Search Results (23)

Objective: The aim of this study was to describe the presenting characteristics and outcomes of neonates with respiratory failure referred for extracorporeal membrane oxygenation (ECMO) support, compare those who received ECMO support (ECMO group) to those who did not (non-ECMO group), and evaluate the predictive variables requiring ECMO support. Methods: All neonates (<15 days) with respiratory failure (without congenital diaphragmatic hernia or congenital heart disease) referred to our regional ECMO center from 2014 to 2023 were included in this retrospective study. Patient demographics, birth history, and clinical and outcome variables were analyzed. Oxygenation indices and vasoactive–inotropic scores obtained at PICU arrival and four hours after arrival were compared between the two groups using ROC analysis, with ECMO initiation as an outcome variable. Youden’s index was used for optimal threshold values. Chi-square, Mann–Whitney U, and binary logistic regression were used for comparative analyses. Results: Out of the 147 neonates, 96 (65%) required ECMO support. The two groups significantly differed in the prevalence of pulmonary hypertension (pHTN; systemic or suprasystemic pulmonary pressures), lactate level, and oxygenation indices. Mortality was not different between the two groups. Presence of oxygen saturation index (OSI) ≥ 10 had a sensitivity 96.8% in predicting the need for ECMO support. On regression analysis, OSI and pHTN were independent predictors of ECMO support. Conclusions: Oxygenation indices and echo findings predict the need for ECMO support in neonatal hypoxemic respiratory failure. These findings help non-ECMO centers make appropriate and timely transfers of neonates with respiratory failure to ECMO centers. Full article

Background/Objectives: To identify the risk factors and clinical outcomes of persistent pulmonary hypertension of the newborn (PPHN) in very low birth weight (VLBW) infants in a resource-limited setting. Methods: We conducted a 1:4 matched case–control study in a Thai neonatal unit between 2014 and 2023. Neonates born at a gestational age (GA) < 32 weeks and with a birth weight (BW) < 1500 g were included. Neonates who died in the delivery room or had major congenital anomalies were excluded. Matching was based on GA, BW, year of birth, and endotracheal intubation at birth. Conditional logistic regression analysis was performed. Results: Over the 10-year study period, the incidence of PPHN among VLBW neonates was 4.6% (31/667). After matching, there were 31 cases and 124 controls. In univariable analysis, PPHN was significantly associated with lower 1 min and 5 min Apgar scores; however, no significant association remained in multivariable analysis. PPHN was significantly associated with composite adverse outcomes—including mortality and major morbidities (adjusted odds ratio [aOR] = 7.51, 95% confidence interval [CI]: 2.41–23.40), mortality alone (aOR = 2.88, 95% CI: 1.06–7.63), major morbidities (aOR = 2.99; 95% CI: 1.29–6.95), and severe neurological injury (aOR = 4.44, 95% CI: 1.56–12.59). Daily hospital costs were also higher in PPHN cases, with an average increase of 97.1 USD. Conclusions: In VLBW infants, PPHN was associated with a lower Apgar score and surfactant administration. PPHN was significantly linked to adverse outcomes, particularly mortality, major morbidities, and severe neurological injury. Full article

Background/Objectives: Persistent pulmonary hypertension of the newborn (PPHN) is characterized by increased pulmonary vascular resistance, resulting in severe hypoxemia. This study determined the factors associated with increased risk of mortality and survival rate in infants with PPHN. Methods: This retrospective study was conducted between 2010 and 2023. The risk factors for mortality were assessed by Cox’s proportional hazard models, and the Kaplan–Meier survival curve was used to analyze the survival rates. Results: This study included 233 neonates with PPHN. Gestational age (GA) less than 28 weeks (adjusted hazard ratio [AHR] = 5.46, 95% confidence interval [CI]: 2.25–13.24, p < 0.001), Small for gestational age (SGA) (AHR = 2.93, 95% confidence interval [CI]: 1.24–6.92, p = 0.026), acute kidney injury (AKI) (AHR = 2.48, 95% CI: 1.27–4.84, p = 0.01), pneumothorax (AHR = 3.03, 95% confidence interval [CI]: 1.48–6.21, p = 0.003), vasoactive-inotropic score (VIS) at 24 h of age (AHR = 1.0026, 95% confidence interval [CI]: 1.0004–1.005, p = 0.026), and score for neonatal acute physiology II (SNAP-II) ≥ 43 (AHR = 4.03, 95% CI: 1.66–9.77, p = 0.005) were associated with an increased risk of mortality. The overall survival rate was 82.4%; it rose from 63.8% to 87.1% after inhaled nitric oxide (iNO) and extracorporeal membrane oxygenation (ECMO) were introduced (p < 0.001). The cumulative survival rates at the end of the 30 days were 62.1% (95% CI: 49.0–78.7) in the Pre-iNO era and 87.5% (95% CI: 82.7–92.6) in the Post-iNO/ECMO era, respectively (p < 0.001). Conclusions: GA less than 28 weeks, SGA, AKI, pneumothorax, high VIS and SNAP-II scores were associated with mortality in infants with PPHN. The improvement in the survival rate was related to the provision of advanced care, including iNO and ECMO therapy. Full article

Background/Objectives: Hypoxic–ischemic encephalopathy (HIE), affecting 1.3–1.7/1000 live births, is treated with conventional therapeutic hypothermia (TH) but carries significant mortality and neurological impairment. Here, we compared intravascular cooling with extracorporeal membrane oxygenation (ECMO) and conventional TH in neonates with moderate to severe HIE. Methods: We retrospectively analyzed single-center neonates born in 2000–2022. Neonates with a 10 min Apgar score ≤ 3 or umbilical artery pH ≤ 6.7, along with persistent pulmonary hypertension of the newborn and an oxygenation index of ≥25 to <40, were divided into ECMO (n = 17) and conventional TH (n = 18) groups and administered the Kyoto Scale of Psychological Development at 18 months. Results: Neonatal and maternal characteristics were similar between the groups. A significantly higher proportion of the ECMO group (70.6% vs. 33.3%) achieved a developmental quotient ≥ 70. Conclusions: Intravascular cooling with ECMO may improve the neurodevelopmental outcomes of neonates with HIE, severe acidosis, and low Apgar scores. Full article

PPHN is a common cause of neonatal respiratory failure and is still a serious condition that is associated with high mortality. Objectives: 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. Methods: 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. Results: 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. Conclusions: 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. Full article

Background: Neonatal hypoxic respiratory failure (HRF) secondary to PPHN (persistent pulmonary hypertension of the newborn) is an uncommon but life-threatening complication. Despite advances in therapeutic interventions, there are neonates who may require ECMO (extracorporeal membrane oxygenation), which improves survival. In establishing the capability of ECMO in transport in New South Wales, significant variation in referral thresholds and management of PPHN in referring hospitals has been noted. Aim: To review cases referred to the Newborn and paediatric Emergency Transport Service (NETS) for consideration of ECMO due to HRF in neonates. The aetiology of HRF, the number of retrievals and their short-term outcomes were reported. Methods: A retrospective audit of referrals to NETS (January 2019 to December 2022) of infants aged <28 days with HRF for ECMO. Patient demographics, management, advice at the time of call and the outcome are described. Results: The mean weight was 3511 g, mean gestation was 37.1 weeks and 69% of the patients were male. The main diagnoses were MAS/PPHN (50%), and there was variation in inotropes and ventilation strategies at the time of the referral. Six (25%) of the fifteen babies who were transported by NETS to paediatric intensive care were placed on ECMO at the referring hospital. A further six babies were stabilised at the referral centre following NETS co-ordinated specialist advice and did not require retrieval or ECMO. All the babies who received ECMO and survived had normal early development (<6 months) with normal head US or MRI imaging. Conclusions: Optimising ventilation and inotrope management can eliminate the need for ECMO prior to or following retrieval. Early referral for the consideration of ECMO and a collaborative discussion can assist in optimising conventional therapy, thus eliminating the need for ECMO. Neonates requiring ECMO for HRF have good survival rates with good short-term neurological outcomes. Full article

Hypoxic-ischemic encephalopathy (HIE) is the leading cause of mortality among term newborns globally. Infants born through meconium-stained amniotic fluid are at risk of developing meconium aspiration syndrome (MAS) and HIE. Simultaneous occurrence of MAS and HIE is a perilous combination for newborns due to the risk of persistent pulmonary hypertension of the newborn (PPHN). Moreover, therapeutic hypothermia (TH), which is the current standard of care for the management of HIE, may increase pulmonary vascular resistance (PVR) and worsen PPHN. Infants with MAS and HIE require close cardiorespiratory and hemodynamic monitoring for PPHN. Therapeutic strategies, including oxygen supplementation, ventilation, use of surfactant, inhaled nitric oxide and other pulmonary vasodilators, and systemic vasopressors, play a critical role in the management of PPHN in MAS, HIE, and TH. While TH reduces death or disability in infants with HIE, infants with MAS and HIE undergoing TH need close hemodynamic monitoring for PPHN. Full article

Fibrillin-1 and fibrillin-2, encoded by FBN1 and FBN2, respectively, play significant roles in elastic fiber assembly, with pathogenic variants causing a diverse group of connective tissue disorders such as Marfan syndrome (MFS) and congenital contractural arachnodactyly (CCD). Different genomic variations may lead to heterogeneous phenotypic features and functional consequences. Recent high-throughput sequencing modalities have allowed detection of novel variants that may guide the care for patients and inform the genetic counseling for their families. We performed clinical phenotyping for two newborn infants with complex congenital heart defects. For genetic investigations, we employed next-generation sequencing strategies including whole-genome Single-Nucleotide Polymorphism (SNP) microarray for infant A with valvular insufficiency, aortic sinus dilatation, hydronephrosis, and dysmorphic features, and Trio whole-exome sequencing (WES) for infant B with dextro-transposition of the great arteries (D-TGA) and both parents. Infant A is a term male with neonatal marfanoid features, left-sided hydronephrosis, and complex congenital heart defects including tricuspid regurgitation, aortic sinus dilatation, patent foramen ovale, patent ductus arteriosus, mitral regurgitation, tricuspid regurgitation, aortic regurgitation, and pulmonary sinus dilatation. He developed severe persistent pulmonary hypertension and worsening acute hypercapnic hypoxemic respiratory failure, and subsequently expired on day of life (DOL) 10 after compassionate extubation. Cytogenomic whole-genome SNP microarray analysis revealed a deletion within the FBN1 gene spanning exons 7–30, which overlapped with the exon deletion hotspot region associated with neonatal Marfan syndrome. Infant B is a term male prenatally diagnosed with isolated D-TGA. He required balloon atrial septostomy on DOL 0 and subsequent atrial switch operation, atrial septal defect repair, and patent ductus arteriosus ligation on DOL 5. Trio-WES revealed compound heterozygous c.518C>T and c.8230T>G variants in the FBN2 gene. Zygosity analysis confirmed each of the variants was inherited from one of the parents who were healthy heterozygous carriers. Since his cardiac repair at birth, he has been growing and developing well without any further hospitalization. Our study highlights novel FBN1/FBN2 variants and signifies the phenotype–genotype association in two infants affected with complex congenital heart defects with and without dysmorphic features. These findings speak to the importance of next-generation high-throughput genomics for novel variant detection and the phenotypic variability associated with FBN1/FBN2 variants, particularly in the neonatal period, which may significantly impact clinical care and family counseling. Full article

Background Meconium-stained amniotic fluid (MSAF) is considered an alarming sign of possible fetal compromise and it has recently been reported that neonatal outcome correlates with the degree of meconium thickness. Methods We retrospectively studied 400 term infants allocated in clear amniotic fluid and grade 1, 2, and 3 MSAF groups on the basis of color and thickness of AF. Multivariable logistic regression analysis was performed to evaluate the potential independent effect of delivery with MSAF of different severity on the risk of a composite adverse neonatal outcome. Results We found that delivery with grade 2 (OR 16.82, 95% Cl 2.12–33.52; p = 0.008) and 3 (OR 33.79, 95% Cl 4.24–69.33; p < 0.001) MSAF is independently correlated with the risk of adverse neonatal outcome, such as the occurrence of at least one of the following: need of resuscitation in the delivery room, blood cord pH < 7.100, occurrence of meconium aspiration syndrome (MAS), persistent pulmonary hypertension (PPH), transient tachypnea of the newborn (TTN), acute respiratory distress syndrome (ARDS), hypoxic-ischemic encephalopathy (HIE), and sepsis. Conclusions There is a positive correlation between the severity of amniotic fluid meconium staining and thickness and the outcomes of term infants. Therefore, the evaluation and grading of MSAF during labor is useful in order to plan for the presence of a neonatologist at delivery for immediate and proper neonatal care. Full article

Acute transient respiratory distress in the first hours of life is usually defined as transient tachypnea of the newborn (TTN). TTN is a respiratory self-limiting disorder consequent to delayed lung fluid clearance at birth. While TTN is the most common etiology of respiratory distress near term, its pathogenesis and diagnostic criteria are not well-defined. Lung ultrasound and targeted neonatal echocardiography are increasingly being used to assess critically ill infants, although their combined use to improve diagnostic precision in neonatal intensive care units has not yet been described. This retrospective pilot analysis aimed to identify possible cardiopulmonary ultrasound (CPUS) patterns in term and late preterm infants suffering from transient respiratory distress and requiring non-invasive respiratory support. After retrospectively revising CPUS images, we found seven potential sonographic phenotypes of acute neonatal respiratory distress. Up to 50% of the patients presented with signs of increased pulmonary vascular resistance, suggesting that those patients may be diagnosed with mild forms of persistent pulmonary hypertension of the newborn. Approximately 80% of the infants with a history of meconium-stained amniotic fluid displayed irregular atelectasis, indicating that they may have suffered from mild meconium aspiration syndrome. CPUS evaluation may improve accuracy in the approach to the infants presenting with transient acute respiratory distress, supporting communication with the parents and carrying important epidemiological consequences. Full article

There are potential benefits and risks to the infant with higher and lower oxygen saturation (SpO₂) targets, and the ideal range for infants with pulmonary hypertension (PH) remains unknown. Targeting high SpO₂ can promote pulmonary vasodilation but cause oxygen toxicity. Targeting lower SpO₂ may increase pulmonary vascular resistance, especially in the presence of acidosis and hypothermia. We will conduct a randomized pilot trial to compare two ranges of target preductal SpO₂ in late-preterm and term infants with hypoxic respiratory failure (HRF) and acute pulmonary hypertension (aPH) of the newborn. We will assess the reliability of a newly created HRF/PH score that could be used in larger trials. We will assess trial feasibility and obtain preliminary estimates of outcomes. Our primary hypothesis is that in neonates with PH and HRF, targeting preductal SpO₂ of 95–99% (intervention) will result in lower pulmonary vascular resistance and pulmonary arterial pressures, and lower the need for pulmonary vasodilators (inhaled nitric oxide—iNO, milrinone and sildenafil) compared to targeting SpO₂ at 91–95% (standard). We also speculate that a higher SpO₂ target can potentially induce oxidative stress and decrease response to iNO (oxygenation and pulmonary vasodilation) for those patients that still require iNO in this range. We present considerations in planning this trial as well as some of the details of the protocol design (Clinicaltrials.gov (NCT04938167)). Full article

Neonatal resuscitation (NRP) guidelines suggest targeting 85–95% preductal SpO₂ by 10 min after birth. Optimal oxygen saturation (SpO₂) targets during resuscitation and in the post-resuscitation management of neonatal meconium aspiration syndrome (MAS) with persistent pulmonary hypertension (PPHN) remains uncertain. Our objective was to compare the time to reversal of ductal flow from fetal pattern (right-to-left), to left-to-right, and to evaluate pulmonary (Q_PA), carotid (Q_CA)and ductal (Q_DA) blood flows between standard (85–94%) and high (95–99%) SpO₂ targets during and after resuscitation. Twelve lambs asphyxiated by endotracheal meconium instillation and cord occlusion to induce MAS and PPHN were resuscitated per NRP guidelines and were randomized to either standard (85–94%) or high (95–99%) SpO₂ targets. Out of twelve lambs with MAS and PPHN, six each were randomized to standard and high SpO₂ targets. Median [interquartile range] time to change in direction of blood flow across the ductus arteriosus from right-to-left, to left-to-right was significantly shorter with high SpO₂ target (7.4 (4.4–10.8) min) compared to standard SpO₂ target (31.5 (21–66.2) min, p = 0.03). Q_PA was significantly higher during the first 10 min after birth with higher SpO₂ target. At 60 min after birth, the Q_PA, Q_CA and Q_DA were not different between the groups. To conclude, targeting SpO₂ of 95–99% during and after resuscitation may hasten reversal of ductal flow in lambs with MAS and PPHN and transiently increase Q_PA but no differences were observed at 60 min. Clinical studies comparing low and high SpO₂ targets assessing hemodynamics and neurodevelopmental outcomes are warranted. Full article

Resuscitation with 21% O₂ may not achieve target oxygenation in preterm infants and in neonates with persistent pulmonary hypertension of the newborn (PPHN). Inhaled nitric oxide (iNO) at birth can reduce pulmonary vascular resistance (PVR) and improve PaO₂. We studied the effect of iNO on oxygenation and changes in PVR in preterm lambs with and without PPHN during resuscitation and stabilization at birth. Preterm lambs with and without PPHN (induced by antenatal ductal ligation) were delivered at 134 d gestation (term is 147–150 d). Lambs without PPHN were ventilated with 21% O₂, titrated O₂ to maintain target oxygenation or 21% O₂ + iNO (20 ppm) at birth for 30 min. Preterm lambs with PPHN were ventilated with 50% O₂, titrated O₂ or 50% O₂ + iNO. Resuscitation with 21% O₂ in preterm lambs and 50%O₂ in PPHN lambs did not achieve target oxygenation. Inhaled NO significantly decreased PVR in all lambs and increased PaO₂ in preterm lambs ventilated with 21% O₂ similar to that achieved by titrated O₂ (41 ± 9% at 30 min). Inhaled NO increased PaO₂ to 45 ± 13, 45 ± 20 and 76 ± 11 mmHg with 50% O₂, titrated O₂ up to 100% and 50% O₂ + iNO, respectively, in PPHN lambs. We concluded that iNO at birth reduces PVR and FiO₂ required to achieve target PaO₂. Full article

Infants born through meconium-stained amniotic fluid (MSAF) are 100 times more likely than infants born through clear amniotic fluid to develop respiratory distress in the neonatal period. Meconium aspiration syndrome (MAS) is a common cause of respiratory distress in term and post-mature neonates. MAS is defined as respiratory distress accompanied by a supplemental oxygen requirement in an infant born with MSAF, in the absence of any other identified etiology to explain the symptoms. Therapy for MAS is supportive, and should be tailored to each infant’s specific pathophysiology. In cases of MAS with severe persistent pulmonary hypertension of the newborn (PPHN), patients may remain hypoxic despite aggressive ventilation, and in these cases surfactant, inhaled nitric oxide (iNO) and extracorporeal membrane oxygenation (ECMO) can be life-saving. Long-term prognosis for MAS is more related to severity of initial hypoxemia and possible neurological insult than to the pulmonary pathology. Full article

Genetic mechanisms are now recognized as rare causes of neonatal lung disease. Genes potentially responsible for neonatal lung disease include those encoding proteins important in surfactant function and metabolism, transcription factors important in lung development, proteins involved in ciliary assembly and function, and various other structural and immune regulation genes. The phenotypes of infants with genetic causes of neonatal lung disease may have some features that are difficult to distinguish clinically from more common, reversible causes of lung disease, and from each other. Multigene panels are now available that can allow for a specific diagnosis, providing important information for treatment and prognosis. This review discusses genes in which abnormalities are known to cause neonatal lung disease and their associated phenotypes, and advantages and limitations of genetic testing. Full article