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.This work was supported by the 2017 (PI0052/2017) and 2019 (ITI-0019-2019) ITI-Cadiz integrated territorial initiative for biomedical research European Regional Development Fund (ERDF) 2014-2020. Andalusian Ministry of Health and Families, Spain

MELAGE: A purely python based Neuroimaging software (Neonatal)

MELAGE, a pioneering Python-based neuroimaging software, emerges as a versatile tool for the visualization, processing, and analysis of medical images. Initially conceived to address the unique challenges of processing 3D ultrasound and MRI brain images during the neonatal period, MELAGE exhibits remarkable adaptability, extending its utility to the domain of adult human brain imaging. At its core, MELAGE features a semi-automatic brain extraction tool empowered by a deep learning module, ensuring precise and efficient brain structure extraction from MRI and 3D Ultrasound data. Moreover, MELAGE offers a comprehensive suite of features, encompassing dynamic 3D visualization, accurate measurements, and interactive image segmentation. This transformative software holds immense promise for researchers and clinicians, offering streamlined image analysis, seamless integration with deep learning algorithms, and broad applicability in the realm of medical imaging

Myocardial Function Maturation in Very-Low-Birth-Weight Infants and Development of Bronchopulmonary Dysplasia

Background: Myocardial function in very-low-birth-weight infants (VLBWIs) develops during early postnatal life, but different patterns of temporal evolution that might be related to the development of bronchopulmonary dysplasia (BPD) are not completely understood. Methods: A prospective cohort study including VLBWIs admitted to our NICU from January 2015 to 2017 was conducted. Plasma N-terminal pro B type natriuretic peptide (NTproBNP) levels were measured, and echocardiograms were performed at 24 and 72 h of life and weekly thereafter until 36 weeks of postmenstrual age (PMA). We measured the tricuspid annular plane systolic excursion (TAPSE) by M-mode; the lateral tricuspid E', A', and S' waves; and the myocardial performance index (MPI) by tissue doppler imaging (TDI). The subjects were divided into non-BPD and BPD groups. Results: We included 101 VLBWIs. The TAPSE and E', A', and S' waves increased while MPI-TDI decreased over time. Birth gestational age (GA) and postnatal PMA impacted these parameters, which evolved differently in those who developed BPD compared to those in the non-BPD group. The NTproBNP levels at 14 days of life and different echocardiographic parameters were associated with the development of BPD in different multivariate models. Conclusion: TAPSE and TDI values depend on GA and PMA and follow a different temporal evolution that is related to the later development of BPD. Combined biochemical and echocardiographic biomarkers can help identify which VLBWIs are at higher risk of developing BDP

Germinal Matrix-Intraventricular Hemorrhage of the Preterm Newborn and Preclinical Models: Inflammatory Considerations

The germinal matrix-intraventricular hemorrhage (GM-IVH) is one of the most important complications of the preterm newborn. Since these children are born at a critical time in brain development, they can develop short and long term neurological, sensory, cognitive and motor disabilities depending on the severity of the GM-IVH. In addition, hemorrhage triggers a microglia-mediated inflammatory response that damages the tissue adjacent to the injury. Nevertheless, a neuroprotective and neuroreparative role of the microglia has also been described, suggesting that neonatal microglia may have unique functions. While the implication of the inflammatory process in GM-IVH is well established, the difficulty to access a very delicate population has lead to the development of animal models that resemble the pathological features of GM-IVH. Genetically modified models and lesions induced by local administration of glycerol, collagenase or blood have been used to study associated inflammatory mechanisms as well as therapeutic targets. In the present study we review the GM-IVH complications, with special interest in inflammatory response and the role of microglia, both in patients and animal models, and we analyze specific proteins and cytokines that are currently under study as feasible predictors of GM-IVH evolution and prognosis

Assessment of the perception of vertical subjectivity in children born preterm

Children born preterm have increased rates of paediatric mortality and morbidity. Prematurity has been associated with impaired visual perception and visuo-motor integration. The alteration of the perception of verticality translates into alterations of the vestibular system at central and/or peripheral level, which may manifest itself in symptoms such as imbalance, dizziness or even vertigo. The aim of this study was to compare subjective visual vertical (SVV) test scores in children born preterm with those of children born at term at ages between 7 and 10. One hundred ten children with no neurodevelopmental disorder of 7 to 10 years of age were studied using a mobile application on a smartphone attached to a wall by means of a rotating plate. The SVV test was compared between two groups: a group of 55 preterm children (53 very preterm children born under 32 weeks of gestational age and 2 preterm with very low birth weight) and another group of 55 children born at term (after 37 weeks of gestational age). The SVV results were analysed for comparison with respect to prematurity, sex and age. We found no significant differences in the SVV study in the comparison between preterm and term children. In addition, no significant differences were observed regarding sex or age between 7 and 10 years.Conclusion: We found no alterations in the perception of vertical subjectivity in children between 7 and 10 years of age, with antecedents of very preterm birth and/or very low birth weight

Parental competences in fathers and mothers of very-low-birth-weight preterm infants

Objective: The goal was to analyze parental competences in Spanish families with very-low-birth-weight infants (≤32 weeks and/or less 1500 g) over 18 months of corrected age. Background: Parenting in families of very preterm infants is an interesting focus of research as we advance in the knowledge of how parental competences can have an important impact on child development. Method: Sixty-eight mothers and 56 fathers completed measures of parental competences, sociofamily risk, parental stress, social support, and emotional symptoms. Clinical characteristics and neonatal medical risk data were collected after birth. Statistical analyses were performed to compare parental competences with those of mothers and fathers of non-preterm infants. Generalized estimating equations were used for analysis, adjusted by family unit. Results: Mothers and fathers of preterm infants score higher in most dimensions of parental competences compared to a control group. Focusing on the preterm population, mothers score higher than fathers in daily involvement and mentalization and lower in parental self-care. When studied separately, we found different scores for fathers and mothers in parental competences (sociofamily risk, parental stress, social support, and emotional symptoms). Conclusion: Parents of preterm infants present better parental competences than parents of non-preterm infants when their children reach 18 months of age. It is important to consider the differences in parental competences between the mothers and fathers of these children. Implications: Our findings suggest the need to address parental competences to develop preventive and adaptive strategies in parents of preterm infants to promote positive parenting.This paper is part of the project PID2019‐110484RB‐I00 funded by MCIN/AEI/ 0.13039/501100011033. It was also funded by the 2017 (PI0052/2017) and 2019 (ITI‐0019‐2019) Cadiz‐integrated territorial initiative for biomedical research and the European Regional Development Fund (ERDF) 2014–2020, Andalusian Ministry of Health and Families, Spain. Funding informatio

Automatic segmentation of ventricular volume by 3D ultrasonography in post haemorrhagic ventricular dilatation among preterm infants

To train, evaluate, and validate the application of a deep learning framework in three-dimensional ultrasound (3D US) for the automatic segmentation of ventricular volume in preterm infants with post haemorrhagic ventricular dilatation (PHVD). We trained a 2D convolutional neural network (CNN) for automatic segmentation ventricular volume from 3D US of preterm infants with PHVD. The method was validated with the Dice similarity coefficient (DSC) and the intra-class coefficient (ICC) compared to manual segmentation. The mean birth weight of the included patients was 1233.1 g (SD 309.4) and mean gestational age was 28.1 weeks (SD 1.6). A total of 152 serial 3D US from 10 preterm infants with PHVD were analysed. 230 ventricles were manually segmented. Of these, 108 were used for training a 2D CNN and 122 for validating the methodology for automatic segmentation. The global agreement for manual versus automated measures in the validation data (n=122) was excellent with an ICC of 0.944 (0.874-0.971). The Dice similarity coefficient was 0.8 (+/- 0.01). 3D US based ventricular volume estimation through an automatic segmentation software developed through deep learning improves the accuracy and reduces the processing time needed for manual segmentation using VOCAL. 3D US should be considered a promising tool to help deepen our current understanding of the complex evolution of PHVD

Ultrasonographic Estimation of Ventricular Volume in Infants Born Preterm with Posthemorrhagic Ventricular Dilatation: A Nested Substudy of the Randomized Controlled Early Versus Late Ventricular Intervention Study (ELVIS) Trial

Objective: To study the potential role of ventricular volume (VV) estimation in the management of posthemorrhagic ventricular dilatation related to the need for ventriculoperitoneal (VP)-shunt insertion and 2-year neurodevelopmental outcome in infants born preterm. Study design: We included 59 patients from the Early vs Late Ventricular Intervention Study from 4 participating centers. VV was manually segmented in 209 3-dimensional ultrasound scans and estimated from 2-dimensional ultrasound linear measurements in a total of 1226 ultrasounds. We studied the association of both linear measurements and VV to the need for VP shunt and 2-year neurodevelopmental outcome in the overall cohort and in the 29 infants who needed insertion of a reservoir. We used general estimating equations to account for repeated measures per individual. Results: Maximum pre-reservoir VV (β coefficient = 0.185, P = .0001) and gestational age at birth (β = −0.338; P = .0001) were related to the need for VP shunt. The estimated optimal single VV measurement cut point of 17 cm3 correctly classified 79.31% with an area under the curve of 0.76 (CI 95% 0.74-0.79). Maximum VV (β = 0.027; P = .012) together with VP shunt insertion (β = 3.773; P = .007) and gestational age (β = −0.273; P = .0001) were related to cognitive outcome at 2 years. Maximum ventricular index and anterior horn width before reservoir insertion were independently associated with the need of VP shunt and the proposed threshold groups in the Early vs Late Ventricular Intervention Study trial were associated with long-term outcome. Conclusions: Pre-reservoir VV measurements were associated with the need for VP-shunt insertion and 2-year cognitive outcome among infants born preterm with posthemorrhagic ventricular dilatation. Trial registration: ISRCTN43171322

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

Left Ventricular Dysfunction and Plasmatic NT-proBNP Are Associated with Adverse Evolution in Respiratory Syncytial Virus Bronchiolitis

Aim: To investigate whether the presence of left ventricular myocardial dysfunction (LVMD) assessed by Tei index (LVTX) impacts the outcomes of healthy infants with Respiratory Syncytial Virus Bronchiolitis (RSVB). To explore whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) increases the accuracy of traditional clinical markers in predicting the outcomes. Methods: A single-centre, prospective, cohort study including healthy infants aged 1–12 months old admitted for RSVB between 1 October 2016 and 1 April 2017. All patients underwent clinical, laboratory and echocardiographic evaluation within 24 h of admission. Paediatric intensive care unit (PICU) admission was defined as severe disease. Results: We enrolled 50 cases of RSVB (median age of 2 (1–6.5) months; 40% female) and 50 age-matched controls. We observed higher values of LVTX in infants with RSVB than in controls (0.42 vs. 0.36; p = 0.008). Up to nine (18%) children presented with LVMD (LVTX > 0.5), with a higher incidence of PICU admission (89% vs. 5%; p < 0.001). The diagnostic performance of NT-proBNP in predicting LVMD was high (area under the receiver operator characteristic curve (AUC) 0.95, CI 95% 0.90–1). The diagnostic yield of the predictive model for PICU admission that included NT-proBNP was excellent (AUC 0.945, CI 95% 0.880–1), and significantly higher than the model without NT-proBNP (p = 0.026). Conclusions: LVMD could be present in healthy infants with RSVB who develop severe disease. NT-proBNP seems to improve traditional clinical markers for outcomes