• Journal of Preventive Medicine and Public Health
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• v.32 no.3
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• pp.317-324
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• 1999

Objectives: Since 1991, nationwide massive neonatal screening program for phenylketonuria (PKU) and congenital hypothyroidism have been performed in Korea. As in many other countries, efficiency of this program has not been definitely concluded. For the purpose of evaluation of this program, from the perspective of efficiency, a cost-benefit analysis was carried out. Methods: Costs of the detection and the treatment program were compared with the projected benefit(avoided costs) that results from the prevention of the mental retardation associated with the disorders due to PKU and hypothyroidism. Costs and benefits were discounted at an annual rate of 5%, and duration of life-long labor was assumed to be 30 years. Cost and benefit were estimated based on the detection rates of one case of PKU per 5,572 and one case of congenital hypothyroidism per 32,554 babies screened during 1991-1997. Results: The benefit-cost ratio was 0.418. The sensitivity analysis for the discount rates and labor durations showed that most cost-benefit ratios were lower than one(1.0) except when discount rate was changed to 3% and detection rate to two- or threefold and/or labor duration to 40 years. Conclusion: The result of this study suggested that present program of mass screening for PKU and congenital hypothyroidism could not be justified in terms of efficiency. It doesn't coincide with the results of previous studies in major developed countries, presumably because of difference in detection rates and welfare cost for the disabled.

• Clinical and Experimental Pediatrics
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• v.63 no.2
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• pp.34-43
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• 2020

Phenylketonuria is a disease caused by congenital defects in phenylalanine metabolism that leads to irreversible nerve cell damage. However, its detection in the early days of life can reduce its severity. Thus, many countries have started disease screening programs for neonates. The present study aimed to determine the worldwide prevalence of classic phenylketonuria using the data of neonatal screening studies.The PubMed, Web of Sciences, Sciences Direct, ProQuest, and Scopus databases were searched for related articles. Article quality was evaluated using the Joanna Briggs Institute Critical Appraisal Evaluation Checklist. A random effect was used to calculate the pooled prevalence, and a phenylketonuria prevalence per 100,000 neonates was reported. A total of 53 studies with 119,152,905 participants conducted in 1964-2017 were included in this systematic review. The highest prevalence (38.13) was reported in Turkey, while the lowest (0.3) in Thailand. A total of 46 studies were entered into the meta-analysis for pooled prevalence estimation. The overall worldwide prevalence of the disease is 6.002 per 100,000 neonates (95% confidence interval, 5.07-6.93). The meta-regression test showed high heterogeneity in the worldwide disease prevalence (I²=99%). Heterogeneity in the worldwide prevalence of phenylketonuria is high, possibly due to differences in factors affecting the disease, such as consanguineous marriages and genetic reserves in different countries, study performance, diagnostic tests, cutoff points, and sample size.

• Molecules and Cells
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• v.44 no.7
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• pp.500-516
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• 2021

Cardiac hypertrophic signaling cascades resulting in heart failure diseases are mediated by protein phosphorylation. Recent developments in mass spectrometry-based phosphoproteomics have led to the identification of thousands of differentially phosphorylated proteins and their phosphorylation sites. However, functional studies of these differentially phosphorylated proteins have not been conducted in a large-scale or high-throughput manner due to a lack of methods capable of revealing the functional relevance of each phosphorylation site. In this study, an integrated approach combining quantitative phosphoproteomics and cell-based functional screening using phosphorylation competition peptides was developed. A pathological cardiac hypertrophy model, junctate-1 transgenic mice and control mice, were analyzed using label-free quantitative phosphoproteomics to identify differentially phosphorylated proteins and sites. A cell-based functional assay system measuring hypertrophic cell growth of neonatal rat ventricle cardiomyocytes (NRVMs) following phenylephrine treatment was applied, and changes in phosphorylation of individual differentially phosphorylated sites were induced by incorporation of phosphorylation competition peptides conjugated with cell-penetrating peptides. Cell-based functional screening against 18 selected phosphorylation sites identified three phosphorylation sites (Ser-98, Ser-179 of Ldb3, and Ser-1146 of palladin) displaying near-complete inhibition of cardiac hypertrophic growth of NRVMs. Changes in phosphorylation levels of Ser-98 and Ser-179 in Ldb3 were further confirmed in NRVMs and other pathological/physiological hypertrophy models, including transverse aortic constriction and swimming models, using site-specific phospho-antibodies. Our integrated approach can be used to identify functionally important phosphorylation sites among differentially phosphorylated sites, and unlike conventional approaches, it is easily applicable for large-scale and/or high-throughput analyses.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.4 no.1
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• pp.13-17
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• 2004

Hereditary tyrosinemia type I (fiunarylacetoacetate hydrolase deficiency) is an autosomal recessive inborn error of tyrosine metabolism that results in liver failure in infancy or chronic liver disease with cirrhosis, frequently complicated by hepatocellular carcinoma in childhood or early adolescence. Early detection of this condition is very important to early intervention for better prognosis of patients. Neonatal screening test using tandem mass spectrometry (MS-MS) is performed, and this method facilitates detection of the inborn error of tyrosine. For early treatment of tyrosinemia type I, phenylalanine and tyrosine restricted diet and NTBC (2-nitro-4-trifluoromethylbenzoyl-1,3-cyclohexanedione) for inhibition of succinylacetone production are recommended. We studied a 10-month-old Korean boy with tyrosinemia type I whose condition was not discovered earlier through conventional neonatal screening testing available in Korea. The patient presented hyperbilirubinemia, liver failure, bleeding tendency, colicky pain and skin melanin pigmentation in neonatal period. MS-MS made it possible to detect tyrosinemia type I and allowed immediate treatment of the patient. This was the first successful NTBC trial on tyrosinemia type I patient in Korea.

• Neonatal Medicine
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• v.16 no.2
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• pp.213-220
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• 2009

Purpose: Hearing loss is one of the common birth defects in humans, with a reported prevalence of 1-3 per 1000 newborns. We investigated the incidence of hearing loss and evaluated the use of neonatal hearing screening test in neonatal intensive care unit (NICU) graduates who are at greater risk for hearing loss than normal newborns. Methods: The neonates admitted to the NICU of Asan Medical Center from 1 March, 2003 to 30 March, 2008 who were available for follow-up were included. Those who failed the first auditory brainstem response prior to discharge were retested with the stapedial reflex test, auditory brainstem response and tympanometry in the Otolaryngology department. Results: Of 2,137 neonates, 2,000 (93.5%) neonates were tested prior to discharge. Sixty-seven neonates (3.4%) failed the first newborn hearing screening test. Of 67 infants, 52 infants were retested for a second hearing test. Excluding 10 infants (19.2%) who were lost during follow-up, 16 infants were confirmed to have hearing impairment of which 12 and 4 infants had unilateral and bilateral hearing loss, respectively. Of 16 infants, 5 did not meet the criteria set by the Korean National Health Insurance Corporation. Conclusion: The prevalence of hearing impairment in NICU graduates is about 0.8%, excluding those who were lost for follow up, necessitating a systemic and effective hearing assessment program among these high risk infants and more generous national insurance coverage.

• Clinical and Experimental Pediatrics
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• v.48 no.7
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• pp.706-710
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• 2005

Purpose : Early diagnosis of congenital hearing loss through the neonatal hearing screening test minimizes language defect. This research intends to identify frequency of congenital hearing loss in infants through neonatal hearing screening test with the aim of communicating the importance of hearing test for infants. Methods : From May 20, 2003 to May 19, 2004, infants were subjected to Automated Auditory Brainstem Response test during one month of birth to conduct the test with 35 dB sound. Infants who passed the 1st round of hearing test, were classified into 'pass' group whereas those who did not were classified into 'refer' group. Infants who did not 'pass' in the hearing test conducted within one month of birth were subjected to re-test one month later, and if classified as 'refer' during the re-test, they were subjected to the diagnosis for validation of hearing loss by requesting test to the hearing loss clinic. Results : There was no difference among the 'pass' and 'refer' group in terms of form of childbirth, weight at birth and gestational age. In the 1st test, total of 45 infants were classified into 'refer' group. Six among 35 who were subjected to re-test(17%) did not pass the re-test, and all were diagnosed with congenital hearing loss. This corresponds to 0.35%(3.5 per 1,000) among total number of 1,718 subjects. Conclusion : In our study the congenital hearing loss tends to be considerably more frequently than congenital metabolic disorder. Accordingly, newly born infants are strongly recommended to undergo neonatal hearing screening test.

• Neonatal Medicine
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• v.28 no.3
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• pp.124-132
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• 2021

Purpose: Neonatal near miss (NNM) allows for the detection of risk factors associated with serious newborn complications and death, the prevention of which could reduce neonatal mortality. This study was conducted with the objective of identifying predictors for NNM in a tertiary hospital in Bangalore city. Methods: This was an unmatched case-control study involving 120 NNM cases and 120 controls. NNM was determined using Pileggi-Castro's pragmatic and management criteria. Data was collected from in-patient hospital records and interviews of postpartum mothers. Multiple logistic regression of exposure variables was performed to calculate adjusted odds ratio (AOR) with 95% confidence interval (CI). Results: Significant predictors were maternal age ≥30 years (AOR, 5.32; 95% CI, 1.12 to 9.29; P=0.041), inadequate antenatal care (ANC) (AOR, 8.35; 95% CI, 1.98 to 51.12; P=0.032), <3 ultrasound scans during pregnancy (AOR, 12.5; 95% CI, 1.60 to 97.27; P=0.016), maternal anaemia (AOR, 18.96; 95% CI, 3.10 to 116.02; P=0.001), and any one obstetric complication (hypertensive disorder in pregnancy, diabetes in pregnancy, preterm premature rupture of membranes, prolonged labour, obstructed labour, malpresentation) (AOR, 4.34; 95% CI, 1.26 to 14.95; P=0.02). Conclusion: The predictors of NNM identified has important implications for public health policy and practice whose modifications can improve NNM. These include expanding essential ANC package to include ultrasound scans, ensuring World Health Organization recommendations of eight ANC visits, capacity building at all levels of health care to strengthen routine ANC and obstetric care for effective screening, referral and management of obstetric complications.

• Neonatal Medicine
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• v.25 no.4
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• pp.137-143
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• 2018

Purpose: This study was performed to determine the clinical features of full-term infants with hypoxemia detected by pulse oximetry and to establish the diagnosis of critical congenital heart disease (CCHD). Methods: We retrospectively reviewed the medical records of neonates who had been admitted to the neonatal intensive care unit within 2 weeks of birth at Korea University Ansan Hospital between January 2013 and October 2017 (n=450). We classified these neonates based on the presence of hypoxemia at admission and investigated neonatal characteristics, initial symptoms, echocardiographic findings, and final diagnosis associated with hypoxemic diseases. Results: Of 450 term infants, 265 infants (58.9%) were identified hypoxemia by pulse oximetry at admission. The most common symptoms of them were cyanosis and tachypnea. Among them, 80.1% of infants (214/265) were diagnosed with respiratory tract disease and 8.3% of infants (22/265) had congenital heart disease. Thirteen infants (13/265, 4.9%) had CCHD and were treated with urgent surgery or transcatheter intervention within 28 days of birth. Majority of infants with respiratory tract disorder were transferred from hospital immediately after birth, but 46.1% of infants (6/13) with CCHD remained asymptomatic after birth and were admitted after 48 hours after birth. In addition, other hypoxemic illnesses were identified as neonatal infectious and neurological diseases. Conclusion: This study showed the importance of assessment in neonates with hypoxemia, including those diagnosed with CCHD. The possibility of CCHD should be considered in the differential diagnosis in neonates demonstrating hypoxemia after 48 hours of birth. A larger prospective study is needed to assess the effectiveness and outcomes of pulse oximetry for neonatal screening in Korea.

• The Journal of the Korean life insurance medical association
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• v.18
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• pp.107-110
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• 1999

The disorders of congenital metabolic errors causing mental retardation can be prevented by early diagnosis and treatment. We analysed 144,000 neonatal blood samples for phenyketonuria(PKU), maple syrup urine disease(MSUD), homocystinuria(HCU) and histidinuria(HE) by bacterial inhibition method, and galactosemia(GAL) by Paigen method. In our survey, the positive were 4 samples in PKU(4mg/dl;2, 6mg/dl;1, 8mg/dl;1), 8 samples in MSUD(4mg/dl;2, 6mg/dl;2, 8mg/dl;3, 10mg/dl;1), 4 samples in HCU(4mg/dl;2, 6mg/dl;2), 4 samples in Galactosemia(4mg/dl;2, 6mg/dl;1, 8mg/dl;1), respectively. while, no one was positive in HE. The frequncy rate were 1/36,000 for PKU, HCU and GAL, 1/18,000 for MSUD, respectively. But those for HE couldn't be detected in our survey. In this study, the hightest frequency rate was 1/18,000 of MSUD, following were 1/36,000 for PKU, HCU and GAL, respectively. As results our data, it is our opinion that neonatal screening should be performed in terms of national policies for ealy diagnosis and theraphy.

• Journal of Genetic Medicine
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• v.12 no.2
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• pp.85-91
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• 2015

Purpose: Noninvasive prenatal test (NIPT) by massively parallel sequencing (MPS) of cell-free fetal DNA in maternal plasma marks a significant advancement in prenatal screening, minimizing the need for invasive testing of fetal chromosomal aneuploidies. Here, we report the initial clinical performance of NIPT in Korean pregnant women. Materials and Methods: MPS-based NIPT was performed on 910 cases; 5 mL blood samples were collected and sequenced in the Shenzhen BGI Genomic Laboratory to identify aneuploidies. The risk of fetal aneuploidy was determined by L-score and t-score, and classified as high or low. The NIPT results were validated by karyotyping for the high-risk cases and neonatal follow-up for low-risk cases. Results: NIPT was mainly requested for two clinical indications: abnormal biochemical serum-screening result (54.3%) and advanced maternal age (31.4%). Among 494 cases with abnormal biochemical serum-screening results, NIPT detected only 9 (1.8%) high-risk cases. Sixteen cases (1.8%) of 910 had a high risk for aneuploidy: 8 for trisomy 21, 2 for trisomy 18, 1 for trisomy 13, and 5 for sex chromosome abnormalities. Amniocentesis was performed for 7 of these cases (43.8%). In the karyotyping and neonatal data, no false positive or negative results were observed in our study. Conclusion: MPS-based NIPT detects fetal chromosomal aneuploidies with high accuracy. Introduction of NIPT as into clinical settings could prevent about 98% of unnecessary invasive diagnostic procedures.