Background: Achieving a definitive genetic diagnosis of unexplained multiple congenital anomalies (MCAs) in neonatal intensive care units (NICUs) infants is challenging because of the limited diagnostic capabilities of conventional genetic tests. Although the implementation of whole genome sequencing (WGS) has commenced for diagnosing MCAs, due to constraints in resources and faculty, many NICUs continue to utilize chromosomal microarray (CMA) and/or karyotyping as the initial diagnostic approach. We aimed to evaluate the diagnostic efficacy of WGS in infants with MCAs who have received negative results from karyotyping and/or CMA. Methods: In this prospective study, we enrolled 80 infants with MCAs who were admitted to a NICU at a single center and had received negative results from CMA and/or karyotyping.The phenotypic characteristics were classified according to the International Classification of Diseases and the Human Phenotype Ontology. We assessed the diagnostic yield of trioWGS in infants with normal chromosomal result and explored the process of diagnosing by analyzing both phenotype and genotype. Also, we compared the phenotype and clinical outcomes between the groups diagnosed with WGS and the undiagnosed group. Results: The diagnostic yield of WGS was 26% (21/80), of which 76% were novel variants.There was a higher diagnostic yield in cases of craniofacial abnormalities, including those of the eye and ear, and a lower diagnostic yield in cases of gastrointestinal and genitourinary abnormalities. In addition, higher rates of rehabilitation therapy and gastrostomy were observed in WGS-diagnosed infants than in undiagnosed infants. Conclusion This prospective cohort study assessed the usefulness of trio-WGS following chromosomal analysis for diagnosing MCAs in the NICU and revealed improvements in the diagnostic yield and clinical utility of WGS.

Objective: To investigate whether reader training improves the performance and agreement of radiologists in interpreting unenhanced breast magnetic resonance imaging (MRI) scans using diffusion-weighted imaging (DWI). Materials and Methods: A study of 96 breasts (35 cancers, 24 benign, and 37 negative) in 48 asymptomatic women was performed between June 2019 and October 2020. High-resolution DWI with b-values of 0, 800, and 1200 sec/mm 2 was performed using a 3.0-T system. Sixteen breast radiologists independently reviewed the DWI, apparent diffusion coefficient maps, and T1-weighted MRI scans and recorded the Breast Imaging Reporting and Data System (BI-RADS) category for each breast. After a 2-h training session and a 5-month washout period, they re-evaluated the BI-RADS categories. A BI-RADS category of 4 (lesions with at least two suspicious criteria) or 5 (more than two suspicious criteria) was considered positive.The per-breast diagnostic performance of each reader was compared between the first and second reviews. Inter-reader agreement was evaluated using a multi-rater κ analysis and intraclass correlation coefficient (ICC). Results: Before training, the mean sensitivity, specificity, and accuracy of the 16 readers were 70.7% (95% confidence interval [CI]: 59.4–79.9), 90.8% (95% CI: 85.6–94.2), and 83.5% (95% CI: 78.6–87.4), respectively. After training, significant improvements in specificity (95.2%; 95% CI: 90.8–97.5; P = 0.001) and accuracy (85.9%; 95% CI: 80.9–89.8; P = 0.01) were observed, but no difference in sensitivity (69.8%; 95% CI: 58.1–79.4; P = 0.58) was observed. Regarding inter-reader agreement, the κ values were 0.57 (95% CI: 0.52–0.63) before training and 0.68 (95% CI: 0.62–0.74) after training, with a difference of 0.11 (95% CI: 0.02–0.18; P = 0.01). The ICC was 0.73 (95% CI: 0.69–0.74) before training and 0.79 (95% CI: 0.76–0.80) after training (P = 0.002). Conclusion Brief reader training improved the performance and agreement of interpretations by breast radiologists using unenhanced MRI with DWI.

Purpose: Hypothermia upon admission to the neonatal intensive care unit (NICU) contributes significantly to various neonatal complications, particularly in preterm infants. This study aimed to assess the impact of quality improvement (QI) interventions, including using plastic bags and head caps, and adjusting delivery room temperatures, on improving the admission body temperature and reducing hypothermia in infants born at less than 32 weeks or weighing 1,500 g. Methods: This study retrospectively analyzed the medical records of infants born at less than 32 weeks or weighing 1,500 g who admitted to the NICU at Samsung Medical Center from January 2022 to February 2024. The QI program that was initiated in April 2023 focused on managing admission temperatures using plastic bags and head caps, and maintaining delivery room temperatures at ≥25 °C. The admission temperature and short-term outcomes pre- and post-QI were compared. Results: In a study of 270 patients, implementing QI initiatives significantly raised the admission temperature from 36.2±0.5 to 36.4±0.4 °C (p<0.01), particularly impacting infants weighing ≥1,000 g, in whom mild hypothermia occurrences dropped from 76.3% to 43.9% (p<0.01). This improvement in temperature management significantly decreased both mild and severe hypothermia rates post-QI. Additionally, implementing all three initiatives was more effective than when two or fewer initiatives were implemented. Conclusion Simple and cost-effective QI interventions can increase admission temperatures and decrease hypothermia in neonates. Further research is essential to explore the long-term outcomes and develop effective hypothermia management strategies in neonatal care.

Purpose: To investigate the risk factors associated with hypospadias in very low birth weight (VLBW) infants (VLBWIs). Methods: We retrospectively analyzed 729 infants born at ≥24 weeks of gestational age and weighing <1,500 g from January 2012 to December 2022. We assessed the prevalence of hypospadias by birth weight percentiles and also compared the demographics and placental histopathology of the infants with hypospadias (n=52) and those without hypospadias (n=677). Results: Of the 729 patients analysed, hypospadias was recorded in 26 (20.3%), 14 (26.9%), and 12 (2.5%) infants in the <3rd, ≥3rd–<10th, and ≥10th–<90th percentiles, respectively. Of all of the patients with hypospadias, 50% had birth weights <3rd percentile (p<0.001). The hypospadias group demonstrated a longer mean gestational age (30.1 weeks vs. 27.9 weeks, p<0.001), lower incidence of maternal pregnancy-induced hypertension (48.1% vs. 17.3%, p<0.001), lower incidence of premature rupture of membrane (11.5% vs. 27.1%, p=0.013), lower acute chorioamniotic maternal response (9.1% vs. 35.2%, p<0.001), and higher maternal underperfusion (95.5% vs. 71.9%, p<0.001). Conclusion The frequency of hypospadias was found to be the highest among VBLWIs <3rd percentile, who were severely small for their gestational age (SGA). Additionally, the incidence increased with a decreasing birth weight. Physical examination is necessary at birth for VLBWIs classified as SGA. Moreover, the data on the incidence of hypospadias among VLBWIs in neonatal intensive care units can assist in tracking counseling from the prenatal to the postnatal period for patients born <3rd percentile.

Background: Despite the popularity of the NeoBase 2 Non-derivatized MSMS assay (PerkinElmer, Turku, Finland), there are no reports of its comprehensive evaluation, including the ability to distinguish transient tyrosinemia of the newborn (TTN) from tyrosinemia type 1 (TYR 1) using succinylacetone (SUAC). No newborn screening (NBS) cutoffs for preterm neonates in the Korean population have been suggested. We evaluated the NeoBase 2 assay and identified analytes requiring different cutoffs in preterm neonates. Methods: Residual NBS dried blood spot samples and proficiency testing (PT) materials of the Newborn Screening Quality Assurance Program and the Korean Association of External Quality Assessment Service were used. Precision, accuracy, limit of detection (LOD), lower limit of quantification (LLOQ), linearity, recovery, carryover, and performance of SUAC were evaluated. Cutoffs were determined, and analytes requiring different cutoffs in preterm neonates were investigated. Results: Mean CVs for within-run and between-day precision were within 15%. Accuracy analysis indicated high agreement with in-house derivatized assay results and results of other PT participants. All analytes demonstrated acceptable LOD, LLOQ, and linearity. Recoveries were acceptable, except for SUAC. Carryover was negligible. Cutoffs were established for all analytes; Tyr, adenosine, and C20:0-lysophosphatidylcholine required different cutoffs in preterm neonates. Differential diagnosis of TYR 1 and TTN was successful with simultaneous Tyr and SUAC measurement. Conclusions The NeoBase 2 assay demonstrated satisfactory performance. The additional analytes provide a wider diagnostic coverage, and the simultaneous measurement of Tyr and SUAC is efficient in excluding TYR 1. The new cutoffs for preterm neonates may decrease false-positive rates, without compromising diagnostic sensitivity.

Intravascular lymphoma is characterized by an exclusively intravascular distribution of tumor cells. Intravascular natural killer/T-cell lymphoma (IVNKTL) is extremely rare, highly aggressive, commonly Epstein-Barr virus (EBV)–positive, and predominantly affects the skin and central nervous system. Here we report a case of IVNKTL diagnosed in a 67-year-old female, presenting with persistent intermittent fever and skin rashes throughout the body. Incisional biopsy of an erythematous lesion on the chest exhibited aggregation of medium to large-sized atypical lymphoid cells confined to the lumen of small vessels that were positive for CD3, granzyme B, and CD56 on immunohistochemistry and EBV-encoded RNA in situ hybridization. EBV DNA was also detected in serum after diagnosis. With a review of 26 cases of IVNKTL to date, we suggest that active biopsy based on EBV DNA detection may facilitate early diagnosis of IVNKTL.

Background: In accordance with the guidelines for the expectant management of women exposed to previable preterm premature rupture of membrane, we compared neonatal outcomes according to the latent period from membrane rupture to delivery among extremely preterm infants exposed to maternal preterm premature rupture of membrane using the Korean Neonatal Network database. Methods: Of the 3,305 extremely preterm infants born at 23–27 weeks' gestation between 2014 and 2017 who were registered in the Korean Neonatal Network, 1,464 infants were born to pregnant women who were exposed to preterm premature rupture of membrane. The short latency group was defined as infants born with a latent period between membrane rupture and delivery < 7 days (n = 450), whereas the prolonged latency group was defined as infants born with a latent period of ≥ 7 days (n = 434). Using well-established risk factors for adverse short-term outcomes, multivariate logistic regression analysis was performed to assess a prolonged latent period in preterm premature rupture of membrane as an independent risk factor for neonatal outcomes in extremely preterm infants exposed to preterm premature rupture of membrane. Results: The mean gestational age at membrane rupture in the prolonged latency group was significantly lower than that in the short latency group (22.7 ± 2.5 vs. 25.4 ± 1.3 weeks, P < 0.001). Nevertheless, the mean gestational age at delivery and birth weight were not significantly different between the two groups. The incidence of oligohydramnios and histologic chorioamnionitis in the prolonged latency group was significantly higher than that in the short latency group (38.7 [155/401] vs. 26.1 [105/403], 69.8 [270/384] vs. 61.0 [242/397], respectively, P < 0.05). The survival rate in the prolonged latency group did not differ from that in the short latency group (71.2 [309/434] vs. 73.3 [330/450], P = 0.478). Although the prolonged latency group was not associated with mortality during hospitalization in the multivariate logistic regression analysis, the prolonged latency group's early pulmonary hypertension and bronchopulmonary dysplasia rates were increased by 1.8 and 1.5 times, respectively. Conclusion A prolonged latent period of 7 days or more does not affect the survival rate but increases the risk of bronchopulmonary dysplasia occurrence among extremely preterm infants who are exposed to maternal preterm premature rupture of membrane.

Background: In accordance with the guidelines for the expectant management of women exposed to previable preterm premature rupture of membrane, we compared neonatal outcomes according to the latent period from membrane rupture to delivery among extremely preterm infants exposed to maternal preterm premature rupture of membrane using the Korean Neonatal Network database. Methods: Of the 3,305 extremely preterm infants born at 23–27 weeks' gestation between 2014 and 2017 who were registered in the Korean Neonatal Network, 1,464 infants were born to pregnant women who were exposed to preterm premature rupture of membrane. The short latency group was defined as infants born with a latent period between membrane rupture and delivery < 7 days (n = 450), whereas the prolonged latency group was defined as infants born with a latent period of ≥ 7 days (n = 434). Using well-established risk factors for adverse short-term outcomes, multivariate logistic regression analysis was performed to assess a prolonged latent period in preterm premature rupture of membrane as an independent risk factor for neonatal outcomes in extremely preterm infants exposed to preterm premature rupture of membrane. Results: The mean gestational age at membrane rupture in the prolonged latency group was significantly lower than that in the short latency group (22.7 ± 2.5 vs. 25.4 ± 1.3 weeks, P < 0.001). Nevertheless, the mean gestational age at delivery and birth weight were not significantly different between the two groups. The incidence of oligohydramnios and histologic chorioamnionitis in the prolonged latency group was significantly higher than that in the short latency group (38.7 [155/401] vs. 26.1 [105/403], 69.8 [270/384] vs. 61.0 [242/397], respectively, P < 0.05). The survival rate in the prolonged latency group did not differ from that in the short latency group (71.2 [309/434] vs. 73.3 [330/450], P = 0.478). Although the prolonged latency group was not associated with mortality during hospitalization in the multivariate logistic regression analysis, the prolonged latency group's early pulmonary hypertension and bronchopulmonary dysplasia rates were increased by 1.8 and 1.5 times, respectively. Conclusion A prolonged latent period of 7 days or more does not affect the survival rate but increases the risk of bronchopulmonary dysplasia occurrence among extremely preterm infants who are exposed to maternal preterm premature rupture of membrane.

Purpose: We aimed to compare two different sedation protocols for brain magnetic resonance imaging (MRI) in preterm infants. One protocol used chloral hydrate (CH) with monitoring conducted by non-anesthesiologists, and the other used a continuous infusion of propofol (PF) with monitoring by anesthesiologists. Methods: A total of 250 preterm infants born between January 2011 and December 2015 who received brain MRI during hospitalization in our neonatal intensive care unit (NICU) were included in this retrospective study. In period 1, sedation for brain MRI was done using a single dose or multiple doses of CH with monitoring conducted by NICU medical staff. In period 2, an anesthesiologist prescribed a continuous infu­sion of PF and titrated the dosage for minimal and adequate sedation. Data on the adverse events, including desaturation and bradycardia, were collected and compared between periods 1 and 2. Results: Despite similar gestational ages of the patients in periods 1 and 2, the infants in period 1 showed a higher risk of developing bradycardia after sedation compared to those in period 2 (30.2% vs. 14.8%; an adjusted odds ratio of 2.35; 95% confidence interval of 1.12 to 4.91). Infants who had an adverse event after sedation had a lower gestational age and corrected age at the time of MRI (26.8 weeks vs. 27.9 weeks, P=0.004; 37.3 weeks vs. 38.3 weeks, P=0.023). The duration of MRI was significantly longer in infants that had an adverse event than those that did not (70.9 minutes vs.64.3 minutes). After adju­sting for various clinical factors, lower gestational age, lower corrected age at the time of MRI, and period 1 increased the risk of developing adverse events after sedation for MRI. Conclusion The use of a continuous PF infusion with dose titration and monitoring by an anesthesiologist is safe and feasible as a sedation protocol for brain MRI in prematurely born infants.

Purpose: To compare respiratory outcomes between less invasive surfactant admi nistration (LISA) and the intubation-surfactant-extubation (INSURE) technique in premature infants with respiratory distress syndrome (RDS). Methods: We performed a retrospective medical chart review for 75 premature in fants who were born at a gestational age (GA) of ≤34 weeks (between January 2017 and December 2019) and developed RDS after birth. Data on the demographic and outcome variables, including respiratory outcomes, were collected and compared between the infants who received LISA and those who received INSURE as a rescue therapy for RDS. Results: No signifcant differences in GA, birth weight, and other demographic characteristics were found between the LISA and INSURE groups (GA: 28.7 weeks vs.28.8 weeks, P=0.449; birth weight: 1,236 g vs. 1,124 g, P=0.714). At the delivery room, although the infants showed no significant difference in positive pressure ventilation rate after birth, the LISA group showed a higher rate of continuous positive airway pressure application than the INSURE group. The infants in the LISA group presented a higher risk of requiring multiple doses of surfactant for RDS than the infants in the INSURE group (57% vs. 17.5%, P=0.001). However, the duration of invasive and/ or noninvasive respiratory support and incidence of bronchopulmonary dysplasia showed no signifciant difference between the two groups. Conclusion In the present study, no significant differences in the incidence of inhospital respiratory outcomes such as bronchopulmonary dysplasia were found between the LISA and INSURE groups. These results suggest that LISA can be an alternative therapeutic option for treating RDS to avoid intubation and mechanica ventilation in premature infants.