Left ventricle phenotyping utilizing tissue doppler imaging in premature infants with varying severity of bronchopulmonary dysplasia

Bronchopulmonary dysplasia (BPD) is characterized by alveolar-capillary simplification and is associated with pulmonary hypertension (PH) in preterm infants. The contribution of left ventricle (LV) disease towards this severe BPD-PH phenotype is not well established. We aimed to describe the longitudinal trajectory of the LV function as measured by tissue Doppler imaging (TDI) and its association with BPD-PH. We retrospectively assessed prospectively acquired clinical and echocardiographic data from 77 preterm infants born between 2011 and 2013. We characterized the LV function by measuring systolic and diastolic myocardial velocities (s\u27, e\u27, a\u27), isovolumetric relaxation time (IVRT), and myocardial performance index with TDI at three time periods from 32 and 36 weeks, postmenstrual age through one year of age. We also measured post systolic motion (PSM), a marker of myocardial dysfunction that results from asynchronous movement of the ventricular walls, and not previously described in preterm infants. Patients were stratified into groups according to BPD severity and the presence of PH and compared over time. Conventional TDI measures of the LV function were similar between groups, but the septal PSM was significantly prolonged over the first year of age in patients with BPD-PH. PSM provides a novel objective way to assess the hemodynamic impact of lung and pulmonary vascular disease severity on LV function in preterm infants with BPD and PH

Cardiac performance in the first year of age among preterm infants fed maternal breast milk

Importance: There is a beneficial association between human breast milk exposure in the neonatal period and cardiac mechanics in adults who were born preterm. It is unknown whether this benefit is apparent in infants in the first year of age. Objective: To test the hypothesis that higher consumption of mother\u27s own milk in preterm infants is associated with enhanced cardiac performance during the first year of age. Design, Setting, and Participants: This cross-sectional study of cardiac and nutritional data at an academic medical center included 80 individuals born preterm and 100 individuals in the control group born full-term. All births were between 2011 and 2013. Two-dimensional echocardiograms were performed at 32 weeks\u27 and 36 weeks\u27 postmenstrual age and at 1 year\u27s corrected age in individuals born preterm and at 1 month and 1 year of age in individuals born full-term. Statistical analysis was performed from January to May 2021. Exposures: Consumption of mother\u27s own milk. Main Outcomes and Measures: Main study outcomes included echocardiography measures of right and left ventricle longitudinal strain (function), left ventricle mass index and right ventricular areas (morphology), and pulmonary vascular resistance (pulmonary hemodynamics) at age 1 year. Results: Of 180 infants included in the study, 97 (54%) were Black infants and 89 (49%) were female infants. Among the 80 infants born in the preterm cohort, 43 (54%) were female infants and 43 (54%) were Black infants. The median gestational age at birth of the preterm infants was 27.0 weeks (interquartile range, 26.0-28.0 weeks) and the median birth weight was 960 g (interquartile range, 800-1138). For each week of exposure to mother\u27s own milk, preterm infants had greater magnitudes of right ventricular strain (eg, right longitudinal strain: β, 0.021; 95% CI, 0.002-0.041; P \u3c .001) and left ventricular strain (eg, left longitudinal strain: β, 0.065; 95% CI, 0.049-0.080; P = .01), larger right ventricle areas (eg, systolic area: β, 0.026; 95% CI, 0.011-0.042; P = .009), larger left ventricle mass index (β, 0.045; 95% CI, 0.024-0.073; P = .003), and decreased pulmonary vascular resistance (eg, pulmonary artery acceleration time: β, 0.041; 95% CI, 0.018-0.063; P \u3c .001) at 1 year\u27s corrected age, even after accounting for gestational age and common neonatal morbidities. Cardiac values approached those seen in controls born full-term with increased mother\u27s own milk exposure. There were no differences in any of the cardiac indices at 32 weeks\u27 postmenstrual age, but with each week of exposure, right ventricle function (eg, right longitudinal strain: β, 0.016; 95% CI, 0.002-0.031; P \u3c .001) was greater and pulmonary pressured (eg, pulmonary artery acceleration time: β, 0.0032; 95% CI, 0.0013-0.0062; P \u3c .001). Conclusions and Relevance: This study found that preterm infants with higher consumption of mother\u27s own milk had enhanced cardiac performance at age 1 year, suggesting that mother\u27s own milk consumption may play a dynamic modulator role on cardiac mechanics in preterm-born infants and help in normalization of the preterm cardiac phenotype

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

First Trimester Prediction of Uteroplacental Disease- Results of the Prospective Handle Study

To assess the ability of non-invasive cardiac output monitoring (NICOM), a novel method of non-invasive maternal hemodynamic assessment using bioreactance, in combination with first trimester biomarkers to predict the evolution of gestational hypertension (GH), pre-eclampsia (PE) and normotensive fetal growth restriction (FGR)

Intra- and inter-rater agreement of superior vena cava flow and right ventricular outflow measurements in late preterm and term neonates

OBJECTIVES: To explore the intra- and inter-rater agreement of superior vena cava (SVC) flow and right ventricular (RV) outflow in healthy and unwell late preterm neonates (33-37 weeks' gestational age), term neonates (≥37 weeks' gestational age), and neonates receiving total-body cooling. METHODS: The intra- and inter-rater agreement (n = 25 and 41 neonates, respectively) rates for SVC flow and RV outflow were determined by echocardiography in healthy and unwell late preterm and term neonates with the use of Bland-Altman plots, the repeatability coefficient, the repeatability index, and intraclass correlation coefficients. RESULTS: The intra-rater repeatability index values were 41% for SVC flow and 31% for RV outflow, with intraclass correlation coefficients indicating good agreement for both measures. The inter-rater repeatability index values for SVC flow and RV outflow were 63% and 51%, respectively, with intraclass correlation coefficients indicating moderate agreement for both measures. CONCLUSIONS: If SVC flow or RV outflow is used in the hemodynamic treatment of neonates, sequential measurements should ideally be performed by the same clinician to reduce potential variability

Investigation of EEG activity compared with mean arterial blood pressure in extremely preterm infants

BackgroundCerebral electrical activity in extremely preterm infants is affected by various factors including blood gas and circulatory parameters.ObjectiveTo investigate whether continuously measured invasive mean arterial blood pressure (BP) is associated with electroencephalographic (EEG) discontinuity in extremely preterm infants.Study designThis prospective observational study examined 51 newborn infants born <29 weeks gestation in the first 3 days after birth. A single channel of raw EEG was used to quantify discontinuity. Mean BP was acquired using continuous invasive measurement and Doppler ultrasound was used to measure left ventricular output (LVO) and common carotid artery blood flow (CCAF).ResultsMedian gestation and birthweight were 25.6 weeks and 760 g, respectively. Mean discontinuity reduced significantly between days 1 and 3. EEG discontinuity was significantly related to gestation, pH and BP. LVO and CCAF were not associated with EEG discontinuity.ConclusionContinuously measured invasive mean arterial BP was found to have a negative relationship with EEG discontinuity; increasing BP was associated with lower EEG discontinuity. This did not appear to be mediated by surrogates of systemic or cerebral blood flow. Infants receiving inotropic support had significantly increased EEG discontinuity on the first day after birth

Effects of antenatal betamethasone on preterm human and mouse ductus arteriosus: comparison with baboon data.

BackgroundAlthough studies involving preterm infants ≤34 weeks gestation report a decreased incidence of patent ductus arteriosus after antenatal betamethasone, studies involving younger gestation infants report conflicting results.MethodsWe used preterm baboons, mice, and humans (≤276/7 weeks gestation) to examine betamethasone's effects on ductus gene expression and constriction both in vitro and in vivo.ResultsIn mice, betamethasone increased the sensitivity of the premature ductus to the contractile effects of oxygen without altering the effects of other contractile or vasodilatory stimuli. Betamethasone's effects on oxygen sensitivity could be eliminated by inhibiting endogenous prostaglandin/nitric oxide signaling. In mice and baboons, betamethasone increased the expression of several developmentally regulated genes that mediate oxygen-induced constriction (K+ channels) and inhibit vasodilator signaling (phosphodiesterases). In human infants, betamethasone increased the rate of ductus constriction at all gestational ages. However, in infants born ≤256/7 weeks gestation, betamethasone's contractile effects were only apparent when prostaglandin signaling was inhibited, whereas at 26-27 weeks gestation, betamethasone's contractile effects were apparent even in the absence of prostaglandin inhibitors.ConclusionsWe speculate that betamethasone's contractile effects may be mediated through genes that are developmentally regulated. This could explain why betamethasone's effects vary according to the infant's developmental age at birth

Maturational Patterns of Systolic Ventricular Deformation Mechanics by Two-Dimensional Speckle Tracking Echocardiography in Preterm Infants over the First Year of Age

BACKGROUND: The aim of this study was to determine the maturational changes in systolic ventricular strain mechanics by two-dimensional speckle-tracking echocardiography in extremely preterm neonates from birth to 1 year of age and discern the impact of common cardiopulmonary abnormalities on the deformation measures. METHODS: In a prospective multicenter study of 239 extremely preterm infants (<29 weeks gestation at birth), left ventricular (LV) global longitudinal strain (GLS) and global longitudinal systolic strain rate (GLSRs), interventricular septal wall (IVS) GLS and GLSRs, right ventricular (RV) free wall longitudinal strain and strain rate, and segmental longitudinal strain in the RV free wall, LV free wall, and IVS were serially measured on days 1, 2, and 5 to 7, at 32 and 36 weeks postmenstrual age, and at 1 year corrected age (CA). Premature infants who developed bronchopulmonary dysplasia or had echocardiographic findings of pulmonary hypertension were analyzed separately. RESULTS: In uncomplicated preterm infants (n = 103 [48%]), LV GLS and GLSRs remained unchanged from days 5 to 7 to 1 year CA (P = .60 and P = .59). RV free wall longitudinal strain, RV free wall longitudinal strain rate, and IVS GLS and GLSRs significantly increased over the same time period (P < .01 for all measures). A significant base-to-apex (highest to lowest) segmental longitudinal strain gradient (P < .01) was seen in the RV free wall and a reverse apex-to-base gradient (P < .01) in the LV free wall. In infants with bronchopulmonary dysplasia and/or pulmonary hypertension (n = 119 [51%]), RV free wall longitudinal strain and IVS GLS were significantly lower (P < .01), LV GLS and GLSRs were similar (P = .56), and IVS segmental longitudinal strain persisted as an RV-dominant base-to-apex gradient from 32 weeks postmenstrual age to 1 year CA. CONCLUSIONS: This study tracks the maturational patterns of global and regional deformation by two-dimensional speckle-tracking echocardiography in extremely preterm infants from birth to 1 year CA. The maturational patterns are ventricular specific. Bronchopulmonary dysplasia and pulmonary hypertension leave a negative impact on RV and IVS strain, while LV strain remains stable

Recommendations for neonatologist performed echocardiography in Europe: Consensus Statement endorsed by European Society for Paediatric Research (ESPR) and European Society for Neonatology (ESN)

Contains fulltext : 171351.pdf (Publisher’s version ) (Open Access

Altered inflammasome activation in neonatal encephalopathy persists in childhood

Neonatal encephalopathy (NE) is characterized by altered neurological function in term infants and inflammation plays an important pathophysiological role. Inflammatory cytokines interleukin (IL)-1 beta, IL-1ra and IL-18 are activated by the nucleotide-binding and oligomerization domain (NOD)-, leucine-rich repeat domain (LRR)- and NOD-like receptor protein 3 (NLRP3) inflammasome; furthermore, we aimed to examine the role of the inflammasome multiprotein complex involved in proinflammatory responses from the newborn period to childhood in NE. Cytokine concentrations were measured by multiplex enzyme-linked immunosorbent assay (ELISA) in neonates and children with NE in the absence or presence of lipopolysaccharide (LPS) endotoxin. We then investigated expression of the NLRP3 inflammasome genes, NLRP3, IL-1 beta and ASC by polymerase chain reaction (PCR). Serum samples from 40 NE patients at days 1 and 3 of the first week of life and in 37 patients at age 4-7 years were analysed. An increase in serum IL-1ra and IL-18 in neonates with NE on days 1 and 3 was observed compared to neonatal controls. IL-1ra in NE was decreased to normal levels at school age, whereas serum IL-18 in NE was even higher at school age compared to school age controls and NE in the first week of life. Percentage of LPS response was higher in newborns compared to school-age NE. NLRP3 and IL-1 beta gene expression were up-regulated in the presence of LPS in NE neonates and NLRP3 gene expression remained up-regulated at school age in NE patients compared to controls. Increased inflammasome activation in the first day of life in NE persists in childhood, and may increase the window for therapeutic intervention