Qualitative analysis of mothers' perception related to the delivery of information regarding preterm births.

BACKGROUND: Preterm birth is a major health issue due to its potential outcomes and socioeconomic impact. Prenatal counseling is of major importance for parents because it is believed that the risk of preterm birth is associated with a higher parental mental burden. Nowadays in France, the content and delivery of antenatal counseling is based on personal experience since there is a lack of official guidelines. The goal of the study was to evaluate maternal perception of antenatal information delivered in the setting of preterm births. METHODS: A qualitative study was performed using semi-structured individual interviews of 15 mothers with a child born > 26-34 GW. Data analysis was based on a constant comparative method. RESULTS: Concerning prenatal counseling content, parents wanted to be informed of their role in the care of their preterm child more so than statistics that were not always considered relevant. Parents' reactions to the announcement of the risk of a preterm birth was dominated by stupefaction, uncertainty and anxiety. When it comes to the setting of prenatal counseling, patients' room was deemed an appropriate setting by parents and ideally the presence of a coparent was appreciated as it increased patients' understanding. The physicians' attitude during the counseling was considered appropriate and described as empathic and optimistic. The importance of support throughout the hospitalization in the form of other parents' experiences, healthcare professionals and the possibility to preemptively visit the NICU was emphasized by participants. Delivery experience was dominated by a sense of uncertainty, and urgency. Some leads for improvement included additional support of information such as virtual NICU visit; participants also insisted on continuity of care and the multidisciplinary aspect of counseling (obstetrician, neonatologist, midwife, nurse, lactation consultant and psychologist). CONCLUSION: Highlighting parents' expectations about prenatal counseling could lead to the establishment of overall general guidelines. However, some topics like the use of statistics and mentioning the risk of death underline the importance of a personalized information.

Risk factors for unexpected infant death among very premature infants in France.

BACKGROUND: Prematurity is one of the risk factors for sudden unexpected infant death (SUID), a phenomenon that remains poorly explained. MATERIALS AND METHODS: The analysis of specific factors associated with SUID among very premature infants (VPI) was performed through a retrospective review of data collected in the French SUID registry from May 2015 to December 2018. The factors associated with SUID among VPI were compared with those observed among full-term infants (FTI). Results are expressed as means (standard deviation [SD]) or medians (interquartile range [IQR)]. RESULTS: During the study period, 719 cases of SUID were included in the registry, 36 (incidence: 0.60 ‰) of which involved VPI (gestational age: 29.2 [2] weeks, 1157 [364]) g] and 313 (0.18 ‰) involved FTI (gestational age: 40 [0.8] weeks, 3298 [452] g). The infants' postnatal age at the time of death was similar in the two groups: 15.5 (12.2-21.8) vs. 14.5 (7.1-23.4) weeks. We observed low breastfeeding rates and a high proportion of fathers with no occupation or unemployment status among the VPI compared to the FTI group (31% vs. 55 %, p = 0.01 and 32% vs. 13 %, p = 0.05, respectively). Among the VPI, only 52 % were in supine position, and 29 % were lying prone at the time of the SUID (compared to 63 % and 17 %, respectively, in the FTI group). CONCLUSION: This study confirms prematurity as a risk factor for SUID with no difference in the SUID-specific risk factors studied except for breastfeeding and socioeconomic status of the fathers. VPI and FTI died at similar chronological ages with a high proportion of infants dying in prone position. These results argue for reinforcement of prevention strategies in cases of prematurity.

Early detection of late-onset neonatal sepsis from noninvasive biosignals using deep learning: A multicenter prospective development and validation study.

BACKGROUND: Neonatal sepsis is responsible for significant morbidity and mortality worldwide. Its accurate and timely diagnosis is hindered by vague symptoms and the urgent necessity for early antibiotic intervention. The gold standard for diagnosing the condition is the identification of a pathogenic organism from normally sterile sites via laboratory testing. However, this method is resource-intensive and cannot be conducted continuously. OBJECTIVE: This study aimed to predict the onset of late-onset sepsis (LOS) with good diagnostic value as early as possible using non-invasive biosignal measurements from neonatal intensive care unit (NICU) monitors. METHODS: In this prospective multicenter study, we developed a multimodal machine learning algorithm based on a convolutional neural network (CNN) structure that uses the power spectral density (PSD) of recorded biosignals to predict the onset of LOS. This approach aimed to discern LOS-related pathogenic spectral signatures without labor-intensive manual artifact removal. RESULTS: The model achieved an area under the receiver operating characteristic score of 0.810 (95 % CI 0.698-0.922) on the validation dataset. With an optimal operating point, LOS detection had 83 % sensitivity and 73 % specificity. The median early detection was 44 h before clinical suspicion. The results highlighted the additive importance of electrocardiogram and respiratory impedance (RESP) signals in improving predictive accuracy. According to a more detailed analysis, the predictive power arose from the morphology of the electrocardiogram's R-wave and sudden changes in the RESP signal. CONCLUSION: Raw biosignals from NICU monitors, in conjunction with PSD transformation, as input to the CNN, can provide state-of-the-art prediction performance for LOS without the need for artifact removal. To the knowledge of the authors, this is the first study to highlight the independent and additive predictive potential of electrocardiogram R-wave morphology and concurrent, sudden changes in the RESP waveform in predicting the onset of LOS using non-invasive biosignals.

Meconium Concentrations of Pesticides and Risk of Hypospadias: A Case-Control Study in Brittany, France.

BACKGROUND: Hypospadias is a male genital tract defect for which an increase in prevalence has been documented over the last few decades. A role for environmental risk factors is suspected, including prenatal exposure to pesticides. OBJECTIVES: To study the risk of hypospadias in association with multiple pesticide measurements in meconium samples. METHODS: The Brittany Registry of Congenital Anomalies (France) conducted a case-control study between 2012 and 2018. Cases were hypospadias, ascertained by a pediatrician and a pediatric surgeon, excluding genetic conditions, following European Surveillance of Congenital Anomalies guidelines (N = 69). Controls (N = 135) were two male infants without congenital anomaly born after each case in the same maternity unit. Mothers in the maternity units completed a self-administered questionnaire, we collected medical data from hospital records, and medical staff collected meconium samples. We performed chemical analysis of 38 pesticides (parent compound and/or metabolite) by UHPLC/MS/MS following strict quality assurance/quality control criteria and blind to case-control status. We carried out logistic regression accounting for frequency-matching variables and major risk factors. RESULTS: Among the 38 pesticides measured, 16 (42%) were never detected in the meconium samples, 18 (47%) were in <5% of samples, and 4 (11%) in ≥5% of the samples. We observed an association between the detection of fenitrothion in meconium and the risk of hypospadias (OR = 2.6 [1.0-6.3] with n cases = 13, n controls = 21), but not the other pesticides. CONCLUSIONS: Our small study provides a robust assessment of fetal exposure. Fenitrothion's established antiandrogenic activities provide biologic plausibility for our observations. Further studies are needed to confirm this hypothesis.

Early exposure to mercury and cardiovascular function of seven-year old children in Guadeloupe (French West Indies).

BACKGROUND: The cardiotoxicity of prenatal exposure to mercury has been suggested in populations having regular contaminated seafood intake, though replications in the literature are inconsistent. METHODS: The Timoun Mother-Child Cohort Study was set up in Guadeloupe, an island in the Caribbean Sea where seafood consumption is regular. At seven years of age, 592 children underwent a medical examination, including cardiac function assessment. Blood pressure (BP) was taken using an automated blood pressure monitor, heart rate variability (HRV, 9 parameters) and electrocardiogram (ECG) characteristics (QT, T-wave parameters) were measured using Holter cardiac monitoring during the examination. Total mercury concentrations were measured in cord blood at birth (median = 6.6 µg/L, N = 399) and in the children's blood at age 7 (median = 1.7 µg/L, N = 310). Adjusted linear and non-linear modelling was used to study the association of each cardiac parameter with prenatal and childhood exposures. Sensitivity analyses included co-exposures to lead and cadmium, adjustment for maternal seafood consumption, selenium and polyunsaturated fatty acids (n3-PUFAs), and for sporting activity. RESULTS: Higher prenatal mercury was associated with higher systolic BP at 7 years of age (ßlog2 = 1.02; 95% Confidence Interval (CI) = 0.10, 1.19). In boys, intermediate prenatal exposure was associated with reduced overall HRV and parasympathetic activity, and longer QT was observed with increasing prenatal mercury (ßlog2 = 4.02; CI = 0.48, 7.56). In girls, HRV tended to increase linearly with prenatal exposure, and no association was observed with QT-wave related parameters. Mercury exposure at 7 years was associated with decreased BP in girls (ßlog2 = -1.13; CI = -2.22, -0.004 for diastolic BP). In boys, the low/high-frequency (LF/HF) ratio increased for intermediate levels of exposure. CONCLUSION: Our study suggests sex-specific and non-monotonic modifications in some cardiac health parameters following prenatal exposure to mercury in pre-pubertal children from an insular fish-consuming population.

Educational Concerns About the Safety of Cataract Surgery During Residency: The E3CAPS Pedagogic Study.

INTRODUCTION: Cataract surgery is the most common surgical procedure performed in France. While the incidence of intraoperative complications affecting visual prognosis is extremely low, given the large number of patients operated on, the absolute number of patients affected by complications is quite high. Complication rates are significantly higher when ophthalmology residents (ORs) perform the surgery. Although lack of experience remains the main risk factor, sleep deprivation may adversely affect ORs' successful surgery rate. The value of the EyeSi® surgical simulator in initial training has been demonstrated to increase cataract surgery safety through the transfer of surgical skills from the simulator to the operating room. However, there is no consensus regarding how much training is needed before the first-time ORs are allowed to operate. There is also no scientific evidence that sleep deprivation is associated with a decrease in surgical performance. Establishing a validated protocol for cataract surgery training using the EyeSi surgical simulator (referred to further as the EyeSi) and identifying risk factors for intraoperative complications related to sleep deprivation will improve cataract surgery safety and lead to the reorganization of our healthcare systems. METHODS AND PLANNED OUTCOMES: This multi-centre educational cohort study will include two distinct axes which will both aim to reduce the risks of cataract surgery. Enrollment will include 16 first-year ORs for Axis 1 and 25 experienced residents for Axis 2, all from the University Hospitals of Nantes, Tours, Angers and Rennes. Axis 1 will focus on investigating the learning curve of first-year ORs using the EyeSi, following the training program recommended by the "College des Ophtalmologistes Universitaires de France" in order to set up a future "licence to operate." Axis 2 will evaluate the impact of sleep deprivation on the surgical performance of experienced ORs using the EyeSi. TRIAL REGISTRATION: ClinicalTrial.gov identifier: NCT05722080.

The development and preliminary evaluation of a clinician e-learning training platform for a neonatal sepsis risk monitor for use in ICU settings.

BACKGROUND: Training clinicians on the use of hospital-based patient monitoring systems (PMS) is vital to mitigate the risk of use errors and of frustration using these devices, especially when used in ICU settings. PMS training is typically delivered through face-to-face training sessions in the hospital. However, it is not always feasible to deliver training in this format to all clinical staff given some constraints (e.g., availability of staff and trainers to attend in-person training sessions and the costs associated with face-to-face training). OBJECTIVE: The literature indicates that E-learning has the potential to mitigate barriers associated with time restrictions for trainers and trainees and evidence shows it to be more flexible, and convenient for learners in healthcare settings. This study aimed to develop and carry out a preliminary evaluation via a case study of an e-learning training platform designed for a novel neonatal sepsis risk monitor system (Digi-NewB). METHODS: A multi-modal qualitative research case study approach was used, including the analysis of three qualitative data sources: (i) audio/video recordings of simulation sessions in which participants were asked to operate the system as intended (e.g., update the clinical observations and monitor the sepsis risk), (ii) interviews with the simulation participants and an attending key opinion leader (KOL), who observed all simulation sessions, and (iii) post-simulation survey. RESULTS: After receiving ethical approval for the study, nine neonatal intensive care unit (NICU) nurses completed the online training and participated in the simulation and follow-up interview sessions. The KOL was also interviewed, and seven out of the nine NICU nurses answered the post-simulation survey. The video/audio analysis of the simulations revealed that participants were able to use and interpret the Digi-NewB interface. Interviews with simulation participants and the KOL, and feedback extracted from the survey, revealed that participants were overall satisfied with the training platform and perceived it as an efficient and effective method to deliver medical device training. CONCLUSIONS: This study developed an online training platform to train clinicians in the use of a critical care medical device and carried out a preliminary evaluation of the platform via a case study. The e-learning platform was designed to supplement and enhance other training approaches. Further research is required to evaluate the effectiveness of this approach.

Evolution of Heart Rate Complexity Indices in the Early Detection of Neonatal Sepsis.

Despite advances in prenatal health care, neonatal sepsis remains a major cause of neonatal mortality. Early diagnosis and adequate treatment are essential to reduce morbidity and mortality related to this disease. In this paper, we propose a new method to detect neonatal sepsis based on heart rate (HR) complexity measures (entropy and compression indices) that takes into consideration neonatal gestational age. First, the percentile curves were computed for all the complexity indices using data from 118 control neonates. Eight indices were computed: the sample entropy (SampEn) and three indices to quantify the multiscale entropy (MSE) curve - the sum, the slope, and the product of the previous two - and the compression ratio (CR), using the bzip2 compressor, as well as the same three indices but related to the multiscale compression (MSC) curve. Then, the corresponding percentile was estimated for 23 sepsis neonates. Results show a significant decrease in the entropy indices SampEn and MSEsum and in the MSCslope a day before the detection of sepsis by the clinicians. The indices CR and MSCsum increased before the antibiotic take. These results imply that sepsis causes a random, uncorrelated pattern on the HR signal. Future studies should include a bigger data set to calculate a compound index comprising information of other physiological signals. Clinical Relevance - Prompt and accurate diagnosis of neona-tal sepsis is essential for the successful clinical management of neonates and significantly reduce morbidity and mortality. Complexity measures applied to the HR time series appear to detect sepsis in neonates starting one day before the clinical detection.

Cardiorespiratory alterations in a newborn ovine model of systemic viral inflammation.

BACKGROUND: Respiratory viruses can be responsible for severe apneas and bradycardias in newborn infants. The link between systemic inflammation with viral sepsis and cardiorespiratory alterations remains poorly understood. We aimed to characterize these alterations by setting up a full-term newborn lamb model of systemic inflammation using polyinosinic:polycytidylic acid (Poly I:C). METHODS: Two 6-h polysomnographic recordings were carried out in eight lambs on two consecutive days, first after an IV saline injection, then after an IV injection of 300 µg/kg Poly I:C. RESULTS: Poly I:C injection decreased locomotor activity and increased NREM sleep. It also led to a biphasic increase in rectal temperature and heart rate. The latter was associated with an overall decrease in heart-rate variability, with no change in respiratory-rate variability. Lastly, brainstem inflammation was found in the areas of the cardiorespiratory control centers 6 h after Poly I:C injection. CONCLUSIONS: The alterations in heart-rate variability induced by Poly I:C injection may be, at least partly, of central origin. Meanwhile, the absence of alterations in respiratory-rate variability is intriguing and noteworthy. Although further studies are obviously needed, this might be a way to differentiate bacterial from viral sepsis in the neonatal period. IMPACT: Provides unique observations on the cardiorespiratory consequences of injecting Poly I:C in a full-term newborn lamb to mimic a systemic inflammation secondary to a viral sepsis. Poly I:C injection led to a biphasic increase in rectal temperature and heart rate associated with an overall decrease in heart-rate variability, with no change in respiratory-rate variability. Brainstem inflammation was found in the areas of the cardiorespiratory control centers.

Functional age estimation through neonatal motion characterization using continuous video recordings.

The follow-up of the development of the premature baby is a major component of its clinical care since it has been shown that it can reveal a pathology. However, no method allowing an automated and continuous monitoring of this development has been proposed. Within the framework of the Digi-NewB European project, our team wishes to offer new clinical indices qualifying the maturation of newborns. In this study, we propose a new method to characterize motor activity from video recordings. For this purpose, we have chosen to characterize the motion temporal organization by drawing inspiration from sleep organization. Thus, we propose a fully automatic process allowing to extract motion features and to combine them to estimate a functional age. By investigating two datasets, one of 28.5 hours (manually annotated) from 33 newborns and one of 4,920 hours from 46 newborns, we show that the proposed approach is relevant for monitoring in clinical routine and that the extracted features reflect the maturation of preterm newborns. Indeed, a compact and interpretable model using gestational age and three motion features (mean duration of intervals with motion, total percentage of time spent in motion and number of intervals without motion) was designed to predict post-menstrual age of newborns and showed an admissible mean absolute error of 1.3 weeks. While the temporal organization of motion was not studied clinically due to a lack of technological means, these results open the door to new developments, new investigations and new knowledge on the evolution of motion in newborns.

Evaluation of Maturation in Preterm Infants Through an Ensemble Machine Learning Algorithm Using Physiological Signals.

This study was designed to test if heart rate variability (HRV) data from preterm and full-term infants could be used to estimate their functional maturational age (FMA), using a machine learning model. We propose that the FMA, and its deviation from the postmenstrual age (PMA) of the infants could inform physicians about the progress of the maturation of the infants. The HRV data was acquired from 50 healthy infants, born between 25 and 41 weeks of gestational age, who did not present any signs of abnormal maturation relative to their age group during the period of observation. The HRV features were used as input for a machine learning model that uses filtering and genetic algorithms for feature selection, and an ensemble machine learning (EML) algorithm, which combines linear and random forest regressions, to produce as output a FMA. Using HRV data, the FMA had a mean absolute error of 0.93 weeks, 95% CI [0.78, 1.08], compared to the PMA. These results demonstrate that HRV features of newborn infants can be used by an EML model to estimate their FMA. This method was also generalized using respiration rate variability (RRV) and bradycardia data, obtaining similar results. The FMA, predicted either by HRV, RRV or bradycardia, and its deviation from the true PMA of the infants, could be used as a surrogate measure of the maturational age of the infants, which could potentially be monitored non-invasively and in real-time in the setting of neonatal intensive care units.

Criteria for assessing the quality of clinical practice guidelines in paediatrics and neonatology: a mixed-method study.

BACKGROUND: Evidenced-based practice is a key component of quality care. This study aims to explore users' expectations concerning paediatric local clinical practice guidelines. METHODS: A mixed method approach was applied, including material from quantitative questionnaire and semi-structured interviews. Data were analysed using descriptive statistics and qualitative content analysis. Data were analysed with constant comparative method. Qualitative data were parsed and categorized to identify themes related to decision-making. RESULTS: A total of 83 physicians answered the survey (response rate 83%). 98% of the participants wanted protocols based on international guidelines, 80% expected a therapeutic content. 24 semi-structured interviews were conducted to understand implementation processes, barriers and facilitators. Qualitative analysis revealed 5 emerging themes: improvement of local clinical practice guidelines, patterns of usage, reasons for non-implementation, alternative sources and perspectives. CONCLUSION: Some criteria should be considered for the redaction of local clinical practice guidelines: focus on therapeutic, ease of access, establish local clinical practice guidelines based on international guidelines adapted to the local setting, document references and include trainees such as residents in the redaction.

Petroleum and Chlorinated Solvents in Meconium and the Risk of Hypospadias: A Pilot Study.

Background: Hypospadias is a male congenital malformation that occurs in ~2 of 1,000 births. The association between hypospadias and fetal exposure to environmental chemicals has been studied, but the results are inconsistent. Although several petroleum and chlorinated solvents are suspected to have teratogenic effects, their role in the occurrence of hypospadias has been little studied and never using biomarkers of exposure. We aimed to evaluate the association between fetal exposure to petroleum and chlorinated solvents measured in meconium and the occurrence of hypospadias. Methods: We conducted a pilot case-control study in the maternity of the University Hospital of Rennes (France). Eleven cases of hypospadias and 46 controls were recruited between October 2012 and January 2014. Data from hospital records and maternal self-reported questionnaires, including socio-demographic characteristics and occupational and non-occupational exposure to chemicals, were collected. Meconium samples were collected using a standardized protocol. Levels of petroleum solvents (toluene, benzene, ethylbenzene, and p, m, and o xylene), certain metabolites (mandelic acid, hippuric acid, methylhippuric acid, S-phenylmercapturic acid, S-benzylmercapturic acid, and phenylglyoxylic acid), and two chlorinated solvents (trichloroethylene and tetrachloroethylene) were measured in meconium by gas and liquid chromatography, both coupled to tandem mass spectrometry. Associations between the concentration of each chemical and the occurrence of hypospadias were analyzed using exact logistic regressions adjusted for maternal age, educational level, pre-pregnancy body mass index, and alcohol, and tobacco consumption during pregnancy. Results are presented with odds ratios (ORs) and their 95% confidence intervals (CIs). Results: Quantification rates for petroleum and chlorinated solvents or metabolites ranged from 2.2% (for methylhippuric acid) to 77.1% (for trichloroethylene) of the meconium samples. We found a significant association between the quantification of phenylglyoxylic acid (metabolite of styrene and ethylbenzene) in the meconium and a higher risk of hypospadias (OR = 14.2, 95% CI [2.5-138.7]). The risk of hypospadias was non-significantly elevated for most of the other solvents and metabolites. Conclusion: This exploratory study, on a limited number of cases, suggests an association between petroleum solvents and hypospadias. Additional studies are needed to confirm these results and identify the determinants for the presence of these solvents in meconium.

Early bradycardia detection and therapeutic interventions in preterm infant monitoring.

In very preterm infants, cardio-respiratory events and associated hypoxemia occurring during early postnatal life have been associated with risks of retinopathy, growth alteration and neurodevelopment impairment. These events are commonly detected by continuous cardio-respiratory monitoring in neonatal intensive care units (NICU), through the associated bradycardia. NICU nurse interventions are mainly triggered by these alarms. In this work, we acquired data from 52 preterm infants during NICU monitoring, in order to propose an early bradycardia detector which is based on a decentralized fusion of three detectors. The main objective is to improve automatic detection under real-life conditions without altering performance with respect to that of a monitor commonly used in NICU. We used heart rate lower than 80 bpm during at least 10 sec to define bradycardia. With this definition we observed a high rate of false alarms (64%) in real-life and that 29% of the relevant alarms were not followed by manual interventions. Concerning the proposed detection method, when compared to current monitors, it provided a significant decrease of the detection delay of 2.9 seconds, without alteration of the sensitivity (97.6% vs 95.2%) and false alarm rate (63.7% vs 64.1%). We expect that such an early detection will improve the response of the newborn to the intervention and allow for the development of new automatic therapeutic strategies which could complement manual intervention and decrease the sepsis risk.

Augmenting Critical Care Patient Monitoring Using Wearable Technology: Review of Usability and Human Factors.

BACKGROUND: Continuous monitoring of the vital signs of critical care patients is an essential component of critical care medicine. For this task, clinicians use a patient monitor (PM), which conveys patient vital sign data through a screen and an auditory alarm system. Some limitations with PMs have been identified in the literature, such as the need for visual contact with the PM screen, which could result in reduced focus on the patient in specific scenarios, and the amount of noise generated by the PM alarm system. With the advancement of material science and electronic technology, wearable devices have emerged as a potential solution for these problems. This review presents the findings of several studies that focused on the usability and human factors of wearable devices designed for use in critical care patient monitoring. OBJECTIVE: The aim of this study is to review the current state of the art in wearable devices intended for use by clinicians to monitor vital signs of critical care patients in hospital settings, with a focus on the usability and human factors of the devices. METHODS: A comprehensive literature search of relevant databases was conducted, and 20 studies were identified and critically reviewed by the authors. RESULTS: We identified 3 types of wearable devices: tactile, head-mounted, and smartwatch displays. In most cases, these devices were intended for use by anesthesiologists, but nurses and surgeons were also identified as potentially important users of wearable technology in critical care medicine. Although the studies investigating tactile displays revealed their potential to improve clinical monitoring, usability problems related to comfort need to be overcome before they can be considered suitable for use in clinical practice. Only a few studies investigated the usability and human factors of tactile displays by conducting user testing involving critical care professionals. The studies of head-mounted displays (HMDs) revealed that these devices could be useful in critical care medicine, particularly from an ergonomics point of view. By reducing the amount of time the user spends averting their gaze from the patient to a separate screen, HMDs enable clinicians to improve their patient focus and reduce the potential of repetitive strain injury. CONCLUSIONS: Researchers and designers of new wearable devices for use in critical care medicine should strive to achieve not only enhanced performance but also enhanced user experience for their users, especially in terms of comfort and ease of use. These aspects of wearable displays must be extensively tested with the intended end users in a setting that properly reflects the intended context of use before their adoption can be considered in clinical settings.

Multiparametric Analysis of Cerebral Development in Preterm Infants Using Magnetic Resonance Imaging.

OBJECTIVES: The severity of neurocognitive impairment increases with prematurity. However, its mechanisms remain poorly understood. Our aim was firstly to identify multiparametric magnetic resonance imaging (MRI) markers that differ according to the degree of prematurity, and secondly to evaluate the impact of clinical complications on these markers. MATERIALS AND METHODS: We prospectively enrolled preterm infants who were divided into two groups according to their degree of prematurity: extremely preterm (<28 weeks' gestational age) and very preterm (28-32 weeks' gestational age). They underwent a multiparametric brain MRI scan at term-equivalent age including morphological, diffusion tensor and arterial spin labeling (ASL) perfusion sequences. We quantified overall and regional volumes, diffusion parameters, and cerebral blood flow (CBF). We then compared the parameters for the two groups. We also assessed the effects of clinical data and potential MRI morphological abnormalities on those parameters. RESULTS: Thirty-four preterm infants were included. Extremely preterm infants (n = 13) had significantly higher frontal relative volumes (p = 0.04), frontal GM relative volumes (p = 0.03), and regional CBF than very preterm infants, but they had lower brainstem and insular relative volumes (respectively p = 0.008 and 0.04). Preterm infants with WM lesions on MRI had significantly lower overall GM CBF (13.3 ± 2 ml/100 g/min versus 17.7 ± 2.5, < ml/100 g/min p = 0.03). CONCLUSION: Magnetic resonance imaging brain scans performed at term-equivalent age in preterm infants provide quantitative imaging parameters that differ with respect to the degree of prematurity, related to brain maturation.

Diagnosis of Neonatal Late-Onset Infection in Very Preterm Infant: Inter-Observer Agreement and International Classifications.

BACKGROUND: The definition of late-onset bacterial sepsis (LOS) in very preterm infants is not unified. The objective was to assess the concordance of LOS diagnosis between experts in neonatal infection and international classifications and to evaluate the potential impact on heart rate variability and rate of "bronchopulmonary dysplasia or death". METHODS: A retrospective (2017-2020) multicenter study including hospitalized infants born before 31 weeks of gestation with intention to treat at least 5-days with antibiotics was performed. LOS was classified as "certain or probable" or "doubtful" independently by five experts and according to four international classifications with concordance assessed by Fleiss's kappa test. RESULTS: LOS was suspected at seven days (IQR: 5-11) of life in 48 infants. Following expert classification, 36 of them (75%) were considered as "certain or probable" (kappa = 0.41). Following international classification, this number varied from 13 to 46 (kappa = -0.08). Using the expert classification, "bronchopulmonary dysplasia or death" occurred less frequently in the doubtful group (25% vs. 78%, p < 0.001). Differences existed in HRV changes between the two groups. CONCLUSION: The definition of LOS is not consensual with a low international and moderate inter-observer agreement. This affects the evaluation of associated organ dysfunction and prognosis.

Early Detection of Late Onset Sepsis in Premature Infants Using Visibility Graph Analysis of Heart Rate Variability.

OBJECTIVE: This study was designed to test the diagnostic value of visibility graph features derived from the heart rate time series to predict late onset sepsis (LOS) in preterm infants using machine learning. METHODS: The heart rate variability (HRV) data was acquired from 49 premature newborns hospitalized in neonatal intensive care units (NICU). The LOS group consisted of patients who received more than five days of antibiotics, at least 72 hours after birth. The control group consisted of infants who did not receive antibiotics. HRV features in the days prior to the start of antibiotics (LOS group) or in a randomly selected period (control group) were compared against a baseline value calculated during a calibration period. After automatic feature selection, four machine learning algorithms were trained. All the tests were done using two variants of the feature set: one only included traditional HRV features, and the other additionally included visibility graph features. Performance was studied using area under the receiver operating characteristics curve (AUROC). RESULTS: The best performance for detecting LOS was obtained with logistic regression, using the feature set including visibility graph features, with AUROC of 87.7% during the six hours preceding the start of antibiotics, and with predictive potential (AUROC above 70%) as early as 42 h before start of antibiotics. CONCLUSION: These results demonstrate the usefulness of introducing visibility graph indexes in HRV analysis for sepsis prediction in newborns. SIGNIFICANCE: The method proposed the possibility of non-invasive, real-time monitoring of risk of LOS in a NICU setting.

Quiet Sleep Organization of Very Preterm Infants Is Correlated With Postnatal Maturation.

Background: Sleep is an important determinant of brain development in preterm infants. Its temporal organization varies with gestational age (GA) and post-menstrual age (PMA) but little is known about how sleep develops in very preterm infants. The objective was to study the correlation between the temporal organization of quiet sleep (QS) and maturation in premature infants without severe complications during their neonatal hospitalization. Methods: Percentage of time spent in QS and average duration of time intervals (ADI) spent in QS were analyzed from a cohort of newborns with no severe complications included in the Digi-NewB prospective, multicentric, observational study in 2017-19. Three groups were analyzed according to GA: Group 1 (27-30 weeks), Group 2 (33-37 weeks), Group 3 (>39 weeks). Two 8-h video recordings were acquired in groups 1 and 2: after birth (T1) and before discharge from hospital (T2). The annotation of the QS phases was performed by analyzing video recordings together with heart rate and respiratory traces thanks to a dedicated software tool of visualization and annotation of multimodal long-time recordings, with a double expert reading. Results are expressed as median (interquartile range, IQR). Correlations were analyzed using a linear mixed model. Results: Five newborns were studied in each group (160 h of recording). Median time spent in QS increased from 13.0% [IQR: 13-20] to 28.8% [IQR: 27-30] and from 17.0% [IQR: 15-21] to 29.6% [IQR: 29.5-31.5] in Group 1 and 2, respectively. Median ADI increased from 54 [IQR: 53-54] to 288 s [IQR: 279-428] and from 90 [IQR: 84-96] to 258 s [IQR: 168-312] in Group 1 and 2. Both groups reach values similar to that of group 3, respectively 28.2% [IQR: 24.5-31.3] and 270 s [IQR: 210-402]. The correlation between PMA and time spent in QS or ADI were, respectively 0.73 (p < 10-4) and 0.46 (p = 0.06). Multilinear analysis using temporal organization of QS gave an accurate estimate of PMA (r 2 = 0.87, p < 0.001). Conclusion: The temporal organization of QS is correlated with PMA in newborns without severe complication. An automated standardized continuous behavioral quantification of QS could be interesting to monitor during the hospitalization stay in neonatal units.