Persistent Pulmonary Hypertension Of The Newborn Research Articles

A Nomogram Prediction Model for Persistent Pulmonary Hypertension of the Newborn in Neonates Hospitalized for the First Time After Birth.

Persistent pulmonary hypertension of the newborn (PPHN) is one of the critical neonatal diseases associated with high morbidity and mortality. This study attempted to conduct a nomogram prediction model for performing early identification of PPHN and providing effective information for clinical practice. A total of 456 newborns who first admitted to the hospital after birth were included in the analysis, including 138 newborns with PPHN and 318 newborns without PPHN (as controls). The optimal predictive variables selection was performed based on LASSO (least absolute shrinkage and selection operator) regression and multivariate logistic regression. Using the selected variables, a nomogram prediction model was developed. To validate the model, the model was assessed using the receiver operating characteristic curve, calibration plot, and clinical impact curve. Six predictors, namely, gestational age, neonatal respiratory distress syndrome, the levels of hemoglobin and creatine kinase-MB, gestational thyroid dysfunction, and Pao2, were identified by LASSO and multivariate logistic regression analysis from the original 30 variables studied. The constructed model, using these predictors, exhibited favorable predictive ability for PPHN, with an area under the receiver operating characteristic of 0.897 (sensitivity = 0.876, specificity = 0.785) in the training set and 0.871 (sensitivity = 0.902, specificity = 0.695) in the validation set, and was well calibrated, as indicated by the PHosmer-Lemeshow test values of 0.233 and 0.876 for the training and validation sets, respectively. The model included gestational age, neonatal respiratory distress syndrome, the levels of hemoglobin and creatine kinase-MB, gestational thyroid dysfunction, and Pao2 had good prediction performance for predicting PPHN among newborns first admitted to the hospital after birth.

Adapting nitric oxide: A review of its foundation, uses in austere medical conditions, and emerging applications

Nitric oxide was first identified as a novel and effective treatment for persistent pulmonary hypertension of the newborn (PPHN), and has since been found to be efficacious in treating acute respiratory distress syndrome (ARDS) and pulmonary hypertension. Physicians and researchers have also found it shows promise in resource-constrained settings, both within and outside of the hospital, such as in high altitude pulmonary edema (HAPE) and COVID-19. The treatment has been well tolerated in these settings, and is both efficacious and versatile when studied across a variety of clinical environments. Advancements in inhaled nitric oxide continue, and the gas is worthy of investigation as physicians contend with new respiratory and cardiovascular illnesses, as well as unforeseen logistical challenges.

Risks of adverse outcomes and neonatal morbidity in pregnant women with SARS-CoV-2 depending on the trimester of infection

Introduction. COVID-19 in pregnant women adversely affects the course of the disease, pregnancy outcomes, and morbidity in newborns. However, studies on the impact of the gestational age at which SARS-CoV-2 infection occurs on the risk of neonatal morbidity are lacking.Aim. To assess the risks of adverse pregnancy outcomes and neonatal morbidity in newborns depending on the gestational age at which women were infected with SARS-CoV-2.Materials and methods. The study included 215 women infected with SARS-CoV-2 in the first, second, and third trimesters of pregnancy and 50 uninfected pregnant women. Newborns formed corresponding groups. Data for analysis (general clinical, anamnestic, childbirth outcomes, and newborn condition) were obtained from the records of pregnant, laboring, and postpartum women.Results. In 4.7% of women infected in the first trimester, pregnancy was accompanied by spontaneous miscarriage and in 1.9% by ectopic pregnancy development. In 1.9% of women infected in the second trimester, antenatal fetal demise in a full-term pregnancy was detected. Patients infected with SARS-CoV-2 more often underwent cesarean section (31.7%). The median weight and height of newborns from mothers infected with SARS-CoV-2 were lower than in the control group. The Apgar score at the first minute showed no differences, but at the fifth minute, it was lower than in the control group. Newborns from mothers infected with SARS-CoV-2 were more frequently diagnosed with cerebral ischemia (26.3%), motor disorder syndrome (20.7%), and persistent fetal circulation (27.8%). Only in newborns from mothers with SARS-CoV-2 were hypertensive syndrome (13.1%), posthypoxic cardiomyopathy (13.1%), and intraventricular hemorrhages (10.1%) detected. The Apgar score at the first minute in newborns from mothers infected with SARS-CoV-2 in the third trimester of pregnancy was higher compared to infections in the second trimester. Neonatal morbidity in this cohort of newborns was characterized by a high frequency of cerebral ischemia, motor disorder syndrome, hypertensive syndrome, and persistent fetal circulation. Infection in the third trimester increased the risk of neonatal morbidity: cerebral ischemia by 5.6 times, motor disorder syndrome by 13.78 times, hypertensive syndrome by 8.61 times, and persistent fetal circulation by 2.76 times.Conclusion. COVID-19 during pregnancy increases the risks of adverse outcomes and the development of neonatal pathology in newborns. The frequency of their development is associated with the gestational age at which women were infected. Infection of women with SARS-CoV-2 in the first and second trimesters of pregnancy increases the risk of spontaneous miscarriage and antenatal fetal death, in the third trimester – the development of intraventricular hemorrhages and posthypoxic cardiomyopathy in newborns.

Occurrence of hyperoxia during iNO treatment for persistent pulmonary hypertension of the newborn: a cohort study

High concentrations of oxygen are often needed to optimize oxygenation in infants with persistent pulmonary hypertension (PPHN), but this can also increase the risk of hyperoxemia. We determined the occurrence of hyperoxemia in infants treated for PPHN. Medical records of infants ≥ 34 + 0 weeks gestational age (GA) who received inhaled nitric oxide (iNO) were retrospectively reviewed for oxygenation parameters during iNO therapy. Oxygen was manually titrated to target arterial oxygen tension (PaO2) 10–13 kPa and peripheral oxygen saturation (SpO2) 92–98%. The main study outcomes were the incidence and duration of hyperoxemia and hypoxemia and the fraction of inspired oxygen (FiO2). A total of 181 infants were included. The median FiO2 was 0.43 (IQR 0.34–0.56) and the maximum FiO2 was 1.0 in 156/181 (86%) infants, resulting in at least one PaO2 > 13 kPa in 149/181 (82%) infants, of which 46/149 (31%) infants had minimal one PaO2 > 30 kPa. SpO2 was > 98% in 179/181 (99%) infants for 17.7% (8.2–35.6%) of the iNO time. PaO2 < 10 kPa occurred in 160/181 (88%) infants, of which 81/160 (51%) infants had minimal one PaO2 < 6.7 kPa. SpO2 was < 92% in 169/181 (93%) infants for 1.6% (0.5–4.3%) of the iNO time.    Conclusion: While treatment of PPHN is focused on preventing and reversing hypoxemia, hyperoxemia occurs inadvertently in most patients.What is Known:• High concentrations of oxygen are often needed to prevent hypoxemia-induced deterioration of PPHN, but this can also increase the risk of hyperoxemia.• Infants with persistent pulmonary hypertension may be particularly vulnerable to the toxic effects of oxygen, and hyperoxemia could further induce pulmonary vasoconstriction, potentially worsening the condition.What is New:• Hyperoxemia occurs in the majority of infants with PPHN during treatment with iNO.• Infants with PPHN spent a considerably longer period with saturations above the target range compared to saturations below the target range.

Comparison of Different Treatments of Persistent Pulmonary Hypertension of the Newborn: A Systematic Review and Network Meta-Analysis.

Persistent pulmonary hypertension of the newborn (PPHN) is a life-threatening disease. Despite being considered the gold standard treatment scheme, inhaled nitric oxide (iNO) is not readily available in settings with limited resources. Therefore, in recent years, research on related drugs is being actively pursued. Herein, we aimed to use random-effects network meta-analysis to evaluate the efficacy and associated mortality of different PPHN therapies. We electronically searched the PubMed, Embase, and Cochrane Library for data up to January 27, 2023. Randomized controlled trials involving neonates with PPHN assessing efficacy and mortality of various treatments. Details of study population, treatments, and outcomes were extracted. Direct pairwise comparisons and a network meta-analysis was performed under random effects. The ranking probability was further assessed based on the surface under the cumulative ranking curve (SUCRA). We analyzed 23 randomized clinical trials involving 902 newborns with PPHN. Sixteen different treatment strategies were compared with each other and conventional therapy (CON). A median concentration of 10-20 parts per million (ppm) iNO (MNO) coupled with sildenafil orally administered at a dose of 1-3 mg/kg/dose every 6-8 hours (OSID) demonstrated the best efficacy (MNO + OSID vs. CON: odds ratio [OR] = 27.53, 95% CI, 2.36-321.75; SUCRA = 0.818, ranking first; moderate quality). OSID combined with milrinone administered IV also performed well in terms of efficacy (OSID + milrinone vs. CON: OR = 25.13, 95% CI = 1.67-377.78; SUCRA = 0.811, ranking second; low quality) and mortality reduction (CON vs. OSID + milrinone: OR = 25.13, 95% CI = 1.67-377.78; SUCRA = 0.786, ranking last; low quality). MNO + OSID is the most effective PPHN treatment. If iNO is not available, OSID + milrinone is preferred.

SSRIs in women of reproductive age; a systematic review of local formularies.

Depression is the second most common chronic condition affecting women of reproductive age; 23.4% of women enter pregnancy with depression and use of Selective Serotonin Reuptake Inhibitors (SSRIs) in pregnancy is often necessary for maternal wellbeing. However, SSRI use during pregnancy can cause congenital malformations, post-partum haemorrhage (PPH) and Persistent Pulmonary Hypertension of the newborn (PPHN). In UK primary care, prescribing formularies are one medium by which prescribers are provided with local medicines advice. To review all local prescribing formularies with respect to prescribing SSRIs in women of reproductive age, during pregnancy and during breastfeeding. Prescribing formularies in England and Wales. A systematic keyword search of all Clinical Commissioning Group (CCG) and Integrated Care Board (ICB) websites in England and Local Health Board (LHB) websites in Wales was undertaken between December 2021-22 to identify prescribing formularies. Data were extracted on prescribing guidance for SSRIs. 74 prescribing formularies were reviewed. 14.9% (11/74) provided links to the Medicines and Healthcare Regulatory products Agency guidance on congenital abnormalities associated with SSRIs, 28.4% (21/74) to guidance on PPH risk and 1.4% (1/74) to guidance on PPHN. Specific local guidance was given on SSRI prescribing for women of reproductive age, during pregnancy and during breastfeeding in 12.2% (9/74), 23% (17/74) and 21.6% (16/74) of formularies respectively. Our results suggest that prescribers may be poorly informed by local formularies about the risks of SSRI use around pregnancy. This may place babies at increased risk of unintentional SSRI exposure.

Challenges in clinical identification of right ventricular dysfunction in preterm infants with persistent pulmonary hypertension of the newborn

BackgroundRight ventricular dysfunction, typically qualitatively diagnosed (Q-RVd) in preterm infants, requires echocardiography which is not always acutely available. We aimed to identify clinical indices of Q-RVd in very preterm infants (gestational age, GA <32 weeks) with persistent pulmonary hypertension of newborn (PPHN) and examine the reliability and validity of Q-RVd. MethodsForty-seven infants with mean ± SD GA of 26.8 ± 2.7 weeks who had targeted neonatal echocardiography (TNE) ≤72 h old, during PPHN, were retrospectively studied. Three standard TNE clips were reviewed by two blinded assessors, and infants categorized as Q-RVd if moderate-severe RVd was diagnosed on ≥2 clips. Cardiopulmonary clinical indices at TNE and quantitative RV functional markers were compared between Q-RVd vs. no-RVd groups. Potential quantitative RVd definitions examined by classifying each measurement as “low” or “normal” using published data. Inter-rater agreement for Q-RVd assessed using Kappa statistics. ResultsMean age at TNE was 25.3 ± 20.4 h with Q-RVd diagnosed in 19(40 %) infants. Q-RVd group demonstrated higher peak oxygen requirements (96 ± 9 % vs. 84 ± 16 %, p < 0.01); however, no clinical parameters at TNE differentiated the groups. Quantitative measures were lower in Q-RVd patients, confirming classification validity. Among tested quantitative definitions, low RV stroke volume was associated with lower systolic blood pressure (41±7 vs. 47±9 mmHg, p = 0.02) and higher shock index (4.02±0.80 vs. 3.44±0.72, p = 0.02). Kappa for Q-RVd was 0.55 (95%CI 0.32–0.77). ConclusionsThe non-specific nature of clinical markers of RVd in preterm infants with PPHN necessitates echocardiographic diagnosis of RVd. Studies should examine prognostic relevance of RVd and establish outcome-based quantitative definitions in preterm infants.

Effect of Sildenafil in Neonates with Persistent Pulmonary Hypertension: An Interventional Study

Introduction: Persistent Pulmonary Hypertension of the Newborn (PPHN) reflects a disruption of the normal perinatal circulatory transition and is characterised by high pulmonary artery pressure. Inhaled Nitric Oxide (iNO) is considered the mainstay of treatment for PPHN. However, many developing and resource limited countries do not have access to such expensive therapy. Therefore, sildenafil, due to its easy availability and low cost, becomes the most commonly used drug in the management of PPHN in such settings. Aim: To study the treatment response and outcomes of neonates who received sildenafil for the management of PPHN. Materials and Methods: The present hospital-based prospective interventional study was conducted in the Neonatal Intensive Care Unit (NICU), BJ Medical College, Civil Hospital, Ahmedabad, Gujarat, between May 1, 2020, and April 30, 2021. Study was conducted on neonates with meconium aspiration syndrome and/or severe birth asphyxia admitted to the NICU. A total of 48 neonates with Two Dimensional (2D) echocardiography-proven PPHN were enrolled. Baseline clinical parameters including heart rate, respiratory rate, preductal and postductal Saturation of Peripheral Oxygen (SpO2), Oxygenation Index (OI), Saturation Oxygen Distending Pressure Index (SOPI), and Non Invasive Blood Pressure (NIBP) were monitored every six hours. Neonates who were on invasive/ non invasive ventilation had their Fraction of Inspired Oxygen (FiO2), Positive End Expiratory Pressure (PEEP), Peak Inspiratory Pressure (PIP), respiratory rate and flow rate monitored every six hours. Data were statistically analysed using Analysis of Variance (ANOVA) test. Results: During the study period, a total of 1080 neonates were admitted with meconium aspiration syndrome and/or severe birth asphyxia, out of which 48 neonates showed findings suggestive of PPHN on 2D echocardiography. A statistically significant improvement in oxygenation after sildenafil treatment was indicated by a significant reduction in OI from 35.3±8.6 to 13.2±2.1 (p-value&lt;0.001), a reduction in SOPI from 3.6±0.3 to 1.5±0.2 (p-value&lt;0.001), a reduction in FiO2 (%) from 94.6±8.19 to 24.2±4.5 (p-value&lt;0.001), an increase in Partial pressure of oxygen (PaO2) (mmHg) from 52±5.6 to 72±3.4 (p-value&lt;0.001), and an increase in SpO2 (%) from 83.5±8.6 to 93.5±5.1 (p-value&lt;0.001). Conclusion: The findings of the present study suggest that oral sildenafil can be successfully used to improve oxygenation in patients with PPHN, especially in a resource limited setting where facilities like Extracorporeal Membrane Oxygenation (ECMO) and iNO are not available, as demonstrated in the present study.

Monitoring persistent pulmonary hypertension of the newborn using the arterial to end tidal carbon dioxide gradient

Persistent pulmonary hypertension of the newborn (PPHN) can be monitored theoretically by the difference of the partial pressure of arterial (PaCO2) to end-tidal CO2 (EtCO2). We aimed to test the hypothesis that the PaCO2–EtCO2 gradient in infants with PPHN would be higher compared to infants without PPHN. Prospective, observational study of term-born ventilated infants with echocardiographically-confirmed PPHN with right-to-left shunting and term-born control infants without respiratory disease. The PaCO2–EtCO2 gradient was calculated as the difference between the PaCO2 measured from indwelling arterial sample lines and EtCO2 measured by continuous Microstream sidestream capnography. Twenty infants (9 with PPHN and 11 controls) were studied with a median (IQR) gestational age of 39.5 (38.7–40.4) weeks, a birthweight of 3.56 (3.15–3.93) kg and a birthweight z-score of 0.03 (− 0.91 to 1.08). The PaCO2–EtCO2 gradient was larger in the infants with PPHN compared to those without PPHN after adjusting for differences in the mean airway pressure and fraction of inspired oxygen (adjusted p = 0.037). In the infants with PPHN the median PaCO2–EtCO2 gradient decreased from 10.7 mmHg during the acute illness to 3.3 mmHg pre-extubation. The median difference in the gradient was significantly higher in infants with PPHN (6.2 mmHg) compared to infants without PPHN (-3.2 mmHg, p = 0.022). The PaCO2–EtCO2 gradient was higher in infants with PPHN compared to term born infants without PPHN and decreased over the first week of life in infants with PPHN. The gradient might be utilised to monitor the evolution and resolution of PPHN.

Prostaglandin-E1 infusion in persistent pulmonary hypertension of the newborn.

Neonates with persistent pulmonary hypertension of the newborn (PPHN) can present with hypoxia and right ventricular dysfunction with resultant inadequate oxygen delivery and end-organ damage. This study describes the use of prostaglandin-E1 (PGE) for ductal patency to preserve right ventricular systolic function and limit afterload in newborns with PPHN. This is a retrospective cohort study that follows the hemodynamics, markers of end-organ perfusion, length of therapeutics, and echocardiographic variables of 57 newborns who used prostglandin-E1 in the setting of PPHN. Tachycardia, lactic acidosis, and supplemental oxygen use improved following PGE initiation. Fractional area change (FAC), to assess right ventricular systolic function, and pulmonary arterial acceleration time indexed to right ventricular ejection time (PAAT/RVET), to assess right ventricular afterload, also improved over three time points relative to PGE use (before, during, and after). Overall, we described the safety and utility of PGE in newborns with severe PPHN for stabilization while allowing natural disease progression.

Comparison of treprostinil and oral sildenafil for the treatment of persistent pulmonary hypertension of the newborn: a retrospective cohort study.

This study aims to evaluate the effectiveness of treprostinil and oral sildenafil in managing persistent pulmonary hypertension of newborns (PPHN). We conducted a retrospective cohort study of 42 neonates with PPHN treated with continuous intravenous treprostinil or oral sildenafil from January 2020 to October 2022 in China. Outcomes assessed included echocardiographic pulmonary artery systolic pressure (PASP), shunt direction, and arterial blood gas measures. Treprostinil lowered PASP and improved oxygenation significantly better than sildenafil on days 1, 2, and 3 of treatment (P < 0.05). Treprostinil also corrected shunt direction faster than sildenafil (P < 0.05). The duration of mechanical ventilation, length of NICU stay, and overall hospital stay did not significantly differ between the two groups (P > 0.05). Treprostinil effectively lowers pulmonary artery pressure and improves oxygenation in neonates with PPHN, without being associated with severe complications. It may serve as a beneficial adjunct therapy for neonates with PPHN.

Current diagnosis and treatment practice for pulmonary hypertension in bronchopulmonary dysplasia-A survey study in Germany (PUsH BPD).

Pulmonary hypertension (PH) is the most severe complication in preterm infants with bronchopulmonary dysplasia (BPD) and associated with significant mortality. Diagnostic and treatment strategies, however, still lack standardization. By the use of a survey study (PH in BPD), we assessed clinical practice (diagnosis, treatment, follow-up) in preterm infants with early postnatal persistent pulmonary hypertension of the newborn(PPHN) as well as at risk for or with established BPD-associated PH between 06/2018 and 10/2020 in two-thirds of all German perinatal centers with >70 very low birthweight infants/year including their cardiology departments and outpatient units. Data wereanalyzed descriptively by measures of locations and distributional shares. In routine postnatal care, clinical presentation and echocardiography were reported as the main diagnostic modalities to screen for PPHN in preterm infants, whereas biomarkers brain natriuretic peptide/N-terminal pro b-type natriuretic peptide were infrequently used. For PPHN treatment, inhaled nitric oxidewas used in varying frequency. The majority of participants agreed to prescribe diuretics and steroids (systemic/inhaled) for infants at risk for or with established BPD-associated PH and strongly agreed on recommending respiratory syncytial virus immunization and the use of home monitoring upon discharge. Reported oxygen saturation targets, however, varied in these patients in in- and outpatient care. The survey reveals shared practices in diagnostic and therapeutic strategies for preterms with PPHN and BPD-associated PH in Germany. Future studies are needed to agree on detailed echo parameters and biomarkers to diagnose and monitor disease next to a much-needed agreement on the use of pulmonary vasodilators, steroids, and diuretics as well as target oxygen saturation levels.

Incidence and outcomes of persistent pulmonary hypertension of the newborn in a tertiary referral center, Indonesia

Background: Persistent pulmonary hypertension of the newborn (PPHN), also known as persistent fetal circulation, is a failure of the transition/adaptation process from fetal to extrauterine life with significant morbidity and mortality rates. This study determined the incidence and outcome of PPHN in infants. Methods: From January 2017 to March 2022, an observational study was conducted on newborns with PPHN who were hospitalized in the second and third-level neonatology wards of Prof. Dr. I.G.N.G. Ngoerah Hospital. Based on a clinical and echocardiographic examination, PPHN was confirmed. Missing data on infants were excluded. PPHN incidence and outcomes were the main outcomes. The clinical profile of newborns with PPHN was one of the secondary outcomes. Results: There were 42 neonates, with a median age of 1 (range 0-5 days) day at diagnosis. PPHN occurred in 2.5 cases per 1000 neonates admitted, with 60% male and 40% female. Referrals accounted for 74% of all PPHN cases. The majority of cases were born cesarean delivery (83%), at term (74%), and with birth weights of more than 2500 grams (65%). In 55% of cases, asphyxia history was discovered. The median oxygen index (OI) was 5.3 (range 1.90-57.30), with pneumonia/sepsis accounting for 95% of the causes. The median length of stay was 9.50 days (range 1-89), and 20 (48%) of the 42 cases had death. Conclusion: The incidence of PPHN in a tertiary referral center in Indonesia is 2.5 cases per 1000 patients treated with a 48% mortality rate.

Novel scoring tool of hypoxemic respiratory failure and pulmonary hypertension for defining severity of persistent pulmonary hypertension of newborn

ObjectiveTo obtain preliminary validity data for a hypoxemic respiratory failure/pulmonary hypertension (HRF/PH) score for classifying persistent pulmonary hypertension of the newborn (PPHN).Study designRetrospective chart review of 100 consecutive neonates admitted to a Children’s hospital from 2016–2021 with PPHN, gestational age ≥34 weeks, and echocardiograms in the first week. We assessed the correlation between HRF/PH score and short-term outcomes using linear and logistic regressions.ResultsHRF/PH scores ranged 2–12 (mean 8.5), and were classified mild (0–5), moderate (6–10), and severe (11–15), with 6%, 77% and 17% infants in respective categories. HRF/PH score category correlated with invasive ventilation, nitric oxide, high frequency ventilation, vasoactive infusions, extracorporeal life support and death. HRF/PH score category did not correlate with duration of support or length of stay.ConclusionThe HRF/PH score offers a promising representation of disease severity for PPHN. The tool requires further validation in prospective studies and evaluation for long-term outcomes.

Fetal pulmonary artery stiffness is a strong predictor of persistent pulmonary hypertension of the newborn - An echocardiographic study

ObjectivePulmonary artery stiffness (PAS) is a strong and independent predictor of mortality in adult patients with pulmonary hypertension (PH). But the change in PAS during perinatal period remains unknown. Here, we aimed to explore the feasibility and performance of PAS on predicting persistent pulmonary hypertension of the newborn (PPHN). Methods1325 fetuses underwent a dedicated echocardiography screening for fetal heart defects during second trimester, third-trimester and neonatal period with the measurement of acceleration time (PAAT) and maximal frequency shift (MFS) of pulmonary artery flow. PAS (MFS/PAAT ratio) was calculated. ResultsSix fetuses were diagnosed as PPHN. Compared with the normal fetuses, those with PH had greater values of PAS during each period of time (second trimester, 52.6(46.2–54.5) vs. 32.4(28.0–39.4) kHz/s, p = 0.0003; third trimester, 52.9(46.1–55.3) vs. 29.7(27.3–33.3) kHz/s, p = 0.0002; neonatal period, 127.4(85.2–150.8) vs. 26.6(22.7–35.0) kHz/s, p < 0.0001). There was a statistically significant correlation between PAS and mean pulmonary artery pressure (p < 0.05) but no correlation between PAS and gestational age (p > 0.05) whether in normal fetuses or not. The area under receiver operating characteristic curve (AUC) of 0.97 for PAS during third trimester was superior to that for PAS during second trimester (AUC, 0.94) in predicting PPHN. The optimal cutoff value of PAS during third trimester was 37.40 KHz/s, with a sensitivity of 100%, a specificity of 91%, and an accuracy of 92%. ConclusionThere was a significant difference in PAS between normal fetuses and those with PH. PAS has a power performance on predicting PPHN.

Meconium aspiration syndrome: a comprehensive review.

Meconium aspiration syndrome (MAS) is a complex respiratory disease that continues to be associated with significant morbidities and mortality. The pathophysiological mechanisms of MAS include airway obstruction, local and systemic inflammation, surfactant inactivation and persistent pulmonary hypertension of the newborn (PPHN). Supplemental oxygen and non-invasive respiratory support are the main therapies for many patients. The management of the patients requiring invasive mechanical ventilation could be challenging because of the combination of atelectasis and air trapping. While studies have explored various ventilatory modalities, evidence to date does not clearly support any singular modality as superior. Patient's pathophysiology, symptom severity, and clinician/unit expertise should guide the respiratory management. Early identification and concomitant management of PPHN is critically important as it contributes significantly to mortality and morbidities.

Evaluation of Postnatal Complications in Clinical and Histological Chorioamnionitis in Extremely Preterm Infants: A Japanese Cohort Study.

Terminating pregnancy appropriately before the intrauterine infection has progressed may have an improved prognosis for preterm infants. We evaluate how the combination of histological chorioamnionitis (hCAM) and clinical chorioamnionitis (cCAM) affects the short-term prognosis of infants. This retrospective multicenter cohort study based on the Neonatal Research Network of Japan included extremely preterm infants born weighing <1,500 g between 2008 and 2018. Demographic characteristics, morbidity, and mortality were compared between the cCAM(-)hCAM(+) and cCAM(+)hCAM(+) groups. We included 16,304 infants. The progression to cCAM in infants with hCAM was correlated with the increase in home oxygen therapy (HOT) (adjusted odds ratio [aOR], 1.27; 95% confidence interval [CI], 1.11-1.44) and persistent pulmonary hypertension of the newborn (PPHN) (1.20, 1.04-1.38). Furthermore, increased progression of the hCAM stage in infants with cCAM correlated with an increase in bronchopulmonary dysplasia (BPD; 1.05, 1.01-1.11), HOT (1.10, 1.02-1.18), and PPHN (1.09, 1.01-1.18). However, it had a negative impact on hemodynamically significant patent ductus arteriosus (hsPDA; 0.87, 0.83-0.92) and death before discharge from the neonatal intensive care unit (NICU; 0.88, 0.81-0.96). Progression to cCAM in infants with hCAM positively correlated with HOT and PPHN. Progression of hCAM staging in infants with cCAM further increases the prevalence of BPD and the need for HOT and PPHN while reducing the prevalence of hsPDA and death before discharge from the NICU. The effects of the progressive hCAM stage in infants with cCAM vary from positive to negative by disease. · Retrospective multicenter cohort study based on the Neonatal Research Network of Japan.. · Clinical and histological chorioamnionitis increases the prevalence of BPD, HOT, and PPHN.. · Progression of histological chorioamnionitis in infants reduces the prevalence of hsPDA and death..

Inhaled iloprost is an effective alternative therapy for persistent pulmonary hypertension in newborns.

Persistent pulmonary hypertension of the newborn(PPHN) is one of the diseases of the neonate with severe potential morbidity and mortality. Inhaled iloprost, a stable prostacyclin analog, has been suggested as an alternative treatment for inhaled nitric oxide (iNO). However, more data on neonates' dosing, setting, and effectiveness still needs to be solved. This study suggests using inhaled iloprost as rescue therapy for PPHN based on our experience. This was a retrospective study. The data from medical records of six newborns diagnosed with PPHN and had received inhaled iloprost from December 2019 to April 2022 were collected. Demographic and clinical features, dosing regimen, changes in oxygenation index, echocardiographic findings, and mortality were evaluated. The inhalation dose was 2-4 mcg/dose, and 3-48 inhalations per day were applied over 2-7 days. Inhaled iloprost was effective in all patients. No side effects were attributable to inhaled iloprost, and no mortality was recorded. Our experience suggests that inhaled iloprost can be used as a first-line therapy in newborn infants with PPHN when iNO is unavailable. However, there are large fluctuations in the oxygenation index due to the setting.

Diastolic ventricular function in persistent pulmonary hypertension of the newborn.

Persistent pulmonary hypertension of the newborn (PPHN) is usually considered a consequence of impaired pulmonary circulation. However, little is known regarding the role of cardiac dysfunction in PPHN. In this study, we hypothesized that the tolerance for pulmonary hypertension in newborn infants depends on the biventricular function. The aim of this study is to evaluate biventricular cardiac performance by using Tissue Doppler Imaging (TDI) in an healthy newborn infants with asymptomatic pulmonary hypertension and in newborn infants with PPHN. Right and left cardiac function were investigated using conventional imaging and TDI in 10 newborn infants with PPHN ("PPHN") and 10 asymptomatic healthy newborn infants ("asymptomatic PH"). Systolic pulmonary artery pressure (PAP) as assessed by TDI and the mean systolic velocity of the right ventricular (RV) free wall were similar in both groups. The isovolumic relaxation time of the right ventricle at the tricuspid annulus was significantly longer in the "PPHN" than in the "asymptomatic PH" group (53 ± 14 ms vs. 14 ± 4 ms, respectively; p < 0.05). Left ventricular (LV) function was normal in both groups with a systolic velocity (S'LV) at the LV free wall groups (6 ± 0.5 cm/s vs. 8.3 ± 5.7 cm/s, p > 0.05). The present results suggest that high PAP with or without respiratory failure is not associated with altered right systolic ventricular function and does not affect LV function in newborn infants. PPHN is characterized by a marked right diastolic ventricular dysfunction. These data suggest that the hypoxic respiratory failure in PPHN results, at least in part, from diastolic RV dysfunction and right to left shunting across the foramen ovale. We propose that the severity of the respiratory failure is more related to the RV diastolic dysfunction than the pulmonary artery pressure.

Inhaled nitric oxide use in newborns.

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.