Objectives
To study the methodology and results of studies assessing the relationship between fetal heart rate and specified neonatal outcomes including, heart rate, infection, necrotizing enterocolitis, intraventricular hemorrhage, hypoxic-ischemic encephalopathy, and seizure.

Methods
Embase, Medline ALL, Web of Science Core Collection, Cochrane Central Register of Controlled Trials, and CINAHL were searched from inception to October 5, 2023.

Results
Forty-two studies were included, encompassing 57,232 cases that underwent fetal monitoring and were evaluated for neonatal outcome. Heterogeneity was observed in the timing and duration of fetal heart rate assessment, classification guidelines used, number of assessors, and definition and timing of neonatal outcome assessment. Nonreassuring fetal heart rate was linked to lower neonatal heart rate variability. A significant increase in abnormal fetal heart rate patterns were reported in neonates with hypoxic-ischemic encephalopathy, but the predictive ability was found to be limited. Conflicting results were reported regarding sepsis, seizure and intraventricular hemorrhage. No association was found between necrotizing enterocolitis rate and fetal heart rate.

Conclusions
There is great heterogeneity in the methodology used in studies evaluating the association between fetal heart rate and aforementioned neonatal outcomes. Hypoxic-ischemic encephalopathy was associated with increased abnormal fetal heart rate patterns, although the predictive ability was low. Further research on developing and evaluating an automated early warning system that integrates computerized cardiotocography with a perinatal health parameter database to provide objective alerts for patients at-risk is recommended.
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Background: Preterm neonates are extensively monitored to require strict oxygen target attainment for optimal outcomes. In daily practice, detailed oxygenation data are hardly used and crucial patterns may be missed due to the snapshot presentations and subjective observations. This study aimed to develop a web-based dashboard with both detailed and summarized oxygenation data in real-time and to test its feasibility to support clinical decision making. Methods: Data from pulse oximeters and ventilators were synchronized and stored to enable real-time and retrospective trend visualizations in a web-based viewer. The dashboard was designed based on interviews with clinicians. A preliminary version was evaluated during daily clinical rounds. The routine evaluation of the respiratory condition of neonates (gestational age < 32 weeks) with respiratory support at the NICU was compared to an assessment with the assistance of the dashboard. Results: The web-based dashboard included data on the oxygen saturation (SpO₂), fraction of inspired oxygen (FiO₂), SpO₂/FiO₂ ratio, and area < 80% and > 95% SpO₂ curve during time intervals that could be varied. The distribution of SpO₂ values was visualized as histograms. In 65% of the patient evaluations (n = 86) the level of hypoxia was assessed differently with the use of the dashboard. In 75% of the patients the dashboard was judged to provide added value for the clinicians in supporting clinical decisions. Conclusions: A web-based customized oxygenation dashboard for preterm neonates at the NICU was developed and found feasible during evaluation. More clear and objective information was found supportive for clinicians during the daily rounds in tailoring treatment strategies.

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Background: Prolonged weaning from mechanical ventilation is associated with poor clinical outcome. Therefore, choosing the right moment for weaning and extubation is essential. Electrical Impedance Tomography (EIT) is a promising innovative lung monitoring technique, but its role in supporting weaning decisions is yet uncertain. We aimed to evaluate physiological trends during a T-piece spontaneous breathing trail (SBT) as measured with EIT and the relation between EIT parameters and SBT success or failure. Methods: This is an observational study in which twenty-four adult patients receiving mechanical ventilation performed an SBT. EIT monitoring was performed around the SBT. Multiple EIT parameters including the end-expiratory lung impedance (EELI), delta Tidal Impedance (ΔZ), Global Inhomogeneity index (GI), Rapid Shallow Breathing Index (RSBI_EIT), Respiratory Rate (RR_EIT) and Minute Ventilation (MV_EIT) were computed on a breath-by-breath basis from stable tidal breathing periods. Results: EELI values dropped after the start of the SBT (p < 0.001) and did not recover to baseline after restarting mechanical ventilation. The ΔZ dropped (p < 0.001) but restored to baseline within seconds after restarting mechanical ventilation. Five patients failed the SBT, the GI (p = 0.01) and transcutaneous CO₂ (p < 0.001) values significantly increased during the SBT in patients who failed the SBT compared to patients with a successful SBT. Conclusion: EIT has the potential to assess changes in ventilation distribution and quantify the inhomogeneity of the lungs during the SBT. High lung inhomogeneity was found during SBT failure. Insight into physiological trends for the individual patient can be obtained with EIT during weaning from mechanical ventilation, but its role in predicting weaning failure requires further study.

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Introduction: In clinical practice, fetal heart rate monitoring is performed intermittently using Doppler ultrasound, typically for 30 minutes. In case of a non-reassuring heart rate pattern, monitoring is usually prolonged. Noninvasive fetal electrocardiography may be more suitable for prolonged monitoring due to improved patient comfort and signal quality. This study evaluates the performance and patient experience of four noninvasive electrocardiography devices to assess candidate devices for prolonged noninvasive fetal heart rate monitoring. Material and methods: Non-critically sick women with a singleton pregnancy from 24 weeks of gestation were eligible for inclusion. Fetal heart rate monitoring was performed during standard care with a Doppler ultrasound device (Philips Avalon-FM30) alone or with this Doppler ultrasound device simultaneously with one of four noninvasive electrocardiography devices (Nemo Fetal Monitoring System, Philips Avalon-Beltless, Demcon Dipha-16 and Dräger Infinity-M300). Performance was evaluated by: success rate, positive percent agreement, bias, 95% limits of agreement, regression line, root mean square error and visual agreement using FIGO guidelines. Patient experience was captured using a self-made questionnaire. Results: A total of 10 women were included per device. For fetal heart rate, Nemo performed best (success rate: 99.4%, positive percent agreement: 94.2%, root mean square error 5.1 BPM, bias: 0.5 BPM, 95% limits of agreement: −9.7 – 10.7 BPM, regression line: y = −0.1x + 11.1) and the cardiotocography tracings obtained simultaneously by Nemo and Avalon-FM30 received the same FIGO classification. Comparable results were found with the Avalon-Beltless from 36 weeks of gestation, whereas the Dipha-16 and Infinity-M300 performed significantly worse. The Avalon-Beltless, Nemo and Infinity-M300 closely matched the performance of the Avalon-FM30 for maternal heart rate, whereas the performance of the Dipha-16 deviated more. Patient experience scores were higher for the noninvasive electrocardiography devices. Conclusions: Both Nemo and Avalon-Beltless are suitable devices for (prolonged) noninvasive fetal heart rate monitoring, taking their intended use into account. But outside its intended use limit of 36 weeks’ gestation, the Avalon-Beltless performs less well, comparable to the Dipha-16 and Infinity-M300, making them currently unsuitable for (prolonged) noninvasive fetal heart rate monitoring. Noninvasive electrocardiography devices appear to be preferred due to greater comfort and mobility.

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Objective. The respiratory rate (RR) is considered one of the most informative vital signals. A well-validated standard for RR measurement in mechanically ventilated patient is capnography; a noninvasive technique for expiratory CO2measurements. Reliable RR measurements in spontaneously breathing patients remains a challenge as continuous mainstream capnography measurements are not available. This study aimed to assess the accuracy of RR measurement using electrical impedance tomography (EIT) in healthy volunteers and intensive care unit (ICU) patients on mechanical ventilation and spontaneously breathing post-extubation. Comparator methods included RR derived from both capnography and bioimpedance electrocardiogram (ECG) measurements.Approach. Twenty healthy volunteers wore an EIT belt and ECG electrodes while breathing through a capnometer within a 10-40 breaths per minute (BPM) range. Nineteen ICU patients underwent similar measurements during pressure support ventilation and spontaneously breathing after extubation from mechanical ventilation. Stable periods with regular breathing and no artefacts were selected, and agreement between measurement methods was assessed using Bland-Altman analysis for repeated measurements.Main result. Bland-Altman analysis revealed a bias less than 0.2 BPM, with tight limits of agreement (LOA) ±1.5 BPM in healthy volunteers and ventilated ICU patients when comparing EIT to capnography. Spontaneously breathing ICU patients had wider LOA (±2.5 BPM) when comparing EIT to ECG bioimpedance, but gold standard comparison was unavailable. RR measurements were stable for 91% of the time for capnography, 68% for EIT, and 64% of the ECG bioimpedance signals. After extubation, the percentage of stable periods decreased to 48% for EIT signals and to 55% for ECG bioimpedance.Significance. In periods of stable breathing, EIT demonstrated excellent RR measurement accuracy in healthy volunteers and ICU patients. However, stability of both EIT and ECG bioimpedance RR measurements declined in spontaneously breathing patients to approximately 50% of the time.

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Introduction: Transcutaneous blood gas monitoring allows for continuous non-invasive evaluation of carbon dioxide and oxygen levels. Its use is limited as its accuracy is dependent on several factors. We aimed to identify the most influential factors to increase usability and aid in the interpretation of transcutaneous blood gas monitoring. Methods: In this retrospective cohort study, transcutaneous blood gas measurements were paired to arterial blood gas withdrawals in neonates admitted to the neonatal intensive care unit. The effects of patient-related, microcirculatory, macrocirculatory, respiratory, and sensor-related factors on the difference between transcutaneously and arterially measured carbon dioxide and oxygen values (ΔPCO2 and ΔPO2) were evaluated using marginal models. Results: A total of 1,578 measurement pairs from 204 infants with a median [interquartile range] gestational age of 273/7 [261/7-313/7] weeks were included. ΔPCO2 was significantly associated with the postnatal age, arterial systolic blood pressure, body temperature, arterial partial pressure of oxygen (PaO2), and sensor temperature. ΔPO2 was, with the exception of PaO2, additionally associated with gestational age, birth weight Z-score, heating power, arterial partial pressure of carbon dioxide, and interactions between sepsis and body temperature and sepsis and the fraction of inspired oxygen. Conclusion: The reliability of transcutaneous blood gas measurements is affected by several clinical factors. Caution is recommended when interpreting transcutaneous blood gas values with an increasing postnatal age due to skin maturation, lower arterial systolic blood pressures, and for transcutaneously measured oxygen values in the case of critical illness.

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Background: Arterial pressure measurements are important to monitor vital function in neonates, and values are known to be dependent of gestational and postnatal age. Current reference ranges for mean arterial pressure in neonates have been derived from small samples and combined data of noninvasive and invasive measurements. We aimed to define reference values for noninvasive mean, systolic, and diastolic blood pressure during the first week of life in otherwise healthy preterm and term neonates defined by gestational and postnatal age. Methods: In this retrospective cohort study in a neonatal intensive care unit (NICU) in a Dutch tertiary paediatric hospital, we included the noninvasive blood pressures of neonates admitted between 2016 and 2018, with exclusion of those with severe comorbidities (major cardiac malformations, intracerebral haemorrhage, and tracheal intubation >6 h). We defined the median (P50) with −2 standard deviations (SD) (P0.23), −1 SD (P16), +1 SD (P84), and +2 SD (P97.7) for gestational age and postnatal age using quantile regression, percentiles provided online (http://bloodpressure-neonate.com/). Results: A total of 607 neonates, with 5885 measurements, fulfilled the inclusion criteria. The P50 values of mean noninvasive arterial blood pressure in extreme preterm infants steeply increased during the first day after birth and gradually increased within a week from 27 to 49 mm Hg at 24 h of gestational age, and from 49 to 61 mm Hg at 41 weeks of gestational age. Conclusions: These reference values for noninvasive blood pressure in neonates in the NICU for various gestational age groups provide guidance for clinical decision-making in healthy and diseased neonates during anaesthesia and sedation.

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Background: In neonates with post-asphyxial neonatal encephalopathy, further neuronal damage is prevented with therapeutic hypothermia (TH). In addition, fluctuations in carbon dioxide levels have been associated with poor neurodevelopmental outcome, demanding close monitoring. This study investigated the accuracy and clinical value of transcutaneous carbon dioxide (tcPCO₂) monitoring during TH. Methods: In this retrospective cohort study in neonates, agreement between arterial carbon dioxide (PaCO₂) values and tcPCO₂ measurements during TH was determined. TcPCO₂ levels during the first 24 h of hypothermia were tested for an association with ischemic brain injury on magnetic resonance imaging (MRI). Results: Thirty-four neonates were included. Agreement (bias (95% limits of agreement)) between tcPCO₂ and PaCO₂ levels was 3.9 (−12.4–20.2) mm Hg. No relation was found between the body temperature and tcPCO₂ levels. TcPCO₂ levels differed significantly between patients with considerable and minimal damage on MRI; after 6 h (P = 0.02) and 9 h (P = 0.04). Conclusions: Although tcPCO₂ provided a limited estimation of PaCO₂, it can be used for trend monitoring during TH. TcPCO₂ levels after birth could provide an early indicator of ischemic brain injury. This relation should be investigated in large prospective studies, in which adjustments for confounders can be made. Impact: Transcutaneous carbon dioxide measurements during therapeutic hypothermia in neonates show limited accuracy similar to measurements reported in normothermic neonates and can be used for trend monitoring.Low transcutaneous carbon dioxide levels during the first 24 h were associated with considerable ischemic brain injury on MRI.The value of transcutaneous carbon dioxide measurements during the first 24 h as an indicator of considerable ischemic brain injury on MRI should be investigated in future studies, adjusting for confounders.Transcutaneous oxygen measurements during therapeutic hypothermia showed an inaccuracy that could not be related to a low body temperature.

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Inside the Neonatal Intensive Care Unit (NICU), exposure to loud sounds such as acoustic medical alarms can have adverse effects on neonates, parents, and medical staff. With the aim of having an accurate overview of which and how often acoustic medical alarms occur, this paper presents a simple signal processing-based approach for detecting and recognizing automatically and permanently patient monitoring alarms inside the NICU. The proposed algorithm leverages from prior knowledge of the spectro-temporal structures of alarms to first detect each single occurrence of an alarm tone, and then group the detected tones into a known alarm pattern. A preliminary evaluation of the algorithm on a small set of 4-channel recordings capturing a simulated NICU soundscape shows that around 99% of the acoustic alarms are correctly recognized, and that around 99% of the recognized alarms are true alarms. The algorithm lends itself to efficient real-time implementation and to generalization to other alarm patterns as defined by the IEC 60601-1-8 standard.

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Introduction: Supplemental oxygen therapy is a mainstay of modern neonatal intensive care for preterm infants. However, both insufficient and excess oxygen delivery are associated with adverse outcomes. Automated or closed loop FiO2 control has been developed to keep SpO2 within a predefined target range more effectively. Methods: The aim of this study was to investigate the feasibility of closed loop FiO2 control by Predictive Intelligent Control of Oxygenation (PRICO) on the Fabian ventilator in maintaining SpO2 within a target range (88/89-95%) in preterm infants on different modes of invasive and noninvasive respiratory support. In two tertiary neonatal intensive care units, preterm infants with an FiO2 >0.21 were included and received an 8 h nonblinded treatment period of closed loop FiO2 control by PRICO, flanked by two 8 h control periods of routine manual control (RMC1 and RMC2). Results: 32 preterm infants were included (median gestational age 26 + 5 weeks [IQR 25 + 5-27 + 6], median birthweight 828 grams [IQR 704-930]). Six patients received invasive respiratory support, while 26 received noninvasive respiratory support (18 CPAP, 4 DuoPAP, and 4 nasal IMV). The time percentage within the SpO2 target range was increased with PRICO (74.4% [IQR 67.8-78.5]) compared to RMC1 (65.8% [IQR 51.1-77.8]; p = 0.011) and RMC2 (60.6% [IQR 56.2-66.6]; p < 0.001) with an estimated median difference of 6.0% (95% CI 1.2-11.5) and 9.8% (95% CI 6.0-13.0), respectively. Conclusion: In preterm infants on invasive and noninvasive respiratory supports, closed loop FiO2 control by PRICO compared to RMC is feasible and superior in maintaining SpO2 within target ranges.

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The aim of this study was to investigate the association between the implementation of a local heart rate variability (HRV) monitoring guideline combined with determination of inflammatory biomarkers and mortality, measures of sepsis severity, frequency of sepsis testing, and antibiotic usage, among very preterm neonates. In January 2018, a guideline was implemented for early detection of late-onset neonatal sepsis using HRV monitoring combined with determination of inflammatory biomarkers. Data on all patients admitted with a gestational age at birth of < 32 weeks were reviewed in the period January 2016–June 2020 (n = 1,135; n = 515 pre-implementation, n = 620 post-implementation). Outcomes of interest were (sepsis-related) mortality, sepsis severity (neonatal sequential organ failure assessment (nSOFA)), sepsis testing, and antibiotic usage. Differences before and after implementation of the guideline were assessed using logistic and linear regression analysis for binary and continuous outcomes respectively. All analyses were adjusted for gestational age and sex. Mortality within 10 days of a sepsis episode occurred in 39 (10.3%) and 34 (7.6%) episodes in the pre- and post-implementation period respectively (P = 0.13). The nSOFA course during a sepsis episode was significantly lower in the post-implementation group (P = 0.01). We observed significantly more blood tests for determination of inflammatory biomarkers, but no statistically significant difference in number of blood cultures drawn and in antibiotic usage between the two periods.

Conclusion: Implementing HRV monitoring with determination of inflammatory biomarkers might help identify patients with sepsis sooner, resulting in reduced sepsis severity, without an increased use of antibiotics or number of blood cultures.

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Introduction: Traditional transcutaneous oxygen (tcPO2) measurements are affected by measurement drift, limiting accuracy and usability. The new potentially drift-free oxygen fluorescence quenching technique has been combined in a single sensor with conventional transcutaneous carbon dioxide (tcPCO2) monitoring. This study aimed to validate optical tcPO2 and conventional tcPCO2 against arterial blood gas samples in preterm neonates and determine measurement drift. Methods: In this prospective observational study, during regular care, transcutaneous measurements were paired to arterial blood gases from preterm neonates aged 24-31 weeks of gestational age (GA) with an arterial catheter. Samples were included based on stability criteria and stratified for sepsis status. Agreement was assessed using the Bland-Altman analysis. Measurement drift per hour was calculated. Results: Sixty-eight premature neonates were included {median (interquartile range [IQR]) GA of 26 4/7 [25 3/7-27 5/7] weeks}, resulting in 216 stable paired samples. Agreement of stable samples in neonates without sepsis (n = 38) and with suspected sepsis (n = 112) was acceptable for tcPO2 and good for tcPCO2. However, in stable samples of neonates with sepsis (n = 66), tcPO2 agreement (bias and 95% limits of agreement) was -32.6 (-97.0 to 31.8) mm Hg and tcPCO2 agreement was 4.2 (-10.5 to 18.9) mm Hg. The median (IQR) absolute drift values were 0.058 (0.0231-0.1013) mm Hg/h for tcPO2 and 0.30 (0.11-0.64) mm Hg/h for tcPCO2. Conclusion: The accuracy of optical tcPO2 in premature neonates was acceptable without sepsis, while electrochemically measured tcPCO2 remained accurate under all circumstances. Measurement drift was negligible for tcPO2 and highly acceptable for tcPCO2.

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This study investigated the accuracy, drift, and clinical usefulness of a new optical transcutaneous oxygen tension (tcPO₂) measuring technique, combined with a conventional electrochemical transcutaneous carbon dioxide (tcPCO₂) measurement and reflectance pulse oximetry in the novel transcutaneous OxiVenT™ Sensor. In vitro gas studies were performed to measure accuracy and drift of tcPO₂ and tcPCO₂. Clinical usefulness for tcPO₂ and tcPCO₂ monitoring was assessed in neonates. In healthy adult volunteers, measured oxygen saturation values (SpO₂) were compared with arterially sampled oxygen saturation values (SaO₂) during controlled hypoxemia. In vitro correlation and agreement with gas mixtures of tcPO₂ (r = 0.999, bias 3.0 mm Hg, limits of agreement − 6.6 to 4.9 mm Hg) and tcPCO₂ (r = 0.999, bias 0.8 mm Hg, limits of agreement − 0.7 to 2.2 mm Hg) were excellent. In vitro drift was negligible for tcPO₂ (0.30 (0.63 SD) mm Hg/24 h) and highly acceptable for tcPCO₂ (− 2.53 (1.04 SD) mm Hg/12 h). Clinical use in neonates showed good usability and feasibility. SpO₂-SaO₂ correlation (r = 0.979) and agreement (bias 0.13%, limits of agreement − 3.95 to 4.21%) in healthy adult volunteers were excellent. The investigated combined tcPO₂, tcPCO₂, and SpO₂ sensor with a new oxygen fluorescence quenching technique is clinically usable and provides good overall accuracy and negligible tcPO₂ drift. Accurate and low-drift tcPO₂ monitoring offers improved measurement validity for long-term monitoring of blood and tissue oxygenation. [Figure not available: see fulltext.].

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Heart rate (HR) detection in premature infants using electrocardiography (ECG) is challenging due to a low signal amplitude and the fragility of the premature skin. Recently, the dynamic light scattering (DLS) technique has been miniaturized, allowing noninvasive HR measurements with a single sensor. Objective: The aim was to determine the accuracy of DLS for HR measurement in infants, compared to ECG-derived HR. Methods: Stable infants with a gestational age of ≥26 weeks, monitored with ECG, were eligible for inclusion. HR was measured with the DLS sensor at 5 different sites for 15 min each. We recorded every 10th second of the DLS-derived HR and the DLS signal-to-noise ratio (SNR), and the ECG-derived HR was extracted for analysis. Patients were randomly divided into 2 groups. In the first group, the optimal SNR cut-off value was determined and then applied to the second group to assess agreement. Results: HR measurements from 31 infants were analyzed. ECG-DLS paired data points were collected at the forehead, an upper extremity, the thorax, a lower extremity, and the abdomen. When applying the international accuracy standard for HR detection, DLS accuracy in the first group (n = 15) was optimal at the forehead (SNR cut-off 1.66). Application of this cut-off to the second group (n = 16) showed good agreement between DLS-derived HR and ECG-derived HR (bias –0.73 bpm; 95% limits of agreement –15.46 and 14.00 bpm) at the forehead with approximately 80% (i.e., 1,066/1,310) of all data pairs remaining. Conclusion: The investigated DLS sensor was sensitive to movement, overall providing less accurate HR measurements than ECG and pulse oximetry. In this study population, specific measurement sites provided excellent signal quality and good agreement with ECG-derived HR. @en

Background: Non-invasive monitoring of cerebral tissue oxygen saturation (rcSO₂) during transition is of growing interest. Different near-infrared spectroscopy (NIRS) techniques have been developed to measure rcSO₂. We compared rcSO₂ values during the immediate transition in preterm neonates measured with frequency-domain NIRS (FD-NIRS) with those measured with continuous-wave NIRS (CW-NIRS) devices in prospective observational studies. Methods: We compared rcSO₂ values measured with an FD-NIRS device during the first 15 min after birth in neonates with a gestational age ≥ 30 weeks but < 37 weeks born at the Erasmus MC- Sophia Children's Hospital, Rotterdam, the Netherlands, with similar values measured with a CW-NIRS device in neonates born at the Medical University of Graz, Austria. Mixed models were used to adjust for repeated rcSO₂ measurements, with fixed effects for time (non-linear), device, respiratory support and the interaction of device and respiratory support with time. Additionally, parameters such as total haemoglobin concentration and oxygenated and deoxygenated haemoglobin concentrations measured by FD-NIRS were analysed. Results: Thirty-eight FD-NIRS measurements were compared with 58 CW-NIRS measurements. The FD-NIRS rcSO₂ values were consistently higher than the CW-NIRS rcSO₂ values in the first 12 min, irrespective of respiratory support. After adjustment for respiratory support, the time-dependent trend in rcSO₂ differed significantly between techniques (p < 0.01). Conclusion: As cerebral saturation measured with the FD-NIRS device differed significantly from that measured with the CW-NIRS device, differences in absolute values need to be interpreted with care. Although FD-NIRS devices have technical advantages over CW-NIRS devices, FD-NIRS devices may overestimate true cerebral oxygenation and their benefits might not outweigh the usability of the more clinically viable CW-NIRS devices.

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Introduction: Evaluation of pharmacotherapy during intensive care treatment is commonly based on subjective, intermittent interpretations of physiological parameters. Real-time visualization and analysis may improve drug effect evaluation. We aimed to evaluate the effects of the respiratory stimulant doxapram objectively in preterm infants using continuous physiological parameters. Methods: In this longitudinal observational study, preterm infants who received doxapram therapy were eligible for inclusion. Physiological data (1 Hz) were used to assess respiration and to evaluate therapy effects. The oxygen saturation (SpO₂)/fraction of inspired oxygen (FiO₂) ratio and the area under the 89% SpO₂ curve (duration × saturation depth below target) were calculated as measures of hypoxemia. Regression analyses were performed in 1-h timeframes to discriminate therapy failure (intubation or death) from success (no intubation). Results: Monitor data of 61 patients with a median postmenstrual age (PMA) at doxapram initiation of 28.7 (IQR 27.6-30.0) weeks were available. The success rate of doxapram therapy was 56%. Doxapram pharmacodynamics were reflected in an increased SpO₂ and SpO₂/FiO₂ ratio as well as a decrease in episodes with saturations below target (SpO₂ <89%). The SpO₂/FiO₂ ratio, corrected for PMA and mechanical ventilation before therapy start, discriminated best between therapy failure and success (highest AUC ROC of 0.83). Conclusion: The use of continuous physiological monitor data enables objective and detailed interpretation of doxapram in preterm infants. The SpO₂/FiO₂ ratio is the best predictive parameter for therapy failure or success. Further implementation of real-time data analysis and treatment algorithms would provide new opportunities to treat newborns.

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Monitoring of respiratory rate (RR) is very important for patient assessment. In fact, it is considered one of the relevant vital parameters in critical care medicine. Nowadays, standard monitoring relies on obtrusive and invasive techniques, which require adhesive electrodes or sensors to be attached to the patient's body. Unfortunately, these procedures cause stress, pain, and frequently damage the vulnerable skin of preterm infants. This paper presents a 'black-box' algorithm for remote monitoring of RR in thermal videos. 'Black-box' in this context means that the algorithm does not rely on tracking of specific anatomic landmarks. Instead, it automatically distinguishes regions of interest in the video containing the respiratory signal from those containing only noise. To examine its performance and robustness during physiological (phase A) and pathological scenarios (phase B), a study on 12 healthy volunteers was carried out. After a successful validation on adults, a clinical study on eight newborn infants was conducted. A good agreement between estimated RR and ground truth was achieved. In the study involving adult volunteers, a mean root-mean-square error (RMSE) of (0.31 ± 0.09) breaths/min and (3.27 ± 0.72) breaths/min was obtained for phase A and phase B, respectively. In the study involving infants, the mean RMSE hovered around (4.15 ± 1.44) breaths/min. In brief, this paper demonstrates that infrared thermography might become a clinically relevant alternative for the currently available RR monitoring modalities in neonatal care.

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Background: Transition immediately after birth is a complex physiological process. The neonate has to establish sufficient ventilation to ensure significant changes from intra-uterine to extra-uterine circulation. If hypoxia or bradycardia or both occur, as commonly happens during immediate transition in preterm neonates, cerebral hypoxia-ischemia may cause perinatal brain injury. The primary objective of the COSGOD phase III trial is to investigate whether it is possible to increase survival without cerebral injury in preterm neonates of less than 32 weeks of gestation by targeting cerebral tissue oxygen saturation (crSO ₂ ) using specified clinical treatment guidelines during the immediate transition period after birth (the first 15 min) in addition to the routine monitoring of arterial oxygen saturation (SpO ₂ ) and heart rate (HR). Methods/Design: COSGOD III is an investigator-initiated, randomized, multi-center, multi-national, phase III clinical trial. Inclusion criteria are neonates of less than 32 weeks of gestation, decision to provide full life support, and parental informed consent. Exclusion criteria are severe congenital malformations of brain, heart, lung, or prenatal cerebral injury or a combination of these. The premature infants will be randomly assigned to study or control groups. Both groups will have a near-infrared spectroscopy (NIRS) device (left frontal), pulse oximeter (right palm/wrist), and electrocardiogram placed immediately after birth. In the study group, the crSO ₂ , SpO ₂ , and HR readings are visible, and the infant will receive treatment in accordance with defined treatment guidelines. In the control group, only SpO ₂ and HR will be visible, and the infant will receive routine treatment. The intervention period will last for the first 15 min after birth during the immediate transition period and resuscitation. Thereafter, each neonate will be followed up for primary outcome to term date or discharge. The primary outcome is mortality or cerebral injury (or both) defined as any intra-ventricular bleeding or cystic periventricular leukomalacia (or both). Secondary outcomes are neonatal morbidities. Discussion: crSO ₂ monitoring during immediate transition has been proven to be feasible and improve cerebral oxygenation during immediate transition. The additional monitoring of crSO ₂ with dedicated interventions may improve outcome of preterm neonates as evidenced by increased survival without cerebral injury.

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The aim was to assess the reproducibility of the Pleth Variability Index (PVI), developed for non-invasive monitoring of peripheral perfusion, in preterm neonates below 32 weeks of gestational age. Three PVI measurements were consecutively performed in stable, comfortable preterm neonates in the first 48 h of life. On each occasion, pulse oximeter sensors were attached to two different limbs for 5 min. Reproducibility was assessed with the intra-class correlation coefficient (ICC) and Bland–Altman analysis. A total of 25 preterm neonates were included. Inter-limb comparison showed fair to moderate ICC’s with 95%-confidence intervals (95%-CI). Left hand–right hand ICC = 0.498, 95%-CI (0.119–0.753); right foot–right hand ICC = 0.314 (−0.088–0.644); right foot–left foot ICC = 0.315 (−0.089–0.628). Intra-limb comparison showed fair to moderate ICC for right foot–right foot ICC = 0.380 (−0.014–0.677); and good ICC for right hand–right hand ICC = 0.646 (0.194–0.852). Bland–Altman plots showed moderate reproducibility of measurements between different limbs and of the same limb in consecutive time periods, with large biases and wide limits of agreement. The findings from this study indicate that PVI measurement is poorly reproducible when measured on different limbs and on the same limb in stable and comfortable preterm neonates.

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The developing human fetus is able to cope with the physiological reduction in oxygen supply occurring in utero. However, it is not known if microvascularization of the fetus is augmented when pregnancy occurs at high altitude. Fifty-three healthy term newborns in Puno, Peru (3,840 m) were compared with sea-level controls. Pre-and postductal arterial oxygen saturation (SpO2) was determined. Cerebral and calf muscle regional tissue oxygenation was measured using near infrared spectroscopy (NIRS). Skin microcirculation was noninvasively measured using incident dark field imaging. Pre-and postductal SpO2 in Peruvian babies was 88.1 and 88.4%, respectively, which was 10.4 and 9.7% lower than in newborns at sea level (P=0.001). Cerebral and regional oxygen saturation was significantly lower in the Peruvian newborns (cerebral: 71.0 vs. 74.9%; regional: 68.5 vs. 76.0%, P=0.001). Transcutaneously measured total vessel density in the Peruvian newborns was 14% higher than that in the newborns born at sea level (29.7 vs. 26.0 mm/mm2; P=0.001). This study demonstrates that microvascular vessel density in neonates born to mothers living at high altitude is higher than that in neonates born at sea level.

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