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.
Purpose: Sacral dimples are common and occur in 1.8% to 7.2% of neonates. Most simple dimples are benign, and concerns have been raised about the routine use of spinal ultrasonography for all such cases. This study aimed to analyze the spinal ultrasound findings in neonates with sacral dimples and evaluate the clinical usefulness of this examination.Methods: We retrospectively reviewed the medical records of 588 infants who underwent spinal ultrasonography for sacral dimples at the National Health Insurance Service Ilsan Hospital between January 1, 2018, and January 1, 2024. Ultrasonography performed within 6 months of birth were included, and examinations were conducted by board-certified pediatric radiologists.Results: The infants in this study had a mean birth weight of 3,002±542 g and a mean gestational age of 37.3±2.0 weeks. Ultrasonography was performed at a mean age of 2 months. Of 588 infants, only two (0.3%) showed significant thickening (2.0 to 2.4 mm) of the filum terminale, and none demonstrated findings of a tethered cord.Conclusion: Most infants who underwent spinal ultrasonography for sacral dimples showed normal (94.8%) or benign (4.8%) findings. Pediatricians should carefully examine whether dimples are accompanied by other cutaneous markers suggestive of spinal dysraphism. As sacral dimples are commonly screened during national infant health check-ups, further large-scale studies are warranted to establish clear guidelines for the use of spinal ultrasonography in this population.
Purpose: Posthemorrhagic ventricular dilatation (PHVD) is a significant complication of intraventricular hemorrhage (IVH) in neonates. This study aimed to evaluate the clinical characteristics, treatment course, and neurodevelopmental outcomes of neonates with PHVD after grades II–IV IVH.Methods: This retrospective single-center cohort study included neonates with grades II–IV IVH admitted between January 2014 and December 2025. Infants with life-threatening congenital anomalies or genetic disorders and those who died within 7 days of IVH diagnosis were excluded. Clinical characteristics, ventricular measurements, treatment course, and outcomes at discharge and at 18 to 24 months of corrected age were analyzed according to PHVD development and treatment strategy.Results: Among the 64 neonates included in the final analysis, 22 developed PHVD and 42 served as controls. Infants with PHVD exhibited a more severe IVH grade distribution, a higher frequency of cystic encephalomalacia, and worse neurodevelopmental outcomes than controls. Among infants with PHVD, 16 underwent neurosurgical intervention and six received conservative management. Infants who underwent intervention had greater ventricular dilatation and a higher frequency of cystic encephalomalacia than those managed conservatively.Conclusion: PHVD after grades II–IV IVH was associated with more severe brain injury and worse neurodevelopmental outcomes. Among infants with PHVD, those requiring neurosurgical intervention had a greater burden of ventricular dilatation and associated brain injury.
Purpose: Moderate-to-late preterm (MLPT) infants born at 32 to 35 weeks of gestation are often considered to be at low risk for developmental delays. However, emerging evidence suggests vulnerabilities in language development. This study aimed to evaluate language outcomes in MLPT infants at a corrected age of approximately 2 years.Methods: We retrospectively analyzed 82 preterm infants (29 early preterm infants aged <32 weeks; 53 MLPT) followed up at the National Health Insurance Service Ilsan Hospital Growth and Development Clinic. Language assessments included the Korean Developmental Screening Test (K-DST); Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III); and Sequenced Language Scale for Infants (SELSI).Results: BSID-III assessments revealed a significant language delay (<–2 standard deviation) in 25.0% of early preterm infants and 10.4% of MLPT infants, with mild delays in 20.8% and 25.0%, respectively. SELSI showed significant language delay (<–2 SD) in 68.8% of early preterm and 56.0% of MLPT infants. No statistically significant differences were observed between early preterm and MLPT infants in the prevalence of severe language delay or the need for speech therapy, suggesting that MLPT infants remain at a comparable risk for language developmental difficulties. Overall, 26.4% of the infants with MLPT required speech therapy.Conclusion: Infants with MLPT were at a considerable risk of language delay. Regular developmental surveillance, language assessment at 2 years of age, and timely intervention are essential for optimizing outcomes.
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: This study investigated the associations between early-life perinatal risk factors, postnatal weight-growth trajectories, and pulmonary function at early school age in children born very preterm.Methods: This longitudinal cohort study included 72 children born before 30 weeks of gestation or with a birth weight below 1,250 g who completed spirometry at 6–7 years of age. Multiple linear and logistic regression analyses (n=69) were performed to examine the associations of gestational age, sex, birth weight z-score, antenatal corticosteroid exposure, Jensen 2019 bronchopulmonary dysplasia severity grade as an adjustment covariate, and two postnatal weight z-score change variables (birth to 36 weeks postmenstrual age [PMA], and 36 weeks PMA to the time of pulmonary function test [PFT]) with forced expiratory volume in 1 second (FEV₁) z-score and FEV₁/forced vital capacity (FVC) z-score.Results: Lower gestational age (β=0.18, P=0.026), male sex (β=−0.57, P=0.038), lower birth weight z-score (β=0.48, P<0.001), and smaller post-discharge weight gain (β= 0.19, P=0.048) were independently associated with lower FEV₁ z-score. For FEV₁/FVC z-score, higher birth weight z-score (β=−0.47, P=0.005), greater in-hospital weight gain PMA (β=−0.63, P=0.009), and higher Jensen BPD grade (β=−0.52, P=0.036) were inversely associated with FEV₁/FVC in multiple linear regression. In logistic regression, higher birth weight z-score (odds ratio [OR], 2.39, P=0.007) and greater in-hospital weight gain (OR, 3.97, P=0.002) were associated with higher odds of FEV₁/FVC.Conclusion: Lower gestational age, male sex, lower birth weight z-score, and smaller post-discharge weight gain were independently associated with lower school-age FEV₁. In contrast, higher birth weight z-score and greater early postnatal weight gain from birth to 36 weeks PMA were associated with lower FEV₁/FVC, consistent with a dysanaptic growth pattern.
Purpose: Korea’s treatment environment for patent ductus arteriosus (PDA) is challenged by specialized personnel shortages and increasing medicolegal risks. This study provides an empirical overview of surgical infrastructure and specialist availability across neonatal intensive care units nationwide to inform strengthening policies.Methods: We conducted a nationwide survey of 64 hospitals in the Korean Neonatal Network from April 3 to 14, 2026. Sixty centers responded (93.8%), covering staffing, surgical capacities, transfer barriers, and medicolegal experiences.Results: Pediatric cardiologists were available in 86.7% of institutions, while pediatric thoracic surgeons were available in only 56.7%, with a pronounced gap in the Gyeonggi/Incheon region (41.7%). In-hospital PDA ligation availability ranged from 68.2% in units <20 beds to 100% in those >40 beds. Neonatologists performed 96.7% of emergency PDA echocardiography during off-hours, indicating a substantial workload. Primary barriers during out-transfer were clinical instability (54.4%) and lack of receiving hospitals (35.1%). Additionally, 15.5% of institutions reported medicolegal disputes related to PDA or neonatal surgery.Conclusion: Korea’s neonatal care system has reached a critical threshold in workforce shortages and medicolegal strain. There is an urgent need to establish regionally integrated care networks, provide substantial incentives for supporting specialties, and implement legal protections such as a special act for essential medical services. Policy should be redesigned to encompass workforce expansion, a stable supply of essential medications, and strategies to mitigate medicolegal risk.
Purpose: The global brain abnormality scoring system is widely used to predict neurodevelopmental outcomes in preterm infants. However, its brain volume cutoff values may not directly apply to Korean infants due to cohort-specific differences. This study aims to establish Korean‑specific cutoff values for brain volume measurements and evaluate their association with neurodevelopmental impairment (NDI) in extremely preterm infants.Methods: This retrospective study included infants born at less than 28 weeks of gestation at Seoul National University Children's Hospital between 2017 and 2022 who underwent term-equivalent age brain MRI and Bayley-III at 18 to 24 months corrected age. NDI included developmental delay, hearing impairment, blindness, or cerebral palsy. New Korean specific cutoff values for corrected biparietal width (cBPW), transcerebellar diameter (cTCD), and deep gray matter area (cDGMA) were calculated, and predictive performance was compared between the original and new systems.Results: Of 99 infants enrolled, median cBPW was 68.8 mm, cTCD was 45.6 mm, and cDGMA was 11.5 cm2. Compared to original global norms, our cohort showed shorter cBPW and cTCD, but larger cDGMA. Multivariate analysis showed that decreased cTCD (adjusted odds ratio [aOR], 0.96; 95% confidence interval [CI], 0.94 to 0.98) and cDGMA (aOR, 0.86; 95% CI, 0.79 to 0.93) were associated with NDI. The new system achieved a higher area under the curve for predicting NDI than the original system (0.793 vs 0.784).Conclusion: Reduced cTCD and cDGMA were associated with NDI. Incorporating Korean‑specific cutoff values improved NDI prediction, providing valuable preliminary data for a tailored brain MRI scoring system.
Paired box 2 (PAX2) encodes a transcription factor essential for renal and ocular development, and its pathogenic variants cause a broad spectrum of PAX2-related disorders. We report the case of a critically ill neonate with antenatally detected bilateral renal hypoplasia accompanied by severe respiratory failure, suggesting a hereditary renal disorder. Rapid trio whole-genome sequencing identified a heterozygous PAX2 variant (c.187G>A, p.Gly63Ser) in the patient and her father, and extended genetic testing confirmed the same variant in the grandfather, establishing a three-generation inheritance pattern. Early genomic diagnosis enabled timely nephrology consultation, initiation of peritoneal dialysis, and evaluation for potential extrarenal manifestations. A definitive diagnosis was achieved on the fifth day of life (with a 3-day turnaround time), underscoring the importance of rapid genomic testing and multigenerational genetic analysis in critically ill neonates with congenital renal hypoplasia and life-threatening respiratory failure. Such approaches can reveal hereditary transmission patterns and guide early management and genetic counseling for affected families.
Purpose Bronchopulmonary dysplasia (BPD) is a chronic lung disease and a major cause of morbidity in preterm infants, especially in those requiring prolonged invasive mechanical ventilation. This quality improvement (QI) initiative aimed to reduce the duration of invasive ventilation, thereby lowering the incidence of BPD in very-lowbirth-weight infants. Methods A multidisciplinary QI initiative was conducted at the neonatal intensive care unit of Seoul National University Bundang Hospital from February 2022 to June 2024 and compared with historical controls from January 2019 to December 2021. Infants born at <32 weeks of gestation or with a birth weight of <1,500 g were included. Interventions involved standardized protocols addressing the following: minimizing unnecessary intubation in the delivery room; increasing the use of noninvasive surfactant administration; and conducting daily assessments of extubation readiness. The invasive ventilation duration, intubation in the delivery room, surfactant administration techniques, and incidence of BPD were assessed. Results A total of 358 infants (186 pre-QI and 172 post-QI) were analyzed. The rate of delivery room intubation decreased from 29.7% to 13.8% (P<0.001), and the use of noninvasive surfactant methods increased from 40.6% to 69.1% (P<0.001). The average ventilation duration decreased (17.1±31.8 days vs. 7.2±15.0 days, P<0.001). The incidence of BPD decreased from 57.5% to 45.9% (P=0.045). According to subgroup analysis of infants born at <29 weeks gestation, ventilation duration was significantly reduced (33.8±34.1 days vs. 20.2±20.7 days, P=0.01), but BPD incidence was not significantly different (85.5% vs. 92.7%, P=0.27). In the multivariate logistic regression analysis, only the duration of invasive ventilation was significantly associated with BPD (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.021 to 1.167; P=0.01), but not birth weight (OR, 0.997; 95% CI, 0.995 to 0.999; P=0.001). Conclusion A structured multidisciplinary intervention effectively reduced the duration of invasive ventilation and BPD. Continued emphasis on comprehensive care bundles may further benefit premature infants.
Amidst the dual crisis of increasing birth rate of high-risk newborns and shortage of neonatologists in Korea, neonatal intensive care units (NICU) have become a complex medical environment that generates vast amounts of data. Artificial Intelligence (AI) technology is gaining attention as an innovative solution in data-driven environments, enabling the early prediction of diseases, optimization of treatment decisions, and reduction of medical staff workload. This review aimed to examine the historical development of AI and explore areas where AI can be applied in various clinical fields of neonatology. Furthermore, it analyzes Korean medical AI research trends and related policies to shed light on their status, proposes effective measures for establishing an AI research infrastructure utilizing NICU data and interdisciplinary collaboration models, and suggests future directions for AI research in the field of neonatology. AI has evolved through two 'winters' into the current era of generative AI, with core technologies such as machine learning, deep learning, and large-language models being applied in neonatology. Key application areas include the early prediction of conditions such as sepsis, necrotizing enterocolitis, and bronchopulmonary dysplasia using heart rate characteristics, medical imaging, and multimodal data, as well as treatment optimization through Clinical Decision Support Systems. In Korea, R&D is being actively promoted under government leadership, including the establishment of the 'Korean Specialized Big Data for Critical Care (K-MIMIC)' and the 'Advanced Research Projects Agency for Health (ARPA-H) Project,' while an institutional foundation is also being established with laws like the 'Digital Medical Products Act.' For the successful implementation of AI, a standardized multicenter data infrastructure such as the Korea Neonatal Network and a clinician-led industry– academia–research–hospital collaboration model are essential. Future AI research in neonatology must move beyond static risk prediction toward a dynamic intervention recommendation system that suggests optimal treatments based on real-time data. Ultimately, the goal is to establish a Smart NICU that realizes precision, automation, and remote capabilities for neonatal care. To this end, by having medical professionals lead the research ecosystem and strengthen interdisciplinary collaboration, AI will play a decisive role in saving the lives of newborns and ensuring their healthy future.
Hepatocyte nuclear factor 1-beta (HNF1B), located on chromosome 17q12, plays a critical role in the embryonic development of the kidneys, pancreas, liver, and genital tract. HNF1B has a heterozygous mutation that is also associated with neurodevelopmental diseases. Here, we describe the case of a female infant with bilateral renal enlargement and multiple cysts detected on prenatal ultrasonography. Postnatal imaging confirmed these findings and laboratory evaluation revealed transient hyperuricemia without hypomagnesemia or elevated liver enzyme levels. Targeted next-generation sequencing identified a novel heterozygous nonsense variant in the Pit-Oct-Unc-specific domain of HNF1B (c.316C>T; p.Gln106Ter), which was predicted to introduce a premature stop codon at amino acid position 106. As the patient grew older, the risk of developmental delays increased. This case illustrates the broad phenotypic spectrum of HNF1B-associated nephropathy and emphasizes the importance of HNF1B analysis in neonates presenting with renal and extra-renal manifestations. Early identification of HNF1B mutations facilitates the appropriate monitoring and management of symptoms, including neurodevelopmental outcomes. Further studies are needed to elucidate genotype-phenotype correlations and expand our understanding of HNF1B-related disorders.
The neonatal microbiome constitutes a dynamic and rapidly evolving ecosystem that exerts profound effects on immune, metabolic, and neurodevelopmental processes during early life. This review synthesizes current evidence on the establishment, maturation, and functional roles of the neonatal microbiome, emphasizing the differences between preterm and term infants and their implications for neonatal diseases. Microbial colonization commences at birth and is shaped predominantly by maternal transmission, mode of delivery, feeding practices, and antibiotic exposure. The early assembly of oral and gut microbiota provides the foundation for immune education, intestinal barrier integrity, and metabolic homeostasis; however, disruptions during this critical developmental window are associated with adverse outcomes. Preterm infants exhibit delayed and dysbiotic microbial development, characterized by reduced diversity, enrichment of Proteobacteria, and depletion of short-chain fatty acid-producing taxa. These alterations are strongly implicated in the pathogenesis of necrotizing enterocolitis, sepsis, bronchopulmonary dysplasia, and neurodevelopmental impairment, predominantly through mechanisms involving exaggerated lipopolysaccharide—Toll-like receptor 4—nuclear factor kappa B signaling, impaired barrier function, and metabolic deficiencies. Advances in germ-free and gnotobiotic models, combined with multi-omics approaches, have elucidated key host–microbe interactions and mechanistic pathways underpinning neonatal health. However, major challenges persist in establishing causality, standardizing analytical methods, and translating mechanistic findings into effective clinical interventions. Understanding the neonatal microbiome as a central regulator of early-life programming holds promise for the development of microbiome-targeted preventive and therapeutic strategies in neonatal and pediatric medicine.
Hydrops fetalis is a condition characterized by excessive fluid accumulation in the fetus, and is classified into immune and non-immune types depending on the underlying disease. Among cases of non-immune hydrops fetalis (NIHF), 15% to 20% are of cardiac origin, and genetic factors such as titin (TTN) gene mutations can contribute to cardiac dysfunction. We report the case of a preterm infant (29+2 weeks, 1,430 g) with hydrops fetalis who developed cardiac tamponade due to major pericardial effusion. Seven hours after birth, the heart rate suddenly decreased, and blood pressure could not be measured. Transthoracic echocardiography revealed substantial pericardial effusion and severely impaired cardiac function, and the preterm infant was diagnosed with pericardial tamponade. Emergency pericardiocentesis was performed, which led to hemodynamic stabilization. Genetic testing identified two heterozygous TTN mutations (c.13898A>T and c.27856G>T), with the latter presumed responsible for the observed cardiac dysfunction. The mother was found to carry the c.13898A>T mutation, but was asymptomatic. This case report highlights the importance of genetic testing in neonates with unexplained NIHF and cardiac complications. Identifying TTN gene mutations provides valuable insights into the underlying pathophysiology and guides clinical management.
Purpose Congenital hypothyroidism (CH) is a major preventable cause of intellectual disability, particularly in very low birth weight (VLBW) infants, who are at increased risk due to hypothalamic-pituitary-thyroid axis immaturity. Early differentiation between transient CH (TCH) and permanent CH (PCH) is crucial to optimize L-thyroxine (LT4) treatment duration. This study aimed to determine the incidence of PCH among Korean VLBW infants and to identify clinical factors that may aid in distinguishing TCH from PCH. Methods This retrospective cohort study included VLBW infants diagnosed with CH and treated with LT4 at a single tertiary neonatal intensive care unit between 2011 and 2020. Infants requiring LT4 beyond 3 years were classified as PCH, while those who discontinued earlier were considered TCH. Clinical characteristics, neonatal morbidities, and thyroid-related parameters were compared between the groups. Results Among 1,292 VLBW infants, 122 (9.4%) were diagnosed with CH. After excluding deaths and those lost to follow-up, 73 infants were included in the final analysis (TCH, n=50; PCH, n=23). The PCH group had a significantly higher mean gestational age and greater LT4 requirements at both 12 and 36 months of age. Major anomalies were more frequently observed in PCH infants, including congenital heart defects. In multivariate analysis, higher gestational age, the presence of major anomalies, screening thyroid-stimulating hormone (TSH) >10 μIU/mL, and higher LT4 dose at 36 months were significantly associated with PCH. Conclusion The incidence of PCH in Korean VLBW infants was relatively higher than that reported in previous studies studies. Screening TSH level and LT4 dose requirements may support individualized follow-up and help distinguish PCH from TCH.
