A recommendation for the use of electrical biosensing technology in neonatology.

Non-invasive cardiac output monitoring, via electrical biosensing technology (EBT), provides continuous, multi-parameter hemodynamic variable monitoring which may allow for timely identification of hemodynamic instability in some neonates, providing an opportunity for early intervention that may improve neonatal outcomes. EBT encompasses thoracic (TEBT) and whole body (WBEBT) methods. Despite the lack of relative accuracy of these technologies, as compared to transthoracic echocardiography, the use of these technologies in neonatology, both in the research and clinical arena, have increased dramatically over the last 30 years. The European Society of Pediatric Research Special Interest Group in Non-Invasive Cardiac Output Monitoring, a group of experienced neonatologists in the field of EBT, deemed it appropriate to provide recommendations for the use of TEBT and WBEBT in the field of neonatology. Although TEBT is not an accurate determinant of cardiac output or stroke volume, it may be useful for monitoring longitudinal changes of hemodynamic parameters. Few recommendations can be made for the use of TEBT in common neonatal clinical conditions. It is recommended not to use WBEBT to monitor cardiac output. The differences in technologies, study methodologies and data reporting should be addressed in ongoing research prior to introducing EBT into routine practice. IMPACT STATEMENT: TEBT is not recommended as an accurate determinant of cardiac output (CO) (or stroke volume (SV)). TEBT may be useful for monitoring longitudinal changes from baseline of hemodynamic parameters on an individual patient basis. TEBT-derived thoracic fluid content (TFC) longitudinal changes from baseline may be useful in monitoring progress in respiratory disorders and circulatory conditions affecting intrathoracic fluid volume. Currently there is insufficient evidence to make any recommendations regarding the use of WBEBT for CO monitoring in neonates. Further research is required in all areas prior to the implementation of these monitors into routine clinical practice.

Effects of nutrition therapy on growth, inflammation and metabolism in immature infants: a study protocol of a double-blind randomized controlled trial (ImNuT).

BACKGROUND: Current nutritional management of infants born very preterm results in significant deficiency of the essential fatty acids (FAs) arachidonic acid (ARA) and docosahexaenoic acid (DHA). The impact of this deficit on brain maturation and inflammation mediated neonatal morbidities are unknown. The aim of this study is to determine whether early supply of ARA and DHA improves brain maturation and neonatal outcomes in infants born before 29 weeks of gestation. METHODS: Infants born at Oslo University Hospital are eligible to participate in this double-blind randomized controlled trial. Study participants are randomized to receive an enteral FA supplement of either 0.4 ml/kg MCT-oil™ (medium chain triglycerides) or 0.4 ml/kg Formulaid™ (100 mg/kg of ARA and 50 mg/kg of DHA). The FA supplement is given from the second day of life to 36 weeks' postmenstrual age (PMA). The primary outcome is brain maturation assessed by Magnetic Resonance Imaging (MRI) at term equivalent age. Secondary outcomes include quality of growth, incidence of neonatal morbidities, cardiovascular health and neuro-development. Target sample size is 120 infants (60 per group), this will provide 80% power to detect a 0.04 difference in mean diffusivity (MD, mm2/sec) in major white matter tracts on MRI. DISCUSSION: Supplementation of ARA and DHA has the potential to improve brain maturation and reduce inflammation related diseases. This study is expected to provide valuable information for future nutritional guidelines for preterm infants. TRIAL REGISTRATION: Clinicaltrials.gov ID: NCT03555019 . Registered 4 October 2018- Retrospectively registered.

Tissue Doppler velocity imaging and event timings in neonates: a guide to image acquisition, measurement, interpretation, and reference values.

Neonatologists can use echocardiography for real-time assessment of the hemodynamic state of neonates to support clinical decision-making. There is a large body of evidence showing the shortcomings of conventional echocardiographic indices in neonates. Newer imaging modalities have evolved. Tissue Doppler imaging is a new technique that can provide measurements of myocardial movement and timing of myocardial events and may overcome some of the shortcomings of conventional techniques. The high time resolution and its ability to assess left and right cardiac function make tissue Doppler a favorable technique for assessing heart function in neonates. The aim of this review is to provide an up-to-date overview of tissue Doppler techniques for the assessment of cardiac function in the neonatal context, with focus on measurements from the atrioventricular (AV) plane. We discuss basic concepts, protocol for assessment, feasibility, and limitations, and we report reference values and give examples of its use in neonates.

Deformation imaging and rotational mechanics in neonates: a guide to image acquisition, measurement, interpretation, and reference values.

Advances in neonatal cardiac imaging permit a more comprehensive assessment of myocardial performance in neonates that could not be previously obtained with conventional imaging. Myocardial deformation analysis is an emerging quantitative echocardiographic technique to characterize global and regional ventricular function in neonates. Cardiac strain is a measure of tissue deformation and strain rate is the rate at which deformation occurs. These measurements are obtained in neonates using tissue Doppler imaging (TDI) or two-dimensional speckle tracking echocardiography (STE). There is an expanding body of literature describing longitudinal reference ranges and maturational patterns of strain values in term and preterm infants. A thorough understanding of deformation principles, the technical aspects, and clinical applicability is a prerequisite for its routine clinical use in neonates. This review explains the fundamental concepts of deformation imaging in the term and preterm population, describes in a comparative manner the two major deformation imaging methods, provides a practical guide to the acquisition and interpretation of data, and discusses their recognized and developing clinical applications in neonates.

Application of Neonatologist Performed Echocardiography in the Assessment and Management of Neonatal Heart Failure unrelated to Congenital Heart Disease.

Neonatal heart failure (HF) is a progressive disease caused by cardiovascular and non-cardiovascular abnormalities. The most common cause of neonatal HF is structural congenital heart disease, while neonatal cardiomyopathy represents the most common cause of HF in infants with a structurally normal heart. Neonatal cardiomyopathy is a group of diseases manifesting with various morphological and functional phenotypes that affect the heart muscle and alter cardiac performance at, or soon after birth. The clinical presentation of neonates with cardiomyopathy is varied, as are the possible causes of the condition and the severity of disease presentation. Echocardiography is the selected method of choice for diagnostic evaluation, follow-up and analysis of treatment results for cardiomyopathies in neonates. Advances in neonatal echocardiography now permit a more comprehensive assessment of cardiac performance that could not be previously achieved with conventional imaging. In this review, we discuss the current and emerging echocardiographic techniques that aid in the correct diagnostic and pathophysiological assessment of some of the most common etiologies of HF that occur in neonates with a structurally normal heart and acquired cardiomyopathy and we provide recommendations for using these techniques to optimize the management of neonate with HF.

The role of Neonatologist Performed Echocardiography in the assessment and management of neonatal shock.

One of the major challenges of neonatal intensive care is the early detection and management of circulatory failure. Routine clinical assessment of the hemodynamic status of newborn infants is subjective and inaccurate, emphasizing the need for objective monitoring tools. An overview will be provided about the use of neonatologist-performed echocardiography (NPE) to assess cardiovascular compromise and guide hemodynamic management. Different techniques of central blood flow measurement, such as left and right ventricular output, superior vena cava flow, and descending aortic flow are reviewed focusing on methodology, validation, and available reference values. Recommendations are provided for individualized hemodynamic management guided by NPE.

Echocardiography parameters used in identifying right ventricle dysfunction in preterm infants with early bronchopulmonary dysplasia: A scoping review.

Background: Bronchopulmonary Dysplasia (BPD) is a chronic condition that affects preterm infants and is associated with long-term complications. Haemodynamic effects of BPD can lead to right ventricular (RV) dysfunction. Objective: To synthesise and map the evidence of echo parameters used in identifying RV dysfunction in the first two weeks-after-birth (WAB) of preterm infants with early BPD. Information Sources: This scoping review included the databases: Medline, CINAHL, PubMed, EMBASE, Scopus, ProQuest, Web of Science, Cochrane Library, JBI Evidence-Based Practise and Gray Literature. Search Strategy: The search utilised Boolean operators and descriptors registered in Medical Subject Headings. Inclusion and exclusion criteria: Included were studies utilising echo parameters to examine RV function in preterm infants with early BPD in the first two WAB. Synthesis of results: The results are presented as a map of the extracted findings in a tabular format with a narrative summary. Results: Eight studies were included. Differences were observed in the number and timing of echo scans performed in the first two WAB and the variations in the echo parameters used to compare preterm infants with and without early BPD. Only echo scans performed at the end of the first WAB, demonstrated significant differences in the echo parameters measurements between preterm infants with and without BPD. Studies using RV Myocardial Performance Index (MPI) to identify RV-dysfunction associated with early BPD demonstrated similar findings. The Pulsed-Wave Doppler technique identified differences in RV-MPI between preterm infants with and without BPD, while Tissue-Doppler-Imaging did not demonstrate similar results. Speckle tracking can measure strain (S) and strain rate (SR) and diagnose RV-dysfunction. However, the findings of studies that utilised speckle tracking varied. Finally, two of the included studies added blood tests to their diagnostic model of early BPD, which was able to demonstrate significant differences in blood test results between BPD-affected and control preterm infants. Conclusion: BPD could adversely affect the myocardium function of the RV; these negative influences can be captured in the first two WAB. However, there are still knowledge gaps regarding the appropriate number, timing and the most suitable echo parameters to assess RV function.

Cardiac morphology in neonates with fetal growth restriction.

OBJECTIVE: Assess effects of fetal growth restriction (FGR) on cardiac modelling in premature and term neonates. STUDY DESIGN: Prospective echocardiographic study of a cohort of FGR neonates (n = 21) and controls (n = 41) with normal prenatal growth and circulation. RESULTS: Unadjusted for gestational age, birth weight, sex, and twin/singleton, Late-FGR neonates had smaller hearts than controls, with globular left ventricles and symmetrical right ventricles. Adjusted estimates showed smaller left ventricles and similarly sized right ventricles, with symmetrical left and right ventricles. Early-FGR (compared with Late-FGR) had smaller hearts and globular left ventricles in unadjusted estimates, but after adjustment, sizes and shapes were similar. CONCLUSION: FGR had significant impact on cardiac modelling, seen in both statistical models unadjusted and adjusted for gestational age, birth weight, sex, and twin/singleton. The adjustments, however, refined the results and revealed more specific effects of FGR, thus underscoring the importance of statistical adjustments in such studies.

Heart function by M-mode and tissue Doppler in the early neonatal period in neonates with fetal growth restriction.

BACKGROUND: Fetal growth restricted (FGR) neonates have increased risk of circulatory compromise due to failure of normal transition of circulation after birth. AIM: Echocardiographic assessment of heart function in FGR neonates first three days after birth. STUDY DESIGN: Prospective observational study. SUBJECTS: FGR- and non-FGR neonates. OUTCOME MEASURES: M-mode excursions and pulsed-wave tissue Doppler velocities normalised for heart size and E/e' of the atrioventricular plane day one, two and three after birth. RESULTS: Compared with controls (non-FGR of comparable gestational age, n = 41), late-FGR (gestational age ≥ 32 weeks, n = 21) exhibited higher septal excursion (15.9 (0.6) vs. 14.0 (0.4) %, p = 0.021) (mean (SEM)) and left E/e' (17.3 (1.9) vs.11.5 (1.3), p = 0.019). Relative to day three, indexes on day one were higher for left excursion (21 (6) % higher on day one, p = 0.002), right excursion (12 (5) %, p = 0.025), left e' (15 (7) %, p = 0.049), right a' (18 (6) %, p = 0.001), left E/e' (25 (10) %, p = 0.015) and right E/e' (17 (7) %, p = 0.013), whereas no index changed from day two to day three. Late-FGR had no impact on changes from day one and two to day three. No measurements differed between early-FGR (n = 7) and late-FGR. CONCLUSIONS: FGR impacted neonatal heart function the early transitional days after birth. Late-FGR hearts had increased septal contraction and reduced left diastolic function compared with controls. The dynamic changes in heart function between first three days were most evident in lateral walls, with similar pattern in late-FGR and non-FGR. Early-FGR and late-FGR exhibited similar heart function.

Neonatal family care for 24 hours per day: effects on maternal confidence and breast-feeding.

In family care (FC) program for neonatal intensive care units (NICUs), parents are encouraged to reside together with their infant for 24 hours a day to actively be involved in the care. The aim of this study was to assess the impact of FC on maternal confidence and breast-feeding. Maternal confidence and rate of breast-feeding were assessed in 31 mothers offered FC that included special family rooms in the NICU, and in 30 mothers from a comparable NICU providing traditional care without such facilities. One week prior to hospital discharge, mothers in the FC group felt better informed regarding nursing issues and had more confidence in interpretation of the infants regarding feeding issues and in caregiving without staff attendance (P < .05). They also reported a higher level of empowerment (P < .05). Three months after discharge, the mothers in the FC group had a higher self-reported skill level for interpretation of the infant's signals and knowledge about breast-feeding (P < .05). Despite similar rate of breast-feeding at discharge, more infants in the FC group were breastfed 3 months after discharge (P < .05). An FC program in the NICU promoted better maternal confidence during the hospital stay and 3 months after discharge compared with traditional care.

Neonatologist Performed Echocardiography for Evaluating the Newborn Infant.

The interest in the use of cardiac ultrasound for hemodynamic evaluation in neonates has increased in the last decades. Several overlapping terms exists, and a non-comprehensive list includes point-of-care ultrasound, clinician-performed ultrasound, focused cardiac ultrasound, targeted neonatal echocardiography, and neonatologist performed echocardiography. This review will use the term neonatologist performed echocardiography. Neonatologist performed echocardiography is primarily echocardiography to obtain snapshots of hemodynamics and heart function, usually as repeated exams during intensive care. It provides the neonatologist with in-depth information on the hemodynamics not available by blood pressure, pulse oximetry, capillary refill time, and various blood tests. The review provides a brief overview of some relevant methods for assessment of hemodynamics and heart function. It does not discuss training, implementation, accreditation, and certification nor in-depth technical aspects and detailed use of neonatologist performed echocardiography. If the information obtainable by neonatologist performed echocardiography had been accessible easily (e.g., via a sensor put on the neonate similarly to a pulse oximeter), neonatologist performed echocardiography would have been more widely used. Acquiring skills for neonatologist performed echocardiography take time and resources. Future developments probably include a stronger focus on education, training, and certification. It is likely that echocardiographic methods will evolve further, probably involving establishing new indexes and methods and implementing artificial intelligence in the analyses procedure to improve accuracy and workflow. It is important to acknowledge that neonatologist performed echocardiography is not a therapeutic intervention; it is a diagnostic tool providing additional information.

Exploring right ventricular function applicability in a prediction model to identify preterm infants with early bronchopulmonary dysplasia (REPORT-BPD study): a mixed-methods observational cohort feasibility study protocol.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is a chronic disease that affects the immature lungs of preterm infants. Infants born before 32 weeks of gestation are at a greater risk of developing BPD due to the need for respiratory support with higher oxygen requirement. Pulmonary vascular remodelling in early BPD can impose an additional burden on the right ventricle (RV) and RV dysfunction. This protocol outlines the study design and aims to formulate a prediction model to identify early BPD through the data generated from echo scans analysis. METHODS: The mixed-methods observational cohort feasibility study, which comprises three work-packages (WPs), will be conducted at the regional neonatal unit, University Hospital Plymouth, Plymouth, UK. WP-I will recruit 40 preterm infants; each participant will have two heart scans performed in the first ten days after birth (DABs). WP-II will collect the documentation of the participating preterm infants' parents in the study neonatal unit diaries in the first 10 DABs. WP-III will involve semi-structured interviews of 10-15 parents of participating preterm infants and 10-15 health professionals who participated in WP-I. The study recruitment will be conducted over 18-months. The start date is 01 June 2022. WP-I and WP-II recruitment will occur during this period, while WP-III recruitment will occur during the second half. The results are expected to be submitted for publication by mid-2024. DISCUSSION: This paper outlines the study design. If the study successfully identifies the most sensitive echo parameter in recognising the RV dysfunction associated with early BPD, it will be an important finding in constructing an early BPD prediction model. TRIAL REGISTRATION: ClinicalTrials.gov Identifier is NCT05235399.

Longitudinal strain and strain rate by tissue Doppler are more sensitive indices than fractional shortening for assessing the reduced myocardial function in asphyxiated neonates.

The function of the heart was studied in 20 asphyxiated term neonates by measuring the longitudinal peak systolic strain and peak systolic strain rate by tissue Doppler in 18 segments of the heart on days 1, 2, and 3 of life. The fractional shortening was assessed at each examination as well. Measurements were compared against measurements in 48 healthy term neonates examined by the same protocol. The function of the heart was lower in the asphyxiated neonates - peak systolic strain (mean (95% confidence interval) -19.4% (-20.4, -18.5), peak systolic strain rate -1.65 (-1.74, -1.56) per second) than in the healthy term neonates (peak systolic strain -21.7% (-22.3, -21.0), peak systolic strain rate -1.78 (-1.84, -1.74) per second; p < 0.001). Fractional shortening was similar in the asphyxiated (29.2% (26.8, 31.5)) and healthy term neonates (29.0% (27.9, 30.1); p = 0.874). The peak systolic strain differed significantly between the asphyxiated and healthy term neonates for the left basal and right basal groups of segments (p < 0.05) but not for the left apical, right apical, septum apical, or septum basal groups of segments. The peak systolic strain rate differed significantly only for the septum apical group of segments. The differences were largest on the second day of life. Measurements were similar in asphyxiated neonates with elevated and normal cardiac troponin T levels. The peak systolic strain and strain rate were in this study more sensitive indices than fractional shortening for assessing the reduced myocardial function in asphyxiated term neonates.

Long-term follow-up and sex differences in adults operated for tetralogy of Fallot.

OBJECTIVE: Adults operated for tetralogy of Fallot (TOF) have high risk of ventricular arrhythmias (VA). QRS duration >180 ms is an established risk factor for VA. We aimed to investigate heart function, prevalence of arrhythmias and sex differences in patients with TOF at long-term follow-up. METHODS: We included TOF-operated patients≥18 years from our centre's registry. We reviewed medical records and the most recent echocardiographic exam. VA was recorded on ECGs, 24-hour Holter registrations and from implantable cardioverter defibrillator. RESULTS: We included 148 patients (age 37±10 years). Left ventricular global longitudinal strain (LV GLS, -15.8±3.1% vs -18.8±3.2%, p=0.001) and right ventricular (RV) GLS (-15.8±3.9% vs -19.1±4.1%, p=0.001) were lower in men at all ages compared with women. Higher RV D1 (4.3±0.5 cm vs 4.6±0.6 cm, p=0.01), lower ejection fraction (55%±8% vs 50%±9%, p=0.02), lower RV GLS (-18.1±4.0 ms vs -16.1±4.8 ms, p=0.04) and N-terminal pro-brain natriuretic peptide (NT-proBNP) over reference range (n=27 (23%) vs n=8 (77%), p<0.001) were associated with higher incidence of VA. QRS duration was longer in men (151±30 ms vs 128±25 ms, p<0.001). No patients had QRS duration >180 ms. QRS duration did not differ in those with and without VA (143±32 ms vs 137±28 ms, p=0.06). CONCLUSIONS: Our results confirmed reduced RV function in adults operated for TOF. Male patients had impaired LV and RV function expressed by lower LV and RV GLS values at all ages. Reduced cardiac function and elevated NT-proBNP were associated with higher incidence of VA and may be important in risk assessment.

Impact of pregnancy and risk factors for ventricular arrhythmias in women with tetralogy of Fallot.

OBJECTIVE: Patients with tetralogy of Fallot (TOF) have high survival rates 30 years after surgical repair. Many patients experience pregnancy; however, the effects of pregnancy on the long-term cardiovascular outcome are not well known. We investigated the association of pregnancy and cardiac function with occurrence of ventricular arrhythmia (VA) in women with TOF. METHODS: We recruited 80 women with repaired TOF from the national database. Holter monitoring or implanted devices detected VA, defined as non-sustained or sustained ventricular tachycardia or aborted cardiac arrest. All patients underwent echocardiography. Blood tests included NT-proBNP (N-terminal pro-brain natriuretic peptide). RESULTS: 55 (69%) women had experienced pregnancy. Mean age was lower in nulliparous compared with those with children (30±9 vs 40±9, p<0.01).VA had occurred in 17 (21%) women. Prevalence of VA was higher in women who had experienced pregnancy (n=16, 94%) compared with nulliparous (n=1, 6%) (p=0.02), also when adjusted for age (OR 12.9 (95% CI 1.5 to 113.2), p=0.02).Right ventricular mechanical dispersion was more pronounced in patients with VA (50±8 ms vs 39±14 ms, p=0.01, age-adjusted OR 2.1 (95% CI 1.3 to 7.5), p=0.01). NT-proBNP was also a marker of VA (211 ng/L (127 to 836) vs 139 ng/L (30 to 465), p=0.007). NT-proBNP >321 ng/L (normal values <170 ng/L) detected women with VA (p=0.019), also independent of age (OR 7.2 (95% CI 1.7 to 30.1), p=0.007). CONCLUSION: Pregnancy was associated with higher prevalence of VA among women with TOF. Right ventricular mechanical dispersion and NT-proBNP were age-independent markers of VA. These may have importance for pregnancy counselling and risk stratification.

Hypothermia and Cardiovascular Instability.

Severely asphyxiated neonates have acute heart failure as part of their multiorgan dysfunction syndrome during the first days of life. Supporting the cardiovascular system during this phase is part of contemporary treatment and regarded as vital for limiting the neurodevelopmental injury. The decision to treat cardiovascular instability should be based on evaluation of end-organ function. Neonatologist-performed echocardiography in combination with other diagnostic modalities enables comprehensive real-time assessment. This review discusses associations between hemodynamics and adverse outcome, modalities for evaluating the hemodynamic state of the infant, and therapeutic approaches during intensive care.

Septal contraction predicts acute haemodynamic improvement and paced QRS width reduction in cardiac resynchronization therapy.

AIMS: Three distinct septal contraction patterns typical for left bundle branch block may be assessed using echocardiography in heart failure patients scheduled for cardiac resynchronization therapy (CRT). The aim of this study was to explore the association between these septal contraction patterns and the acute haemodynamic and electrical response to biventricular pacing (BIVP) in patients undergoing CRT implantation. METHODS AND RESULTS: Thirty-eight CRT candidates underwent speckle tracking echocardiography prior to device implantation. The patients were divided into two groups based on whether their septal contraction pattern was indicative of dyssynchrony (premature septal contraction followed by various amount of stretch) or not (normally timed septal contraction with minimal stretch). CRT implantation was performed under invasive left ventricular (LV) pressure monitoring and we defined acute CRT response as ≥10% increase in LV dP/dtmax. End-diastolic pressure (EDP) and QRS width served as a diastolic and electrical parameter, respectively. LV dP/dtmax improved under BIVP (737 ± 177 mmHg/s vs. 838 ± 199 mmHg/s, P < 0.001) and 26 patients (68%) were defined as acute CRT responders. Patients with premature septal contraction (n = 27) experienced acute improvement in systolic (ΔdP/dtmax: 18.3 ± 8.9%, P < 0.001), diastolic (ΔEDP: -30.6 ± 29.9%, P < 0.001) and electrical (ΔQRS width: -23.3 ± 13.2%, P < 0.001) parameters. No improvement under BIVP was observed in patients (n = 11) with normally timed septal contraction (ΔdP/dtmax: 4.0 ± 7.8%, P = 0.12; ΔEDP: -8.8 ± 38.4%, P = 0.47 and ΔQRS width: -0.9 ± 11.4%, P = 0.79). CONCLUSION: Septal contraction patterns are an excellent predictor of acute CRT response. Only patients with premature septal contraction experienced acute systolic, diastolic, and electrical improvement under BIVP.

Tissue Doppler derived longitudinal strain and strain rate during the first 3 days of life in healthy term neonates.

Tissue Doppler derived longitudinal strain and strain rate were studied in 48 healthy term neonates by measuring peak systolic strain (PSS) and peak systolic strain rate (PSSR) in 18 heart segments on day 1-3 of life. The mean PSS for each examination was -21.8% (-22.1, -21.4) [mean (95%CI)], and the mean PSSR was -1.78/s (-1.81, -1.74). Age (d), fetal shunts, and heart rate had negligible impact on measurements for any segment. The fractional shortening had negligible impact on septum and left heart segments and the pulmonary artery pressure had no impact on the right heart segments. Values varied significantly between segments and individuals, and were lower (closer to zero) in images of low quality than in images of high quality (p < 0.05). Both apical and basal segments values were lower in the septum and higher in the right ventricle than in the left ventricle (p < 0.05), except for no difference between the basal left and right segments PSSR. Apical segments values were higher than basal segments values in the right ventricle (p < 0.05) but not in the septum or the left ventricle. At present, PSS and PSSR are more feasible for quantifying differences between segment groups and patient groups than between individuals and segments within individuals.