Shape of Pulmonary Artery Doppler Flow Profile and Right Ventricular Hemodynamics in Neonates.

OBJECTIVES: To characterize pulmonary artery Doppler flow profile (PAFP) patterns among infants receiving care in neonatal intensive care units and to examine the association of PAFP patterns with pulmonary and right ventricular (RV) hemodynamics. STUDY DESIGN: This is a retrospective study at 2 tertiary intensive care units over 4 years that included neonates who demonstrated a complete tricuspid regurgitation envelope on targeted neonatal echocardiography. Separate personnel reviewed TNEs to characterize PAFP patterns, divide cohort into PAFP groups, and measure quantitative indices of RV hemodynamics (RV systolic pressure, pulmonary artery acceleration time and its ratio with RV ejection time, tricuspid annular plane systolic excursion, and RV output), for intergroup comparisons. RESULTS: We evaluated TNEs from 186 neonates with median gestational age of 28.5 weeks (IQR, 25.9-35.9 weeks). Four distinct PAFP patterns were identified (A) near-isosceles triangle (22%), (B) right-angled triangle (29%), (C) notching (40%), and (D) low peak velocity (<0.4 m/s; 9%). Groups A-C demonstrated a stepwise worsening in all indices of PH, whereas pattern D was associated with lower tricuspid annular plane systolic excursion and RV output. Using common definitions of pulmonary hypertension (PH), pattern A performed best to rule out PH (sensitivity range, 81%-90%) and pattern C for diagnosing PH (specificity range, 63%-78%). CONCLUSIONS: Inspection of PAFP is a simple bedside echocardiography measure that provides clinically meaningful information on underlying RV hemodynamics and may aid in screening and monitoring of patients for PH in intensive care units.

Clinical impact of less invasive surfactant administration using video laryngoscopy in extremely preterm infants.

BACKGROUND: Examine the real-world clinical impact of adopting less invasive surfactant administration (LISA) as the primary surfactant administration method in extremely preterm infants. METHODS: Single-center pre-post cohort study conducted over a 4-year period comparing outcomes of spontaneously breathing inborn infants 24+0-28+6 weeks gestational age (GA) receiving surfactant via endotracheal tube (pre-cohort, n = 154) or LISA via thin catheter (post-cohort, n = 70). Primary outcome was need for invasive mechanical ventilation (IMV, ≥2 h) ≤72 h of age. Secondary outcomes were a composite of mortality, bronchopulmonary dysplasia, intraventricular hemorrhage ≥grade 3 or necrotizing enterocolitis, and its individual components. Groups were compared using propensity score methods, including covariates: GA, birth weight, sex, small for GA, SNAP II ≥20, premature rupture of membranes, maternal hypertension/diabetes, and C-section. RESULTS: GA and birth weight were 27.1 (26, 28.1) weeks and 914 (230) g, and 27.1 (26.1, 28.1) weeks and 920 (236) g for pre- and post-cohorts, respectively. Pre-cohort had higher C-section rates, (67% vs. 51%, p = 0.03). After adjustment for covariates, LISA was associated with reduced IMV exposure [AOR (95% CI) 0.07 (0.04, 0.11)], lower odds of the composite clinical outcome [0.49 (0.33, 0.73)], and most of its individual components. CONCLUSION: Real-world experience favors LISA as the primary method in extremely preterm infants with established spontaneous respiration. IMPACT: Less invasive surfactant administration (LISA) is associated with a reduction in respiratory morbidity, but real-world data of routine use among extremely preterm infants are limited. LISA is associated with reduced frequency of exposure to and duration of IMV in both ≤72 h after birth and during hospital stay. LISA is associated with a reduction in mortality, and most other major morbidities including bronchopulmonary dysplasia, and interventricular hemorrhage. Data from a large North American center providing real-world clinical outcomes following LISA as the primary method of surfactant administration.

Organ dysfunction and mortality in preterm neonates with late-onset bloodstream infection.

BACKGROUND: Organ dysfunction (ODF) in late-onset bloodstream infection (LBSI) is associated with increased risk of adverse outcomes. However, no established definition of ODF exists among preterm neonates. Our objective was to describe an outcome-based ODF definition for preterm infants, and assess factors associated with mortality. METHODS: This is a six-year retrospective study of neonates <35 weeks gestational age, >72 h of age, with non-CONS bacterial/fungal LBSI. Discriminatory ability of each parameter for mortality was evaluated: base deficit ≤-8 mmol/L (BD8), renal dysfunction (urine output <1 cc/kg/h or creatinine ≥100 µmol/L), hypoxic respiratory failure (HRF, ventilated, FiO2 = 1.0), or vasopressor/inotrope use (V/I). Multivariable logistic regression analysis was performed to derive a mortality score. RESULTS: One hundred and forty-eight infants had LBSI. BD8 had the highest individual predictive ability for mortality (AUROC = 0.78). The combination BD8 + HRF + V/I was used to define ODF (AUROC = 0.84). Fifty-seven (39%) infants developed ODF, among which 28 (49%) died. Mortality increased inversely relative to GA at LBSI-onset (aOR 0.81 [0.67, 0.98]) and directly relative to ODF occurrence (12.15 [4.48, 33.92]). Compared to no-ODF, ODF infants had lower GA and age at illness, and higher frequency of Gram-negative pathogen. CONCLUSIONS: Among preterm neonates with LBSI, significant metabolic acidosis, HRF, and vasopressor/inotrope use may identify infants high risk for mortality. These criteria could help identify patients for future studies of adjunctive therapies. IMPACT: Sepsis-related organ dysfunction is associated with increased risk of adverse outcomes. Among preterm neonates, significant metabolic acidosis, use of vasopressors/inotropes, and hypoxic respiratory failure may identify high-risk infants. This can be used to target research and quality improvement efforts toward the most vulnerable infants.

Dopamine or norepinephrine for sepsis-related hypotension in preterm infants: a retrospective cohort study.

The purpose of this study is to compare the clinical effectiveness of dopamine (DA) versus norepinephrine (NE) as first-line therapy for sepsis-related hypotension in preterm infants. This is a retrospective cohort study over 10 years at two tertiary neonatal units. Preterm infants born < 35 weeks post-menstrual age (PMA), who received DA or NE as primary therapy for hypotension during sepsis, defined as culture-positive or culture-negative infections or necrotizing enterocolitis (NEC), were included. Episode-related mortality (< 7 days from treatment), pre-discharge mortality, and major morbidities among survivors were compared between two groups. Analyses were adjusted using the inverse probability of treatment weighting estimated by propensity score (PS). A total of 156 infants were included, 113 received DA and 43 NE. The mean ± SD PMA at birth and at treatment for the DA and NE groups were 25.8 ± 2.3 vs. 25.2 ± 2.0 weeks and 27.7 ± 3.0 vs. 27.1 ± 2.6 weeks, respectively (p > 0.05). Pre-treatment, the NE group had higher mean airway pressure (14 ± 4 vs. 12 ± 4 cmH2O), heart rate (185 ± 17 vs. 175 ± 17 beats per minute), and median (IQR) fraction of inspired oxygen [0.67 (0.42, 1.0) vs. 0.52 (0.32, 0.82)] (p < 0.05 for all). After PS adjustment, NE was associated with lower episode-related mortality [adjusted odds ratio (95% CI) 0.55 (0.33, 0.92)], pre-discharge mortality [0.60 (0.37, 0.97)], post-illness new diagnosis of significant neurologic injury [0.32 (0.13, 0.82)], and subsequent occurrence of NEC/sepsis among the survivors [0.34, (0.18, 0.65)]. CONCLUSION: NE may be more effective than DA for management of sepsis-related hypotension among preterm infants. These data provide a rationale for prospective evaluation of these commonly used agents. WHAT IS KNOWN: •Dopamine is the commonest vasoactive agent used to support blood pressure among preterm infants. •For adult patients, norepinephrine is recommended as the preferred therapy over dopamine for septic shock. WHAT IS NEW: •This is the first study examining the relative clinical effectiveness of dopamine and norepinephrine as first-line pharmacotherapy for sepsis-related hypotension among preterm infants. •Norepinephrine use may be associated with lower mortality and morbidity than dopamine in preterm infants with sepsis.

Trends in cyclicity and amplitudes on amplitude-integrated electroencephalography during transition in extremely low gestational age infants.

AIM: The aim of the study was to describe amplitude integrated electroencephalography (aEEG) cyclicity, background pattern, voltage margins and maturation scores in extremely low gestational age neonates (ELGANs) in the first 72 h. METHODS: Fifty infants with gestational age (GA) 23+0-27+6 weeks were prospectively studied. Infants with intraventricular haemorrhage ≦ Grade I and no disorders of transition (persistent pulmonary hypertension, hypotension, pulmonary haemorrhage) belonged to the 'Uncomplicated' group and those with intraventricular haemorrhage > Grade I and/or disorders of transition, to the 'Complicated' group. RESULTS: Thirty-six infants without opioid exposure were included: 23 with GA 25.9 (23.1-27.7) weeks in the 'Uncomplicated' group and 13 with GA 24.6 (23.3-27.4) weeks in the 'Complicated' group. Cyclicity was more common in the 'Uncomplicated' group [20/23 (87%) vs. 7/13 (54%), p = 0.045] with more cycles/hour [0.2 (0-0.78) vs. 0.03 (0-67), p = 0.036]. Age at appearance of cyclicity was similar [20 (7.7-40.7) hours in 'Uncomplicated' vs. 23.7 (5.4-60) hours in 'Complicated' group, p = 0.8]. In the 'Uncomplicated' group, maturation scores (p = 0.02), high (p < 0.0001) and low (p = 0.03) base voltage increased over time. CONCLUSION: During the first 72 h, clinically stable ELGANs without neurological injury demonstrate increased cyclicity compared to those with a complicated course. Maturation score, high and low base voltage increase over time.

Rectal Acetaminophen Improves Shunt Volume and Reduces Patent Ductus Arteriosus Ligation in Extremely Preterm Infants.

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..

Hemodynamic dysfunction in neonatal sepsis.

Cardiovascular disturbances are a frequent occurrence in neonatal sepsis. Preterm and term infants are particularly vulnerable due to the unique features of their cardiovascular function and reserve, compared to older children and adults. The clinical manifestations of neonatal sepsis are a product of the variable inflammatory pathways involved (warm vs. cold shock physiology), developmental state of the cardiovascular system, and hormonal responses. Targeted neonatal echocardiography has played an important role in advancing our knowledge, may help delineate specific hemodynamic phenotypes in real-time, and supports an individualized physiology-based management of sepsis-associated cardiovascular dysfunction. IMPACT: Cardiovascular dysfunction is a common sequela of sepsis. This review aims to highlight the pathophysiological mechanisms involved in hemodynamic disturbance in neonatal sepsis, provide insights from targeted neonatal echocardiography-based clinical studies, and suggest its potential incorporation in day-to-day management.

Blood pressure, organ dysfunction, and mortality in preterm neonates with late-onset sepsis.

BACKGROUND: The objective of this study was to investigate the association between systolic, diastolic, and mean blood pressures (SBP, DBP, and MBP) and adverse outcomes in preterm neonates with late-onset sepsis (LOS). METHODS: This is a two-center retrospective study over 6 years. Neonates <35 weeks gestational age (GA) with blood ± cerebrospinal fluid culture positive for organisms other than coagulase-negative Staphylococcus at >72 h age were included. Outcome measures were organ dysfunction (ODF) using the predefined criteria and post-ODF mortality (≤7 days from LOS onset). The lowest noninvasive blood pressures (BPs) recorded at baseline (24-48 h pre-LOS) and 0-12, 13-24, 25-36, and 37-48 h post LOS were analyzed. RESULTS: Of 147 neonates, ODF occurred in 70 (48%), of which 20 (29%) died. ODF was associated with a drop in all BP components, starting 0-12 h post-LOS onset (p < 0.01 for all); BPs remained unchanged in the non-ODF group. Mortality was associated with a greater reduction in SBP [-13 (-19, -8) vs. -4 (-8, 0); p < 0.01] and MBP [-9 (-13, -5) vs. +1 (-1, +4); p = 0.03] 0-12 h post-LOS onset. SBP had a higher area under the curve for mortality than MBP and DBP (0.83, 0.81, and 0.78, respectively). An inverse relation may exist between corrected GA and percentage reduction in SBP from baseline for equivalent risk of death. CONCLUSIONS: Reduction in BPs early in illness may identify preterm neonates at the highest risk of ODF and mortality from LOS. IMPACT: Drop in BPs from baseline starting in the immediate post-illness onset period may identify preterm neonates at the highest risk of developing ODF and mortality in LOS. Lowest systolic followed by mean BP measured during the first 12 h of illness provided the highest discriminating ability for LOS-related mortality. Absolute BPs recorded during the first 12 h of illness performed better than relative change from baseline for identifying neonates at risk of LOS-related mortality. The specific BP thresholds identified in this study may inform future therapeutic trials.

Clinical burden associated with therapies for cardio-pulmonary critical decompensation in preterm neonates across Canadian neonatal intensive care units.

The aim of this retrospective cohort study was to study the clinical burden associated with cardio-pulmonary critical decompensations (CPCDs) in preterm neonates and factors associated with mortality. Through the Canadian Neonatal Network (30 tertiary NICUs, 2010-2017), we identified infants < 32-week gestational age with CPCDs, defined by "significant exposure" to cardiotropes and/or inhaled nitric oxide (iNO): (1) either therapy for ≥ 3 consecutive days, (2) both for ≥ 2 consecutive days, or (3) any exposure within 2 days of death. Early CPCDs (≤ 3 days of age) and late CPCDs (> 3 days) were examined separately. Outcomes included CPCD-incidence, mortality, and inter-site variability using standardized ratios (observed/adjusted expected rate) and network funnel plots. Mixed-effects analysis was used to quantify unit-level variability in mortality. Overall, 10% of admissions experienced CPCDs (n = 2915). Late CPCDs decreased by ~ 5%/year, while early CPCDs were unchanged during the study period. Incidence and CPCD-associated mortality varied between sites, for both early (0.6-7.5% and 0-100%, respectively) and late CPCDs (2.5-15% and 14-83%, respectively), all p < 0.01. Units' late-CPCD incidence and mortality demonstrated an inverse relationship (slope = -2.5, p < 0.01). Mixed-effects analysis demonstrated clustering effect, with 6.4% and 8.6% of variability in mortality after early and late CPCDs respectively being site-related, unexplained by available patient-level characteristics or unit volume. Mortality was higher with combined exposure than with only-cardiotropes or only-iNO (41.3%, 24.8%, 21.5%, respectively; p < 0.01). CONCLUSIONS: Clustering effects exist in CPCD-associated mortality among Canadian NICUs, with higher incidence units showing lower mortality. These data may aid network-level benchmarking, patient-level risk stratification, parental counseling, and further research and quality improvement work. WHAT IS KNOWN: • Preterm neonates remain at high risk of acute and chronic complications; the most critically unwell require therapies such as cardiotropic drugs and inhaled nitric oxide. • Infants requiring these therapies are known to be at high risk for adverse neonatal outcomes and for mortality. WHAT IS NEW: • This study helps illuminate the national burden of acute cardio-pulmonary critical decompensation (CPCD), defined as the need for cardiotropic drugs or inhaled nitric oxide, and highlights the high risk of morbidity and mortality associated with this disease state. • Significant nationwide variability exists in both CPCD incidence and associated mortality; a clustering effect was observed with higher incidence sites showing lower CPCD-associated mortality.

La prise en charge de la persistance du canal artériel chez les nouveau-nés prématurés.

La prise en charge de la persistance du canal artériel est l'un des aspects les plus litigieux des soins aux nouveau-nés prématurés. On peut la classer en deux grandes catégories : la prophylaxie et le traitement en cas de symptômes. L'administration prophylactique d'indométacine par voie intraveineuse chez les nouveau-nés d'extrême petit poids à la naissance peut limiter les graves hémorragies intraventriculaires. L'échocardiographie est systématiquement recommandée pour confirmer une persistance du canal artériel avant d'envisager le traitement en cas de symptômes, qui peut prendre la forme d'un traitement conservateur, d'une pharmacothérapie ou d'une fermeture invasive. L'ibuprofène doit être considéré comme le traitement pharmacologique de première intention dans cette situation. Une forte dose peut être à privilégier, particulièrement chez les nouveau-nés prématurés de plus de trois à cinq jours de vie. Si deux traitements pharmacologiques consécutifs échouent ou si la pharmacothérapie est contre-indiquée, on peut envisager une fermeture invasive en cas de symptômes marqués lorsque l'échocardiographie révèle des signes de shunt à fort volume à travers le canal artériel et de circulation pulmonaire excessive.

Management of the patent ductus arteriosus in preterm infants.

Management of the patent ductus arteriosus (PDA) is one of the most contentious topics in the care of preterm infants. PDA management can be broadly divided into prophylactic and symptomatic therapy. Prophylaxis with intravenous indomethacin in extremely low birth weight infants may reduce severe intraventricular hemorrhage. Echocardiography should be routinely used to confirm the presence of a PDA before considering symptomatic therapy. A symptomatic PDA can be managed conservatively, using pharmacotherapy or with procedural closure. Ibuprofen should be considered as the pharmacotherapy of choice for a symptomatic PDA. High-dose ibuprofen may be preferable, especially for preterm infants beyond the first 3 to 5 days of age. If pharmacotherapy fails (after two courses) or is contraindicated, procedural closure may be considered for infants with a persistent PDA with significant clinical symptoms in addition to echocardiographic signs of a large PDA shunt volume and pulmonary over-circulation.

Physiology of Low Blood Pressure During the First Day After Birth Among Extremely Preterm Neonates.

OBJECTIVE: To investigate the circulatory physiology of hypotension during the first day after birth among stable extremely preterm neonates. STUDY DESIGN: Case-control study of neonates born at ≤276/7 weeks gestational age with hypotension, defined as mean blood pressure in mmHg less than gestational age in weeks for at least 1 hour during the first 24 hours after birth, who underwent comprehensive echocardiography assessment before commencement of cardiovascular drugs. Neonates with hypotension (n = 14) were matched by gestational age and intensity of respiratory support with normotensive neonates (n = 27) who underwent serial echocardiography during the first day after birth, and relatively contemporaneous echocardiography assessments were used for comparison. RESULTS: Neonates with hypotension had a higher frequency of patent ductus arteriosus ≥1.5 mm (71% vs 15%; P < .001) and ductal size (median diameter, 1.6 mm [IQR, 1.4-2.1] vs 1.0 mm [IQR, 0-1.3]; P = .002), higher echocardiography indices of left ventricular systolic function (mean shortening fraction, 34 ± 7% vs 26 ± 4%; P < .001; mean longitudinal strain, -16 ± 5% vs -14 ± 3%; P = .04; and mean velocity of circumferential fiber shortening, 1.24 ± 0.35 circ/s vs 1.01 ± 0.28 circ/s; P = .03), lower estimates of left ventricular afterload (mean end-systolic wall stress, 20 ± 7 g/cm2 vs 30 ± 9 g/cm2; P < .001 and mean arterial elastance, 43 ± 19 mmHg/mL vs 60 ± 22 mmHg/mL; P = .01), without significant difference in stress-velocity index z-score (-0.42 ± 1.60 vs -0.88 ± 1.30; P = .33). Neonates with hypotension had higher rates of any degree of intraventricular hemorrhage (71% vs 22%; P = .006). CONCLUSIONS: Low blood pressure in otherwise well extremely low gestational age neonates was associated with low systemic afterload and larger patent ductus arteriosus, but not left ventricular dysfunction.

Bloodstream Infections in Preterm Neonates and Mortality-Associated Risk Factors.

OBJECTIVE: To investigate the association of early (±4 hours after onset of bloodstream infection) clinical and laboratory variables with episode-related mortality (<7 days). STUDY DESIGN: This 2-site retrospective study included 142 neonates born at <35 weeks of gestational age with positive blood/cerebrospinal fluid (CSF) culture at >72 hours of age from organisms other than coagulase-negative Staphylococcus. Early variables were compared between those with bloodstream infection-related mortality and survivors. Multivariable analysis was conducted for the primary outcome, and the area under the curve (AUC) was estimated for relevant variables. RESULTS: The neonates who died were of lower gestational age at disease onset. After adjusting for relevant variables, lowest mean blood pressure (MBP) (aOR, 0.10; 95% CI, 1.02-1.19) and highest base deficit (aOR, 1.18; 95% CI, 1.06-1.32) were independently associated with mortality. The AUC was 0.87 (95% CI, 0.78-0.96) for base deficit, increasing to 0.91 (95% CI, 0.83-0.99) with the addition of MBP. CONCLUSION: Low MBP and high base deficit within ±4 hours of bloodstream infection onset identify preterm neonates at risk of mortality.

Cardiac Function and Ventricular Interactions in Persistent Pulmonary Hypertension of the Newborn.

OBJECTIVES: The aim of this study was to use a comprehensive imaging protocol to identify echocardiographic correlations of right and left ventricular size, function, and hemodynamics in neonates with persistent pulmonary hypertension of newborn and describe their relationship with key clinical variables. DESIGN: Retrospective case-control echocardiography-based study of persistent pulmonary hypertension of newborn. SETTING: A tertiary neonatal ICU in Canada. PATIENTS: Forty-nine neonates (gestational age ≥ 35 wk old) diagnosed with persistent pulmonary hypertension of newborn within first 3 days after birth and 50 age-matched controls. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The echocardiographic measurements comprised of right ventricular and left ventricular functional markers, including tricuspid annular plane systolic excursion, fractional area change, tissue Doppler imaging, and deformation imaging. Sample size was based on detecting an intergroup difference of 10% in tricuspid annular plane systolic excursion, which was considered the primary outcome. Linear correlations between the right and left ventricular indices, as well as their association with the outcome of death or extracorporeal membrane oxygenation were evaluated. Persistent pulmonary hypertension of newborn was associated with lower tricuspid annular plane systolic excursion (6.81 ± 1.92 vs 9.25 ± 1.30 mm), right-ventricular global longitudinal strain (16.9% ± 5.4% vs -21.6% ± 4.6%); left ventricular ejection fraction (49% ± 7% vs 55% ± 6%), left ventricular global longitudinal strain (-16.7% ± 3.3% vs -21.4% ± 2.0%) (all p < 0.01). Right and left ventricular diastolic and global function was also lower in persistent pulmonary hypertension of newborn, with more pronounced changes seen for the right ventricle. Moderate-to-strong linear correlations were observed between the right and left ventricular functional markers, with right ventricular global longitudinal strain and left ventricular global longitudinal strain being the strongest (r = 0.8). Within persistent pulmonary hypertension of newborn group, hypoxic ischemic encephalopathy was associated with lower right and left ventricular systolic and right ventricular diastolic performance. Tricuspid annular plane systolic excursion (p =0.08) and left ventricular systolic velocity (p = 0.09) tended to be lower in patients who subsequently died/needed extracorporeal membrane oxygenation. CONCLUSIONS: Persistent pulmonary hypertension of newborn is characterized by global cardiac dysfunction, involving both the right and left ventricles, with significant interventricular functional correlation. Cardiac dysfunction early in disease course may identify patients at highest risk of adverse outcome.

Association between changes in urine output and successful indomethacin treatment for patent ductus arteriosus in preterm neonates.

AIM: To investigate the relationship between changes in urine output during indomethacin treatment and ductal closure in preterm neonates. METHODS: It is a retrospective study in neonates ≤32 weeks who had received two courses of indomethacin for PDA treatment over a 5-year period. Indomethacin courses with pre- and post-echocardiography confirmation of PDA status were included. Various urine output indices were collected and compared between successful versus unsuccessful indomethacin courses. Indomethacin treatment success was defined as: (i) where PDA closed or became haemodynamically insignificant (hisPDA) after treatment and (ii) only including neonates where PDA had complete closure after treatment. ROC analysis was performed to examine predictive ability of urine output during indomethacin for treatment success. RESULTS: One hundred and eight indomethacin courses (first course: 52, second course: 56) in 80 neonates were included. The mean gestational age and birthweight were 25.4 ± 1.3 weeks and 762 ± 165 g, respectively. Irrespective of the definition used, there was no significant differences seen in any of urine output parameters between groups, except for a higher urine output during indomethacin associated with complete PDA closure (3.6 ± 1.3 vs. 3.0 ± 1.0 mL/kg/h, P = 0.02). The incidence of significant oliguria, hyponatraemia and need to withhold/delay indomethacin doses were also similar across groups. CONCLUSION: Urine output was not a useful predictor of ductal response to indomethacin treatment in preterm neonates.

Relationship of Patent Ductus Arteriosus Echocardiographic Markers With Descending Aorta Diastolic Flow.

OBJECTIVES: To characterize the relationship of echocardiographic markers of left heart overload and flow in peripheral major end-organ vessels (eg, celiac artery) with the presence of reversed holodiastolic flow in the descending aorta, considered a surrogate marker of an increased transductal shunt volume, in preterm patients with a patent ductus arteriosus (PDA). METHODS: This work was a retrospective study of data from echocardiography performed to investigate the hemodynamic significance of a PDA in preterm patients. We studied differences in echocardiographic markers of the PDA shunt volume according to patterns of flow in the postductal descending aorta (no PDA, PDA with antegrade diastolic flow, and PDA with reversed diastolic flow). The strength of the association between each echocardiographic marker and the presence of aortic holodiastolic flow reversal was investigated. RESULTS: We studied 137 patients with a median (interquartile range) birth weight of 850 (694-1030) g and a median gestational age of 25 (24-27) weeks. Among patients with a PDA (113), those with diastolic flow reversal in the descending aorta (44) presented had increased echocardiographic markers representative of the shunt volume (increased left ventricular output, left atrial-to-aortic ratio, pulmonary vein D wave, and shorter isovolumic relaxation time) compared to those with aortic antegrade diastolic flow. A positive, albeit weak, correlation between diastolic flow reversal and shunt volume echocardiographic markers was found. Abnormal diastolic flow in the celiac artery had the strongest correlation (R2  = 0.24). CONCLUSIONS: In preterm patients with a PDA, echocardiographic markers of the shunt volume were more abnormal in patients with reversed diastolic flow in the descending aorta. These data support the assumption that variance in these markers are related to the shunt volume, which needs consideration when adjudicating hemodynamic significance.

Neonatal Intensive Care Unit-Level Patent Ductus Arteriosus Treatment Rates and Outcomes in Infants Born Extremely Preterm.

OBJECTIVES: To assess associations between neonatal intensive care unit (NICU)-level patent ductus arteriosus (PDA) treatment rates (pharmacologic or surgical) and neonatal outcomes. STUDY DESIGN: This cohort study included infants born at 24-28 weeks of gestation and birth weight <1500 g in 2007-2015 in NICUs caring for ≥100 eligible infants in 6 countries. The ratio of observed/expected (O/E) PDA treatment rates was derived for each NICU by estimating the expected rate using a logistic regression model adjusted for potential confounders and network. The primary composite outcome was death or severe neurologic injury (grades III-IV intraventricular hemorrhage or periventricular leukomalacia). The associations between the NICU-level O/E PDA treatment ratio and neonatal outcomes were assessed using linear regression analyses including a quadratic effect (a square term) of the O/E PDA treatment ratio. RESULTS: From 139 NICUs, 39 096 infants were included. The overall PDA treatment rate was 45% in the cohort (13%-77% by NICU) and the O/E PDA treatment ratio ranged from 0.30 to 2.14. The relationship between the O/E PDA treatment ratio and primary composite outcome was U-shaped, with the nadir at a ratio of 1.13 and a significant quadratic effect (P<.001). U-shaped relationships were also identified with death, severe neurologic injury, and necrotizing enterocolitis. CONCLUSIONS: Both low and high PDA treatment rates were associated with death or severe neurologic injury, whereas a moderate approach was associated with optimal outcomes.

Preventing disease in the 21st century: early breast milk exposure and later cardiovascular health in premature infants.

Cardiovascular health of premature infants reaching early adulthood is an area of ongoing research. There is emerging evidence delineating the challenges faced by those individuals. Young adults born premature demonstrate a unique cardiac phenotype characterized by reduced biventricular volume, relatively lower systolic and diastolic function, and a disproportionate increase in muscle mass. This may clinically manifest by an increased risk of cardiovascular incidents, hypertension, and reduced exercise tolerance. Those consequences appear to result from early postnatal cardiac remodeling due to premature birth and associated co-morbidities. Recent evidence suggests that early exposure to breast milk slows down or even arrests those pathophysiological changes, thereby mitigating the long-term adverse effects of premature birth on cardiovascular health. In this review article, we discuss the role of breast milk in preventing early adulthood cardiovascular disease in infants born premature. We explore the emerging evidence and examine the possible mechanistic pathways mediating this phenomenon. Furthermore, we aim to demonstrate the vital role of early breast milk exposure in preventing cardiovascular disease in preterm infants.

Predictors of Early Extubation after Patent Ductus Arteriosus Ligation among Infants Born Extremely Preterm Dependent on Mechanical Ventilation.

We conducted a retrospective study of 166 ventilator-dependent neonates born extremely preterm in whom patent ductus arteriosus was surgically ligated and evaluated the association of preoperative characteristics and time-to-successful postoperative extubation. Larger patent ductus arteriosus diameter ([>2.5 mm], adjusted hazard ratio 0.51, 95% CI 0.36-0.72) and left-ventricular dilatation (z score ≥2, adjusted hazard ratio 0.61, 95% CI 0.42-0.87) were associated with earlier extubation.

Merits and perils of targeted neonatal echocardiography-based hemodynamic research: a position statement 1.

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.