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1 Korean Journal of Obstetrics and Gynecology Vol. 52 No. 5 May 2009 저체중태아를동반한만기임신의주산기예후예측을위한제대동맥도플러혈류속도파형의유용성 아주대학교의과대학산부인과학교실 김호연 김행수 양정인 공태욱이경미 장석준 김용미 The efficacy of umbilical artery blood flow velocity waveform to predict the perinatal outcome of term pregnancies with small for gestational age Ho-Yeon Kim, M.D., Haeng-Soo Kim, M.D., Jeong-In Yang, M.D., Tae-Wook Kong, M.D. Kyoung-Mi Lee, M.D., Suk-Jun Chang, M.D., Yong-Mi Kim, M.D. Department of Obstetrics and Gynecology, Ajou University School of Medicine, Suwon, Korea Objective: To investigate whether umbilical artery Doppler blood flow velocity waveform is effective in predicting perinatal outcome of term pregnancies with small for gestational age (SGA). Methods: A total of 381 patients at 37~41 weeks of gestational age (GA) who received antenatal umbilical artery Doppler blood flow test and delivered singleton SGA infants. The ratio of peak-systolic to end-diastolic (S/D) blood flow velocities in the umbilical artery was measured in each patient. The patients were divided into a normal group (n=307) with a S/D ratio equal to or less than 3.0, and an abnormal group with a S/D ratio of greater than 3.0 (n=74). These groups were comparatively analysed with respect to maternal characteristics and neonatal outcomes. Results: There were no significant differences between the two groups in mean maternal age, gestational age at the time of delivery, and cesarean section rate due to fetal distress. There was significantly increased incidence of hypertensive disorders in pregnancy in the abnormal S/D ratio group. And the abnormal S/D ratio group showed lower neonatal birthweight, higher incidence of admission to neonatal intensive care unit (NICU), and longer stay in neonatal intensive care unit. According to linear regression, in pregnancies complicated by SGA, abnormal S/D ratio was still a risk factor for low birthweight even after controlling for the incidence of hypertension. Conclusion: In term pregnancies accompanied by SGA, abnormal umbilical artery S/D ratio is an independent predictor of neonatal birth weight, incidence of admission to NICU, and NICU stay. Key Words: Small for gestational age, Term pregnancy, Umbilical artery blood flow velocity 서 론 접수일 : 채택일 : 교신저자 : 김행수 kimhs7@ajou.ac.kr 태아의성장은선천적으로부모로부터물려받은잠재적성장능력과이에영향을미칠수있는태아, 태반및산모의건강등에영향을받는다. 1 일반적으로저체중태아 (small for gestational age) 는예상태아체중혹은신생아

2 대한산부회지제 52 권제 5 호, 2009 체중이해당임신주수의 10 백분위미만인경우를말하며, 사산, 양수과소증, 태아곤란증에의한제왕절개분만, 낮은 Apgar 치, 7 미만의제대동맥폐하 (ph) 등과관련이있어주산기이환및사망률이높다. 또한분만후신생아시기에도적혈구증가증, 저혈당, 저체온, 무호흡, 패혈증, 경련및신생아사망률등이증가하며, 2 성인이되어서도심혈관질환, 비인슐린의존성당뇨등의위험도가높다. 3 이러한저체중태아는체질적으로작은건강한태아와상기위험도가높은병적발육제한아가모두포함되기때문에이들을산전에정확히구분하기가어렵고따라서많은경우이들을혼용하여사용하고있다. 한편임신 37주이후에보이는저체중태아의주산기예후에대한연구에서저체중아는정상체중아 (appropriate for gestational age) 보다저체온증과증상을보이는저혈당의빈도가높으며 Apgar 치가낮다. 4,5 출생체중 10 백분위미만의발육제한아에서는 1분 Apgar 치가낮고신생아중환자실입원율이높으며호흡부전, 저혈당, 저혈소판증및고빌리루빈혈증등이증가하고, 6 특히 3 백분위이하의발육제한아는정상체중태아에비해신생아사망률과이환율이증가하고, 7 생후 12세와 18세에불량한학습수행도를보여, 8 만삭에저체중태아를동반한임신에대한집중적인산전관리가필요하다. 제대동맥도플러혈류속도파형검사는임신이진행되면서제대동맥의이완기저항이감소하는현상을이용한방법으로태반기능부전을예측할수있는비침습적방법중의하나이다. 따라서저체중태아나고혈압등이동반된고위험임신군에서제대동맥도플러혈류속도파형검사를이용하여불량한예후를예측할수있고, 9,10 주산기사망률을낮출수있다. 11 저체중태아는태아기형이없고제대동맥도플러혈류속도파형이정상인체질적인저체중아와병적인발육제한아로구분할수있고, 12 발육제한아에서제대동맥도플러지수와주산기합병증빈도와는밀접한상관관계를보인다. 13 특히 35주이전의조산아들중발육제한이동반된임신의경우제대동맥의도플러혈류가소실되거나역류되는것은신생아사망이나뇌성마비의독립적인예측인자로작용한다. 14 이처럼조산에동반된저체중태아의경우제대동맥도플러혈류속도측정은태아의안녕평가를위해가장기본적으로시행하는항목으로평가받고있다. 그러나임신 37주이후만기임신에서저체중태아를동반한경우제대동맥도플러혈류파형이주산기예후판정에유용한가에대해서는연구가많지않다. 따라서본연구에서는저체중태아를동반한임신 37주이후의만기임신에서제대동맥도플러혈류속도파형이주산기예후예측에유용한가를알아보고자한다. 연구대상및방법임신 37주부터 41주사이에본원에서단태의저체중태아를분만한산모와신생아의의무기록을후향적으로검토하였다. 대상산모들은임신 20주이전에시행한산전초음파검사로임신주수를확인한산모를대상으로하였고, 제대동맥도플러검사를하지않았던경우, 태아의구조적이상이나염색체이상, 다태임신및감염이의심되는경우는제외하였다. 저체중태아는분만후신생아체중이재태연령별체중분포에서 10 백분위미만인경우로정의하였다. 15 연구에사용된초음파기기는 ATL HDI-UM9 (Advanced Technology Laboratories, Bothwell, Wash, USA) 과 Aloka SSD-5500 (Aloka Ltd, Japan) 이었다. 제대동맥의도플러혈류속도분석은태아복벽과태반부착부위사이의중간지점에서 5개이상의동일한혈류속도파형을얻은후, 최고수축기혈류속도 (peak systolic flow velocity: S) 대이완기말혈류속도 (end diastolic velocity: D) 의비 (S/D) 로하였으며 S/D 는 5개이상의파형의평균치로하였다. S/D 가 3 이하이면정상군으로 3을초과하면비정상군으로나누어모체의특성과신생아의주산기예후를각각비교하였다. 제대동맥의도플러초음파검사는분만전 1 주일이내에마지막으로시행된것을분석하였다. 산모의나이, 신장, 체중, 산과력, 고혈압및당뇨유무, 분만시주수, 양수과소증 ( 양수지수 5 cm) 유무, 분만방법, 태아곤란증에의한제왕절개분만빈도를비교하였고, 신생아예후로태아성별, 태아체중, 7 미만의낮은 5분 Apgar 치빈도, 주산기사망, 신생아중환자실입원, 중환자실입원기간, 기계적호흡기사용여부및사용기간및신생아합병증 ( 호흡부전증후군, 괴사성장염, 기관지폐이형성증, 뇌주위백질연화증, Grade III 혹은 IV 뇌실내출혈 ) 등을비교분석하였다. 신생아들은모두출생후에단순흉부및복부 X선검사, 뇌초음파와복부초음파검사및뇌출혈이의

3 김호연외 6 인. 저체중태아를동반한만기임신의주산기예후예측을위한제대동맥도플러혈류속도파형의유용성 심되면뇌컴퓨터단층촬영을시행하여확진하였다. 불량한주산기예후는 7 미만의낮은 5분 Apgar 치, 주산기사망, 신생아중환자실입원, 기계적호흡기사용, 신생아합병증중한가지이상에이환되었을경우로정의하였다. Student t-test, Chi-square test와 logistic regression (SPSS version 12) 을사용하여통계분석하였고 P<0.05 를통계학적으로유의하다고간주하였다. 결과 1. 임상적특징총 381 명의대상산모중제대동맥도플러혈류속도의 S/D 가 3 이하인정상군은 307 명이었고 S/D 가 3을초과하는비정상군은 74명이었다. 산모의나이, 산과력과분만시임신주수는양군에서차이가없었다. 대상산모의임신중고혈압빈도 (12.3% vs. 25.0%, P=0.005) 는비정상군에서유의하게높았다. 그러나양수과소증 (12.3% vs. 12.1%), 당뇨 (3.3% vs. 6.3%) 와태아곤란증에의한제왕절개분만빈도 (12.3% vs. 18.8%) 등은양군에서차이를보이지않았다 (Table 1). 2. 신생아특징및주산기예후출생시신생아체중은정상군에서 2,415.2±258.9 g, 비정상군에서 2,296.7±325.0 g으로유의한차이를보였다 (P=0.003). 신생아의중환자실입원빈도 (27.0% vs. 51.3%, P<0.001) 는비정상군에서유의하게높았고입원기간 (2.7±5.9일 vs. 5.7±8.8일, P=0.005) 역시비정상군에서유의하게길었다. 7 미만의낮은 5분 Apgar 치 (2.7% vs. 2.6%) 와주산기사망은양군에서차이가없었으며, 그외의기계적호흡빈도와신생아합병증등도양군에서차이를보이지않았다. 그러나불량한주산기예후빈도 (34.3% vs. 52.5%, P=0.003) 는비정상군에서유의하게높았다 (Table 2). 한편, 선형회귀분석을시행한결과고혈압성질환의빈도를보정한후에도비정상제대동맥도플러혈류속도는출생시신생아체중감소와유의한관계가있음을확인하였다 (P<0.001) (Table 3). 고찰우리의연구결과만기임신에동반된저체중태아에서제대동맥의도플러지수가비정상인경우는정상을보이는경우와비교하여출생시신생아체중이유의하게작고신생 Table 1. Maternal characteristics Normal UASD (n=307) Abnormal UASD (n=74) Maternal age (yr) 29.2± ±4.2 NS Height (cm) 158.7± ±4.6 NS Weight (kg) 52.8± ±9.3 NS Parity 0 0 NS Hypertension 37 (12.1%) 20 (27.0%) Diabetes 10 (3.3%) 5 (6.8%) NS GA at delivery (wks) 38.1± ±1.1 NS Oligohydramnios 38 (12.3%) 9 (12.1%) NS Mode of delivery NS Vaginal delivery 179 (58.3%) 40 (54.0%) Cesarean section 132 (41.7%) 32 (46.0%) C/S for fetal distress 37 (12.1%) 15 (20.3%) NS * yr: year, wks: weeks, UASD: umbilical artery S/D, GA: gestational age, C/S: cesarean section. P

4 대한산부회지제 52 권제 5 호, 2009 Table 2. Neonatal outcome Normal UASD (n=307) Abnormal UASD (n=74) Sex NS Male 145 (47.2%) 30 (40.5%) Female 162 (52.8%) 44 (59.5%) Birthweight (g) 2,415.2± ,296.7± Apgar score < 7 at 5 min 8 (2.6%) 2 (2.7%) NS Perinatal deaths 1 (0.3%) 0 NS Admission to NICU 81 (26.4%) 41 (55.4%) <0.001 Hospital days in NICU (d) 2.7± ± Care with ventilator 4 (1.3%) 3 (4.1%) NS RDS 1 (0.3%) 0 NS BPD 0 0 NS NEC 0 1 (1.4%) NS ICH 1 (0.3%) 1 (1.4%) NS PVL 0 0 NS Poor perinatal outcome 103 (34.3%) 42 (52.5%) * min: minute, UASD: umbilical artery S/D, RDS: Respiratory distress syndrome, BPD: Bronchopulmonary dysplasia, NEC: Necotizing enterocolitis, IVH: Intraventricular hemorrhage (Grade III, IV), PVL: Periventricular leukomalacia, NICU: Neonatal intensive care unit. P Table 3. Linear regression for the effect of UASD and hypertension on fetal weight Factors Standardized Coefficient, β P 95% Confidence Interval Lower Limit Upper Limit Hypertension UASD < * UASD: umbilical artery S/D. 아중환자실입원빈도가높으며입원기간도유의하게길어지는것을알수있었다. 저체중태아를동반한조산에서제대동맥에의한주산기예후예측에대해서는많은연구가진행되어추후산전관리지침이나분만시기에대한지침들이정립된데반해만삭임신에동반된저체중태아들의주산기예후예측을위한도플러검사의유용성이나분만시기등에대해서는현재많은논란이있다. 우리의연구결과는만삭임신에동반된저체중태아의주산기예후예측에제대동맥도플러지수측정이유용하다는것을의미한다. 저체중태아를동반한만기임신에대한기존의연구들중 Soothill 등은저체중태아라도제대동맥도플러지수가정상이면정상저체중태아로간주하였다. 16 또한다양한도플러파형을이용하여불량한예후를예측한결과제대동맥 박동지수 (pulsatility index) 만이독립적으로유의하게저체중때문에입원한경우를제외한신생아중환자실입원을예측하였고, 17 34주이후분만된저체중태아들에서자궁동맥도플러혈류속도파형이비정상적인경우불량한신생아예후의위험도가 4배증가하여, 18 제대동맥혹은자궁동맥도플러검사가저체중태아들의주산기예후예측에유용하다고하겠다. 우리의연구결과는이러한연구들을뒷받침하는결과라고하겠다. 본연구에서는태반기능부전에의한저체중태아만을대상으로하기위하여태아의기형이나감염, 염색체이상이있는경우를제외하였고, 제대동맥혈류속도파형에따라정상과비정상으로구분하여양군에서신생아출생체중, 중환자실입원빈도및중환자실입원기간등이유의한차

5 김호연외 6 인. 저체중태아를동반한만기임신의주산기예후예측을위한제대동맥도플러혈류속도파형의유용성 이가있음을밝혔다. 이는대상산모들에서나타난임신성고혈압의빈도차이를보정한이후에도통계적으로유의하여만삭임신에동반된저체중태아에서비정상제대동맥도플러지수는신생아체중이작고신생아중환자실입원및입원기간이길어짐을예측할수있는독립인자로작용함을알수있었다. 그러나태아곤란증에의한제왕절개술, 7 미만의 5분 Apgar 치, 기계적호흡, 주산기사망및신생아합병증유무등은대상군이작아제대동맥도플러혈류속도파형단독으로주산기예후를예측하는지를밝히기가어려웠다. 또한본연구에서는불량한예후를암시하는이완기혈류의소실및역전의경우가네명에서나타났으나대상수가적어통계적유의성을찾을수는없었다. 한편본연구에서도플러지수가비정상인군은정상인군에비해비수축검사, 양수량측정, 생물리학적계수측정등의산전태아안녕검사를보다집중적으로받았지만그것이신생아체중이나주산기예후에불리한영향을주지는않았을것으로생각된다. 한편저체중태아를동반한만기임신에서제대동맥도플러지수는신생아체중이작고신생아중환자실입원빈도가증가하고입원기간이길어짐을예측할수있는독립인자로작용함을알수있지만제대동맥도플러지수가정상이라도단기적혹은장기적으로불량한결과를초래할수있다. 정상제대동맥도플러혈류속도파형을보이는 129 명의저체중태아군과정상체중태아군의비교에서저체중태아군은높은신생아중환자실입원율 (15.5% vs. 3.9%, P<0.001) 과신생아이환 (2.3% vs. 0.0%, P<0.04) 및생후 24개월에낮은신경학적발달을보였으며, 19 제대동맥도플러지수가정상인저체중태아에서자궁동맥과중뇌혈류파형이비 정상일경우태아곤란증및이에따른제왕절개술이증가하였다. 20 또한 Eixarch 등은제대동맥도플러지수가정상인저체중태아에서중뇌동맥혈류의재분배에따른주산기예후에는차이가없어도중뇌동맥혈류의재분배를보인군에서생후 2세때신경학적발달에손실을보여제대동맥보다중뇌동맥박동지수를불량한신경학적결과에대한예측인자로제시하였다. 21 저체중태아를동반한만기임신의분만시기에대해서는집중감시하에경과를관찰하는경우와유도분만을하는경우의신생아및모성예후에대해현재진행중인연구 (DIGITAT: Disproportionate intrauterine growth intervention trial at term) 결과가나오면진료지침을얻을수있을것으로생각된다. 22 한편 Illa 등은정상제대동맥도플러지수를보이는만삭의저체중태아에서 customized optimal fetal weight curve 와실제태아의성장곡선사이의성장결핍 (growth deficit) 을측정하여성장결핍이불량한주산기예후를예측하는데사용될수있다고하였다. 23 결론적으로제대동맥도플러혈류파형이만기임신에동반된저체중태아의신생아체중, 신생아중환자실입원빈도및입원기간등을예측하는데유용한독립인자로작용하지만그외의신생아예후예측에는한계가있으므로자궁동맥혈류파형이나정맥관, 중뇌혈관등과같은다른혈관의도플러혈류파형측정이나생물리학적계수등을종합하여적극적인산전관리와적절한분만계획을세워주산기합병증을낮추는데주력해야할것이다. 또한향후더많은환자를대상으로전향적연구가시행되어야할것이다. 1. Baschat AA, Hecher K. Fetal growth restriction due to placental disease. Semin Perinatol 2004; 28: American College of Obstetricians and Gynecologists. Intrauterine growth restriction. ACOG Practice Bulletin No. 12. Washington DC: ACOG; Barker DJ, Gluckman PD, Godfrey KM, Harding JE, Owens JA, Robinson JS. Fetal nutrition and cardiovascular disease in adult life. Lancet 1993; 341: 참고문헌 4. Kramer MS, Olivier M, McLean FH, Willis DM, Usher RH. Impact of intrauterine growth retardation and body proportionality on fetal and neonatal outcome. Pediatrics 1990; 86: Doctor BA, O Riodan MA, Kirchner HL, Shah D, Hack M. Perinatal correlates and neonatal outcomes of small for gestational age infants born at term gestation. Am J Obstet Gynecol 2001; 185: Minior VK, Divon MY. Fetal growth restriction at term: myth or reality? Obstet Gynecol 1998; 92: McIntire DD, Bloom SL, Casey BM, Leveno KJ. Birth weight in relation to morbidity and mortality among newborn infants. N Engl J Med 1999; 340: Larroque B, Bertrais S, Czernichow P, Léger J. School difficulties in 20-year-olds who were born small for gestational age at term in a regional cohort study. Pediatrics 2001; 108:

6 대한산부회지제 52 권제 5 호, Trudinger BJ, Cook CM, Giles WB, Ng S, Fong E, Connelly A, et al. Fetal umbilical artery velocity waveforms and subsequent neonatal outcome. Br J Obstet Gynaecol 1991; 98: Neilson JP, Alfirevic Z. Doppler ultrasound for fetal assessment in high risk pregnancies. Cochrane Database Syst Rev 2000; CD Westergaard HB, Langhoff-Roos J, Lingman G, Marsál K, Kreiner S. A critical appraisal of the use of umbilical artery Doppler ultrasound in high-risk pregnancies: use of meta-analyses in evidence-based obstetrics. Ultrasound Obstet Gynecol 2001; 17: Bobrow CS, Soothill PW. Fetal growth velocity: a cautionary tale. Lancet 1999; 353: Soregaroli M, Bonera R, Danti L, Dinolfo D, Taddei F, Valcamonico A, et al. Prognostic role of umbilical artery Doppler velocimetry in growth restricted fetuses. J Matern Fetal Neonatal Med 2002; 11: Spinillo A, Montanari L, Bergante C, Gaia G, Chiara A, Fazzi E. Prognostic value of umbilical artery Doppler studies in unselected preterm deliveries. Obstet Gynecol 2005; 105: Alexander GR, Himes JH, Kaufman RB, Mor J, Kogan M. A United States national reference for fetal growth. Obstet Gyencol 1996; 87: Soothill PW, Bobrow CS, Holmes R. Small for gestational age is not a diagnosis. Ultrasound Obstet Gynecol 1999; 13: Vergani P, Andreotti C, Roncaglia N, Zani G, Pozzi E, Pezzullo JC, et al. Doppler predictors of adverse neonatal outcome in the growth restricted fetus at 34 weeks gestation or beyond. Am J Obstet Gynecol 2003; 189: Vergani P, Roncaglia N, Andreotti C, Arreghini A, Teruzzi M, Pezzullo JC, et al. Prognostic value of uterine artery Doppler velocimetry in growth-restricted fetuses delivered near term. Am J Obstet Gynecol 2002; 187: Figueras F, Eixarch E, Meler E, Iraola A, Figueras J, Puerto B, et al. Small-for-gestational-age fetuses with normal umbilical artery Doppler have suboptimal perinatal and neurodevelopmental outcome. Eur J Obstet Gynecol Reprod Biol 2008; 136: Severi FM, Bocchi C, Visentin A, Falco P, cobellis L, Florio P, et al. Uterine and fetal cerebral Doppler predict the outcome of third-trimester small-forgestational age fetuses with normal umbilical artery Doppler. Ultrasound Obstet Gynecol 2002; 19: Eixarch E, Meler E, Iraola A, Illa M, Crispi F, Hernandez-Andrade E, et al. Neurodevelopmental outcome in 2-year-old infants who were small-forgestational age term fetuses with cerebral blood flow redistribution. Ultrasound Obstet Gynecol 2008; 32: Boers KE, Bijilenga D, Mol BWJ, LeCessie S, Birnie E, Pampus MG, et al. Disproportionate intrauterine growth intervention trial at term: DIGITAT. BMC Pregnancy Childbirth 2007; 7: Illa M, Coloma JL, Eixarch E, Meler E, Iraola A, Gardosi J, et al. Growth deficit in term small-frogestational fetuses with normal umbilical artery Doppler is associated with adverse outcome. J Perinat Med 2009; 37: = 국문초록 = 목적 : 제대동맥도플러혈류속도파형이저체중태아를동반한만기임신의주산기예후예측에유용한가를살펴보고자한다. 연구방법 : 임신 37주부터 41주사이에단태의저체중태아를분만한산모와신생아의의무기록을후향적으로검토하였다. 총 381명의단태임신환자의최고수축기혈류속도 (S) 에대한이완기말혈류속도 (D) 의비를측정하여 S/D치 3.0 이하인정상군 (n=307) 과 3.0 초과인비정상군 (n=74) 으로구분하여산모의임상적특징및신생아예후를비교하였다. 결과 : 두군모두에서산모연령, 분만시재태연령, 태아곤란증에의한제왕절개분만빈도등에서차이를보이지않았다. 제대동맥도플러지수가비정상인군에서산모의고혈압성질환의빈도 (12.3% vs. 25.0%, P=0.005) 가통계학적으로유의하게높았다. 신생아출생체중 (2,415.2±258.9 g vs. 2,296.7±325.0 g, P=0.003), 신생아의중환자실입원빈도 (27.0 vs. 51.3%, P<0.001) 및중환자실입원기간 (2.7±5.9 vs. 5.7±8.8 days, P=0.005) 등은유의한차이를보였으나, 7 미만의낮은 5분 Apgar치, 기계적호흡빈도, 주산기사망및신생아합병증등은차이를보이지않았다. 선형회귀분석을시행한결과고혈압성질환의빈도를보정한후에도비정상제대동맥도플러지수와작은출생시신생아체중은유의한관계가있었다 (P<0.001). 결론 : 제대동맥도플러혈류파형이만삭임신에동반된저체중태아의신생아체중, 신생아중환자실입원빈도및입원기간등을예측하는데유용한독립인자로작용하지만그외의신생아예후예측에는한계가있으므로자궁동맥혈류파형이나정맥관, 중뇌혈관등과같은다른혈관의도플러혈류파형측정이나생물리학적계수등을종합하여주산기합병증을낮추도록해야할것이다. 중심단어 : 저체중태아, 만기임신, 제대동맥혈류속도

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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