Cystatin C as a Renal Function Marker for Neonates

The prediction of acute kidney injury (AKI) is important in the management of neonates, and several renal biomarkers have been tested for clinical application. Cystatin C (CysC) is a promising marker of renal function, and its application in neonatal care showed several benefits. First, CysC levels are not affected by endogenous substances such as bilirubin, hemoglobin, and ketones in laboratory tests. Second, its level is not influenced by inflammation (e.g., sepsis), muscle mass, age, gender, or nutritional status. Third, CysC is not transmitted through the placenta. Fourth, standardized automated measurement methods are available. Fifth, CysC was shown to reflect renal maturation better than creatinine. Lastly, CysC was reported to change with a wider amplitude than creatinine, which allows a more sensitive detection of renal deterioration. Recently, several reference CysC levels for neonates, including premature infants, were reported. In the present review, we summarized information on serum CysC reference values from different studies. Few studies investigated the usefulness of CysC for predicting AKI in neonates with various diseases such as neonatal respiratory distress syndrome, sepsis, and neonatal asphyxia. Recent studies showed an association between serum CysC level and cardiovascular diseases or Alzheimer's disease, indicating that CysC may play a role as a marker for various diseases in the future. Although the use of CysC as a marker in neonatal care showed several benefits, reliable and detailed reference ranges need to be established, including those for neonates with diseases. In addition, other novel renal markers need to be tested in neonates.

Low Basophil Count and Red Cell Distribution Width at Birth May Predict the Development of Neonatal Necrotizing Enterocolitis: A Matched Control Study

OBJECTIVE: The pathophysiology of necrotizing enterocolitis (NEC) is incompletely understood. There were some reports that the pathogenesis of NEC involves intrauterine process and infants with fulminant NEC had low lymphocyte count. Thus, we investigated complete blood count (CBC) parameters of infants at birth and their mothers near delivery. METHODS: We retrospectively reviewed the medical records of NEC patients and controls. The CBC parameters were compared between infants with NEC (modified Bell's criteria stage > or =Ia, n=82) and controls matched for gestational age, birth weight, gender, and race (n=169). The blood test findings were obtained from infants within the first 2 hours of life and from mothers as the latest one before delivery. RESULTS: Statistically different findings at birth were found in NEC infants; red cell distribution width (RDW) and basophil count. In the multiple logistic regression analysis after adjustment for gestational age, birth weight, and gender, several infantile independent risk factors were identified; basophil count <40/microL (odds ratio [OR], 4.60; 95% confidence interval [CI], 2.18 to 9.73; P<0.001) and low RDW (OR, 7.15; 95% CI, 2.93 to 17.41; P<0.001). CONCLUSION: We found that NEC was associated with low infantile RDW and basophil count at birth. These findings might support roles of red blood cell and basophil in the pathogenesis of NEC, which might predict development of NEC with neonatal findings at birth.

Clinical Study of Neonatal Pelvicectasia

OBJECTIVE: This study was conducted to investigate the different cause of pelvicectasia and its clinical outcome. The most important management of pelvicectasia consist of the early diagnosis and evaluation of the pathologic abnormalities of congenital pelvicectasia. This will help to offer the guideline on management of neonatal pelvicectasia. METHODS: We examined one hundred and seventy-one live neonates who were hospitalized and diagnosed with pelvicectasia at Soonchunhyang University Cheonan Hospital from January 2008 to December 2008. A retrospective study was carried out in these patients for last three years. Renal ultrasonography was repeated at 1 month after birth and then 3 months interval. Diuretic renal scan with (99m)Tc-labeled diethylenetriamine pentaacetic acid augmented with furosemide and voiding cystourethrogram was done after 4 to 6 weeks of first renal ultrasonography. Patients were followed-up for 1 to 30 months (average, 7.2 months). RESULTS: Pelvicectasia was postnatally detected in 171 cases (33.7%) among 507 neonates. Males were twice than females. Additional imaging studies revealed that normal kidney structure was the most common postnatal diagnosis (97.1%), followed by ureteropelvic obstruction, vesicoureteral reflux, multicystic kidney, ureteric duplication. Spontaneous regression of pelvicectasia was revealed in 165 renal units (67.6%). CONCLUSION: There are many cause of spontaneous regression in mild to moderate pelvicectasia. Urinary tract infection occurs in many neonates with pelvicectasia. Mild to moderate neonatal pelvicectasia without vesicoureteral reflux is clinically much less significant. Accordingly, close observation with serial renal ultrasonography may be sufficient.

The Importance of Gases in Portal Veins and Liver Parenchyme is Characterized by Liver Ultrasonography in Full-term Neonates with Necrotizing Enterocolitis

PURPOSE: Although early treatment of neonatal necrotizing enterocolitis (NEC) is very important, there exists no definite way of diagnosing NEC at an early stage. Previous reports argue that gases in portal veins and liver parenchyme are detected by liver ultrasonography (USG) even when no symptoms corresponding to NEC are provoked. This study demonstrates the importance of liver USG for early diagnosis of NEC. METHODS: Abdominal USG was performed on 1381 newborn infants who were admitted to the neonatal intensive care unit of Soonchunhyang University Cheonan Hospital between February 2003 and September 2005. Twelve infants were diagnosed with NEC by liver USG and their individual pathologies were compared. RESULTS: All of the patients described here were full-term and the most frequent symptom observed was watery diarrhea; four had no symptoms at all. Severe metabolic acidosis was seen in two patients, a rise of C-reactive protein (CRP) in five patients and rotavirus antigen positivity in five patients. One of the patients showed portal vein gas, pneumatosis intestinalis and ileus in a simple abdominal radiography and another patient showed ileus only. However, all of the other 10 patients presented with no abnormal symptoms, according to simple abdominal radiography. CONCLUSION: NEC should be considered in neonates with gases present in portal veins, intestinal walls and liver parenchyme, as detected by liver USG even when no symptoms corresponding to NEC are provoked.

Relationship between Pulmonary Surfactant Protein and Lipid Peroxidation in Lung Injury due to Paraquat Intoxication in Rats

BACKGROUND: Pulmonary damage resulting from lipid peroxidation is a principal effect of paraquat intoxication. The host-defense functions of surfactant are known to be mediated by the surfactant proteins A and D (SP-A and SP-D, respectively). The primary objective of this study was to evaluate the variations over time in levels of surfactant protein and lipid peroxidation (LPO) in lung tissue following free-radical-induced injury. METHODS: 42 adult, male, Sprague-Dawley rats were administered intraperitoneal injections of paraquat (35 mg/kg body weight). SP-A and SP-D levels were determined via Western blot. LPO in the left lung homogenate was measured via analyses of the levels of thiobarbituric acid-reactive substances. RESULTS: LPO levels peaked at 6 hours, with no associated histological changes. SP-D levels increased until hour 12 and declined until hour 48; SP-D levels subsequently began to increase again, peaking at hour 72. SP-A levels peaked at hour 6, declining thereafter. CONCLUSIONS: We suggest that in the early phase of paraquat injury, SP-D levels reflect alveolar damage and that de novo synthesis of SP-D takes 72 hours. Levels of SP-A, on the other hand, reflect abnormalities in the surfactant system in the late stage of paraquat intoxication. Surfactant proteins may play a role in protecting the lungs from reactive oxygen injury. A time-dependent variation has been observed in the levels of surfactant proteins A and D following paraquat injury, and it has been suggested that these proteins play a role in the protection of lung tissue against ROS-induced injuries.

Allele Distribution of Human Surfactant Protein A in Otitis Media with Effusion / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Surfactant protein A (SP-A) which plays a role in the innate host defense of lung is also expressed in Eustachian tube. However the genes underlying the susceptibility to otitis media with effusion (OME) are known insufficiently. The current study attempts to evaluate the difference in the allele distribution of SP-A1 and SP-A2 between normal subjects and subjects with otitis media with effusion. SUBJECTS AND METHOD: PCR-cRFLP-based methodology was used to detect SP-A genotypes in the 38 children with OME, and in the 55 normal newborns for control. RESULTS: The frequencies of specific genotypes such as 6A(2), 1A(2) were increased in OME group, but the frequency of 6A3 was increased in control group. CONCLUSION: It is presumed that SP-A alleles may be inductive (6A(2), 1A(2)) or protective (6A(3)) factors for OME. Specific genoytypes of SP-A may be an important determinant for the predisposition to OME.

Association between the Human Surfactant Protein-A(SP-A) Gene Locus and Chronic Obstructive Pulmonary Disease in Korean Population / 결핵및호흡기질환

BACKGROUNDS: This study investigated whether or not a polymorphism in the gene encoding the surfactant protein A(SP-A) has any bearing on the individual susceptibility to the development of chronic obstructive pulmonary disease(COPD) in a genetically homogenous Korean population. METHODS: The genotypes of 19 COPD patients and 20 healthy neonates as controls were tested using a polymerase chain reaction followed by restriction fragment length polymorphism analysis for the SP-A gene. RESULTS: The specific frequencies of the 6A2 and 6A18 alleles of SP-A1 and the 1A2 allele of SP-A2 were much higher in the COPD group than control group (p<0.05). However, the frequencies of the 6A3 and 6A4 alleles of SP-A1 and the 1A0 allele of SP-A2 in the COPD group were significantly lower than the control group. In the COPD group, the frequencies of the +50 locus genotypes GG of SP-A1 and the +9 locus genotypes CC of SP-A2 were 85.0% and 60.6%, respectively, and 19.7% and 24.8% in the control group, respectively. The frequencies of the polymorphic genotypes or alleles showed a statistically significant difference between the COPD group and the control group (P<0.05). CONCLUSION: A genetic polymorphism in SP-A is associated with the development of COPD in the Korean population.

A Study on the Relationship Between the Morphologic Change and Surfactant Protein (SP)-A and Surfactant Protein (SP)-D Levels in Intratracheal Bleomycin-Induced Pulmonary Fibrosis in White Rats / 대한주산의학회잡지

OBJECTIVE: Surfactant protein (SP)-A and SP-D are involved in host defense mechanism. The author was prompted to perform a study on morphologic change and SP-A, SP-D level of surfactant after pulmonary injury inflicted by intratracheal bleomycin injection. METHODS: Fifteen white adult rats each weighing 250 g (Sprague-Daw ley) were divided into study (receiving bleomycin, n=9) and control groups (n=6). Study group were given a intratracheal injection of belomycin (5 mg/kg). Two groups were grown for five weeks at twenty five degrees Celsius, after which lung tissue were examined for morphologic change and SP-A and SP-D levels were measured using Western blot assay with densitometer. RESULTS: Before the study, the average weight of the study group was 286.69+/-14.54 g, and control was 286.69+/-14.54 g. Five weeks later, the average weight of the study group was 347.31.31+/-60.53 g and control group 352.71+/-16.84 g. However, no statistical significance was noted. On light microscopy, the control group exhibited normal findings while widening of lung interstitium and fibrotic change coupled with more prominent inflammatory cell infiltration were noted in the study group. The SP-A level were 15.34+/-1.52 ODU/microgram in the study group and 7.70+/-2.81 ODU/microgram in the control. SP-D level were 3.53+/-1.46 ODU/microgram and 7.51+/-2.33 ODU/microgram in the study and control groups respectively, there was a statistical significance (p<0.05). CONCLUSION: The morphologic change after pulmonary fibrosis induced by intratracheal bleomycin injection in white rats can be summarized as chronic inflammatory cell infiltration, fibroblast proliferation, deposition of collagen tissues, and lowering of SP-D level were noted. The increase of SP-A level is subject to further study in the future.

Successful Removal of Common Bile Duct Stone Using Endoscopic Papillary Balloon Dilation (EPBD), in A 28-month-old Child with Down's Syndrome / 대한소화기내시경학회지

Although cholelithiasis is an uncommon condition in infants, a recent study documented the increasing detection of this disorder. This increase may be explained by the wide use and improvement in abdominal ultrasound. Choledocholithiasis with cholestatic jaundice in infants usually requires therapeutic intervention, even though the incidence of spontaneous resolution has been reported to be higher in infants than adults. Choledocholithiasis in children has traditionally been managed surgically with open common duct exploration. Recently, endoscopic stone removal was accepted as a standard therapy in pediatric choledocholithiasis. We report a case of the successful removal of common bile duct stone using endoscopic papillary balloon dilation (EPBD), in a 28-month-old infant with Down's syndrome.

Comparative Study between Bayley Scales of Infant Development-II and Korean Infant and Child Developmental Test in Infants Younger than 12 Months / 대한소아신경학회지

PURPOSE: Currently, there are many developmental tests of scale and screening for infants and children. However, it has been questioned about the discriminating power and the correlation among developmental tests of scale and screening. So we comprared the Bayley Scales of Infant Development-II(BSID-II) and Korean Infant and Child Developmental Test(KICDT) in terms of correlations and agreement. METHODS: Seventy two infants were studied, who visited the pediatric outpatient clinic at Cheonan Soonchunhyang University Hospital between December 2002 and September 2003. They were classified into three groups, group A of 24 full term infants, group B of 24 preterm infants, and group C of 24 disabled full term infants. We performed both tests to the all infants. RESULTS: The mean scores of mental and psychomotor developmental indices of BSID-II of group A were higher than those of group B and group C, which was statistically significant. Also, the mean scores of personal-social, language and cognitive- adaptive fields of KICDT of group A were much higher than those of group B and group C. The correlation coefficients between BSID-II and KICDT were high in many indices. The kappa coefficient by Cohen between BSID-II and KICDT is 0.45(0.24-0.66). CONCLUSION: There was a reasonable corrrelation between BSID-II and Korean infant and child developmental test in infants younger than 12 months. The kappa coefficient by Cohen between BSID-II and KICDT is not so good in this study. Further study is needed to standardize the items of KICDT.

Two Cases of Influenza-associated Encephalopathy / 대한소아신경학회지

Influenza-associated encephalopathy is typically associated with a sudden onset of high fever, severe convulsions, rapidly progressive coma and death within 2 or 3 days. It has been actively researched in Japan as it caused a tremendous increase in the number of deaths from 1997 to 2002. But there has been reported only one case in Korea, who was diagnosed on the basis of serologic testing by hemagglutinin inhibition. We report here a 14-month-old boy who was taken supportive care and a 3-year-old girl who was taken amantadine and methyprednisolone pulse therapy. Both of them were admitted under the diagnosis of influenza-associated encephalopathy on the basis of reverse transcription-polymerase chain reaction of nasopharyngeal fluid and cerebrospinal fluidm, brain magnetic resonance imagings. The first case was confirmed by the identification of influenza A/H3N2 in the cerebrospinal fluid culture by RT-PCR for the first time in Korea.

Human Surfactant Protein-A(SP-A) Gene Locus Associated with Mycoplasma pneumoniae Pneumonia in Korean Children / 소아과

PURPOSE: Mycoplasama pneumoniae is a leading cause of pneumonia and exacerbates other respiratory conditions such as asthma. Surfactant protein A(SP-A) is involved in surfactant physiology and surfactant structure, and plays a major role in innate host defense and inflammatory processes in the lung. In this study, SP-A mediated mycoplasma cidal activity. The candidate-gene approach was used to study the association between the SP-A gene locus and Mycoplasama pneumoniae pneumonia in the genetically homogeneous Korean population. METHODS: PCR-cRFLP-based methodology was used to detect SP-A genotype. The forty nine children with Mycoplasama pneumoniae pneumonia were matched to 50 nomal neonates. RESULTS: The specific frequencies for the alleles of the SP-A1 and SP-A2 gene in the study population were:6A2=21 percent, 6A3=45 percent, 6A4=11 percent, 6A8=9 percent, 6A14=8 percent, 1A=11.3 percent, 1A0=38 percent, 1A1=12.7 percent, 1A2=9.2 percent, 1A5=15.5 percent, 1A7=2.9 percent, 1A8=4.9 percent, 1A9=2.2 percent, others=3.3 percent. The frequencies of specific genotypes such as 1A2 was higher than control group, significantly. CONCLUSION: 1A2 are susceptible factors for Mycoplasama pneumoniae pneumonia. We conclude that the SP-A gene locus(1A2) is an important determinant for predisposition to Mycoplasama pneumoniae pneumonia in children.

A Case of Kawasaki Disease in a 16-year-old Girl Associated with Congestive Heart Failure

Kawasaki disease is an acute febrile vasculitis of childhood and leading cause of acquired heart disease in children. The illness occurs predominantly in young children and only occasionally occurs in teenagers and adults. So we report a case of adolescent-onset Kawasaki disease associated with congestive heart failure and development of coronary dilatation. A 16-year-old girl presented with fever, truncal rash, congestive heart failure due to myocarditis, bilateral conjunctival injection, strawberry tongue, redness of hands and feet, and cervical adenopathy. After Kawasaki disease was diagnosed, intravenous gamma globulin(2 g/kg) and aspirin(70 mg/kg/day) were administered. On the 20th hospital day, echocardiography showed moderate dilatation of right coronary artery. Four months after the discharge, follow up echocardiography showed sustained dilatation of right coronary artery.

A Case of Kawasaki Disease in a 16-year-old Girl Associated with Congestive Heart Failure

Kawasaki disease is an acute febrile vasculitis of childhood and leading cause of acquired heart disease in children. The illness occurs predominantly in young children and only occasionally occurs in teenagers and adults. So we report a case of adolescent-onset Kawasaki disease associated with congestive heart failure and development of coronary dilatation. A 16-year-old girl presented with fever, truncal rash, congestive heart failure due to myocarditis, bilateral conjunctival injection, strawberry tongue, redness of hands and feet, and cervical adenopathy. After Kawasaki disease was diagnosed, intravenous gamma globulin(2 g/kg) and aspirin(70 mg/kg/day) were administered. On the 20th hospital day, echocardiography showed moderate dilatation of right coronary artery. Four months after the discharge, follow up echocardiography showed sustained dilatation of right coronary artery.

Association between the Human Surfactant Protein-A(SP-A) Gene Locus and Respiratory Distress Syndrome in Korean Neonates / 소아과

PURPOSE: Respiratory distress syndrome(RDS) is caused by a deficiency of pulmonary surfactant, which is a lipoprotein complex. Both low levels of surfactant protein A(SP-A) and SP-A alleles have been associated with RDS. However, the genes underlying susceptibility to RDS are insufficiently known. The candidate-gene approach was used to study the association between the SP-A gene locus and RDS in the genetically homogeneous Korean population. METHODS: A PCR-cRFLP-based methodology was used to detect SP-A genotype. Twenty four neonates with RDS were matched pairwise to those without RDS. RESULTS: The frequencies of specific genotypes such as 6A(2), 1A(0) were increased, but the frequency of specific 1A(2) genotype was increased in control group. 6A(2)/1A(0) were also increased in the RDS group. Infants who did not have RDS develop, despite prematurity and lack of steroid therapy, had a higher frequency of the 1A(2) allele than infants who had received steroid therapy and had RDS develop. However, infants who had received steroid therapy and had RDS develop had a higher frequency of the 1A(0) allele than infants who did not have RDS develop, despite prematurity and lack of steroid therapy. CONCLUSION: SP-A alleles/haplotypes are susceptible(6A(2), 1A(0), 6A(2)/1A(0)) or protective(1A(2)) factors for RDS. We conclude that the SP-A gene locus is an important determinant for predisposition to RDS in neonates

Assessment of Cardiac Function in Neonates by Using Tissue Doppler Imaging / 소아과

PURPOSE: Tissue Doppler imaging(TDI) is recently being used for assessement of regional ventricular function in adults. However, data in neonates have not been established yet. The aim of this study is to establish reference values of TDI velocities and to investigate the effect of other factors on TDI velocites in the neonatal population. METHODS: Forty eight healthy neonates with anatomically normal hearts from July 2003 to August 2003 were enrolled. Blood was collected after 12 hours of birth and Troponin T(TnT) was measured. TDI of mitral and tricuspid annulus was obtained from apical four chamber views within three days. TDI measurements included peak early diastolic annular velocity, peak diastolic annular velocity with atrial contraction, peak systolic annular velocity and duration of systole. RESULTS: In neonates, peak systolic velocity and peak diastolic velocity were lower than those of children and adults. The ratio of peak early diastolic velocity to peak diastolic velocity with atrial contraction(e'/a') was lower compared with known data in children and adults. With faster heart rates, peak early diastolic velocity and peak systolic velocity of mitral septal annulus and peak early diastolic velocity of tricuspid lateral annulus were significantly increased. PFO, PDA and TR did not affect TDI parameters. CONCLUSION: Annular TDI parameters of neonates were different from those of children and adults. TDI is a simple, rapid tool for assessing global ventricular function and the data of this study can be used as reference values for ventricular dysfunction in the neonatal period.

A Case of Idiopathic Restless Legs Syndrome in a Child / 대한소아신경학회지

Restless legs syndrome(RLS) is a common but frequently undiagnosed sensorimotor disorder. It has distinct clinical manifestations and also it is fairly common in late adulthood. However, it is rarely recognized in children because of the difficulties in expressing the signs and symptoms and the lacks of experience of pediatricians about the disease. Although its underlying pathophysiology is not fully understood, the diagnostic criteria of RLS in children were established in the year of 2003. We experienced a case of idiopathic restless legs syndrome in a 10-year-old boy and we present the case with a brief review of related literature.

Clinical Progress of Three Cases of Shaken Baby Syndrome / 대한소아신경학회지

Shaken baby syndrome develop as a form of child abuse, with the majority of cases occurring during the first year of life. It results from extreme rotational cranial acceleration and deceleration effects induced by violent shaking of an infant. The characteristic injuries include subdural and subarachnoid hemorrhages, and retinal hemorrhages. We experienced three cases of shaken baby syndrome. Although the history of trauma was little known, all of these cases had subdural hemorrhages. We present the cases with a review of related literature.

Differential Response of Surfactant Protein-A Genetic Variants to Dexamethasone Treatment

PURPOSE: Surfactant protein A(SP-A) is involved in surfactant physiology and structure, and plays a major role in innate host defense and inflammatory processes in the lung. Steroid therapy is widely used for mothers who threaten to deliver prematurely and also used commonly in the management of preterm infants with chronic lung disease. Two SP-A genes(SP-A1, SP-A2) and several alleles have been characterized for each SP-A gene in human. Preliminary evidence indicates that differences may exist among alleles in response to Dexamethasone(Dexa) and that the SP-A 3'UTR plays a role in this process. We studied whether 3'UTR-mediated differences exist among the most frequently found SP-A alleles in response to Dexa. METHODS: Constructs containing the 3'UTR from eight different SP-A alleles were made using luciferase as a the reporter gene. These constructs were driven by the SV40 promotor and were transfected along with a transfection control vector in H441 cells that express SP-A. The activity of the reporter gene in the presence or absence of Dexa(100 nM) treatment was measured. All the experiments for the eight SP-A alleles studied, were performed in triplicate and repeated five times. The results were normalized to the transfection control. RESULTS: Expression of alleles of 6A3, 6A, 1A were significantly decreased in response to Dexa. CONCLUSION: Three UTR mediated differences exist among human SP-A variants both in the basal expression and in response to Dexa. These genotype-dependent differences may point to a need for a careful consideration of individual use of steroid treatment in the prematurely born infant.

Allele Distribution and Frequency of Human Surfactant Protein-A2 in Korean Neonates

PURPOSE: We evaluated allele frequencies and distribution of surfactant protein A2(SP-A2) in Korean neonates in order to estimate the prevalence of RDS, to find out new SP-A alleles, and to establish new steroid therapy. METHODS: Genomic DNA was extracted from 71 neonates and served as a template in PCR for genotype analysis. SP-A gene-specific amplications and gene-specific allele determinations were performed using PCR-cRFLP methods. RESULTS: The distribution for the alleles of the SP-A2 gene in the study population was 1A, 1A0, 1A1, 1A2, 1A3, 1A5, 1A6, 1A7, 1A8, 1A9, 1A11, 1A12. The specific frequencies for the alleles of the SP- A2 gene in the study population were : 1A=11.3%, 1A0=38%, 1A1=12.7%, 1A2=9.2%, 1A5=15.5%, 1A7= 2.9%, 1A8=4.9%, 1A9=2.2%, others=3.3%. CONCLUSION: The frequency of 1A0 was higher than the other SP-A2 alleles in Korean neonates. This finding suggests that the prevalence of RDS in Korea may be low compared with other countries. However, this finding also suggests that Korean neonates have a high risk of infection.