Persistent Pulmonary Hypertension Of The Newborn Research Articles

Mortality Prediction in Newborns With Persistent Pulmonary Hypertension: A Comparison of Four Illness Severity Scores.

This study aimed to compare the accuracy of four neonatal illness severity scores for predicting mortality in persistent pulmonary hypertension of the newborn (PPHN). This retrospective study included neonates diagnosed with PPHN between 2013 and 2022. The illness severity scores of four commonly used tools were completed for each infant: the Clinical Risk Index for Babies-II (CRIB-II), the Score for Neonatal Acute Physiology-Perinatal Extension version II (SNAPPE-II) in the first 12 h after admission and maximum oxygenation index (OI) and Vasoactive-Inotropic score (VIS) during the first 24 h (OI24max and VIS24max), 48 h (OI48max and VIS48max), and 72 h (OI72max and VIS72max) after admission. We constructed a receiver operating characteristic (ROC) curve to assess the discrimination and accuracy of the scores and determine the cutoff values for predicting mortality. We enrolled 146 neonates (131 survivors and 15 nonsurvivors). The CRIB-II, SNAPPE-II, maximum OI, and VIS were significantly higher in nonsurvivors than in survivors. An OI72max score of 41 showed the highest accuracy in predicting mortality (area under the ROC curve [AUC] of 0.88) with an OI48max score of 31 (AUC: 0.86) and VIS72max score of 430 (AUC: 0.80) showing good accuracy. The best CRIB-II and SNAPPE-II cutoff scores for predicting mortality were 4 (AUC: 0.74) and 32 (AUC: 0.84), respectively. The most accurate illness severity score for predicting mortality was OI72max score of 41. However, the OI48max, SNAPPE-II, and VIS72max scores also showed good accuracy. Mortality prediction using these scores can guide early management and close monitoring.

Metagenomic Analysis of Gut Microbiome of Persistent Pulmonary Hypertension of the Newborn.

Persistent pulmonary hypertension of the newborn (PPHN) is one of the most common diseases in the neonatal intensive care unit which severely affects neonatal survival. Gut microbes play an increasingly important role in human health, but there are rarely reported how gut microbiota contribute to PPHN. In our study, the metagenomic sequencing of feces from 12 PPHN's neonates and 8 controls were performed to expose the relation between neonatal gut microbes and PPHN disease. Firstly, we found that the abundance of Actinobacteria, Proteobacteria, Bacteroidetes were significantly increased in PPHN compared with controls, but the Firmicutes components was reduced. And some pathogenic strains (like Vibrio metschnikovii) were significantly enriched in the PPHN compared with controls. Secondly, functional annotation of genes found that PPHN up-regulated transmembrane transport, but down-regulated ribosome and ATP binding. Lastly, microbial metabolic pathway enrichment analysis indicated that some metabolic pathway in PPHN were conflicting and contradictory, showed that an abnormally increased metabolism, disturbed protein synthesis and genomic instability in the PPHN neonate. Our results contribute to understanding the changes in the species and function of gut microbiota in PPHN, thus providing a theoretical basis for the explanation and treatment of PPHN.

Influence of inhaled nitric oxide on bronchopulmonary dysplasia in preterm infants with PPHN or HRF at birth: a propensity score matched study.

Bronchopulmonary Dysplasia (BPD) is a chronic lung disease affecting preterm infants, with limited prevention and treatment options. Inhaled Nitric Oxide (iNO) is sometimes used to treat Persistent Pulmonary Hypertension of the Newborn (PPHN) and Hypoxemic Respiratory Failure (HRF), and its impact on BPD development remains debated. To assess whether iNO-related factors are potential contributors to the development of BPD Grade Ⅱ-Ⅲ in very premature infants (VPI) diagnosed with PPHN or HRF at birth using Propensity Score Matching (PSM). We conducted a retrospective cohort study of infants born at 22-32weeks gestation with PPHN or HRF, treated with iNO for over 3h. PSM matched groups by gestational age, birth weight, and gender, etc. Multivariate logistic regression evaluated the association between iNO treatment and BPD outcomes to identify influencing factors, while Restricted Cubic Spline (RCS) and mediation analysis examined iNO dose effects and potential mediators like mechanical ventilation time and oxygenation index (OI). A higher initial iNO dose was significantly associated with a reduced risk of BPD Grade Ⅱ-Ⅲ (adjusted OR = 0.68, 95% CI: 0.52-0.89, p < 0.01). Additionally, administration of iNO within the first 7 days of life was identified as an important influencing factor No significant mediation effects were observed for factors such as mechanical ventilation time and OI. A higher initial iNO dose within the first 7days was associated with a reduced risk of BPD Grade Ⅱ-Ⅲ in VPI with PPHN or HRF.

LncRNA H19 Promotes Angiogenesis in Mouse Pulmonary Artery Endothelial Cells by Regulating the HIF-1α/VEGF Signaling Pathway.

Persistent pulmonary hypertension of the newborn (PPHN) is a syndrome of acute respiratory failure characterized by systemic hypoxemia and elevated pulmonary arterial pressure, which leads to pathological changes in pulmonary vascular remodeling and endothelial cell function. Long non-coding RNA (lncRNA) H19 has been shown to be involved in the regulation of arterial endothelial cell function, but its regulatory role in PPHN is not fully understood. In the present study, mouse pulmonary artery endothelial cells (MPAECs) were cultured in a hypoxic conditions. Subsequently, the regulatory function of lncRNA H19 on MPAECs was explored by constructing adenoviruses knocking down and overexpressing lncRNA H19. The results revealed that the hypoxic conditions could induce the proliferation and migration of MPAECs, as well as the high expression of lncRNA H19 in MPAECs. Knockdown of lncRNA H19 expression in MPAECs reversed hypoxic environment-induced functional changes in endothelial cells, whereas overexpression of lncRNA H19 further enhanced the proliferation and migration of MPAECs. In addition, lncRNA H19 upregulated the hypoxia-inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) pathway through sponge of miNA-20a-5p, which in turn promoted changes in endothelial cell function. LncRNA H19 may interfere with vascular remodeling in hypoxia-induced pulmonary hypertension by upregulating the expression of HIF-1α and VEGF in vascular endothelial cells.

Antidepressant exposure patterns during pregnancy and risk of adverse newborn outcomes

Studies on antidepressant use during pregnancy often rely on a simplified exposure classification. We introduce a novel data-driven method to identify complex antidepressant exposure patterns during pregnancy and estimates the risk of 24-hour hospitalization, congenital heart defects (CHD) and persistent pulmonary hypertension of the newborn (PPHN).We constructed a nationwide cohort of all newborns born to women who filled at least one antidepressant prescription 24 weeks before pregnancy in Denmark during 1997–2016 using national registries. Antidepressant exposure patterns were identified by hierarchical cluster analysis based on number of antidepressants, Anatomical Therapeutic Chemical code and timing similarities. Risk ratios were estimated using the cumulative incidences in the inverse probability treatment weighted population.The study included 33,776 newborns. Discontinuing antidepressant use during pregnancy was associated with significant decreased risk of hospitalization compared to continued exposure to Citalopram throughout pregnancy. Moreover, discontinuing monotherapy was associated with significant decreased risk of PPHN compared to continued exposure to Citalopram. No risk ratios were statistically significant for the risk of CHD.Our study suggests a potential decreased risk of 24-hour hospitalization for any reason and PPHN if mothers discontinue antidepressant use during pregnancy as compared with continuous Citalopram use.

Experience of patent ductus arteriosus ligation during extracorporeal membrane oxygenation treatment in newborns with severe respiratory failure due to persistent pulmonary hypertension: a single-center retrospective study

BackgroundThe aim of this study is to summarize our center’s experience with patent ductus arteriosus (PDA) ligation during extracorporeal membrane oxygenation (ECMO) treatment in newborns with severe respiratory failure due to persistent pulmonary hypertension of the newborn (PPHN).MethodsWe retrospectively collected and analyzed clinical data from five newborns with severe respiratory failure due to PPHN who underwent PDA ligation during ECMO treatment at our hospital between January 2021 and August 2023.ResultsAll five patients had large PDAs, measuring 10 mm, 6 mm, 6 mm, 7 mm, and 6 mm, respectively. Significant left-to-right shunting through the PDA was observed after 29 h, 14 h, 3 h, 7 h, and 5 h of ECMO treatment, respectively, at which point successful PDA ligation was performed. The surgical durations were 52 min, 45 min, 55 min, 50 min, and 40 min, respectively. Post-ligation, blood lactate levels significantly decreased compared to preoperative values. Four patients were successfully weaned off ECMO, with ECMO support durations of 64 h, 92 h, 70 h, and 87 h, respectively. After ECMO removal, mechanical ventilation was discontinued after 5.2 days, 7.2 days, 9.5 days, and 5.5 days, respectively. None of the four surviving patients experienced complications such as residual shunting, bleeding, chylothorax, neurologic injury, pneumothorax, poor wound healing, or sepsis.ConclusionDuring ECMO treatment for PPHN in newborns with large PDAs, the direction of blood flow through the PDA should be closely monitored. PDA ligation is a feasible and reasonable intervention when pulmonary artery pressure decreases and left-to-right shunting through the PDA becomes evident.

Increased Risk of Persistent Pulmonary Hypertension of the Newborn in Twin Anaemia Polycythaemia Sequence Donors

Plain Language SummaryTwin anaemia polycythaemia sequence (TAPS) is a condition in identical twins, occurring in the womb and causing one twin to have too little blood (known as anaemia) and the other to have too much (known as polycythaemia). This can lead to various health problems in TAPS newborns from blood issues up to severe brain damage and even death. Breathing problems could occur due to their abnormal blood conditions. In our study, the prevalence of several adverse neonatal breathing conditions like persistent pulmonary hypertension of the newborn (PPHN), bronchopulmonary dysplasia (BPD), and respiratory distress syndrome (RDS) were studied. PPHN is a condition where blood vessels in the lungs of babies do not open properly, making it hard for babies to get enough oxygen into their blood. In BPD, the neonate’s lungs get inflamed and damaged, most often because of a prolonged time of ventilation. RDS happens because the baby’s lungs are not fully developed and cannot make enough surfactant, a substance that helps the lungs expand and stay open. This study aimed to investigate these breathing problems in TAPS twins and to identify potential risk factors for the development of these respiratory complications.

Impact of persistent pulmonary hypertension on cerebral oxygenation in infants with neonatal encephalopathy.

Persistent pulmonary hypertension of the newborn (PPHN) affects systemic oxygenation and may worsen brain injury in infants with neonatal encephalopathy (NE). Evidence suggests that higher cerebral regional oxygenation (crSO2) indicates derangement in cerebral autoregulation, energy metabolism, and blood flow following NE. Our aim was to evaluate the impact of PPHN on crSO2, in infants with NE treated with therapeutic hypothermia (TH). We retrospectively evaluated infants with NE and PPHN vs without PPHN, between 2018-2022. Linear regression analysis was performed to evaluate the impact of PPHN on crSO2 and total MRI score, adjusted for perinatal factors. 164 infants were analyzed, including 19(12%) with PPHN and 145(88%) without. PPHN-infants had significantly higher crSO2 during rewarming and post-rewarming compared to non-PPHN infants (87 ± 6 vs 80 ± 6, p = 0.001; 87 ± 5 vs 80 ± 7, p = 0.008, respectively), and a significantly higher total MRI score [7(2-19) vs 1(0-3), p < 0.001]. PPHN was significantly associated with higher crSO2 during rewarming (b = 6.21, 95% CI 2.37-10.04, p = 0.002) and post-rewarming (b = 8.60, 95% CI 2.28-14.91, p = 0.009), and total MRI score (b = 7.42, 95% CI 4.88-9.95, p < 0.001). PPHN was associated with higher crSO2 during and after rewarming, and worse brain MRI score, indicating a significant impact of PPHN on brain injury in infants with NE undergoing TH. Cerebral oxygenation was significantly higher in infants with neonatal encephalopathy (NE) and persistent pulmonary hypertension (PPHN) compared to infants without PPHN, during the rewarming and post-rewarming periods of therapeutic hypothermia (TH). PPHN is associated with brain injury in infants with NE undergoing TH. In infants with NE and PPHN, monitoring of cerebral oxygenation would help detect infants at higher risk of adverse outcomes.

Oral sildenafil versus bosentan for treatment of persistent pulmonary hypertension of the newborn: a randomized controlled trial

BackgroundAccess to inhaled nitric oxide (iNO) is limited in low resource settings due to non-availability and high cost. There is a need for research on low-cost alternative therapies for management of persistent pulmonary hypertension of the newborn (PPHN). We aimed to compare oral sildenafil and bosentan as monotherapy in the treatment of neonates with PPHN.Study designIn this single-centre open-label randomized controlled trial (RCT), term and late preterm neonates with PPHN, defined as pulmonary arterial systolic pressure (PASP) > 35 mmHg and requiring fraction of inspired oxygen (FiO2) > 0.21, were randomized to receive oral sildenafil and bosentan. The primary outcome was reduction of PASP by 25% within 48 h after start of drug.ResultsThirty-six neonates were analyzed (18 in each group). Initial PASPs were similar in both groups. The median (IQR) time for the primary outcome (PASP to reduce by 25% within 48 h) was 36 (24–48) h and 96 (48–120) h in sildenafil and bosentan groups respectively (p = 0.008). There was also a higher need to add other pulmonary vasodilators in bosentan group as compared to sildenafil group (p = 0.006).ConclusionSildenafil was associated with quicker reduction of PASP and FiO2 in neonates with PPHN, as compared to bosentan. Large multicentre blinded trials to assess efficacy and safety of bosentan in comparison with other pulmonary vasodilators would help to get a clearer understanding of its role in the management of PPHN, particularly for use in resource-limited settings that lack iNO.Clinical trial registration:https://ctri.nic.in/Clinicaltrials/rmaindet.php? trialid=63997&EncHid=39716.16132&modid=1&compid=19[CTRI/2022/06/043328].

Clinical Characteristics and Outcomes of SARS-CoV-2 Infection in Neonates with Persistent Pulmonary Hypertension of the Newborn (PPHN): A Systematic Review.

To analyze the clinical characteristics and outcomes of SARS-CoV-2 infection in neonates with PPHN to identify neonatal cases at risk to develop severe illness. For this systematic review, we adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and searched Medline, Embase, CINAHL, and PubMed for studies on the development of COVID-19 in neonates with PPHN, published from 1 December 2019 to 29 February 2024, with an English language restriction. Of the 2406 papers that were identified, 21 articles were included in the systematic review. Studies involving thirty-six neonates with PPHN and infected with SARS-CoV-2 were analyzed (twenty-nine survived, six died, and one is still hospitalized). The main causes of PPHN in neonates who had COVID-19 were neonatal respiratory distress syndrome (NRDS) (41.7%), meconium-stained amniotic fluid (MSAF) (16.7%), preterm premature rupture of membranes (PPROM) (11.1%), hypoxic ischemic encephalopathy (HIE) (5.5%), pneumonia (5.5%), and idiopathic (2.8%). Most of those neonates were male (33.3%), belonged to Indian ethnicity (50%), and were delivered via caesarean section (44.4%). COVID-19 in cases with PPHN commonly occurred in neonates born with a pregnancy range from 32 to <37 weeks (moderate to late preterm) (36.1%). The maternal severity of COVID-19 was reported to be severe in three cases only (8.3%); however, SARS-CoV-2 infection in neonates with PPHN was either severe (44.4%) or critical (22.2%). Most of these neonates experienced acute respiratory distress syndrome (ARDS) (58.3%). Early and late multisystem inflammatory syndrome in neonates (MIS-N) were reported in 50% and 11.1%, respectively. A high proportion of neonates were admitted to the intensive care unit (ICU) (58.3%) or needed mechanical ventilation (MV) (47.2%). Neonates with concurrent PPHN and SARS-CoV-2 infection who died had worse severity of COVID-19 [i.e., severity of COVID-19 was critical in 10% (neonates with PPHN who survived group) vs. 83.3% (neonates with PPHN who died group); p = 0.026]. Neonates with PPHN and COVID-19 had a higher relative risk of death if they received more antibiotics (RR 4.14, 95% CI 0.64-6.88) and if their COVID-19 was defined as critical (RR 2.84, 95% CI 0.86-9.39). Male neonates with PPHN and COVID-19 (RR 2.60, 95% CI 0.30-1.17) and those requiring prolonged invasive positive pressure ventilation (RR 2.22, 95% CI 0.64-7.73) also showed an increased relative risk for death. COVID-19 in neonates with PPHN is challenging and may be associated with increased mortality, severity, ICU admission, ARDS, MIS-N, and MV usage. The results should be interpreted with caution owing to the small number of studies and substantial heterogeneity and indicate a need for future research in this area. Due to its benefits, testing for SARS-CoV-2 should be encouraged for newborns with symptoms consistent with COVID-19, especially in neonates with a history of SARS-CoV-2 exposure. Effective protection measures should be implemented during delivery and post-delivery care as necessary.

Neurodevelopmental outcome in children between one and five years after persistent pulmonary hypertension of term and near-term newborns.

Persistent pulmonary hypertension of the newborn (PPHN) is a serious condition that affects 1-2 per 1,000 newborns. Scientific data report the existence of neurological developmental abnormalities between 10 and 30%, but the description of these disorders linked with this situation of cerebral hypoxia and haemodynamic failure remains poorly documented. The main goal of this study was to describe the prevalence of neuro-psychomotor developmental disorders in children aged between one and five years old who have been hospitalised at birth in a neonatal intensive care unit for the management of PPHN. All of the newborns ≥34 weeks of gestational age (WGA) with PPHN, treated with inhaled nitric oxide in our neonatal intensive care unit between January 2015 and December 2019 were retrospectively enrolled. An ASQ-3 standardised questionnaire, adapted to the appropriate age (12, 24, 36, 48 and 60 months) was performed by the parents. Fifty-five children (81% of answers) with a median age of 36 months (11-68), whose real age was close to the one of the questionnaire (12, 24, 36, 48 and 60 months), have been included in this study. There was 47% of pathological score [borderline: less than 1 standard deviation (SD) or suspect: less than 2SD] in at least one of the five studied domains, mainly in communication (25%) and individual and social skills (22%), despite a high overall score of 250 [220; 285] out of 300 that improved with age. This study showed a significant prevalence of neuro-psychomotor developmental disorders which justifies making more accessible a prolonged and adapted follow-up for early and multidisciplinary screening and management of these children with PPHN history. Larger cohorts are needed to better explore long term outcome of these vulnerable term neonates.

63 Utilization of vasopressin and norepinephrine in neonates with cardiorespiratory compromise: A multicenter retrospective cohort study in Canada

Abstract Background Data regarding neonatal clinical experience with Vasopressin (VA) and Norepinephrine (NE) are limited to small studies. The lack of large-scale studies with safety and efficacy data is preventing the widespread adoption of these agents. Objectives To describe epidemiological data on utilization of NE and VA in neonates including their indications, effectiveness and overall outcomes across 3 tertiary Neonatal Intensive Care Units (NICU) in Canada. Design/Methods This retrospective cohort study involved neonates who received NE or VA between January 1, 2015-December 31, 2020 at 3 tertiary NICUs. Data regarding demographic information, indications of use, dosing details, and clinical outcomes were described using mean, standard deviations (SD), frequencies and percentages. When appropriate, a comparative analysis was performed using Mann-Whitney U tests or the chi-square test as appropriate. Post-initiation changes in physiological variables and laboratory parameters over time were analyzed using repeated measure ANOVA. Results 133 neonates (VA:70, NE:63) were included in this study. Baseline demographic features, clinical characteristics at initiation, indication of use, dosing details and clinical response in neonates exposed to both agents are summarized in Table 1. VA was commonly used for oxygenation failure due to persistent pulmonary hypertension of the newborn (PPHN), while NE was commonly used for hypotension due to septic shock. NE was frequently used as a 1st line inotropic agent, whereas VA was used more as an additive agent [30 (47.6%) vs 12 (18.6%); p=&amp;lt;0.001]. During treatment, lower sodium levels were recorded in the VA group vs the NE group [126.5 (8.6) vs 132 (7); p=.035], but other safety parameters were similar. The time to reach predefined stability parameters were similar in both groups. Significant improvement in physiological parameters were seen over time with both agents (Figure 1). Mortality within 7 days of use was high in the cohort, but comparable between VA and NE groups [18 (25.7%) vs 22 (34.9%), p=0.206]. Other neonatal morbidities were comparable between groups (Table 1). Conclusion This multicenter study provides pragmatic insights into the current use of NE and VA in neonates. Our study reports the effective use of each agent in distinct patient subgroups. This cohort represented neonates with high illness severity; however, exposure to either agent did not independently increase the risk of mortality or adverse outcomes. Further prospective studies exploring its optimal use and cardiopulmonary effects would be interesting.

Clinical Analysis of Inhaled Nitric Oxide Therapy in Preterm Infants at Different Gestational Ages: A National Retrospective Multicenter Study.

This study aimed to investigate clinical features of inhaled nitric oxide (iNO) in preterm infants with a gestational age (GA) < 34 weeks in China. The clinical data of 434 preterm infants with GA < 34 weeks, treated with iNO in the neonatology departments of eight Class A tertiary hospitals in China over a 10-year period from January 2013 to December 2022, were included in this retrospective multicenter investigation. The infants were divided into three groups based on GA: 24 to 27 weeks (extremely preterm infants), 28 to 31 weeks (very preterm infants), and 32 to 33 weeks (moderate preterm infants). The use of iNO, perinatal data, incidence and mortality of indication for iNO treatment, therapeutic effects of iNO, incidence of short-term complications for iNO treatment, and mortality were compared among these three groups. Over the past 10 years, the proportion of iNO use was highest in extremely preterm infants each year. The lower the GA, the higher the iNO use rate: 4.20% for GA 24 to 27 weeks, 1.54% for GA 28 to 31 weeks, and 0.85% for GA 32 to 33 weeks. There was no significant difference in the therapeutic effect of iNO among the three groups. The incidence of neonatal pulmonary hemorrhage, neonatal shock, late-onset diseases, retinopathy of prematurity requiring intervention, intracranial hemorrhage (grade 3 or 4), periventricular leukomalacia, neonatal necrotizing enterocolitis (≥stage II), and moderate to severe bronchopulmonary dysplasia was highest in extremely preterm infants and increased with decreasing GA. Mortality was negatively correlated with GA and birth weight. The highest rate of iNO treatment in 24 to 27 weeks' preterm infants was due to hypoxic respiratory failure (HRF), whereas the highest rate of iNO treatment in 32 to 33 weeks' preterm infants was due to documented persistent pulmonary hypertension of the newborn (PPHN). The rates of iNO treatment due to HRF and documented PPHN were 54.3 and 60.6%, respectively, in extremely preterm infants, significantly higher than in very preterm and moderate preterm infants (all p < 0.05). Within the same GA group, the proportion of preterm infants treated with iNO for HRF was lower than that for documented PPHN (all p < 0.05), but there was no statistically significant difference in mortality between HRF and documented PPHN treated with iNO (all p > 0.05). Among preterm infants with GA < 34 weeks, the rate of iNO usage was highest in extremely preterm infants. However, iNO failed to improve the clinical outcome of extremely preterm infants with refractory hypoxemia, and there was no significant difference in the therapeutic effect of iNO among preterm infants with different GAs.

Impact of Persistent Pulmonary Hypertension of the Newborn in Neonates with Dextro-transposition of the Great Arteries

This study aimed to assess the impact of persistent pulmonary hypertension of the newborn (PPHN) on perioperative morbidity and mortality in patients with dextro-transposition of the great arteries. Secondarily, we evaluated the association between postoperative outcomes and intraoperative variables including the duration of cardiopulmonary bypass, cerebral oxygen desaturation, and hypotension. Retrospective observational study. Beatrix Children's Hospital, University Medical Center Groningen, Groningen, the Netherlands, over a 14-year period from January 2005 to December 2018. The study included 99 consecutive patients with simple dextro-transposition of the great arteries with or without a ventricular septal defect. All patients received preoperative management including intravenous prostaglandin E1 and, when necessary, a balloon atrial septostomy. Patients were then scheduled for an arterial switch operation. Patients were divided into a PPHN and a non-PPHN group. The outcomes assessed included mortality (overall, preoperative, 30-day postoperative and late mortality) and postoperative morbidity (length of ventilatory support, intensive care unit and hospital stay, delayed sternal closure and resternotomy). PPHN was present in 31% of patients. Overall mortality was 8.1%, with no difference between PPHN and non-PPHN patients (9.7 v 7.4%, p = 0.70). PPHN had no effect on morbidity outcomes. A lower weight at birth was associated with preoperative mortality. Duration of cardiopulmonary bypass and intraoperative hypotension were associated with longer intensive care unit stay. Intraoperative hypotension and cerebral oxygen desaturation had no significant impact on mortality. PPHN did not significantly affect perioperative morbidity and mortality in d-TGA patients, suggesting a more favorable prognosis than previously reported.

Echocardiographic markers at diagnosis of persistent pulmonary hypertension of the newborn.

Clinical parameters along with echocardiographic markers are used to interrogate the haemodynamics in persistent pulmonary hypertension of the newborn (PPHN). The aim of this study was to compare different echocardiographic markers in recent cohort of newborn infants with and without PPHN. In this retrospective study, common echocardiographic markers were examined in infants>34weeks' gestation with PPHN (cases) and without PPHN (controls). Infants with congenital heart disease were excluded. Binary regression testing was used to evaluate echocardiographic markers predicting PPHN and death. In addition, diagnostic accuracy testing of echocardiographic markers using ROC was also performed. Intra-observer reliability for echocardiographic markers was examined using coefficient of variation (CoV) and intraclass correlation. Fifty-two infants were studied; 22 (42 %) infants with PPHN had significantly higher oxygen requirement, oxygenation index and ventilation days when compared with controls. Echocardiographic markers such as TR Vmax, S/D TR, PAAT, TAPSE and eccentricity index (EI) were significantly different between cases and controls. Receiver operator characteristics analysis of echocardiographic markers revealed TR Vmax 0.96 (0.9-1.0), S/D TR 0.95 (0.87-1.0) and end systolic EI 0.94 (0.87-1.0). These markers were found to predict death in this cohort of infants. CoV and Intra-observer reliability was good for various echocardiographic markers. Among the various echocardiographic markers studied, TR Vmax when present along with S/D TR and end systolic EI had good intra-observer reliability and were diagnostic of PPHN and predicted death in this cohort. Future trials could use these markers in studies examining PPHN.

Current Pharmaceutical Strategies in the Management of Persistent Pulmonary Hypertension of the Newborn (PPHN): A Comprehensive Review of Therapeutic Agents.

Persistent Pulmonary Hypertension of the Newborn (PPHN) is a life-threatening condition characterized by the failure of normal circulatory transition after birth, leading to sustained pulmonary hypertension and severe hypoxemia. Despite advancements in neonatal care, PPHN remains a significant cause of morbidity and mortality among newborns, particularly in full-term and near-term infants. This review provides a comprehensive overview of current pharmaceutical strategies for managing PPHN, focusing on various therapeutic agents' mechanisms, efficacy, and safety. Key interventions include inhaled nitric oxide, which has become the standard treatment for reducing pulmonary vascular resistance, alongside prostacyclin analogs, phosphodiesterase inhibitors, and endothelin receptor antagonists. Additionally, extracorporeal membrane oxygenation (ECMO) is highlighted as a critical intervention for severe, refractory cases. The review also discusses emerging therapies and the potential role of personalized medicine in improving treatment outcomes. Despite the progress made, challenges remain, including the timely diagnosis of PPHN and the need for accessible treatments in resource-limited settings. As research continues to uncover the underlying pathophysiology of PPHN, it is crucial to develop more targeted and effective pharmaceutical strategies. This review aims to inform clinicians and researchers of the current state of PPHN management and the ongoing advancements that may shape future therapeutic approaches.

Persistent pulmonary hypertension and short-term neurological outcomes in infants with moderate to severe hypoxic ischemic encephalopathy.

Our aim was to investigate the relationship between persistent pulmonary hypertension of the newborn (PPHN), short-term brain injury or death, and clinical parameters in infants with moderate to severe hypoxic ischemic encephalopathy (HIE). Retrospective single-center cohort study of 274 HIE infants, 230 underwent Therapeutic Hypothermia (TH). Primary outcome was severe HIE brain injury on MRI and/or death within the first month of life in relation to presence and severity of PPHN (clinical or echocardiographic). Secondary outcomes were HIE brain injury pattern, abnormal electroencephalogram (EEG), seizures, clinical, and laboratory differences. A logistic regression model was performed to evaluate PPHN presence and severity as risk factor for brain injury or death. The combined outcome of severe brain injury or death was higher in the clinical PPHN group vs non-PPHN (32.6 vs 22.8%, p = 0.014). There was no difference in brain injury, seizure burden or EEG abnormalities associated with PPHN, despite those with PPHN being sicker with higher ventilation needs and worse laboratory values than those without. Mortality had a strong correlation with echocardiographic PPHN with the highest incidence in severe (36%) vs moderate (7.7%) vs mild PPHN (10%, p = 0.002). Highest mortality had those with 'early exit' who did not complete 72 hours of TH (71.4%). In infants with HIE, PPHN was not associated with increased risk of brain injury as evident on MRI, nor seizure burden, despite being sicker with worse laboratory values. However, mortality rates were higher the worse the PPHN, especially with early exit from TH.

Vasodilators for persistent pulmonary hypertension of the newborn: A network meta-analysis.

To compare the efficacy and safety of different vasodilators in the treatment of persistent pulmonary hypertension of the newborn (PPHN) by a Bayesian network meta-analysis. We searched databases (Cochrane, PubMed, Embase, and Web of Science) from January, 1990 up to December, 2023. Randomized controlled trials on the use of vasodilators in the treatment of PPHN. We extracted details of population, intervention, and outcome indicators. R and STATA software were used for data analysis. Sixteen articles were included, encompassing 776 neonates with PPHN. Among them, 12articles were included in the quantitative analysis. The vasodilators included Sildenafil, Bosentan, Milrinone, Magnesium, Adenosine, and Tadalafil. The Bayesian network meta-analysis results suggested that compared to placebo, Milrinone [OR = 0.125, 95% CI (0.0261, 0.562)], Sildenafil [OR = 0.144, 95% CI (0.0428, 0.420)], and Sildenafil_Milrinone [OR = 0.0575, 95% CI (0.00736, 0.364)] reduced the mortality, but the difference among the three was not significant. There was also no significant difference in the incidence of hypotension, the duration of mechanical ventilation, and the use of extracorporeal membrane oxygenationamong the vasodilators. Compared to Bosentan, Adenosine was more effective in reducing the oxygenation index [MD = -12.78, 95% CI (-25.56, -0.03)], and Magnesium was less effective in reducing the oxygenation index than Sildenafil [MD = 5.19, 95% CI (1.23, 9.2)]. Milrinone, Sildenafil, and Sildenafil_Milrinone reduced the mortality of neonates with PPHN. More clinical trials are needed to verify the efficacy and safety of vasodilators in the treatment of PPHN.

A multicenter epidemiological survey of iNO use in preterm infants in China.

To investigate the use of inhaled nitric oxide (iNO) in hospitalized preterm infants in China over 10 years and its clinical outcomes. A total of 616 premature infants who were administered iNO in the Neonatology Departments of 5 Class A tertiary hospitals in China for ten years from January 2013 to December 2022 were included retrospectively. Based on their enrollment periods, the patients were divided into two groups: Group 1 from January 2013 to December 2017 and Group 2 from January 2018 to December 2022, respectively. The perinatal characteristics, short-term clinical outcomes, and mortality rates were compared between these two groups. The utilization of iNO in preterm infants grew annually over the past10 years; the utilization of iNO in Group 2 infants increased approximately one-fold when compared with Group 1 (1.52% vs. 0.80%, p < .001), and the increase was greater in gestational age (GA) < 34 weeks compared with 34-36 weeks preterm infants. Moreover, the iNO usage in Group 1 infants with GA < 34 weeks increased from 1.14% to 2.46% and 0.60% to 0.99% in 34-36 weeks preterm infants (p < .001) in Group 2, respectively. Apart from a smaller GA (32.9 w vs. 33.5 w, p < .001) and birth weight (BW, 1900 g vs. 2141 g, p < .001), the initial [14 parts per million (ppm) versus 10 ppm, p < .001] and maximum (15 ppm vs. 10 ppm, p < .001) doses of Group 2 were larger; however, their recent clinical outcomes did not improve with increasing iNO utilization (p > .05)as compared to Group 1, respectively. Although the overall iNO preterm mortality rates over the past 10 years were 25.8%, the mortality rates for preterm infants at 34-36 weeks were significantly lower than for preterm infants at GA < 34 weeks (15.4% vs. 33.8%, p < .001). Nonetheless, no improvement in mortality was observed in Group 2 preterm infants with GA < 34 weeks for the past 5 years when compared with Group 1 (32.9% vs. 35.8%, p > .05) infants, and significantly lower mortality rates were noticed in preterm infants with 34-36 weeks (11.2% vs. 22.7%, p < .001). Patients with hypoxic respiratory failure (HRF) or persistent pulmonary hypertension of the newborn (PPHN) iNO preterm infants did not show lower mortality rates with the increase of iNO use rate (p > .05). The overall mortality rates of preterm PPHN infants with iNO were lower than that of HRF (20.2% vs. 36.5%, p < .001), while the mortality rates of Group 2 preterm PPHN infants with iNO significantly lower than that of HRF (17.7% vs 36.0%, p < .001). The iNO has been extensively used in Chinese preterm infants over the past 10 years, this increase was more significant in preterm infants with GA < 34 weeks. Moreover, preterm infants using iNO have lower GA and BW, larger initial and maximum doses, and more aggressive strategies in the last past 5 years. Although iNO use in preterm infants with GA of 34-36 weeks has significantly reduced mortality, mortality rates and short-term clinical outcomes of iNO in preterm infants <34 weeks of GA has no obvious improvement. Further studies are required to investigate the efficacy and safety of iNO in preterm infants <34 weeks of GA.

International treatment outcomes of neonates on extracorporeal membrane oxygenation (ECMO) with persistent pulmonary hypertension of the newborn (PPHN): a systematic review

BackgroundPPHN is a common cause of neonatal respiratory failure and is still a serious condition and associated with high mortality.ObjectivesTo compare the demographic variables, clinical characteristics, and treatment outcomes in neonates with PHHN who underwent ECMO and survived compared to neonates with PHHN who underwent ECMO and died.MethodsWe adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline and searched ProQuest, Medline, Embase, PubMed, CINAHL, Wiley online library, Scopus and Nature for studies on the development of PPHN in neonates who underwent ECMO, published from January 1, 2010 to May 31, 2023, with English language restriction.ResultsOf the 5689 papers that were identified, 134 articles were included in the systematic review. Studies involving 1814 neonates with PPHN who were placed on ECMO were analyzed (1218 survived and 594 died). Neonates in the PPHN group who died had lower proportion of normal spontaneous vaginal delivery (6.4% vs 1.8%; p value > 0.05) and lower Apgar scores at 1 min and 5 min [i.e., low Apgar score: 1.5% vs 0.5%, moderately abnormal Apgar score: 10.3% vs 1.2% and reassuring Apgar score: 4% vs 2.3%; p value = 0.039] compared to those who survived. Neonates who had PPHN and died had higher proportion of medical comorbidities such as omphalocele (0.7% vs 4.7%), systemic hypotension (1% vs 2.5%), infection with Herpes simplex virus (0.4% vs 2.2%) or Bordetella pertussis (0.7% vs 2%); p = 0.042. Neonates with PPHN in the death group were more likely to present due to congenital diaphragmatic hernia (25.5% vs 47.3%), neonatal respiratory distress syndrome (4.2% vs 13.5%), meconium aspiration syndrome (8% vs 12.1%), pneumonia (1.6% vs 8.4%), sepsis (1.5% vs 8.2%) and alveolar capillary dysplasia with misalignment of pulmonary veins (0.1% vs 4.4%); p = 0.019. Neonates with PPHN who died needed a longer median time of mechanical ventilation (15 days, IQR 10 to 27 vs. 10 days, IQR 7 to 28; p = 0.024) and ECMO use (9.2 days, IQR 3.9 to 13.5 vs. 6 days, IQR 3 to 12.5; p = 0.033), and a shorter median duration of hospital stay (23 days, IQR 12.5 to 46 vs. 58.5 days, IQR 28.2 to 60.7; p = 0.000) compared to the neonates with PPHN who survived. ECMO-related complications such as chylothorax (1% vs 2.7%), intracranial bleeding (1.2% vs 1.7%) and catheter-related infections (0% vs 0.3%) were more frequent in the group of neonates with PPHN who died (p = 0.031).ConclusionECMO in the neonates with PPHN who failed supportive cardiorespiratory care and conventional therapies has been successfully utilized with a neonatal survival rate of 67.1%. Mortality in neonates with PPHN who underwent ECMO was highest in cases born via the caesarean delivery mode or neonates who had lower Apgar scores at birth. Fatality rate in neonates with PPHN who underwent ECMO was the highest in patients with higher rate of specific medical comorbidities (omphalocele, systemic hypotension and infection with Herpes simplex virus or Bordetella pertussis) or cases who had PPHN due to higher rate of specific etiologies (congenital diaphragmatic hernia, neonatal respiratory distress syndrome and meconium aspiration syndrome). Neonates with PPHN who died may need a longer time of mechanical ventilation and ECMO use and a shorter duration of hospital stay; and may experience higher frequency of ECMO-related complications (chylothorax, intracranial bleeding and catheter-related infections) in comparison with the neonates with PPHN who survived.