A deep sift convolutional neural networks for total brain volume estimation from 3D ultrasound images.

Preterm infants are a highly vulnerable population. The total brain volume (TBV) of these infants can be accurately estimated by brain ultrasound (US) imaging which enables a longitudinal study of early brain growth during Neonatal Intensive Care (NICU) admission. Automatic estimation of TBV from 3D images increases the diagnosis speed and evades the necessity for an expert to manually segment 3D images, which is a sophisticated and time consuming task. We develop a deep-learning approach to estimate TBV from 3D ultrasound images. It benefits from deep convolutional neural networks (CNN) with dilated residual connections and an additional layer, inspired by the fuzzy c-Means (FCM), to further separate the features into different regions, i.e. sift layer. Therefore, we call this method deep-sift convolutional neural networks (DSCNN). The proposed method is validated against three state-of-the-art methods including AlexNet-3D, ResNet-3D, and VGG-3D, for TBV estimation using two datasets acquired from two different ultrasound devices. The results highlight a strong correlation between the predictions and the observed TBV values. The regression activation maps are used to interpret DSCNN, allowing TBV estimation by exploring those pixels that are more consistent and plausible from an anatomical standpoint. Therefore, it can be used for direct estimation of TBV from 3D images without needing further image segmentation.

Alteraciones en resonancia magnética asociadas a tratamiento con vigabatrina / Magnetic resonance imaging abnormalities associated with vigabatrin therapy

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Neonatal arterial stroke location is associated with outcome at 2 years: a voxel-based lesion-symptom mapping study.

OBJECTIVE: In contrast to motor impairments, the association between lesion location and cognitive or language deficits in patients with neonatal arterial ischaemic stroke remains largely unknown. We conducted a voxel-based lesion-symptom mapping cross-sectional study aiming to reveal neonatal arterial stroke location correlates of language, motor and cognitive outcomes at 2 years of age. DESIGN: Prospective observational multicentre study. SETTING: Six paediatric university hospitals in Spain. PARTICIPANTS: We included 53 patients who had a neonatal arterial ischaemic stroke with neonatal MRI and who were followed up till 2 years of age. MAIN OUTCOME MEASURES: We analysed five dichotomous clinical variables: speech therapy (defined as the need for speech therapy as established by therapists), gross motor function impairment, and the language, motor and cognitive Bayley scales. All the analyses were controlled for total lesion volume. RESULTS: We found that three of the clinical variables analysed significantly correlated with neonatal stroke location. Speech therapy was associated with lesions located mainly at the left supramarginal gyrus (p=0.007), gross motor function impairment correlated with lesions at the left external capsule (p=0.044) and cognitive impairment was associated with frontal lesions, particularly located at the left inferior and middle frontal gyri (p=0.012). CONCLUSIONS: The identification of these susceptible brain areas will allow for more precise prediction of neurological impairments on the basis of neonatal brain MRI.

Ultrasonographic Estimation of Total Brain Volume: 3D Reliability and 2D Estimation. Enabling Routine Estimation During NICU Admission in the Preterm Infant.

Objectives: The aim of this study is to explore if manually segmented total brain volume (TBV) from 3D ultrasonography (US) is comparable to TBV estimated by magnetic resonance imaging (MRI). We then wanted to test 2D based TBV estimation obtained through three linear axes which would enable monitoring brain growth in the preterm infant during admission. Methods: We included very low birth weight preterm infants admitted to our neonatal intensive care unit (NICU) with normal neuroimaging findings. We measured biparietal diameter, anteroposterior axis, vertical axis from US and MRI and TBV from both MRI and 3D US. We calculated intra- and interobserver agreement within and between techniques using the intraclass correlation coefficient and Bland-Altman methodology. We then developed a multilevel prediction model of TBV based on linear measurements from both US and MRI, compared them and explored how they changed with increasing age. The multilevel prediction model for TBV from linear measures was tested for internal and external validity and we developed a reference table for ease of prediction of TBV. Results: We used measurements obtained from 426 US and 93 MRI scans from 118 patients. We found good intra- and interobserver agreement for all the measurements. US measurements were reliable when compared to MRI, including TBV which achieved excellent agreement with that of MRI [ICC of 0.98 (95% CI 0.96-0.99)]. TBV estimated through 2D measurements of biparietal diameter, anteroposterior axis, and vertical axis was comparable among both techniques. We estimated the population 95% confidence interval for the mean values of biparietal diameter, anteroposterior axis, vertical axis, and total brain volume by post-menstrual age. A TBV prediction table based on the three axes is proposed to enable easy implementation of TBV estimation in routine 2D US during admission in the NICU. Conclusions: US measurements of biparietal diameter, vertical axis, and anteroposterior axis are reliable. TBV segmented through 3D US is comparable to MRI estimated TBV. 2D US accurate estimation of TBV is possible through biparietal diameter, vertical, and anteroposterior axes.

Lung ultrasound score and diuretics in preterm infants born before 32 weeks: A pilot study.

OBJECTIVE: To describe if weekly determined lung ultrasound (LU) scores in preterm infants born before 32 weeks (PTB32W) change with diuretic therapy. DESIGN: We included infants who received diuretics and compared LU scores according to their evolution on respiratory support (RS) before and after diuretics. RESULTS: We included 18 PTB32W divided into two groups. Both groups were similar in terms of median gestational age: 26 weeks (interquartile range [IQR]: 25-28) in the responders' group and 27 weeks (IQR: 24-28) in the other. They differed, however, in the median number of days on invasive mechanical ventilation: 27 (IQR: 11-43) versus 76 (IQR: 35-117), p = .03; in addition to the number of infants with moderate-severe bronchopulmonary dysplasia: 3 (33%) versus 8 (89%), p = .025. The responders' group showed lower LU scores 2 days after diuretics, with a median LU score of 6 (IQR: 3-12) versus 14 (IQR: 12-17) in the nonresponders group, p = .03; 1 week after (3 [IQR: 0-10] versus 12 [12-12], p = .04); and 3 weeks after (5 [IQR: 3-6] versus 12 [10-15], p = .01). RS also decreased at the same time: 7 out of 9 (78%) were extubated in the responders' group, and 1 out of 9 (11%) in the nonresponders group, p = .02, and these differences remained throughout the entire follow-up. CONCLUSIONS: There is a group of PTB32W patients whose LU score improves after diuretics. This change appears only in those patients that can be weaned off from RS, and at the same period of time as the administration of diuretics.

Pleural line thickness reference values for preterm and term newborns.

BACKGROUND: In lung ultrasound (LUS), the pleural line is an artifact whose thickness depends on the underlying lung pathology. To date there are no published studies on normal values of pleural line thickness (PLT) in newborns. OBJECTIVE: The aim of our study is to describe normal PLT values in term newborn (TN) and preterm newborn (PTN). METHODS: We recruited eupneic TN and PTN, under 34 weeks of gestation, on their first 24 hours of life. Newborns presenting any respiratory distress since birth were excluded. LUS was performed in four areas: upper anterior, lower anterior, lateral and posterior. At each location, we measured PLT and values where compared. Intraobserver and interobserver agreement were assessed using the intraclass correlation coefficient (ICC), and the kappa coefficient. RESULTS: We included 23 TN with a median birth weight of 3365 g (interquartile range [IQR] 3100-3575 g) and a median gestational age of 39 weeks (IQR, 38-40 weeks). In the PTN group, 23 patients were included with a median birth weight of 1350 g (IQR, 1150-1590 g) and a median gestational age of 31 weeks (IQR, 30-32 weeks). Median PLT values were less than 1 mm, and there were no significant differences between groups at any locations, with the exception of the left lower anterior field (0.79 mm [IQR, 0.72-0.89 mm] vs 0.68 mm [IQR, 0.62-0.72 mm]). Intraobserver agreement was high: consistency ICC 0.77 (95% confidence interval [CI], 0.32-0.92) and absolute ICC 0.78 (95% CI, 0.34-0.93). Interobserver agreement was high for the definition of thin pleural line as less than 1 mm. CONCLUSIONS: TN and asymptomatic PTN have similar PLT values. Overall, PLT in healthy newborns should be less than 1 mm.

Reproducibility and reference values of diaphragmatic shortening fraction for term and premature infants.

BACKGROUND: New ultrasound measurements to diagnose diaphragmatic dysfunction, including diaphragmatic shortening fraction (DSF), have been studied in adults and children, but there are no data on reference values for neonates. OBJECTIVE: To describe DSF reference values for term neonate (TN) and preterm neonate (PTN), and to calculate its reproducibility. METHODS: We included asymptomatic TN and PTN during their first 24 hours of life. We measured DSF at the zone of apposition in both hemithoraces. Reproducibility of image acquisition, including inter- and intra-rater agreement of the measurements were calculated among an experienced and a novel operator (after completion of a 1-day course on lung ultrasound [LU] and performance of 10 diaphragm ultrasounds [DUs] under supervision), and a more-trained examiner (completion of a 1-day course on LU and performance of 60 DUs under supervision). RESULTS: Two groups of 33 TN and 33 PTN were studied. Median DSF values did not differ between the groups, although diaphragm thickness was higher in the TN group. Intra-observer reproducibility: the intraclass correlation coefficient (ICC) was 0.95 (95% confidence interval [95% CI] 0.86-0.98). Interobserver reproducibility with novel operator had an ICC of 0.42 (95% CI -0.74 to 0.81), and with a more experienced operator improved to 0.76 (95% CI 0.27-0.92). Both intra- and interobserver agreement were high. CONCLUSIONS: Asymptomatic TN and PTN have similar DSF values in the first 24 hours of life. The intra- and interobserver agreement is high. Reproducibility is acceptable, but intensive training is necessary to perform adequate DU.

Lung ultrasound score as early predictor of bronchopulmonary dysplasia in very low birth weight infants.

BACKGROUND: Lung ultrasound (LU) has been widely used to diagnose and monitor acute lung diseases in neonates, but its role in chronic diseases has not been elucidated. OBJECTIVE: We aim to describe the evolution of a lung ultrasound score (LU score) in very low birth weight infants (VLBWI) with and without bronchopulmonary dysplasia (BPD). METHODS: We prospectively included 59 VLBWI and performed LU in the first 24 and 72 hours of life, and then weekly until 36 weeks´ postmenstrual age (PMA). We calculated the LU score as a semiquantitative score representing the aeration (0-3) in three different areas of each lung. RESULTS: The non-BPD group (n = 38) had lower LU score at 1, 2, 3, 4, and 36 weeks' PMA than the BPD group: median score of 1 (0-4) vs 7 (3-10), P < .001; 0 (0-1) vs 7 (4-9), P < .001; 0 (0-1) vs 8 (7-11), P < .001; 0 (0-2) vs 9 (4-12), P < .001; 0 (0-0) vs 3 (0-6), P < .001. A LU score of 5 or above at 1 week of life predicted BPD with a sensitivity (Se) of 71%, specificity (Sp) 80%, area under the ROC curve (AUC) 0.8, and at 2 weeks of life with Se 74%, Sp 100%, and AUC 0.93. An LU score of 4 or above at 4 weeks predicted moderate-severe BPD (Se 100%, Sp 80%, and AUC 0.89). CONCLUSION: In VLBWI without BPD, LU score increases during the first week of life and decreases thereafter, whereas among subjects with BPD, the LU score remains high until 36 weeks´ PMA. LU score can predict the diagnosis of BPD at 1 week and 2 weeks of life, and may predict moderate-severe BPD at 4 weeks of life.

NT-proBNP plasma levels as biomarkers for pulmonary hypertension in healthy infants with respiratory syncytial virus infection.

Aim: To explore NT-proBNP as biomarker for pulmonary hypertension (PH) in infants with respiratory syncytial virus infection (RSVI). Patients & methods: We prospectively enrolled 93 healthy infants with RSVI aged 1-12 months. NT-proBNP determination and echocardiography were performed at admission. Results: PH was found in 22% of patients and associated with a severe course of the disease. NT-proBNP >1635 pg/ml resulted an independent predictor for PH (odds ratio: 16.46 [95% CI: 4.10-66; p < 0.001]). The diagnostic performance of NT-proBNP to detect PH in RSVI was high (area under receiver operator curve of 0.932 [95% CI: 0.883-0.981; p < 0.001]). Conclusions: The presence of PH in healthy infants with RSVI is associated with worse outcomes. NT-proBNP resulted an accurate biomarker for PH in this setting.

Broad spectrum antibiotics in newborns increase multi-drug resistant infections.

Our objective was to determine if broad spectrum antibiotics (BSA) are associated with multi-resistant bacterial (MRB) infections in neonatal patients. We conducted a case-control study with two groups of patients: those with and without a MRB infection. We included 43 cases and 43 controls. MRB strains were: 21 S. maltophila (49%), 11 ESBL-producing Enterobacteriae (25%), 8 P. aeruginosa (19%) and 3 MRSA (7%). Odds ratio (OR) for MRB after seven days of carbapenems was 4.25 (95% confidence interval (CI) 1.4-17.4) and OR for MRB after seven days of third generation cephalosporin was 8 (95% CI 1.1-34.9). BSA longer than seven days, increases MRB infections 22.5 times in patients with bronchopulmonary dysplasia (BPD). Our data show a clear association between the use of BSA and the development of MRB infections, especially in BPD. Although we cannot state this is a causal relationship, we can recommend avoiding prolonged treatment with these antibiotics in preterm babies at risk of BPD.

Late stillbirth due to listeriosis

Listeriosis is a sporadic infectious disease, which affects high-risk populations, such as the elderly, pregnant women, newborns, and immunocompromised patients. During pregnancy, listeriosis usually presents like a mild non-specific infection, but it may be responsible for fetal loss, preterm labor, early onset neonatal sepsis, and neonatal death. We report the case of a late stillbirth secondary to maternal chorioamnionitis. Listeria monocytogenes was isolated from the amniotic fluid and the fetal pleural fluid. The fetal autopsy revealed a disseminated inflammatory response with multi-organ involvement. This case illustrates the importance of the prevention and the diagnosis of listeriosis during gestation and may help us to understand the physiopathology of fetal loss due to listeriosis.

Monitoring of Blood Pressure is not Enough to Avoid Neonatal Postoperative Encephalopathy.

Background Neonatal encephalopathy with seizures after general anesthesia not occurring in infants undergoing cardiac or major neurosurgery is very uncommon. An ischemic origin due to cerebral hypoperfusion from perioperative hypotension has been suggested, but there is a lack of a consensus definition for intraoperatory hypotension in neonates. Case Report We report the first case of neonatal encephalopathy with seizures in a neonate with anorectal malformation. He underwent a colostomy with caudal anesthesia combined with light general anesthesia. Intraoperative systolic blood pressure and mean blood pressure values were considered normal. Thirty-two hours after the intervention, the patient presented electroclinical seizures. Diffusion-weighted imaging showed bilateral involvement with reduced diffusivity in the watershed areas of the middle cerebral artery and posterior cerebral artery. Conclusion Perioperative monitoring of blood pressure is not enough in neonatal surgery. Cerebral magnetic resonance imaging should be considered in infants with noncardiac congenital anomalies after neonatal surgery and long-term follow-up is required.

Feasibility of Helmet-delivered Continous Positive Airway Pressure in Very Low Birthweight Infants.

We describe our experience with helmet-delivered continuous positive airway pressure in five preterm newborns. We analyzed oxygen requirement, arterial oxygen saturation, respiratory rate, medium arterial pressure, heart rate, apneic spells and patient's comfort. The patients' vital signs or pain scale were not different before and after treatment.

Late stillbirth due to listeriosis.

Listeriosis is a sporadic infectious disease, which affects high-risk populations, such as the elderly, pregnant women, newborns, and immunocompromised patients. During pregnancy, listeriosis usually presents like a mild non-specific infection, but it may be responsible for fetal loss, preterm labor, early onset neonatal sepsis, and neonatal death. We report the case of a late stillbirth secondary to maternal chorioamnionitis. Listeria monocytogenes was isolated from the amniotic fluid and the fetal pleural fluid. The fetal autopsy revealed a disseminated inflammatory response with multi-organ involvement. This case illustrates the importance of the prevention and the diagnosis of listeriosis during gestation and may help us to understand the physiopathology of fetal loss due to listeriosis.

Empiema intraventricular piogénico por Veillonella parvula en un recién nacido prematuro / Pyogenic intraventricular empyema owing to Veillonella parvulain a preterm infant

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Prognostic Value of the Apparent Diffusion Coefficient in Newborns with Hypoxic-Ischaemic Encephalopathy Treated with Therapeutic Hypothermia.

BACKGROUND: Apparent diffusion coefficient (ADC) quantification has been proven to be of prognostic value in term newborns with hypoxic-ischaemic encephalopathy (HIE) who were treated under normothermia. OBJECTIVES: To evaluate the prognostic value of ADC in standardized brain regions in neonates with HIE who were treated with therapeutic hypothermia (TH). METHODS: This prospective cohort study included 54 term newborns who were admitted with HIE and treated with TH. All magnetic resonance imaging examinations were performed between days 4 and 6 of life, and ADC values were measured in 13 standardized regions of the brain. At 2 years of age we explored whether ADC values were related to composite outcomes (death or survival with abnormal neurodevelopment). RESULTS: The severity of HIE is inversely related to ADC values in different brain regions. We found that lower ADC values in the posterior limb of the internal capsule (PLIC), the thalami, the semioval centre, and frontal and parietal white matter were related to adverse outcomes. ADC values in the PLIC and thalami are good predictors of adverse outcomes (AUC 0.86 and 0.76). CONCLUSIONS: Low ADC values in the PLIC, thalamus, semioval centre, and frontal and parietal white matter in full-term infants with HIE treated with TH were associated with a poor outcome.

Low-voltage pattern and absence of sleep-wake cycles are associated with severe hemorrhage and death in very preterm infants.

UNLABELLED: Amplitude integrated electroencephalogaphy (aEEG) is becoming an important tool for the assessment of cerebral activity in preterm newborns. Describing the relationship between early aEEG patterns and intraventricular hemorrhage (IVH) can improve our knowledge of neurological injury in the preterm newborn. The aim of this prospective study was to identify early changes in the aEEG in premature newborns that could be associated to severe neurological lesion/death. Preterm newborns with a birth weight ≤1,500 g and/or 32 weeks of gestation were included. aEEG monitoring was performed during the first 72 h of life. A qualitative analysis of the aEEG recordings was performed, based on continuity, sleep-wake cycles (SWCs), inferior lower margin amplitude (LMA), and bandwidth (BW). Key outcomes were severe IVH and/or death. Ninety-two subjects were included (mean gestational age 28 weeks). In 28.6 % of subjects with HIV III/IHP, a low-voltage pattern was observed. A statistically significant relationship was found between low-voltage tracings and death and neurological lesion/death. Absent SWCs during the first 72 h were also related to death. CONCLUSION: Early aEEG patterns can be predictive of neurological outcome in the preterm newborn. Low-voltage tracing and absence of SWCs are associated with severe neurological lesions/death.