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Ultrasound assessment in twin-twin transfusion syndrome
Introduction
The ultrasound assessment of patients with TTTS can be particularly challenging. The presence of oligohydramnios in the sac of the donor twin frequently impairs adequate visualization of the fetal anatomy, fetal gender, the dividing membrane itself and occasionally, adequate Doppler interrogation of the different vessels of this fetus. Polyhydramnios is typically associated with a frequently moving recipient twin, which makes the Doppler assessment of this fetus particularly difficult. Polyhydramnios may also result in significant maternal discomfort with back pain or light-headedness in the recumbent position, hindering further the completion of the ultrasound examination. Lastly, the exam is typically done under an atmosphere of psychological tension from maternal anxiety, given the grave prognosis in most cases. Despite these limitations, a thorough and complete ultrasound examination is necessary to correctly diagnose, assess the status and develop a therapeutic plan for patients with TTTS.
We have developed a systematic approach to the ultrasound assessment of patients with TTTS. We have proposed that the assessment be performed in several steps or levels. These steps include a) Confirming the diagnosis b) Staging of the disease c) Assessment of cervical length and d) Pre-operative mapping.
Step One: Diagnosis of TTTS
Twin-twin transfusion syndrome (TTTS) is a complication of monochorionic multiple gestations defined sonographically as the combined presence of polyhydramnios in one sac and oligohydramnios in the other sac in a monochorionic-diamniotic twin gestation. Polyhydramnios is defined as a maximum vertical pocket (MVP) ≥ 8 cm, and oligohydramnios as an MVP ≥2 cm (poly8-oligo2). Monochorionicity is established by the presence of a single placenta, absence of a twin-peak sign, thin dividing membrane, and same gender between twins.
Variations in the definition
Although the condition affects mostly twin pregnancies, TTTS can also occur in triplet or higher order multiple gestations provided at least two fetuses are monochorionic. In monoamniotic twins, the lack of a dividing membrane precludes the presence of oligohydramnios, but the syndrome can be suspected by the presence of polyhydramnios and differences in bladder filling or Doppler studies of the two fetuses. In monochorionic triplet pregnancies, two or all three fetuses may be involved, but the sonographic MVP criteria remain.
Definitions no longer used
Until a few years ago, TTTS was only diagnosed postnatally if an intertwin hemoglobin difference >5 gm/dL1 and a birth weight difference >20% 2 existed between the twins. However, in a classic study by Danskin and Neilson 3 in 178 twin pairs, only four pairs had a hemoglobin difference >5g/dL and a weight difference >20%, yet none of these pregnancies showed evidence of polyhydramnios or oligohydramnios. In another study, percutaneous umbilical blood sampling in nine patients with TTTS, defined by standard sonographic criteria, showed a hemoglobin differences >5 g/dL in only one pregnancy 4. A hemoglobin difference of only 1.7 g/dL was found in 4 patients by Saunders and collaborators5 Because of these findings, the previous neonatal criteria based on birthweight discordance and hemoglobin differences are no longer used.
Ultrasound diagnosis of TTTS
Over the years, the sonographic definition of twin-twin transfusion syndrome (TTTS) has been particularly marred by lack of standardization. Unfortunately such lack of standardization has resulted in the inclusion of patients in treatment series or even advisement of patients to interrupt their pregnancies despite not having TTTS. Hence, the need to establish a standard sonographic approach to TTTS cannot be overemphasized.
The original ultrasound criteria used to diagnose TTTS were based on biometric discrepancies (greater than 10 mm of either the biparietal diameter or the transverse diameter of the trunk between the twins) in addition to polyhydramnios of the larger twin 6. Brennan et al suggested that the presence of same sex, disparity in size or in the number of vessels in the umbilical cords, single placenta with different echogenicity of the cotyledons supplying the two cords, and evidence of hydrops in either twin or congestive heart failure in the recipient twin be added to the criteria 7. Doppler studies were also used in the definition of the syndrome, with disparate results. 8-12 With the introduction of the sonographic staging system13, it is now easy to understand why there were conflicting Doppler findings in the original reports that used Doppler to define the disease.
Current ultrasound definition of TTTS.
Several important achievements have been made in the last decade in defining TTTS. First, for the reasons mentioned above, the condition requires a sonographic diagnosis. This is important as it establishes ultrasound as the sole reliable diagnostic tool for the condition. As a corollary, the postnatal diagnosis of TTTS in patients with monochorionic twin pregnancies with an adverse pregnancy outcome and birthweight discordance may only be presumptive. Second, there has been a gradual acceptance of the sonographic criteria by which TTTS is defined, namely the presence of polyhydramnios, defined as a maximum vertical pocket of 8 cm or greater in one sac, and oligohydramnios, defined as a vertical pocket of 2 cm or less in the other sac. Finally, some sonographic parameters are no longer part of the definition, namely abnormal Doppler studies or growth discordance, as will be explained below.
Definition of polyhydramnios and oligohydramnios
Polyhydramnios and oligohydramnios are defined as sonographic estimates of amniotic fluid volumes above and below the 95th percentile for gestational age, respectively.
Ultrasound assessment of amniotic fluid volume has been either subjective, or semi-quantitative using the maximum vertical pocket (MVP), amniotic fluid index (AFI), or the 2-dimentional pocket (2-d). The MVP is defined as the largest vertical pocket of amniotic fluid without the presence of umbilical cord or other fetal parts. The AFI is the sum of the 4 MVPs taken in each quadrant with the transducer aligned in the sagittal plane. The 2-d diameter is the product of the MVP times the maximum transverse diameter in any particular quadrant Both the MVP and the AFI have been shown to behave similarly in singletons, dichorionic twins, and monochorionic twins, whereas the 2-D pocket is smaller in twins than in singletons 14 . The decision to use the MVP instead of the AFI in terms of the sonographic definition of TTTS is based on several grounds. First, the AFI is known to increase, with gestational age until approximately 33 weeks 15, 16 (Figure 1 from Magann AJOG 2000), whereas the MVP remains relatively stable throughout the second trimester (Figure 2 of Magann, AJOG 2000). Second, the AFI is impractical in twins, because of the varying location of the dividing membrane. Lastly, the uterine fundus may not have surpassed the umbilicus in some patients, which hinders the designation of the four quadrants for the AFI.
Figure 1.
Figure 2.
Some disagreement has existed as to which MVP cut-off values should be used in the definition of oligohydramnios and polyhydramnios. Most authors agree on 2 cm or less for the definition of oligohydramnios, and 8 cm or more for the definition of polyhydramnios. Oligohydramnios defined as 2 cm or less corresponds to the 5th percentile in MVP estimates, and changes little throughout gestation 16-19 The 95th percentile corresponds to an MVP of approximately 8 cm 14. Because of the known inaccuracy of amniotic fluid volume estimates, regardless of the sonographic technique used, the 2 and 8 cm cut-offs should be viewed as the minimum criteria to diagnose TTTS.
The importance of adhering to a standard definition of TTTS cannot be overemphasized because of the grave implications of treating non-TTTS patients or not treating bona fide TTTS patients. Non-descriptive terms such as poly/oli, or twin-polyhydramnios-oligohydramnios-sequence (TOPS), used in the past, are slowly being abandoned. While there has been universal acceptance of an MVP of 2 cm or less as part of the definition of TTTS, some authors have argued using <1 cm as more stringent criteria. If one agrees that Stage III and Stage IV TTTS patients represent the extreme of the spectrum in terms of disease severity, the use of a 1 cm cut off would declassify 26.9% of patients as having TTTS (Figures 3a and 3b).
Figure 3a. Frequency distribution of the maximum vertical pocket of the donor.
Figure 3b. Frequency distribution of the maximum vertical pocket of the donor in Stage III-IV patients. Approximately 25% of patients have a maximum vertical pocket greater than 1 cm and less than 2 cm.
Although the MVP rises slightly with gestational age before 16 weeks of gestation, use of an MVP < 8 cm, as suggested by some authors, is unwarranted, as it is likely to result in significant overlap with the normal population (Figures 4a and 4b). Similarly, some authors have proposed using a cut-off of 10 cm as the definition of polyhydramnios, particularly after 20 weeks. Our data show that such a decision would declassify 43% of Stage III and Stage IV TTTS patients.
Figure 4a. Frequency distribution of the maximum vertical pocket of the recipient.
Figure 4b. Frequency distribution of the maximum vertical pocket of the recipient twin in Stage III-IV patients from 20-26 weeks of gestation. Thirty-five percent of patients had a maximum vertical pocket of less than 10 cm.
Sonographic pitfalls: the cocoon sign.
Because of the presence of oligohydramnios, the donor twin is usually stuck against the walls of the uterus. Thus the term “stuck twin” Has been used However, in approximately 15% of TTTS patients, the donor twin is enveloped by the dividing membrane, such that it is connected to the uterine wall by a stalk of these membranes (Figure 5a, 5b and 5c)... As a result, the donor twin, despite having anhydramnios, may not be stuck to the uterine wall. We have called this potential sonographic pitfall “the cocoon sign”, as the term implies 20. Thus, a non-stuck donor twin may not necessarily be in a better condition than a stuck one. The importance of the recognition of the cocoon sign lies in the ability to correctly diagnose anhydramnios of the donor twin and not measure fluid of the recipient twin mistakenly as belonging to the donor twin. Because the donor can move, despite having severe oligohydramnios, the sonographer may erroneously conclude that the fetus does have ample amniotic fluid.
Figure 5a. Ultrasound view of the cocoon sign. The donor twin is enveloped between the two layers of the dividing membrane. The maximum vertical pocket in the sac of this twin is zero and not the distance between the membrane and the uterine wall.
Figure 5b. Correct and incorrect measurement of maximum vertical pocket in the presence of the cocoon sign.
Figure 5c. Endoscopic view of the cocoon sign.
Step two. Staging of TTTS
Our current understanding of the heterogenous presentation of TTTS explains the seemingly conflicting reports of pioneer investigators regarding the role of Doppler in TTTS. 8-12 Indeed, we now know that only a sub-group of TTTS patients present with abnormal Doppler findings. Thus, Doppler studies are more important in terms of assessing disease severity rather than in defining the syndrome. TTTS is known to be a heterogeneous condition with different presentations. Variations of the syndrome include visualization or lack thereof of the bladder of the donor twin, and the presence or absence of abnormal Doppler studies or hydrops. TTTS may also present with demise of one or both twins. The heterogeneity may result from a direct consequence of determinant factors (e.g., abnormal Doppler studies due to placental insufficiency, or superficial anastomoses), or more often, the expression of dynamic changes occurring over time, which eventually may result in demise of one or both twins. In 199913, we proposed a sonographic staging system to account for all of the different presentations. Inherent in the staging system is the notion that the higher the stage, the worse the prognosis. For all stages, patients meet the basic criteria of polyhydramnios > 8 cm, and oligohydramnios <2 cm. The proposed staging system is as follows:
Stage I: The bladder of the donor is visible (Figure 6).
Figure 6.
Stage II: The bladder of the donor is not visible (Figure 7). The typical ultrasound examination of patients with TTTS lasts approximately 60 minutes. Non-visualization of the bladder of the donor therefore is defined as lack of visualization of the bladder of the donor twin in 60 minutes of ultrasound examination.
Is there a difference between Stage I and Stage II?
A recent editorial suggested that Stage I and Stage II are one and the same. The article argued that visualization of the donor twin’s bladder is often dependent upon the duration of observation and that the fetal bladder is rarely subjected to continuous observation over at least an hour in order to characterize urine production. The editorial argued further that a visible bladder in the donor does not exclude fetal anuria, with 3-D studies showing that 48% (14/29) of cases classified as Stage I showed no significant urine production and that around 6% of Stage II (2/31) cases produced some urine in a 5–30-min observation period. The basis for these arguments is unsubstantiated. First, our definition of lack of visualization of the bladder of the donor was based on over 60 minutes of observation. Our typical ultrasound evaluation of patients with TTTS is approximately 90 minutes. We cannot comment on the time of observation spent in the assessment of TTTS patients by the authors of the editorial. Furthermore, data from our referral pattern shows that lack of bladder visualization was noted by the referring physicians as well, in at least 7 days prior to referral. Thus, patients classified as Stage I in our classification show bladder filling, whereas Stage II patients do not show bladder filling in over 60 minutes of observation. Second, by definition, because Stage II patients should not have a visible bladder. Therefore, 3-D bladder measurements are not possible in Stage II patients. Thus, the 6% of patients in Yamamoto study found to have bladder filling would have been classified as Stage I patients at our institution. Interestingly, we have not argued that bladder visualization equates to urine production. In fact, patients with atypical Stage III-Donor (see below) TTTS may show anhydramnios in the sac of the donor twin yet a visible bladder in the donor twin. In addition, our data show that in fact, there may be an underlying biological reason for the sonographic distinction between Stage I and Stage II patients. Indeed, the incidence of superficial anastomoses is significantly higher in Stage I than in Stage II patients (50% vs, 12%, p < .001). Therefore, Stage I patients may be biologically different than Stage II patients, which is ultimately reflected in visualization or lack thereof of the bladder of the donor twin.