Rotavirus hospitalization in early childhood: fine motor skills and cognition at six years old-Population-based cohort study.

Rotavirus is linked to severe childhood gastroenteritis and neurological complications, but its impact on neurodevelopment remains uncertain. We examined data from 1,420,941 Korean children born between 2009 and 2011, using the Korean National Health Insurance System. At age 6, we assessed neurodevelopmental outcomes using the validated Korean Developmental Test, covering six major domains. Utilizing propensity score-based Inverse Probability Weighting to ensure covariates including considering covariates including sex, birth weight, changes in body weight from birth to 4-6 months of age, head circumference at 4-6 months of age, residence at birth, economic status, infant feeding types, and birth year. The main analysis that encompassed 5,451 children with rotavirus hospitalization and 310,874 unexposed individuals reveled heightened odds of suspected delays in fine motor skills and cognition among exposed children. Our results suggest an association between rotavirus-related hospitalization in infancy and suspected delays in fine motor function and cognition in 6-year-olds.

Familial focal segmental glomerulosclerosis associated with a WT1 gene missense mutation: A case report.

Focal s egmental glomerulosclerosis (F SGS) can cause protei nuria and loss o f k idney fun ction, leading to e ndstage renal di s ease (ESRD). Podocyte injury is the ce ntral pathophysiologi cal mechanis m of hereditary FSGS. Numerous mutations in genes e ncoding or affe cting the transcriptional regulation of podocyte cell compar tments have been detected in patients with genetic FSGS. Herein, we report a rare case of familial FSGS with an autosomal dominant WT1 mutation. A 63-year- old man developed pro teinuri a; his reading showed over 1g prote in/day. A pa thological diagn osis of FSG S was made after rena l biops y. H is elder brother an d a 36-year- old son also had ESRD. Heterozygous variant of WT1 (NM_024426.4) c.1373G>A (p.Arg458Gln ) mi s sense was dete cted in the patient a nd his son , by whole-exome sequen cing. Although genetic screening is not a par t of routine practice, it s hould be per for med in such cases to a id a ppropriate tre atment options sel ecting, revealing extra ren al symptoms, and family planning.

Growth hormone deficiency in a boy with Wiedemann-Steiner syndrome: A case report and review.

Wiedemann-Steiner syndrome (WSS) is a rare genetic disorder characterized by a broad phenotypic spectrum, including facial dysmorphism, hypertrichosis, hypotonia, short stature, and developmental delay. Mutations in the lysine (K)-specific methyltransferase 2A (KMT2A) gene are known to cause WSS. A 2 year-old boy with a short stature visited our pediatric endocrinology clinic for a diagnostic examination. In addition to his short stature, he had other symptoms characteristic of WSS including dysmorphic features and developmental delay. Whole-exome sequencing was performed in order to diagnose any underlying genetic condition; the test detected the presence of the mutant variant of KMT2A:c.731T>G(p.Leu244*). Since the patient showed a decreased growth velocity after 18 months of age, a growth hormone provocation test was performed to check for growth hormone (GH) deficiency. The patient's peak GH level was found to be 6.96 ng/mL and recombinant human GH treatment was started. This case of WSS along with growth hormone deficiency (GHD) in a pediatric patient is the first report of its kind in Korea, to the best of our knowledge. WSS should be considered as a possibility in pediatric patients with short stature, especially in the presence of additional clinical symptoms, such as dysmorphic features and developmental delay.

Diagnostic performance of automated, streamlined, daily updated exome analysis in patients with neurodevelopmental delay.

BACKGROUND: The diagnostic yield of whole-exome sequencing (WES) varies from 30%-50% among patients with mild to severe neurodevelopmental delay (NDD)/intellectual disability (ID). Routine retrospective reanalysis of undiagnosed patients has increased the total diagnostic yield by 10-15%. Here, we performed proband-only WES of 1065 patients with NDD/ID and applied a prospective, daily reanalysis automated pipeline to patients without clinically significant variants to facilitate diagnoses. METHODS: The study included 1065 consecutive patients from 1056 nonconsanguineous unrelated families from 10 multimedical centers in South Korea between April 2018 and August 2021. WES data were analyzed daily using automatically updated databases with variant classification and symptom similarity scoring systems. RESULTS: At the initial analysis, 402 patients from 1056 unrelated families (38.0%, 402/1,056 families) had a positive genetic diagnosis. Daily prospective, automated reanalysis resulted in the identification of 34 additional diagnostic variants in 31 patients (3%), which increased our molecular diagnostic yield to 41% (433/1056 families). Among these 31 patients, 26 were diagnosed with 23 different diseases that were newly discovered after 2019. The time interval between the first analysis and the molecular diagnosis by reanalysis was 1.2 ± 0.9 years, which was shorter in the patients enrolled during the latter part of the study period. CONCLUSION: Daily updated databases and reanalysis systems enhance the diagnostic performance in patients with NDD/ID, contributing to the rapid diagnosis of undiagnosed patients by applying the latest molecular genetic information.

Changes in childhood growth after adenotonsillectomy: a population-based cohort study.

OBJECTIVES: This study aimed to investigate the association between adenotonsillectomy (T&A) and serial changes in growth in children through a population-based nationwide study as well as the national health insurance service (NHIS) database. METHODS: Propensity score (PS) matched children with and without T&A were selected in NHIS database, which includes all individuals born in Korea in 2008-2009. Serial changes of BMI and height were compared in children with and without T&A, and growth changes depending on the time of operation were also considered. The outcomes were differences in age-/sex-standardized BMI (BMI-z) and height (height-z) between the groups. Changes in BMI-z and height-z were further analyzed according to the timing of operation. RESULTS: Of 919,707 individuals born in Korea in 2008-2009, 3172 children were included in the operation group and 31,663 PS-matched children were included in the control group. T&A was related to increased weight and height in the operation group than in the control group. At 66-71 months of age, BMI-z and height-z were 0.41 (0.02) and 0.42 (0.02), respectively, in the operation group and 0.18 (0.01) and 0.35 (0.01), respectively, in the control group. On adjustment with preoperative BMI-z, more weight gain was noted in the operation group (p < 0.001). Shortly after T&A, BMI-z increased significantly in the operation group; a significant increase in height-z was observed more than 1 year after T&A. CONCLUSIONS: Children who underwent T&A tended to experience a growth spurt; when surgical intervention such as T&A is required, care should be taken to minimize or reverse the anticipated weight gain.

Assessment of vitamin D, exercise, and lipid profile associated with excessive daytime sleepiness in school children.

Previous research reported associations of excessive daytime sleepiness (EDS) with a low vitamin D level, obesity, and sexual maturity. The aim of this study was to identify the association and rank the importance of these with EDS. This study examined 618 children who were 10-12 year-old. The pediatric daytime sleepiness scale (PDSS) was used to evaluate EDS and sleep patterns. EDS was defined as a total PDSS score above 17. We ranked the importance of the relationship of these factors with EDS using random forest analysis. EDS (n = 111, 18%) was positively associated with more advanced pubertal stage in girls, chronic cough, urticaria, and allergic rhinitis. Multivariable analysis with adjustment for confounding indicated that children with low level of 25-hydroxyvitaminD3 (25(OH)D3 (<20 ng/mL) and high-density lipoprotein-cholesterol (HDL-C) (<40 mg/dL) levels had an increased risk of EDS (25(OH)D3:adjusted odds ratio [aOR] = 1.73; 95% confidence interval [CI]: 1.06 to 2.81; P = 0.028; HDL-C: aOR = 2.84; 95% CI: 1.05 to 7.68; P = 0.039). Random forest analysis indicated that 25(OH)D3 level, exercise, and body mass index (BMI) were over three. This study indicated high levels of 25-(OH)D3 and HDL-C and performing regular exercise decreased the risk of EDS.

Potentiation of cord blood cell therapy with erythropoietin for children with CP: a 2 × 2 factorial randomized placebo-controlled trial.

BACKGROUND: Concomitant administration of allogeneic umbilical cord blood (UCB) infusion and erythropoietin (EPO) showed therapeutic efficacy in children with cerebral palsy (CP). However, no clinical studies have investigated the effects of UCB and EPO combination therapy using a 2 × 2 four-arm factorial blinded design with four arms. This randomized placebo-controlled trial aimed to identify the synergistic and individual efficacies of UCB cell and EPO for the treatment of CP. METHODS: Children diagnosed with CP were randomly segregated into four groups: (A) UCB+EPO, (B) UCB+placebo EPO, (C) placebo UCB+EPO, and (D) placebo UCB+placebo EPO. Based on the UCB unit selection criteria of matching for ≥ 4/6 of human leukocyte antigen (HLA)-A, -B, and DRB1 and total nucleated cell (TNC) number of ≥ 3 × 107/kg, allogeneic UCB was intravenously infused and 500 IU/kg human recombinant EPO was administered six times. Functional measurements, brain imaging studies, and electroencephalography were performed from baseline until 12 months post-treatment. Furthermore, adverse events were closely monitored. RESULTS: Eighty-eight of 92 children enrolled (3.05 ± 1.22 years) completed the study. Change in gross motor performance measure (GMPM) was greater in group A than in group D at 1 month (△2.30 vs. △0.71, P = 0.025) and 12 months (△6.85 vs. △2.34, P = 0.018) post-treatment. GMPM change ratios were calculated to adjust motor function at the baseline. Group A showed a larger improvement in the GMPM change ratio at 1 month and 12 months post-treatment than group D. At 12 months post-treatment, the GMPM change ratios were in the order of groups A, B, C, and D. These results indicate synergistic effect of UCB and EPO combination better than each single therapy. In diffusion tensor imaging, the change ratio of fractional anisotropy at spinothalamic radiation was higher in group A than group D in subgroup of age ≥ 3 years. Additionally, higher TNC and more HLA-matched UCB units led to better gross motor outcomes in group A. Adverse events remained unchanged upon UCB or EPO administration. CONCLUSIONS: These results indicate that the efficacy of allogeneic UCB cell could be potentiated by EPO for neurological recovery in children with CP without harmful effects. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01991145 , registered 25 November 2013.

Reconsideration of urine culture for the diagnosis of acute pyelonephritis in children: a new challenging method for diagnosing acute pyelonephritis.

Acute pyelonephritis (APN) should be detected and treated as soon as possible to reduce the risk of the development of acquired renal scarring. However, in the medical field, urine culture results are not available or considered when the prompt discrimination of APN is necessary and empirical treatment is started. Furthermore, urine culture cannot discriminate APN among children with febrile urinary tract infection (UTI) (pyelitis, lower UTI with other fever focus). Therefore, the usefulness of urine culture for diagnostic purposes is small and the sampling procedure is invasive. Congenital hypoplastic kidney is the most common cause of chronic kidney injury in children. Thus, it is desirable that a main target be detected as early as possible when imaging studies are performed in children with APN. However, if APN does not recur, no medical or surgical treatment or imaging studies would be needed because the acquired renal scar would not progress further. Therefore, the long-term prognosis of APN in young children, particularly infants, depends on the number of recurrent APN, not other febrile UTI. New methods that enable prompt, practical, and comfortable APN diagnosis in children are needed as alternatives to urinary catheterization for urine culture sampling.

Antinatriuretic phenomena seen in children with acute pyelonephritis may be related to the activation of intrarenal RAAS.

We investigated whether antinatriuretic phenomena [decreases in urinary sodium (uNa) and fractional excretion of sodium (FENa)] seen in children with acute pyelonephritis (APN) are associated with the renin-angiotensin-aldosterone system (RAAS).We examined 114 children experiencing their first episode of febrile urinary tract infection (fUTI) consecutively admitted to our hospital from July 2012 to June 2014. Blood tests [C-reactive protein, white blood cell count, erythrocyte sedimentation rate, and aldosterone (Aldo)] and urine tests [uNa, urine potassium (uK) and FENa] were performed upon admission. All enrolled children underwent a 99m-dimercaptosuccinic acid renal scanning (DMSA) at admission. Areas with cortical defects (AreaCD) and uptake counts (UptakeCD) on their DMSA scans were calculated. Data were compared between children with positive DMSA results (APN), lower urinary tract infection (L-UTI), and controls; and between children with high and low Aldo levels.uNa, uNa/K, and FENa negatively correlated with AreaCD%, UptakeCD, and Aldo; were significantly lower in APN patients than in LUTIs and controls regardless of Aldo level; were lower in the high Aldo group than in the low Aldo group. However, there is no difference in AreaCD% and UptakeCD between APN children with the high and low Aldo level.Decreases in uNa, uNa/K, and FENa in children with APN may result from an antinatriuretic effect of RAAS and be related to the activation of the intrarenal RAAS.

Effects of school time on sleep duration and sleepiness in adolescents.

Delaying the time of start of school allows for longer sleep duration, better mood, and better school performance. In South Korea, a campaign was launched in 2014 to delay the school start time to 9 a.m. We analyzed the campaign's effects on adolescents' total sleep duration, sleepiness (presented as weekend catch-up sleep), emotions, and school performance. Based on data from 2013, changes of sleep patterns, emotions, and academic achievement in adolescents were evaluated using the 2012-2016 Korea Youth Risk Behavior Web-based survey from two educational districts: Gyeonggi (fully participated in the delayed school start time campaign; intervention group) and Daegu/Gyeongbuk/Ulsan (DGU, never participated; control group). The primary outcomes were sleep duration, time of sleep onset, and difference in sleep duration between weekdays and the weekend. Secondary outcomes were the proportional changes of mood, stress, and school performance. The sleep duration of students in the intervention group temporarily increased in 2015. However, because there was a simultaneous delay in time of sleep onset, sleep duration returned to pre-campaign levels in 2016. Although sleep duration did not increase, weekend catch-up sleep decreased by approximately 19 minutes for students in the intervention group. Meanwhile, in the control group sleep duration tended to decrease over the same period. The impact of the campaign on students' emotions and school performance could not be confirmed. This study demonstrated that delaying the school start time to 9 a.m. reduced duration of weekend catch-up sleep with a transient increase in sleep duration in adolescents.

My child cannot breathe while sleeping: a report of three cases and review.

BACKGROUND: Sudden breath-holding episodes during sleep in young children are potentially related to sudden infant death syndrome and other life-threatening events. Additionally, these episodes can negatively affect child's growth and development. CASE PRESENTATION: Here, we present 3 cases of preschool children with similar paroxysmal nocturnal waking events associated with choking that had different etiologies (nocturnal frontal lobe epilepsy, nocturnal gastroesophageal reflux disease, and parasomnia, respectively). CONCLUSIONS: It is important to take into consideration the fact that breath spells during sleep can occur as a rare manifestation of parasomnia due to gastroesophageal reflux or as a symptom of nocturnal frontal lobe epilepsy. Full video electroencephalography, polysomnography, and simultaneous gastric pH monitoring should be used for the differential diagnosis of sleep-related disorders, such as breath spells, in children.

Sleep-wake cycle on amplitude-integrated EEG and neuroimage outcomes in newborns.

BACKGROUND: The aim of this study was to evaluate the results of sleep-wake cycle monitoring using amplitude-integrated EEG (aEEG) and neuroimaging in newborn infants with a possible perinatal hypoxic insult, investigate the correlation between the findings, and determine the relevance of the findings to reasonably predict neurological outcome. METHODS: aEEG was recorded among newborn infants suspected of perinatal asphyxia between November, 2014 and June, 2015 in one neonatal intensive care unit facility. Brain imaging with serial ultrasonography and MRI when available were performed, and the infants were divided into two groups according to findings and potential neurological outcome: Group I (favorable findings) and Group II (severe findings such as high grade intraventricular hemorrhage, cerebral infarction or white matter injury). Established sleep-wake cycle times after birth was compared between the two groups. RESULTS: Among 107 newborn infants, 85 subjects were classified as Group I and the remaining 22 subjects as Group II. The total number of aEEG sessions was 207 and recording time was 2,796 h with a mean of 14.43 ± 13.40 h per study. Estimated times of cyclicity were earlier in Group I (113.34 h, 95 % CI 82.31-144.37) as compared to Group II (504.39 h, 95 % CI 319.91-688.88; p < 0.001). CONCLUSIONS: Delayed cyclicity on aEEG has a strong correlation with unfavorable brain neuroimages in newborns with possible perinatal asphyxia. If sleep-wake cycles do not appear during initial period after birth, follow-up aEEG studies are recommended. TRIAL REGISTRATION: Retrospectively registered Registration number: BD 2015-148 Name of registry: amplitude integrated EEG in neonate Date of registration: September 9, 2015.

Pandemic influenza A vaccination and incidence of Guillain-Barré syndrome in Korea.

BACKGROUND: Many studies have investigated the association between Guillain-Barré syndrome (GBS) and vaccinations during the influenza A H1N1 pandemic of 2009 (pH1N1). Based on a nationally representative sample, we estimated the incidence of GBS during the pandemic period in Korea. MATERIALS AND METHODS: All medical records of GBS cases were reviewed in 28 randomly selected hospitals during 2008-2010, and the number of GBS cases at the national level was extrapolated using emergency care utilization data. The GBS rate per 100,000 person-years was estimated in the reference and pandemic periods. RESULTS: The incidence of GBS was 0.63 (95% CI: 0.37-0.89) per 100,000 person-years in the reference period and 0.87 (0.49-1.26) in the pandemic period. During the vaccination season, the pandemic period GBS incidence rate was not significantly higher than the reference period incidence rate (rate ratio: 1.52; 0.99-2.32), but difference was observed among persons aged 20-34 years. Rate of GBS increased after pH1N1 vaccination compared to the reference period (1.46, 1.26-1.68). DISCUSSION: The incidence of GBS increased slightly but not significantly during the pandemic period, although pH1N1 vaccination increased the GBS rate. Therefore, mass influenza vaccination programs should not be precluded on the basis of GBS.

Depression and marital intimacy level in parents of infants with sleep onset association disorder: a preliminary study on the effect of sleep education.

PURPOSE: Sleep onset association disorder (SOAD) is a form of behavioral insomnia observed in children that is caused by inappropriate sleep training. SOAD typically disturbs the sleep of not only infants and children but also their parents. We investigated levels of depression and marital intimacy among parents of infants with typical SOAD, to understand the influence of SOAD on family dynamics, as well as examine ways for improving depression and marital intimacy through behavioral training. METHODS: Depression and marital intimacy were assessed using the Beck Depression Inventory (BDI) and Waring Intimacy Questionnaire (WIQ). These measures were administered to 65 parents of infants (n=50) diagnosed with SOAD. We conducted sleep education and behavioral training for the parents and compared levels of depression and marital intimacy after 2-6 weeks of training. RESULTS: The 65 parents consisted of 50 mothers and 15 fathers. Depressive symptoms were higher among mothers than fathers (P =0.007). Marital intimacy was negatively correlated with depressive symptoms. Twenty-six parents were assessed again after sleep training. We found that mothers' depressive symptoms and marital intimacy improved post training. CONCLUSION: SOAD can be detrimental to both infants and parents, especially for parents who sleep with their infants. For instance, disruption of sleep patterns in such parents can reduce marital intimacy. However, behavioral modification is an effective treatment for infants with frequent nighttime waking, as well as for diminishing the depressive symptoms of sleep-deprived parents.

Percutaneous endoscopic gastrostomy in children.

PURPOSE: Percutaneous endoscopic gastrostomy (PEG) can improve nutritional status and reduce the amount of time needed to feed neurologically impaired children. We evaluated the characteristics, complications, and outcomes of neurologically impaired children treated with PEG. METHODS: We retrospectively reviewed the records of 32 neurologically impaired children who underwent PEG between March 2002 and August 2008 at our medical center. Forty-two PEG procedures comprising 32 PEG insertions and 10 PEG exchanges, were performed. The mean follow-up time was 12.2 (6.6) months. RESULTS: Mean patient age was 9.4 (4.5) years. The main indications for PEG insertion were swallowing difficulty with GI bleeding due to nasogastric tube placement and/or the presence of gastroesophageal reflux disease (GERD). The overall rate of complications was 47%, with early complications evident in 25% of patients and late complications in 22%. The late complications included one gastro-colic fistula, two cases of aggravated GERD, and four instances of wound infection. Among the 15 patients with histological evidence of GERD before PEG, 13 (87%) had less severe GERD, experienced no new aspiration events, and showed increased body weight after PEG treatment. CONCLUSION: PEG is a safe, effective, and relatively simple technique affording long-term enteral nutritional support in neurologically impaired children. Following PEG treatment, the body weight of most patients increased and the levels of vomiting, GI bleeding, and aspiration fell. We suggest that PEG with post-procedural observation be considered for enteral nutritional support of neurologically impaired children.

Sleep patterns and school performance of Korean adolescents assessed using a Korean version of the pediatric daytime sleepiness scale.

PURPOSE: Korean adolescents have severe nighttime sleep deprivation and daytime sleepiness because of their competitive educational environment. However, daytime sleep patterns and sleepiness have never been studied using age-specific methods, such as the pediatric daytime sleepiness scale (PDSS). We surveyed the daytime sleepiness of Korean adolescents using a Korean translation of the PDSS. METHODS: We distributed the 27-item questionnaire, including the PDSS and questions related to sleep pattern, sleep satisfaction, and emotional state, to 3,370 students in grades 5-12. RESULTS: The amount of nighttime sleep decreased significantly with increasing age. During weekday nights, 5-6(th) graders slept for 7.95±1.05 h, 7-9(th) graders for 7.57±1.05 h, and 10-12(th) graders for 5.78±1.13 h. However, the total amounts of combined daytime and nighttime sleep during weekdays were somewhat greater, 8.15±1.12 h for 5-6(th) graders, 8.17±1.20 h for 7-9(th) graders, and 6.87±1.40 h for 10-12(th) graders. PDSS scores increased with age, 11.89±5.56 for 5-6(th) graders, 16.57±5.57 for 7-9(th) graders, and 17.71±5.24 for 10-12(th) graders. Higher PDSS scores were positively correlated with poor school performance and emotional instability. CONCLUSION: Korean teenagers sleep to an unusual extent during the day because of nighttime sleep deprivation. This negatively affects school performance and emotional stability. A Korean translation of the PDSS was effective in evaluating the severity of daytime sleepiness and assessing the emotional state and school performance of Korean teenagers.