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Background: Characteristic changes in cerebral saturation (CrSO2), amplitude-integrated electroencephalography (aEEG), and echocardiography (ECHO) may be associated with intraventricular hemorrhage (IVH); however, the feasibility of their combined application is not known. Objective: The aim of this work was to investigate the feasibility and safety of combined multimodal cerebral and hemodynamic monitoring in extremely low gestational age (ELGA) infants in the first 72 h after birth. Methods: In this prospective -observational study of 50 infants born between 23 + 0 and 27 + 6 weeks gestation, we measured CrSO2 and aEEG, starting <8 h until 72 h of age. Sequential echocardiography and head ultrasound were performed at 4–8, 12–18, 24–30, and 48–60 h of age. The primary outcome was feasibility of multimodal monitoring, defined as >75% of the subjects satisfying at least 3/4 criteria: (a) CrSO2 and (b) aEEG monitoring each for >75% of the time, and (c) at least 2 out of 4 ECHO and (d) head ultrasounds (at least one by age 24 h). Adverse reactions to sensors, desaturation, and bradycardia during ultrasound studies were recorded. Results: Fifty infants were enrolled over 14 months. Multimodal monitoring was feasible in 49 (98%) infants. Forty-one (82%) infants fulfilled all 4 criteria. Mild erythema below CrSO2 sensors lasting 3–8 h without skin breakdown was noted in 8/50 subjects (16%). Desaturation was noted during 17/197 (8.6%) of the ultrasound studies. In total, 26/50 (52%) infants developed IVH (grade I/II, n = 22; grade III/IV, n = 4). Conclusion: Multimodal monitoring is feasible, safe, and well tolerated in ELGA infants in the first 72 h after birth. [ABSTRACT FROM AUTHOR]

Background: Non-invasive cardiac output monitoring (NICOM; NICOM™) may be useful in the management of extremely premature preterm infants. Objectives: To evaluate a new bioreactance-based method of continuous NICOM in preterm infants following patent ductus arteriosus (PDA) ligation. Methods: Infants underwent three paired NICOM and echocardiography assessments of stroke volume (SV) and left ventricular output (LVO) in the postoperative period: at 1, 6-8, and 16-18 h postoperatively. NICOM- and echocardiography-measured SV and LVO during those periods were compared using Bland-Altman analysis and the intraclass correlation coefficient (ICC). Results: Twenty-five infants with a median (interquartile range) gestational age and birth weight of 25.0 weeks (24.5-25.9) and 700 g (615-775), respectively, were included. The overall systematic bias (limits of agreement) across all time points between the NICOM and echocardiography SV readings was 39% (8-69) with NICOM consistently underestimating echocardiography values. There was moderate consistency between NICOM and echocardiography SV values (ICC 0.78, p < 0.001). Compared with the 1-hour scans, the 6- to 8- and 16- to 18-hour scans had increased biases of 7.9% (95% CI 2.5-13.2) and 9.7% (95% CI 3.6-15.8), respectively. Conclusion: Continuous LVO measurement using NICOM was feasible and demonstrated a consistent systematic bias compared with echocardiography in unstable extremely preterm infants without a PDA ligation. NICOM may be used as a trending tool for continuous monitoring in this population, but wide limits of agreement and increasing bias over time suggest it is not interchangeable with echocardiography. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objectives: Non-invasive cardiac output monitoring is a potentially useful clinical tool in the neonatal setting. Our aim was to evaluate a new method of non-invasive continuous cardiac output (CO) measurement (NICOM™) based on the principle of bioreactance in neonates. Methods: In this prospective observational study, 10 neonates underwent 97 paired NICOM and echocardiography (echo) assessments of left ventricular output (LVO). For each neonate, NICOM measurements of left ventricular stroke volume (SV) and LVO over a 2- to 4-hour period were correlated with blinded, simultaneous, discrete echo measurements of SV and LVO. The precision and accuracy of the NICOM monitor relative to echo during periods of steady state were assessed. Results: The infants' median birth weight was 2.72 kg (IQR 1.56-3.23 kg, range 1.44-4.00) and their median gestation was 37 weeks (IQR 31-40 weeks, range 31-41). Median NICOM SV and LVO readings were consistently lower than echo (2.6 ml [IQR 1.4-3.2, range 0.6-5.3] vs. 3.5 ml [IQR 2.1-4.4, range 1.1-6.8], and 400 ml/min [IQR 233-476] vs. 559 ml/min [IQR 386-652], p < 0.001). The NICOM LVO readings were lower than the echo readings by a mean of 153 ± 56 ml/kg. NICOM consistently under-read LVO by 31 ± 8%, and this systematic difference was constant across the range of LVOs obtained. There was a strong correlation between NICOM and echo measurements of LVO (r = 0.95, p < 0.001). Conclusion: Non-invasive cardiac output monitoring is feasible in neonates. Further validation studies in neonatal animal experimental models and human neonates need to be conducted before routine clinical use. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective An alternative therapy for preterm infants with a hemodynamically significant patent ductus arteriosus (hsPDA) is needed when cyclooxygenase inhibitors fail or where treatment is contraindicated due to coexisting renal failure, necrotizing enterocolitis, and/or intestinal perforation. No studies have evaluated the efficacy of per rectum (PR) acetaminophen. The study aimed to evaluate the efficacy of PR acetaminophen in modulating the risk of PDA ligation. Study Design A retrospective matched case–control study was conducted to compare neonates born <29 weeks' gestation with evidence of hsDA, in an era when rescue rectal acetaminophen was used (January 2014–March 2018) as a treatment strategy, versus historical controls (July 2006–August 2012). All patients underwent comprehensive echocardiography assessment of ductal shunt volume according to a standardized protocol. Acetaminophen treated neonates were matched according to demographics, gestation, preintervention echocardiography features, and comorbidities. Control patients were selected when an echocardiography was performed at an equivalent postnatal age. Infants with a genetic syndrome, severe congenital malformation, or major forms of congenital heart disease excluding small atrial septal defect or ventricular septal defect, PDA, or patent formale ovale were excluded. The primary outcome was surgical ligation of the PDA. Secondary outcomes included echocardiography indices of hemodynamic significance, the composite of death, or severe BPD (defined by ventilator dependence at 36 weeks postmenstrual age). Descriptive statistics and univariate (t -tests, Fisher's exact test, and Mann–Whitney U test) analyses were used to evaluate clinical and echocardiography characteristics of the groups and compare outcomes. Results Forty infants (20 cases and 20 controls), with similar demographic and echocardiography features, were compared. Cases received 6.8 ± 0.7 days (60 mg/kg/day) of PR acetaminophen. Responders (n = 12, 60%) had echocardiography evidence of reduced ductal diameter (2.2 mm [1.9–2.6] to 1.1 mm [0–1.7], p = 0.002), left ventricular output (363 ± 108–249 ± 61 mL/min/kg; p = 0.002) and left atrium to aortic root ratio (1.7 ± 0.3–1.3 ± 0.2; p = 0.002) following treatment. The rate of PDA ligation was 50% lower (p = 0.02) and composite outcome of death or severe bronchopulmonary dysplasia was reduced (p = 0.04) in the acetaminophen group. Conclusion Rectal acetaminophen was associated with improvement in echocardiography indices of PDA shunt volume, a 50% reduction in PDA ligation rates and a reduction in the composite outcome of death or severe BPD. Pharmacologic and further prospective clinical studies are needed. Key Points Many preterm infants encounter the clinical consequences of a hemodynamically significant PDA. The merits and optimal timing of PDA ligation remains an area of controversy amongst neonatologists. Cyclooxygenase inhibitors are associated with adverse events or are often contraindicated. [ABSTRACT FROM AUTHOR]

Background The transitional circulation and its effect on myocardial performance are poorly understood in preterm infants. Aims We assessed myocardial performance in infants less than 29 weeks gestation in the first 48 h of life using a comprehensive echocardiographic assessment. Design Infants < 29 weeks gestation were prospectively enrolled. Small for gestation, infants on inotropes and/or inhaled nitric oxide and septic infants were excluded. Conventional echocardiography, left ventricular (LV), septal and right ventricular (RV) tissue Doppler imaging (TDI) and tissue Doppler-derived strain and strain rate (SR), tricuspid annular plane systolic excursion (TAPSE) and global RV fractional area change (FAC) were assessed at a median of 10 and 45 h post-delivery. Results Fifty-four infants with a median [IQR] gestation and birth weight of 26.5 weeks [25.8–28.0 weeks] and 915 g [758–1142 g] were included. There was no change in shortening or ejection fraction across the two time points. Systolic and diastolic TDI of the LV, septum and RV increased across the two time points (all p values ≤ 0.01). There was an increase in septal peak systolic and early diastolic SR (p = 0.002). Septal systolic strain and late diastolic SR did not change. With the exception of RV strain and early diastolic SR, all RV functional parameters including SR, late diastolic SR, TAPSE, and FAC increased across the two time points (all p values < 0.01). Conclusion Describing the normal hemodynamic adaptations in stable preterm infants during the transitional period provides the necessary information for the assessment of those parameters in various disease states. [ABSTRACT FROM AUTHOR]

Right ventricular dysfunction, typically qualitatively diagnosed (Q-RVd) in preterm infants, requires echocardiography which is not always acutely available. We aimed to identify clinical indices of Q-RVd in very preterm infants (gestational age, GA <32 weeks) with persistent pulmonary hypertension of newborn (PPHN) and examine the reliability and validity of Q-RVd. Forty-seven infants with mean ± SD GA of 26.8 ± 2.7 weeks who had targeted neonatal echocardiography (TNE) ≤ 72 h old, during PPHN, were retrospectively studied. Three standard TNE clips were reviewed by two blinded assessors, and infants categorized as Q-RVd if moderate-severe RVd was diagnosed on ≥2 clips. Cardiopulmonary clinical indices at TNE and quantitative RV functional markers were compared between Q-RVd vs. no-RVd groups. Potential quantitative RVd definitions examined by classifying each measurement as "low" or "normal" using published data. Inter-rater agreement for Q-RVd assessed using Kappa statistics. Mean age at TNE was 25.3 ± 20.4 h with Q-RVd diagnosed in 19(40 %) infants. Q-RVd group demonstrated higher peak oxygen requirements (96 ± 9 % vs. 84 ± 16 %, p < 0.01); however, no clinical parameters at TNE differentiated the groups. Quantitative measures were lower in Q-RVd patients, confirming classification validity. Among tested quantitative definitions, low RV stroke volume was associated with lower systolic blood pressure (41 ± 7 vs. 47 ± 9 mmHg, p = 0.02) and higher shock index (4.02 ± 0.80 vs. 3.44 ± 0.72, p = 0.02). Kappa for Q-RVd was 0.55 (95%CI 0.32–0.77). The non-specific nature of clinical markers of RVd in preterm infants with PPHN necessitates echocardiographic diagnosis of RVd. Studies should examine prognostic relevance of RVd and establish outcome-based quantitative definitions in preterm infants. • Right ventricular dysfunction (RVd) is difficult to detect clinically in preterms. • Study supports use of timely echocardiography in preterm pulmonary hypertension. • Qualitative RVd diagnosis may be valid but is only moderately reliable in preterms. • Qualitative method may over-diagnose RVd in preterm pulmonary hypertension. • Normative dataset of quantitative echocardiography measures in preterms is needed. [ABSTRACT FROM AUTHOR]

Background: Subjective assessment of right ventricular (RV) function by neonatal echocardiography lacks validation. Incorrect diagnostic assignment in patients with suspected pulmonary hypertension (PH) may lead to unnecessary treatment or missed treatment opportunities. Methods: Six evaluators (experts [n = 3], novice [n = 3]) were asked to independently rate RV characteristics (global function, dilation, and septal flattening) based on standardized echocardiography images. We randomly selected 60 infants, ≥35 weeks gestation at birth, of whom 30 were clinically unwell with acute pulmonary hypertension (aPH) and 30 were healthy controls. aPH was defined by echocardiography presence of right‐left shunting across transitional shunts or elevated right ventricular systolic pressure as estimated by the magnitude of the regurgitant jet across the tricuspid valve with impaired oxygenation. Inter‐rater comparative evaluation within groups and between groups was performed using Kappa statistics. Results: Global agreement between evaluators for subjective assessment of RV function (0.3 [0.03], P < 0.001), size (0.14 [0.02], P < 0.001), and septal flattening (0.2 [0.02], P < 0.001) was uniformly poor. Agreement in RV function assessment was marginally better for both expert (0.32 [0.08], P < 0.001 vs 0.13 [0.081], and P < 0.001) and novice (0.4 [0.08], P < 0.001 vs 0.06 [0.07], and P < 0.001) evaluators. Overall, the diagnosis of aPH vs control was misclassified in 18% of cases. Conclusion: This study demonstrated significant variability in qualitative assessment of RV size and function by trained evaluators, regardless of level of expertise attained. The reliability of objective measures of RV hemodynamics requires prospective evaluation. [ABSTRACT FROM AUTHOR]

In the neonatal setting, point-of-care ultrasound is increasingly being used to help clinicians with the evaluation of heart function. Practices in neonatology, particularly with regard to acute and chronic hemodynamic managements, were traditionally more driven on dogma and predefined thresholds and not always supported by demonstrable physiology. For the first time, targeted neonatal echocardiography (TNE) provided neonatal intensivists with a bedside tool that made real-time assessment of neonatal hemodynamics status feasible in even the tiniest of babies. This opened the door towards more targeted physiological driven practices, allowing us to test historical approaches to clinical problems in a more precise way. Despite the standardization of TNE training and the creation of a formalized curriculum, little attention has been paid to the establishment of an empirical framework to adjudicate scientific investigation. In this position statement, we reflect on the evolution of TNE in Canadian neonatal intensive care units, appraise its strengths and limitations, and suggest guiding principles for clinicians and researchers to consider as they take this field forward. [ABSTRACT FROM AUTHOR]

Objective This article compares hemodynamic characteristics of neonates with hypoxic ischemic encephalopathy (HIE) receiving therapeutic hypothermia (TH) with normal versus abnormal brain magnetic resonance imaging (MRI). Methods Serial echocardiography (echo) was performed within 24 hours, after 48 to 72 hours of cooling, within 24 hours of normothermia, and after starting feeds. Pulmonary hemodynamics, cardiac output, and ventricular function were evaluated. All neonates underwent brain MRI (day 4-5), per clinical standard of care. Clinical cardiovascular and echocardiography characteristics were compared between patients with normal versus abnormal MRI. Cardiovascular changes during TH and after rewarming were identified. Results Twenty neonates at median gestation and birth weight of 40 weeks (inter-quartile range [IQR]: 39, 41) and 3,410 g (IQR: 2,885, 4,093), respectively, were enrolled. Increased median left ventricular output (LVO) (106-159 mL/kg/min, p < 0.001) and reduced isovolumic relaxation time (IVRT) (48-42 ms, p < 0.001) were seen after rewarming. Echocardiography evidence of pulmonary hypertension (PH) was identified in five neonates. Eight neonates (40%) had brain injury identified on MRI (watershed [n = 4], basal ganglia [n = 4]); this subgroup were more likely to have echo evidence of PH at 24 hours. Conclusion Longitudinal changes in cardiac output were noted in neonates with HIE during TH and rewarming. Echocardiography evidence of PH, however, was associated with abnormal MRI brain. The prognostic relevance of these physiologic changes requires more comprehensive delineation. [ABSTRACT FROM AUTHOR]

Background: Failure of first course of indomethacin (FCI) for patent ductus arteriosus (PDA) treatment in preterm neonates often prompts clinicians to consider a second course (SCI).Objective: To identify factors including baseline characteristics and response to FCI that are associated with non-response to SCI for PDA treatment in preterm neonates.Methods: In this retrospective observational study, neonates ≤32 weeks admitted to a tertiary NICU over 5 years who received two indomethacin courses for PDA treatment were reviewed. Only neonates with echocardiograms (ECHO) immediately before and after receipt of each indomethacin course were included. Primary outcome was non-response to SCI. Baseline characteristics and response to FCI were compared between responders and non-responders of SCI.Results: Of the 98 neonates enrolled, 47 (48%) had non-response to SCI. Of them, 27 patients (57%) had prior non-response to FCI, while of the 51 neonates who responded to SCI, 24 neonates (47%) had prior non-response to FCI. The adjusted risk of non-response to SCI in patients who had non-response to FCI was 37% higher (relative risk = 1.37, 95%CI: 0.87-1.80; p = .07) compared to those who had response to FCI. Multivariable analysis showed that increasing gestational age (AOR: 1.6, 95%CI: 1.1-2.3, p = .03) was associated with a higher odds of non-response to SCI while the odds of non-response to SCI increased by 90% in patients with non-response to FCI (AOR: 1.9, 95%CI: 0.8-4.5; p = .15) compared to those with success of FCI, although no statistical significance was observed.Conclusions: Advanced gestational age was the predictor of non-response to SCI in preterm neonates. [ABSTRACT FROM AUTHOR]

Chronic neonatal pulmonary hypertension (PHT) frequently results in early death. Systemically administered Rho-kinase (ROCK) inhibitors prevent and reverse chronic PHT in neonatal rats, but at the cost of severe adverse effects, including systemic hypotension and growth restriction. Simvastatin has pleiotropic inhibitory effects on isoprenoid intermediates that may limit activity of RhoA, which signals upstream of ROCK. We therefore hypothesized that statin treatment would safely limit pulmonary vascular RhoA activity and prevent and reverse experimental chronic neonatal PHT via downstream inhibitory effects on pathological ROCK activity. Sprague-Dawley rats in normoxia (room air) or moderate normobaric hypoxia (13% O2) received simvastatin (2 mg·kg-1 ·day-1 ip) or vehicle from postnatal days 1–14 (prevention protocol) or from days 14 –21 (rescue protocol). Chronic hypoxia increased RhoA and ROCK activity in lung tissue. Simvastatin reduced lung content of the isoprenoid intermediate farnesyl pyrophosphate and decreased RhoA/ROCK signaling in the hypoxiaexposed lung. Preventive or rescue treatment of chronic hypoxiaexposed animals with simvastatin decreased pulmonary vascular resistance, right ventricular hypertrophy, and pulmonary arterial remodeling. Preventive simvastatin treatment improved weight gain, did not lower systemic blood pressure, and did not cause apparent toxic effects on skeletal muscle, liver or brain. Rescue therapy with simvastatin improved exercise capacity. We conclude that simvastatin limits RhoA/ROCK activity in the chronic hypoxia-exposed lung, thus preventing or ameliorating hemodynamic and structural markers of chronic PHT and improving long-term outcome, without causing adverse effects. [ABSTRACT FROM AUTHOR]

Objective: To compare the effect of oral glucose given with or without facilitated tucking (FT), versus placebo (water) to facilitate image acquisition during a targeted neonatal echocardiography (TNE). Design: Factorial, double blind, randomized controlled trial. Setting: Tertiary neonatal intensive care unit (NICU). Patients: Infants born between 26 and 42 weeks of gestation (GA). Interventions: One of four treatment groups: oral water (placebo), oral glucose (25%), facilitated tucking with oral water or facilitated tucking with oral glucose, during a single, structured TNE. All infants received a soother. Main Outcome Measure: Change in Behavioral Indicators of Infant Pain (BIIP) scores. Results: 104 preterm infants were randomized (mean ± SD GA: 33.4 ± 3.5 weeks). BIIP scores remained low during the echocardiography scan (median, [IQ range]: 0, [0 to 1]). There were no differences in the level of agitation of infants amongst the treatment groups, with estimated reductions in mean BIIP relative to control of 0.27 (95%CI -0.40 to 0.94) with use of oral glucose and .04 (-0.63 to 0.70) with facilitated tucking. There were also no differences between treatment groups in the quality and duration of the echocardiography scans. Conclusions: In stable infants in the NICU, a TNE can be performed with minimal disruption in a majority of cases, simply by providing a soother. The use of 25% glucose water in this context did not provide further benefit in reducing agitation and improving image acquisition. Clinical Trial Registration: Clinical Trials.gov: [ABSTRACT FROM AUTHOR]

In this article, the author offers information on the use of targeted neonatal echocardiography (TNE) in the cardiovascular management of sick infants in neonatal intensive care unit (NICU). It mentions that the TNE can be performed with minimal disruption of infants simply by observing a set of soothing measures, including the use of a pacifier and prewarming the sonographic gel. It also mentions that the oral glucose solutions are recommended to reduce procedure-related stress in infants.