1 Centre for Fetal Care, Department of Materno-Fetal Medicine and 2 Department of Perinatal Pathology, Imperial College School of Medicine, Queen Charlotte's & Chelsea Hospital, Goldhawk Road, London W6 0XG, UK
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Abstract |
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Key words: arterio-arterial anastomoses/Doppler/monochorionic twins/twin-twin transfusion
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Introduction |
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The pathophysiology of TTTS remains poorly understood but has been attributed to unbalanced intertwin transfusion mediated by deep unidirectional arterio-venous anastomoses (Fisk and Taylor, 2000). Superficial bidirectional anastomoses, either arterio-arterial anastomoses (AAA) or veno-venous anastomoses (VVA), have the capacity to compensate for any net imbalance in intertwin transfusion. Several placental injection studies have shown that TTTS is associated with a paucity of superficial anastomoses and in particular, an absence of AAA (Bajoria et al., 1995
; Machin et al., 1996
; Denbow et al., 2000
). AAA can be identified using colour Doppler and support for this compensatory role has come from an in-vivo study which suggested that the presence of AAA protects against the development of TTTS (Denbow et al., 1998
). More recently, our group has shown that such protection extends to improving survival in established disease (Taylor et al., 2000
) in the few cases of TTTS that have AAA.
To date, detection of AAA has largely been performed as a part of research projects in a tertiary referral centre (Hecher et al., 1994; Denbow et al., 1998
). Our hypothesis for this study was that demonstration of AAA is now sufficiently accurate that routine antenatal detection is feasible. We evaluated this prospectively in a large cohort of MC twins.
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Materials and methods |
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Following routine biophysical assessment for evidence of TTTS (vide infra) the presence of AAA was sought as described previously (Denbow et al., 1998). Power or spectral Doppler were used to identify chorionic plate vessels crossing the vascular equator, which were then insonated by pulse wave Doppler. AAA were identified by their characteristic bidirectional interference pattern (Figure 1
), whose frequency can be shown on computer modelling to occur with a periodicity reflecting the net difference between the two twins' different fetal heart rates (Hecher et al., 1994
; Taylor et al., 1999
). These patterns have also been validated by observation of dynamic normalization of the waveform at the time of single fetal death (Taylor et al., 1999
). Power Doppler was used initially, but by the last half of this series, it became apparent that spectral Doppler on the Acuson Sequoia was also sufficiently sensitive but had the added advantage of displaying a characteristic `speckled' pattern due to the bidirectional flow which facilitated AAA detection. Power Doppler on the other hand had the advantage of angle independence and thus the ability to detect low flow, which is particularly useful at earlier gestations. Therefore a combination of techniques was used in practice. Search for an AAA was limited to a maximum of 30 min per scanning session. Insonation was stopped when one AAA was confirmed, and the presence of multiple AAA was not sought. Thus for the purposes of this study, ultrasonic surveillance for the presence of an AAA was discontinued at subsequent visits. The actual length of insonation time was recorded in a subgroup (n = 20) with duration of scanning recorded categorically in 5 min intervals. All women gave oral consent to the additional insonation sequences for research purposes as approved by the institutional ethics committee.
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Gestational age was based on the date of the last menstrual period if certain or ultrasonography in the first trimester. Placental site was documented as anterior, posterior or fundal according to where the bulk of the placenta between the two cord insertions was situated.
Following delivery, fresh placentae were collected and, blind to the Doppler results, injection studies were performed by the perinatal pathologist (P.C.) as described previously (Denbow et al., 2000). Blinding was felt to be necessary to avoid observation bias in interpreting the results of injection studies. The presence of a single AAA/multiple AAA identified at injection study was compared with Doppler findings to calculate the sensitivities and specificities for antenatal assessment. The diameter of each AAA was documented. Data collection was incomplete for AAA diameters in 6/68 cases due to technical difficulties at injection study due to placental damage in five cases and in one case diameter was not documented.
Statistical analysis was undertaken using SPSS for Windows. Data were analysed for the association between AAA findings on ultrasound with both histopathology and an absence of TTTS using sensitivities, specificities, likelihood ratios (LR) for positive and negative tests and odds ratios (OR). Categoric comparisons were evaluated by 2 testing. A P-value <0.05 was considered significant. Data from the first 40 of these cases have been described previously (Denbow et al., 1998
).
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Results |
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AAA were detected in 37/59 cases (63%) at the first scan, 13/59 (22%) at the second, 4/59 (7%) at the third, 3/59 (5%) at the fourth and 2/59 (3%) at the fifth. Only one of the 68 placentae with AAA present at injection study had more than one AAA in this case only one of the two was detected by Doppler. Thirty-seven out of 105 pregnancies (35%) were complicated by TTTS.
Table I shows the relationship between AAA identified at scan and injection study, and between AAA identified at scan and the presence or absence of TTTS. Table II
shows the accuracy of AAA detection and likelihood ratios for positive and negative tests and the ability of an AAA to predict the absence of TTTS development and corresponding likelihood ratios. The cumulative sensitivity and specificity for the detection of AAA was 85.3 and 97.3% respectively. One AAA diagnosed antenatally was not identified at injection study. However, in this pregnancy, one of the twins died in utero at 28 weeks, 2 weeks after an AAA was identified. Delivery did not occur until 38 weeks, after which placental injection showed only a VVA in the presence of considerable sclerosis of the dead fetus's placental territory, rendering injection study problematic and the findings difficult to interpret.
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Discussion |
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The predictive value of detecting AAA in vivo is highlighted by the 9-fold reduction in risk of developing TTTS when one is found. While not eliminating this risk entirely, patients may well derive some reassurance from this information. Indeed, since the perinatal mortality is reduced in MC pregnancies with an AAA present whether or not TTTS develops (Denbow et al., 2000), the whole pregnancy can be regarded as being at lesser risk of this complication. Moreover, should TTTS develop, the presence of an AAA is associated with substantially increased chances of both twins surviving (Taylor et al., 2000
). Clinically, the demonstration of an AAA in MC twins goes some way to reassuring parents that a favourable outcome can be anticipated and that the excess risks associated with TTTS do not apply in their case.
The detection of an AAA also serves to confirm monochorionic placentation. If chorionicity has not been determined in early pregnancy, the standard techniques used become less reliable after the first trimester (Stagiannis et al., 1995), whereas demonstration of an AAA establishes this with 100% reliability. This information is highly relevant to genetic counselling, the management of imminent single fetal demise, discordant growth restriction or fetal anomaly, and is also of great importance in selecting the appropriate technique for karyotype determination or selective feticide. We acknowledge, however, that absence of AAA on Doppler does not definitively indicate dichorionicity. Indeed, 37/105 (35%) MC pregnancies did not have an AAA at injection study. Although an AAA appears to protect against TTTS, AAA may increase the chances of co-twin death after single intrauterine death and/or neurological morbidity (Bejar et al., 1990
; Bajoria et al., 1999
).
There are three potential obstacles to uptake of this technique: poor equipment, lack of necessary operator skill and insufficient time. High resolution ultrasound equipment with the necessary colour Doppler facilities is now readily available in most obstetric ultrasound units and will become increasingly so as costs fall. This study was performed by two research fellows (M.T. and M.D.) with little prior scanning experience, both of whom acquired the necessary skills within a 23 month period, suggesting that learning this technique lies within the grasp of all ultrasonographers. Finally, the average time to detect an AAA was only 10 min and this may fall further with increasing experience.
There are several limitations to this test. The test is a positive outcome predictor, in that its identification confers a lower complication risk on that pregnancy. Absence of an AAA on Doppler, however, could be either because an AAA is genuinely absent and hence a negative predictor, or simply because it has not yet been detected. The likelihood ratio of 0.2 for a negative test suggests that there is five times less chance of not detecting an AAA that is present than correctly identifying absence of an AAA. In this study, the percentage of AAA detected at a particular gestation which are eventually detected ranges from 78% at 16 weeks to 100% at >28 weeks (Figure 4). Thus, this implies firstly that AAA can be identified with a high degree of reliability in the mid-trimester and secondly that the sensitivity at a particular gestation does not differ substantially from the overall cumulative sensitivity of 85%. Ideally, AAA need to be identified at a stage before the average time that TTTS develops, which in our unit is at ~22 weeks (Taylor et al., 2000
). We expect detection in future to occur at earlier gestations because of increasing experience with the technique and because of earlier referrals of MC twins for assessment. Future ultrasound developments such as three-dimensional Doppler (Pretorius et al., 1998
) may also enable earlier detection especially of the smaller vessels which proved elusive in the current study.
Notwithstanding the above limitations, this study shows detection of AAA to be the first accurate and clinically useful example of in-vivo mapping of chorionic plate vessels in MC twins. TTTS accounts for a substantial proportion of the increased perinatal mortality and morbidity of MC twins. Detection of an AAA gives a risk of TTTS 9-fold lower than if one is not detected. We suggest that antenatal detection of AAA by colour Doppler is a clinically valuable tool in the assessment of MC twins.
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Acknowledgments |
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Notes |
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References |
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Bajoria, R., Wee, L.Y., Anwar, S. et al. (1999) Outcome of twin pregnancies complicated by single intrauterine death in relation to vascular anatomy of the monochorionic placenta. Hum. Reprod., 14, 21242130.
Bejar, R., Vigliocco, G., Gramajo, H. et al. (1990) Antenatal origin of neurologic damage in newborn infants. II. Multiple gestations. Am. J. Obstet. Gynecol., 162, 12301236.[ISI][Medline]
Brennan, J.N., Diwan, R.V., Rosen, M.G. et al. (1982) Fetofetal transfusion syndrome: prenatal ultrasonographic diagnosis. Radiology, 143, 535536.[ISI][Medline]
Denbow, M., Cox, P., Talbert, D. et al. (1998) Colour Doppler energy insonation of placental vasculature in monochorionic twins: absent arterio-arterial anastomoses in association with twintwin transfusion syndrome. Br. J. Obstet. Gynaecol., 105, 760765.[ISI][Medline]
Denbow, M.L., Cox, P., Taylor, M. et al. (2000) Placental angioarchitecture in monochorionic twin pregnancies: relationship to fetal growth, fetofetal transfusion syndrome, and pregnancy outcome. Am. J. Obstet. Gynecol., 182, 417426.[ISI][Medline]
Deprest, J.A., Audibert, F., Van Schoubroeck, D. et al. (2000) Bipolar coagulation of the umbilical cord in complicated monochorionic twin pregnancy. Am. J. Obstet. Gynecol., 182, 340345.[ISI][Medline]
Fisk, N.M. and Bennett, P. (1995) Prenatal determination of chorionicity and zygosity. In Ward, H. and Whittle, M. (eds), Proceedings of the RCOG Study Group on Multiple Pregnancy. RCOG Press, London.
Fisk, N.M. and Taylor, M.J.O. (2000) The fetus(es) with twintwin transfusion syndrome. In Harrison, M., Evans, M., Adzick, S. and Holzgreve, W. (eds) The Unborn Patient: The Art and Science of Fetal Therapy. W.B. Saunders Company, Philadelphia, in press.
Hecher, K., Jauniaux, E., Campbell, S. et al. (1994) Artery-to-artery anastomosis in monochorionic twins. Am. J. Obstet. Gynecol., 171, 570572.[ISI][Medline]
Machin, G., Still, K. and Lalani, T. (1996) Correlations of placental vascular anatomy and clinical outcomes in 69 monochorionic twin pregnancies. Am. J. Med. Genet., 61, 229236.[ISI][Medline]
Mari, G. (1998) Amnioreduction in twintwin transfusion syndrome a multicenter registry, evaluation of 579 procedures. Am. J. Obstet. Gynecol., 178, S28.
Phelan, J.P., Ahn, M.O., Smith, C.V. et al. (1987) Amniotic fluid index measurements during pregnancy. J. Reprod. Med., 32, 601604.[ISI][Medline]
Pretorius, D.H., Nelson, T.R., Baergen, R.N. et al. (1998) Imaging of placental vasculature using three-dimensional ultrasound and color power Doppler: a preliminary study. Ultrasound Obstet. Gynecol., 12, 4549.[ISI][Medline]
Saade, G.R., Belfort, M.A., Berry, D.L. et al. (1998) Amniotic septostomy for the treatment of twin oligohydramnios-polyhydramnios sequence. Fetal Diagn. Ther., 13, 8693.[ISI][Medline]
Saunders, N.J., Snijders, R.J. and Nicolaides, K.H. (1992) Therapeutic amniocentesis in twintwin transfusion syndrome appearing in the second trimester of pregnancy. Am. J. Obstet. Gynecol., 166, 820824.[ISI][Medline]
Stagiannis, K.D., Sepulveda, W., Southwell, D. et al. (1995) Ultrasonographic measurement of the dividing membrane in twin pregnancy during the second and third trimesters: a reproducibility study. Am. J. Obstet. Gynecol., 173, 15461550.[ISI][Medline]
Taylor, M.J., Talbert, D.G. and Fisk, N.M. (1999) Mapping the monochorionic equator the new frontier. Ultrasound Obstet. Gynecol., 14, 372374.[ISI][Medline]
Taylor, M.J.O., Denbow, M.L., Duncan, K.R. et al. (2000) Antenatal factors at diagnosis predictive of survival in severe twintwin transfusion syndrome. Am. J. Obstet. Gynecol., in press.
Ville, Y., Hecher, K., Gagnon, A. et al. (1998) Endoscopic laser coagulation in the management of severe twin-to-twin transfusion syndrome. Br. J. Obstet. Gynaecol., 105, 446453.[ISI][Medline]
Wittmann, B.K., Baldwin, V.J. and Nichol, B. (1981) Antenatal diagnosis of twin transfusion syndrome by ultrasound. Obstet. Gynecol., 58, 123127.[Abstract]
Submitted on December 2, 1999; accepted on April 7, 2000.