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.

Cardiorespiratory Instability after Percutaneous Patent Ductus Arteriosus Closure: A Multicenter Cohort Study.

OBJECTIVE: To evaluate postprocedural clinical characteristics of preterm infants undergoing transcatheter patent ductus arteriosus (PDA) closure, including oxygenation/ventilation failure and cardiovascular compromise. STUDY DESIGN: Multicenter retrospective cohort study of preterm infants who were ≤2 kg at the time of percutaneous PDA closure between August 2018 and July 2021. Indices of cardiorespiratory stability were collected pre-closure, immediately post-closure, and subsequently averaged every 4 hours for the first 24 hours post-procedure. The primary outcome was incidence of post-transcatheter cardiorespiratory syndrome: composite of hemodynamic instability (defined by systemic hypotension, systemic hypertension, or use of new inotropes/vasopressors in the first 24 hours after catheterization) and at least one of the following: (i) ventilation failure or (ii) oxygenation failure. RESULTS: A total of 197 patients were included with a median [IQR] age and weight at catheterization of 34 [25, 43] days and 1090 [900, 1367] grams, respectively. The primary composite outcome of post-transcatheter cardiorespiratory syndrome was reported in 46 (23.3%). CONCLUSION: Post-transcatheter cardiorespiratory syndrome is characterized primarily by systemic hypertension and oxygenation failure, with a very low incidence of hypotension and need for inotropes.

Secular Trends in Patent Ductus Arteriosus Management in Infants Born Preterm in the National Institute of Child Health and Human Development Neonatal Research Network.

We evaluated changes in patent ductus arteriosus (PDA) diagnosis and treatment from 2012 through 2021 in a network of US academic hospitals. PDA treatment decreased among infants born at 26-28 weeks but not among infants born at 22-25 weeks. Rates of indomethacin use and PDA ligation decreased while acetaminophen use and transcatheter PDA closure increased.

PDA management strategies and pulmonary hypertension in extreme preterm infants with bronchopulmonary dysplasia.

BACKGROUND: Premature infants are at risk for developing pulmonary hypertension (PH) in the context of bronchopulmonary dysplasia (BPD). Studies suggest a potential link between prolonged patent ductus arteriosus (PDA) exposure and BPD-PH, though management strategies remain controversial. METHODS: Retrospective echocardiographic evaluation of newborns <29 weeks gestational age with BPD at two distinct centers. Primary objective was to evaluate the relationship between center-specific PDA management strategies (interventional or conservative) and the prevalence of BPD-PH. BPD was defined as oxygen or respiratory support at 36 weeks post-menstrual age (PMA). The presence of PH was defined as either an estimated sPAP of ≥40 mmHg or sEI ≥1.3. Center A has a conservative PDA policy. Center B has a targeted interventional policy. RESULTS: PH rates were similar between sites (21% vs 17%), while rates of PDA treatment was different (7% vs 81). Adjusted models did not demonstrate an association for center or PDA treatment exposure for PH and EI, although infants from Center A had echocardiography evidence of higher systolic eccentricity index (EI; 1.12 ± 0.19 vs 1.06 ± 0.15, p = 0.04). Markers of RV function (TAPSE and RV-FAC) were similar between groups. CONCLUSION: In preterm infants <29 weeks with BPD, conservative PDA treatment policy was not associated with higher rate of pulmonary hypertension diagnosis. IMPACT: The association between PDA-management approaches and the occurrence of BPD-associated pulmonary vascular disease in premature infants has sparsely been described. We found that a conservative policy, regarding the PDA, was not associated with an increase in pulmonary hypertension diagnosis. We identified that, in patients with BPD, echocardiographic metrics of LV performance were lower.

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

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

Impact of Early Hemodynamic Screening on Extremely Preterm Outcomes in a High-Performance Center.

Rationale: Increasing survival of extremely preterm infants with a stable rate of severe intraventricular hemorrhage represents a growing health risk for neonates. Objectives: To evaluate the role of early hemodynamic screening (HS) on the risk of death or severe intraventricular hemorrhage. Methods: All eligible patients 22-26+6 weeks' gestation born and/or admitted <24 hours postnatal age were included. As compared with standard neonatal care for control subjects (January 2010-December 2017), patients admitted in the second epoch (October 2018-April 2022) were exposed to HS using targeted neonatal echocardiography at 12-18 hours. Measurements and Main Results: A primary composite outcome of death or severe intraventricular hemorrhage was decided a priori using a 10% reduction in baseline rate to calculate sample size. A total of 423 control subjects and 191 screening patients were recruited with a mean gestation and birth weight of 24.7 ± 1.5 weeks and 699 ± 191 g, respectively. Infants born at 22-23 weeks represented 41% (n = 78) of the HS epoch versus 32% (n = 137) of the control subjects (P = 0.004). An increase in perinatal optimization (e.g., antepartum steroids) but with a decline in maternal health (e.g., increased obesity) was seen in the HS versus control epoch. A reduction in the primary outcome and each of severe intraventricular hemorrhage, death, death in the first postnatal week, necrotizing enterocolitis, and severe bronchopulmonary dysplasia was seen in the screening era. After adjustment for perinatal confounders and time, screening was independently associated with survival free of severe intraventricular hemorrhage (OR 2.09, 95% CI [1.19, 3.66]). Conclusions: Early HS and physiology-guided care may be an avenue to further improve neonatal outcomes; further evaluation is warranted.

Echocardiographic evaluation of left atrial volume and comparative analysis to left atrial to aortic root ratio in premature neonates and infants with patent ductus arteriosus.

PURPOSE: Left atrium to aortic root ratio (LA/Ao) is an echocardiographic marker of hemodynamically significant patent ductus arteriosus (PDA). Since 2-dimensional measurement of the ratio is geometrically limited, left atrial volume (LAV) which has 3-dimensional characteristics was investigated. The aim of this study was to determine a correlation between LA/Ao ratio and LAV as well as holodiastolic flow reversal in preterm neonates with and without a PDA. METHODS: A retrospective evaluation of neonates with and without PDA was performed. Targeted neonatal echocardiography evaluation of LA/Ao and LAV was measured from parasternal long-axis view and the apical 4 and 2-chamber views, respectively. Univariate and linear regression analysis were performed. RESULTS: 200 patients were included of whom 158 (79.0%) had a PDA shunt. The median gestational age at the time of echo was 27.4 weeks (IQR: 25.7-29.4 weeks). The median LA/Ao ratio was 1.51 (IQR: 1.26-1.83) and median LAV indexed to weight was  .91 mL/kg (IQR: .65-1.18 mL/kg). There was a significant correlation between LA/Ao and LAV indexed to weight in the PDA group (r2 = .080, p = .0003). LA/Ao ratio and LAV indexed to weight differed significantly between those with diastolic flow reversal versus no-flow reversal (LA/Ao, p = .003; LAV, p = .001). CONCLUSIONS: This study demonstrated a significant correlation between LA/Ao and LAV in preterm infants with PDA, with greater magnitude of discordance for LAV. The power of LAV versus LA/Ao in monitoring hemodynamically significant PDA requires prospective evaluation.

Transcatheter Patent Ductus Arteriosus Closure in Premature Infants: Comparison of Echocardiogram and Angiogram Measurements.

Transcatheter patent ductus arteriosus (PDA) closure (TCPC) utilizing transthoracic echocardiogram (TTE) as the sole imaging guide could simplify care. This single-center study compares PDA dimensions obtained from the TTE and angiogram images of patients who underwent attempted TCPC at Stead Family Children's Hospital from 10/01/2019 to 10/31/2020. Blinded investigators measured these dimensions solely for this study and had no impact on clinical care. Also, a hypothetical Piccolo device size was chosen based on the TTE dimensions and another on the angiographic dimensions, and then the correlation was analyzed. Sixty-two patients underwent TCPC attempts. TTE tends to overestimate the PDA narrowest dimension and underestimate the PDA length and aortic end dimension. Linear regression analysis revealed a weak correlation between the length and aortic diameter (R = 0.37 and 0.21, respectively). A modest correlation was observed for the smallest dimension without color Doppler (R = 0.57) and with color Doppler, which was utilized when needed (R = 0.6). Bland-Altman analysis revealed a smaller mean difference between the TTE and angiogram measurements of the narrowest diameter without color Doppler (0.4 mm) and with color Doppler (used as needed) (0.4 mm). However, the mean difference is larger for the aortic end (- 1.64 mm) and the length (- 1.73 mm). TTE accurately predicted the Piccolo device size in 43 (72%) patients and overestimated the size in 17 (28%) patients to the next size. Our findings should be verified with further studies, and additional development of protocols is needed to use TTE to guide TCPC without fluoroscopy.

Patent ductus arteriosus closure in small infants weighing less than 1500 g using KA micro plug: steps and tips.

BACKGROUND: Transcatheter patent ductus arteriosus closure in premature infants is gaining attention with rapidly growing experience. The KA micro plug device poses many favourable features for ductus arteriosus closure in premature infants. The study aimed to describe the technique and outcomes of a KA micro plug in closing the ductus arteriosus in premature infants weighing less than 1500 g. METHODS: This is a single-centre retrospective study in premature infants with patent ductus arteriosus weighing less than 1500 g who underwent off-label use of a KA micro plug at the Stead Family Children's Hospital from February 2022 to December 2023. RESULTS: Eighteen premature infants weighing less than 1500 g underwent attempted transcatheter ductus arteriosus closure using a KA micro plug device. Median weight, age, and corrected gestational age at the procedure were 943 g (682-1225), 26 days (9-79), and 28.5 weeks (25.6-32), respectively. The procedure was successful with complete closure achieved in all patients. No major haemodynamic instabilities were encountered. No catheterization-related complications were encountered. On a median follow-up of 10.9 months (0.1-19), all patients are alive with the device in a good position without residual shunt or abnormal findings. CONCLUSION: KA micro plug device for patent ductus arteriosus in infants weighing less than 1500 g is feasible, safe, and effective. We recommend that manufacturers of devices used to close the ductus arteriosus in small infants enhance both the devices and their delivery systems to simplify the procedure and mitigate the risk of haemodynamic instability.

Safety and Feasibility of Riociguat Therapy for the Treatment of Chronic Pulmonary Arterial Hypertension in Infancy.

The effects of riociguat, an oral-soluble guanylate-cyclase stimulator, were studied in 10 infants with chronic pulmonary arterial hypertension. Respiratory status (n = 8/10), right heart dilation (n = 7/10), function (n = 9/10), and chronic pulmonary arterial hypertension (n = 8/10) improved. Median decrement in systolic (12 [4, 14]), diastolic (14 [7, 20]), and mean arterial (14 [10, 17]) pressures were noted; no critical hypotension or hypoxemia occurred.

Left ventricular function before and after percutaneous patent ductus arteriosus closure in preterm infants.

BACKGROUND: Definitive closure of the patent ductus arteriosus (PDA) is associated with significant changes in the loading conditions of the left ventricle (LV), which may lead to cardiovascular and respiratory instability. The objective of the study was to evaluate targeted neonatal echocardiography (TnECHO) characteristics and the clinical course of preterm infants ≤2 kg undergoing percutaneous PDA closure. METHODS: Retrospective cohort study of prospectively acquired pre- and post-closure TnECHOs to assess hemodynamic changes. Cardiorespiratory parameters in the first 24 h following PDA closure were also evaluated. RESULTS: Fifty patients were included with a mean age of 30.6 ± 9.6 days and weight of 1188 ± 280 g. LV global longitudinal strain decreased from -20.6 ± 2.6 to -14.9 ± 2.9% (p < 0.001) after 1 h. There was a decrease in LV volume loading, left ventricular output, LV systolic and diastolic parameters. Cardiorespiratory instability occurred in 24 (48%) [oxygenation failure in 44%] but systolic hypotension and/or need for cardiovascular medications was only seen in 6 (12%). Patients with instability had worse baseline respiratory severity score and lower post-closure early diastolic strain rates. CONCLUSIONS: Percutaneous PDA closure leads to a reduction in echocardiography markers of LV systolic/diastolic function. Post-closure cardiorespiratory instability is characterized primarily by oxygenation failure and may relate to impaired diastolic performance. IMPACT: Percutaneous patent ductus arteriosus closure leads to a reduction in echocardiography markers of left ventricular volume loading, cardiac output, and left ventricular systolic/diastolic function. Post-procedural cardiorespiratory instability is characterized primarily by oxygenation failure. Post-procedural cardiorespiratory instability may relate to impaired diastolic performance.

Quaternary Ammonium Compounds (QACs) in Wastewater Influent and Effluent Throughout the COVID-19 Pandemic.

Quaternary ammonium compounds (QACs) are used in consumer and industrial products, including disinfectants. Due to the COVID-19 pandemic, disinfectant use has increased, purportedly increasing loads to wastewater treatment plants and the environment. To understand how the increased usage has affected QAC loadings to treatment plants and to determine how effectively plants remove QACs from liquid effluent that is discharged to surface and groundwaters, influent and effluent wastewater samples were collected from four treatment plants (treatment capacities < 5 MGD to > 100 MGD) for 21 months beginning in May 2020. Influent QAC concentrations were hundreds of µg/L and effluent QAC concentrations were < 1 µg/L, corresponding to an average removal of 98% from all four plants. The most prevalent QACs in influent were those used most commonly in disinfectants, specifically benzylalkyldimethylammonium compounds (BACs) and short-chain dialkyldimethylammonium compounds (DADMACs), and influent levels of these compounds were correlated with QAC sales. Prior to this study, ethylbenzylalkyldimethylammonium compounds (EtBACs) had not been studied, and they comprised 13 ± 6% of QACs in influent. While removal was high at all plants, low µg/L concentrations were still continuously discharged into the environment. For QACs with equivalent alkyl chain lengths, those with aromatic substituents (BACs and EtBACs) appear to be removed more effectively than those with only alkyl chains (DADMACs).

Growth of targeted neonatal echocardiography in Chinese neonatal intensive care units: gaps in practice and training.

To evaluate clinical practice, neonatologists' attitudes, and the extent of training and accreditation regarding targeted neonatal echocardiography (TnEcho) among Chinese neonatologists. A web-based questionnaire was emailed to 331 neonatologists across China who completed training in subspecialty neonatology. The survey covered various aspects of TnEcho, including the characteristics of clinical practice, attitudes towards its usefulness, and perceived barriers to implementation and training methods. Survey response rate was 68.0% (225/331). Seventy-nine (35.1%) respondents stated that TnEcho was utilized in their NICUs. Most respondents reported the use of echocardiography to evaluate hemodynamic significance of the patent ductus arteriosus (PDA, 94.9%). The eyeballing technique was most used to evaluate left (82.3%) and right (77.2%) ventricular function. Most respondents (87.3-96.2%) positively valued the role of TnEcho in providing timely and longitudinal hemodynamic information to guide cardiovascular care. Access to TnEcho was more likely in centers with on-site pediatric cardiology service (p = .003), larger bed capacity (p = .004), or level IV status (p = .003). Lack of experienced practitioners with echocardiography expertise (88.9%) and accredited training programs (85.8%) was perceived to be the major barrier to implementation. Of concern, most practitioners with TnEcho skills received training in an informal manner through workshops (60.8%) or self-directed learning (54.4%). Conclusions: The use of TnEcho for longitudinal evaluation of infants with hemodynamic instability is growing within Chinese NICUs. There is an urgent need to develop standardized training programs and accreditation for TnEcho which are adapted to the Chinese context.

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..

Impact of patent ductus arteriosus shunt size and duration on risk of death or severe respiratory morbidity in preterm infants born in China.

The purpose of this study is to assess whether duration and size of the arterial duct were associated with severe respiratory morbidity and mortality in preterm infants. All echocardiography evaluations for patent ductus arteriosus (PDA) in a cohort of preterm infants, born at a gestational age less than 28 weeks, from birth up to 36 weeks of postconceptional age or final ductal closure were reviewed. Ductal size was measured at the pulmonary end. PDA was classified as small (E1: ductal diameter (DD) ≤ 1.5 mm), moderate (E2: 1.5 mm < DD ≤ 2.5 mm), or large (E3) (DD > 2.5 mm). The primary outcome was adverse outcome defined by the composite outcome of bronchopulmonary dysplasia (BPD) or death. Infants in whom the primary outcome occurred were classified as "high-risk" whereas patients who did not satisfy this outcome were classified as "low-risk". Intergroup comparison (high vs. low risk) was performed using univariate and multivariate analyses. A total of 135 infants, born between 2010 and 2020, were evaluated. The primary outcome was satisfied in 46 (34.1%) patients. The high-risk group was characterized by increased duration of exposure to PDA of any (E1/E2/E3) grade (44 vs. 25.5 days, p = .0004), moderate or large (E2/E3) PDA (30.5 vs. 11.5 days, p < .0001), moderate (E2) PDA (10.8 vs.6 days, p = 0.05), and large (E3) PDA (11.5 vs.0 days, p < .0001) compared with low-risk group. Lower gestational age, prolonged duration of mechanical ventilation, higher rate of inotrope use, pharmacological therapy, and PDA ligation were also associated with development of BPD or death (high-risk group). After adjusting for confounders, the rate of inotrope use [OR 2.688, 95% CI (1.011-7.142), p = 0.047], duration of large (E3) PDA [OR 1.060, 95% CI (1.005-1.118), p = 0.03], and mechanical ventilation [OR 1.130, 95% CI (1.064-1.200), p = 0.0001] were independently associated with the composite of BPD or death. Among infants who developed BPD, 27 were classified as grade I and 18 as grade II BPD, respectively. Infants with grade II BPD had prolonged MV (20.0 vs. 9.0 days, p = 0.024), prolonged exposure to PDA of any grade (55.8 vs. 36.0 days, p = 0.03), and prolonged exposure to large (E3) PDA compared with infants with grade I BPD.   Conclusion: Prolonged exposure to a large PDA was associated with severe respiratory morbidity and mortality in preterm infants. The modulator role of early intervention, in the most pathologic shunts, on severe respiratory morbidity in preterm infants should be tested in well-designed clinical trials. What is Known: • Current guidelines recommended against accelerating PDA closure of preterm infants within 2 weeks of life, with low certainty evidence indicating improved long-term outcomes. • Recent studies suggest that conservative approach regarding PDA management has detrimental effects on the respiratory outcomes in a subgroup population. What is New: • Persistent patency of significant PDA is associated with increased risk of BPD/death in extremely preterm infants. • Targeted intervention of PDA is beneficial for the at-risk preterm infants with increased PDA hemodynamic significance.

Lung ultrasound score parallels trends in systemic haemodynamics after PDA ligation: a case series.

B-lines in lung ultrasound (LU) are non-specific but highly informative sign of interstitial pulmonary oedema (iPE). Sustained exposure to a high-volume left-to-right patent ductus arteriosus (PDA) shunt is associated with iPE. Cardiorespiratory deterioration, named post-ligation cardiac syndrome (PLCS), may follow surgical ligation between 6 and 12 h post-operatively. We conducted a pilot longitudinal evaluation of peri-procedural LU score change. Infants < 32-week gestational age or < 1500-g birthweight undergoing PDA ligation, where pre-, 1 h and 6-12 h LU were performed, were included. Two independent raters evaluated LU score (LUS). Neonatologist performed echocardiography (NPE) was performed concurrently to appraise changes in left ventricular output (LVO). Milrinone was initiated if LVO was < 200 mL/kg/min 1 h after surgery, to prevent PLCS. The primary outcome was peri-procedural LUS change. Secondary outcomes included PLCS. Five infants were included (birthweight 787(88) g; gestational age 25.6(0.7) weeks). Postnatal age and weight at the intervention were 41(14) days and 1175(295) g. All infants, but one, received milrinone prophylaxis. None of the patients developed PLCS or required rescue HFOV. Post-interventional LUS were lower compared to pre-operative LUS (p = 0.041 vs 1 h, p = 0.042 vs 6-12 h). A concurrent fall post-operative LVO was noted (p < 0.05 vs pre-operative). CONCLUSION: A sustained fall in LUS after PDA ligation was identified, which most likely reflects reduction in pulmonary blood flow and interstitial edema. Changes in LUS paralleled changes in LVO, suggesting physiologic linkage. These data suggest that LU may be a useful tool to guide monitoring the biologic nature of pulmonary disease after PDA ligation. WHAT IS KNOWN: • Sustained exposure to a high-volume left-to-right patent ductus arteriosus (PDA) shunt is associated with interstitial pulmonary oedema. • In the most immature patients, cardiorespiratory deterioration, named post-ligation cardiac syndrome, presents 6-12 h post-operatively. WHAT IS NEW: • An early and sustained fall in lung ultrasound score (LUS) after PDA ligation most likely reflects reduction in pulmonary blood flow and interstitial oedema. LUS changes parallel changes in left ventricular output, suggesting linkage. • LU is a promising adjunctive tool in the post-operative management of PDA ligation.

Survey highlighting the lack of consensus on diagnosis and treatment of patent ductus arteriosus in prematurity.

To gain insight in the availability of guidelines, diagnostic criteria, and treatment strategies and whether clinical equipoise regarding optimal treatment for patent ductus arteriosus (PDA) in prematurity is present. We hypothesized that (co-)authors of PDA-related papers were more likely to screen for a PDA and would treat earlier and more aggressively. An international internet-based survey between September 2019 and March 2020 in which we collected (1) baseline characteristics; (2) availability of guidelines; (3) screening strategy for PDA; (4) diagnostic criteria for hemodynamic significance; (5) treatment strategy; and (6) metrics of treatment efficacy. Finally, ten clinical equipoise statements were posed on a Likert scale. In total, 144 surveys were sent, of which 71/144 (49%) surveys could be analyzed with 56/71 (79%) fully completed surveys. The respondents, mainly neonatologists in a level III neonatal intensive care unit, of whom 36/71 (51%) had (co-)authored a publication on the PDA, highlighted a lack of national guidelines, heterogeneous approach to screening strategies, and marked variability in diagnostic criteria to assess hemodynamic significance, treatment strategies and effect measurement. No major significant differences were observed between respondents who did or did not (co-)author a publication on the PDA. Respondents who screened for PDA scored significantly higher on the need for screening, early and aggressive treatment. Remarkably, the scores of all statements regarding clinical equipoise varied widely.   Conclusions: Our survey highlights the lack of guidelines and enormous heterogeneity in current practice. Current evidence is not robust enough to harmonize current treatment strategies into (inter)national guidelines. What is Known: • Patent ductus arteriosus (PDA) incidence is inversely related to gestational age. • Although early pharmacological treatment induces PDA closure, optimal treatment is debated due to the lack of beneficial effects on outcome. What is New: • In the absence of (inter)national guidelines, diagnostic and treatment strategies are heterogeneous and contradictory, even in a selected hemodynamically- interested group. • Different PDA screening strategies did, while PDA publication status did not, show significant differences in treatment strategy and responses to equipoise statements.

A practical approach toward interpretation of amplitude integrated electroencephalography in preterm infants.

The developing preterm brain is vulnerable to injury, especially during periods of clinical instability; therefore, monitoring the brain may provide important information on brain health. Over the last 2 decades, a growing body of literature has been reported on preterm amplitude integrated electroencephalography (aEEG) with regards to normative data and associations with adverse outcomes. Despite this, the use of aEEG for preterm infants remains mostly a research tool with limited clinical applicability. In this article, we review the literature on normal and abnormal aEEG patterns in preterm infants and propose a stepwise clinical algorithm for aEEG assessment at the bedside that takes into account assessment of maturation and identification of pathological patterns. CONCLUSION: This algorithm may be used by clinicians at the bedside for interpretation to integrate it in clinical practice for neurological surveillance of preterm infants. WHAT IS KNOWN: • Studies have reported normative data on aEEG in preterm infants for different gestational ages. • Burst suppression pattern and absent sleep-wake cycling have been described to be associated with brain pathology and adverse outcomes in preterm infants. WHAT IS NEW: • We have synthesized aEEG characteristics in preterm infants across the spectrum of prematurity reported in the literature. • We present a stepwise approach for clinically applicable interpretation of aEEG in preterm infants.

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.