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ORIGINAL ARTICLE Korean J Obstet Gynecol 2012;55(3):158-165 http://dx.doi.org/10.5468/kjog.2012.55.3.158 pissn 2233-5188 eissn 2233-5196 ASSOCIATION OF GENITAL MYCOPLASMAS INFECTION IN WOMEN WHO HAD PRETERM DELIVERY AND OUTCOMES IN PREMATURE INFANTS Hyun Kyung Chung, MD 1, So Yun Park, MD 1, Mi Hye Park, MD, PhD 1, Yong Ju Kim, MD, PhD 1, Sun Hee Chun, MD, PhD 1, Su Jin Cho, MD, PhD 2, Eun Ae Park, MD, PhD 2 Departments of 1 Obstetrics and Gynecology, 2 Pediatrics, Ewha Womans University School of Medicine, Seoul, Korea Objective We conducted this study to evaluate the relationship between genital Mycoplasmas infection in women who had preterm delivery and the neontal outcomes. Methods We studied 116 women with preterm delivery (gestational age, ranged from 24 to 37 weeks) and their 116 premature infants born at Ewha Womans University Mokdong Hospital from August 2009 to December 2010. Culture for genital Mycoplasmas or a polymerase chain reaction was performed in vaginal fluid obtained from women who had preterm delivery. For perinatal outcomes, chorioamnionitis, funisitis and puerperal infection were analysed. We also evaluated the following neonatal data; birth weight, sex, small for gestational age, Apgar score, cord blood ph, ventilator care, hospital days, incidence of respiratory distress syndrome, bronchopulmonary dysplasia, sepsis, intraventricular hemorrhage and patent ductus arteriosus. Results Genital Mycoplasmas were isolated in 36.2% (42 of 116 patients). History of prior preterm birth was significantly higher and the cervical length at admission was significantly shorter in patients with genital Mycoplasmas infection (P < 0.05). Perinatal outcomes according to the Mycoplasmas infection and the neonatal outcomes were not statistically different between study and control groups. The relative risk of respiratory distress syndrome and bronchopulmonary dysplasia were 1.55 (95% confidence interval [CI], 0.65-3.70), and 1.24 (95% CI, 0.42-3.67), respectively. Conclusion There is higher incidence of prior preterm birth and shorter cervical length in patient with genital Mycoplasmas infection. However, genital Mycoplasmas infection does not affect the neonatal outcomes Keywords: Genital Mycoplasmas; Mycoplasma hominis; Ureaplasma urealyticum; Preterm birth; Premature infants 조산은재태연령 37주미만에분만되는것으로세계적으로전체분만의 10% 에서발생되고신생아사망의 70%, 이환의 75% 를차지하고있는산과학과신생아학의주요문제이다 [1]. 지난 50년동안조산방지를위한여러가지치료법개발에도불구하고그발생빈도는감소되지않고있어원인규명및그에따른치료방법은많은의학적관심이되고있다. 조산의병인론은다양하며이중생식기감염은전체조산의원인중 30% 이상을차지한다고알려져있다. 이러한감염이조기진통및조기양막파수를일으키고, 조산아의사망과이환에영향을미치는것으로알려져왔으며 [2], 감염의원인균으로 group B streptococcus, Ureaplasma urealyticum과 Mycoplasma hominis 등 Received: 2011.9.21. Revised: 2011.12.5. Accepted: 2011.12.19. Corresponding author: Sun Hee Chun, MD, PhD Department of Obstetrics and Gynecology, Ewha Womans University School of Medicine, 1071 Anyangcheon-ro, Yangcheongu, Seoul 158-710, Korea Tel: +82-2-2650-2866 Fax: +82-2647-9860 E-mail: shchun@ewha.ac.kr This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/ by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright 2012. Korean Society of Obstetrics and Gynecology 158 WWW.KJOG.ORG

Hyun Kyung Chung, et al. Mycoplasmas in preterm delivery and neonatal outcomes 을포함하는 Mycoplasmas, Chlamydia trachomatis, Escherichia coli, Klebsiella spp, Hemophylus influenza 등이알려져있다. 이중가장흔한원인균은 Ureaplasma urealyticum (U. urealyticum) 과 Mycoplasma hominis (M. hominis) 같은 Mycoplasmas이다 [3]. 최근생식기감염이단순히조기진통또는조산을일으키기보다는자궁내혹은양수내감염을일으켜이에대한반응으로여러종류의염증성싸이토카인이분비되어결국태아조직의손상을일으키는태아염증반응증후군 (fetal inflammatory response syndrome) 으로이해되고있으며따라서이미조기진통을가지고있는임신부의자궁내태아는폐나뇌의조직손상이진행되어있을수있어출생후기관지폐형성이상 (bronchopulmonary dysplasia, BPD) 이나뇌성마비등이발병될가능성을설명하고있다 [4,5]. 이런관점에서조기진통이발생되기전인임신초기의생식기감염, 특히 Mycoplasmas와관련있는세균성질염 (bacterial vaginosis) 을미리진단하여조기항생제치료를시행함으로써조산발생을감소시켰다는연구보고가있다 [6]. M. hominis와 U. urealyticum은사춘기이후의여성과남성의비뇨생식기계에집락하며, 임신여성에서그집락률은 40%-90% 를차지한다 [7]. 여성생식기의 Mycoplasmas 감염은특히조기양막파수및조산, 불임등에관여한다고알려져있다. 또한분만중에는감염된산도를통해신생아에게도여러가지질환을유발할수있다고밝혀졌다 [8]. 최근 Mycoplasmas 감염과신생아질환의관련성에대한연구보고를보면, 선천성폐렴, 뇌수막염, 패혈증등의원인균으로관찰되었다 [9,10]. 신생아의호흡기미숙으로기관지폐형성이상과의연관성과 Mycoplasmas 감염이연관성이있다는연구들이발표되고있어임신중 Mycoplasmas 감염의중요성을다시한번인식시켜주었다 [11]. M. hominis와 U. urealyticum에대한연구는국내에서도활발히진행되어조기진통과조기양막파수가있는산모에게서의감염률등에대한보고는있었다 [12,13]. 그러나이들감염이있는임신부에서분만된조산아들의이환이어느정도인지에대한연구는아직미미하다. 이에저자는조산아를분만한산모의분만전 Mycoplasmas의감염여부를파악하고이들에게서태어난신생아의질환과의연관성을분석하여조기분만시 Mycoplasmas 감염이산과적합병증및신생아의이환율에미치는영향을알아보고자하였다. 2009년 8월부터 2010년 12월까지이화여자대학교이대목동병원산부인과에입원하여분만한산모는 1,062명이었으며이중임신 37 주이전에조산을한경우는 190명이었다. 쌍태아를분만한 26명을제외하고단태아를분만한 164명에서, Mycoplasmas 검사를시행하지못한 43명과검사결과 M. hominis 및 U. urealyticum 이외의균이발견된 5명을제외후, 최종 116명의산모및이들에게서태어나신생아실이나신생아집중치료실에입원한신생아들을대상으로하였다. 조산 은월경주기가규칙적인경우는마지막월경시작일을, 월경주기가불규칙한경우는초기임신시초음파소견을기준으로임신 24주이후와 37완전주 (37 completed weeks) 이전에분만한경우로정의하였다. 분만전산모의자궁경부분비물검체의 Mycoplasmas 배양또는중합요소연쇄반응법 (polymerase chain reaction, PCR) 을시행하여두검사중어느하나의검사결과에서, M. hominis 및 U. urealyticum 둘중하나라도양성인경우를연구군으로, M. hominis와 U. urealyticum에모두음성인경우를대조군으로하였다. 본연구는의무기록분석을통한후향적연구를시행하였다. 내원당시산모의조기양막파수는질경검사에서질내양수가고여있거나 nitrazine test 양성인경우로진단하였다. 입원시내진및경질초음파로자궁경부길이를측정하였으며, 초음파기기는 Prosound SSD- 3500 (Aloka Co. Ltd, Tokyo, Japan) 을사용하였다. 자궁경부길이는환자의방광을완전히비운후쇄석위로눕히고질식탐촉자를질앞천장에부드럽게넣은후, 영상을화면의 75% 이상을차지하게확대시켜자궁경부내구부터외구까지가장긴길이를일직선으로측정하였다 [14]. 산모의합병증중자간전증은 National High Blood Pressure Education Program Working Group (2000) 기준에따라임신 20주이후수축기혈압 140 mm Hg 이상, 이완기혈압 90 mm Hg 이상의혈압을보이며 24시간에 300 mg 이상의단백뇨가함께있는경우로진단하였다 [15]. 임신성당뇨는공복시와 100 g 포도당복용 1시간, 2 시간, 3시간후정맥혈장의혈당치가각각 105 mg/dl, 190 mg/dl, 165 mg/dl, 145 mg/dl 중 2회이상에서기준치를초과하는경우 [16] 또는 75 g 포도당복용 2시간후정맥혈장의혈당치가 140 mg/dl를초과하는경우로진단하였다 [17]. 검체채취는내진전질경으로자궁경부를확인후질벽에닿지않도록주의하여자궁경부에 swab (Yuhan Lab Tech Co., Ltd., Seoul, Korea) 을삽입하여채취하였고 MYCOFAST Evolution 2 (International Microbio, Signes, France) 의 transport medium에접종하여지침에따라배양검사를시행하거나 PCR로검사한후 M. hominis 및 U. urealyticum 감염여부를판정하였다. PCR의경우 STI 1 Real-time Test kit (Seegene, Seoul, Korea) 를사용하여제조사의지시에따라시행하였으며 GeneAmp PCR system 9700 (Applied biosystems Inc., California, CA, USA) 을사용하였다. 산과적합병증으로는임상적융모양막염 (clinical chorioamnionitis), 조직학적융모양막염 (histologic chorioamnionitis) 및제대염 (histologic funisitis), 산욕기감염여부를살펴보았다. 임상적융모양막염은산모의체온이 37.8 o C 이상이면서자궁압통, 악취나는질분비물, 백혈구증가증 (>15,000/μL), 임신부빈맥 (>100회/ 분 ), 태아빈맥 (>160회/ 분 ) 중 2가지이상존재하는경우로진단하였다 [18]. 조직학적융모양막염및제대혈관염은분만후태반과제대를 10% 포르말린에고정후 hematoxylin eosin (H&E) 염색을실시하여병리학자에의해태반, 융모양막및제대혈관등에서다형핵백혈구 (polymorphonuclear WWW.KJOG.ORG 159

KJOG Vol. 55, No. 3, 2012 leukocyte) 의침윤이관찰될경우로진단하였다 [19]. 산욕기감염여부는산욕열, 상처감염, 자궁내막염여부등을파악하였다. 신생아의경우는출생체중과부당경량아여부, 성별, 1분및 5분 Apgar 점수, 제대동맥혈검사, 인공환기기사용여부, 입원기간등을비교하였다. 부당경량아는해당제태연령체중백분위가 10백분위이하로정의하였다 [20]. 신생아이환, 즉신생아호흡곤란증후군 (respiratory distress syndrome, RDS) 은다른폐질환의증거가없는상태에서임상소견상특징적인호흡곤란, 흉곽함몰, 신음및청색증을보이고, 산소요구량의증가 (fraction of inspired oxygen 0.4) 를보이면서흉부의방사선학적검사상망상과립상, 공기-기관지음영등특징적소견이관찰되는경우로, 패혈증 (sepsis) 은전신증상이나혈액검사상이상소견이동반된경우로, 뇌실내출혈 (intraventricular hemorrhage, IVH) 은신생아뇌초음파를시행하여 Volpe 분류에따라각각진단하였다 [21]. BPD은 2001년 National Institute of Child Health workshop에서합의된내용을바탕으로방사선학적소견과는상관없이재태기간 32주미만의미숙아의경우월경후주령 36주와퇴원시점중빠른시기에 21% 가넘는산소를적어도 28일이상투여한경우로 [22], 동맥관개존 (patent ductus arteriosus, PDA) 은심장초 음파에의해진단되고, 인도메타신이나수술적방법을사용하여치료한경우로각각정의하였다. 통계분석은 SAS ver. 9.1 (Institute Inc., Cary, NC, USA) 를사용하였고, Mycoplasma 감염빈도및두군간의빈도분석은카이제곱검정을이용하였으며, 평균은 Student t-검정을이용하여산출하였고 P 값이 0.05 미만인경우에통계적으로유의하다고판단하였다. Proc genmode를사용하여상대위험비 (relative risk, RR) 값을산출하였다. 총 116명의대상산모중 M. hominis와 U. urealyticum에모두음성인경우가 74명 (63.8%), M. hominis 및 U. urealyticum 둘중하나라도양성인경우가 42명 (36.2%) 이었다. 이중 M. hominis 단독감염이 7명 (6.0%), U. urealyticum 단독감염이 25명 (21.6%) 이었으며혼합감염은 Table 1. Mycoplasma hominis and Ureaplasma urealyticum infection No. of infection Infection rate (%) M (+) U (+) 10 8.6 M (+) U (-) 7 6.0 M (-) U (+) 25 21.6 M (-) U (-) 74 63.8 M, Mycoplasma hominis; U, Ureaplasma urealyticum. Table 2. Clinical characteristics M. hominis or U. urealyticum (+) (n = 42) M. hominis or U. urealyticum ( ) (n = 74) P value Maternal age (yr) 31.5 ± 4.2 32.5 ± 4.6 0.25 Gestational age (wk) 33.6 ± 2.8 33.0 ± 2.7 0.33 Primiparity 25 (59.5) 43 (58.1) 0.56 Prior preterm delivery (n=48) a 9 (52.9) (n=17) a 6 (19.3) (n=31) a 0.02 b Preeclampsia 7 (16.7) 9 (12.2) 0.69 GDM 1 (2.4) 5 (6.8) 0.42 PROM 22 (52.4) 39 (52.7) 1.00 Cervical length (mm) 22.5 ± 12.1 26.6 ± 9.5 0.04 b Tocolytics 18 (43.0) 30 (40.5) 0.96 Antenatal steroid 19 (45.2) 43 (58.1) 0.25 Antibiotics 29 (69.1) 63 (85.1) 0.07 Values are presented as mean ± standard deviation or number (%). M, Mycoplasma hominis; U, Ureaplasma urealyticum; GDM, gestational diabetic mellitus; PROM, premature rupture of membrane. a This is the number except primiparity. b P < 0.05 160 WWW.KJOG.ORG

Hyun Kyung Chung, et al. Mycoplasmas in preterm delivery and neonatal outcomes 10 명 (8.6%) 을차지하였다 (Table 1). 연구군과대조군산모의평균연령은 31.5 ± 4.2세와 32.5 ± 4.6세, 재태연령은 33.6 ± 2.8주와 33.0 ± 2.7주로두군사이에유의한차이는없었다 (P > 0.05). 이전의조산과거력은연구군에서 22.0% 로대조군의 8.1% 보다유의하게높았으며 (P = 0.03), 자궁경부길이도연구군이 22.5 ± 12.1 mm로대조군의 26.6 ± 9.5 mm보다유의하게짧았다 (P = 0.04). 조기양막파수의경우, 연구군은 16.7%, 대조군은 12.2% 로두군사이에유의한차이는없었다 (P > 0.05). 임신성고혈압이합병된경우는연구군이 16.7%, 대조군이 12.2% 였으며, 임신성당뇨도각각 2.4%, 6.8% 로모두두군사이에유의한차이는보이지않았다 (P > 0.05). 그밖에진통억제제, 스테로이드, 항생제사용여부는두군사이에통계학적유의한차이는없었다 (P > 0.05) (Table 2). 임상적융모양막염은연구군은 16.7%, 대조군은 12.2% 로두군사이에발생빈도의유의한차이를보이지않았다 (P > 0.05). 조직학적융모양막염, 제대혈관염의발생빈도도또한두군간에차이가없었다 (P > 0.05). 산욕기감염여부에대해비교하였을때도연구군이 7.5%, 대조군이 2.7% 로통계학적으로유의한차이를보이지않았다 (P > 0.05) (Table 3). 연구군과대조군에서태어난조산아의평균몸무게를분석한결 Table 3. Delivery outcomes according to Mycoplasma hominis and Ureaplasma urealyticum infection M. hominis or U. urealyticum (+) (n = 42) M. hominis or U. urealyticum ( ) (n = 74) P value Clinical chorioamnionitis 7 (16.7) 9 (12.2) 0.69 Histologic chorioamnionitis 10 (27.0) 31 (43.7) 0.14 Histologic funisitis 5 (13.5) 4 (5.6) 0.14 Puerperal infection 3 (7.5) 2 (2.7) 0.34 Values are presented as number (%). Table 4. Effect of Mycoplasma hominis and Ureaplasma urealyticum infection on neonatal morbidity M. hominis or U. urealyticum (+) (n = 42) M. hominis or U. urealyticum ( ) (n = 74) P value Relative risk 95% CI Birth weight (g) 2073.8 ± 621.0 2008.0 ± 637.7 0.59 Male sex 28 (66.7) 47 (63.5) 0.89 SGA 3 (7.1) 10 (13.5) 0.15 Apgar score<7 (1 min) 14 (33.3) 28 (37.8) 0.78 Apgar score<7 (5 min) 5 (11.9) 7 (9.5) 0.75 Cord blood ph 7.4 ± 0.2 7.3 ± 0.1 0.12 Ventilator care 7 (16.7) 22 (29.7) 0.18 Hospital days a (day) 15.0 (8.0 26) 20 (11 48) 0.16 8 11 (26.2) 13 (17.6) 0.29 36 23 (54.8) 38 (51.4) >36 8 (19.1) 23 (31.1) RDS 8 (19.1) 9 (12.3) 0.48 1.55 0.65 3.70 Sepsis 3 (7.1) 5 (6.9) 1.00 1.04 0.26 4.15 IVH 1&2 8 (19.05) 10 (13.70) 0.62 1.39 0.60 3.25 BPD 5 (11.90) 7 (9.59) 0.76 1.24 0.42 3.67 PDA 5 (11.90) 14 (19.18) 0.44 0.62 0.24 1.60 Values are presented as mean ± standard deviation or number (%). CI, confi dence interval; SGA, small for gestational age; RDS, respiratory distress syndrome; IVH, intraventricular hemorrhage; BPD, bronchopulmonary dysplasia; PDA, patent ductus arteriosus. a Non parametric analysis using Wilcoxon rank sum test. WWW.KJOG.ORG 161

KJOG Vol. 55, No. 3, 2012 과각각 2,073.8 ± 621.0 g, 2,008.0 ± 637.7 g으로통계학적으로유의한차이는없었다 (P > 0.05) 성별및부당경량아비율에서도두군간의차이를보이지않았다 (P > 0.05). 1분및 5분 Apgar 점수가 7점이하인경우를살펴본결과, 연구군은각각 33.3% 와 11.9% 였고, 대조군은 37.8% 와 9.5% 로나왔으며, 제대동맥혈 ph를비교해본결과연구군은 7.4 ± 0.2, 대조군은 7.3 ± 0.1이었고, 모두유의한차이는없었다 (P > 0.05). 인공환기기사용여부, 입원기간에서도두군간에차이를보이지않았다 (P > 0.05). RDS의경우 RR가 1.55 (95% confidence interval [CI], 0.65-3.70) 였으며, IVH 1, 2단계및 BPD의경우각각 1.39 (95% CI, 0.60-3.25), 1.24 (95% CI, 0.42-3.67) 였다. 그러나모두연구군과대조군간에통계학적으로유의한차이는없었다 (P > 0.05) (Table 4). Mycoplasmas는세포벽이없는가장작은세균으로세포벽에작용하는 ß-lactam 항생제에반응하지않고배양도잘되지않는다. Mycoplasma hominis가 1937년 Bartholin 농양으로부터처음분리되어보고된이후, 현재까지약 12종의 Mycoplasmas가사람에서분류되었는데, 6종의 Mycoplasma와 2종의 Ureaplasma가비뇨생식기계에집락을형성하고있다 [23]. 이중에서 M. hominis와 U. urealyticum이산모와신생아에게영향을미치며다양한질환을유발하는주요병원체로알려져있다. 이들을분리하기위해서는특수배지를이용한배양방법을통해가능하였으나최근에는 PCR을이용하여진단이가능해졌고이로인해검체분리시간도단축할수있게되었다 [24]. 임신중 Mycoplasmas 감염의빈도는저자에따라상당한차이가있는데 M. hominis 감염의경우 McCormack 등 [25] 은 21.3% 의분리율을, 그리고국내 Chang 등 [26] 은 8% 의분리율을보고하였고, U.urealyticum의경우 Mårdh와 Weström [27] 은 68.4%, 국내 Chang 등 [26] 은 51.6% 의분리율을보고하였다. 본연구에서는 M. hominis 단독감염이 6.0%, U. urealyticum 단독감염이 21.6% 이었으며혼합감염은 8.6% 로기존의연구와달리조기분만한산모를대상으로조사한것으로감염율에차이가나타난것으로보인다. Mycoplasmas 감염이조산및신생아질환과밀접한관계가있음을밝히는많은논문들이보고되었다. Klein 등 [28] 과 Braun 등 [29] 은대조군에비해 U. urealyticum과 M. hominis 감염군에서출산된태아의평균몸무게가더적다고보고하였으나, Embree 등 [30] 은 Ureaplasma 감염과저체중아출산과관련이없다고보고하였다. 2003년 Yoon 등 [31] 은양수내의 U. urealyticum 감염에따른산모와신생아들의임상양상을살펴보았다. 양수내 U. urealyticum은배양과 PCR을통하여검출하였으며, 그결과 PCR 양성이면서배양검사에서는음성인조기진통산모에게서조산을하는비율이높았으며, 주산기예후에도영향을미치는것으로나타났다. 또한출산된태아의몸무게도더적었으며주요질병의이환율도통계학적으로의미있게높은것으로나타났다. 그 러나본연구에서는연구군과대조군사이에출산된태아의평균몸무게및이환율을비교하였을때통계학적으로의미있는차이를보이지않았는데이는양수내감염이아닌질내감염결과로만비교하였기에위결과와다른결과가나온것으로생각된다. 이외에 Ureaplasma 감염과 RDS 및 BPD 발생률과의관계를살펴본연구발표도있었다. 여러연구에서자궁내 Ureaplasma 감염이미숙아에게서 RDS 발생률을줄이는것으로보고하였으며이는태내에서의하부기도내감염은아급성의폐포내염증반응을일으키고폐성숙과폐표면활성제의생산을증가시켜미숙아의급성호흡기질환의발생을낮추는효과를나타내기때문이다 [32,33]. BPD의경우에는발병률을높인다는연구발표도있었는데 [34-36], U. urealyticum에의한 BPD의발생기전은기도상피세포에집락형성을한후섬모운동의혼란및군집을형성하고탐식세포를자극해 IL-6, TNF-alpha 등의 BPD 발생과관련된염증성인자를생산하는것으로생각되어진다 [37]. 이와반대로재태연령을비롯한몇가지변수를보정한결과연관성이관찰되지않았다는발표도있었다 [38]. 본연구에서는 RDS 및 BPD 발생률의차이를비교한결과 BPD 경우상대위험도를계산하였을때연구군이대조군에비해 1.24배높았으며 RDS경우 1.55배높게나타났으나통계학적으로의미있는차이를보이지않았다. 신생아패혈증의경우임신부의산도를통한감염으로인해일어날수있으며, 자궁내태아에게도감염된양수와태반을통해감염을일으킬수있다 [39]. 기존의연구에서 Ureaplasma 양성신생아의혈액배양검사에서혈액중의 Ureaplasma의동정을확인하여보고한바있었다 [40]. 그러나본연구에서는산모의질내 Mycoplasmas 감염이신생아패혈증의발생률을높이지는않는것으로나타났다. 본연구는조산아를분만한산모의분만전 Mycoplasmas의감염여부를파악하고이들에게서태어난신생아의질환과의연관성을분석하여분만전 Mycoplasmas 감염이임신및신생아의예후에미치는영향을알아보고자하였다. 대상산모들의특징으로는연구군에서조산과거력이더많고, 자궁경부길이가더짧은것으로확인되었다. 그러나본연구는후향적으로의무기록을조사하여이루어진연구로신생아의여러발생질환이실제모체의 Mycoplasmas 감염으로인한것인지정확히구분하기어렵다. 임신초기의생식기감염이지속적으로존재하여태아염증반응을일으켜조산을유발할수있으며따라서임신초기의세균성질염진단과조기치료가조산및신생아이환의발생을감소시킬수있다는발표가있었다 [6]. 따라서세균성질염이있는산모는조기진통이나조기양막파수의위험이높아질수있으나본연구에서는세균성질염의유무를함께평가하지못하였기에이로인한영향여부를분석하지못한한계가있으며향후이에대한연구필요하겠다. References 1. Challis JR, Lye SJ, Gibb W, Whittle W, Patel F, Alfaidy N. Under- 162 WWW.KJOG.ORG

Hyun Kyung Chung, et al. Mycoplasmas in preterm delivery and neonatal outcomes standing preterm labor. Ann N Y Acad Sci 2001;943:225-34. 2. Romero R, Mazor M. Infection and preterm labor. Clin Obstet Gynecol 1988;31:553-84. 3. Romero R, Shamma F, Avila C, Jimenez C, Callahan R, Nores J, et al. Infection and labor. VI. Prevalence, microbiology, and clinical signifi cance of intraamniotic infection in twin gestations with preterm labor. Am J Obstet Gynecol 1990;163:757-61. 4. Yoon BH, Romero R, Park JS, Kim M, Oh SY, Kim CJ, et al. The relationship among infl ammatory lesions of the umbilical cord (funisitis), umbilical cord plasma interleukin 6 concentration, amniotic fl uid infection, and neonatal sepsis. Am J Obstet Gynecol 2000;183:1124-9. 5. Romero R, Gomez R, Ghezzi F, Yoon BH, Mazor M, Edwin SS, et al. A fetal systemic infl ammatory response is followed by the spontaneous onset of preterm parturition. Am J Obstet Gynecol 1998;179:186-93. 6. Lamont RF, Duncan SL, Mandal D, Bassett P. Intravaginal clindamycin to reduce preterm birth in women with abnormal genital tract fl ora. Obstet Gynecol 2003;101:516-22. 7. Anagrius C, Loré B, Jensen JS. Mycoplasma genitalium: prevalence, clinical signifi cance, and transmission. Sex Transm Infect 2005;81:458-62. 8. Kataoka S, Yamada T, Chou K, Nishida R, Morikawa M, Minami M, et al. Association between preterm birth and vaginal colonization by mycoplasmas in early pregnancy. J Clin Microbiol 2006;44:51-5. 9. Cassell GH, Waites KB, Watson HL, Crouse DT, Harasawa R. Ureaplasma urealyticum intrauterine infection: role in prematurity and disease in newborns. Clin Microbiol Rev 1993;6:69-87. 10. Velemínský M, Tosner J. Relationship of vaginal microfl ora to PROM, pprom and the risk of early-onset neonatal sepsis. Neuro Endocrinol Lett 2008;29:205-21. 11. Katz B, Patel P, Duffy L, Schelonka RL, Dimmitt RA, Waites KB. Characterization of ureaplasmas isolated from preterm infants with and without bronchopulmonary dysplasia. J Clin Microbiol 2005;43:4852-4. 12. Kim MJ, Choi MH, Seong WJ, Koo TB, Park IS. The detection rate of Ureaplasma urealyticum and Mycoplasma hominis in patients with impending preterm birth and mid-trimester cervical swab. Korean J Perinatol 2008;19:370-6. 13. Kim SY, Lee YJ, Meen H, Lee SH, Park IY, Ahn HY, et al. Analysis of mycoplasma hominis and ureaplasma urealyticum infection in preterm labor and prom patients. Korean J Obstet Gynecol 2004;47:1469-73. 14. Iams JD, Goldenberg RL, Meis PJ, Mercer BM, Moawad A, Das A, et al. The length of the cervix and the risk of spontaneous premature delivery. National Institute of Child Health and Human Development Maternal Fetal Medicine Unit Network. N Engl J Med 1996;334:567-72. 15. Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy. Am J Obstet Gynecol 2000;183:S1-S22. 16. Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance. National Diabetes Data Group. Diabetes 1979;28:1039-57. 17. WHO Expert Committee on Diabetes Mellitus: second report. World Health Organ Tech Rep Ser 1980;646:1-80. 18. Gibbs RS, Blanco JD, St Clair PJ, Castaneda YS. Quantitative bacteriology of amniotic fluid from women with clinical intraamniotic infection at term. J Infect Dis 1982;145:1-8. 19. Hollander D. Diagnosis of chorioamnionitis. Clin Obstet Gynecol 1986;29:816-25. 20. Lubchenco LO, Hansman C, Dressler M, Boyd E. Intrauterine Growth as Estimated from Liveborn Birth-Weight Data at 24 to 42 Weeks of Gestation. Pediatrics 1963;32:793-800. 21. Volpe JJ. Neonatal intracranial hemorrhage. Pathophysiology, neuropathology, and clinical features. Clin Perinatol 1977;4:77-102. 22. Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med 2001;163:1723-9. 23. Taylor-Robinson D, McCormack WM. The genital mycoplasmas (fi rst of two parts). N Engl J Med 1980;302:1003-10. 24. Kong F, Ma Z, James G, Gordon S, Gilbert GL. Species identification and subtyping of Ureaplasma parvum and Ureaplasma urealyticum using PCR-based assays. J Clin Microbiol 2000;38:1175-9. 25. McCormack WM, Rosner B, Lee YH. Colonization with genital mycoplasmas in women. Am J Epidemiol 1973;97:240-5. 26. Chang MW, Choi TK, Yoshii Z, Matsuo Y. Isolation of Ureaplasma urealyticum and Mycoplasma hominis from patients with genitourinary tract infection. Hiroshima J Med Sci 1984;33:53-6. 27. Mårdh PA, Weström L. T-mycoplasmas in the genito-urinary tract of the female. Acta Pathol Microbiol Scand B Microbiol Immunol 1970;78:269. 28. Klein JO, Buckland D, Finland M. Colonization of newborn infants by mycoplasmas. N Engl J Med 1969;280:1025-30. 29. Braun P, Lee YH, Klein JO, Marcy SM, Klein TA, Charles D, et al. Birth weight and genital mycoplasmas in pregnancy. N Engl J WWW.KJOG.ORG 163

KJOG Vol. 55, No. 3, 2012 Med 1971;284:167-71. 30. Embree JE, Krause VW, Embil JA, MacDonald S. Placental infection with Mycoplasma homonis and Ureaplasma urealyticum: clinical correlation. Obstet Gynecol 1980;56:475-81. 31. Yoon BH, Romero R, Lim JH, Shim SS, Hong JS, Shim JY, et al. The clinical signifi cance of detecting Ureaplasma urealyticum by the polymerase chain reaction in the amniotic fl uid of patients with preterm labor. Am J Obstet Gynecol 2003;189:919-24. 32. Hannaford K, Todd DA, Jeffery H, John E, Blyth K, Gilbert GL. Role of ureaplasma urealyticum in lung disease of prematurity. Arch Dis Child Fetal Neonatal Ed 1999;81:F162-7. 33. Cultrera R, Seraceni S, Germani R, Contini C. Molecular evidence of Ureaplasma urealyticum and Ureaplasma parvum colonization in preterm infants during respiratory distress syndrome. BMC Infect Dis 2006;6:166. 34. Benstein BD, Crouse DT, Shanklin DR, Ourth DD. Ureaplasma in lung. 2. Association with bronchopulmonary dysplasia in premature newborns. Exp Mol Pathol 2003;75:171-7. 35. Colaizy TT, Morris CD, Lapidus J, Sklar RS, Pillers DA. Detection of ureaplasma DNA in endotracheal samples is associated with bronchopulmonary dysplasia after adjustment for multiple risk factors. Pediatr Res 2007;61:578-83. 36. Walsh WF, Butler J, Coalson J, Hensley D, Cassell GH, delemos RA. A primate model of Ureaplasma urealyticum infection in the premature infant with hyaline membrane disease. Clin Infect Dis 1993;17 Suppl 1:S158-62. 37. Patterson AM, Taciak V, Lovchik J, Fox RE, Campbell AB, Viscardi RM. Ureaplasma urealyticum respiratory tract colonization is associated with an increase in interleukin 1-beta and tumor necrosis factor alpha relative to interleukin 6 in tracheal aspirates of preterm infants. Pediatr Infect Dis J 1998;17:321-8. 38. Ollikainen J, Korppi M, Heiskanen-Kosma T, Heinonen K. Chronic lung disease of the newborn is not associated with Ureaplasma urealyticum. Pediatr Pulmonol 2001;32:303-7. 39. Cassell GH, Davis RO, Waites KB, Brown MB, Marriott PA, Stagno S, et al. Isolation of Mycoplasma hominis and Ureaplasma urealyticum from amniotic fl uid at 16-20 weeks of gestation: potential effect on outcome of pregnancy. Sex Transm Dis 1983;10:294-302. 40. Cassell GH, Waites KB, Crouse DT, Rudd PT, Canupp KC, Stagno S, et al. Association of Ureaplasma urealyticum infection of the lower respiratory tract with chronic lung disease and death in very-low-birth-weight infants. Lancet 1988;2:240-5. 164 WWW.KJOG.ORG

Hyun Kyung Chung, et al. Mycoplasmas in preterm delivery and neonatal outcomes 조산임신부의분만전생식기 Mycoplasmas 감염과임신및신생아예후에관한연구 이화여자대학교의학전문대학원 1 산부인과학교실, 2 소아청소년과학교실정현경 1, 박소연 1, 박미혜 1, 김영주 1, 전선희 1, 조수진 2, 박은애 2 목적조기분만시 Mycoplasmas 감염이임신및신생아의이환율에미치는영향을알아보고자하였다. 연구방법본연구는의무기록분석을통한후향적연구로, 2009년 8월부터 2010년 12월까지이화여자대학교이대목동병원산부인과에입원하여단태아조산아를분만한 116명의산모및이들에게서태어난신생아들을대상으로하였다. 검체는자궁경부에서채취하여배양혹은중합효소연쇄반응법을시행하였으며, 감염에따른신생아이환율을비교분석하였다결과총 116명의대상산모중생식기 Mycoplasmas 감염된경우가 42명 (36.2%) 이었다. 연구군에서대조군보다자궁경부길이가유의하게짧았고, 조산기왕력의빈도는높았다. 산과적합병증으로임상적융모양막염과조직학적융모양막염, 제대혈관염의발생빈도및산욕기감염발생을비교하였을때두군간에차이를보이지않았으며, 연구군과대조군에서태어난신생아의평균몸무게, 성별, 부당경량아비율, 1분및 5분 Apgar 점수, 제대동맥혈 ph, 인공환기기사용여부, 입원기간, 신생아호흡곤란증후군 (respiratory distress syndrome, RDS), sepsis, 뇌실내출혈 (intraventricular hemorrhage), 동맥관개존 (patent ductus arteriosus) 이환율을분석한결과통계학적으로유의한차이는없었다. RDS 및기관지폐형성이상 (bronchopulmonary dysplasia) 의상대위험비 (relative risk) 는각각 1.55 (95% confidence interval [CI], 0.65-3.70), 1.24 (95% CI, 0.42-3.67) 였다. 결론임상적특징으로는연구군에서조산과거력이더많고, 자궁경부길이가더짧은것으로나타났다. 그러나조산모의질내 Mycoplasmas 감염은여러신생아의질환발생에거의영향을주지않는것으로확인되었다. 중심단어 : 생식기마이코플라즈마, 조산, 조산아 WWW.KJOG.ORG 165