The pathophysiology of patent ductus arteriosus (PDA) is conventionally attributed to increased pulmonary blood flow and reduced systemic organ perfusion caused by left-to-right ductal shunting. Although PDA has been associated with major complications of prematurity and neurodevelopmental impairment, establishing direct causality remains challenging due to multiple confounders, including interactions among risk factors inherent to prematurity, variability in PDA severity and exposure duration, and the effects of interventions themselves. Accumulating evidence supports interpreting PDA in preterm infants as a biomarker of physiological vulnerability and comorbidity severity rather than as a primary causative condition. Prophylactic or early routine pharmacological closure has not demonstrated consistent benefits over conservative management with expectant closure in terms of mortality, short-term morbidity, or long-term neurodevelopmental outcomes. Prospective studies have confirmed that conservative management is a viable treatment strategy even in extremely preterm infants born before 28 weeks of gestation. Major international guidelines recommend that closure be considered only when echocardiographic evidence of hemodynamic compromise is accompanied by clinical symptoms, with pharmacological therapy as the first-line treatment. When pharmacological treatment fails or is contraindicated, the choice and timing of transcatheter ductal occlusion or surgical ligation should be determined based on the patient’s cardiorespiratory status, comorbidities, institutional availability, and anticipated risks. PDA management should be guided by the clinical judgment of experienced neonatologists with comprehensive knowledge of each patient rather than by adherence to uniform protocols. In the domestic neonatal care setting, individualized management strategies developed through multidisciplinary collaboration should be given appropriate consideration.
Purpose: Early extubation from mechanical ventilation (MV) in preterm infants may reduce MV-related complications in this population. However, extubation failure (EF) remains a common clinical challenge associated with short-term morbidity and potentially adverse long-term neurodevelopmental outcomes. This study investigated the association between EF and subsequent neurodevelopment in very preterm infants using Bayley assessments performed at a corrected age of 12–18 months.Methods: This retrospective cohort study included preterm infants born at <32 weeks’ gestation between January 2017 and December 2021. Infants who required reintubation within 7 days of at least one extubation attempt were classified as having EF, whereas those who did not require further MV after extubation were classified as extubation success (ES). The infants were matched 1:1 by gestational age and birth weight. Clinical characteristics were compared between the two groups and neurodevelopmental outcomes were assessed during outpatient follow-up using the Bayley Scales of Infant and Toddler Development at a corrected age of 12–18 months.Results: The corrected age at Bayley assessment did not differ between the EF and ES groups (EF: 14.75 months [interquartile range, IQR, 12 to 19.1] vs. ES: 14.42 months [IQR, 11.7 to 21.7], P=0.95). Infants in the EF group demonstrated significantly lower composite scores across all developmental domains than those in the ES group, including cognition (93.88 vs. 94.41, P=0.021), language (89.24 vs. 89.76, P=0.030), and motor function (86.12 vs. 88.53, P=0.016).Conclusion: EF may be a clinically useful marker for identifying preterm infants at an increased risk of adverse short-term clinical courses, such as prolonged hospitalization and subsequent neurodevelopmental vulnerability. Accordingly, infants who experience EF should undergo structured, ongoing developmental surveillance, and early rehabilitative interventions should be considered when developmental delay is suspected.
Purpose: This study compared short-term morbidity, mortality, and long-term neurological outcomes among preterm infants with necrotizing enterocolitis (NEC) and those with spontaneous intestinal perforation (SIP).Methods: We conducted a retrospective analysis using data collected between 2013 and 2023 from the Korean Neonatal Network. The study included preterm infants born at <32 weeks of gestation or with a birth weight of <1,500 g who were diagnosed with NEC or SIP. A total of 18,446 infants were classified into four groups: control, medical NEC, surgical NEC, and SIP.Results: Short-term morbidities and mortality were most prevalent in the surgical NEC group, whereas hypotension was most prevalent in the SIP group. Post hoc analysis showed that bronchopulmonary dysplasia and intraventricular hemorrhage were more common in the surgical NEC group than in the SIP group. Compared with the control and medical NEC groups, the surgical NEC group had significantly higher rates of hypotension, seizures, periventricular leukomalacia, sepsis, and retinopathy of prematurity but did not differ significantly from the SIP group. The surgical NEC and SIP groups required a longer time to achieve full enteral feeding, longer duration of total parenteral nutrition, and longer hospital stay. At a corrected age of 18–24 months, cerebral palsy and vision loss were more common in the surgical NEC group. At 33–39 months, cerebral palsy and eye disorders were more prevalent in the surgical NEC group, whereas hearing outcomes were worse in the SIP group.Conclusion: Surgical NEC was associated with the poorest short- and long-term outcomes in preterm infants, and SIP showed comparable outcomes.
Molybdenum cofactor deficiency (MoCD) is a rare autosomal recessive neurodegenerative disorder that often mimics hypoxic-ischemic encephalopathy (HIE) in neonates, leading to delayed diagnosis. Here, a term female neonate developed refractory seizures on day 3 of life with persistent hypouricemia. Magnetic resonance imaging revealed diffuse cortical and subcortical diffusion restriction, basal ganglia and thalamic involvement, white matter injury, and cerebellar hypoplasia, which were initially misinterpreted as HIE in the absence of a sentinel hypoxic-ischemic event. Serial neuroimaging showed rapidly progressive leukomalacia, and trio-based whole-genome sequencing ultimately identified a homozygous likely pathogenic variant in the MOCS2 gene, c.265T>C, p.*89Glnext*3. Both parents were confirmed as heterozygous carriers, establishing a diagnosis of MoCD type B and representing the first genetically confirmed case in South Korea. Despite aggressive anti-seizure therapy, dietary protein restriction, and supportive care, the patient exhibited severe global developmental delay and spasticity at 12 months of age, underscoring the poor prognosis of early-onset MoCD and the need to consider this entity in neonates with HIE-like encephalopathy, negative standard metabolic workup, and unexplained hypouricemia.
Purpose: Treprostinil is used off-label for refractory pulmonary hypertension (PH) in very-low-birth-weight infants (VLBWI); however, real-world outcome data remain scarce. This study aimed to describe the clinical and long-term neurodevelopmental outcomes of treprostinil-treated VLBWI with PH.Methods: Data from 21,645 VLBWI in a nationwide, multicenter registry (Korean National Network) admitted between 2013 and 2023 were retrospectively analyzed to identify those receiving treprostinil for PH. Baseline characteristics and in-hospital morbidities were compared between survivors and non-survivors. Long-term neurodevelopmental outcomes at 18–24 months and 3 years of corrected age were evaluated in survivors.Results: Treprostinil was administered to 2.0% (39/1,962) of VLBWI with PH, typically as combination therapy. Among the 32 infants (14 survivors, 18 non-survivors), in-hospital mortality was 56.3%, predominantly due to cardiopulmonary causes (83.3%). Lower cord blood pH was a potential predictor of mortality (odds ratio, 0.924 per 0.01 increase in pH; 95% confidence interval, 0.812 to 0.989; P=0.016). Survivors had higher rates of moderate-to-severe bronchopulmonary dysplasia, treated patent ductus arteriosus, and retinopathy of prematurity requiring intervention. This likely reflects a time-at-risk bias, as non-survivors died early (median, 9.5 days). By 3 years corrected age, all survivors were weaned off oxygen and PH medications. However, growth failure (87.5%) and developmental delay (50.0%) persisted despite continuous rehabilitation (85.7%) and speech therapy (50.0%).Conclusion: Treprostinil is reserved for refractory PH, which involves high mortality. Despite discontinuation of cardiopulmonary support, survivors experienced substantial long-term growth failure and neurodevelopmental impairment up to 3 years of age, highlighting the critical need for multidisciplinary follow-up.
