic utility of early postnatal cUS linear measures as potential markers of neurodevelopment in later childhood.

Cystic Periventricular Leukomalacia Worsens Developmental Outcomes of Very-Low-Birth Weight Infants with Intraventricular Hemorrhage-A Nationwide Cohort Study.

Cystic periventricular leukomalacia (cPVL) is a major brain injury involving periventricular white matter that leads to neurodevelopmental impairment in very-low-birth weight (VLBW) infants. We investigated the neurodevelopmental outcomes (motor, cognition, visual, and hearing) of 5734 VLBW infants born between 2013 and 2019 and enrolled in the Korean Neonatal Network. Cranial ultrasound results were stratified by the presence of cPVL and severity of intraventricular hemorrhage (IVH) (no, low-grade [I/II], high-grade [III]). Neurodevelopmental impairment was evaluated using cerebral palsy for motor and Bayley Scales of Infant Development for cognition. cPVL was associated with motor, cognitive, and visual impairments in those without IVH and with low-grade IVH in pairwise comparisons (Cochran−Mantel−Haenszel p < 0.001). Conversely, cPVL was non-significantly correlated with cognitive impairment in high-grade IVH. In regression models adjusted for neonatal variables, isolated cPVL was strongly associated with motor (22.04; 11.39−42.63) and cognitive (3.10; 1.54−6.22) impairments. This study underlines the overall considerable significance of cPVL on NDI with divergent impacts depending on the severity of IVH and developmental indices.

Consensus Approach for Standardizing the Screening and Classification of Preterm Brain Injury Diagnosed With Cranial Ultrasound: A Canadian Perspective.

Acquired brain injury remains common in very preterm infants and is associated with significant risks for short- and long-term morbidities. Cranial ultrasound has been widely adopted as the first-line neuroimaging modality to study the neonatal brain. It can reliably detect clinically significant abnormalities that include germinal matrix and intraventricular hemorrhage, periventricular hemorrhagic infarction, post-hemorrhagic ventricular dilatation, cerebellar hemorrhage, and white matter injury. The purpose of this article is to provide a consensus approach for detecting and classifying preterm brain injury to reduce variability in diagnosis and classification between neonatologists and radiologists. Our overarching goal with this work was to achieve homogeneity between different neonatal intensive care units across a large country (Canada) with regards to classification, timing of brain injury screening and frequency of follow up imaging. We propose an algorithmic approach that can help stratify different grades of germinal matrix-intraventricular hemorrhage, white matter injury, and ventricular dilatation in very preterm infants.

Development and Characterization of Medical Phantoms for Ultrasound Imaging Based on Customizable and Mouldable Polyvinyl Alcohol Cryogel-Based Materials and 3-D Printing: Application to High-Frequency Cranial Ultrasonography in Infants.

This work presents an affordable and easily customizable methodology for phantom manufacturing, which can be used to mimic different anatomic organs and structures. This methodology is based on the use of polyvinyl alcohol-based cryogels as a physical substitute for biologic soft tissues and of 3-D printed polymers for hard tissues, moulding and supporting elements. Thin and durable soft-tissue mimicking layers and multilayer arrangements can be obtained using these materials. Special attention was paid to the acoustic properties (sound speed, attenuation coefficient and mechanical impedance) of the materials developed to simulate soft tissues. These properties were characterized as a function of the additives concentration (propylene-glycol and alumina particles). The polyvinyl alcohol formulation proposed in this work is stable over several freeze-thaw cycles, allowing the manufacturing of multilayer materials with controlled properties. The manufacturing methodology presented was applied to the development of a phantom for high-frequency cranial ultrasonography in infants. This phantom was able to reproduce the main characteristics of the ultrasound images obtained in neonates through the anterior fontanel, down to 8-mm depth.

Brain Volumes of very Low Birth Weight Infants Measured by Two-dimensional Cranial Ultrasonography: A Prospective Cohort Study.

BACKGROUND: Cranial ultrasonography is the main neuroimaging technique for very low birth weight infants. Low brain volume is associated with poor neurologic outcome. This study aimed to calculate brain volumes of preterm infants with two-dimensional measurements of cranial ultrasonography. METHODS: Intracranial height, anteroposterior diameter, bi-parietal diamater, ventricular height, thalamo-occipital distance and ventricular index were measured with routine cranial ultrasonographic scanning. Brain considered a spheric, ellipsoid model and estimated brain volume (EBV) was calculated by subtracting two lateral ventricular volumes from the total brain volume. RESULTS: One hundred and twenty-one preterm infants under a birth weight of 1500 g and 32 weeks of gestational age were included in this study. The mean gestational age of study population was 27.7 weeks, and mean birthweight was 1057 grams. Twenty-two of 121 infants had dilated ventricle, in this group, EBV was lower than normal group (202 ± 58 cm3 vs 250 ± 53 cm3, respectively, p<0.01). Advanced resuscitation, bronchopulmonary dysplasia and late-onset sepsis were found to be independent risk factors for low brain volume in our data. CONCLUSION: Estimated brain volume can be calculated by two-dimensional measurements with cranial ultrasonography.

Analysis of the intensity of radio-frequency signals in intracranial ultrasonography of preterm infants.

PURPOSE: The purpose of this study was to evaluate the usefulness of analysis of the intensity of radio-frequency (RF) signals in intracranial ultrasonography of preterm infants. METHODS: Twenty neonatal infants admitted to the neonatal intensive care unit of our hospital were included in this study. Their gestational age was 33-35 weeks. The studies were performed with a System 5 ultrasound system with 3.0-and 5.0-MHz transducers. The transducer was placed on the anterior fontanel to obtain images. Regions of interest were determined based on B-mode images and were positioned at the thalamus, caudate nucleus, cerebral white matter, cerebellum, brain stem, and lateral ventricle. The software used for analysis of the RF signals was EchoMAT (Vingmed Ultrasound). RESULTS: The RF signals of the ventricle and the choroid plexus showed the lowest and the highest intensities, respectively. The intensities of the brain stem and vermis signals were the same, and were higher than the intensity of the cerebellar hemisphere. The thalamus and caudate nucleus showed macroscopically identical brightness levels; however, the intensity of the thalamus was lower than that of the caudate nucleus. The intensity of subependymal hemorrhage was lower than that of the caudothalamic groove. The intensity of subependymal cyst was the same as that of the lateral ventricle. The RF signal frequencies and intensities were distinctive in each tissue. CONCLUSION: The results of this study suggest that measurement of RF signal intensity may be useful to differentiate macroscopically similar lesions.

Reliability in cerebellar size assessment by 2D cranial ultrasonography in neonates.

BACKGROUND: Cerebellar size appears to be correlated with the long-term outcome of preterm infants. Two-dimensional cranial ultrasonography (2D-cUS) is the first-line, routine tool to characterize newborn cerebral structures. Information regarding the accuracy of 2D-cUS for assessing cerebellar size is scarce. OBJECTIVES: To assess the reliability of cerebellar size using 2D-cUS. METHODS: Fifty infants were prospectively scanned for a variety of clinical indications. The scans were stored and then independently analyzed offline by two observers. The transverse cerebellar diameter coronally from the anterior and mastoid fontanels (TCD-AF and TCD-MF, respectively); the midsagittal cerebellar vermis height and the anterior-posterior diameter from the AF; and the width and height of the fourth ventricle coronally from the MF view were measured. Interobserver variability was assessed using the intraclass correlation (ICC) with 95% confidence interval (CI) for each of the paired measures. RESULTS: A total 294 images were included in the analysis. The interobserver ICCs were TCD-AF = 0.85 (0.76-0.91), TCD-MF = 0.9 (0.83-0.94), vermis height = 0.79 (0.66-0.88), anterior-posterior vermis diameter = 0.71 (0.5-0.84), width of the fourth ventricle = 0.72 (0.33-0.9), height of the fourth ventricle = 0.86 (0.7-0.92). The ICC for the TCD comparing the AF and the MF approach was ≥0.9 for both observers. CONCLUSIONS: The reliability of the offline 2D-cUS cerebellar size assessments is good, and TCD-MF is the most consistent measure. Further studies should address the predictive value for the neurodevelopmental outcome of serial cerebellar size assessments by 2D-cUS for preterm infants.

Quantitative analysis of cranial ultrasonographic periventricular echogenicity in relation to early neuromotor development in preterm infants.

BACKGROUND: Periventricular white matter (WM) hyperechoic flares that do not evolve into cystic lesion(s) are frequently encountered on cranial ultrasonography (CUS) of preterm infants. Subjective interpretation of its presence, however, is challenging and its association with maturation and neurodevelopment remains undefined. OBJECTIVES: To determine the relationship between quantitative WM echogenicity and postnatal and postmenstrual ages and the relationship between quantitative WM echogenicity and neuromotor development at term equivalent. METHODS: We measured the mean pixel brightness intensity at the frontoparietal and parieto-occipital WM, choroid plexus and calvarium bone on sequential neonatal CUS scans of preterm infants born at <34 weeks gestation. The relative echogenicity (RE) was derived by dividing the mean WM echogenicity to that of the choroid plexus (RE(CP)) or bone (RE(BN)). The Lacey Assessment of the Preterm Infant was administered before discharge. RESULTS: 58 preterm infants (the mean gestational age 30.6±2.3 weeks and the mean birth weight 1211.9±224.7 g) were included. The RE(CP) of the frontoparietal WM decreased significantly with advancing postnatal and postmenstrual ages (r=-0.4, p<0.0001). The RE(BN) values of the frontoparietal and parieto-occipital WM during intermediate and late predischarge CUS studies, respectively, were significantly associated with neuromotor status at term (p<0.05). The RE(CP) and RE(BN) measured during the first week of life were not associated with neuromotor status at term. CONCLUSIONS: Quantitative measurements of the periventricular WM echogenicity are feasible in neonatal CUSs of premature infants and may reflect microstructural developmental changes. An optimal echogenicity quantification technique and its correlation with long-term outcome remain to be determined.

Cranial ultrasonography of the immature cerebellum: Role and limitations.

Cranial ultrasonography (CUS) is a reliable and non-invasive tool to detect frequently occurring brain abnormalities and to monitor brain development and maturation in high risk neonates. Standard CUS views are obtained through the anterior fontanel. However, evaluation of the posterior fossa is often suboptimal with this approach. Cerebellar injury occurs frequently in preterm infants and has important prognostic consequences. Early detection is therefore important. This review focuses on techniques that optimize the performance of CUS when studying the preterm cerebellum, including the use of the mastoid fontanel and the adaptation of focus points and scan frequencies. For illustration, CUS images of the normal posterior fossa anatomy as well as examples of abnormalities that may be encountered in preterm infants are included. We also discuss the limitations of CUS and the role of magnetic resonance imaging.

Respiratory inhibition after crying and feeding hypoxemia in infants.

OBJECTIVE: To determine the incidence, risk factors and natural history of respiratory inhibition after crying (RIAC) and feeding hypoxemia. METHODS: We screened for RIAC and feeding hypoxemia among 393 infants with a gestational age ≥ 36 weeks using pulse oximetry. Twenty-seven infants were treated in the neonatal intensive care unit. RESULTS: RIAC and feeding hypoxemia were observed in 95 (24.2%) and 124 (31.6%) infants, respectively. RIAC correlated with feeding hypoxemia (p < 0.001), grade II increased echogenicity in the ganglionic eminence (p = 0.005), dilation of the lateral ventricle (p = 0.044), threatened premature labor (p = 0.033) and twin gestation (p = 0.089). Feeding hypoxemia correlated with RIAC (p < 0.001), abnormal cranial ultrasound findings (p < 0.001), maternal smoking during pregnancy (p = 0.083), asymmetric intrauterine growth restriction (p = 0.012) and twin gestation (p = 0.067). All infants recovered from RIAC in an average of 4.5 (2.0-7.0) d. Fifteen infants recovered from feeding hypoxemia, but 10 infants needed additional assistance and monitoring by nursing until the day of discharge. The day of discharge was day 8.0 (5.0-12.4). CONCLUSIONS: RIAC and feeding hypoxemia are observed among healthy infants, and these infants experience repeated events of prolonged hypoxemia.