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Background: Congenital anomalies (CAs) encompass a wide spectrum of structural and functional abnormalities during fetal development, commonly presenting at birth. Identifying the cause of CA is essential for accurate diagnosis and treatment. Using a target-gene approach, genetic variants could be found in certain CA patients. However, some patients were genetically undiagnosed; therefore, it is imperative to identify the causative variants from whole genome sequence (WGS) data of these patients. Results: An in-house pipeline utilizing DRAGEN-GATK-Hail was established for trio-based WGS data analysis (n = 18 undiagnosed CA patients and their parents) and thirty-five candidate variants, including SNV/Indel, CNV, and SV were identified. Among them, 10 variants of seven coding genes were selected as possible causal variants by variant pathogenicity, genotype–phenotype analysis, and a multidisciplinary team. Finally, functional validation of six genes including RYR3, NRXN1, FREM2, CSMD1, RARS1, and NOTCH1, revealed various phenotypes in zebrafish models that aligned with those observed in each patient. In addition to the above findings, eleven diagnostic variants initially discovered in a targeted-gene analysis from a previous study were also identified as diagnostic variants and the in-house pipeline demonstrated a significant advantage in accurately and efficiently identifying de novo variants (DNVs), compound heterozygous (CH), and homozygous variants. Conclusions: Taken together, the in-house pipeline established in this study provides a highly valuable diagnostic tool for the identification of potential candidate variants in patients with CA. Further research into the molecular mechanisms related to the development of CAs could shed light on the functional aspects of these genetic variations and contribute to the development of therapeutic drugs. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]