Search Results (48)

Neonatal pulmonary hypertension (PH) is a major cause of illness and death in newborns. Neonatologist-performed echocardiography (NPE) is increasingly used as a bedside tool to assess heart function, shunt patterns, and pulmonary blood flow in real time, helping clinicians better understand the severity and type of PH. This narrative review summarizes current evidence on the use of NPE in diagnosing, monitoring, and treating neonatal PH, drawing on clinical studies, guidelines, and expert recommendations. NPE provides key diagnostic and therapeutic information, including evaluation of ventricular function, estimation of pulmonary pressures, and assessment of shunt direction. Advanced measures—such as tricuspid annular plane systolic excursion (TAPSE), myocardial performance index, pulmonary artery acceleration time (PAAT), and deformation imaging—improve accuracy and help guide therapies like inhaled nitric oxide, milrinone, and sildenafil. NPE is also useful in chronic conditions such as bronchopulmonary dysplasia (BPD)- and congenital diaphragmatic hernia (CDH)-associated PH. Despite its clear clinical value, NPE use remains limited by variations in training, protocols, and resource availability. Standardized curricula, accreditation, and unified reporting practices are needed to ensure safe, consistent integration of NPE into neonatal care pathways. Full article

Background: Persistent pulmonary hypertension of the newborn (PPHN) remains a life-threatening condition resulting from failure of postnatal circulatory adaptation. Inhaled nitric oxide (iNO) is the standard first-line therapy; however, limited access or inadequate response highlight the need for alternative treatments. Milrinone, a selective phosphodiesterase-3 inhibitor with nitric oxide-independent vasodilatory and inotropic properties, has been proposed as one such option. Methods: In this study we present a case series of three neonates with PPHN—term (41 weeks), late preterm (35 weeks), and extremely preterm (23 weeks)—treated with intravenous milrinone in a neonatal unit without immediate access to iNO. A narrative literature review was also conducted, focusing on clinical outcomes, safety, and therapeutic applicability. Results: Milrinone was initiated within the first 24 h of life. In the term and late-preterm infants, oxygenation and echocardiographic parameters improved within 48 h, with normalization of shunt direction and successful extubation by days 4–10. Transient systemic hypotension occurred in both cases and required dose adjustment or vasoactive support. In the extremely preterm neonate, only temporary hemodynamic improvement was achieved, followed by severe intraventricular hemorrhage and coagulopathy, possibly exacerbated by vasodilatory and antiplatelet effects of milrinone. Conclusions: Milrinone may serve as a feasible adjunct or bridging therapy for PPHN when iNO is unavailable. However, its use requires careful hemodynamic and neurological monitoring, particularly in very preterm infants. Further studies are needed to confirm safety and define optimal dosing across gestational ages. Full article

Background: Pulmonary hypertension (PH) occurs in ~25% of infants with moderate-to-severe bronchopulmonary dysplasia (BPD) and is associated with substantial morbidity and mortality. The American Heart Association and American Thoracic Society recommend routine echocardiographic screening for PH in preterm infants with BPD at 36 weeks’ postmenstrual age (PMA), yet the true incidence remains unclear owing to non-uniform diagnostic criteria. Emerging evidence suggests a potential role for earlier screening. Objectives: (i) to determine the incidence of pulmonary hypertension (PH) and bronchopulmonary dysplasia (BPD) in preterm infants of extremely low gestational age; (ii) to determine the incidence of PH among infants diagnosed with BPD (BPD-PH); and (iii) to evaluate the utility of early screening at 7 days of life and late screening at discharge in relation to subsequent BPD. Methods: We conducted a prospective cohort study of all infants born at 22 + 0 to 28 + 6 weeks’ gestation and admitted to our tertiary NICU between 1 September 2022 and 31 December 2024. Clinical and echocardiographic assessments for PH and BPD were performed by neonatologists trained in neonatal echocardiography. Results: Seventy-eight infants born at 22 + 0–28 + 6 weeks’ gestation were enrolled; 71 underwent early screening and 57 underwent late screening. Early echocardiography at day 7 and late screening at discharge identified no cases of PH. PH was diagnosed clinically and/or echocardiographically in 10 infants before day 7 and in one infant at 38 weeks’ PMA. BPD developed in 42 of 57 infants (73.7%). Conclusions: In this cohort of extremely low-gestational-age infants, echocardiographic screening performed by neonatologists detected no PH at day 7 and only one case at late screening (at 38 weeks’ PMA/before discharge). Most PH was identified prior to day 7 on clinical and/or echocardiographic grounds. Full article

The vein of Galen malformations (VoGMs) is mainly correlated with the retention of an embryonic pattern of vascularity, inducer of vein of Galen dilation, and formation of arteriovenous communications that give rise to the risk of systemic shunting, causing cardiac dysfunction, vascular steal, and venous hypertension. This is a rare cerebral vascular malformation in the newborn, accounting for 1% of all cerebral arteriovenous malformations and occurring in approximately 1 in 25,000–50,000 live births. We review nine cases of newborns diagnosed with vein of Galen malformations (VoGMs) to assess whether this pathology demonstrates a marked improvement over the past 13 years in diagnostic accuracy, treatment approaches, and patient survival rates within our clinic. Medical treatment was focused on providing inotropic support and tightly controlled peripheral and pulmonary vasodilation with the aim of overriding the effects of high output heart failure. Most of the patients underwent liver failure and flow-mediated pulmonary hypertension, while half of the newborns expressed anomalies of the nervous system due to impaired cerebral hemodynamics. Given the unavailability of endovascular treatment in our unit, which predisposes the newborns to a higher vital risk, we recognize the importance of delivering tailored intensive care aimed at maintaining cardiorespiratory and hemodynamic stability until a curative intervention can be performed in a specialized center. Full article

Persistent pulmonary hypertension of the newborn (PPHN) results from disrupted fetal–neonatal circulatory transition, characterized by elevated pulmonary vascular resistance (PVR), right-to-left shunting, and refractory hypoxemia. Despite improved perinatal care, PPHN remains a major source of neonatal morbidity and mortality. This review details PPHN phenotypes, pathophysiology, etiology, diagnostics including echocardiography and biomarkers like B-type Natriuretic Peptide (BNP) or N-terminal pro-B-type Natriuretic Peptide (NT-proBNP), and current therapeutic modalities, from lung recruitment and surfactant to targeted vasodilator therapy (iNO, sildenafil, milrinone, bosentan) and extracorporeal membrane oxygenation (ECMO). We emphasize the role of endothelial and molecular mechanisms in precision therapy and outline guidelines for clinical decision-making in diverse care settings. Full article

Background: Pulmonary hypertension (PH) in newborns is a rare but serious condition and potentially life-threatening disorder, often initially confused with congenital heart disease due to overlapping echocardiographic findings in the late third trimester. Evidence on prenatal predictors of postnatal PH is limited. We aimed to describe detailed third-trimester echocardiographic findings associated with postnatal PH in infants with prenatally suspected CoA based on a retrospective case series. Methods: We reviewed 18 years of fetal echocardiography (2004–2022) in a tertiary maternal–fetal–neonatal center. We identified fetuses with suspected coarctation of the aorta (CoA) in late gestation who were delivered at term (≥37 weeks) and had prolonged neonatal hospitalization (>10 days) without cardiac surgery or catheterization. Z-scores for cardiac dimensions were calculated. All examinations were performed by experienced fetal cardiologists. Postnatal evaluations confirmed PH based on echocardiographic and clinical findings. Results: Among 19,836 fetuses examined, 138 were prenatally suspected of CoA. In 70 cases, this diagnosis was not confirmed postnatally (false positives). Of these, eight infants (0.04% of the total cohort) developed postnatal PH. Postnatally, all eight neonates required intensive care. Prenatal features included ventricular/atrial disproportion (7/8), cardiomegaly (8/8), main pulmonary artery dilatation (10.2 ± 2.2 mm; Z-score +2.7 ± 1.3), tricuspid regurgitation (8/8), pulmonary regurgitation (4/8), and interventricular septal hypertrophy (>4.5 mm in 5/8). Postnatal evaluations confirmed PH based on echocardiographic criteria (elevated right ventricular pressure, septal flattening/bowing, right ventricular dilation or dysfunction, and abnormal shunt direction) combined with clinical compromise. All infants received prostaglandin E1 (PGE1) initially; none required extracorporeal membrane oxygenation-ECMO. Three died, while five survived with medical management (oxygen, inhaled nitric oxide, sildenafil). Conclusions: Specific functional abnormalities on late third-trimester echocardiography may indicate impaired pulmonary vascular adaptation and predict postnatal PH, particularly in cases initially suspected of CoA. Recognition and awareness of these findings can guide delivery planning, neonatal surveillance, and timely intervention. Prospective multicenter studies are needed to validate these associations and refine prenatal screening protocols. Full article

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

This research aimed to assess the influence of prenatal and postnatal factors on the remodeling of the pulmonary microvasculature. Methods: The investigation analyzed 67 cases of preterm infants, whose lifespans ranged from 1 day to 149 days. After selecting the cases from the autopsy database, two lung tissue microarrays were created. Histological slides were stained using the hematoxylin and eosin technique to precisely capture the microscopic details. For the assessment of pulmonary microvascularization and the media layer of the vascular walls, an immunohistochemical analysis was performed utilizing CD34 and SMA markers. Results: Following the assessment of the quantity of capillaries positive for CD34, a negative correlation was identified between the average capillary count per alveolus and the duration of oxygen therapy. Preterm infants who developed pulmonary fibrosis exhibited an average reduction of 5.43 capillaries in comparison to other newborns. Preterm neonates born to mothers with preeclampsia exhibited an average reduction of 2.82 capillaries compared to those born to mothers unaffected by this pregnancy complication. A positive correlation was evident between increased thickness of the arteriolar media, lifespan, and the duration of oxygen therapy, as well as in those preterm infants who developed pulmonary fibrosis. Conclusions: Antenatal risk factors did not exert a significant impact on pulmonary vascular remodeling, whereas postnatal influences, particularly oxygen therapy, demonstrated a detrimental effect on the density of capillary structures within the alveolocapillary membrane. Premature neonates with increased thickness of the arteriolar media had a greater susceptibility to pulmonary hypertension. 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

Omphalocele is a rare congenital abdominal wall defect, occurring in approximately 3.38 per 10,000 pregnancies. It is characterized by the herniation of abdominal organs through the base of the umbilical cord, enclosed by a peritoneal sac. While omphalocele can occur as an isolated anomaly, it is more commonly associated with congenital syndromes and structural abnormalities. Among its most significant complications, pulmonary hypoplasia (PH) and pulmonary hypertension (PPH) have been shown to negatively impact neonatal prognosis. These conditions result from impaired pulmonary vascular development, leading to respiratory distress and hypoxemia. Unlike many congenital disorders, there is no universally accepted surgical approach for omphalocele repair. The choice of surgical strategy depends on multiple factors, including the size of the abdominal wall defect, presence of herniated solid organs, associated anomalies, and severity of pulmonary complications. Notably, giant omphaloceles are frequently linked to lung hypoplasia, as reduced intra-abdominal space restricts fetal lung expansion, leading to structural lung abnormalities and increased pulmonary vascular resistance. These factors contribute to a higher risk of respiratory morbidity and mortality in affected neonates. This literature review examines the prevalence, significance, and clinical implications of the association between omphalocele and pulmonary abnormalities. Through a systematic analysis of published studies, we evaluated 157 full-text articles along with available titles and abstracts. Our findings indicate that infants with omphalocele often exhibit respiratory complications detectable prenatally and at birth. Severe respiratory insufficiency, particularly due to pulmonary hypoplasia and pulmonary hypertension, significantly increases neonatal morbidity and mortality. While surgical correction may initially exacerbate respiratory challenges, most patients demonstrate short-term recovery with appropriate multidisciplinary management. This review highlights the importance of early diagnosis, comprehensive prenatal assessment, and tailored postnatal management to improve outcomes in newborns with omphalocele and associated pulmonary complications. Further research is needed to establish standardized treatment protocols and optimize long-term respiratory outcomes in these patients. Full article

L-citrulline (L-CIT), a precursor to L-arginine (L-ARG), is a key contributor to the nitric oxide (NO) signaling pathway. Endothelial dysfunction, characterized by deficient nitric oxide synthesis, is implicated in the pathogenesis of various neonatal conditions such as necrotizing enterocolitis (NEC) and bronchopulmonary dysplasia (BPD) associated pulmonary hypertension (PH). This review summarizes the current evidence around the possible role of L-CIT supplementation in the treatment of these conditions. Detoxification of endogenously produced superoxide radicals is inadequate in preterm infants due to immature antioxidants that leads to the production of peroxynitrite, a reactive oxygen-free radical that is cytotoxic and causes damage to organelles and cellular membranes, further disrupting the coupling of endothelial NO synthase enzyme and the generation of high levels of reactive nitrogen and oxygen species. Animal studies in lipopolysaccharide-induced models of chorioamnionitis and hyperoxia- and inflammation-induced BPD-PH in rodent lung models revealed that L-CIT supplementation significantly mitigated structural changes in the pulmonary vasculature, preserved alveolar growth, and increased vascular endothelial growth factor gene expression, highlighting the anti-inflammatory and antioxidant effects of L-CIT supplementation. Similar benefits were noted in newborn piglet models of chronic hypoxia-induced PH and NEC. Pharmacokinetic studies in neonates have shown doses of 100–300 mg/kg/day to be safe and well tolerated. A few studies have shown the beneficial effects of L-CIT supplementation in pulmonary hypertension secondary to congenital heart disease, but evidence of efficacy in the neonatal population is lacking. While L-CIT shows promise in the treatment of various neonatal conditions, adequately powered studies to evaluate the safety and efficacy of L-CIT supplementation post-surgical NEC and BPD ± PH in the extremely preterm population are needed to translate this novel therapy to clinical practice. 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

High-flow oscillatory ventilation (HFOV) is a common rescue treatment in infants and children with respiratory failure. This type of ventilation is an effective technique in numerous diseases that affect a child in the postnatal period, such as ARDS, meconium aspiration syndrome (MIS), postnatal pulmonary bleeding and idiopathic pulmonary hypertension (IPH). Although this ventilation technique is commonly recognized as a valuable therapeutic option in the general pediatric population, this is not the same for children with congenital cardiovascular diseases. The key mechanism of oscillatory ventilation is continuous positive pressure administered within the airways via a small tidal volume at high frequency. Tidal volumes are between 1 and 3 mL/kg delivered at 5–15 Hz, equivalent to 300–900 breaths per minute. A few older studies conducted on humans and animals highlight that HFOV may be dangerous for congenital heart patients. According to these evidences, hemodynamic parameters such as blood pressure, wedge pressure, central venous pressure, heart rate and inotrope level can be dangerously changed for patients with congenital heart disease; therefore, oscillatory ventilation should be avoided. Numerous retrospective studies have pointed out how oscillatory ventilation constitutes a valid therapeutic option in children with congenital heart disease. Recently, new evidences have highlighted how hemodynamic parameters are modified in a non-significant way by this type of ventilation, remaining beneficial as in the normal pediatric population. This narrative review aims to describe the mechanisms of oscillatory ventilation and collect all the available evidences to support its use in pediatric patients with congenital heart problems. Full article