Shin Ae Yoon, et al. : - Clinical Characteristics of Early Onset Sepsis in Micropreemie Born - 이어렵다. 이러한초극소미숙아치료의어려움과조기패혈증의위중함으로인하여미숙아에서광범위항생제의예방적투여가공

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1 Original article 대한주산회지제 27 권제 1 호, 2016 Korean J Perinatol Vol.27, No.1, Mar., 초극소미숙아 ( 재태연령 25 주이하 ) 에서발생한조기패혈증의임상적특징 성균관대학교의과대학삼성서울병원소아청소년과윤신애 ^ 전지영 ^ 호요한 ^ 김지숙 ^ 유혜수 ^ 성세인 ^ 안소윤 ^ 장윤실 ^ 박원순 Clinical Characteristics of Early Onset Sepsis in Micropreemie Born at 25 or Less than 25 Weeks of Gestational Age Shin Ae Yoon, M.D., Ji Young Chun, M.D., Yo Han Ho, M.D., Ji Sook Kim, M.D., Hye Soo Yoo, M.D., Se In Sung, M.D., So Yoon Ahn, M.D., Yun Sil Chang, M.D. and Won Soon Park, M.D. Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea Purpose: The aim of this study is to determine the clinical characteristics of early onset sepsis (EOS) in micropreemie. Methods: We retrospectively reviewed medical records of 107 extremely preterm infants born at 25 or less than 25 weeks of gestation and admitted to the neonatal intensive care unit of Samsung Medical Center from January 2013 to August Infants were divided into two groups based on the presence of culture-proven EOS in the first 7 days of life. Retrospective analysis of perinatal factors and laboratory findings within the first week of life was done between two groups. We compared the neonatal outcomes among two groups. Results: Culture-proven EOS was diagnosed in 11 of 107 infants (10.3%). Main pathogen of EOS was Staphylococcus epidermidis (45.5%). There were no significant differences between control group and EOS group in gestational age, birth weight, Apgar score, delivery type and pathologic chorioamnionitis. Among 11 infants with EOS, 9 showed fetal tachycardia (P=0.001). And presented lower platelet count at 3 rd day and 7 th day of life than that of control group (P=0.033, P=0.045). Neonatal outcomes in were compatible with control group. Main cause of death was sepsis in. Conclusion: In micropreemie, EOS is important factor of mortality. Our data suggest that fetal tachycardia and low platelet count during the first 7 days of life were associated with EOS. Key Words: Early onset sepsis, Extremely preterm infants Received: 5 February 2016, Revised: 25 February 2016 Accepted: 27 February 2016 Correspondence to: So Yoon Ahn, M.D. Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro, Gangnam-gu, Seoul 06351, Korea Tel: , Fax: soyoon.ahn@samsung.com Copyrightc 2016 by The Korean Society of Perinatology This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided that the original work is properly cited. The Korean Journal of Perinatology pissn eissn e-kjp.org 국내초극소미숙아의출생률은매년증가하고있으며이들의생존율또한신생아집중치료의발달로증가하고있다. 적은재태연령과출생체중은조기패혈증의위험인자로알려져있으며, 조기패혈증은신생아의이환율및사망률과밀접한관련이있다. 1-3 현재까지조기패혈증의위험인자로알려진조기양막파수와조기진통등이초극소미숙아에서동반되는경우가많으며신생아에서나타나는조기패혈증의증상은비특이적으로특히, 초극소미숙아의생후 1주일이내의불안정한활력징후는감염과의감별

2 Shin Ae Yoon, et al. : - Clinical Characteristics of Early Onset Sepsis in Micropreemie Born - 이어렵다. 이러한초극소미숙아치료의어려움과조기패혈증의위중함으로인하여미숙아에서광범위항생제의예방적투여가공공연히이루어지고있다. 그러나미숙아에서광범위항생제의예방적투여는지발형패혈증과괴사성장염, 사망의위험인자로알려져있다. 4 이에따라최근미숙아에서불필요한항생제사용을줄이며조기패혈증을예측하고적절한치료를하기위하여예측인자와예측모형에대한많은연구들이있었으나아직까지그효과는미미한수준이다. 5-7 그리고최근대두되고있는많은생체표지자를이용한감염과비감염성질환의감별방법은혈액량이적은초극소미숙아에게적용하는데에는제한적인부분이있다. 8 최근국내신생아네트워크 (Korean Neonatal Network, KNN) 정보를이용하여국내극소저체중출생아에서조기패혈증의발생률과원인균에대한보고가있었으나 9 초극소미숙아에서조기패혈증의양상과조기패혈증을예측할수있는인자에대해서는자세히알려진바가없다. 이에저자들은재태연령 25주이하의초극소미숙아에서조기패혈증의발생률및원인균, 사망률과이환율에대해알아보고자하였으며주산기인자와생후 1주일이내의혈액학적검사결과를분석하여초극소미숙아에서조기패혈증의임상적특징에대해알아보고자하였다. 대상및방법 1. 대상 2013 년 1월부터 2015 년 8월까지삼성서울병원에서출생하여신생아집중치료실에입원한환자들중재태연령 25주이하의미숙아 107 명의의무기록을후향적으로분석하였다. 조기패혈증은생후 7일이내에시행한혈액배양검사에서균이동정되고호흡부전및무호흡, 기계환기치료중산소요구량증가및평균기도압상승, 서맥또는빈맥, 저혈당또는고혈당, 산소포화도저하, 활동력저하, 불안정한체온조절, 구역, 구토, 복부팽만, 잔류량증가, 피부색의변화, 저혈압, 핍뇨등의전신증상을보이면서항생제를 5일이상치료한경우로정의하였다. 많은문헌에서극소저체중출생아에서조기패혈증의정의를 72시간이내 에균이동정된경우로정의하고 3, 10, 11 있으나저자들은초극소미숙아의생후 1주일의불안정한경과와조기패혈증의임상적특징을비교하고자생후 1주일이내에균이동정된경우로조기패혈증을정의하였다. 대상환자들은조기패혈증발생여부에따라조기패혈증군 (n=11) 과대조군 (n=96) 으로분류하였다. 2. 방법정보수집은의무기록의후향적조사를통하여이루어졌으며주산기위험인자와관련하여산모의양막파수기간및산전항생제사용여부, 산전항생제투여기간, 산전스테로이드사용여부, 산모의발열 (38.0 이상 ), 산모의백혈구증가증 (>15,000 /μl), 산모의빈맥 (>100 회 / 분 ), 태아의빈맥 (>160 회 / 분 ), 산모의 C-reactive protein (CRP, >0.3 mg/dl) 증가여부, 산모의질분비물배양검사결과, 병리학적융모양막염여부와질식분만여부를조사하였다. 산모의양막파수란양막파수가 18시간이상이되는경우로정의하였으며병리학적융모양막염은태반조직검사로확진된경우로정의하였다. 신생아요인과관련하여재태연령, 출생체중, 성별, 부당경량아여부, 1분과 5분아프가점수, 생후 1주일이내백혈구, CRP, 혈소판결과와생후 1주일이내에강심제사용여부및하이드로코르티손투여여부, 인슐린투여가필요했던고혈당 ( 300 mg/dl) 12 여부를조사하였다. 생후 1주일이내의혈액검사는생후 1일째, 3일째, 그리고 7일째일반혈액검사와 CRP를포함한일반화학검사를시행하였다. 혈액배양검사는전체신생아집중치료실입원환자들을대상으로정규검사로생후 1일째에시행하였으며감염이의심되는증상및징후를보이는경우추가적으로시행하였다. 혈액배양검사는숙련된의료진이멸균장갑을착용한상태에서 0.5% chlorhexidine 으로피부를소독한뒤채혈하였다. 신생아의예후와관련하여중등도이상의기관지폐이형성증, 13 3단계이상의뇌실내출혈, 14 뇌실주위백질연화증, modified Bell s criteria 에따른 2단계이상의괴사성장염, 15 레이저치료가필요했던미숙아망막증, 16 사망률에대해조사하였다. 통계적분석은 SPSS for window (SPSS Inc.,

3 윤신애외 : - 초극소미숙아에서발생한조기패혈증의임상적특징 - Chicago, IL, USA) 를이용하여분석하였으며범주형변수의비교는 Chi-square test(fisher s extract test) 를이용하였다. 독립집단인두군사이의평균분석은 Student s t-test 를이용하였으며모든통계적검정은양측검정을하였으며 P 값이 0.05 미만인경우에만통계적으로유의한것으로정의하였다. 본연구는삼성서울병원기관윤리위원회 (Institutional Review Board) 심의를통과하였다. 결과총대상환자는 107 명이었으며대상환자들의평균재태연령은 24.1±1.0 주이었고평균출생체중은 657.5± g이었다. 조기패혈증으로진단된환자는총 11명으로발생률은 10.3% 이었으며, 평균진단시기는 4.0± 2.1일이었다. 생후 72시간이내에균이동정된환자는 4 명이었으며나머지환자는 72시간이후에동정되었다. 동정된균의종류는 Staphylococcus epidermidis (5 건 ), Staphylococcus aureus (2 건 ), Klebsiella pneumoniae (2건), Escherichia coli (2건), Acinetobacter baumannii/hemolyticus (1건 ) 이었으며한명의환자가 K. pneumoniae와 E. coli가동시에동정되었다. 조기패혈증군과대조군의재태연령과출생체중은유의한차이가없었으며, 조기패혈증군에서질식분만의빈도가낮았으나유의한차이는없었다 (Table 1). 주산기인자로조기양막파수의빈도가조기패혈증군에서 54.5% 로대조군 (28.1%) 보다높았으나통계적으로유의하지않았다. 조기양막파수기간, 산전항생제사용및기간에서도두군간의통계적차이는없었다. 임상적융모양막염의진단기준인산모의발열과빈맥, 백혈구증가증은두군간의의미있는차이는없었으며, 산모의 CRP 상승여부도두군간에차이가없었다. 산모의질분비물배양검사는대조군에서 66명, 조기패혈증군에서 7 명이시행하였으며대조군의양성율이조기패혈증군보다더높았으나유의한차이는없었다 (Table 2). 대조군산모의질분비물배양검사에서 E. coli (9 건 ), Streptococcus agalactiae (7 건 ), K. pneumoniae (5 건 ), Candida (5 건 ), Staphylococcus aureus (2 건 ), Enterobacter aerogenes (2건) 의순으로나타났으며, 조기패혈증군의산모는 K. pneumoniae가동정되었다. 태아빈맥이조기패혈증군의 90.9% 에서관찰되었으며이는대조군의 38.5% 보다통계적으로의미있게높았다 (P=0.001, Table 2). 전체대상환자들은생후 1일째혈액검사를시행하였으며, 생후 1주일이내에대조군에서 4명, 조기패혈증군에서 1명이사망하여생후 3일째혈액검사는대조군에서 95명, 조기패혈증군에서 11 명시행하였고, 생후 7일째혈액검사는대조군에서 92명, 조기패혈증군에서 10 명이시행하였다. 생후 1일째시행한혈액검사에서백혈구, CRP, 그리고혈소판은대조군과조기패혈증군이유사하였으나생 Table 1. Demographics of Subjects Variable Control group (N=96) P- value Gestational age (wks) 24.2±0.9 ( ) 23.5±1.5 ( ) Birth weight (g) 664.7±159.9 (300-1,150) 593.6±141.3 ( ) Male 57 (59.4%) 6 (54.5%) One-minute Apgar score 4.1± ± Five-minute Apgar score 6.7± ± Delivery type, C/sec 27 (28.1%) 6 (54.5%) Small for gestational age 18 (18.8%) 2 (18.2%) Antenatal steroids 90 (93.8%) 10 (90.9%) Pathologic chorioamnionitis 51 (53.1%) 6 (54.5%) Pregnancy-induced hypertension 11 (11.5%) 0 (0%) Gestational diabetes mellitus 4 (4.2%) 0 (0%) The values in the table are expressed as mean±sd or number (%). Abbreviation: EOS, early onset sepsis

4 Shin Ae Yoon, et al. : - Clinical Characteristics of Early Onset Sepsis in Micropreemie Born - Table 2. Perinatal Factors Associated with Early Onset Sepsis Control group (N=96) P- value PROM 27/96 (28.1%) 6/11 (54.5%) PROM duration (hrs)* 124 ( ) 83 (72-216) Maternal antibiotics use 67/96 (69.8%) 8/11 (72.7%) Duration of maternal antibiotics use (days)* 3.0 (1-30) 4.5 (2-12) Maternal fever 2/96 (2.1%) 1/11 (9.1%) Maternal tachycardia 44/96 (45.8%) 2/11 (18.2%) Maternal leukocytosis 30/94 (31.9%) 4/10 (40%) Maternal CRP rising 56/72 (77.8%) 9/9 (100%) Maternal vaginal colonization 21/66 (31.8%) 1/7 (14.3%) Fetal tachycardia 37 (38.5%) 10 (90.9%) The values in the table are number (%). * Median (range). Abbreviations: EOS, early onset sepsis; PROM, premature rupture of membrane; CRP, C-reactive protein. Table 3. Laboratory Findings within the First Week of Life Related to Early Onset Sepsis Control group (N=96) WBC count* (K/µL) CRP level* (mg/dl) Platelet count (K /µl) Control group (N=96) Control group (N=96) 1 st day 6,070 (620-44,640) 6,510 (1,370-34,310) 0.03 ( ) 0.03 ( ) 200.1± ± rd day 10,600 (490-73,230) 9,700 (1,330-23,120) 0.2 ( ) 0.2 ( ) 164.3± ± th day 13,720 (490-68,230) 16,915 (6,750-51,140) 0.1 ( ) 0.8 ( ) 130.2± ±79.5 The values in the table are expressed as mean±sd *Median (range), P< 0.05 Abbreviations: EOS, early onset sepsis; WBC, white blood cell; CRP, C-reactive protein. 후 3일째와생후 7일째시행한혈액검사에서조기패혈증군의혈소판수치가대조군에비해의미있게낮았다 (P= 0.033, P=0.045). 백혈구수치와 CRP 수치는생후 3일째와생후 7일째결과에서두군간의유의한차이는없었다 (Table 3). 전체대상환자모두에서생후 1주일이내에조기패혈증의발생과관계없이인슐린치료가필요했던고혈당이관찰되었다. 생후 1주일이내에강심제와하이드로코르티손의투여빈도는조기패혈증군이대조군보다높았으나유의한차이는없었다 (P=0.276, P=0.205). 생후 1 일째예방적항생제투여비율은대조군에서 23명 (24.0%), 조기패혈증군에서 1명 (9%) 로대조군에서높았으나의미있는차이는없었다. 조기패혈증군과대조군간의중등도이상의기관지폐이형성증, 3단계이상의뇌실내출혈, 뇌실주위백질연화증, 2단계이상의괴사성장염, 레이저치료가필요했던미숙아망막증의빈도와사망률은통계적으로유의한차이가 Table 4. Comparison of Clinical Outcomes between Control and Early onset Sepsis Group Outcome Control group (N=96) P- value BPD ( moderate) 34/85 (40%) 4/9 (44.4%) IVH ( 3) 17/95 (17.9%) 3/10 (30%) PVL 7/95 (7.4%) 1/10 (10%) NEC ( Stage 2b) 9/96 (9.3%) 0 (0%) ROP requiring laser treatment 23/76 (30.3%) 2/8 (25%) Mortality 22/96 (22.9%) 4/11 (36.4%) The values in the table are number (%) Abbreviation: EOS, early onset sepsis; BPD, bronchopulmonary dysplasia; IVH, intraventricular hemorrhage; PVL, periventricular leukomalacia; NEC, necrotizing enterocolitis; ROP, retinopathy of prematurity. 없었다 (Table 4). 조기패혈증군에서사망한 4 명의환자들 중 3 명의직접사인이조기패혈증이었으며한명의환자 는생후 6 개월경에기관지폐이형성증과지발형패혈증의 증으로사망하였다. 대조군에서생후 1 주일이내직접사망

5 윤신애외 : - 초극소미숙아에서발생한조기패혈증의임상적특징 - 원인은신생아항혈소판항체증후군 (1 명 ), 뇌실내출혈 4 기 (2 명 ), 장천공 (1 명 ) 이었다. 고찰현재까지조기패혈증에대한진료지침은산모의발열과조기양막파수시간등의산모의임상적융모양막염의증상및징후에기반하여이루어졌으며이는만삭아와후기미숙아에적용할수있었다. 17 초극소미숙아에서조기패혈증에대한예방적항생제투여에대한지침에대한근거가많이부족한실정으로저자들은 25주이하의초극소미숙아에서조기패혈증의임상적특징을알아보고자하였다. 본연구에서초극소미숙아의조기패혈증의발생률은 10.3% 이었으며, 이는이전에발표된 KNN 보고와유사하다. 9 원인균은그람양성세균의비율이높았으나대상군의숫자가작아기존의보고와 2, 9, 18, 19 비교가어려웠다. 한명의환자만생후 1일째시행한혈액배양검사에서균이동정되었으며나머지대상환자들은이후에조기패혈증의심으로시행한혈액배양검사에서균이동정되었다. 생후 1 일째시행한혈액배양검사에서음성의결과가나온것은불충분한혈액양또는초기혈액내균주의수가적었을가능성이있겠다. 조기패혈증군에서 S. epidermidis가가장많이동정되었으며한명의환자는다시시행한혈액배양검사에서도양성결과를보여진성감염가능성이높았으며나머지환자들은재시행한혈액배양검사에서음성결과를보여검사과정중에오염가능성을완전히배제할수없었다. 그러나환자가산소요구량증가, 저혈압과고혈당등의임상증상을보이고항생제를즉각사용한후재검사한혈액배양검사에서음성이나왔으며환자의상태도임상적호전된상황을고려하였을때패혈증에합당한것으로고려된다. 모든환자들에게서동정된 S. epidermidis 는항생제내성은없었다. 본연구에서산모의질분비물배양검사의양성결과와조기패혈증군에서동정된원인균간의연관성은보이지않았으며이는산모의질분비물배양검사에근거하여예방적항생제를투여하는것은근거가부족함을반영한다. 그러나조기패혈증군의 11 명중질분비물배양검사를시행한환자가 7명으로정확한평가를 하기어려웠고임상적융모양막염의진단기준에서가장중요한인자인산모의발열은대조군과조기패혈증군모두에서낮은빈도로관찰되었다. 조기양막파수는조기패혈증군에서더높은빈도로관찰되었으나통계적으로유의한차이는없었으며조기양막파수의기간도유의한차이는없었다. 조직학적융모양막염의빈도도두군간의차이를보이지않았다. 본연구에서는기존의문헌들과 11, 20, 21 다르게산모적인자들과조기패혈증은의미있는관련성을보이지않았다. 이는최근산모의분만중예방적항생제사용의증가로산모의감염에대한징후와증상의발현의감소를조심스럽게유추하는바이다. 저자들은조기패혈증군의 90% 이상에서출생전에태아빈맥을관찰하였으며이는대조군과통계적으로유의한차이가있었다. 태아빈맥은이미알려진임상적융모양막염의진단기준중의하나이나현재까지그중요성에대해서는알려진바가없었다. 단일기관에서시행된연구로연구대상자수가작아일반화하기에는제한점이있으나 25 주미만의초극소미숙아에서태아빈맥이가지는임상적중요성을시사하며향후산모의감염의징후가뚜렷하지않은상태에서자궁내감염이의심될경우분만시기와초기항생제투여에대한기준이될수있을것으로본다. 앞으로태아빈맥이있는경우조기패혈증의예측정도에대한전향적인연구가필요할것으로생각된다. 최근감염성질환과비감염성질환을감별하기위한여러가지생체표지자에대한연구들이 8, 이루어지고있으나초극소미숙아에서정상참고치가없고어려운채혈로인하여 CRP를대체할유용한진단적방법은없는상황이다. 그러나 CRP는조기패혈증에서예방적항생제투여를위한기준으로사용하기에는반영시기가늦어제한이있으며본연구에서도조기패혈증이있었던 11명의환자들모두생후 1일째 CRP는정상범위이었으며조기패혈증군에서생후 3일째와생후 7일째에 CRP가상승하는소견을보였으나대조군과통계적으로유의한차이를보이지않았다. 감염상황에서상승하는백혈구수치는현재까지재태연령에따른정상범위가확립되지않은상태로초극소미숙아에서감염의지표로사용하기에는어려운실정이며 25 본연구결과에서도백혈구수는조기패혈증과연관성을

6 Shin Ae Yoon, et al. : - Clinical Characteristics of Early Onset Sepsis in Micropreemie Born - 보이지않았다. 그러나혈소판은재태연령에관계없이정상범위가일정하며기존의많은연구에서신생아세균성감염과의연관성이보고되어왔다 혈소판감소는신생아집중치료실에입원한환자들에게서많이발견되는소견으로출생시에보이는혈소판감소는자궁내성장지연이나산모의특발성혈소판감소와연관성이알려져있다. 대상환자들의생후 1일째평균혈소판수치는정상범위이었으며조기패혈증군에서생후 1주일이내에혈소판수치감소가관찰되었다. 저자들은초극소미숙아에서도혈소판감소가초기에조기패혈증을예측할수있는인자로유용함을확인하였다. 본연구의대상인 25주이하의초극소미숙아에서조기패혈증군과대조군사이의재태연령과출생체중의차이는없었으며두군간의기관지폐이형성증등의주요질환이환율과사망률은유의한차이를보이지않았다. 조기패혈증은주요질환의이환율을높이는것으로알려져있으나본연구결과는초극소미숙아의미숙자체가갖는한계점의중요성을시사하였다. 그러나조기패혈증군에서사망한 4명의환자들중 3명의환자가직접사인이조기패혈증이었으며이는조기패혈증의초기적절한치료는초극소미숙아의생존율을향상시키는데에중요한부분임을알수있다. 본연구에서생후 72시간이내에진단된조기패혈증의발생률은 3.7% 로낮았으나출생후예방적항생제투여의비율은 22.4% 로높았으며, 이는초극소미숙아에서적절한예방적항생제투여의치료지침의필요성을시사한다. 기존의문헌에서조기패혈증에대한예측인자로태아빈맥과혈소판수치의영향에대한보고는없었으며향후대규모연구를통하여이를이용한조기패혈증의예측모형의개발에대한연구가필요할것으로생각된다. References 1) Stoll BJ, Gordon T, Korones SB, Shankaran S, Tyson JE, Bauer CR, et al. Early-onset sepsis in very low birth weight neonates: a report from the national institute of child health and human development neonatal research network. J Pediatr 1996;129: ) Stoll BJ, Hansen NI, Sanchez PJ, Faix RG, Poindexter BB, Van Meurs KP, et al. Early onset neonatal sepsis: the burden of group B Streptococcal and E. coli disease continues. Pediatrics 2011;127: ) Simonsen KA, Anderson-Berry AL, Delair SF, Davies HD. Early-onset neonatal sepsis. Clin Microbiol Rev 2014;27: ) Muller-Pebody B, Johnson AP, Heath PT, Gilbert RE, Henderson KL, Sharland M. Empirical treatment of neonatal sepsis: are the current guidelines adequate? Arch Dis Child Fetal Neonatal Ed 2011;96:F4-8. 5) Martius JA, Roos T, Gora B, Oehler MK, Schrod L, Papadopoulos T. et al. Risk factors associated with early-onset sepsis in premature infants. Eur J Obstet Gynecol Reprod Biol 1999;85: ) Selimovic A, Skokic F, Bazardzanovic M, Selimovic Z. The predictive score for early-onset neonatal sepsis. Turk J Pediatr 2010;52: ) Coggins SA, Wynn JL, Hill ML, Slaughter JC, Ozdas- Weitkamp A, Jalloh O, et al. Use of a computerized C- reactive protein (CRP) based sepsis evaluation in very low birth weight (VLBW) infants: a five-year experience. PLoS One 2013;8:e ) Steinberger E, Hofer N, Resch B. Cord blood procalcitonin and Interleukin-6 are highly sensitive and specific in the prediction of early-onset sepsis in preterm infants. Scand J Clin Lab Invest 2014; 74: ) Lee SM, Chang M, Kim KS. Blood culture proven early onset sepsis and late onset sepsis in very-low-birth-weight infants in Korea. J Korean Med Sci 2015;30 Suppl 1:S ) Mukhopadhyay S, Puopolo KM. Risk assessment in neonatal early onset sepsis. Semin Perinatol 2012;36: ) Stoll BJ, Hansen N, Fanaroff AA, Wright LL, Carlo WA, Ehrenkranz RA, et al. Changes in pathogens causing earlyonset sepsis in very-low-birth-weight infants. N Engl J Med 2002; 347: ) Yoo HS, Ahn SY, Lee MS, Han YM, Sung SI, Chang YS, et al. Permissive hyperglycemia in extremely low birth weight infants. J Korean Med Sci 2013;28: ) Ehrenkranz RA, Walsh MC, Vohr BR, Jobe AH, Wright LL, Fanaroff AA, et al. Validation of the national institutes of health consensus definition of bronchopulmonary dysplasia. Pediatrics 2005; 116: ) Papile LA, Burstein J, Burstein R, Koffler H. Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm. J Pediatr 1978; 92: ) Walsh MC, Kliegman RM, Fanaroff AA. Necrotizing

7 윤신애외 : - 초극소미숙아에서발생한조기패혈증의임상적특징 - enterocolitis: a practitioner's perspective. Pediatr Rev 1988; 9: ) Fierson WM. Screening examination of premature infants for retinopathy of prematurity. Pediatrics 2013;131: ) Polin RA, Committee on F, Newborn. Management of neonates with suspected or proven early-onset bacterial sepsis. Pediatrics 2012;129: ) Ozkan H, Cetinkaya M, Koksal N, Celebi S, Hacimustafaoglu M. Culture-proven neonatal sepsis in preterm infants in a neonatal intensive care unit over a 7 year period: coagulasenegative Staphylococcus as the predominant pathogen. Pediatr Int 2014;56: ) Ronnestad A, Abrahamsen TG, Medbo S, Reigstad H, Lossius K, Kaaresen PI, et al. Septicemia in the first week of life in a Norwegian national cohort of extremely premature infants. Pediatr 2005; 115:e ) Klinger G, Levy I, Sirota L, Boyko V, Reichman B, Lerner- Geva L, Israel Neonatal N: Epidemiology and risk factors for early onset sepsis among very-low-birthweight infants. Am J Obstet Gynecol 2009;201:38 e ) Schuchat A, Zywicki SS, Dinsmoor MJ, Mercer B, Romaguera J, O'Sullivan MJ, et al. Risk factors and opportunities for prevention of early-onset neonatal sepsis: a multicenter case-control study. Pediatrics 2000;105(1 Pt 1): ) Bhandari V. Effective biomarkers for diagnosis of neonatal sepsis. J Pediatric Infect Dis Soc 2014; 3: ) Delanghe JR, Speeckaert MM. Translational research and biomarkers in neonatal sepsis. Clin Chim Acta 2015; 451(Pt A): ) Basu S, Agarwal P, Anupurba S, Shukla R, Kumar A. Elevated plasma and cerebrospinal fluid interleukin-1 beta and tumor necrosis factor-alpha concentration and combined outcome of death or abnormal neuroimaging in preterm neonates with early-onset clinical sepsis. J Perinatol 2015; 35: ) Hornik CP, Benjamin DK, Becker KC, Benjamin DK, Jr., Li J, Clark RH, et al. Use of the complete blood cell count in early-onset neonatal sepsis. Pediatr Infect Dis J 2012;31: ) Roberts I, Murray NA. Neonatal thrombocytopenia: causes and management. Arch Dis Child Fetal Neonatal Ed 2003; 88:F ) Charoo BA, Iqbal J, Iqbal Q, Mushtaq S, Bhat AW, Nawaz I. Nosocomial sepsis-induced late onset thrombocytopenia in a neonatal tertiary care unit. Hematol Oncol Stem Cell Ther 2009;2: ) Arif SH, Ahmad I, Ali SM, Khan HM. Thrombocytopenia and bacterial sepsis in neonates. Indian J Hematol Blood Transfus 2012;28: = 국문초록 = 목적 : 재태연령 25 주이하의초극소미숙아에서조기패혈증의발생률및원인균, 임상적특징을알아보고자하였다. 방법 : 2013 년 1월부터 2015 년 8월까지삼성서울병원에서출생하여신생아집중치료실에입원한환자들중재태연령 25 주이하의미숙아 107 명의의무기록을후향적으로분석하였다. 조기패혈증군과대조군간의재태연령, 출생체중, 주요질환의이환율과사망률을비교하였으며, 주산기인자와생후 1주일이내의혈액학적검사결과를비교하였다. 결과 : 총 107 명의환자들중 11 명이조기패혈증으로진단되었으며주원인균은 Staphylococcus epidermidis (45.5%) 이었다. 조기패혈증군과대조군간의재태연령, 출생체중, 아프가점수, 질식분만빈도, 조직학적융모양막염빈도의통계적차이는없었다. 조기패혈증군의 11 명중 9명에서태아빈맥을보였으며 (P=0.001), 조기패혈증군에서생후 3일째와생후 7일째에낮은혈소판수치를보였다 (P=0.033, P=0.045). 주요질환의이환율과사망률은두군간의차이가없었으나조기패혈증군의사망환아 4명중 3명의직접사인이조기패혈증이었다. 결론 : 조기패혈증의초기적절한치료는초극소미숙아의생존과밀접한관련이있으며, 태아빈맥과낮은혈소판수치는조기패혈증과연관성을보였다. 중심단어 : 조기패혈증, 초극소미숙아

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386-390.hwp 386 HANYANG MEDICAL REVIEWS Vol. 29 No. 4, 2009 우리나라 미숙아의 통계와 의료비용 Statistics and Medical Cost of Preterm in Korea 윤혜선 을지대학교 노원을지병원 소아청소년과학교실 Hye Sun Yoon, M.D., Ph.D., Department of Pediatrics, Nowon