한국에서 최근 50년간 신생아, 주산기 관련 역학 통계의 변화: OECD 국가와의비교

조자향,최서경,정성훈,최용성,배종우 대한신생아학회 2013 Neonatal medicine Vol.20 No.4

Purpose: Of numerous health status indicators, those of neonate and peripartum encompass nation’s maternal, birth, neonatal and infantile health level. The goal of this study was to investigate the changes during the past 50 years of neonatal and perinatal indicators in Korea. Methods: We analyzed the changes of population, number of live births per year, crude birth rate (CBR), total fertility rate (TFR), incidence of low birth weight infant (LBWI) and preterm infants, neonatal mortality rate (NMR), infant mortality rate (IMR), perinatal mortality rate (PMR), and maternal mortality ratio (MMR) of Korea, and especially compared those indicators of Korea with those of other OECD nations during the past 50 years. Results: Korea has accomplished a marked improvement in the above indicators during the past 50 years. The average index of OECD and Korean rank among 34 OECD nations in the above health indicators in 2010 are as follows: population 49,410,370 (36,285,235, 9th), CBR 9.4 (12.1, 4th), TFR 1.23 (1.75, 1st), LBWI incidence 5.0 (6.8, 6th), NMR 1.8 (2.9, 8th), IMR 3.2 (4.3, 10th), PMR 3.3 (6.0, 4th), MMR 15.7 (8.7, 29th). Conclusion: Birth rate of Korea was very low among OECD nations with relatively low LBWI incidence. It is inspiring that NR, IMR, and PMR were lower than the average. However, MMR was very higher than the average of OECD. The present review provides the neonatal and perinatal health indicators in Korea and it might be helpful to improve clinical practice and outcome in the future. 목적: 한 국가의 신생아 및 주산기 분야에 대한 지표는 그 나라의 산모, 출생, 신생아, 영아의 건강과 보건 상태를 반영한다. 이에 지난 50년간의 변화를 살펴보고자 본 연구를 실시하였다. 방법: OECD에서 발표되는 각종 통계 중에서 총인구, 연간 생존출생수, 조출생률, 총출산율, 저체중출생아 및 미숙아발생률, 신생아 사망률, 영아 사망률, 주산기 사망률, 모성 사망비 항목에 대해서 한국을 포함한 OECD국가의 지난 50년간의 변화를 살펴보고, 특히 한국의 변화 추이를 OECD국가와 비교하였다. 결과: 한국은 지난 50년간 상기 지표들에서 큰 개선을 이루었다. 2010년을 기준으로 볼 때 각각의 수치(OECD 평균, 34개 국가 중의 랭킹)는 다음과 같다. 총인구 49,410,370명(9위), 조출생률 9.4 (12.2, 4위), 총출산율 1.23 (1.75, 1위), 저체중출생아 발생률 5.0 (6.7, 6위), 신생아 사망률 1.8 (2.8, 8위), 영아 사망률 3.2 (4.2, 10위), 주산기 사망률 3.3 (5.9, 4위), 모성 사망비 15.7 (8.5, 29위) 이었다. 결론: 한국은 OECD 국가들 중에서 아주 낮은 출산율을 보이고 있었고, 저체중출생아 빈도는 다소 낮았다. 신생아, 영아 및 주산기 부분의 사망률은 평균보다 낮아 고무적이었으나, 모성 사망비 부분은 평균 보다 아주 높아서 모성사망 부분의 개선이 필요한 부분으로 판단되었다. 본 연구는 한국의 신생아 및 주산기 지표를 체계적으로 분석하였으며, 향후 한국에서 이에 대한 관리 및 질 향상을 위한 기초 자료를 제공하는 의의를 가진다.

Long-term clinical outcome and the identification of homozygous CYP27B1 gene mutations in a patient with vitamin D hydroxylation-deficient rickets type 1A

조자향,강은구,김구환,이범희,최진호,유한욱 대한소아내분비학회 2016 Annals of Pediatirc Endocrinology & Metabolism Vol.21 No.3

Vitamin D hydroxylation-deficient rickets type 1A (VDDR1A) is an autosomal recessively-inherited disorder caused by mutations in CYP27B1 encoding the 1α-hydroxylase enzyme. We report on a female patient with VDDR1A who presented with hypocalcemic seizure at the age of 13 months. The typical clinical and biochemical features of VDDR1A were found, such as hypocalcemia, increased alkaline phosphatase, secondary hyperparathyroidism and normal 25-hydroxyvitamin D3 (25(OH)D3). Radiographic images of the wrist showed metaphyseal widening with cupping and fraying of the ulna and distal radius, suggesting rickets. A mutation analysis of the CYP27B1 gene identified a homozygous mutation of c.589+1G>A in the splice donor site in intron 3, which was known to be pathogenic. Since that time, the patient has been under calcitriol and calcium treatment, with normal growth and development. During the followup period, she did not develop genu valgum, scoliosis, or nephrocalcinosis.

당원병1b형의 임상양상 및 분자유전학적 특징

조자향,김유미,최진호,이범희,김구환,유한욱,Cho, Ja Hyang,Kim, Yoo-Mi,Choi, Jin-Ho,Lee, Beom Hee,Kim, Gu-Hwan,Yoo, Han-Wook 대한유전성대사질환학회 2015 대한유전성대사질환학회지 Vol.15 No.1

당원병 Ib형은 드문 유전 대사 질환 중 하나로 SLC37A4 유전자의 장애로 인해 발생한다. 특징적으로 간비대, 저혈당, 고젖산혈증, 고지혈증, 고뇨산증의 임상양상을 보인다. 총 3명(남자 1명, 여자 2명)이 포함되었고 의무기록을 후향적으로 분석하였다. 평균 진단시 나이는 각각 8개월, 26개월, 10세이다. 2명의 환자가 영유아기에 간비대, 저혈당 등으로 발견되었고, 다른 환자는 사춘기에 성장 발육 부전으로 인한 저신장으로 진단되었다. 유전학적 검사에서 c.412T>C (p.Trp 138Arg) (3/6 alleles, 50.0%)가 가장 흔했고 다음으로 p.Leu348Valfs*53 (1 allele), p.Pro191Leu (1 allele), p.Ala148Val (1 allele)가 확인되었다. 요산 강하제, 생 옥수수 전분 복용을 시작하였으며, 모든 환자가 중성구 감소 소견이 관찰되어 G-CSF 투여하였다. 이들 모두 구내염, 장염, 뇌농양과 같은 반복적인 감염이 관찰되었다. 또한 2명은 심한 골다공증으로 칼슘 보충제가 필요하였다. 비교적 일찍 진단된 2명에 비해 10세에 진단된 경우 중증 감염 및 간과 신장의 합병증을 보이고 있었다. 통계학적으로 유의하지 않지만, 비교적 전자의 환자들이 비교적 예후가 좋았다. 본 연구를 통해 동시에 한국의 GSD Ib형 환자의 임상적, 생화학적, 분자유전학적인 특징과 후기 합병증에 대해 보고하는 바이다. Glycogen storage disease type Ib (GSD Ib) is one of the rare inherited metabolic disease caused by mutation of SLC37A4 gene. Clinical characteristics include hepatomegaly, hypoglycemia, lactic acidosis, hyperlipidemia and high serum uric acid concentration. The authors analyzed clinical and molecular characteristics of three Korean patients (one male and two females) with GSD Ib by retrospective review of medical records. Two patients were diagnosed in toddler period by hypoglycemia and hepatomegaly. One patient was diagnosed by growth retardation and short stature in puberty. c.412T>C (p.Trp138Arg) (3/6 alleles, 50.0%) was most frequently observed, following by p.Leu348Valfs*53 (1 allele), p.Pro191Leu (1 allele), p.Ala148Val (1 allele) in molecular analysis. Uncooked corn starch and allopurinol was administered. Because all three patients had neutropenia and recurrent infections, G-CSF was administered. Two patients had severe osteoporosis needing calcium supplement. The patient who diagnosed at puberty had relatively poor prognosis demonstrated by having severe infection and complications in liver and kidney.

Aflatoxin $B_1$이 계배 간조직의 미세구조에 미치는 영향

조자향,전향미,서숙재,Cho, Ja-Hyang,Cheon, Hyang-Mi,Seo, Sook-Jae 한국현미경학회 1996 Applied microscopy Vol.26 No.2

To investigate the effect of aflatoxin $B_1$, on survival rate and ultrastructure of liver during chick embryogenesis electron microscopic methods were used. After injection of aflatoxin $B_1$ into the yolk, ultrastructural changes in the liver of chicken embryo were observed. The results were as followed. 1. 12-day old chicken embryos were treated with single injection of aflatoxin $B_1$ with the dose of $0.0005{\mu}g,\;0.005{\mu}g,\;0.05{\mu}g,\;0.5{\mu}g,\;2.5{\mu}g,\;5.0{\mu}g$ each. Chicken embryos treated with the dose of $0.5{\mu}g$ of aflatoxin $B_1$ had survival rate of 22%. The embryos treated with $2.5{\mu}g$ of aflatoxin $B_1$ hardly survived. 2. Chicken embryos treated with $0.05{\mu}g$ of afatoxin $B_1$ had hatched in 30%, but once hatched, they all survived. 3. After administration of $0.05{\mu}g$ of aflatoxin $B_1$ into the 12-day old chicken embryo, the electron microscopic studies were examined during development stages. The nuclei of hapatocytes became irregularly shaped and the structures of endoplasmic reticulum were changed to spherical types at 20-day old chicken embryo. Also, mitochondria became to be dilated and severe fibrosis was induced in the cytoplasm. However, the hepatocytes became almost normal in 30-day old young chicken.

The Prevalence of Abdominal Obesity and Metabolic Syndrome in Korean Children and Adolescents

조자향 대한비만학회 2023 Journal of obesity & metabolic syndrome Vol.32 No.2

DEND Syndrome with Heterozygous KCNJ11 Mutation Successfully Treated with Sulfonylurea

조자향,강은구,이범희,김구환,최진호,유한욱 대한의학회 2017 Journal of Korean medical science Vol.32 No.6

Permanent neonatal diabetes mellitus (PNDM) is caused by mutations in the ATP-sensitive potassium channel (KATP channel) subunits. Developmental delay, epilepsy, and neonatal diabetes (DEND) syndrome is the most severe form of PNDM and is characterized by various neurologic features. We report on a patient with DEND syndrome following initial misdiagnosis with type 1 DM, who was successfully switched from insulin to sulfonylurea therapy. A 50-day-old male presented with fever and seizure, complicated by persistent hyperglycemia. Insulin therapy was initiated. At 10 months of age, the patient was unable to hold his head up and make eye contact with others. At 17.9 years of age, direct sequencing of KCNJ11 identified a heterozygous mutation of c.602G>A (p.R201H). Since then, treatment with gliclazide was initiated and the insulin dose was gradually reduced. Following 3 months, insulin was discontinued with a gliclazide dose of 2.4 mg/kg. The patient continued to have excellent glycemic control with a glycated hemoglobin (HbA1c) level of 5.8% after 5 months. However, the patient's psychomotor retardation did not improve. This study reports the first case of DEND syndrome in Korea caused by a KCNJ11 mutation and emphasizes the necessity to screen mutations in KATP channel genes in patients with neonatal diabetes.

Near final height in Korean children referred for evaluation of short stature: clinical utility and analytical validity of height prediction methods

정승우,조자향,정해운,심계식 대한소아내분비학회 2018 Annals of Pediatirc Endocrinology & Metabolism Vol.23 No.1

Purpose: Predicted adult height (PAH) is often crucial to decision-making about treatment with human growth hormone (GH) or gonadotropin-releasing hormone agonist in children with short stature. This study compares final adult height (FAH) with different methods used to determine PAH and assesses the clinical utility and analytical validity of height prediction for children not treated with GH. Methods: Clinical findings were retrospectively analyzed, and the heights of 44 children (22 males and 22 females) who visited our clinic between August 2006 and June 2017 and reached near final adult height (NFAH) were evaluated. Children treated with GH were excluded. We compared measured NFAH to PAH using the Bayley-Pinneau (BP), Tanner-Whitehouse Mark 2, and Roche-Wainer-Thissen (RWT) methods. Results: Pearson correlation between all 3 prediction methods and NFAH showed high positive correlations in males and females (P<0.05). The average difference between PAH and NFAH for the BP method (0.4±3.9 cm) was significantly lower than those for the RWT and TW 2 methods in females (P=0.000, analysis of variance). Furthermore, only PAH by the BP method in females was very close to measured NFAH (paired t-test). A Bland-Altman plot verified that 95% of the differences between the PAH and NFAH exist between limits of agreement (mean±1.96 standard deviation). Conclusion: The BP method is more useful to predict NFAH in females than other methods. Careful attention is still required when using such tools because PAH can be inaccurate. Therefore, a more accurate FAH prediction model for Korean children is needed.

Onychodysplasia를 동반한 선천성 모세혈관확장성 대리석양 피부 1예

문주영,조자향,양윤석,장지영,배종우 대한신생아학회 2012 Neonatal medicine Vol.19 No.2

Cutis marmorata telangiectatica congenita (CMTC) is a rare congenital vascular disorder, and its pathophysiology is still unclear and most cases occur sporadically. Cutaneous lesions are observed at birth with a marbled bluish and deep-purple appearance. The associated anomaly is manifest as body asymmetry, macrocephaly, hydrocephalus, mental retardation, syndactyly and congenital glaucoma. We report our experience of CMTC1 in a female infant with the gestational age of 34 weeks and 6 days and birth weight of 2,300 g who was born by cesarean section with abnormal skin lesions. The cutaneous lesions covered most of the lower body and they faded as she continues to grow. She also had onychodysplasia in her left 2nd phalanges. In this case, close follow up by not only pediatricians but also ophthalmologist and neurologists to treat various forms of lesions involved, though the prognosis of CMTC is generally good.

Etiology and therapeutic outcomes of children with gonadotropin-independent precocious puberty

강은구,조자향,최진호,유한욱 대한소아내분비학회 2016 Annals of Pediatirc Endocrinology & Metabolism Vol.21 No.3

Purpose: This study was performed to investigate the etiology, clinical features, and outcomes of patients with gonadotropin-independent precocious puberty (GIPP). Methods: The study included 16 patients (14 female and 2 male patients) who manifested secondary sexual characteristics, elevated sex hormones, or adrenal androgens with prepubertal luteinizing hormone levels after gonadotropin releasing hormone stimulation diagnosed between May 1994 and December 2015. Patients with congenital adrenal hyperplasia were excluded. Clinical features, laboratory findings, treatment modalities, and outcomes were retrospectively reviewed. Results: The median age at diagnosis was 2.6 years (range, 0.7–7.9 years) and median follow-up duration was 4.6 years (range, 1 month–9.8 years). Patients with McCune-Albright syndrome (n=5) and functional ovarian cysts (n=4) presented with vaginal bleeding and elevated estradiol levels (23.3±17.5 pg/mL); adrenocortical tumors (n=4) with premature pubarche and elevated dehydroepiandrosterone sulfate levels (87.2–6,530 μg/dL); and human chorionic gonadotropin (hCG)- producing tumor (n=1) with premature pubarche and elevated β-human chorionic gonadotropin levels (47.4 mIU/mL). Two patients were idiopathic. Six patients transited to gonadotropin-dependent precocious puberty median 3.3 years (range, 0.3–5.1 years) after the onset of GIPP. Initial and follow-up height standard deviation scores (0.99±0.84 vs. 1.10±1.10, P=0.44) and bone age advancement (1.49±1.77 years vs. 2.02±1.95 years, P=0.06) were not significantly different. Conclusion: The etiologies of GIPP are heterogeneous, and treatment and prognosis is quite different according to the etiology. Efficacy of treatment with aromatase inhibitors needs to be evaluated after long-term follow-up.

파브리병에서 효소대치요법의 장기적 효과

김자혜,조자향,최진호,이범희,유한욱,Kim, Ja Hye,Cho, Ja Hyang,Choi, Jin-Ho,Lee, Beom Hee,Yoo, Han-Wook 대한유전성대사질환학회 2014 대한유전성대사질환학회지 Vol.14 No.1

Fabry disease is an X-linked disease caused by deficiency of the lysosomal enzyme alpha-galactosidase A. Affected males present anhydrosis, acroparesthesia and angiokeratoma, and subsequently cardiac, cerebral and renal complications are followed. Females and atypical variants show heterogeneous clinical symptoms. In 2001, two recombinant enzymes were approved for Fabry disease: agalsidase alpha and agalsidase beta. Since the introduction of enzyme replacement therapy (ERT), the number of long-term follow-up studies has been reported. Long-term ERT showed effectiveness on renal function in patients with chronic kidney disease, decrease or stabilization of left ventricular mass, and improvement of pain and quality of life. However, there were limited effects on cerebrovascular events and their mortality. Current literatures on the clinical effect of ERT have reported limited datain adult patients who have already advanced disease. Therefore, further study for pre-symptomatic patients and atypical variants is needed to verify the impact of ERT. This review summarized recent progresses in ERT and limitations of long-term effect of ERT in patients with Fabry disease.