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Résumé Le monoxyde d’azote inhalé (NOi), un vasodilatateur pulmonaire sélectif, est utilisé pour le traitement des nouveau-nés en insuffisance respiratoire hypoxémique (IRH) associée à une hypertension pulmonaire persistante du nouveau-né. Idéalement, il doit commencer à être administré après la confirmation échocardiographique de ce type d’hypertension. L’utilisation de NOi est recommandée chez les nouveau-nés peu prématurés ou à terme chez qui survient une IRH malgré des stratégies d’oxygénation ou de ventilation optimales. Cependant, il n’est pas recommandé d’y recourir systématiquement chez les nouveau-nés prématurés sous assistance respiratoire. On peut l’envisager comme traitement de secours chez les nouveau-nés prématurés en IRH précoce associée à une rupture prolongée des membranes ou à un oligoamnios, ou en IRH tardive en cas d’hypertension pulmonaire liée à une dysplasie bronchopulmonaire et accompagnée d’une insuffisance ventriculaire droite marquée. On peut aussi l’envisager chez les nouveau-nés atteints d’une hernie diaphragmatique congénitale qui présentent une IRH persistante, malgré un recrutement pulmonaire optimal, des signes échocardiographiques d’hypertension pulmonaire suprasystémique et un fonctionnement ventriculaire gauche approprié.

Inhaled nitric oxide (iNO), a selective pulmonary vasodilator, is used as a therapeutic modality in infants with hypoxemic respiratory failure (HRF) associated with persistent pulmonary hypertension of the newborn (PPHN). iNO should ideally be initiated following echocardiographic confirmation of PPHN. Use of iNO is recommended in late preterm and term infants who develop HRF despite optimal oxygenation and ventilation strategies. However, routine iNO use in preterm infants on respiratory support is not recommended. iNO may be considered as a rescue modality in preterm infants with early-onset HRF when associated with prolonged rupture of membranes or oligohydramnios, or late-onset HRF in the context of bronchopulmonary dysplasia-associated pulmonary hypertension (PH) with severe right ventricular failure. A trial of iNO may also be considered for infants with congenital diaphragmatic hernia with persistent HRF despite optimal lung recruitment, and with echocardiographic evidence of supra-systemic PH and adequate left ventricular function.

Background: In newborns with hypoxic-ischaemic encephalopathy, more profound altered right and left ventricular function has been associated with mortality or brain injury. Mechanisms underlying cardiac dysfunction in this population are thought to be related to the persistence of increased pulmonary vascular resistance and myocardial ischaemia. We sought to compare cardiac function in newborns with hypoxic-ischaemic encephalopathy to controls using echocardiography. Methods: We did a retrospective case–control study with moderate or severe hypoxic-ischaemic encephalopathy between 2008 and 2017. Conventional and speckle-tracking echocardiography measures were extracted to quantify right and left ventricular systolic and diastolic function. Fifty-five newborns with hypoxic-ischaemic encephalopathy were compared to 28 controls. Results: Hypoxic-ischaemic encephalopathy newborns had higher estimated systolic pulmonary pressure (62.5 ± 15.0 versus 43.8 ± 17.3 mmHg, p < 0.0001) and higher systolic pulmonary artery pressure/systolic blood pressure ratio [101 ± 16 (iso-systemic) versus 71 ± 27 (2/3 systemic range) %, p < 0.0001]. Tricuspid annular plane systolic excursion was decreased (7.5 ± 2.2 versus 9.0 ± 1.4 mm, p = 0.002), E/e’ increased (7.9 ± 3.3 versus 5.8 ± 2.0, p = 0.01), and right ventricle-myocardial performance index increased (68.1 ± 21.5 versus 47.8 ± 9.5, p = 0.0001) in hypoxic-ischaemic encephalopathy. Conventional markers of left ventricle systolic function were similar, but e’ velocity (0.059 ± 0.019 versus 0.070 ± 0.01, p = 0.03) and left ventricle-myocardial performance index were statistically different (77.9 ± 26.2 versus 57.9 ± 11.2, p = 0.001). The hypoxic-ischaemic encephalopathy group had significantly altered right and left ventricular deformation parameters by speckle-tracking echocardiography. Those with decreased right ventricle-peak longitudinal strain were more likely to have depressed left ventricle-peak longitudinal strain. Conclusion: Newborns with hypoxic-ischaemic encephalopathy have signs of increased pulmonary pressures and altered biventricular systolic and diastolic function.

Objective This study aimed to evaluate the prevalence of adverse outcomes, specifically pulmonary hypertension (PH) and suspected or confirmed necrotizing enterocolitis (NEC), and their associated risk factors, in neonates treated with diazoxide. Study Design A retrospective study in infants born ≥ 316/7 weeks and admitted between January 2014 and June 2020. Combined adverse outcomes possibly associated to diazoxide were PH (systolic pulmonary pressure of ≥40 mm Hg or an eccentricity index ≥1.3) and suspected or confirmed NEC (suspected: stop feeds and antibiotics and confirmed: modified Bell stage ≥2). Echocardiography data extractors were masked to infants' characteristics. Results A total of 63 infants were included; 7 (11%) with suspected and 1 (2%) with confirmed NEC. Of the 36 infants with an available echocardiography after initiation of diazoxide treatment, 12 (33%) had PH. All infants with suspected or confirmed NEC were males (p = 0.01), whereas PH occurred mostly in females (75%, p = 0.02). The combined adverse outcome occurred in 14/26 (54%) infants exposed to >10 mg/kg/day, compared to 6/37 (16%) exposed to ≤10 mg/kg/day (p = 0.006). This association remained significant after adjustment for sex, small for gestational age status, and gestational age at birth (odds ratio: 6.1, 95% confidence interval: 1.7–21.7, p = 0.005). Left ventricular dysfunction was found in 19 infants (30%) but was not discriminative for the combined outcome. Conclusion PH and suspected or confirmed NEC were identified frequently in neonates treated with diazoxide. A total dose >10 mg/kg/day was associated with an increased occurrence of these complications. Key Points

Hypertensive disorders of pregnancy (HDP) are associated with neonatal hematological disturbances, such as thrombocytopenia. The association of HDP to platelet counts in the context of extreme prematurity, to trends of platelet counts during neonatal hospitalization, and to frequency of platelet transfusions remain to be explored.Retrospective study of infants born at less than 29 weeks born between 2015 and 2019. Platelet counts were collected on initial complete blood count, at 2 weeks, 32 weeks post-menstrual age (PMA), 36 weeks PMA, and closest to discharge. We examined the association between HDP and platelet counts at each time point, frequency of platelet transfusions and intraventricular hemorrhage (IVH) grade 3 or more.Total 296 infants were included, 43 exposed to HDP. Infants exposed had lower platelet counts at each time point, as well as a higher prevalence of platelet less than 150 × 10Premature infants exposed to HDP have a higher prevalence of thrombocytopenia, increased frequency of platelet transfusion, and an altered trend in platelet counts during neonatal hospitalization.

Evaluate factors associated with significant pulmonary hypertension [PH] (≥2/3 systemic) and its impact on ventricular function at 36 weeks postmenstrual age (PMA).Retrospective cohort of infants born at29 weeks who survived to their echocardiography screening for PH at 36 weeks PMA. Masked experts extracted conventional and speckle-tracking echocardiography [STE] data.Of 387 infants, 222 were included and 24 (11%) categorized as significant PH. Significant PH was associated with a decrease in tricuspid annular plane systolic excursion (0.79 vs 0.87 cm, p = 0.03), right peak longitudinal strain [pLS] by STE (-19.6 vs -23.1%, p = 0.003) and left pLS (-25.0 vs -22.7%, p = 0.02). The association between biventricular altered function by STE and significant PH persisted after adjustment for potential confounders - LV-pLS (p = 0.007) and RV-pLS (p = 0.01).Our findings are suggestive that premature newborns with significant PH at 36 weeks PMA have a biventricular cardiac involvement to their pathophysiology.

This study was aimed to describe the cardiopulmonary profiles of adult patients with bronchopulmonary dysplasia (BPD), comparing them to normative adult values.This study presents a retrospective chart review of all BPD patients followed in the adult BPD clinic, identified from institutional and archive databases, born preterm at ≤33 weeks of estimated gestational age (EGA) between January 1980 and December 2000.Forty-four patients with BPD (26.4 ± 2.7 weeks of EGA) were included. Average age at follow-up was 19 years. Majority (61.4%) of the patients had a diagnosis of asthma. Mean spirometry values were: first second of forced expiration (FEV1) 74.1%, forced vital capacity (FVC) 80.7%, and FEV1/FVC 82.5%. Echocardiography (ECHO) images were reviewed, left ventricular (LV) structure and performance did not differ between obstructive and nonobstructive pulmonary function test (PFT) groups, but values of LV longitudinal strain were 4.8% lower than expected normal for adults. Patients with obstructive PFT had additional decreased right ventricular (RV) function by ECHO.BPD patients in this study were found to have a burden of cardiorespiratory alterations that persisted into adulthood, with RV performance abnormalities found among patients with obstructive PFT.· BPD patients born at extremes of prematurity have cardiorespiratory alterations in adulthood.. · Among patients with obstructive lung function, subtle cardiac performance abnormalities were found.. · Future directions should include systematic follow-up of premature newborns with BPD..

Objective Pulmonary hypertension (PH) has been described in the neonatal omphalocele population. This study was aimed to describe cardiac function and PH severity using echocardiography in newborns with giant omphalocele (GO) and with non-GO and determine if right ventricular (RV) dysfunction is associated with mortality. Study Design Retrospective, single-center analysis of first echocardiography among neonatal omphalocele patients born between 2004 and 2017 was conducted. Multivariate logistic and univariate Cox's regression was constructed to measure hazard ratio (HR) for death outcome. Results There were 32 newborns, of whom 18 were GO and 7 died. GO had increased systolic pulmonary arterial to systolic systemic blood pressure ratio (97% [isosystemic] vs. 73% [three-fourths systemic] p = 0.03). RV performance parameters (tricuspid annular plane excursion, HR = 0.40; fractional area change, HR = 0.90; and RV peak global longitudinal strain, HR = 1.39) were associated with mortality. These RV performance parameters remained associated in a multiple logistic regression accounting for gestational age and GO status. The overall population had abnormal eccentricity index and pulmonary artery acceleration time to RV ejection time ratio, two markers of PH. Conclusion Patients with omphalocele have increased pulmonary pressure, with GO being worse than non-GO. RV dysfunction at initial echocardiography was significantly associated with mortality.

Background: Individuals born preterm present left ventricle changes and increased risk of cardiac diseases and heart failure. The pathophysiology of heart disease after preterm birth is incompletely understood. Mitochondria dysfunction is a hallmark of cardiomyopathy resulting in heart failure. We hypothesized that neonatal hyperoxia in rats, a recognized model simulating preterm birth conditions and resulting in oxygen-induced cardiomyopathy, induce left ventricle mitochondrial changes in juvenile rats. We also hypothesized that humanin, a mitochondrial-derived peptide, would be reduced in young adults born preterm. Methods: Sprague-Dawley pups were exposed to room air (controls) or 80% O 2 at postnatal days 3 to 10 (oxygen-induced cardiomyopathy). We studied left ventricle mitochondrial changes in 4 weeks old males. In a cohort of young adults born preterm (n=55) and age-matched term (n=54), we compared circulating levels of humanin. Results: Compared with controls, oxygen-exposed rats showed smaller left ventricle mitochondria with disrupted integrity on electron microscopy, decreased oxidative phosphorylation, increased glycolysis markers, and reduced mitochondrial biogenesis and abundance. In oxygen-exposed rats, we observed lipid deposits, increased superoxide production (isolated cardiomyocytes), and reduced Nrf2 gene expression. In the cohort, left ventricle ejection fraction and peak global longitudinal strain were similar between groups however humanin levels were lower in preterm and associated with left ventricle ejection fraction and peak global longitudinal strain. Conclusions: In conclusion, neonatal hyperoxia impaired left ventricle mitochondrial structure and function in juvenile animals. Serum humanin level was reduced in preterm adults. This study suggests that preterm birth–related conditions entail left ventricle mitochondrial alterations that may underlie cardiac changes perpetuated into adulthood. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03261609.

Neurodevelopmental delay (NDD) affects congenital diaphragmatic hernia (CDH) infants. Initial assessment by experienced developmental pediatricians, supported by Bayley-3 tests, is a viable pathway for NDD identification and surveillance. We risk stratified CDH infants to observe differences in incidence and type of NDD based on disease severity.Patients from a CDH long-term follow-up database started in 2012 were reviewed (REB#2019-4583). Risk stratification into low, moderate, and high-risk cohorts was performed using the CDH Study Group Mortality Prediction Score. Patients requiring ECLS, supplemental oxygen at 30 days and patch repair were also considered high-risk (i.e. usual clinical criteria). Post-discharge NDD assessments by developmental pediatricians and occupational therapists (Bayley-3) were analyzed for all patients18months. NDD incidence and type per risk group was determined using descriptive statistics.Of 102 CDH patients included for study, 26% (27/102) had NDD. Risk stratification identified 2(2%), 7(7%), and 18(18%) patients with NDD in the low, moderate and high-risk groups, respectively. Language delay (2 low; 6 moderate; 10 high) was the most prevalent. Three patients had both expressive and receptive language delay. Motor deficits were observed almost exclusively in the high-risk group.Based on our experience, NDD affects one-quarter of CDH infants. Risk stratification helped identify infants at increased risk of NDD. While language delays predominated across all risk groups, multiple deficits occurred in higher risk cohorts. These patients should receive structured NDD assessment as part of an optimal interdisciplinary CDH care pathway.

To evaluate multi-organ dysfunction (MOD) in newborns treated with therapeutic hypothermia (TH) for hypoxic ischemic encephalopathy (HIE), and to compare MOD in those with normal/mild magnetic resonance imaging (MRI) findings to those with moderate to severe MRI findings or death.Retrospective single-center observational study of infants treated with TH. A total of 16 parameters across 7 organ systems were analyzed. Primary outcome was death or moderate to severe brain injury on MRI.Of 157 infants treated with TH, 77% had ≥2 organ systems with dysfunction. The number of organ systems with dysfunction was strongly associated with death or moderate-to-severe brain injury (p 0.0001). Hematologic (68%) and hepatic (65%) dysfunction were most common. Neurologic and renal dysfunction were most strongly associated with the primary outcome (OR 13.5 [6.1-29.8] and 11.2 [4.1-30.3], respectively), while pulmonary hypertension was not.MOD is prevalent in infants undergoing TH for HIE, and the association between MOD and adverse outcomes may impact clinical care and counseling.

Cardiovascular disease, and particularly ischemic heart disease, is a leading cause of maternal morbidity and mortality in high-income countries. The incidence of acute myocardial infarction has been rising over the past 2 decades due to increasing maternal age and a higher prevalence of cardiovascular risk factors in the pregnant population. Causes of acute myocardial infarction in pregnancy are diverse and may require specific considerations for their diagnosis and management. In this narrative review, we provide an overview of physiologic changes, risk factors, and etiologies leading to acute myocardial infarction in pregnancy, as well as diagnostic tools, reperfusion strategies, and pharmacological treatments for this complex condition. In addition, we outline considerations for labor and delivery planning and long-term follow-up of patients with acute myocardial infarction in pregnancy.

Objective Describe the association between cardiac dysfunction and death or moderate-to-severe abnormalities on brain magnetic resonance imaging (MRI) in neonates undergoing therapeutic hypothermia for hypoxic ischemic encephalopathy (HIE). Study design Retrospective study in neonates with moderate or severe HIE undergoing therapeutic hypothermia between 2008 and 2017. Primary outcome was death or moderate-to-severe brain injury using the Barkovich score. Conventional and speckle-tracking echocardiography measures were extracted from available echocardiograms to quantify right (RV) and left (LV) ventricular functions. Results A total of 166 newborns underwent therapeutic hypothermia of which 53 (36.5%) had echocardiography performed. Ten (19%) died prior to hospital discharge, and 11 (26%) had moderate-to-severe brain injury. There was no difference in chronologic age at echocardiography between the normal and adverse outcome groups (22 [±19] vs. 28 [±21] hours, p = 0.35). Cardiac findings in newborns with abnormal outcome included lower systolic and diastolic blood pressure (BP) at echocardiography (p = 0.004) and decreased tricuspid annular plane systolic excursion (a marker of RV systolic function; p = 0.01), while the ratio of systolic pulmonary artery (PA) pressure to systolic BP indicated isosystemic pressures (>2/3 systemic) in both groups. A multilogistic regression analysis, adjusting for weight and seizure status, indicated an association between abnormal outcome and LV function by longitudinal strain, as well as by ejection fraction. Conclusion Newborns who died or had moderate-to-severe brain injury had a higher incidence of cardiac dysfunction but similar PA pressures when compared with those who survived with mild or no MRI abnormalities. Key points · Newborns with HIE with functional LV/RV dysfunction are at risk for death or brain injury.. · All neonates with HIE had elevated pulmonary pressure, but neonates with poor outcome had RV dysfunction.. · When evaluating newborns with HIE by echocardiography, beyond estimation of pulmonary pressure, it is important to assess biventricular function..

OBJECTIVE Evaluate spontaneous closure of the patent ductus arteriosus (PDA) in extremely preterm infants and their respiratory outcomes, especially at

Preterm birth increases risk of cardiovascular disease and early death. A body of evidence suggests left ventricle (LV) echocardiographic alterations in children and adults born preterm. We aimed to determine if neonatal characteristics were associated with alterations in LV structure and function in preterm adults. We evaluated a cohort of 86 young adults born preterm below 30 weeks of gestation, and 85 full-term controls. We determined LV dimensions and function using tissue Doppler imaging, conventional and speckle tracking echocardiography (STE). Adults born preterm had smaller LV dimensions, but these differences did not remain after adjustment for body surface area (BSA), which was smaller in the preterm group. Stroke volume and cardiac output were reduced even after adjustment for BSA. We found a smaller e’ wave in the preterm group, but other markers of systolic and diastolic function did not differ. Use of antenatal steroids may be associated with a further reduced cardiac output in those born preterm. Adults born preterm show alterations in markers of LV dimensions and function. Identification of these markers may represent opportunities for early prevention of cardiovascular events in this at-risk population.

Background Near-infrared spectroscopy (NIRS) measures of cerebral saturation (Csat) and renal saturation (Rsat) in extreme premature newborns may be affected by systemic blood flow fluctuations. Despite increasing clinical use of NIRS to monitor tissue saturation in the premature infant, validation of NIRS measures as a correlate of blood flow is still needed. We compared echocardiography (ECHO) derived markers of ascending aorta (AscAo) and descending aorta (DesAo) blood flow with NIRS measurements obtained during the ECHO. Methods Newborns Results Forty-nine neonates with 75 Csat-ECHO and 62 Rsat-ECHO observations were studied. Mean post-menstrual age was 28.3 ± 3.8 weeks during the ECHO. Preductal measures including AscAo velocity time integral (VTI) and AscAo output were correlated with Csat or cFTOE, while postductal measures including DesAo VTI, DesAo peak systolic velocity, and estimated DesAo output were more closely correlated with Rsat or rFTOE. Conclusions NIRS measures are associated with aortic blood flow measurements by ECHO in the extremely premature population. NIRS is a tool to consider when following end organ perfusion in the preterm infant.

BACKGROUND Near-infrared spectroscopy measures cerebral saturation (Csat), although correlation with cerebral blood flow remains unclear in premature newborns at risk for intraventricular hemorrhage (IVH). OBJECTIVES Compare Doppler markers of anterior cerebral artery (ACA) flow with Csat obtained during head ultrasound (HUS). METHOD Newborns

Introduction: Preterm (PT) birth is associated with increased risk of cardiovascular diseases (CVD) and heart failure. We previously reported left ventricular (LV) mitochondrial dysfunction in a rat model mimicking the deleterious conditions associated with PT birth. Whether mitochondrial function is altered in humans born PT and associated with LV function changes is unknown. We aimed to determine if serum humanin levels, a mitochondrial-derived peptide with cytoprotective effects, are altered in humans born PT and are associated with impaired myocardial function. Methods: Data were obtained from 55 young adults born PT ( Results: Individuals were evaluated at 23.3 (21.4, 25.3) years, and age and sex distribution were similar between groups. Median GA was 27.5 (26.2, 28.4) weeks in the PT group. Humanin levels (pg/ml) were 132.9 (105.1, 189.3) and 161.1 (123.6, 252) in the PT and the T groups, respectively (p=0.0414). LVEF was within the normal range and similar between groups. Lower LVEF was associated with lower humanin levels (p Conclusions: Serum humanin levels are lower in adult born PT. Since lower humanin levels are also associated with lower LVEF, our results suggest that mitochondrial alterations could play a role in the long-term adverse cardiovascular consequences of PT birth. Humanin analogs improve LV function in experimental models. Our results pave the way for future studies exploring humanin as a therapeutic avenue for the prevention and treatment of CVD in individuals born PT.

A large hepatic mixed echoic mass occupying the left fetal abdomen was identified at 266/7 weeks. The mass showed peripheral and internal vascularity. Other ultrasound findings included edema of the fetal head and face, macrosomia, shortened long bones, abnormal posture of hands, small stomach, polyhydramnios and biventricular hypertrophy. Fetal magnetic resonance imaging confirmed a hypervascular mass replacing the lateral left hepatic lobe, suggestive of a congenital hemangioma. The fetus was delivered by cesarean section at 282/7 weeks. The baby was stabilized at day 3 of life, and underwent successful selective tumor embolization. The baby remained stable for 3 days, then deteriorated with a progressive thickening of the myocardium. The child then passed away on day 11 from severe progressive hypertrophic cardiomyopathy, with almost complete obliteration of the left ventricular cavity; an autopsy was declined. Postnatal investigations reported a de novo heterozygous pathogenic HRAS variant (NM_005343.3(HRAS): c.35_36 delinsTT, p.Gly21Val), previously reported in 8 cases associated with the early, lethal form of Costello syndrome.

OBJECTIVES Primary objective of this pilot study is to evaluate the feasibility and acceptability of the NeuroN-QI and the study procedures. Secondary objectives are to assess the feasibility and acceptability of the NeuroN-QI by the nurses, assess the nurses' training needs about the components of the NeuroN-QI, and estimate the preliminary effects of the NeuroN-QI on infants' neurodevelopment as well as maternal stress and anxiety at infants' 36 weeks of gestational age. DESIGN A two-group pilot parallel randomized clinical trial stratified by center. METHODS The pilot study will be conducted in two neonatal intensive care units (NICUs). A sample of 24 mother-infant dyads born between 26 and 316/7 gestational age will be randomized into an experimental or control group. Fifty nurses will be recruited. The NeuroN-QI consists of four 2-hour skin-to-skin contact sessions/week with a 15-minute auditory stimulation by mothers with controlled ambient levels of light and noise. A 1-hour quiet period will follow where infants will rest in their incubator/crib with their mother's milk for olfactory stimulation and where the light and noise control will be continued. In the control group, mother-infant dyads will do four skin-to-skin contacts per week and receive standard care. Acceptability and feasibility of the NeuroN-QI in addition to maternal stress and anxiety will be measured through questionnaires, while infants' neurodevelopment will be assessed with Assessment of Preterm Infant Behaviour and General Movement Assessment. CONCLUSIONS This pilot trial will address knowledge gaps and generate evidence in neonatal care by evaluating the feasibility and acceptability of a multi-component developmental care intervention. IMPACT This project is an innovative step towards optimizing the neurodevelopmental trajectory of infants in NICUs and consequently promoting their long-term health outcomes. TRIAL REGISTRATION NCT04593095.

Adults born preterm are at a higher risk of cardiopulmonary disease and premature death. Preterm birth is associated with abnormalities in right ventricular (RV) structure and function, but the impact of bronchopulmonary dysplasia (BPD), a common complication of extremely preterm birth, on these parameters remains unknown.Are preterm birth and BPD associated with alterations in RV structure and function in early adulthood?Echocardiographic and spirometry data were obtained from the Health of Adults Born Preterm Investigation (HAPI). RV structure and performance were evaluated by using echocardiography, and respiratory function was assessed by using spirometry.The study comprised 86 young adults born preterm before 30 weeks of gestation, including 28 with moderate to severe BPD, and 85 adults of the same age born full term. Individuals were assessed at a mean age of 23 years. RV systolic function was altered in the preterm group, with lower tricuspid annular plane systolic excursion and lower RV s' and RV outflow tract velocity time integral values, especially in those born preterm with BPD. Nine (36%) participants born preterm with BPD, six (13%) participants born preterm without BPD, and six (8%) participants born full term had a tricuspid annular plane systolic excursion value 16 mm, a marker of RV systolic dysfunction (P value for the comparison between preterm no BPD and BPD, .032). No difference was found in RV diastolic function or estimates of pulmonary artery pressure between groups. Although respiratory function was altered in those born preterm, and more so in the case of BPD, no association was observed between spirometry indices of respiratory function and RV systolic function.Preterm birth is associated in adulthood with alterations in RV systolic function, which are more pronounced in the case of BPD.ClinicalTrials.gov; No.: NCT03261609; URL: www.clinicaltrials.gov.

Newborns with congenital diaphragmatic hernia (CDH) have varying degrees of pulmonary hypoplasia and pulmonary hypertension (PH), and there is limited evidence that cardiac dysfunction is present. We sought to study early neonatal biventricular function and performance in these patients by reviewing early post-natal echocardiography (ECHO) measurements and comparing them to normal term newborns. Retrospective case–control study reviewing clinical and ECHO data on term newborns with CDH and normal controls born between 2009 and 2016. Patients were excluded if major anomalies, genetic syndromes, or no ECHO available. PH was assessed by ductal shunting and tricuspid regurgitant jet velocity. Speckle-tracking echocardiography was used to assess myocardial deformation using velocity vector imaging. Forty-four patients with CDH and 18 age-matched controls were analyzed. Pulmonary pressures were significantly higher in the CDH cohort (systolic pulmonary arterial pressure to systolic blood pressure of 103 ± 13 vs. 78 ± 29%, p = 0.0001). CDH patients had decreased RV fractional area change (FAC − 28.6 ± 11.1 vs. 36.2 ± 9.6%, p = 0.02), tricuspid annular plane of systolic excursion (TAPSE—5.6 ± 1.6 vs. 8.6 ± 1.6 mm, p = 0.0001), and RV outflow tract stroke distance (8.6 ± 2.7 vs. 14.0 ± 4.5 cm, p = 0.0001) compared with controls. The left ventricular (LV) ejection fraction was similar in both groups, but CDH patients had a decreased LV end-diastolic volume by Simpson’s rule (2.7 ± 1.0 vs. 5.0 ± 1.8 mL, p = 0.0001) and LVOT stroke distance (9.7 ± 3.4 vs. 12.6 ± 3.6 cm, p = 0.004). Biventricular global longitudinal strain (GLS) was markedly decreased in the CDH population compared to controls (RV-GLS: − 9.0 ± 5.3 vs. − 19.5 ± 1.4%, p = 0.0001; LV GLS: − 13.2 ± 5.8 vs. − 20.8 ± 3.5%, p = 0.0001). CDH newborns have evidence of biventricular dysfunction and decreased cardiac output. Abnormal function may be a factor in the non-response to pulmonary arterial vasodilators in CDH patients. A two-pronged management strategy aimed at improving cardiac function, as well as reducing pulmonary artery pressure in CDH newborns, may be warranted.

Primary Subject area Neonatal-Perinatal Medicine Background Extremely preterm newborns are at risk of prolonged patency of the ductus arteriosus (PDA). Current literature has failed to indicate improvement in outcomes after exposure to strategies promoting ductal closure. As such, our center abandoned these practices in 2013. Objectives Describe the spontaneous PDA closure in premature infants, including those infants born at the extreme of gestational age (< 26 weeks). Design/Methods Retrospective study of newborns < 29 weeks, admitted within 24 hours after birth between 2015 and 2019 and without genetic or congenital anomalies. Newborns who were last known to be alive, with an available echocardiography, and who were not exposed to any intervention to accelerate PDA closure were included. Images were reviewed by experts blinded to the outcomes. Results 296 infants were analyzed. 37 (12%) did not survive their hospitalization, and 16 were exposed to interventions to accelerate ductal closure at some point during their lifetime (4 ligations, 4 catheter-closure, 5 ibuprofen and 3 acetaminophen). Out of the 243 remaining newborns, 214 had at least one echocardiography to ascertain ductal patency or closure (100% of those Conclusion The majority of newborns < 29 weeks, and even those at the extreme of gestational age (< 26 weeks) spontaneously closed their PDA before term-corrected age. While BPD rate was similar to previous cohorts, post-natal steroids use was high.

Objective To evaluate the change in the proportion of deaths/bronchopulmonary dysplasia (BPD) among premature infants (born Study design We examined 1249 infants (341 born Results Baseline characteristics were similar across sites and epochs. Medical treatment/ligation use remained stable at site 1 but declined progressively to 0% at site 2, indicating adherence to policy. We saw no difference in death/BPD among infants born at 26-29 weeks of gestational age (12%, 95% CI -1% to 24%). However, incidence of death/BPD increased by 31% among infants born Conclusions Adherence to a strict conservative policy did not impact death or BPD among 26 weeks but was associated with a significant rise in infants born

Pulmonary vascular disease and resultant pulmonary hypertension (PH) have been increasingly recognized in the preterm population, particularly among patients with bronchopulmonary dysplasia (BPD). Limited data exist on the impact of PH severity and right ventricular (RV) dysfunction at PH diagnosis on outcome. The purpose of this study was to evaluate if echocardiography measures of cardiac dysfunction and PH severity in BPD-PH were associated with mortality. The study is a retrospective analysis of the echocardiography at three months or less from time of PH diagnosis. Survival analysis using a univariate Cox proportional hazard model is presented and expressed using hazard ratios (HR). We included 52 patients with BPD and PH of which 16 (31%) died at follow-up. Average gestational age at birth was 26.3 ± 2.3 weeks. Echocardiography was performed at a median of 43.3 weeks (IQR: 39.0–54.7). The median time between PH diagnosis and death was 117 days (range: 49–262 days). Multiple measures of PH severity and RV performance were associated with mortality (sPAP/sBP: HR 1.02, eccentricity index: HR 2.02, tricuspid annular plane systolic excursion Z-score: HR 0.65, fractional area change: HR 0.88, peak longitudinal strain: HR 1.22). Hence, PH severity and underlying RV dysfunction at PH diagnosis were associated with mortality in BPD-PH patients. While absolute estimation of pulmonary pressures is not feasible in every screening echocardiography, thorough evaluation of RV function and other markers of PH may allow to discriminate the most at-risk population and should be considered as standard add-ons to the current screening at 36 weeks.

OBJECTIVE Describe renal function of preterm infants

The primary objective was to describe the early “natural history” of pulmonary hypertension (PH) in the premature population. The secondary objective was to describe factors associated with poor outcomes in the premature population with PH at 36 weeks post-menstrual age (PMA). Retrospective chart review of patients followed at our institution from 2000 to 2017 with echocardiographic (ECHO) evidence of PH at 36 weeks PMA, and born ≤ 32 weeks estimated gestational age (GA). Cox regression was used for survival analysis. Sixty-one patients with PH (26.5 ± 1.5 weeks at birth) were included. All PH patients had bronchopulmonary dysplasia (BPD), with 89% considered severe; 38% were small for gestational age. Necrotizing enterocolitis requiring surgery was common (25%). Use of post-natal steroids (HR 11.02, p = 0.01) and increased severity of PH (HR 1.05, p

Right ventricular (RV) function as assessed by deformation has been evaluated prenatally and after palliation in hypoplastic left heart syndrome (HLHS). However, limited data exist about the immediate postnatal cardiac adaptation and RV function in HLHS. We compared echocardiographic measures of cardiac performance in HLHS versus controls in their first week of life. As a secondary objective, we evaluated if markers at the first echocardiogram were associated with mid- and long-term outcomes. Clinical and echocardiographic data of patients with HLHS between 2013 and 2016 were reviewed. The study population was matched with controls whose echocardiograms were obtained due to murmur or rule out coarctation. Speckle-tracking echocardiography was used to assess deformation. Thirty-four patients with HLHS and 28 controls were analyzed. Age at echocardiogram was similar between HLHS and controls. The RV of HLHS was compared to both RV and left ventricle (LV) of controls. HLHS deformation parameters [RV peak global longitudinal strain (GLS), global longitudinal strain rate (GLSR)] and tricuspid annular plane systolic excursion (TAPSE) were decreased compared to RV of controls. The LV-fractional area change, peak GLS, GLSR, circumferential strain, and strain rate of controls were higher than the RV of HLHS. Calculated cardiac output (CO) was higher in the HLHS group (592 vs. 183 mL/kg/min, p = 0.0001) but similar to the combined LV and RV output of controls. Later mortality or cardiac transplantation was associated with the RV CO and RV stroke distance at initial echocardiogram. Cox proportional hazard regression determined that restriction at atrial septum, decreased initial RV stroke distance and decreased TAPSE had a higher risk of death or cardiac transplantation. TAPSE and RV stroke distance by velocity time integral had adequate inter-reader variability by Bland–Altman plot and Pearson’s correlation. Our study found that the HLHS RV deformation is decreased in the early postnatal period when compared to both LV and RV of controls, but deformation was not associated with mid- and long-term outcomes. Later mortality or cardiac transplantation was associated with decreased initial stroke distance and cardiac output. Early evaluation of patients with HLHS should include an assessment of stroke distance and future research should evaluate its implication in management strategies.

We report a rare case of an extremely low birth weight (ELBW) baby with oesophageal perforation secondary to an oro-gastric tube insertion and concomitant milk pleural effusion diagnosed on chest radiography. Area of perforation was determined with lateral chest radiography. This is the first case described in the literature of a milk pleural effusion in the context of perforation of the inferior third of the oesophagus in an ELBW infant.

To compare short-term and long-term outcomes of preterm infants born at

Background: For neonates with congenital heart disease (CHD), left-sided (LL) and right-sided (RL) single ventricular physiologies (LL, hypoplastic left heart syndrome; RL, tricuspid atresia or pulmonary atresia with intact ventricular septum) may demonstrate distinct changes in tissue saturation in the first 72 h of life. Near-infrared spectroscopy (NIRS) can measure regional cerebral saturation (Csat) and renal saturation (Rsat) to clarify differences between LL and RL over time. Objectives: Our primary objective was to measure changes in Csat and Rsat in the first 72 h of life using NIRS between CHD infants with LL compared to RL. The secondary objective was to correlate NIRS values to an echocardiographic marker of perfusion. Method: Newborns with hypoplastic left heart syndrome, tricuspid atresia, and pulmonary atresia with intact ventricular septum from 2013 to 2016 underwent routine NIRS monitoring. Csat, Rsat, and systemic saturations (SpO2) in the first 72 h of life were retrospectively analyzed and the echocardiographic descending aorta velocity time integral (VTI) was measured. Mixed effects models compared differences over time between LL and RL. Results: The final cohort included 13 LL, 12 RL, and 4 controls. Csat decreased for RL compared to LL (p = 0.005), while Rsat decreased for both (p = 0.008). Over time, SpO2 increased for LL but decreased for RL (p = 0.046). Compared to the controls, infants with CHD had lower Csat, lower Rsat, and lower SpO2. The descending aorta VTI was correlated with Rsat (R2 = 0.24, p = 0.02). Conclusion: NIRS Csat measures were better preserved in LL compared to RL. Rsat decreased in both groups through time. The correlation between the descending aorta VTI and Rsat suggests an association between NIRS measures of renal saturation and renal perfusion.

Objective The aim was to compare survival of patients with septic shock receiving or not hydrocortisone (HC) and to analyze the hemodynamic response to HC. Study Design It is a retrospective study of 62 premature neonates with septic shock (confirmed bacteremia) and/or necrotizing enterocolitis (NEC) stage 2 and above receiving inotropes with or without HC. We analyzed survival and hemodynamic response to HC. Results Thirty-nine (63%) premature neonates received HC and were compared with 23 (37%) who only received inotropes. Vasoactive index score (VAI) decreased and blood pressure, urine output, and oxygen requirements improved significantly following HC. Despite receiving more inotropes (VAI of 33 [20–53] vs 10 [8–20], p Conclusion HC was used in infants with increased inotropic support. HC during septic shock was associated with similar survival from episode, but with decreased survival at 1-year postmenstrual age.

Objective To compare echocardiography (ECHO) findings of patients with congenital diaphragmatic hernia (CDH) who required extracorporeal membrane oxygenation (ECMO) to non-ECMO treated patients. Study design We reviewed clinical and ECHO data of newborns with CDH born between 2009 and 2016. Exclusions included major anomalies, genetic syndromes, or no ECHO prior to ECMO. Pulmonary hypertension was assessed by ductal shunting and tricuspid regurgitant jet. Speckle tracking echocardiography (STE) assessed function by quantifying deformation. Results Patients with CDH (15 ECMO and 29 with no ECMO) were analyzed. Most patients had a left CDH (88.6%). Age at ECHO was similar between groups. Outborn status ( P = .009) and liver position ( P = .009) were associated with need for ECMO. Compared with non-ECMO patients, patients who required ECMO had significantly decreased left and right ventricular function by both conventional and STE measures, as well as decreased right and left ventricular output. The right ventricular eccentricity index was higher in ECMO vs non-ECMO patients (2.2 vs 1.8, P = .02). There was no difference in pulmonary hypertension between CDH groups. Conclusions Need for ECMO was associated with decreased left and right ventricular function, as assessed by standard and STE measures. There was no difference in pulmonary hypertension between non ECMO and ECMO patients. Abnormal cardiac function may explain nonresponse to pulmonary vasodilators in patients with CDH. Management strategies to improve cardiac function may reduce the need for ECMO in newborns with CDH.

BACKGROUND Twin pregnancies and fetal therapies are associated with increased risk of preterm delivery. Limited literature exists on outcomes for extremely preterm infants born in the context of a pregnancy complicated with twin-twin transfusion syndrome (TTTS). OBJECTIVES To compare mortality of preterm newborns who received laser therapy for TTTS to preterm controls born in the context of a dichorionic-diamniotic (di-di) pregnancy. Secondary outcomes are: short-term neonatal morbidities and neurodevelopmental measures at 18 months of corrected gestational age (cGA). DESIGN/METHODS Case-control retrospective study of all twins infant born RESULTS Thirty-three preterms with TTTS (TTTS-laser group) were compared to 101 preterms without TTTS (non-TTTS group). Demographic data and comparisons for short-term morbidities are presented in Table 1. TTTS status was not associated with increased mortality when adjusting for birth weight and antenatal steroids (Table 2). No differences were found for Bayley-3rd edition score, cerebral palsy, vision impairment, hearing impairment and growth parameters at 18-month cGA. CONCLUSION Extremely premature newborns exposed to fetal laser therapy due to TTTS had similar survival and neurodevelopmental outcomes compared to contemporaneous extremely preterm di-di twins.

Background Nitric oxide (NO) is a major endogenous regulator of vascular tone. Inhaled nitric oxide (iNO) gas has been investigated as treatment for persistent pulmonary hypertension of the newborn. Objectives To determine whether treatment of hypoxaemic term and near-term newborn infants with iNO improves oxygenation and reduces rate of death and use of extracorporeal membrane oxygenation (ECMO), or affects long-term neurodevelopmental outcomes. Search methods We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 1), MEDLINE via PubMed (1966 to January 2016), Embase (1980 to January 2016) and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to January 2016). We searched clinical trials databases, conference proceedings and reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. We contacted the principal investigators of studies published as abstracts to ascertain the necessary information. Selection criteria Randomised studies of iNO in term and near-term infants with hypoxic respiratory failure, with clinically relevant outcomes, including death, use of ECMO and oxygenation. Data collection and analysis We analysed trial reports to assess methodological quality using the criteria of the Cochrane Neonatal Review Group. We tabulated mortality, oxygenation, short-term clinical outcomes (particularly use of ECMO) and long-term developmental outcomes. Statistics: For categorical outcomes, we calculated typical estimates for risk ratios and risk differences. For continuous variables, we calculated typical estimates for weighted mean differences. We used 95% confidence intervals and assumed a fixed-effect model for meta-analysis. Main results We found 17 eligible randomised controlled studies that included term and near-term infants with hypoxia. Ten trials compared iNO versus control (placebo or standard care without iNO) in infants with moderate or severe severity of illness scores (Ninos 1996; Roberts 1996; Wessel 1996; Davidson 1997; Ninos 1997; Mercier 1998; Christou 2000; Clark 2000; INNOVO 2007; Liu 2008). Mercier 1998 compared iNO versus control but allowed back-up treatment with iNO for infants who continued to satisfy the same criteria for severity of illness after two hours. This trial enrolled both preterm and term infants but reported most results separately for the two groups. Ninos 1997 studied only infants with congenital diaphragmatic hernia. One trial compared iNO versus high-frequency ventilation (Kinsella 1997). Six trials enrolled infants with moderate severity of illness scores (oxygenation index (OI) or alveolar-arterial oxygen difference (A-aDO2)) and randomised them to immediate iNO treatment or iNO treatment only after deterioration to more severe criteria (Barefield 1996; Day 1996; Sadiq 1998; Cornfield 1999; Konduri 2004; Gonzalez 2010). Inhaled nitric oxide appears to have improved outcomes in hypoxaemic term and near-term infants by reducing the incidence of the combined endpoint of death or use of ECMO (high-quality evidence). This reduction was due to a reduction in use of ECMO (with number needed to treat for an additional beneficial outcome (NNTB) of 5.3); mortality was not affected. Oxygenation was improved in approximately 50% of infants receiving iNO. The OI was decreased by a (weighted) mean of 15.1 within 30 to 60 minutes after the start of therapy, and partial pressure of arterial oxygen (PaO2) was increased by a mean of 53 mmHg. Whether infants had clear echocardiographic evidence of persistent pulmonary hypertension of the newborn (PPHN) did not appear to affect response to iNO. Outcomes of infants with diaphragmatic hernia were not improved; outcomes were slightly, but not significantly, worse with iNO (moderate-quality evidence). Infants who received iNO at less severe criteria did not have better clinical outcomes than those who were enrolled but received treatment only if their condition deteriorated. Fewer of the babies who received iNO early satisfied late treatment criteria, showing that earlier iNO reduced progression of the disease but did not further decrease mortality nor the need for ECMO (moderate-quality evidence). Incidence of disability, incidence of deafness and infant development scores were all similar between tested survivors who received iNO and those who did not. Authors' conclusions Inhaled nitric oxide is effective at an initial concentration of 20 ppm for term and near-term infants with hypoxic respiratory failure who do not have a diaphragmatic hernia.