Reference Ranges for Arterial Oxygen Saturation, Heart Rate, and Cerebral Oxygen Saturation during Immediate Postnatal Transition in Neonates Born Extremely or Very Preterm.

OBJECTIVE: To define percentile charts for arterial oxygen saturation (SpO2), heart rate (HR), and cerebral oxygen saturation (crSO2) during the first 15 minutes after birth in neonates born very or extremely preterm and with favorable outcome. STUDY DESIGN: We conducted a secondary-outcome analysis of preterm neonates included in the COSGOD III trial with visible cerebral oximetry measurements and with favorable outcome, defined as survival without cerebral injuries until term age. We excluded infants with inflammatory morbidities within the first week after birth. SpO2 was obtained by pulse oximetry, and electrocardiogram or pulse oximetry were used for measurement of HR. CrSO2 was assessed with near-infrared spectroscopy. Measurements were performed during the first 15 minutes after birth. Percentile charts (10th to 90th centile) were defined for each minute. RESULTS: A total of 207 preterm neonates with a gestational age of 29.7 (23.9-31.9) weeks and a birth weight of 1200 (378-2320) grams were eligible for analyses. The 10th percentile of SpO2 at minute two, five, ten and 15 was 32%, 52%, 83% and 85%, respectively. The 10th percentile of HR at minute two, five, ten and 15 was 70bpm, 109bpm, 126bpm and 134bpm, respectively. The 10th percentile of crSO2 at minute two, five, ten and 15 was 15%, 27%, 59% and 63%, respectively. CONCLUSIONS: This study provides new centile charts for SpO2, HR, and crSO2 for extremely preterm neonates with favorable outcome. Implementing these centiles in guiding interventions during the stabilization process after birth might help to more accurately target oxygenation during postnatal transition period.

Neonatal somatic oxygenation and perfusion assessment using near-infrared spectroscopy : Part of the series on near-infrared spectroscopy by the European Society of Paediatric Research Special Interest Group "Near-Infrared Spectroscopy".

In this narrative review, we summarize the current knowledge and applications of somatic near-infrared spectroscopy (NIRS), with a focus on intestinal, renal, limb, and multi-site applications in neonates. Assessing somatic oxygenation at various body locations in neonates may aid in the understanding of underlying pathophysiology of organ injury. Considering cerebral autoregulation may be active to protect the brain during systemic circulatory failure, peripheral somatic oxygenation may potentially provide an early indication of neonatal cardiovascular failure and ultimate hypoxemic injury to vital organs including the brain. Certain intestinal oxygenation patterns appear to be associated with the onset and course of necrotizing enterocolitis, whereas impaired renal oxygenation may indicate the onset of acute kidney injury after various types of hypoxic events. Peripheral muscle oxygenation measured at a limb may be particularly effective in the early prediction of shock in neonates. Using multi-site NIRS may complement current approaches and clinical investigations to alert for neonatal tissue hypoxemia, and potentially even guide management. However, somatic NIRS has its inherent limitations in regard to accuracy. Interpretation of organ-specific values can also be challenging. Last, currently there are limited prospective intervention studies, and clinical benefits need to be examined further, after the clarification of critical threshold-values. IMPACT: The assessment of somatic oxygenation using NIRS may contribute to the prediction of specific diseases in hemodynamically challenged neonates. Furthermore, it may give early warning signs for impending cardiovascular failure, and impaired cerebral circulation and oxygenation. We present a comprehensive overview of the literature on applications of NIRS to various somatic areas, with a focus on its potential clinical applicability, including future research directions. This paper will enable prospective standardized studies, and multicenter collaboration to obtain statistical power, likely to advance the field.

Pulse oximetry signal loss during hypoxic episodes in preterm infants receiving automated oxygen control.

The aim of this study was to analyze signal loss (SL) resulting from low signal quality of pulse oximetry-derived hemoglobin oxygen saturation (SpO2) measurements during prolonged hypoxemic episodes (pHE) in very preterm infants receiving automatic oxygen control (AOC). We did a post hoc analysis of a randomized crossover study of AOC, programmed to set FiO2 to "back-up FiO2" during SL. In 24 preterm infants (median (interquartile range)) gestational age 25.3 (24.6 to 25.6) weeks, recording time 12.7 h (12.2 to 13.6 h) per infant, we identified 76 pHEs (median duration 119 s (86 to 180 s)). In 50 (66%) pHEs, SL occurred for a median duration of 51 s (33 to 85 s) and at a median frequency of 2 (1 to 2) SL-periods per pHE. SpO2 before and after SL was similar (82% (76 to 88%) vs 82% (76 to 87%), p = 0.3)).  Conclusion: SL is common during pHE and must hence be considered in AOC-algorithm designs. Administering a "backup FiO2" (which reflects FiO2-requirements during normoxemia) during SL may prolong pHE with SL.  Trial registration: The study was registered at www. CLINICALTRIALS: gov under the registration no. NCT03785899. WHAT IS KNOWN: • Previous studies examined SpO2 signal loss (SL) during routine manual oxygen control being rare, but pronounced in lower SpO2 states. • Oxygen titration during SL is unlikely to be beneficial as SpO2 may recover to a normoxic range. WHAT IS NEW: • Periods of low signal quality of SpO2 are common during pHEs and while supported with automated oxygen control (SPOC), FiO2 is set to a back-up value reflecting FiO2 requirements during normoxemia in response to SL, although SpO2 remained below target until signal recovery. • FiO2 overshoots following pHEs were rare during AOC and occurred with a delayed onset; therefore, increased FiO2 during SL does not necessarily lead to overshoots.

Prospective cohort study on facial profile changes in infants with Robin sequence and healthy controls.

BACKGROUND: Various conservative and surgical approaches exist to treat Robin sequence (RS), but their effects on facial profile and mandibular catch-up growth are unclear. A functional treatment concept, used in our centre for 25 years, includes an individualized palatal plate with a velo-pharyngeal extension and intensive feeding training. METHODS: We performed a prospective study to objectively describe facial profiles in infants with RS treated with the above concept. Infants with isolated RS were admitted to our tertiary perinatal and national referral centre for craniofacial malformations between May 2018 and Nov 2019. Infants with RS received 3D-photographs during clinically indicated visits. Healthy controls were recruited from Dec 2018 to Sep 2019 and received 3D-photographs every 3 months. The digitally measured jaw index (JI), defined as alveolar overjet (O) x maxillary arch (U)/mandibular arch (L), and the soft tissue reference points A'-point, Nasion', B'-point angle (ANB'), describing the relative position of maxilla to mandible, were evaluated. Linear mixed models were used to examine time trajectories in JI and ANB'. RESULTS: A total of 207 3D images, obtained in 19 infants with RS and 32 controls, were analysed. JI and ANB' decreased over time in both groups [for JI - 0.18 (95% CI - 0.25 to - 0.10); for ANB': - 0.40° per month [(95% CI - 0.48 to - 0.32)]] but remained lower in controls [for JI - 2.5 (95% CI - 3.2 to - 1.8); for ANB'-1.7° (95% CI - 2.4 to - 1.0)]. Also, the ANB' model showed a significant effect of the interaction term diagnosis x age. CONCLUSIONS: Based on longitudinal 3D images, we describe changes in objective parameters of facial profile in infants with and without RS during the first year of life. Our findings indicate catch-up growth in infants treated for RS. Video Abstract.

Randomised crossover study on pulse oximeter readings from different sensors in very preterm infants.

OBJECTIVE: In extremely preterm infants, different target ranges for pulse oximeter saturation (SpO2) may affect mortality and morbidity. Thus, the impact of technical changes potentially affecting measurements should be assessed. We studied SpO2 readings from different sensors for systematic deviations. DESIGN: Single-centre, randomised, triple crossover study. SETTING: Tertiary neonatal intensive care unit. PATIENTS: 24 infants, born at <32 weeks' gestation, with current weight <1500 g and without right-to-left shunt via a patent ductus arteriosus. INTERVENTIONS: Simultaneous readings from three SpO2 sensors (Red Diamond (RD), Photoplethysmography (PPG), Low Noise Cabled Sensors (LNCS)) were logged at 0.5 Hz over 6 hour/infant and compared with LNCS as control using analysis of variance. Sensor position was randomly allocated and rotated every 2 hours. Seven different batches each were used. OUTCOMES: Primary outcome was the difference in SpO2 readings. Secondary outcomes were differences between sensors in the proportion of time within the SpO2-target range (90-95 (100)%). RESULTS: Mean gestational age at birth (±SD) was 274/7 (±23/7) weeks, postnatal age 20 (±20) days. 134 hours of recording were analysed. Mean SpO2 (±SD) was 94.0% (±3.8; LNCS) versus 92.2% (±4.0; RD; p<0.0001) and 94.5% (±3.9; PPG; p<0.0001), respectively. Mean SpO2 difference (95% CI) was -1.8% (-1.9 to -1.8; RD) and 0.5% (0.4 to 0.5; PPG). Proportion of time in target was significantly lower with RD sensors (84.8% vs 91.7%; p=0.0001) and similar with PPG sensors (91.1% vs 91.7%; p=0.63). CONCLUSION: There were systematic differences in SpO2 readings between RD sensors versus LNCS. These findings may impact mortality and morbidity of preterm infants, particularly when aiming for higher SpO2-target ranges (eg, 90-95%). TRIAL REGISTRATION NUMBER: DRKS00027285.

Early initiation of antibiotic therapy and short-term outcomes in preterm infants: a single-centre retrospective cohort analysis.

BACKGROUND: Sepsis is one of the most important complications in preterm infants. For this reason, many such infants receive antibiotics during their hospital stay. However, early antibiotic therapy has also been associated with adverse outcome. It is yet largely unclear if the time of onset of antibiotic therapy influences the outcome. We here investigated whether the timing of initiation of antibiotic therapy plays a role in the association between antibiotic exposure and short-term outcome. METHODS: Retrospective analysis of data from 1762 very low birthweight infants born in a German neonatal intensive care unit (NICU) between January 2004 and December 2021. RESULTS: Antibiotics were administered to 1214 of the 1762 (68.9%) infants. In 973 (55.2%) of the 1762 of infants, antibiotic therapy was initiated within the first two postnatal days. Only 548 (31.1%) infants did not have any antibiotic prescription during their stay in the NICU. Antibiotic exposure at every timepoint was associated with an increased risk of all short-term outcomes analysed in univariable analyses. In multivariable analyses, initiation of antibiotic therapy within the first two postnatal days and initiation between postnatal days 3 and 6 was independently associated with an increased risk of developing bronchopulmonary dysplasia (BPD) (OR 3.1 and 2.8), while later initiation of antibiotic therapy was not. CONCLUSION: Very early initiation of antibiotic therapy was associated with an increased risk of BPD. Due to the study design, no conclusions on causality can be drawn. If confirmed, our data suggest that an improved identification of infants at low risk of early-onset sepsis is needed to reduce antibiotic exposure.

Cerebral regional tissue Oxygen Saturation to Guide Oxygen Delivery in preterm neonates during immediate transition after birth (COSGOD III): multicentre randomised phase 3 clinical trial.

OBJECTIVE: To investigate whether monitoring of cerebral tissue oxygen saturation using near infrared spectroscopy in addition to routine monitoring combined with defined treatment guidelines during immediate transition and resuscitation increases survival without cerebral injury of premature infants compared with standard care alone. DESIGN: Multicentre, multinational, randomised controlled phase 3 trial. SETTING: 11 tertiary neonatal intensive care units in six countries in Europe and in Canada. PARTICIPANTS: 1121 pregnant women (<32 weeks' gestation) were screened prenatally. The primary outcome was analysed in 607 of 655 randomised preterm neonates: 304 neonates in the near infrared spectroscopy group and 303 in the control group. INTERVENTION: Preterm neonates were randomly assigned to either standard care (control group) or standard care plus monitoring of cerebral oxygen saturation with a dedicated treatment guideline (near infrared spectroscopy group) during immediate transition (first 15 minutes after birth) and resuscitation. MAIN OUTCOME MEASURE: The primary outcome, assessed using all cause mortality and serial cerebral ultrasonography, was a composite of survival without cerebral injury. Cerebral injury was defined as any intraventricular haemorrhage or cystic periventricular leukomalacia, or both, at term equivalent age or before discharge. RESULTS: Cerebral tissue oxygen saturation was similar in both groups. 252 (82.9%) out of 304 neonates (median gestational age 28.9 (interquartile range 26.9-30.6) weeks) in the near infrared spectroscopy group survived without cerebral injury compared with 238 (78.5%) out of 303 neonates (28.6 (26.6-30.6) weeks) in the control group (relative risk 1.06, 95% confidence interval 0.98 to 1.14). 28 neonates died (near infrared spectroscopy group 12 (4.0%) v control group 16 (5.3%): relative risk 0.75 (0.33 to 1.70). CONCLUSION: Monitoring of cerebral tissue oxygen saturation in combination with dedicated interventions in preterm neonates (<32 weeks' gestation) during immediate transition and resuscitation after birth did not result in substantially higher survival without cerebral injury compared with standard care alone. Survival without cerebral injury increased by 4.3% but was not statistically significant. TRIAL REGISTRATION: ClinicalTrials.gov NCT03166722.

Agreement of Cardiac Output Estimates between Electrical Cardiometry and Transthoracic Echocardiography in Very Preterm Infants.

INTRODUCTION: The aim was to evaluate the agreement between cardiac output estimates obtained by electrical cardiometry (EC) and transthoracic echocardiography (TTE) in very preterm infants. METHODS: This is a single-center prospective observational study in infants born<32 weeks gestational age within 48 h of birth. Continuous EC was recorded and simultaneous TTE obtained on day 1 and day 2 of life. Blinded TTE measurements were performed within a 10 s timeframe using beat-to-beat EC data. The primary outcome was %error of left ventricular (LV) output in milliliters per kilogram per minute (cardiac index (CI)) obtained by TTE compared to LV-CI from EC. Secondary outcome parameters were bias, %bias, limits of agreement and include measures of right ventricular (RV) output and LV systolic time intervals. RESULTS: Analysis was performed for 34 infants (median (IQR) gestational age 29 + 0 (24 + 5 to 30 + 6) weeks + days, birthweight 960 (748 to 1,490) grams) including 44 pairwise LV output measurements on 24 participants (22 on day 1 and day 2). The %error was 54% for LV-CI (EC: 214 (38) mL/kg/min vs. TTE: 163 (47) mL/kg/min). The %error was 78% for RV-CI (EC: 213 (37) mL/kg/min vs. TTE: 241 (77) mL/kg/min). While only LV-CI values affected LV-CI bias, signal quality, heart rate, and RV-CI values affected RV-CI bias. CONCLUSION: EC is not interchangeable with TTE to estimate indices of LV or RV output in very preterm infants within the first 48 h postnatally. EC may not measure LV output distinctly in very preterm infants with intra- and extracardiac shunts.

Gas in scattering media absorption spectroscopy as a potential tool in neonatal respiratory care.

Gas in scattering media absorption spectroscopy (GASMAS) is a novel optical technology employing near-infrared light. It has a potential use in the medical setting as a monitoring and diagnostic tool by detecting molecular oxygen within gas pockets and thus may be a useful adjunct in respiratory monitoring. GASMAS has potential advantages over other monitoring devices currently used in clinical practice. It is a non-invasive, continuous, non-ionising technology and provides unique information about molecular oxygen content inside the lungs. GASMAS may have a future role in optimising respiratory management of neonates in different clinical scenarios such as monitoring cardiorespiratory transition in the delivery room, assessing surfactant deficiency, and optimising endotracheal tube positioning. This article aims to summarise current evidence exploring GASMAS application in a neonate, discuss possible clinical benefits, and compare with other devices that are currently used in neonatal care. IMPACT: This article presents a novel optical technique to measure lung oxygen concentrations that may have important clinical uses. This review summarises the current literature investigating the concept of optical lung oxygen measurement. Information from this review can guide researchers in future studies.

Early cerebral hypoxia in extremely preterm infants and neurodevelopmental impairment at 2 year of age: A post hoc analysis of the SafeBoosC II trial.

BACKGROUND: The SafeBoosC II, randomised clinical trial, showed that the burden of cerebral hypoxia was reduced with the combination of near infrared spectroscopy and a treatment guideline in extremely preterm infants during the first 72 hours after birth. We have previously reported that a high burden of cerebral hypoxia was associated with cerebral haemorrhage and EEG suppression towards the end of the 72-hour intervention period, regardless of allocation. In this study we describe the associations between the burden of cerebral hypoxia and the 2-year outcome. METHODS: Cerebral oxygenation was continuously monitored from 3 to 72 hours after birth in 166 extremely preterm infants. At 2 years of age 114 of 133 surviving children participated in the follow-up program: medical examination, Bayley II or III test and the parental Ages and Stages Questionnaire. The infants were classified according to the burden of hypoxia: within the first three quartiles (n = 86, low burden) or within in the 4th quartile (n = 28, high burden). All analyses were conducted post hoc. RESULTS: There were no statistically significant differences between the quantitative assessments of neurodevelopment in the groups of infants with the low burden of cerebral hypoxia versus the group of infants with the high burden of cerebral hypoxia. The infants in the high hypoxia burden group had a higher-though again not statistically significant-rate of cerebral palsy (OR 2.14 (0.33-13.78)) and severe developmental impairment (OR 4.74 (0.74-30.49). CONCLUSIONS: The burden of cerebral hypoxia was not significantly associated with impaired 2-year neurodevelopmental outcome in this post-hoc analysis of a feasibility trial.

Randomised crossover trial comparing algorithms and averaging times for automatic oxygen control in preterm infants.

OBJECTIVE: Automatic control (SPOC) of the fraction of inspired oxygen (FiO2), based on continuous analysis of pulse oximeter saturation (SpO2), improves the proportion of time preterm infants spend within a specified SpO2-target range (Target%). We evaluated if a revised SPOC algorithm (SPOCnew, including an upper limit for FiO2) compared to both routine manual control (RMC) and the previously tested algorithm (SPOCold, unrestricted maximum FiO2) increases Target%, and evaluated the effect of the pulse oximeter's averaging time on controlling the SpO2 signal during SPOC periods. DESIGN: Unblinded, randomised controlled crossover study comparing 2 SPOC algorithms and 2 SpO2 averaging times in random order: 12 hours SPOCnew and 12 hours SPOCold (averaging time 2 s or 8 s for 6 hours each) were compared with 6-hour RMC. A generated list of random numbers was used for allocation sequence. SETTING: University-affiliated tertiary neonatal intensive care unit, Germany PATIENTS: Twenty-four infants on non-invasive respiratory support with FiO2 >0.21 were analysed (median gestational age at birth, birth weight and age at randomisation were 25.3 weeks, 585 g and 30 days). MAIN OUTCOME MEASURE: Target%. RESULTS: Mean (SD) [95% CI] Target% was 56% (9) [52, 59] for RMC versus 69% (9) [65, 72] for SPOCold_2s, 70% (7) [67, 73] for SPOCnew_2s, 71% (8) [68, 74] for SPOCold_8s and 72% (8) [69, 75] for SPOCnew_8s. CONCLUSIONS: Irrespective of SpO2-averaging time, Target% was higher with both SPOC algorithms compared to RMC. Despite limiting the maximum FiO2, SPOCnew remained significantly better at maintaining SpO2 within target range compared to RMC. TRIAL REGISTRATION: NCT03785899.

In-Silico Evaluation of Anthropomorphic Measurement Variations on Electrical Cardiometry in Neonates.

Non-invasive cardiac output methods such as Electrical Cardiometry (EC) are relatively novel assessment tools for neonates and they enable continuous monitoring of stroke volume (SV). An in-silico comparison of differences in EC-derived SV in relation to preset length and weight was performed. EC (ICON, Osypka Medical) was simulated using the "demo" mode for various combinations of length and weight representative of term and preterm infants. One-centimetre length error resulted in a SV-change of 1.8-3.6% (preterm) or 1.6-2.0% (term) throughout the tested weight ranges. One-hundred gram error in weight measurement resulted in a SV-change of 5.0-7.1% (preterm) or 1.5-1.8% (term) throughout the tested length ranges. Algorithms to calculate EC-derived SV incorporate anthropomorphic measurements. Therefore, inaccuracy in physical measurement can impact absolute EC measurements. This should be considered in the interpretation of previous findings and the design of future clinical studies of EC-derived cardiac parameters in neonates, particularly in the preterm cohorts where a proportional change was noted to be greatest.

Near-infrared spectroscopy for perioperative assessment and neonatal interventions.

Perioperative applications of near-infrared spectroscopy (NIRS) to monitor regional tissue oxygenation and perfusion in cardiac and noncardiac surgery are of increasing interest in neonatal care. Complex neonatal surgery can impair adequate oxygen delivery and tissue oxygen consumption and increase the risk of neurodevelopmental delay. Coupled with conventional techniques, NIRS monitoring may enable targeted hemodynamic management of the circulation in both cardiac and noncardiac surgical procedures. In this narrative review, we discuss the application of perioperative NIRS in specific neonatal interventions, including surgical intervention for congenital heart defects, definitive closure of the patent ductus arteriosus, neurological and gastrointestinal disorders, and use of extracorporeal membrane oxygenation. We identified areas for future research within disease-specific indications and offer a roadmap to aid in developing evidence-based targeted diagnostic and management strategies in neonates. IMPACT: There is growing recognition that perioperative NIRS monitoring, used in conjunction with conventional monitoring, may provide critical hemodynamic information that either complements clinical impressions or delivers novel physiologic insight into the neonatal circulatory and perfusion pathways.

Signal Quality of Electrical Cardiometry and Perfusion Index in Very Preterm Infants.

OBJECTIVE: The use of noninvasive monitoring of neonatal hemodynamics is increasing in neonatal care. Methods include noninvasive cardiac output estimated by electrical cardiometry (EC) and peripheral perfusion as perfusion index (PI) using pulse oximetry. Our aim was to evaluate the feasibility to continuously monitor preterm infants with EC and PI during the first 2 postnatal days and the effects of averaging EC data in signal quality (SigQ) analysis. DESIGN: Prospective observational study. SETTING: Tertiary neonatal academic hospital. PATIENTS: Preterm infants <32 weeks gestation from birth until 48 h. MAIN OUTCOME MEASURES: Continuous EC and PI measurements. Feasibility was quantified as the time with high SigQ, classified using SigQ index in EC and exception codes in PI. Our predefined threshold for good feasibility was minimum of 24 h with high SigQ for both. RESULTS: Twenty-two preterm infants (median [IQR] gestational age 28 + 6 (26 + 0, 30 + 4) weeks + days, birth weight 960 [773, 1,500] g) were included. We recorded a minimum of 24 h with high SigQ in 14 infants for EC (unaveraged data) and 22 infants for PI measurements. The median (range) % of recording time with high SigQ was 74% (50%, 88%) for EC and 94% (82%, 96%) for PI. Using 1 minute averaging for EC data resulted in an increase of infants with minimum 24 h of high SigQ to 21 infants. CONCLUSIONS: EC and PI monitoring are feasible in preterm infants within the first 48 h, but SigQ remains problematic for EC. Signal dropout is masked in averaged EC values.

A Framework for AI-Assisted Detection of Patent Ductus Arteriosus from Neonatal Phonocardiogram.

The current diagnosis of Congenital Heart Disease (CHD) in neonates relies on echocardiography. Its limited availability requires alternative screening procedures to prioritise newborns awaiting ultrasound. The routine screening for CHD is performed using a multidimensional clinical examination including (but not limited to) auscultation and pulse oximetry. While auscultation might be subjective with some heart abnormalities not always audible it increases the ability to detect heart defects. This work aims at developing an objective clinical decision support tool based on machine learning (ML) to facilitate differentiation of sounds with signatures of Patent Ductus Arteriosus (PDA)/CHDs, in clinical settings. The heart sounds are pre-processed and segmented, followed by feature extraction. The features are fed into a boosted decision tree classifier to estimate the probability of PDA or CHDs. Several mechanisms to combine information from different auscultation points, as well as consecutive sound cycles, are presented. The system is evaluated on a large clinical dataset of heart sounds from 265 term and late-preterm newborns recorded within the first six days of life. The developed system reaches an area under the curve (AUC) of 78% at detecting CHD and 77% at detecting PDA. The obtained results for PDA detection compare favourably with the level of accuracy achieved by an experienced neonatologist when assessed on the same cohort.

In vitro evaluation of delays in the adjustment of the fraction of inspired oxygen during CPAP: effect of flow and volume.

BACKGROUND: Adjusting the fraction of inspired oxygen (FiO2) delivered to preterm infants to keep their oxygen saturation within target range remains challenging. Closed-loop automated FiO2 control increases the time infants spend within the assigned target range. The delay with which FiO2 adjustments at the ventilator result in a change in the inspired gas limits the performance of both manual and automated controls. OBJECTIVE: To evaluate the equilibration time (Teq) between FiO2 adjustments and changes in FiO2 reaching the patient. METHODS: In vitro determination of the delay in FiO2 adjustments at the ventilator at 5 and 8 L/min of gas flow and two different humidifier/ventilator circuit volumes (840 and 432 mL). RESULTS: Teq values were 31, 23, 20 and 17 s for the volume-flow combinations 840 mL+5 L/min, 840 mL+8 L/min, 432 mL+5 L/min and 432 mL+8 L/min, respectively. CONCLUSION: The identified delay seems clinically relevant and should be taken into account during manual and automatic control of FiO2.

Management of Neonatal Hypotension and Shock.

The current standard approach to manage circulatory insufficiency is inappropriately simple and clear: respond to low blood pressure to achieve higher values. However, the evidence for this is limited affecting all steps within the process: assessment, decision making, therapeutic options, and treatment effects. We have to overcome the 'one size fits all' approach and respect the dynamic physiologic transition from fetal to neonatal life in the context of complex underlying conditions. Caregivers need to individualize their approaches to individual circumstances. This paper will review various clinical scenarios, including managing transitional low blood pressure, to circulatory impairment involving different pathologies such as hypoxia-ischemia and sepsis. We will highlight the current evidence and set potential goals for future development in these areas. We hope to encourage caregivers to question the current standards and to support urgently needed research in this overlooked but crucial field of neonatal intensive care.

Non-invasive Cardiac Output Monitoring in Neonates.

Circulatory monitoring is currently limited to heart rate and blood pressure assessment in the majority of neonatal units globally. Non-invasive cardiac output monitoring (NiCO) in term and preterm neonates is increasing, where it has the potential to enhance our understanding and management of overall circulatory status. In this narrative review, we summarized 33 studies including almost 2,000 term and preterm neonates. The majority of studies evaluated interchangeability with echocardiography. Studies were performed in various clinical settings including the delivery room, patent ductus arteriosus assessment, patient positioning, red blood cell transfusion, and therapeutic hypothermia for hypoxic ischemic encephalopathy. This review presents an overview of NiCO in neonatal care, focusing on technical and practical aspects as well as current available evidence. We discuss potential goals for future research.

Is faster better? A randomised crossover study comparing algorithms for closed-loop automatic oxygen control.

OBJECTIVE: Closed-loop automatic control (CLAC) of the fractional inspired oxygen (FiO2) improved oxygen administration to preterm infants on respiratory support. We investigated whether a revised CLAC algorithm (CLACfast, ≤2 FiO2 adjustments/min), compared with routine manual control (RMConly), increased the proportion of time with arterial haemoglobin oxygen saturation measured by pulse oximetry within prespecified target ranges (Target%) while not being inferior to the original algorithm (CLACslow: ≤0.3 FiO2 adjustments/min). DESIGN: Unblinded randomised controlled crossover study comparing three modes of FiO2 control in random order for 8 hours each: RMC supported by CLACfast was compared with RMConly and RMC supported by CLACslow. A computer-generated list of random numbers using a block size of six was used for the allocation sequence. SETTING: Two German tertiary university neonatal intensive care units. PATIENTS: Of 23 randomised patients, 19 were analysed (mean±SD gestational age 27±2 weeks; age at randomisation 24±10 days) on non-invasive (n=18) or invasive (n=1) respiratory support at FiO2 >0.21. MAIN OUTCOME MEASURE: Target%. RESULTS: Mean±SD [95% CI] Target% was 68%±11% [65% to 71%] for CLACfast versus 65%±11% [61% to 68%] for CLACslow versus 58%±11% [55% to 62%] for RMConly. Prespecified hypothesis tests of: (A) superiority of CLACfast versus RMConly and (B) non-inferiority of CLACfast versus CLACslow with margin of 5% yielded one-sided p values of <0.001 for both comparisons. CONCLUSIONS: This revised and faster CLAC algorithm was still superior to routine care in infants on respiratory support and not inferior to a previously tested slower algorithm. TRIAL REGISTRATION NUMBER: NCT03163108.

Beta blocker therapy in recipients of twin-to-twin transfusion syndrome.

Recipients of severe twin-to-twin transfusion syndrome (TTTS) may suffer from low cardiac output caused by myocardial hypertrophy and sudden postnatal drop in preload. Our hypothesis was that selective beta-1 adrenergic blockers improve cardiac function in TTTS recipients with left ventricular outflow tract obstruction. We analysed data from two TTTS recipients treated with esmolol/metoprolol. Despite intense circulatory support, both patients showed severe hypotension and tachycardia before therapy. Echocardiographic findings included hypertrophic ventricles with thickened intraventricular septum, reduced aortic valve velocity time integral (AV-VTI), left ventricular outflow tract obstruction and collapsing ventricles in systole. Beta blocker improved blood pressure as well as AV-VTI, which served as a surrogate parameter for left ventricular stroke volume, reduced heart rate and need for circulatory support. In conclusion, beta blockade may improve left ventricular function in TTTS recipients with low cardiac output due to myocardial hypertrophy.