Hyun Ho Kim

Background/Objectives: Delayed achievement of full enteral feeding (FEF) is common in neonatal intensive care unit (NICU) infants but is closely linked to gestational age (GA). We examined whether time to FEF is associated with gut microbiome development from birth to 6 months of corrected age (CA) beyond GA. Methods: We profiled 694 stool samples from 328 NICU infants, collected at first stool, discharge, and 4- and 6-month CA, by 16S rRNA gene sequencing. Infants were classified as Early FEF (Streptococcus (q = 0.028), and a different community structure in unadjusted analyses, but none of these differences remained after GA adjustment. No phylum showed a GA-adjusted trajectory difference, and alpha diversity did not differ. In an exploratory continuous analysis, longer time to FEF was associated with higher Bacteroidetes at discharge and 4-month CA. Conclusions: Most microbiome differences associated with delayed FEF were not independent of GA. Time to FEF may reflect maturity and illness severity rather than act as an independent determinant of the gut microbiome.

Adhesive electrocardiography (ECG) electrodes used in neonatal intensive care units (NICUs) may cause skin injury in premature infants. Although photoplethysmography (PPG)-based ECG reconstruction has been explored, existing studies have mainly focused on adult data and often rely on direct PPG-to-ECG mapping or artificial signal alignment, which may be unsuitable for neonates with highly variable pulse arrival time (PAT). In this study, we propose an alignment-free RoPE-based dual-stream Transformer for reconstructing missing neonatal ECG segments using concurrent PPG signals and bidirectional ECG context. A total of 52,566 10-second ECG–PPG windows were extracted from 159 NICU patients and split at the patient level to prevent data leakage. The model was designed to learn ECG–PPG temporal coupling without forced synchronization by integrating PPG-derived hemodynamic timing information with lead-specific ECG context. In the primary reconstruction analysis under a 40% random missing condition, the model achieved a Pearson correlation coefficient of 0.96, mean absolute error of 0.04, and root mean square error of 0.07. In stress-test analyses, the model maintained PCC values of at least 0.90 under both 4.0-second continuous block loss and 60% random patch loss. These findings suggest that the proposed framework may serve as a signal imputation module for maintaining ECG monitoring continuity in NICU environments. Prospective validation is required before clinical diagnostic use.

Background/Objectives: This study investigated whether meconium microbial profiles differed according to postnatal growth failure (PGF) and whether gestational age (GA)-related microbial maturation patterns appeared to vary according to subsequent growth status. Methods: Meconium samples were collected from 310 neonates born at 22–40 weeks of gestation, and 16S rRNA sequencing was conducted. After excluding small-for-gestational-age infants, the analyses included 151 samples from PGF+ infants and 131 samples from PGF− infants. Microbial composition, alpha and beta diversity were compared according to PGF status. Distance-based redundancy analyses (dbRDA) were conducted to evaluate the independent association between PGF and microbiome composition. Results: The core meconium microbiome differed between groups. PGF+ infants showed a predominance of Proteobacteria (36.60% vs. 27.96%), whereas PGF− infants had relatively higher abundances of Firmicutes (35.47% vs. 30.64%) and Bacteroidetes (28.96% vs. 26.19%) than PGF+ infants. GA-related microbial maturation patterns also differed between groups. At the genus level, the PGF− group showed significant positive correlations with GA for Faecalibacterium, Sutterella, Dialister, Megamonas, Escherichia/Shigella, and Roseburia after false discovery rate correction, whereas no genus-level correlation remained significant in the PGF+ group. Alpha diversity did not differ significantly between groups, whereas beta diversity differed modestly (R² = 0.0087, p = 0.042). After adjustment for GA and birth weight, the PGF effect remained significant in the Bray–Curtis-based dbRDA model, whereas it was not significant in the Jaccard-based model. Conclusions: PGF was associated with abundance-based shifts within shared meconium taxa, suggesting subtle differences in early microbial developmental patterns among infants who later developed PGF.

Background: Intraoperative arterial carbon dioxide partial pressure monitoring is essential for pediatric ventilatory management but requires invasive arterial sampling. While end-tidal carbon dioxide offers a noninvasive alternative, its reliability is limited by individual physiological gradients. This study developed a machine learning model to estimate arterial carbon dioxide partial pressure using end-tidal carbon dioxide and intraoperative clinical features in children. Methods: We retrospectively analyzed 8,853 paired end-tidal carbon dioxide and arterial carbon dioxide partial pressure measurements from 3,586 pediatric patients in the VitalDB database. Clinical and ventilatory features were used to train four machine learning algorithms, with missing data managed via age-group–based imputation. Model performance was verified through internal temporal validation using a recent dataset of 2,138 pairs and external validation using an independent dataset of 92 pairs from a distinct hospital. Feature importance was assessed using Shapley Additive Explanations values. Results: The Gradient Boosting model performed best, yielding a mean absolute error of 2.73 mmHg and root mean squared error of 4.13 mmHg. External validation confirmed generalizability with a mean absolute error of 3.65 mmHg (institutional) and 3.67 mmHg (temporal). End-tidal carbon dioxide, body temperature, fraction of inspired oxygen, and preoperative hemoglobin emerged as the most impactful features. Conclusions: Our machine learning model accurately estimates intraoperative arterial carbon dioxide partial pressure using noninvasive parameters. The model demonstrates stable performance across temporal and external cohorts.

Very early-onset autosomal dominant polycystic kidney disease (VEO-ADPKD) caused by biallelic PKD1 mutations is extremely rare and often phenocopies autoso

Neonatal long QT syndrome (LQTS) is associated with substantial mortality and poses significant therapeutic challenges, particularly in cases refractory to beta-blocker monotherapy. Mexiletine is established for LQT3 caused by SCN5A gain-of-function mutations, but its role in potassium-channel-related neonatal LQTS is limited. We present two neonates with LQTS refractory to nadolol monotherapy: one with a heterozygous pathogenic SCN5A c.5287G > A (p.Val1763Met) variant (LQT3), and one with a heterozygous KCNQ1 exon 13–15 deletion (LQT1). In both cases, addition of mexiletine to nadolol was associated with QTc shortening, reduction in ectopic burden, and resolution of 2:1 atrioventricular conduction in Case 1; no adverse events were documented. We describe the clinical experience descriptively, without proposing a generalizable mechanistic claim regarding mexiletine outside LQT3. No ICD implantation was performed and no deaths occurred during follow-up. These observations support further evaluation of mexiletine as an adjunct in refractory neonatal LQTS, including non-LQT3 subtypes.

Background: Retinopathy of prematurity (ROP) remains a leading cause of preventable childhood blindness. While gestational age (GA) and oxygen therapy are established risk factors, prior research has largely treated oxygen exposure as an aggregate variable, without disaggregating the impact of specific respiratory support modalities. This study investigated whether the mode and duration of respiratory support independently influence ROP risk. Methods: We conducted a single-center retrospective cohort study of 83 preterm infants (GA 2), mean airway pressure (MAP), positive end-expiratory pressure (PEEP), and peak inspiratory pressure (PIP)] at postnatal days 1, 3, 7, and 10 were extracted from continuous electronic medical records (EMRs). Associations with ROP were evaluated using Firth’s penalized logistic regression, with and without GA adjustment. Results: ROP was diagnosed in 52 infants (62.7%). In unadjusted analyses, GA [odds ratio (OR) =0.54; 95% confidence interval (CI): 0.35–0.80; P2), or respiratory severity index showed an independent association after adjustment for GA. Conclusions: NCPAP duration is independently associated with ROP in infants born before 28 weeks, with each additional day associated with a 4% increase in risk after adjustment for GA. This association was independent of mean FiO₂, suggesting that oxygenation variability during spontaneous breathing may be a more proximal pathophysiological driver; however, as oxygen saturation (SpO₂) variability was not directly measured, this interpretation should be regarded as hypothesis-generating. NCPAP duration may serve as a practical EMR-derived metric for ROP risk stratification in the NICU.

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.

Background: Genetic disorders are major causes of morbidity and mortality in neonatal intensive care units (NICUs), yet traditional tests like karyotyping and chromosomal microarray (CMA) often fail to provide a diagnosis, resulting in a "diagnostic odyssey". Trio whole-genome sequencing (WGS) has emerged as a comprehensive tool capable of detecting a wide range of variants beyond protein-coding regions, potentially offering higher diagnostic yields and rapid, actionable results for critical care management. Methods: This prospective study evaluated 16 neonates with multiple congenital anomalies who had previously received negative results from conventional genetic investigations. Trio WGS was performed using the Illumina NovaSeq 6000 platform, targeting a mean coverage of 30x. A stringent bioinformatics pipeline and a three-step filtering process were applied to prioritize rare functional variants (MAF < 0.1%) and genes specifically curated for NICU-associated conditions. Results: A molecular diagnosis was achieved in 37.5% (6/16) of the cases within the first 6 months of age. Pathogenic or likely pathogenic variants were identified in genes including SCN4A, DLL1, ACTA1, KLHL40, CHD7, and CNTNAP1, covering both autosomal recessive and autosomal dominant inheritance patterns. These findings provided definitive diagnoses for complex conditions such as arthrogryposis, congenital myopathy, and CHARGE syndrome. Conclusion: Trio WGS is a highly effective and feasible diagnostic tool for neonates with clinically heterogeneous anomalies, successfully identifying causes where standard-of-care testing fails. Its implementation in the NICU facilitates targeted medical management, informs prognosis, and provides essential data for family planning.