Byung Min Choi

Utility of Rapid B-Type Natriuretic Peptide Assay for Diagnosis of Symptomatic Patent Ductus Arteriosus in Preterm Infants

Objective. In preterm infants, the rapid and accurate determination of the presence of a hemodynamically significant patent ductus arteriosus (PDA) is extremely important, but this is often difficult. Plasma B-type natriuretic peptide (BNP) measurement has been reported to be a helpful aid in the diagnosis of hemodynamically significant PDA in preterm infants. The aim of our study was to investigate the usefulness of a rapid BNP assay as a diagnostic marker of symptomatic PDA (sPDA) in preterm infants. Methods. Sixty-six preterm infants, ranging from 25 to 34 gestational weeks of age, underwent clinical and echocardiographic examinations for PDA every other day from the third day of life until the disappearance of ductal flow. Blood samples were collected and plasma BNP concentrations were measured simultaneously using a commercial kit, (Triage BNP test kit; Biosite Diagnositics, San Diego, CA). When ≥2 clinically significant features of PDA were noted, and a large ductal flow was confirmed by color Doppler echocardiography, sPDA was diagnosed and treated with indomethacin. Results. On the third day after birth, the mean BNP concentration in the sPDA group (n = 23) was significantly higher than in the control group (n = 43) (2896 ± 1627 vs 208 ± 313 pg/mL). Seventeen infants (74%) in the sPDA group became asymptomatic after an initial course of indomethacin and their BNP levels concomitantly decreased. Moreover, BNP concentrations were significantly correlated with the magnitudes of the ductal shunt, such as the ratio of left atrial to aortic root diameter and the diastolic flow velocity of the left pulmonary artery (r = 0.726 and 0.877). The area under the receiver operator characteristic curve for the detection of sPDA was high: 0.997 (95% confidence interval: 0.991–1.004). The best cutoff of BNP concentration for the diagnosis of sPDA was determined to be 1110 pg/mL (sensitivity: 100%; specificity: 95.3%). Conclusion. In preterm infants, the circulating BNP levels correlated well with the clinical and echocardiographic assessments of PDA. Although not a stand-alone test, the rapid BNP assay provides valuable information for the detection of infants with sPDA that require treatment. Moreover, serial BNP measurements may be of value in determining the clinical course of PDA in preterm infants.

Utility of the Rapid B-Type Natriuretic Peptide Assay for Detection of Cardiovascular Problems in Newborn Infants with Respiratory Difficulties

Background: Because the major problems of respiratory difficulties in newborn infants are due to cardiopulmonary problems, improving the early detection and referral of newborn infants with cardiovascular problems has been considered one of the primary goals of care in the neonatal intensive care unit. Objective: To evaluate whether rapid plasma B-type natriuretic peptide (BNP) assay could be used as a screening test to detect the cardiovascular problems in newborn infants with respiratory difficulties. Methods: We studied 73 newborn infants ≧34 weeks gestational age presenting with respiratory difficulties during the first few days after birth; they were divided into a cardiovascular problem group (CP group, n = 32) and a noncardiac problem group (NP group, n = 41) according to the presence of cardiovascular problems by clinical and/or echocardiographic studies in newborn infants with respiratory difficulties. Results: On admission, the median (25–75%) BNP concentration of the CP group was significantly higher than that of the NP group [1,038 (578–1,435) vs. 240 (118–388) pg/ml, p < 0.001]. The best cutoff BNP values for differentiating the CP group were 346.0, 421.0, 570.5 and 191.5 pg/ml within 18 h, at 18–36 h, at 36–60 h and after 60 h of life, respectively. Although the plasma BNP measurement was not a single confirmative test, it was found to have a high sensitivity and a high negative predictive value for rapidly ruling out serious cardiovascular problems in neonatal respiratory difficulties. Conclusion: A rapid plasma BNP assay may be useful for detection of cardiovascular problems in newborn infants with respiratory difficulties during the first few days after birth.

Indomethacin Treatment Decreases Renal Blood Flow Velocity in Human Neonates

This study was designed to evaluate the effect of indomethacin (ID) on renal perfusion in 13 neonates with symptomatic patent ductus arteriosus (PDA). Serial blood flow velocity in the left renal artery was measured just before and at 10, 30, 45, 60, 75 and 90 min after ID administration. Serum creatinine (Cr), sodium (Na), and osmolarity were measured just before, at 12 and 24 h, and at 3 days after ID administration. Timed urine also was collected for measurement of amount, fractional excretion of Na (FENa), and creatinine clearance (CCr). ID decreased end-diastolic flow velocity of renal artery and increased Pourcelot’s index, starting at 10 min and lasting for 75 min (p < 0.05). Serum Cr significantly increased at 12 h, and hourly urine output and CCr decreased for 24 h. Serum Na and osmolarity decreased for a period of at least 3 days (p < 0.05). FENa decreased at 12–24 h (p < 0.05). We conclude that ID treatment can induce significant renal dysfunction due to diminution of renal perfusion in human neonates.

Serum Kisspeptin Levels in Korean Girls with Central Precocious Puberty

Central precocious puberty (CPP) is caused by premature activation of hypothalamic gonadotropin-releasing hormone (GnRH) secretion. Kisspeptin and G-protein coupled receptor-54 system is the essential gatekeeper of the reproductive system, playing a key role in the activation of the gonadotropic axis at puberty. We aimed to determine whether serum kisspeptin may function as a marker for CPP by investigating serum kisspeptin levels in Korean girls with CPP and their prepubertal controls. Serum kisspeptin levels of Korean girls with CPP (n = 30) and age-matched healthy prepubertal controls (n = 30) were measured with a competitive enzyme immunoassay. Serum kisspeptin levels were significantly higher in CPP group than in control group (4.61 ± 1.78 vs 2.15 ± 1.52 pM/L, P < 0.001). Serum kisspeptin was positively correlated with peak luteinizing hormone (LH), peak/basal LH ratio and peak LH/follicular-stimulating hormone (FSH) ratio during GnRH stimulation test. CPP is supposed to be triggered by premature increase of kisspeptin. Serum kisspeptin may be used as a marker of CPP. Further studies on KISS1 gene polymorphisms leading to higher risk of premature increase of kisspeptin and upstream regulator of kisspeptin are also needed.

Association of serum retinol binding protein 4 with adiposity and pubertal development in Korean children and adolescents.

Retinol binding protein 4 (RBP4) has been postulated to provide a new link between obesity and insulin resistance. We aimed to assess the relationship between serum RBP4 and insulin resistance by investigating serum RBP4 levels in children and adolescents according to degree of obesity and pubertal stage. A total of 103 (30 lean, 39 overweight, 34 obese) were evaluated for serum RBP4, adiponectin, insulin, glucose and lipid profiles. RBP4 levels of obese and overweight groups were higher than those of lean group. RBP4 level was higher in pubertal group than in prepubertal group. RBP4 was positively correlated with age, height, weight, body mass index (BMI), abdominal circumference, systolic blood pressure, fasting insulin, homeostatic model assessment of insulin resistance (HOMA-IR), total cholesterol and triglyceride, and inversely with adiponectin. In the multiple linear regression analysis, RBP4 was found to be independently associated with pubertal stage, BMI and triglyceride but not with HOMA-IR. In conclusion, serum RBP4 level is related with degree of adiposity and pubertal development. The association of RBP4 with insulin resistance is supposed to be secondary to the relation between RBP4 and adipose tissue in children and adolescents.

Can early B-type natriuretic peptide assays predict symptomatic patent ductus arteriosus in extremely low birth weight infants?

Background: Earlier and more accurate identification of a high-risk group of preterm infants that are likely to develop a hemodynamically significant patent ductus arteriosus (hsPDA) would allow specific targeting of early treatment and thus possibly minimize the morbidity and mortality associated with a PDA in extremely low birth weight (ELBW) infants. Objective: To investigate the predictability of B-type natriuretic peptide (BNP) for early targeted treatment of hsPDA in ELBW infants. Methods: 73 ELBW infants that underwent echocardiographic evaluation and plasma BNP measurement after birth were enrolled. 31 infants developed hsPDA (HsPDA group) and 42 infants did not develop hsPDA (nPDA group). Results: BNP levels of the HsPDA group were significantly higher than those of the nPDA group at 24 h of age (921 [318–2,133] vs. 152 [91–450] pg/ml) but not different at 12 h of age. BNP levels at 24 h of age were significantly correlated with the magnitudes of the ductal shunt but not at 12 h of age. The area under the receiver operator characteristic curve of BNP levels for prediction of hsPDA at 24 h of age was 0.830. At the cutoff BNP levels of 200 and 900 pg/ml at 24 h of age, sensitivity was 83.9 and 54.8% and specificity was 61.9 and 95.2%, respectively. Conclusions: BNP levels at 24 h of age can be used as a guide for early targeted treatment of hsPDA and avoid the unnecessary use of cyclooxygenase inhibitors in ELBW infants.

Angiotensin-converting enzyme inhibition modulates mitogen-activated protein kinase family expressions in the neonatal rat kidney.

Among the mitogen-activated protein kinase (MAPK) family members, extracellular signal–regulated kinase (ERK) promotes cell proliferation or differentiation, whereas c-jun N terminal kinase (JNK) and p38 MAPK are thought to inhibit cell growth and induce apoptosis. The MAPK family may plays some role during kidney development, when large-scale proliferation and apoptosis have been observed to occur. Also, in this period, the renin-angiotensin system is markedly activated. We have demonstrated that angiotensin-converting enzyme inhibition in the developing rat kidney increases apoptosis and decreases cell proliferation, which may account for renal growth impairment. The aim of this study, therefore, was to examine the relationship between the MAPK family and renin-angiotensin system during neonatal renal development. Newborn rat pups were treated with enalapril (30 mg · kg−1 · d−1) or normal saline for 7 d. Right kidneys of both groups were selected for immunohistochemical stains of MAPKs and activating transcription factor-2 (ATF-2), and left kidneys were selected for reverse transcriptase–PCR and immunoblot analysis of MAPKs, phospho-MAPKs, and ATF-2. To determine whether apoptosis is involved in the same tubules that highly expressed JNK and p38, we performed terminal deoxynucleotide transferase-mediated nick-end labeling stain for apoptotic cells and immunohistochemical stains for JNK-2, p38, and ATF-2 expression in the serial sections from the same kidney of the enalapril-treated group. In the enalapril-treated group, JNK-2, p38, phospho-JNK-2, phospho-p38, and ATF-2 protein expressions were significantly increased, and their immunoactivities were strongly detected in the proximal tubular epithelial cells in the cortex, compared with the control group. Especially JNK-2 and p38 expressions were highly activated and were spatially in accordance with the occurrence of apoptosis. ERK1/2 and phospho-ERK expressions were not changed by enalapril. These results suggest that the expressions of the MAPK family are modulated by angiotensin-converting enzyme inhibition in the developing kidney. JNK and p38 may be implicated to participate in angiotensin II–related intracellular signaling pathways of renal apoptosis in the developing kidney.

Genetic polymorphism of the renin-angiotensin system on the development of primary vesicoureteral reflux

Background: The familial clustering of vesicoureteral reflux (VUR) has suggested a genetic basis. This study was designed to investigate the genetic polymorphism of the renin-angiotensin system (RAS) in Korean children. Methods: Genetic polymorphism of angiotensin-converting enzyme (ACE) and angiotensin II receptor genes was evaluated in 67 primary VUR patients and compared to 58 controls with no urological abnormalities. To detect the relation of the risk factors of primary VUR with the genetic polymorphism, the distribution of ACE, AT1 and AT2 genotypes after stratification by risk factors was also studied in the primary VUR patients. Results: The incidence of AT2 A-1332G transition was significantly lower in primary VUR patients (p = 0.047). Furthermore, in the case of combination of ACE and AT2 gene, a significantly lower incidence of primary VUR was seen with II genotype of ACE and A-1332G transition in the AT2 receptor gene (p = 0.003). Concerning the risk factors of primary VUR, there were no biologically significant results. Conclusions: These findings indicate that a lower incidence of AT2 A-1332G transition is seen in primary VUR patients, at least in the Korean population. Also, in the case of combination of ACE and AT2 gene, the combination of ACE II genotype and AT2 A-1332G transition occurs infrequently in primary VUR.

Outbreak of Late-onset Group B Streptococcal Infections in Healthy Newborn Infants after Discharge from a Maternity Hospital : A Case Report

During a four-week period, four healthy term newborn infants born at a regional maternity hospital in Korea developed late-onset neonatal group B Streptococcus (GBS) infections, after being discharged from the same nursery. More than 10 days after their discharge, all of the infants developed fever, lethargy, and poor feeding behavior, and were subsequently admitted to the Korea University Medical Center, Ansan Hospital. GBS was isolated from the blood cultures of three babies; furthermore, GBS was isolated from 2 cerebral spinal fluid cultures. Three babies had meningitis, and GBS was isolated from their cerebral spinal fluid cultures. This outbreak was believed to reflect delayed infection after early colonization, originating from nosocomial sources within the hospital environment. This report underlines the necessity for Korean obstetricians and pediatricians to be aware of the risk of nosocomial transmissions of GBS infection in the delivery room and/or the nursery.

Aldosterone Modulates Cell Proliferation and Apoptosis in the Neonatal Rat Heart

In the present study, we investigated whether and how the mineralocorticoid receptor antagonist spironolactone affects cardiac growth and development through apoptosis and cell proliferation in the neonatal rat heart. Newborn rat pups were treated with spironolactone (200 mg/kg/d) for 7 days. The cell proliferation was studied by PCNA immunostaining. The treatment with spironolactone decreased proliferating myocytes by 32% (P<0.05), and reduced myocytes apoptosis by 29% (P<0.05). Immunoblot and immunohistochemistry for the expression of p38, p53, clusterin, TGF-β2, and extracellular signal-regulated kinase were performed. In the spironolactone group, p38, p53, clusterin, and TGF-β2 protein expression was significantly decreased (P<0.05). These results indicate that aldosterone inhibition in the developing rat heart induces cardiac growth impairment by decreasing proliferation and apoptosis of myocytes.