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1 SFWJFX Korean J Obstet Gynecol 2011;54:1-10 doi: /KJOG pissn eissn NEW ASPECT IN MANAGEMENT OF FETAL GROWTH RESTRICTION Jong-Woon Kim, MD Department of Obstetrics and Gynecology, Chonnam National University Medical School, Gwangju, Korea Fetal growth restriction (FGR) is one of the most common and complex diseases and it is associated with increased perinatal mortality and morbidity. FGR influences the long-term health of neonates and their offspring. The aim of obstetric management is to identify growth-restricted fetuses at risk of severe intrauterine hypoxia, to monitor their health and to deliver when the adverse outcome is imminent. This review aims to investigate the new aspects of FGR including the diagnosis, antenatal surveillance, and clinical management. Keywords: Fetal growth restriction, Small for gestational age, Management 정상적인태아의성장은건강한임신유지에필수적이며, 출생후건강에도장기적인영향을미친다. 태아발육제한 (fetal growth restriction, FGR) 은유전또는환경인자로인해자궁내태아성장이지연되거나정지하여임신기간동안에나타나는비정상적인발육상태를의미한다 [1,2]. 발육제한으로태어날경우성인이되어제2형당뇨병과심혈관계질환처럼만성질환에이환될가능성이높다 [3]. 따라서태아발육제한은태아, 신생아, 소아및성인에서뿐만아니라향후부모가되어서도, 그리고사회적으로도중요한의미를가진다. 태아발육제한이산전에진단되지않고출생한신생아는산전에진단되어적절한관리를받고출생한신생아에비해주산기이환율및사망률의증가와같은불량한예후에대한위험이높으므로산전진단및관리의중요성이강조되고있다 [4,5]. 시한다양한계산법을이용하는것이다. 주기적인초음파계측은 2주이상의간격을두어야하는데, 이는더짧은간격으로계측할때 10% 의위양성률을보이기때문이다 [11]. 때로는복부둘레만으로발육제한을평가하기도한다 [12]. 하지만이러한방법들은초음파계측에있어서 2차원적인측정과관찰자간또는관찰자내오차등으로태아체중의정확한예측에한계가있다. 이를보완하기위하여최근에는상박 (upper arm), 넓적다리 (thigh), 복부 (abdomen) 및어깨 (shoulder) 의피하조직 (subcutaneous tissue) 과볼간거리 (cheek-to-cheek diameter) 등의연부조직 (soft tissue) 을측정하거나 [13-17], 상박또는넓적다리의 3차원적계측을통한보다정확한출생체중예측방법이제시되었다 [18-20]. 태아의성장정도를정확히평가하기위해서는민족, 임신부의키, 몸무게등의모체측특징이고려된계측법에대한전향적인연구가필요하다. 임신주수와태아성장의정확한측정 태아의성장을평가하기위해서는정확하게임신주수를측정하는것이중요하다. 임신주수는임신부의마지막월경기간의첫날을기준으로산정하지만이는오차가발생할수있으므로초음파검사를이용하여정하는것이비교적정확하다. 임신제1 삼분기에측정한머리엉덩길이 (crown-rump length, CRL) 를기준으로정하거나 [6], 임신 28주이전에측정한양두정지름 (biparietal diameter, BPD) 측정으로 5-7일의오차내에서임신주수를예측할수있다 [7]. 임신제3 삼분기에는대퇴골길이 (femur length, FL) 를사용한다 [8]. 태아성장을측정하는가장신뢰할만한방법은초음파검사로양두정지름, 머리둘레 (head circumference), 복부둘레 (abdominal circumference), 대퇴골길이를각각측정하여 Shepard 등 [9] 이나 Hadlock 등 [10] 이제 Received: Revised: Accepted: Corresponding author: Jong-Woon Kim, MD Department of Obstetrics and Gynecology, Chonnam National University Medical School, 8 Hak-dong, Dong-gu, Gwangju , Korea Tel: Fax: jwkimmd@jnu.ac.kr * This study was supported by a grant from Department of Obstetrics and Gynecology, Chonnam National University Medical School. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright c Korean Society of Obstetrics and Gynecology 1

2 KJOG Vol. 54, No. 1, 2011 부당경량아와태아발육제한 부당경량아 (small for gestational age, SGA) 는특정임신주수의모든태아또는신생아에서 10 백분위수미만의체중으로 [21], 태아발육제한은태아의크기가작으면서태반기능의장애와같은병적인성장 (pathologic growth) 의증거가있는경우로정의한다 [3]. 태아발육제한은부당경량아와혼동되어사용되고있는데이들을감별하는것이중요하다. 임신주수의 10 백분위수미만의예측체중을가진태아가모두발육이제한된것이아니며, 임신후기에는성장속도가감소하므로발육제한이있더라도 10 백분위수이상일수있기때문이다. 이를고려하지않으면건강하지만체질적으로작은태아가과진단 (over-diagnosis) 되어불필요한처치를받을수있고, 예측체중이 10백분위수이상이지만병적으로성장이제한된태아의진단및처치가어려울수있다. 이들을감별하기위해태아의크기와함께태반의상태가고려되어야하는데, 이는임신부와태아의초음파도플러소견, 생화학적지표 (biochemical marker), 생물리학계수 (biophysical profile), 유전학검사등으로평가될수있다. Fig. 1. Diagnostic approach to the small fetus with a decreased abdominal circumference. AC, abdominal circumference; AFI, amniotic fluid index; A/REDV, absent/reversed end-diastolic velocity (Baschat AA. J Perinat Med 2010; 38: , with permission from du Gruyter). 태아발육제한의진단 태아의크기만으로는주산기이환및사망을예측할수없기때문에태아와태반의상태를평가할수있는다른지표들이사용되고있다. 태아의상태를평가하는방법으로는태아심박동분석, 양수양측정, 생물리학계수측정, 초음파도플러검사등이있다. 정상적인도플러검사소견을보이는부당경량아는적량아 (appropriate for gestational age, AGA) 에비해이환율의증가가없었고, 단지체질적으로작을뿐이며병적으로성장이제한되지않았는데 [22,23], 그에반해도플러검사에서이상소견을보일경우에는이환율이증가하였다 [24,25]. 따라서태아의예측체중또는복부둘레길이에임신부와태아의혈관의도플러검사를추가하면태아발육제한의진단율을높일수있다. 선천성기형이없는대다수의태아발육제한이태반부전과같은병적원인에의해발생되므로, 태반의상태를평가하는것이진단에도움이된다 [26,27]. 만삭훨씬전에발생한태아발육제한에서는생물리학계수의이상소견이발생하기전에태반순환의부전, 혈류의재분배등이일어나므로, 자궁동맥및제대동맥도플러검사가태반의상태를알아보는선별적검사로사용되고있다 [28,29]. 많은혈청표지자들이태아성장이나태반기능과의연관에대해보고되고있는데, 알파태아단백 (alpha-fetoprotein), 임신-관련혈청단백질-A (pregnancy-associated plasma protein-a), 융모성성선자극호르몬 (human chorionic gonadotrophin), 에스트리올 (estriol), 인히빈 -A (inhibin- A) 등은염색체이상뿐만아니라태아발육제한이나임신합병증과도관련이있다 [30-32]. 최근에는 vascular endothelial growth factor (VEGF), placenta growth factor (PlGF), soluble human vascular endothelial growth factor receptor-1 (svegfr-1), soluble endoglin 등이조발형 (early-onset) 태아발육제한과연관이있다고보고되었다 [33-35]. 이러한생화학적지표와임신제2 삼분기에임신부의자궁동맥도플러검사를병행할때진단율이더욱향상될수있다 [32]. 하지만임상적으로유용할정도의민감도와특이도를갖기에는더많은연구가필요하다. 제한된연구결과이지만 insulin-like growth factors-i (IGF-I), IGF-II, 인슐린에대한유전자의변이와태아성장과의연관에대해보고되고있는데 [36,37], 최근시행되는 DNA 다형분석등의유전자검사로태아성장과의유의한관계가입증된다면태아성장장애를예측및진단하는데도움이될것이다. 태아발육제한은주로태반의이상에의하는데, 임상적으로는증상이없어부당경량아가확인되고, 태반및태아상태의기능이상 (malfunctioning) 이나타나야발육제한이진단된다. 부당경량아가발견되면여러검사를통해체질적으로작은태아와발육이제한된태아를구별해야하는데복부둘레가작은태아에서 Fig. 1과같은진단적접근방법이권고된다 [38]. 산전태아감시 1. 도플러를이용한태반순환평가도플러검사는다른태아감시방법에비해태반및태아의혈류역학 (hemodynamics) 에대해중요한정보를제공한다. 1) 제대동맥제대동맥에서의도플러파형은태반으로부터의혈류에대한저항을반영하고, 파형의변화는태아의상태및임신의예후와연관이있다 2

3 Jong-Woon Kim. New aspect in management of fetal growth restriction [39,40]. 따라서부당경량아태아에서제대동맥의비정상적인도플러파형은태반혈류의이상이태아발육제한의원인이라는증거가된다. 태반부전이심해질수록이완기말혈류의소실또는역전 (absent or reverse end-diastolic flow) 과같은심한비정상파형이나타나는데, 이때주산기사망률이각각 4배와 10.6배로증가한다 [41]. 특히, 이완기말혈류의역전이보인경우에는역전정도가심할수록주산기사망률이높아지며, 장기적인신경학적발달이상의위험도증가한다 [42]. 그러나다른다기관연구인 Growth Restriction Intervention Trial (GRIT) 연구에서는만삭전의발육이제한된태아에서제대동맥이완기말혈류의역전이있어즉각적인분만을하더라도사망률과신경학적예후를향상시키지못하므로, 폐성숙을위해스테로이드투여의효과를볼수있는 시간의기간이필요하다고보고하였다 [43]. 분만전에제대동맥도플러검사를시행하였을때주산기사망률, 산전입원횟수, 유도분만이감소하였는데 [44], 이러한효과는자간전증이나태아발육제한처럼태반기능이상에의한고위험임신부를대상으로한것이었으며, 반대로저위험군을대상으로한무작위연구에서는제대동맥도플러파형의평가가태아발육제한의선별검사로서의의가없었다 [45]. 따라서제대동맥에대한선별검사는태아발육제한과자간전증등의고위험임신에서사용되어야하며, 이들의임상적처치는임신주수, 태아및임신부의상태를고려하여시행되어야한다. 2) 자궁동맥자궁동맥에대한도플러검사는임신제1, 2 삼분기에조발형 (early-onset) 자간전증과태아발육제한에대한선별검사로제안되었으나 [46], Cochrane 보고에서는선별검사로서의유용성에대한증거가부족하였다 [47]. 그러나지발형 (late-onset) 태아발육제한에서는제대동맥및대뇌동맥도플러검사와함께주산기예후를예측하는부가적인검사로유용하다 [48]. 박동지수 (pulsatility index) 의증가, 이완기함요 (diastolic notch) 출현등이임신예후와연관되며 [49], 드물게나타나는이완기함요의역전은모체혈류의융모간강 (intervillous space) 으로의유입이극히제한되고있음을의미하므로철저한태아감시를시작해야한다. 3) 중대뇌동맥만성저산소증은태아발육제한에서뇌로가는혈류가증가하는재분배 (redistribution) 를일으키고, 뇌보존 (brain sparing) 현상이일어난다. 대뇌동맥중도플러검사가용이한중대뇌동맥의도플러검사에서박동지수는감소하고수축기평균혈류속도는증가한다 [50]. 만삭에가까운부당경량아태아에서시행한중대뇌동맥도플러검사가불량한예후를예측할수있다는보고가있는반면 [51,52], 반대의연구결과도있다 [53]. 이러한차이는대뇌혈관의확장이방어기전으로여겨지거나, 반대로신경학적발달이상의원인으로보고되기때문이다. 신경발달결과에대한초기연구에서는뇌보존이심한뇌손상을막기위한적응이라고보고되었지만 [54], 최근만삭의부당경량아태아에서중대뇌동맥재분배만있는경우신생아에서비정상적인신경행동의위험이 있고 [55], 2세가되었을때약간의신경발달지연이있어재분배가오히려불량한예후의예측인자가될수있다 [56]. 중대뇌동맥의도플러소견과신경학적예후와의관련에대한추가적인연구가필요하다. 4) 대뇌태반의비대뇌태반의비 (cerebroplacental ratio, CPR) 는중대뇌동맥의박동지수를제대동맥의박동지수로나눈태아말초혈류분배의지표이다. 뇌로혈류의재분배가일어나게되면이완기에뇌혈류가정상보다높아지고제대의혈류는낮아져대뇌태반의비값이 1.0 이하가된다. 5) 정맥관정맥관 (ductus venosus) 은제대정맥에서후상방향으로주행하는작은정맥으로산소포화도가높은혈액을간을거치지않고우심방으로보낸다. 이혈액이난원공 (foramen ovale) 을통해좌심방으로유입된후관상동맥과뇌로가는혈액의산소포화도를상승시킨다 [57]. 태아발육제한에서저산소증이지속되면제대정맥에서간으로가는혈류는감소하고, 정맥관을통해심장으로바로가는혈류가증가하며, 정상태아에비해정맥관크기가커진다. 도플러검사에서박동지수가증가하고심방기혈류가소실되거나역전 (absent or reversed ductus venosus atrial wave) 되는데이시기는비정상혈류의마지막단계이며, 조발형태아발육제한에서발견될때주산기사망률이 % 에이른다 [58,59]. 도플러파형의이상소견이태아가사가진행된단계에서발견되지만, 태아심박동의단기변이성소실 (loss of short-term variability) 보다선행하는경우는 50% 에불과하며 [60], 90% 에서는생물리학계수 (biophysical profile) 검사에서변화를보이기겨우 2-3일전에이상소견을보이므로 [28], 심혈관계의악화위험성이있는태아에서의상태를평가하는데정맥관도플러검사가도움이되지만, 만삭전의태아발육제한에서는생물리학계수검사를동시에시행해야한다. 6) 제대정맥태아가사 (fetal asphyxia) 가매우진행된시기의징후로정맥관의기능이상이있고, 태아의심장부전이임박하면제대정맥내박동 (pulsation) 이나타날수있다 [61]. 2. 심장기능의평가태아발육제한은전부하 (preload), 후부하 (afterload), 심실탄성 (ventricular compliance), 심근수축력 (myocardial contractility) 등의심장기능의이상과도연관이있다. 태반순환에서저항의증가로우심실에서의후부하가증가하고, 뇌보존으로인해대뇌혈관의저항이감소하여좌심실에서의후부하는감소한다. 이로인해우심장에서좌심장으로심박출의재분배가일어난다 [62]. 심실충만 (ventricular filling) 의감소와저혈량증 (hypovolemia) 으로인해방실판막에서의전부하는감소하여심실확장기능을반영하는 E/A ratio가감소하고, 심박출량을반영하는승모판과삼첨판에서의시간-속도적 (time-velocity integral, VTI), 즉혈류가지 3

4 KJOG Vol. 54, No. 1, 2011 나간총거리가감소한다 [63]. 심실구혈력 (ventricular ejection force) 의감소가있는태아발육제한에서는감소가없는대조군에비해더이른임신주수에분만하고, 비정상적인태아심박동의발생률이높았다 [64]. 심근수행지수 (myocardial performance index) 를측정하여전반적인심장기능을평가할수있는데혈류도플러검사에서 0.5 이상이면심장기능의저하를의미한다. 태아발육제한으로진단되어임신 34주이전에분만하였던태아의산전도플러검사에서발육제한이진단되었을때보다분만일에가까울수록심근수행지수가증가하였다 [65]. 발육제한된태아의심장은저산소증과태반부전에대하여적응하는데중요한역할을한다. 중심정맥에서의이상소견은대개심근기능의이상을동반한태아곤란상태 (fetal compromise) 를반영한다. 따라서제대동맥, 중대뇌동맥등의말초동맥과정맥관, 하대정맥등의중심정맥, 비수축검사등과함께태아심장의도플러검사가태아발육제한의임상적처치에도움을줄수있다. 5. 양수양양수양은대개초음파기기를이용하여반정량적인양수지표 (amniotic fluid index) 로표시된다 [67]. 양수양의감소나양수감소증 (oligohyrdamnios) 은좀더심한태아발육제한과연관되어있으나예후를예측하기에는제한점이있다 [68]. 6. 생물리학계수저산소증에노출된태아는종종태아호흡 (fetal breathing) 과함께체부와사지 (extremity) 의움직임이감소한다. 더욱심한저산소증에서는근육의긴장도 (muscle tone) 의소실이나타난다. 생물리학계수는태아운동 (fetal movement), 태아호흡운동, 태아긴장도, 비수축검사, 양수양등의검사를통해점수로표시된다. 낮은점수는나쁜예후와연관되어있으나도플러파형의변화보다늦게나타나므로상태의악화를확인할수있는보조적인방법으로사용되어야한다 [28]. 3. 도플러이상소견의진행태아발육제한에서도플러이상소견은발병임신주수와태반부전의정도에따라단계적인변화를보인다. Turan 등 [66] 은 5 백분위수미만의복부둘레를보이는 104명의부당경량아태아에서제대동맥, 중대뇌동맥, 정맥관, 제대정맥의도플러검사를시행하고, 처음이상이발견된시기, 이상소견이악화된시기, 그리고분만시기를확인하고각각의간격을비교하였다. 제대동맥박동지수증가, 대뇌태반의비감소, 제대동맥이완기말혈류소실, 뇌보존, 제대동맥이완기말혈류역전, 정맥관박동지수증가, 제대정맥박동, 정맥관심방기혈류의역전순으로도플러이상소견이발생하였고, 분만까지의평균간격이점점짧아졌다. 태반기능부전의정도와발병시기에따라비교하였을때평균 26.3주의이른시기에진단된그룹에서제대동맥과중대뇌동맥에만이상이있는경증그룹보다다른도플러이상소견의발생간격이짧았다. 따라서태아발육제한이이른시기에진단될수록, 그리고중증의도플러이상소견이보일수록산전감시검사를더욱자주시행하여야한다. Cruz-Martinez 등 [65] 은평균 29.0주에태아발육제한으로진단되어 30.6주에분만한 115명의신생아에서산전에대동맥잘룩 (aortic isthmus) 과정맥관의박동지수와함께심근수행지수를측정하였는데, 심근수행지수의이상소견이가장빨리나타났고, 대동맥잘룩, 정맥관순이었다. 임신주수의증가에따른이상소견의증가율도심근수행지수에서가장높았다. 중증의태반부전이동반된태아발육제한에서태아심장의도플러검사가예후를예측하는데도움이될것이다. 4. 비수축검사태아심박동감시검사의반복횟수는발육제한의정도, 임신부의상태, 다른검사결과에따라결정한다. 태아심박동의단기변이성은태아의산증, 과탄산혈증과연관되어있고, 심박수의증가나심박동간변이가없는경우예후가매우불량할것으로예측된다. 태아발육제한의자궁내치료 침상안정 (bed rest) 은과거에태아발육제한과조기진통환자에서흔히시도되었으나, 태아성장과의연관성은증명되지않았다 [69]. 임신부에게포도당이나아미노산등의영양분을경구또는정맥주사로공급하여태아성장을관찰하였으나, 포도당의정맥주사가과다한경우태아산증 (fetal acidemia) 을일으킬수있으며, 아직은이론적근거가부족하다 [70]. 태아의저산소증이태반부전을동반한태아발육제한의병태생리에서중요한역할을하므로, 임신부에게산소를공급하여비교하였지만태아성장을향상시키지못했고, 지속적으로산소공급을유지하는것이어려우며, 오히려산소공급의중단이태아심박동감소의위험을증가시킬수있다 [71]. 칼슘통로차단제는평활근과혈관수축력에변화를가져오는데 100명의태아발육제한의임신부에서차단제를투여후출생체중에서유의한결과를얻었으나향후대규모연구가필요하다 [70,72]. 이처럼태아발육제한에서많은치료방법이시도되었지만자궁내치료의효과는제한적이며아직까지태아성장을향상시킨다고입증된방법은없다. 태아발육제한의임상적처치 효과적인자궁내치료가제한적이므로태아발육제한의임상적처치의목표는저산소증의위험에처해있는태아발육제한을진단하고, 적절한태아감시를하면서좋지않은결과가발생하기전에분만하는것이다. 태아감시검사에서중증의이상소견이발견되지않는다면외래추적관찰하고, 이상소견이심해질경우입원하여자주검사를하며필요할경우즉각적인분만을할수있도록한다. 입원후침상안전의효과에대해서증명되지않았지만, 태아감시가용이하며외부활동으로인한 4

5 Jong-Woon Kim. New aspect in management of fetal growth restriction 육체적긴장을피할수있다. 태아발육제한에서는대개만삭이전에분만하는데, 자궁내가사 (asphyxia) 로인한태아사망의위험과조산으로인한합병증의위험을함께고려하여분만시기를결정하여야한다. 임신주수가매우작은경우에위험도의측정은특히어려우므로태아의상태에대한모든유용한정보를평가하고, 당시의임신주수로태어났을때의신생아의예후에기초하여판단해야하며부모뿐만아니라신생아전문의를포함한주산기의료진과의견을나누어야한다. 1. 임신주수에따른처치태아발육제한의발병당시의임신주수가임상증상, 진단및처치에중요한영향을미친다. 1) 임신 34주미만임신 34주미만에발생한조발형에서는신생아의생존율이지발형에비해유의하게낮으며 [73], 임신주수와출생체중이예후에중요한데 [74], 특히임신 28주미만의태아에서자궁내에서의하루연장은 1-2% 의생존율증가로이어진다 [74]. 따라서조발형태아발육제한에서는안전하게임신기간을연장하는것이처치의목적이라할수있다. 매우미숙한임신 30주전에는분만결정이어려우므로, 태아상태에대한모든정보에기초하여야한다. 단기변이성을포함한비수축검사뿐만아니라도플러검사와태아의크기, 성장속도, 양수양등이이에해당된다. 또산과및신생아전문의가상주하는주산기센터에서의처치가필요하다. 비수축검사에서태아곤란증 (fetal distress) 으로분만이임박했을때도플러검사와태아심박수의단기변이성의변화에대한연구에서박동지수가증가하고심방기혈류의점진적인소실혹은역전되는정맥관소견, 제대정맥의박동소견, 점진적인이완기말혈류의역전을보이는제대동맥소견과태아심박수의단기변이성소실이태아상태의악화를나타내는가장강력한검사결과였다 [28,60,61]. 이와같은프로토콜을적용하여분만하였을때 2년생존율이 90% 였으나 [59,75], 좋은예후를보이지못한연구결과도있었다 [74]. 최근유럽의다기관에서비수축검사결과와정맥관도플러파형의변화를기준으로분만시기를달리하여출생 2년후에신경발달장애 (neurodevelopmental impairment) 가없는생존율을알아보고자하는 Trial of umbilical and fetal flow in Europe (TRUFFLE) 연구가진행중인데이결과가향후분만시기를결정하는임상적인프로토콜을정하는데중요한역할을할것이다. 조발형태아발육제한의대부분에서태반부전으로인한제대동맥의 Table 1. Management algorithm for pregnancies complicated by fetal growth restriction Abnormal UA and/or CPR; Normal MCA & veins BPS 8/10 AFV normal Low MCA Normal veins BPS 8/10 AFV normal UA A/REDV Normal veins BPS 6/10 Oligohydramnios Increased DV pulsatility BPS 6/10 Oligohydramnios Finding Interpretation Action Absent or reversed DV a wave Pulsatile UV BPS<6/10 Oligohydramnios Asphyxia extremely rare Increased risk for intrapartum distress Blood flow redistribution Hypoxemia possible, Asphyxia rare Increased risk for intrapartum distress Significant blood flow redistribution Hypoxemia common Acidemia or asphyxia possible Onset of fetal compromise Fetal compromise Hypoxemia common Acidemia or asphyxia likely Fetal decompensation Cardiovascular instability Metabolic compromise Stillbirth imminent High perinatal mortality irrespective of intervention Deliver for obstetric, or maternal factors only Fortnightly Doppler Weekly BPS Deliver for obstetric, or maternal factors only Weekly Doppler BPS 2 time/wk >34 wk; deliver <32 wk; antenatal steroids repeat all testing daily >32 wk; deliver <32 wk; admit, steroids individualize testing daily vs. tid Deliver at tertiary center with the highest level of NICU care UA, umbilical artery; CPR, cerebroplacental ratio; MCA, middle cerebral artery; BPS, biophysical profile score; AFV, amniotic fluid volume; A/REDV, absent/reversed end-diastolic velocity; DV, ductus venosus; tid, three times daily; UV, umbilical vein; NICU, neonatal intensive care unit (Baschat AA. J Perinat Med 2010; 38: , with permission from du Gruyter). 5

6 KJOG Vol. 54, No. 1, 2011 도플러이상소견이나타난다. 따라서임신 30-32주이후에는비수축검사결과가정상이고다른이상소견이없다면, 제대동맥의도플러검사가태아위험에대한가장중요한검사이다. 이완기말혈류의역전소견은일반적으로분만의적응증에해당된다. 이완기말혈류의소실소견또한태아상태의악화가능성이임신을연장시킴으로써얻을수있는이익을상회하는중증소견이다. 이완기말혈류의소실로분만을고려하는임신주수는 30-34주로의료기관마다차이가있다 [76]. 2) 임신 34주이후임신 34주이후에발병한지발형태아발육제한에서는분만시기결정에대한고민은비교적적으나만삭임신에서예기치못한사산의 50% 를차지한다는점에서주의가필요하다 [77]. 진단자체가되지않는경우가있고, 태아상태의악화를반영하는도플러또는생물리학계수의이상소견이약하게나타나며, 제대동맥의도플러검사나비수축검사에서정상소견을보이는단독뇌보존 (isolated brain sparing) 소견이특징적이다 [78-80]. 따라서지발형에서는태아발육제한을진단하는것자체가중요하다. 2. 검사간격아직까지발병시기에따른태아발육제한의감시프로토콜이정립되어있지않으나 Table 1과같은처치가권고되고있다 [38]. 1) 임신 34주미만조발형에서는단계적인도플러검사의이상소견이후에생물리학계수의이상이나타나고, 도플러이상소견이발생하고평균 4-6주후분만한다 [66]. 제대동맥의이완기말혈류가있고다른이상소견이없다면매주검사를하고, 이완기말혈류의소실또는역전, 정맥관도플러지수의상승, 양수양감소소견이있다면질환이심해짐을의미하며, 임신주수가매우작아분만지연이필요하다면검사간격을줄여하루에 1회에서 3회까지시행한다. 2) 임신 34주이후지발형에서는단계적인도플러이상소견은드물지만새롭게발생한단독뇌보존, 양수양감소, 태아심박동에서반응성소실, 태아호흡운동소실소견은예기치못한사산에선행할수있으므로주 2-3회의검사가필요하고중대뇌동맥도플러를측정하여뇌보존정도를평가해야한다 [78]. 3. 분만방법태반의기능이상이있는대부분의태아발육제한에서는분만진통의스트레스를잘견디지못한다. 만약진통시작이전에태아의저산소증이이미존재한다면, 정상적인자궁수축에도태아로의산소공급이지장을받고태아곤란증이발생할수있다. 그러므로저위험군의임신부보다수술적분만 (operative delivery) 이더빈번하다. 비정상적인도플러검사결과를보이는극히미숙한태아에서는제왕절개가가장추천되는분만방법이다. 최근두연구에서도임신 30주미만의태아발육제한에서제왕절개분만율이각각 100% 와 88% 였다 [59,75]. 제대동맥의이완기말혈류의소실또는역전이있을때도제왕절개분만이추천된다. 분만방법을결정할때는도플러검사소견뿐만아니라임신주수, 분만력, 자궁경부개대및소실정도등도고려해야한다. 진통이있을때는주산기전문의료진이상주하고신생아집중치료실및고위험임신부의관리가가능한곳에서태아곤란증을염두에두고주의깊게관찰해야한다. 태아발육제한에서신경학적발달 발육제한으로출생한신생아에서신경학적발달 (neurodevelopment) 에영향을미치는가장중요한인자는임신주수와출생체중이다 [43, 81,82]. 태반부전정도를반영하는제대동맥이완기말혈류의역전소견은분만전에확인되는유일한예측인자인데, 경증의태아발육제한에서도혈류의재분배소견은신경학적발달이상과관계가있다 [54,56, 82,83]. 이는태반부전으로인하여태아에서임상증상이나타나기전에, 그리고조발형태아발육제한에서분만시기를결정하기도전에이미신경학적발달에영향을미쳤을수있다는점에서중요하다. 따라서조발형태아발육제한의선별과예방에대한연구의중요성이대두되고있다. 최근에는모체측위험인자, 태반형성 (placentation) 의생물표지자 (biomarkers) 와자궁동맥도플러검사를조합하여좀더이른시기에고위험환자를선별하고자하는연구들이있는데, 이는고위험환자에서임신제1 삼분기부터치료를시작하여태반부전을감소시킬수있다는점에서의의가있다 [38]. 결론 태아발육제한은태아의크기, 태아및태반의건강상태, 그리고성장속도를고려하여정의되지만, 다양한원인이관련되어있어서특정인자로체질적또는병적으로작은태아를구분하기는어렵다. 임신초기에초음파검사를이용하여측정한임신주수를기준으로부당경량아가진단될경우임신부, 태아, 태반등에서발육제한의원인유무를확인하고주기적인초음파계측을통해태아의성장속도를알아내며, 태반기능이상과관련되어있는혈관들에대한도플러검사를시행하여, 이상소견발견시중증도와임신주수등을고려하여분만시기를고려한다. 산전검사로알수있는임상적상태의악화보다신경학적손상이선행하므로향후태아발육제한이예상되는고위험임신부를조기진단할수있는표지자의발견이나정확한태아체중예측방법, 태아발육제한의자궁내치료와극히미숙한태아발육제한에서의관리에대한연구가 6

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10 KJOG Vol. 54, No. 1, 2011 Early intervention in management of very preterm growthrestricted fetuses: 2-year outcome of infants delivered on fetal indication before 30 gestational weeks. Ultrasound Obstet Gynecol 2009;34: Marsal K. Obstetric management of intrauterine growth restriction. Best Pract Res Clin Obstet Gynaecol 2009;23: Froen JF, Gardosi JO, Thurmann A, Francis A, Stray-Pedersen B. Restricted fetal growth in sudden intrauterine unexplained death. Acta Obstet Gynecol Scand 2004;83: Baschat AA, Berg C, Turan O, Turan S, Galan H, Thilaganathan B, et al. Natural history of stillbirth in placenta based fetal growth restriction-implications for surveillance. Annual Meeting of the Society for Maternal-Fetal Medicine. Am J Obstet Gynecol 2008;199:S Bahado-Singh RO, Kovanci E, Jeffres A, Oz U, Deren O, Copel J, et al. The Doppler cerebroplacental ratio and perinatal outcome in intrauterine growth restriction. Am J Obstet Gynecol 1999; 180: Hecher K, Spernol R, Stettner H, Szalay S. Potential for diagnosing imminent risk to appropriate- and small-for-gestational-age fetuses by Doppler sonographic examination of umbilical and cerebral arterial blood flow. Ultrasound Obstet Gynecol 1992;2: Kaukola T, Rasanen J, Herva R, Patel DD, Hallman M. Suboptimal neurodevelopment in very preterm infants is related to fetal cardiovascular compromise in placental insufficiency. Am J Obstet Gynecol 2005;193: Baschat AA, Viscardi RM, Hussey-Gardner B, Hashmi N, Harman C. Infant neurodevelopment following fetal growth restriction: relationship with antepartum surveillance parameters. Ultrasound Obstet Gynecol 2009;33: Roza SJ, Steegers EA, Verburg BO, Jaddoe VW, Moll HA, Hofman A, et al. What is spared by fetal brain-sparing? Fetal circulatory redistribution and behavioral problems in the general population. Am J Epidemiol 2008;168: = 국문초록 = 태아발육제한처치의최신지견 전남대학교의과대학산부인과학교실 김종운 태아발육제한은가장흔하고복잡한질환중하나로서주산기이환율과사망률의증가와연관이있으며, 신생아및그자손의건강에도장기적인영향을미친다. 태아발육제한에서의산과적처치의목적은발육이제한되고중증의자궁내저산소증의위험에처해있는태아를발견하고, 적절히감시하여유해한결과가발생하기전에분만시키는것이다. 본종설에서는태아발육제한의진단, 산전감시및임상적처치에대하여알아보고자한다. 중심단어 : 태아발육제한, 부당경량아, 처치 10