• Journal of Preventive Medicine and Public Health
• /
• 제32권3호
• /
• pp.317-324
• /
• 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
• /
• 제63권2호
• /
• pp.34-43
• /
• 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
• /
• 제44권7호
• /
• pp.500-516
• /
• 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.

• 대한유전성대사질환학회지
• /
• 제4권1호
• /
• pp.13-17
• /
• 2004

저자들은 생후 28일된 발열, 간종대, 출혈성 경향, 구토, 잦은 보챔, 전신의 황달 증상을 보이던 환아를 MS-MS 이용한 신생아 대사 이상 검사와 혈중 아미노산 분석, 뇨중 유기산 분석을 통하여 hereditary tyrosinemia type I으로 진단하였다. 저 페닐알라닌/타이로신 식이와 NTBC 사용으로 국내 첫 타이로신혈증 I 치료 성공례를 경험하였다.

• Neonatal Medicine
• /
• 제16권2호
• /
• pp.213-220
• /
• 2009

목 적 : 의미 있는 난청은 정상 신생아에서 1,000명당 1-3명의 비율로 발생하는 흔한 질환으로 신생아 중환자실 집중치료를 받은 경우 1,000명당 2-4명의 비율로 발생하는 것으로 보고되고 있고, 난청의 발생률이 높은 신생아 집중치료를 받은 신생아들도 보험혜택의 제한과 추적관찰 실패율이 높은 실정이다. 이에 저자들은 지난 5년간 신생아 집중치료실에서 퇴원한 아기들의 난청 발병률 및 외래추적 관찰률을 확인하고, 신생아중환자실에서의 청각 선별검사의 의의에 대하여 알아보고자 하였다. 방 법 : 2003년 3월부터 2008년 3월까지 울산대학교 의과대학 서울아산병원 신생아 중환자실에서 집중치료를 받은 총 2,137명 중 2,000명을 대상으로 하였다. 신생아 중환자실 퇴원하기 전 신경과에 의뢰되어 뇌간유발 반응검사(AEP)로 1차 선별검사를 시행 후 비정상으로 나올 경우 신생아중환자실내 혹은 이비인후과 및 신생아 외래에서 추적관찰을 하였다. 결 과 : 2,123명 중 67명이 재검판정을 받아 재검률은 3.35%이었고 52명이 2차 청력검사를 시행 받았다. 세 번 이상의 청력검사를 받고 최종적으로 16명(0.8%)이 치료적 중재가 필요하거나 언어치료와 함께 외래 추적관찰이 필요한 비정상군으로 분류되었다. 비정상군의 평균 재태주령은 36주 6일, 평균 출생체중은 2,180 g, 1분 평균 아프가 점수는 각각 1분에 5점, 5분에 7점이었으며, 1차부터 3차까지의 평균 청력 검사 시행일은 각각 17일, 53일, 152일이었다. 전체 16명 중 남아는 6명이었으며 양측성 청력손실 4명, 편측성 청력손실 2명이었고, 여아는 양측성 청력손실 6명, 편측성 청력손실 4명으로 전체 남녀의 비율은 1:1.67 이었다. 경증, 중증도, 중증 난청 환아 수는 각각 3명, 1명, 2명이었고 최중증 난청 환아는 9명으로 이 중 5명은 양측성 4명은 편측성 청력손실이 있었다. 16명중 5명은 대한민국 보험공단에서 제시하는 고위험군에 포함되는 위험요소가 없었다. 결 론 : 본원 신생아중환자실에서 집중치료를 받은 환아의 0.8%에서 인공와우이식이나 언어치료가 필요한 청각이상을 나타내었다. 이는 정상 신생아에서 보고되는 청각이상에 비하여 약 10배 가량 높은 비율로 향후 의료진들의 신생아 난청의 심각성에 대한 의식변화와 제도적인 측면에서 더 많은 뒷받침으로 향상된 예후를 기대하여 본다.

• Clinical and Experimental Pediatrics
• /
• 제48권7호
• /
• pp.706-710
• /
• 2005

목 적 : 출생 후 3세까지는 언어와 청각신경로의 발달의 가장 중요한 시기로 신생아 청력 선별검사를 통해서 선천성 난청의 조기 진단은 청력 손실로 인한 언어장애를 최소화 하고 언어 발달을 위한 재활 교육의 기회를 제공하여 정상적인 언어 생활을 하는데 중요한 역할을 하게 된다. 우리나라에는 아직 충분한 통계가 없지만 미국의 경우 정상 신생아의 1,000명당 2-7명이 선천성 영구적 난청을 가지고 태어나는 것으로 알려져 있고, 2세 이전에 난청이 발견되어 치료하지 않는다면 언어발달의 중요한 시기를 놓치게 되어 행동장애나 학습장애를 초래하게 된다. 이 연구는 신생아 청력 선별검사를 통해 신생아 난청의 빈도를 파악하여 신생아 청력검사의 중요성을 알리고자 한다. 방 법 : 2003년 5월 20일부터 2004년 5월 19일까지 좋은문화 병원에서 출생한 신생아 2,755명 중 부모의 동의를 얻은 1,718명을 대상으로 생후 1개월 이내 내간유발반응검사(AABR. ALGO-3)를 이용하여 35 dB의 소리를 주어 시행하였다. 난청의 위험요소가 있는 군과 위험요소가 없는 군으로 구분하였고 1차 청력검사에서 통과된 경우 'pass'군 통과되지 않는 경우 'refer'군으로 하였다. 생후 1개월내 청력검사에서 'pass'되지 않았으면 1개월 뒤에 재검사를 받도록 하였고 재검사에서 'refer'가 나온 경우 난청 클리닉에 의뢰하여 난청을 확진하였다. 결 과 : 총 1,718명 중 'pass'군과 'refer'군 사이의 분만형태 출생체중 재태연령에는 차이가 없었다. 1차 검사에서 'refer'가 나온 경우는 총 45명(2.6%)이었으며 이중 35명이 재검사를 받았으며 10명은 재검사를 거절하였다. 재검사한 35명 중 6명(17.0%)이 재검사를 통과하지 못하였고 모두 선천성 난청으로 진단되었다. 이는 전체 검사자 1,718명의 0.35%(1,000명당 3.5명) 해당되었다. 'refer'군에서 한 가지 이상 위험요소가 동반되는 경우는 45명 중 10명(22.2%) 'pass'군에서 위험요소가 있는 경우는 1,673명 중 263명(15.7%)으로, 위험 요소가 있으면서 'refer'가 나온 군이 위험요소가 없으면서 'refer'가 나온 군과 비교했을 때 통계적으로 의미가 없었다. 결 론 : 본 연구의 결과는 신생아기의 난청의 빈도가 1,000명 당 3.5명으로 외국 통계와 비슷한 것으로 나타났으며, 이는 선천성 대사질환보다 월등히 빈도가 높으며, 태어나는 신생아에서 반드시 신생아 청력선별검사를 해야 할 것으로 사료된다.

• Neonatal Medicine
• /
• 제28권3호
• /
• pp.124-132
• /
• 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
• /
• 제25권4호
• /
• pp.137-143
• /
• 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.

• 보험의학회지
• /
• 제18권
• /
• pp.107-110
• /
• 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
• /
• 제12권2호
• /
• pp.85-91
• /
• 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.