Monochorionic Twin with Selective Intrauterine Growth Restriction

Transcription

1 R E V I E W A R T I C L E Monochorionic Twin with Selective Intrauterine Growth Restriction Yao-Lung Chang* A monochorionic twin pregnancy with selective intrauterine growth restriction (IUGR) of one twin is defined as one twin with an estimated fetal weight below the 10 th percentile for gestational age. Selective IUGR occurs in about 12% of twin pregnancies. The incidence of IUGR is similar in dichorionic and monochorionic twin pregnancies, but the risk of neurologic damage to the fetus is greater in monochorionic twin pregnancy. Monochorionic twins have the highest risk of complications, because the well-being of one fetus crucially depends on that of the other because of vascular anastomoses in the common placenta. The spontaneous demise of the twin with selective IUGR may result in the concomitant demise of the twin who is appropriate for gestational age (AGA) in up to 40% of cases or in neurologic damage of the AGA twin in up to 30% of cases. However, even in the absence of single intrauterine fetal death, the risk of neurologic damage is still increased in monochorionic as compared with dichorionic twin pregnancies. Because monochorionic twins with selective IUGR lack a definite treatment process as in twin-twin transfusion syndrome, this article reviews the ultrasound diagnosis, etiologies, Doppler findings, classification, and the management of such high risk pregnancies. KEY WORDS intrauterine growth restriction, monochorionic twin, umbilical artery Doppler, placental share J Med Ultrasound 2008;16(3): Introduction Twin gestation is more complex and has increased perinatal morbidity and mortality rates compared with singleton pregnancies [1]. Poor perinatal outcome is not only the result of prematurity, fetal growth restriction, and structural and chromosomal anomalies. Monochorionic twins (MC) have well known and unique complications, including twintwin transfusion syndrome (TTTS) and twin reversed arterial perfusion (TRAP) sequence [2]. However, MC with selective intrauterine growth restriction (IUGR), which is also a unique complication in MC, is less discussed. MC have the highest risk of complications and the well-being of one fetus crucially depends on that of the other because of vascular Received: April 7, 2008 Accepted: July 15, 2008 Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Tao-Yuan, Taiwan. *Address correspondence to: Dr. Yao-Lung Chang, Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Linkou Medical Center, 5, Fu-Shin Street, Kweishan, Taoyuan 333, Taiwan. j12054@cgmh.org.tw 194 J Med Ultrasound 2008 Vol 16 No 3 Elsevier & CTSUM. All rights reserved.

2 Monochorionic Twin with Selective IUGR anastomoses in the common placenta. Even excluding these unique complications, the prognosis of MC is still poorer than that of dichorionic twins [3]. Twin pregnancy with selective IUGR occurs in about 12% of twin pregnancies [4 6], and the incidence of IUGR is similar in both dichorionic and monochorionic twin pregnancies. Unequal placental sharing has been found to be the primary contributor to birth weight discordance in MC [5]. MC with selective IUGR usually presents with significant discordance in fetal size and, on first impression, can be assumed to be TTTS. These cases vary from simple amniotic fluid volume discordance to isolated polyhydramnios and isolated oligohydramnios. The main pathophysiologic basis for MC with selective IUGR is the placental territory factor, which arises from unequal sharing of the placenta in MC, and is different from the vascular communicating factor in TTTS. Since September 2005, there have been approximately 20 cases of MC with selective IUGR transferred to Chang Gung Memorial Hospital, Linko Medical Center, and half of these cases were initially diagnosed as TTTS at other hospitals. Three of the cases eventually met the criteria for TTTS after a few weeks of follow-up. Thus, there is the possibility that MC with an unequal placental share and an eventual superimposed vascular factor will be diagnosed with TTTS. After years of testing, the treatment of TTTS has become more definite [7]. However, the optimal management of MC with selective IUGR is still lacking [8]. In this article, we will discuss the unique high-risk MC pregnancy. Definition and Diagnosis of MC with Selective IUGR Before the diagnosis of MC with selective IUGR is made, it is necessary to know how to diagnosis MC using ultrasound. Among the criteria used to predict MC using ultrasound, the most reliable indicator for dichorionicity (to exclude the diagnosis of MC) is the presence of two separate placentas which have a sensitivity and a specificity of 97.4% and 100%, respectively. The most useful test to predict monochorionicity is the T sign which has a sensitivity of 100% and a specificity of 98.2% [9]. The accuracy is increased when ultrasound is performed before 14 weeks gestation [10]. Every twin pregnancy has to be tested for chorionicity in the first trimester. If two separate sacs are seen in the first trimester, then a dichorionic pregnancy is diagnosed. MC with selective IUGR is defined as a MC pregnancy with a small fetus, and the estimated fetal weight determined by sonography is usually below the 10 th percentile [11]. To define IUGR in a twin pregnancy is somewhat different from a singleton pregnancy [12]. However, using the definition of IUGR in a singleton pregnancy to predict IUGR in a twin pregnancy is acceptable [8] because IUGR is a poor prognostic indicator for the fetus, and using a looser definition to predict IUGR in a twin pregnancy in order to obtain closer fetal monitoring may be acceptable. Some authors have suggested that intertwine weight discordance should be considered in the definition of MC with selective IUGR. However, IUGR could increase perinatal complications, so we did not use intertwine weight discordance in the diagnostic criteria in this article. Differential Diagnosis of MC with Selective IUGR and TTTS The etiology of TTTS appears to result from a net unbalanced blood flow between two monochorionic fetuses through placental vascular communications, which results in a donor twin and a recipient twin. Actual documentation of this unbalanced blood flow remains elusive [13]. The most unique feature of MC with selective IUGR is the lack of the polyhydramnios/oligohydramnios sequel. Generally, the etiology of TTTS is a vascular factor and that of MC with selective IUGR is a placental territory factor. However, a previous study has shown that when the vascular factor in the etiology of TTTS is removed, an unequal placental share would also be found [14]. In MC with selective IUGR, an unbalanced vascular communication would exist, but the vascular factor would not be severe enough to cause J Med Ultrasound 2008 Vol 16 No 3 195

3 Y.L. Chang marked amniotic fluid discordance as in TTTS. We have had experience of cases initially diagnosed as MC with selective IUGR even without discordant amniotic fluid (AF), which progressed to TTTS weeks later. Etiologies of MC with Selective IUGR Placental factors The placenta has a striking functional reserve capacity, which has been shown in studies where fetal oxygen consumption has been artificially increased [15,16]. It was thus concluded that the placenta is usually small because the infant is small, but its small size does not act as a contributory factor to fetal growth restriction [15]. Quintero et al found that the individual placental mass could be determined in MC [17], so we also used the same concept to estimate the placental share in MC with selective IUGR. In our previous publication [18], the placental share was severely unequal in MC with selective IUGR (Fig. 1). The discordance in estimated fetal weight detected by ultrasound before birth was less than the degree of discordance in unequal placental share in such cases. We confirmed that the placental territory factor plays a major role in MC with selective IUGR. Territory of AGA twin Territory of IUGR twin Fig. 1. Unequal placental sharing in the monochorionic twin with selective intrauterine growth restriction (IUGR). The IUGR twin had a much smaller-than-normal placental share for appropriate-for-gestational age twin. Vascular factors In our series of MC with selective IUGR [18], all the AGA twins had the largest placental share. However, in MC without IUGR, there was one case where the smaller twin had the larger placental share. It has been hypothesized that in such cases (larger twin with the smaller placental share), there may be net arteriovenous anastomosis from the larger twin to the smaller twin [19,20]. Therefore, we cannot rule out the possibility that there is net flow from the twin with a larger placental territory to perfuse the twin with a smaller placental mass. However, the incidence of the small twin having a larger placental share in MC has been reported to be only 1.37% (7/509) and the type of vascular anastomosis has been proven not to be significantly associated with the birth weight discordance in MC [19]. So, the communicating vascular factor possibly plays a role in the etiology of IUGR in MC, but the role is less important than the placental share factor. Genetic factors As the twins are identical, genetic factors would not be involved in MC. Doppler Findings in MC with Selective IUGR Umbilical artery (UA) Doppler MC with selective IUGR has been classified into three types using UA Doppler of the IUGR twin [21]. These three types of MC with selective IUGR are based on UA Doppler findings: (1) normal, defined as positive diastolic velocity; (2) persistent, absent or reversed end-diastolic velocity (AREDV); and (3) intermittent AREDV. Doppler assessment of the UA is an established test of fetal well-being in high-risk pregnancies. In singleton pregnancies, AREDV has been attributed to increased downstream placental resistance because of a reduction in the number of small muscular arteries [22,23]. AREDV in TTTS has also been associated with poor perinatal outcome [24,25]. The etiology of AREDV in the donor 196 J Med Ultrasound 2008 Vol 16 No 3

4 Monochorionic Twin with Selective IUGR twin has also been studied in cases receiving laser therapy; small placental territory and intertwined artery to artery anastomoses have been recognized as the cause [14]. However, there have been very few cases of MC with selective IUGR which have been treated with laser therapy, so other than the small placental territory, the type of intertwined anastomoses has been suspected but has not been proven as the cause of AREDV in the IUGR twin. Interestingly, intermittent AREDV in TTTS was not recognized as an abnormal Doppler finding in the Quintero staging system [26]. However, in MC with selective IUGR, intermittent UA AREDV has been recognized as a subgroup with an elevated risk of intrauterine demise in the smaller twin and neurologic damage in the larger twin. This latter finding is not restricted to this condition but has also been found in cases of intrauterine fetal death of the cotwin [27]. Therefore, UA Doppler of the IUGR twin has the strongest prognostic role in MC with selective IUGR. Umbilical venous (UV) Doppler UV blood flow reflects the placental circuit of fetal circulation and is crucial for intrauterine development [28]. Placental blood flow, which represents approximately 30% of the biventricular fetal cardiac output [29], is reported to be reduced in IUGR [30 32]. Although the significant fetal weight discordance can be estimated in twin pregnancy before birth [33], the degree of unequal placental share cannot be predicted before delivery. In a previous study of TTTS, the donor twin had a significantly smaller UV flow before laser therapy [34,35]. In our experience, the UV flow was also decreased in the IUGR twin compared with the AGA counterpart in MC with selective IUGR. This decrease in UV flow has been detected as early as 16 weeks gestation. Middle cerebral artery (MCA) Doppler MCA peak systolic velocity (PSV) in singleton pregnancies has been widely used in the detection of fetal anemia and has also proved useful in TTTS following laser therapy [36]. Currently, MCA PSV has no obvious role in MC with IUGR if there is no twin intrauterine demise. In MC, the MCA PSV has been reported to be unstable because of the vascular anastomoses [37]. The role of MCA PSV may be related to the detection of the severity of agonal transfusion in IUGR twin intrauterine fetal death. If MCA PSV is significantly elevated after one twin intrauterine fetal death, the possibility of severe anemia in the surviving twin is high. Amniotic fluid (AF) level MC with selective IUGR could present with discordance in AF level between the twins but is not necessary for the diagnosis. AF is produced by fetal urine after 20 weeks of gestation. In the case of MC with extreme AF discordance, this condition was categorized as TTTS. Usually the IUGR twin would have a lower level of AF than the AGA counterpart in MC with selective IUGR. Currently, there are no studies comparing the outcomes of MC with selective IUGR with or without AF discordance. However, in MC with selective IUGR, those with discordance in AF level and UA AREDV would have an adverse perinatal outcome compared with those with normal IUGR twin UA Doppler [38]. Therefore, UA Doppler findings may be a stronger prognostic marker than AF level. Classification The classification of MC with IUGR mainly depends on the pattern of UA Doppler in the IUGR twin [21,39]. The reason for the classification of MC with IUGR is that the spontaneous demise of the twin with selective IUGR may result in the concomitant demise of the twin who is AGA in up to 40% of cases or in neurologic damage in the AGA twin in up to 30% of cases [39]. AREDV of the UA in the IUGR twin also poses an increased risk of fetal [21] and neonatal death [18]. The MC with selective IUGR were subsequently classified into one of three types according to the characteristics of UA Doppler flow as evaluated on the first examination: type I (positive end-diastolic flow in the UA), type II J Med Ultrasound 2008 Vol 16 No 3 197

5 Y.L. Chang (AREDV constantly observed during the examination) or type III which was defined as the clear observation of AREDV alternating with a short period of positive diastolic flow, in the absence of fetal and maternal breathing. This classification may be of help in clinical decision making and when comparing clinical studies [21]. However, in our experience, only AREDV in the IUGR twin has prognostic value [18]. Individual Fetal/Placental Ratio in MC with Selective IUGR The placenta, as the maternal fetal interface, is responsible for the exchange of oxygen and all nutrients between the mother and the fetus, and is, thereby, a principal determining factor in fetal birth weight. Because placental weight and birth weight are available on patient records, these parameters are accessible. In general, placental size and fetal size are directly related and experimental reduction of placental size by uterine carunclectomy prior to pregnancy has been shown to result in smaller fetuses in sheep [40]. In MC, the placental share plays a role in the ratio of intertwine birth weight; the exact placental share between the two fetuses can only be detected after delivery by placenta examination. Therefore, prenatal diagnosis of unequal placental sharing is not possible, but the significant intertwined birth weight discordance can be predicted by sonographic examination [33]. The weight of placentas from small-for-gestational age infants has been reported to be reduced when compared with those of AGA infants. However, changes in the fetal/placental (F/P) ratio in singletons depends on gestational age at delivery, and even at the same gestational age, the ratio varies quite widely [15,41]. We have found that the individual F/P ratios between the twin fetuses in MC with selective IUGR were significantly different [18]. The F/P ratio in the IUGR twin was significantly larger than that in the AGA twin. The fetal weights were not proportional to the placental mass in the twins; the degree of birth weight discordance has to be smaller than that of the discordance in the placental share in order for the F/P ratio to reach statistical significance. In these IUGR twins, their birth weights are low, but their placental weights are even lower. The discordance in estimated fetal weight by ultrasound detected before birth did not reflect the degree of discordance in placental sharing in such cases. So, by studying the F/P ratio in MC with selective IUGR, we have found that the etiology of IUGR in one twin can mainly be attributed to the small placental factor. However, a smaller placenta territory does not necessarily make the twin smaller. If the placental territory is small enough, then the affected twin would have IUGR. In MC with selective IUGR, the F/P ratio of the IUGR twin is significantly higher than that of the AGA counterpart, so the fetal weights are not proportional to the placental masses of the twins. The discordance in estimated fetal weight by ultrasound detected before birth does not reflect the degree of discordance in placental share. Management of MC with Selective IUGR Current management of MC with selective IUGR involves expectant management and early delivery (if warranted), termination of pregnancy, selective laser photocoagulation of communicating vessels or umbilical cord occlusion [39]. Most cases of MC with selective IUGR are managed by expectant management. The key steps are close monitoring and prompt delivery. There have been reports that the use of daily biophysical profiles to monitor such cases can prolong pregnancy with an acceptable perinatal outcome [42]. In our hospital, MC with selective IUGR are managed conservatively; for those MC with selective IUGR and normal IUGR twin UA Doppler, follow-up visits in the clinic at 2-week intervals and patient education to self-monitor fetal movement and check daily body weight are encouraged. If fetal movement decreases or the UA Doppler shows abnormal results, then hospital admission is required. In cases with abnormal IUGR twin UA Doppler, these cases are admitted to hospital after weeks of gestation. After admission, 198 J Med Ultrasound 2008 Vol 16 No 3

6 Monochorionic Twin with Selective IUGR Repeat deceleration of the fetal heart rate of the IUGR twin Fig. 2. The fetal heart beat monitor in the monochorionic twin with selective intrauterine growth restriction (IUGR). The fetal heart beat of the IUGR twin showed repeat variable deceleration. patients are monitored by continuous fetal monitoring, if repeated fetal heart beat deceleration is detected (Fig. 2) (usually detected in the IUGR twin), then corticosteroids are given to improve fetal lung maturity followed by prompt delivery. In our preliminary report [18], MC with selective IUGR with normal IUGR twin UA Doppler had a 100% survival rate and had a perinatal death rate of 20% when the UA Doppler of the IUGR twin was abnormal. The perinatal deaths in these cases of abnormal IUGR twin UA Doppler were not confined to the IUGR twin. Some of the MC with selective IUGR would progress to TTTS after only weeks of followup. These fetuses usually had abnormal IUGR twin UA Doppler. If these cases met the criteria for TTTS, they were usually at least stage III TTTS. In addition, because they were highly suspected of having small placental territory in the donor (previous IUGR) twin, the prognosis was usually poor even after laser therapy [14]. Quintero et al conducted a pioneering study using laser therapy to convert the monochorionic placenta to a functioning dichorionic placenta. It was claimed that the neurologic deficit in the IUGR twin would decrease; however, the mortality rate in the small twin was the same [39]. Laser therapy of the communicating vessels in MC with selective IUGR is more difficult than in TTTS, because MC with IUGR usually lack polyhydramnios. Thus, to insert a fetoscope and to carry out laser therapy on the communicating vessels would be more difficult than in TTTS, owing to a lack of adequate operating field. In unfamiliar hands, this could make the condition worse. If the diagnosis of MC with selective IUGR is detected relatively early in the gestational period, and the IUGR twin faced impending death, then selective feticide of the IUGR twin can be performed. This would reduce the risk of exsanguination in the AGA twin and could be performed by bipolar cord coagulation, ligation of the cord or laser photocoagulation. Laser photocoagulation to occlude the cord can usually only be performed at a relatively early gestational age because of the cord size. At a later gestational age, cord occlusion by bipolar coagulation or ligation under fetoscopic guidance can be performed. The management of MC with selective IUGR is currently still a dilemma; however, close monitoring and prompt delivery are the key steps in management. The differential diagnosis between MC with selective IUGR and TTTS is important, because TTTS has more agreeable management methods [7]. Laser therapy of the communicating vessels between the two fetuses in MC with selective IUGR is more difficult than in TTTS, and can only be performed by experienced personnel. References 1. Taylor MJ. The management of multiple pregnancy. Early Hum Dev 2006;82: Chang YL. Unique complications of monochorionic twins: diagnosis and management. J Med Ultrasound 2007;15: Leduc L, Takser L, Rinfret D. Persistence of adverse obstetric and neonatal outcomes in monochorionic twins after exclusion of disorders unique to monochorionic placentation. Am J Obstet Gynecol 2005; 193: Gaziano EP, De Lia JE, Kuhlmann RS. Diamnionic monochorionic twin gestations: an overview. J Matern Fetal Med 2000;9: Gratacos E, Carreras E, Becker J, et al. Prevalence of neurological damage in monochorionic twins with selective intrauterine growth restriction and intermittent absent or reversed end-diastolic umbilical artery flow. Ultrasound Obstet Gynecol 2004;24: J Med Ultrasound 2008 Vol 16 No 3 199

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