The Bronchopulmonary Dysplasia score: A predictive model for bronchopulmonary dysplasia or death in high-risk preterm infants.

AIM: Progressive respiratory deterioration in infants at high risk of bronchopulmonary dysplasia (BPD) is associated with patent ductus arteriosus (PDA) exposure. This study aimed to design an early predictive model for BPD or death in preterm infants using early echocardiographic markers and clinical data. METHODS: Infants born with gestational age (GA) ≤ 29 weeks and/or birth weight (BW) < 1500 g at Cork University Maternity Hospital, Ireland were retrospectively evaluated. Those with echocardiography performed between 36 h and 7 days of life were eligible for inclusion. Exclusion criteria were pulmonary hypertension and major congenital anomalies. The primary outcome was a composite of BPD and death before discharge. RESULTS: The study included 99 infants. A predictive model for the primary outcome was developed, which included three variables (BW, Respiratory Severity Score and flow pattern across the PDA), and yielding an area under the curve of 0.98 (95% CI 0.96-1.00, p < 0.001). Higher scores were predictive of the primary outcome. A cut-off of -1.0 had positive and negative predictive values of 89% and 98%, and sensitivity and specificity of 98% and 88%, respectively. CONCLUSION: Our prediction model is an accessible bedside tool that predicts BPD or death in premature infants.

The use of milrinone in neonates with persistent pulmonary hypertension of the newborn - a randomised controlled trial pilot study (MINT 1).

OBJECTIVE: To assess the impact of milrinone administration on time spent on nitric oxide (iNO) in infants with acute pulmonary hypertension (aPH). We hypothesized that intravenous milrinone used in conjunction with iNO would reduce the time on iNO therapy and the time spent on invasive ventilation in infants ≥34 weeks gestation with a diagnosis of aPH. We aimed to assess the practicality of instituting the protocol and contributing to a sample size calculation for a definitive multicentre study. STUDY DESIGN: This was a multicentre, randomized, double-blind, two arm pilot study, with a balanced (1:1) allocation. Infants with a gestation ≥34 weeks and a birth weight ≥2000 grams aPH, an oxygenation index of ≥10, and commenced on iNO were eligible. Participants on iNO were assigned to either a milrinone infusion (intervention) or a normal saline infusion (placebo) for up to 35 h. The primary outcome was time on iNO and feasibility of conducting the protocol. RESULTS: The trial was terminated early after 4 years of enrollment due to poor recruitment. Four infants were allocated to the intervention arm and 5 to the placebo arm. The groups were well matched for baseline variables. No differences were seen in any of the primary or secondary outcomes. CONCLUSION: Conducting an interventional trial in the setting of acute pulmonary hypertension in infants is not feasible using our current approach. Future studies in this area require alternative trial design to improve recruitment as this topic remains understudied in the neonatal field. TRIAL REGISTRATION: www.isrctn.com ; ISRCTN:12949496; EudraCT Number:2014-002988-16.

Serial Assessment of Cardiac Function and Pulmonary Hemodynamics in Infants With Down Syndrome.

BACKGROUND: There is a dearth of longitudinal data describing the evolution of cardiopulmonary hemodynamics in infants with Down syndrome (DS) beyond infancy. We hypothesized that babies with DS, independent of the presence of congenital heart disease (CHD), demonstrate biventricular systolic and diastolic impairment and sustained elevation of pulmonary pressures compared with controls over the first 2 years of age. METHODS: This was a prospective observational cohort study of 70 infants with DS (48 with CHD and 22 without CHD) and 60 controls carried out in 3 tertiary neonatal intensive care units in Dublin, Ireland. Infants with DS with and without CHD and non-DS controls underwent serial echocardiograms at birth, 6 months, 1 year, and 2 years of age to assess biventricular systolic and diastolic function using deformation analysis. Pulmonary vascular resistance was assessed using pulmonary artery acceleration time and left ventricular (LV) eccentricity index. RESULTS: Infants with DS exhibited smaller LV (birth: 27 ± 4 vs 31 ± 2 mm, P < .01; 2 years: 43 ± 5 vs 48 ± 4 mm, P < .01) and right ventricular (birth: 28 ± 3 vs 31 ± 2 mm, P < .01; 2 years: 40 ± 4 vs 44 ± 3 mm, P < .01) lengths and lower LV (birth: -19% ± 3% vs -22% ± 2%, P < .01; 2 years: -24% ± 2% vs -26% ± 2%, P < .01) and right ventricular (birth: -19% ± 4% vs -22% ± 3%, P < .01; 2 years: -29% ± 6% vs -33% ± 4%, P < .01) systolic strain over the 2-year period. Pulmonary artery acceleration time was lower in the DS group throughout the study period (birth: 44 ± 10 vs 62 ± 14 ms, P < .01; 2 years 71 ± 12 vs 83 ± 11 ms, P < .01). No differences were observed between DS infants with and without CHD (all P > .05). CONCLUSIONS: Infants with DS exhibit impaired maturational changes in myocardial function and pulmonary vascular resistance. Such novel findings provide valuable insights into the pathophysiology affecting cardiorespiratory morbidity in this population.

Relationship Between Postnatal Pulmonary Arterial Pressure and Altered Diastolic Function in Neonates with Down Syndrome.

OBJECTIVE: To assess the influence of diastolic dysfunction on the evolution of pulmonary hypertension in neonates with Down Syndrome over the early newborn period. STUDY DESIGN: This was a prospective observational cohort study. Echocardiography was performed three times over the first week of life in both Down syndrome and control cohorts. Measurements of pulmonary arterial pressure in addition to left ventricular (LV) and right ventricular systolic and diastolic function were collected. RESULTS: Seventy babies with Down syndrome and 60 control infants were enrolled. Forty-eight of the infants with Down syndrome (69%) were born with congenital heart disease (CHD). Echocardiography surrogates of pulmonary hypertension and myocardial function remained significantly impaired in the Down syndrome group in comparison with control infants (all P < .01). In the Down syndrome group, LV early diastolic strain rate was independently associated with measures of pulmonary hypertension while controlling for gestational age, cesarean delivery, and the presence of CHD (P < .01). CONCLUSIONS: Intrinsic LV diastolic impairment is directly associated with higher indices of pulmonary hypertension in infants with Down syndrome and may be a contributing factor to its evolution.

Hemodynamic considerations in preterm infants born at less than 25 weeks gestation.

As survival rates continue to improve for infants born at less than 25 weeks gestation, delineating normal cardiovascular physiology from pathophysiology becomes much more challenging. With a paucity of 'normative' data for such infants, an over-reliance on studies at older gestations can result in a 'best guess' approach. Here we offer a pragmatic approach to these diagnostic challenges from a cardiovascular viewpoint. An appreciation of the unique physiology, from the immature myocardium and altered vascular tone to an innately large patent ductus arteriosus is essential, as is a thorough history for case specific contributing factors. We explore the additional difficulties in achieving a balance between minimal handling at the bedside and delineating important objective markers of perfusion. Finally, we discuss treatment approaches including inotrope therapy and patent ductus treatment, acknowledging the limited data available to guide these decisions.

Patent ductus arteriosus shunt elimination results in a reduction in adverse outcomes: a post hoc analysis of the PDA RCT cohort.

OBJECTIVE: A post hoc appraisal of the PDA RCT to assess the relationship between early patent ductus arteriosus (PDA) shunt elimination and chronic lung disease or death (CLD/Death). STUDY DESIGN: Infants <29 weeks were divided into four groups: intervention arm in whom PDA closure was achieved (n = 17); intervention arm in whom PDA closure was not achieved (n = 13); placebo arm (n = 30); low risk infants (n = 13). The main outcome measure was CLD/Death. RESULTS: The rates of CLD/Death were lower in the Intervention Success Group (29%) when compared to the Intervention Failure Group (85%) or the Placebo Group (60%, all p < 0.05). There was no difference in CLD/Death between the Intervention Success and Low Risk Groups (8%, p > 0.05). A persistent PDA beyond Day 8 was associated with CLD/Death (aOR 6.5 [1.7-25.5]). CONCLUSIONS: Early shunt elimination in preterm infants with a PDA may reduce respiratory morbidity when compared to infants with prolonged shunt exposure.

Comparison of left ventricular rotational mechanics between term and extremely premature infants over the first week of age.

OBJECTIVE: Left ventricle (LV) rotational mechanics is an emerging tool to characterise LV function, but warrants further evaluation in neonates. The aim of this study was to compare LV rotational mechanics between term and extremely preterm babies over the first week of age. METHODS: In this prospective study, we serially assessed LV rotational parameters in 50 term infants and compared them with a historical dataset of 50 preterm infants born <29 weeks gestation. LV basal and apical rotation, LV twist, LV twist/untwist rate and torsion were derived using two-dimensional speckle tracking echocardiography at three time points over the first week of age. RESULTS: There was no change in LV twist, LV torsion, basal rotation or apical rotation in term infants over the study period (all p>0.05). LV twist and torsion were higher in preterm infants, and increased over time. In preterm infants, basal rotation evolved from anticlockwise to clockwise rotation. Apical rotation remained anticlockwise in both groups (all p>0.05). LV twist rate (LVTR) and untwist rate was higher in preterm infants and increased over the three time points (all p>0.05). There was a strong positive correlation between LV torsion and LV untwist rate (LVUTR) in the entire cohort during the third scan. CONCLUSION: Term infants exhibit minimal LV twist which remains unchanged over the first week of age. This is in contrast to premature infants who demonstrate increasing indices of twist, torsion, LVTR and LVUTR over the first week, likely as a compensatory mechanism for reduced LV compliance.

The impact preload on left ventricular three-plane deformation measurements in extremely premature infants.

BACKGROUND: Left Ventricular (LV) deformation analysis using two-dimensional speckle tracking echocardiography (STE) is an emerging modality in premature infants. AIMS: To assess the impact of increased preload on LV deformation in three planes: longitudinal, circumferential and radial in premature infants. STUDY DESIGN AND SUBJECTS: Infants recruited to the PDA RCT (ISRCTN 13281214) and survived to discharge were included with the cohort divided into infants who closed their patent ductus arteriosus (PDA) by Day 8 (Low preload, PDA Closed) and those who maintained ductal patency (high preload, PDA Open). OUTCOME MEASURES: Longitudinal, circumferential and radial strain and systolic strain rate (SRs) were measured at 36 h, Days 4 & 8 and 36 weeks. RESULTS: 61 infants were included. The PDA open Group had a lower gestation (26.4 vs. 27.4 weeks, p < 0.01) with a median PDA exposure of 30 days (vs. 2 days, p < 0.01), and demonstrated echocardiography evidence of pulmonary overcirculation. There was higher LV longitudinal strain and SRs over the first 3 scans in the PDA Open Group. Circumferential strain was higher over the first 2 scans while circumferential SRs was higher at 36 h. Radial Strain and SRs were only higher on Day 4. CONCLUSION: Increased preload is associated with higher strain and systolic strain rate values in the premature population indicating that preload has a significant effect on deformation measurements in this population across all three planes.

A Pilot Randomized Controlled Trial of Early Targeted Patent Ductus Arteriosus Treatment Using a Risk Based Severity Score (The PDA RCT).

OBJECTIVES: To evaluate the feasibility of recruiting preterm infants to a randomized controlled trial of patent ductus arteriosus (PDA) treatment based on a PDA severity score (PDAsc) and to characterize challenges in obtaining consent, compliance with the protocol, and PDA closure rates. STUDY DESIGN: This single-center, randomized control pilot study of 60 infants <29 weeks of gestation with a high PDAsc (≥5.0) at 36-48 hours of age receiving either ibuprofen or placebo intravenously. The study protocol did not allow for additional PDA therapy within the first 2 weeks. We reported the rate of consent, open label treatment, and PDA closure rates. The primary outcome was chronic lung disease or death. RESULTS: We approached 83 families for enrollment with 73 (88%) providing consent; 13 infants had a PDAsc of <5; of the remaining infants, 30 were assigned ibuprofen and 30 received placebo. Eight infants received open label treatment in the first 2 weeks (12%). The overall PDA closure rate after treatment was 57% in the intervention group and 17% in the control group (P < .01). There was no difference in the primary clinical outcome (OR, 0.8; 95% CI, 0.3-2.1). CONCLUSIONS: Using a PDAsc for infant recruitment to a PDA treatment randomized controlled trial is feasible. There is a high rate of consent and relatively low rate of open-label PDA treatment. The overall PDA closure rate in the intervention arm was low placing the emphasis on devising more effective PDA closure strategies in future randomized controlled trials. TRIAL REGISTRATION: ISRCTN (13281214) and European Union Drug Regulating Authorities Clinical Trials Database (2015-004526-33).

Prenatal prediction of neonatal haemodynamic adaptation after maternal hyperoxygenation.

The reactivity of the pulmonary vascular bed to the administration of oxygen is well established in the post-natal circulation. The vasoreactivity demonstrated by the fetal pulmonary artery Doppler waveform in response to maternal hyperoxia has been investigated. We sought to investigate the relationship between the reactivity of the fetal pulmonary arteries to hyperoxia and subsequent neonatal cardiac function in the early newborn period. METHODS: This explorative study with convenience sampling measured pulsatility index (PI), resistance index (RI), acceleration time (AT), and ejection time (ET) from the fetal distal branch pulmonary artery (PA) at baseline and following maternal hyperoxygenation (MH). Oxygen was administered for 10 min at a rate of 12 L/min via a partial non-rebreather mask. A neonatal functional echocardiogram was performed within the first 24 h of life to assess ejection fraction (EF), left ventricular output (LVO), and neonatal pulmonary artery AT (nPAAT). This study was conducted in the Rotunda Hospital, Dublin, Ireland. RESULTS: Forty-six women with a singleton pregnancy greater than or equal to 31 weeks' gestational age were prospectively recruited to the study. The median gestational age was 35 weeks. There was a decrease in fetal PAPI and PARI following MH and an increase in fetal PAAT, leading to an increase in PA AT:ET. Fetuses that responded to hyperoxygenation were more likely to have a higher LVO (135 ± 25 mL/kg/min vs 111 ± 21 mL/kg/min, p < 0.01) and EF (54 ± 9% vs 47 ± 7%,p = 0.03) in the early newborn period than those that did not respond to MH prenatally. These findings were not dependent on left ventricular size or mitral valve (MV) annular diameter but were related to an increased MV inflow. There was no difference in nPAAT. CONCLUSION: These findings indicate a reduction in fetal pulmonary vascular resistance (PVR) and an increase in pulmonary blood flow and left atrial return following MH. The fetal response to hyperoxia reflected an optimal adaptation to postnatal life with rapid reduction in PVR increasing measured cardiac output.

Early targeted patent ductus arteriosus treatment in premature neonates using a risk based severity score: study protocol for a randomised controlled trial (PDA RCT).

A patent ductus arteriosus (PDA) in preterm infants is associated with increased ventilator dependence and chronic lung disease, necrotizing enterocolitis, intraventricular haemorrhage, and poor neurodevelopmental outcome. Randomised controlled trials of early PDA treatment have not established a drop in the aforementioned morbidities. Those trials did not physiologically categorise PDA severity. Incorporating the specific physiological features of a haemodynamic significant PDA may evolve our understanding of this phenomenon, allowing accurate triaging using echocardiography and targeted treatment.  Our group has recently demonstrated that a PDA severity score (PDAsc) derived at 36-48 hours of age can accurately predict the later occurrence of chronic lung disease or death (CLD/Death). Using echocardiography, we assessed PDA characteristics, as well as left ventricular diastolic function and markers of pulmonary overcirculation, and from this formulated a PDAsc. Gestation was also incorporated into the score. We hypothesise that in preterm infants at high risk of developing CLD/Death based on a PDAsc, early treatment with Ibuprofen compared with placebo will result in a reduction in CLD/Death. This is a single centre double-blind two arm randomised controlled trial conducted in the neonatal intensive care unit in the Rotunda Hospital, Dublin. Echocardiogram is carried out in the first 36-48 hours of life to identify preterm infants with a PDAsc ≥ 5.0 and these infants are randomised to Ibuprofen or placebo. Primary outcomes are assessed at 36 weeks post menstrual age. This pilot study's purpose is to assess the feasibility of performing the trial and to obtain preliminary data to calculate a sample size for a definitive multi-centre trial of early PDA treatment using a PDAsc. We aim to recruit a total of 60 infants with a high risk PDA over three years. Trial Registration: ISRCTN ISRCTN13281214 (26/07/2016) and the European Union Drug Regulating Authorities Clinical Trials Database 2015-004526-33 (03/12/2015).

Myocardial function in late preterm infants during the transitional period: comprehensive appraisal with deformation mechanics and non-invasive cardiac output monitoring.

BACKGROUND: There is a paucity of functional data on mid-to-late preterm infants between 30+0 and 34+6 weeks gestation. We aimed to characterise transitional cardiopulmonary and haemodynamic changes during the first 48 hours in asymptomatic mid-to-late preterm infants. METHODS: Forty-five healthy preterm newborns (mean ± standard deviation) gestation of 32.7 ± 1.2 weeks) underwent echocardiography on Days 1 and 2. Ventricular mechanics were assessed by speckle tracking-derived deformation, rotational mechanics, tissue Doppler imaging, and right ventricle-focused measures (tricuspid annular plane systolic excursion, fractional area change). Continuous haemodynamics were assessed using the NICOM™ system to obtain left ventricular output, stroke volume, heart rate, and total peripheral resistance by non-invasive cardiac output monitoring. RESULTS: Right ventricular function increased (all measures p < 0.005) with mostly stable left ventricular performance between Day 1 and Day 2. NICOM-derived left ventricular output [mean 34%, 95% confidence interval 21-47%] and stroke volume [29%, 16-42%] increased with no change in heart rate [5%, -2 to 12%]. There was a rise in mean blood pressure [11%, 1-21%], but a decline in total peripheral resistance [-14%, -25 to -3%]. CONCLUSION: Left ventricular mechanics remained persevered in mid-to-late premature infants, but right ventricular function increased. Non-invasive cardiac output monitoring is feasible in preterm infants with an increase in left ventricular output driven by an improvement in stroke volume during the transitional period.

Circumferential and radial deformation assessment in premature infants: Ready for primetime?

BACKGROUND: Speckle tracking echocardiography (STE) is a validated method to measure longitudinal deformation in premature infants, but there is a paucity of data on STE-derived circumferential and radial strain in this population. We assessed the feasibility and reproducibility of circumferential and radial deformation measurements in premature infants. METHODS: In a prospective study of 40 premature infants (<29 weeks of gestation at birth), STE-derived circumferential and radial strain, systolic strain rate (SRs), early diastolic strain rate (SRe), and late diastolic strain rate (SRa) were measured on day 2 and day 8. Intra- and inter-observer reproducibility analysis were performed using Bland-Altman analysis, coefficient of variation (COV), and intra-class correlation coefficient (ICC). The impact of a persistent patent ductus arteriosus (PDA) was analyzed. RESULTS: Deformation analysis was feasible in 98% of the acquisitions. Circumferential parameters demonstrated excellent intra- and inter-observer reproducibility with an ICC between 0.89 and 0.99 (all P < 0.001) and a COV between 4% and 13%. Radial parameters demonstrated acceptable intra- and inter-observer reproducibility with an ICC between 0.73 and 0.96 (all P < 0.001) and a COV between 14% and 27%. Infants with a PDA on day 8 (n = 21, 53%) demonstrated higher radial strain, SRs and SRe. There were no differences in circumferential parameters with a PDA at either time point. CONCLUSION: This study demonstrates clinical feasibility and reproducibility of circumferential and radial strain by STE in premature infants. A PDA elevates radial deformation measures, suggesting that the increased LV preload from a PDA may augment intrinsic contractility in the radial but not circumferential plane.

Hyperoxygenation in pregnancy exerts a more profound effect on cardiovascular hemodynamics than is observed in the nonpregnant state.

BACKGROUND: Supplemental oxygen is administered to pregnant women in many different clinical scenarios in obstetric practice. Despite the accepted uses for maternal hyperoxygenation, the impact of hyperoxia on maternal hemodynamic indices has not been evaluated. As a result, there is a paucity of data in the literature in relation to the physiological changes to the maternal circulation in response to supplemental oxygen. OBJECTIVE: The hemodynamic effects of oxygen therapy are under-recognized and the impact of hyperoxygenation on maternal hemodynamics is currently unknown. Using noninvasive cardiac output monitoring which employs transthoracic bioreactance, we examined the effect of brief hyperoxygenation on cardiac index, systemic vascular resistance, blood pressure, stroke volume, and heart rate in pregnant mothers during the third trimester, compared with those effects observed in a nonpregnant population subjected to the same period of hyperoxygenation. STUDY DESIGN: Hemodynamic monitoring was performed in a continuous manner over a 30-minute period using noninvasive cardiac output monitoring. Hyperoxygenation (O2 100% v/v inhalational gas) was carried out at a rate of 12 L/min via a partial non-rebreather mask for 10-minutes. Cardiac index, systemic vascular resistance, stroke volume, heart rate, and blood pressure were recorded before hyperoxygenation, at completion of hyperoxygenation, and 10 minutes after the cessation of hyperoxygenation. Two-way analysis of variance with repeated measures was used to assess the change in hemodynamic indices over time and the differences between the 2 groups. RESULTS: Forty-six pregnant and 20 nonpregnant women with a median age of 33 years (interquartile range, 26-38 years) and 32 years (interquartile range, 28-37 years) were recruited prospectively, respectively (P=.82). The median gestational age was 35 weeks (33-37 weeks). In the pregnant group, there was a fall in cardiac index during the hyperoxygenation exposure period (P=.009) coupled with a rise in systemic vascular resistance with no recovery at 10 minutes after cessation of hyperoxygenation (P=.02). Heart rate decreased after hyperoxygenation exposure and returned to baseline by 10 minutes after cessation of therapy. There was a decrease in stroke volume over the exposure period, with no change in systolic or diastolic blood pressure. In the nonpregnant group, there was no significant change in the cardiac index, systemic vascular resistance, stroke volume, heart rate, or systolic or diastolic blood pressure during the course of exposure to hyperoxygenation. CONCLUSION: Hyperoxygenation during the third trimester is associated with a fall in maternal cardiac index and a rise in systemic vascular resistance without recovery to baseline levels at 10 minutes after cessation of hyperoxygenation. The hemodynamic changes that were observed in this study in response to hyperoxygenation therapy during pregnancy could counteract any intended increase in oxygen delivery. The observed maternal effects of hyperoxygenation call for a reevaluation of the role of hyperoxygenation treatment in the nonhypoxemic pregnant patient.

Postnatal Myocardial Function in Monochorionic Diamniotic Twins with Twin-to-Twin Transfusion Syndrome following Selective Laser Photocoagulation of the Communicating Placental Vessels.

BACKGROUND: Monochorionic diamniotic (MCDA) twins are at risk for developing twin-to-twin transfusion syndrome (TTTS) throughout pregnancy. This may lead to myocardial dysfunction in the recipient and/or donor twin that persists beyond delivery. Selective laser photocoagulation of the communicating placental vessels (SLPCV) attempts to mitigate the cardiovascular outcomes. The objective of this study was to characterize early postnatal myocardial performance in MCDA twins with TTTS with and without SLPCV. METHODS: A prospective study was performed of four MCDA twin groups: (1) uncomplicated MCDA twins, (2) MCDA twins with selective fetal growth restriction, (3) MCDA twins with TTTS following SLPCV (TTTS with SLPCV), and (4) MCDA twins with TTTS who did not undergo SLPCV (TTTS without SLPCV). Fifty-four twin pairs were enrolled: 23 uncomplicated MCDA twin pairs, 15 pairs with selective fetal growth restriction, seven TTTS pairs with SLPCV, and seven TTTS pairs without SLPCV. In each group, twin pairs were divided by birth weight into donor (smaller) and recipient (larger) and compared. Echocardiography was performed on day 1, day 2, and between days 5 and 7 of age, and myocardial performance was characterized by speckle-tracking echocardiography-derived left ventricular and right ventricular longitudinal strain (LS) and systolic strain rate (LSR). Longitudinal strain and longitudinal systolic strain rate are expressed as absolute values. RESULTS: Compared with all recipient groups, recipient TTTS without SLPCV infants had lower left ventricular LS (16 ± 3% vs 22%-24%, P < .01) and right ventricular LS (15 ± 5% vs 21%-24%, P < .01) on day 1 that persisted throughout the first week of age. Left ventricular LSR (1.7 ± 0.3 vs 2.3 ± 0.3 sec-1, P < .05) and right ventricular LSR (1.5 ± 0.4 vs 1.7 ± 0.5 sec-1, P < .05) were both lower in the recipient compared with the donor twin in the TTTS without SLPCV group. LS and LSR measurements were similar among all four donor twin groups. CONCLUSIONS: Biventricular performance is diminished in recipient MCDA twins with TTTS who are not treated with SLPCV, highlighting the need for close monitoring of their hemodynamic status during the early neonatal period.

Cardiac mechanics in infants with Down syndrome in the early neonatal period.

OBJECTIVE: The objective of this study is to test whether myocardial performance is impaired over the first week of age in infants with Down syndrome (DS) without congenital heart disease (CHD). STUDY DESIGN: A prospective cohort study of 20 infants with DS without CHD and 17 healthy term infants comparing echocardiographic measures of left (LV) and right (RV) ventricular function and pulmonary hypertension (PH) on days 1, 2, and 5-7. RESULTS: Indices of PH were higher in the DS group over the study period. Infants with DS had larger RV and smaller LV dimensions. Fractional area change and RV longitudinal strain values were lower in the DS group. LV shear strain values were lower in infants with DS driven by a lack of basal rotation. CONCLUSION: Infants with DS without CHD and echocardiographic evidence of PH during the early neonatal period demonstrate reduced RV systolic function with impaired LV rotational mechanics, reflective of the ventricular interdependence.

Future perspectives on the use of deformation analysis to identify the underlying pathophysiological basis for cardiovascular compromise in neonates.

The assessment of the wellbeing of the cardiovascular status in premature infants has come to the forefront in recent years. There is an increasing realisation that myocardial performance, systemic blood flow and end-organ perfusion (particularly during the transitional period) play an important role in determining short and long-term outcomes in this population. The recent open access series on Neonatologist Performed Echocardiography (NPE) published in this journal outline the necessary techniques for image acquisition and analysis and provide a framework for the potential clinical applications of NPE in neonatal, and specifically preterm care. In this "Future Perspectives" review, we describe the important determinants of adequate cellular metabolism and myocardial performance (e.g. loading conditions, intrinsic contractility and morphological change), we discuss the maladaptive state of the preterm cardiovascular system, and highlight the emerging role that non-invasive echocardiography techniques, such as deformation analysis, serve in identifying the underlying physiological basis for cardiovascular instability.

Left ventricular diastolic function influences right ventricular - Pulmonary vascular coupling in premature infants.

INTRODUCTION: Reduced left ventricular (LV) diastolic function can exert significant load to the right ventricle (RV) that can affect RV-pulmonary vasculature (PV) coupling. RV-PV can be assessed with the RV length-force relationship (tricuspid annular plane systolic excursion [TAPSE] to pulmonary artery acceleration time [PAAT] ratio). We aimed to determine the association between LV diastolic function measured using tissue Doppler imaging (TDI) and TAPSE/PAAT. METHODS: A study of premature infants <29 weeks gestation. TAPSE/PAAT, LV e' and a' waves were measured on Day 1 following birth. Correlation between diastolic indices and TAPSE/PAAT was performed. The independent effect of LV diastolic function and TAPSE/PAAT was assessed using linear regression. RESULTS: One hundred and sixty-two infants with a mean ±â€¯SD gestation & birthweight of 26.6 ±â€¯1.5 weeks & 938 ±â€¯241 g. There was a significant positive correlation between LV e' (r = 0.44, p < 0.01)/LV a' (r = 0.44, p < 0.01) and TAPSE/PAAT. This relationship remained significant when adjusting for important confounders (all p < 0.01). Infants with LV a' values in the lowest quartile had lower TAPSE values (4.2 ±â€¯1.2 vs. 5.1 ±â€¯1.1 mm, p < 0.01) without a difference in PAAT (41 ±â€¯8 vs. 41 ±â€¯10 ms, p = 0.97). CONCLUSIONS: We observed a direct correlation between LV diastolic function and RV-PV coupling in the first day of age, highlighting the importance ventricular interdependence in premature infants. TAPSE/PAAT, as the index of the RV-PV interaction may be further explored for its potential to assess RV reserve under stress with preterm infants in health and disease.

The use of milrinone in neonates with persistent pulmonary hypertension of the newborn - a randomised controlled trial pilot study (MINT 1): study protocol and review of literature.

Persistent pulmonary hypertension of the newborn (PPHN) is a relatively common condition which results in a mortality of up to 33%. Up to 40% of infants treated with nitric oxide (iNO) either have a transient response or fail to demonstrate an improvement in oxygenation. Milrinone, a selective phosphodiesterase 3 (PDE3) inhibitor with inotropic and lusitropic properties may have potential benefit in PPHN. This pilot study was developed to assess the impact of milrinone administration on time spent on iNO in infants with PPHN. This is a multicentre, randomized, double-blind, two arm pilot study, with a balanced (1:1) allocation of 20 infants. In this pilot study, we hypothesise that infants ≥34 weeks gestation and ≥ 2000 g with a clinical and echocardiography diagnosis of PPHN, intravenous milrinone used in conjunction with iNO will result in a reduction in the time spent on iNO. In addition, we hypothesise that milrinone treatment will lead to an improvement in myocardial performance and global hemodynamics when compared to iNO alone. We will also compare the rate of adverse events associated with the milrinone, and the pre-discharge outcomes of both groups. The purpose of this pilot study is to assess the feasibility of performing the trial and to obtain preliminary data to calculate a sample size for a definitive multi-centre trial of milrinone therapy in PPHN. Trial registration: www.isrctn.com; ISRCTN:12949496; EudraCT Number:2014-002988-16.