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1 ORIGINAL ARTICLE Korean J Obstet Gynecol 2011;54(2):79-85 doi: /KJOG pissn eissn THE RELATIONSHIP BETWEEN AMNIOTIC FLUID WHITE BLOOD CELL COUNT AND INFLAMMATORY LESIONS OF THE PLACENTA IN WOMEN WITH PRETERM PREMATURE RUPTURE OF MEMBRANES Eun Ha Jeong, MD, Kyo Hoon Park, MD, PhD, Kyung Joon Oh, MD, Sung Youn Lee, MD, Shi Nae Kim, MD, Hee Jung Jung, MD, Jeong Yeun Lee, RN Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea Objective To examine the relationship between amniotic fluid (AF) white blood cell (WBC) count and the presence and severity of inflammatory lesions of the placenta in women with preterm premature rupture of membranes (PPROM). Methods This retrospective cohort study included 90 consecutive women with PPROM ( weeks) who met the following criteria: singleton gestation; transabdominal amniocentesis performed to obtain AF for culture and WBC count; delivery within 72 hours of amniocentesis; placental histologic examination after preterm delivery. Results The prevalence of histologic chorioamnionitis was 32% (29/90) and that of positive amniotic fluid culture was 21% (19/90). Patients with histologic chorioamnionitis had a significantly higher AF WBC count than those without this lesion. Logistic regression analysis demonstrated that AF WBC count had a significant relationship with histologic chorioamnionitis after controlling for gestational age and AF culture. The median AF WBC count increased significantly according to the higher severity of inflammation in each type of placental histologic section. According to receiver operating characteristic curve analysis, the best cut-off value of AF WBC count for predicting histological chorioamnionitis was 25 cells/mm 3, with a sensitivity of 62% and a specificity of 77%. Conclusion Both the presence and greater severity of inflammatory lesions of the placenta are associated with an elevated AF WBC count. AF WBC count is an important and independent predictor for inflammatory lesions of the placenta in women with PPROM. Keywords: Amniotic fluid, White blood cell, Placenta, Inflammatory lesions, Preterm premature rupture of membranes 만삭전조기양막파수는다양한원인에의하여발생하지만그중에서도자궁내감염이중요한원인으로알려져있다 [1-4]. 조직학적융모양막염 (histologic chorioamnionitis) 은자궁내감염의표준진단법으로조기양막파수임신부의태반에서흔히발견되는태반의주요한조직학적병변이다 [5,6]. 조직학적융모양막염이존재하는경우이때분만된조산아는패혈증, 뇌성마비, 기관지폐이형성증등을포함한신생아이환및사망이증가하기때문에이의존재유무를산전에진단하는것은매우중요하다 [7-11]. 그러나조직학적융모양막염은분만이후에야진단이가능하기때문에산전에임신부의산과적처치혹은분만직후신생아처치에는이용할수없는제한점이있다. 만삭전조기양막파수임신부대상의여러연구에서양수내백혈구수측정은조직학적융모양막염예측에매우유용한검사로보고되고있다 [3,4,12,13]. 특히양수내백혈구수측정은싸이토카인과같은다 Received: Revised: Accepted: Corresponding author: Kyo Hoon Park, MD, PhD Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam , Korea Tel: Fax: pkh0419@snubh.org *This study was supported by a grant from Seoul National University Bundang Hospital ( ). This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright Korean Society of Obstetrics and Gynecology 79

2 KJOG Vol. 54, No. 2, 2011 른염증성지표와달리신속하고간편하며비용이적게들기때문에임상적으로유용하게이용할수있다 [14]. 조직학적융모양막염은융모양막의백혈구침윤으로정의되고 [15] 자궁내감염이발생하면숙주반응기전 (host-response mechanism) 에의하여양수내백혈구수가증가하게된다는점을고려하면태반과양수에서발견되는백혈구의존재또는정도등이서로밀접한관련성이있다는논리는가능하다. 본연구진의조기진통임신부대상의이전연구에서도양수내백혈구수는조직학적융모양막염의존재및정도와밀접한상관관계가존재한다는것을보고한바있었다 [16]. 그러나현재까지만삭전조기양막파수임신부에서조직학적융모양막염과양수내백혈구수의상관관계에대한체계적인연구는부족한실정이다. 본연구의목적은만삭전조기양막파수임신부에서태반의급성염증성병변의존재및정도와양수내백혈구수와의관련성을확인하고자하였다. 2004년 6월부터 2010년 2월사이에만삭전조기양막파수를주소로분당서울대학교병원산부인과에입원한임신부를대상으로연구를시행하였다. 본연구대상의조건은 1) 단태임신이고, 2) 양수내백혈구수측정및양수배양검사를위하여경복부양수천자가시행되고, 3) 양수천자후 72시간내에분만되었으며 ( 양수분석과태반조직학적소견의시간적상호관련성이중요하기때문 ), 4) 조기분만 ( 임신 주사이 ) 후태반에서조직학적검사가시행된경우등으로하였다. 조기양막파수는분만진통이전에양막이파수되었다는병력과무균소독된질경검사를통한질내양수확인, 나이트라진검사 (nitrazine test) 등으로양막파수여부를확인하여진단하였다. 본연구는분당서울대학교병원생명윤리심의위원회의승인을거친후수행되었다. 양수천자는모든대상환자에서사전동의를얻은후초음파로산모의배를통해자궁내부를관찰하면서 22게이지척수천자바늘을가능한한태반을피하여삽입하여무균적원칙에의해양수를채취하였다. 채 취된양수의일부는양수내백혈구수측정과양수배양등을위해사용하였고, 사용되지않은양수는원심분리한뒤 polypropylene관에담아 -70 o C에서보관하였다. 양수내백혈구수의측정은채취된양수를 ethylenediamine tetraacetic acid가함유된용기에담아검사실에보내 hemocytometer chamber에서백혈구수를측정하였으며 mm 3 당개수로나타내었다. 양수배양은호기성세균, 혐기성세균및 mycoplasma에대한배양을실시하였다. 호기성및혐기성세균배양은양수채취후즉시혈액배양병에담아검사실로보내어 BACTEC 9240 및 FX 시스템 (Becton Dickinson, Sparks, MD, USA) 에서배양하였고배지는 blood agar, McKonkey agar, thioglycollate broth, brucellar blood agar, phenylethylglycol blood agar를사용하였으며혐기성균주의배양을위해혐기성방 (anaerobic chamber) 을이용하였다. Mycoplasma의배양은상품화된키트 (MYCOFAST ; International Microbio Co., Signes, France) 를이용하여배양하였다. 태반의조직학적검사는제대 (umbilical cord), 융모판 (chorionic plate), 태반막 (placental membrane) 에서조직을얻어 10% 포르말린에고정시킨후파라핀에포매 (embedding) 시켰다. 조직절편을 hematoxylin과 eosin으로염색하였으며임상정보가없는상태에서조직학적검사를실시하였다. 조직학적융모양막염의진단은이미보고된기준을사용하여진단하였으며 [3], 양막, 융모탈락막, 제대, 융모판의 4가지조직중어느한조직이상에서급성염증성병변이발견되는경우로정의하였다. 각조직에서급성염증성병변이있는경우염증이심한정도에따라 grade 1과 grade 2로나누었다 (Table 1). 두군사이의비교는정규분포를가정할수없었기때문에연속형변수는비모수적검정법인 Mann-Whitney U test를사용하였고, 비율의비교는 chi-square test 혹은 Fisher s exact test를사용하였다. 양수내백혈구수가임신주수등과같은교란변수의영향을보정한후에도조직학적융모양막염의독립적예측인자임을증명하기위하여다변량논리회기분석을시행하였다. Receiver operating characteristic (ROC) 곡선을사용하여태반의조직학적융모양막염을예측하는데있어양수내 Table 1. Histological grade for acute intrauterine infl ammation Amnion Grade 1: at least one focus of >5 neutrophils Grade 2: diffuse neutrophilic infi ltration Chorion-decidua Grade 1: at least one focus of >5 neutrophils Grade 2: diffuse neutrophilic infi ltration Umbilical cord Grade 1: neutrophilic infi ltration confi ned to umbilical vessel wall Grade 2: extension of neutrophilic infi ltration into Wharton s jelly Chorionic plate Grade 1: >1 focus of at least 10 neutrophilic collections or diffuse infi ltration in subchorionic plate Grade 2: diffuse and dense infl ammation, neutrophilic infi ltration into connective tissue of placental plate, or placental vasculitis 80

3 Eun Ha Jeong, et al. The relationship between amniotic fluid white blood cell and histologic chorioamnionitis Table 2. Demographic and clinical characteristics of the study population according to the histologic chorioamnionitis Characteristics Histologic chorioamnionitis Absent (n=61) Present (n=29) P value Maternal age (yr) 30.8± ± Nulliparity 49% (30/61) 52% (15/29) 1.0 Gestational age at amniocentesis (wk) 34.0± ±3.3 <0.001 Amniotic fl uid WBC count (cells/mm³) 103±345 2,047±3, Positive amniotic fl uid culture 8% (5/61) 48% (14/29) <0.001 Values are given as mean±standard deviation or % (n). Table 3. Risk factors associated with histologic chorioamnionitis after adjustment of confounding variables by logistic regression Odds ratio 95% CI P-value Gestational age at amniocentesis (wk) Amniotic fl uid WBC count (cells/mm³) Positive amniotic fl uid culture CI, confi dence interval; WBC, white blood cell. 백혈구수의민감도와위양성률사이의관련성을평가하여조직학적융 1.0 모양막염진단에가장유용한절단치 (cut-off value) 를결정하였다. 양막, 융모탈락막, 제대, 융모판각각의조직에서염증정도에따른양수내백혈구수의비교는 Kruskal-wallis test를사용하였고양성양수배양빈도 0.8 의변화는 chi-square test for trend 를사용하여분석하였다. 양막, 융모 탈락막, 제대, 융모판각각에서조직학적염증의정도를모두합산한값에따른양수내백혈구수의비교는 Kruskal-wallis test를사용하였다. 통계프로그램은 SPSS ver (SPSS Inc., Chicago, IL, USA) 을사용하였으며, 양측검정을통해 P-value가 0.05미만인경우통계적유의성이있는것으로하였다. Sensitivity cells/mm 본연구대상조건에맞는만삭전조기양막파수임신부는 90명이었으며그중 32% (29/90) 에서조직학적융모양막염이발견되었고 21% (19/90) 에서양수배양검사에서미생물이분리되었다. 조직학적융모양막염이발견된 29명중에서태반의부위별염증의빈도는융모탈락막이 28명 (97%) 으로가장빈도가높았으며다음으로제대 13명 (45%), 융모판 11명 (38%), 양막 7명 (24%) 순이었다. 분리된세균의종류는 Ureaplasma urealyticum (n=16), Mycoplasma hominis (n=11), Streptococcus sp. (n=3), Lactobacillus (n=1) 로 Ureaplasma urealyticum이 84% (16/19) 에서분리되어가장높은빈도를차지하였고, 두가지이상의미생물이분리된경우는 12명이었다. Table 2는조직학적융모양막염존재유무에따른임상적특성을나타낸표이다. 임신부의나이, 분만력과같은인구통계학적특성은두군사이에유의한차이가없었다. 그러나조직학적융모양막염이존재한경우는조직학적융모양막염이존재하지않은경우보다임신주수가유 Specificity Fig. 1. Receiver operating characteristic curve for amniotic fluid white blood cell in predicting the occurrence of histologic chorioamnionitis. Number next to solid dots represents cut-off value of white blood cell (area under the curve 0.716; standard errors 0.065; P=0.001). 의하게낮았고양수내백혈구수와양성양수배양빈도는유의하게높았다. 조직학적융모양막염은임신주수와같은교란변수에영향을받기때문에이러한교란변수의영향을보정한후에도양수내백혈구수가조직학적융모양막염과유의한관련성이있는지알아보기위하여다변량논리회기분석을시행하였다. 임신주수, 양성양수배양의영향을보정한후에도양수내백혈구수는조직학적융모양막염과유의한관련성을나타내었다 (Table 3). 81

4 KJOG Vol. 54, No. 2, 2011 Table 4. Amniotic fl uid culture and white blood cell count according to the presence and severity of infl ammation in each type of placental histologic section Tissue n Positive amniotic fluid culture P value * Amniotic fluid WBC P value Amnion Grade (17) ( ) Grade (50) 910 (0 8160) Grade (100) Chorion decidua Grade (8) < (0 2020) Grade (50) 55 (0 8160) Grade (50) 2120 ( ) Umbilical cord Grade (14) < ( ) <0.001 Grade (50) 975 (5 5440) Grade (71) 1600 ( ) Chorionic plate Grade (18) (0 9760) Grade (33) 17.5 (0 1680) Grade (60) 8160 ( ) Values are given as n (%) or median (range). WBC, white blood cell. *Chi square test for trend, Kruskal wallis test. Table 5. Amniotic fl uid white blood cell count according to the total grade of histologic chorioamnionitis Total grade of histologic chorioamnionitis n Amniotic fluid white blood cell P value * Grade (0 2020) <0.001 Grade 1 or (0 1880) Grade 3 or (0 9760) Grade 5 or ( ) Grade 7 or 8 0 Values are given as median (range). *Kruskal wallis test. Fig. 1은조직학적융모양막염을예측하는데있어양수내백혈구수의진단적민감도와위양성률의관계를기술한 ROC 도표이다 (area under the curve 0.716, standard errors 0.065, P=0.001). 조직학적융모양막염을산전에예측하는데양수내백혈구수 25개 /mm 3 를진단적지표로정하는것은민감도와특이도모두를동시에증가시킬수있는적절한절단치로생각되며, 조직학적융모양막염을예측하는데있어양수내백혈구수 25개 /mm 3 이상은민감도 62%, 특이도 77%, 양성예측도 56%, 음성예측도 81% 를나타내었다. Table 4는양막, 융모탈락막, 제대, 융모판각각의염증성병변의정도와양수내백혈구수및양수배양검사결과와의관련성을나타낸표이다. 양막, 융모탈락막, 제대, 융모판조직각각에서염증성병변의정도가심할수록양성양수배양빈도가유의하게증가하였다. 양수내백혈구수도유사한결과를보여융모탈락막, 제대, 융모판조직각각에서 염증성병변의정도가심할수록양수내백혈구수가유의하게증가하였고양막의경우염증성병변의정도가심할수록양수내백혈구수가증가하는경향을보였으나통계적유의성에는이르지못하였다. Table 5는양막, 융모탈락막, 제대, 융모판의조직학적염증정도를모두합산한값과양수내백혈구수와의관계를나타낸표이다. 태반 4 가지조직의조직학적염증정도를합산한값 (total grade of histologic chorioamnionitis로정의 ) 이클수록양수내백혈구수는유의하게증가하였다. 본연구에서는만삭전조기양막파수임신부에서양수내백혈구수 82

5 Eun Ha Jeong, et al. The relationship between amniotic fluid white blood cell and histologic chorioamnionitis 는태반의급성염증성병변의존재및정도와유의한관련성이있음을확인하였다. 또한다변량논리회기분석에서양성양수배양, 임신주수등의교란변수의영향을보정한후에도양수내백혈구수는조직학적융모양막염과독립적관련성이있음을보여주었다. 이러한결과는만삭전조기양막파수임신부대상의 Kim과 Yoon [12] 의연구결과와일치하며양막파수없는조기진통임신부대상의본연구팀의이전연구결과와도일치한다 [16]. 본연구에서조직학적융모양막염예측을위한양수내백혈구수의가장적절한절단치는 25개 /mm 3 을나타내었는데이러한결과는조기양막파수임신부대상의 Yoon 등 [4] 과 Kim과 Yoon [12] 의양수내백혈구수의절단치 20개 /mm 3 와거의일치한다. 다른한편으로본연구에서만삭전조기양막파수임신부에서조직학적융모양막염진단을위한양수내백혈구수측정의위음성률 ( 양수내백혈구수 25개 /mm 3 미만이지만조직학적융모양막염이존재하는경우 ) 은 38% (11/29) 를나타내었다. 이러한위음성이발생하는원인의가능한설명으로첫째, 양수천자에서태반만출까지시간경과를생각할수있다. 즉자궁내감염초기혹은자궁내감염이존재하지않았을경우양수천자시양수에서백혈구가발견되지않지만이후염증반응이지속되거나또는양막파수로인한상행성감염으로분만시태반에서조직학적염증소견이발견될수있다. 실제본연구에서위음성을나타낸 11명의임신부중 10명에서융모탈락막에염증성병변이존재하였지만이중 9명은양막에는염증성병변이존재하지않아양수외에서시작된자궁내감염이양막강까지도달하지않았음을암시하는소견을나타내었다. 둘째, 균주크기가작은세균에감염되었을수있다. 즉양수내미생물의균주크기는양수에서발견되는백혈구수와밀접한관계가있음을주장한 Romero 등 [3] 의보고와같이양수내균주크기가작을경우태반에염증성병변이발견되지만양수내백혈구수증가는유발하지못하였을수있다. 본연구에서양수내백혈구수는태반염증성병변 ( 융모탈락막, 제대, 융모판혹은전체태반 ) 의존재및정도와유의한관련성을나타내었다. 이러한연구결과는연구대상및연구방법이유사한 Kim과 Yoon [12] 의연구와일치하며임상적으로매우중요한의미를가진다. 즉조직학적융모양막염은임신부에서조산, 임상적융모양막염을유발하고분만후신생아에서는패혈증과같은단기합병증및뇌성마비, 기관지폐이형성증등과같은장기합병증과밀접한관련성이이미확인되었기때문에 [7-11] 산전에간단하고적은비용으로조직학적융모양막염을진단하고염증정도를예측할수있는방법을제시하였다는점에서중요하다. 양수분석을통하여자궁내감염을예측하는방법에는양수내백혈구수측정외에도양수배양검사, 양수내싸이토카인혹은포도당농도측정, 그람염색등의유용성이보고되어있다 [4,17,18]. Romero 등 [6] 은양수배양검사는조직학적융모양막염예측에유용하지만, 배양기간이필요하고위음성의위험이높기때문에만삭전조기양막파수임신부처치에신속하게이용할수없는제한점이있다고주장하였다 [19,20]. Interleukin (IL)-6, IL-8 등과같은양수싸이토카인측정은양수배양검사에비해위음성의위험은줄일수있지만정량적인검사로서 상용화되지못하여간편하게이용할수없는제한점이있다 [21,22]. 이와달리양수내백혈구수측정은적은비용으로간편하고신속하게결과를확인할수있기때문에조기양막파수임신부의초기치료방침을결정하는데유용하게적용할수있을것으로생각된다. 만삭전조기양막파수임신부대상의본연구에서는 21% 에서양수배양검사에서미생물이분리되었고 32% 에서조직학적융모양막염이발견되었다. 이러한연구결과는 Kim과 Yoon [12] 의양성양수배양 33% 조직학적융모양막염 68% 보다낮은결과를나타내었다. 두연구사이의이러한차이를명확하게설명하기는어렵지만자궁내감염의빈도는양수천자시임신주수, 양막파수의진단기준, 만삭전조기양막파수임신부에서양수검사를시행하는병원마다의한계점 (threshold) 과관련이있을것으로생각된다. 본연구대상조건의임신주수는 24 주에서 35주사이분만한환자를대상으로하였으나 Kim과 Yoon [12] 의환자도포함되었을가능성이있겠다. 본연구에서양수내백혈구수증가는임신주수, 양성양수배양과같은교란변수의영향을보정한후에도조직학적융모양막염과유의한관련성을나타내었다. 이러한연구결과는 Yoon 등 [4] 의연구결과와일치하는소견으로조직학적융모양막염 ( 특히융모탈락막에염증이국한된경우 ) 은자궁내감염발생의초기단계로생각되고있고 [23] 양수내백혈구수로간단히진단할수있다는점에서중요하다. 자궁내감염의표준진단기법은태반에서조직학적검사를통하여염증성병변을확인하거나양수배양검사를통하여미생물을분리하는것이다 [23]. 최근까지자궁내감염을초기에진단하기위한많은연구가있어왔으나대부분의연구는양수내감염을진단하는것에초점이맞추어져왔고태반조직학적융모양막염의조기진단방법에관한연구는부족하였다. 그러나양수배양검사는자궁내감염과정중가장마지막단계에해당되기때문에 [23] 양수내감염이진단된경우는이미진행된상태의자궁내감염으로치료에제한이있을수있다. 따라서향후조기양막파수임신부에서양수내백혈구수가증가된경우항생제치료가조기분만된신생아의단기혹은장기합병증발생을줄일수있는지에관한전향적무작위임상연구가필요할것으로생각된다. 결론적으로만삭전조기양막파수임신부에서양수내백혈구수는태반의염증성병변의존재및정도와유의한관련성을가지고있으며산전에이의존재유무를예측할수있는독립적인자이다. References 1. Gauthier DW, Meyer WJ, Bieniarz A. Correlation of amniotic fl uid glucose concentration and intraamniotic infection in patients with preterm labor or premature rupture of membranes. Am J Obstet Gynecol 1991;165: Goldenberg RL, Culhane JF, Iams JD, Romero R. Epidemiology and causes of preterm birth. Lancet 2008;371: Romero R, Yoon BH, Mazor M, Gomez R, Gonzalez R, Dia- 83

6 KJOG Vol. 54, No. 2, 2011 mond MP, et al. A comparative study of the diagnostic performance of amniotic fl uid glucose, white blood cell count, interleukin-6, and gram stain in the detection of microbial invasion in patients with preterm premature rupture of membranes. Am J Obstet Gynecol 1993;169: Yoon BH, Jun JK, Park KH, Syn HC, Gomez R, Romero R. Serum C-reactive protein, white blood cell count, and amniotic fl uid white blood cell count in women with preterm premature rupture of membranes. Obstet Gynecol 1996;88: Zlatnik FJ, Gellhaus TM, Benda JA, Koontz FP, Burmeister LF. Histologic chorioamnionitis, microbial infection, and prematurity. Obstet Gynecol 1990;76: Romero R, Salafi a CM, Athanassiadis AP, Hanaoka S, Mazor M, Sepulveda W, et al. The relationship between acute infl ammatory lesions of the preterm placenta and amniotic fl uid microbiology. Am J Obstet Gynecol 1992;166: Shatrov JG, Birch SC, Lam LT, Quinlivan JA, McIntyre S, Mendz GL. Chorioamnionitis and cerebral palsy: a meta-analysis. Obstet Gynecol 2010;116: Soraisham AS, Singhal N, McMillan DD, Sauve RS, Lee SK; Canadian Neonatal Network. A multicenter study on the clinical outcome of chorioamnionitis in preterm infants. Am J Obstet Gynecol 2009;200:372.e Aziz N, Cheng YW, Caughey AB. Neonatal outcomes in the setting of preterm premature rupture of membranes complicated by chorioamnionitis. J Matern Fetal Neonatal Med 2009;22: Watterberg KL, Demers LM, Scott SM, Murphy S. Chorioamnionitis and early lung infl ammation in infants in whom bronchopulmonary dysplasia develops. Pediatrics 1996;97: Yoon BH, Romero R, Kim KS, Park JS, Ki SH, Kim BI, et al. A systemic fetal inflammatory response and the development of bronchopulmonary dysplasia. Am J Obstet Gynecol 1999;181: Kim JC, Yoon BH. The relationship between amniotic fluid white blood cell count and the presence and severity of acute placental infl ammation in preterm premature rupture of membrane. Korean J Obstet Gynecol 2000;43: Kim M, Yoon BH. The diagnostic and prognostic value of amniotic fl uid white blood cell count in patients with preterm premature rupture of the membranes. Korean J Obstet Gynecol 2002;45: Romero R, Quintero R, Nores J, Avila C, Mazor M, Hanaoka S, et al. Amniotic fl uid white blood cell count: a rapid and simple test to diagnose microbial invasion of the amniotic cavity and predict preterm delivery. Am J Obstet Gynecol 1991;165: Steel JH, O Donoghue K, Kennea NL, Sullivan MH, Edwards AD. Maternal origin of inflammatory leukocytes in preterm fetal membranes, shown by fl uorescence in situ hybridisation. Placenta 2005;26: Park KH, Yoon BH, Choe G, Jun JK, Syn HC. Prenat Neonatal Med. The relationship between the presence, severity, and pattern of acute placental infl ammation and amniotic fl uid white blood cell count in preterm labor 1997;2: Romero R, Yoon BH, Mazor M, Gomez R, Diamond MP, Kenney JS, et al. The diagnostic and prognostic value of amniotic fl uid white blood cell count, glucose, interleukin-6, and gram stain in patients with preterm labor and intact membranes. Am J Obstet Gynecol 1993;169: Romero R, Jimenez C, Lohda AK, Nores J, Hanaoka S, Avila C, et al. Amniotic fl uid glucose concentration: a rapid and simple method for the detection of intraamniotic infection in preterm labor. Am J Obstet Gynecol 1990;163: Yoon BH, Romero R, Kim CJ, Jun JK, Gomez R, Choi JH, et al. Amniotic fl uid interleukin-6: a sensitive test for antenatal diagnosis of acute infl ammatory lesions of preterm placenta and prediction of perinatal morbidity. Am J Obstet Gynecol 1995;172: Greig PC, Ernest JM, Teot L, Erikson M, Talley R. Amniotic fl uid interleukin-6 levels correlate with histologic chorioamnionitis and amniotic fl uid cultures in patients in premature labor with intact membranes. Am J Obstet Gynecol 1993;169: Park KH, Yoon BH, Kim MH, Kim GJ, Kim T, Lee HK, et al. A comparative study of the diagnostic value of amniotic fluid interleukin-6 and culture for the antenatal diagnosis of intrauterine infection and prediction of perinatal morbidity in patients with preterm premature rupture of membranes. Korean J Obstet Gynecol 2000;43: Shim SS, Romero R, Hong JS, Park CW, Jun JK, Kim BI, et al. Clinical signifi cance of intra-amniotic infl ammation in patients with preterm premature rupture of membranes. Am J Obstet Gynecol 2004;191: Goncalves LF, Chaiworapongsa T, Romero R. Intrauterine infection and prematurity. Ment Retard Dev Disabil Res Rev 2002;8:

7 Eun Ha Jeong, et al. The relationship between amniotic fluid white blood cell and histologic chorioamnionitis 만삭전조기양막파수임신부에서양수내백혈구수와태반염증성병변의관련성에관한연구 서울대학교의과대학분당서울대학교병원산부인과정은하, 박교훈, 오경준, 이성윤, 김시내, 정희정, 이정연 목적만삭전조기양막파수임신부에서양수내백혈구수와태반염증성병변의존재및정도와의관련성을확인하고자한다. 연구방법만삭전조기양막파수로입원한단태임신임신부중양수내백혈구수측정및양수배양검사를위해경복부양수천자가시행되고, 양수천자후 72시간내에조기분만 ( 임신 주사이 ) 되었으며, 태반의조직학적검사가시행된 90명의임신부를대상으로하였다. 결과조직학적융모양막염의빈도는 32% 였으며양성양수배양인경우는 21% 였다. 태반염증성병변이존재하는경우는존재하지않는경우에비하여양수내백혈구수가유의하게많았다. 양수내백혈구수는교란변수의영향을보정한후에도태반염증성병변의존재와유의한관련성을나타내었다. 또한양수내백혈구수는각각의태반부위별염증정도가심할수록유의하게증가하였다. 태반염증성병변존재를가장잘예측할수있는양수백혈구수의절단치는 25개 /mm 3 였고이때민감도 62%, 특이도 77% 를나타내었다. 결론 만삭전조기양막파수임신부에서양수내백혈구수는태반의염증성병변의존재및정도와유의한관련성을가지고있으며산전에이의존재유무를예측할수있는독립적인자이다. 중심단어 : 양수, 백혈구, 태반, 염증성병변, 만삭전조기양막파수 85

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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