Many biophysical techniques are used to assess fetal well being in multiple pregnancy, including ultrasonography, Doppler velocimetry and cardiotocography. Considering the specific characteristics of multiple pregnancies in terms, higher rate of preterm delivery, higher incidence of fetal growth restriction andhigher rates of obstetric complications as compared to singleton gestation, as well as specific problems alsorelated to chorionicity and to the number of fetuses, it is difficult to summarize in general terms the usefulnessand role of each technique or to provide a general standard of management. Rather it is advisable to individually assess and manage each case on the basis of the presence of recognized risk factors, making use ofeach technique or of a combination of different techniques according to the specific information desired. These complexities also demand that the information obtained need to be interpreted on the basis of a thorough understanding of the pathophysiological basis involved. In twin pregnancy the development of chronic and acute hypoxemia is a main contributor to morbidity andmortality. Aim of this presentation is to summarize the current evidence related to the role of the fetal Doppler velocimetry, biophysical profile and cardiotocography evaluation in the diagnosis of fetal oxygen deficiencyin twin pregnancy, focusing also on the description of the role of modern techniques for intrapartum fetal monitoring as represented by the analysis of fetal electrocardiogram.
Doppler evaluation of fetal hemodynamic adaptation
Considering the processes which lead to the manifest utero-placental vascular insufficiency the fetal hemodynamic profile might remain "normal" even for a long period of time. In such circumstances the umbilical artery velocity waveform would show a positive blood-flow pattern throughout the whole cardiaccycle and the impedance to flow values expressed as pulsatility index (PI) would be normal with a non significant increase. The Doppler velocimetry of the remaining main fetal vessels and districts (particularlyaorta, renal artery, femoral artery, cerebral vessels, etc.) would also be in the range of normality with non significant alterations. Under these so called "normal" conditions, the mean PI of the middle cerebral arteries(MCA) would be higher than that of either the internal carotid (ICA) or the anterior cerebral arteries (ACA),while that of the posterior cerebral artery (PCA) would be lower than that of MCA and ACA and higher thanthat of the umbilical artery (UA). In the early stage of fetal blood flow redistribution Fetal Doppler velocimetry shows an increase in the impedance to flow values as expressed by an increase of pulsatility index of the umbilical artery but also of theaorta and the renal artery. The increase of the vascular resistance of the aorta is probably related to differentfactors, including the increase in vascular impedance in the umbilico-placental vessels and arterial vasoconstriction of peripheral vessels due to progressive hypoxemia. During this phase, it is possible to observesome hemodynamic modifications which involve the whole fetal organism. These are related to the substantialredistribution of the cardiac output that goes in the direction of the tissues which are important for fetal urvival. The inversion of cerebro-placental ratio, called "brain sparing", is the most evident hemodynamiceffect. In this stage a statistically significant increase of the blood flow and a decrease of the resistance in allthe cerebral vessels examined can be documented. At the some time, due to the hemodynamic redistribution, adecrease of the peripheral flow in the umbilical artery, abdominal aorta, renal artery, femoral artery and othervessels, along with high impedance to flow values can be observed. During this stage, the pulsatility index of the umbilical artery and of the fetal aorta is elevated but Doppler velocimetry frequency values continue to be positive throughout the whole cardiac cycle, even in theend-diastolic phase. On the other hand, it is possible to find high velocity frequencies during diastole in allcerebral vessels, suggesting an increase of the fetal cerebral blood flow. The following phase, the so called advanced stage of fetal hemodynamic redistribution, is essentially characterized by a further increase in the impedance to flow in the umbilical artery, the fetal aorta and the renalartery. Looking at the umbilical artery flow velocity profile, a decrease of the diastolic frequencies is observedprogressing towards the absence of diastolic flow. End-diastolic frequency disappears first, but subsequentlythe lack of blood flow is evident in the whole diastolic phase. Usually this occurs when 80% of villi arteriolesare occluded. In the decompensatory phase the cardiac output and the peak velocity of the main arterial trunks graduallydecline and, as a consequence, cardiac filling is impaired, suggesting a progressive deterioration of cardiacfunction. Therefore, these factors cause changes that induce hemodynamic alterations in all cardio-vascular districts (intracardiac, arterial and venous districts). The incipient heart failure produces a decrease cardiac output which causes a decrease in the peak velocity of the outflow tracts leading to the reverse flow in theaorta, in the umbilical artery and, finally, as a terminal sign, in many other arterial vessels such as the cerebralvessels. During this phase, the increased viscosity of the fetal blood, the decrease in cardiac output and, probably the cerebral edema all tend to produce a decrease of brain perfusion, as shown by the decrease ofblood velocity especially during diastole and, thus, the disappearance of the "brain sparing effect".
The biophysical profile in multiple pregnancy
The number of reports on the usefulness of the fetal biophysical profile in multiple pregnancy are few. Medinademonstrated that the use of Manning’s sonographyc criteria to predict still birth had a sensitivity of 66.7%, aspecificity of 98.8%, a positive predictive value of 50% and a negative predictive value of 99.4%. The biophysical profile has been recommended in high-order multiple gestations when cardiotocography istechnically difficult to perform. However, the biophysical profile can be difficult too, because of difficultassessment of the amniotic fluid volume. The presence of synchronous patterns of fetal activity might alsointerfere in interpretation, because gross body movements, breathing movements and accelerations of the fetalheart independent of chorionocoty may be synchronous in 25, 50 and 50-60% respectively. One of the more difficult variables to assess in multiple pregnancies is the amniotic fluid volume, becauseabnormalities occur more frequently than in singletons secondary to placental insufficiency, placental vascularanastomoses and maternal hemodynamic alterations. No agreement exists on the optimal sonographyc methodof evaluating amniotic fluid volume in multiple pregnancies, and no method has been validated for predictingperinatal outcome in multiple gestation. Chau and colleagues found that the AFI, the vertical depths and thetwo diameter pockets measured at 2 week interval were not significantly different between dichorionic andmonochorionic pregnancies. Furthermore, the intraobserver variation in evaluating the amniotic fluid volume indiamniotic twin pregnanciy was about 2-3%, approximately the figure cited for singleton pregnancies. Theaccuracy of the 2 by 2 cm pocket as a cut off value for low amniotic fluid volume in twin pregnancies wasstudied by Magann and associates. The sensitivity was 6.1%, the specificity 98.8%, the positive predictivevalue 66.6% and the negative predictive value 73.5%.
Techniques of intrapartum fetal surveillance
yContinuous fetal heart rate (FHR) and uterine contraction recording (cardiotocography or CTG) is widely usedto assess fetal well being during labour. This method has, however, certain limitations. A normal CTG tracereflects optimal fetal oxygenation and is of reassurance regarding fetal conditions. In contrast the significance of FHR changes is often unclear and therefore difficult to interpret. In the clinical scenario, this can result in unnecessary interventions for suspected fetal hypoxia or inappropriate delay in action with potentially disastrous consequences for the fetus. Some of these difficulties can be overcome by a better training of medical and midwifery staff. Evidences also suggests that the use of expert systems for decision making wouldprovide a valuable contribution in improving the detection and clinical management of cases with abnormal CTG patterns. However, it is also evident that there are situations in which the CTG changes are not specificenough for the presence of fetal hypoxia and additional information is necessary for appropriate decision making. Thus the limitations of cardiotocography in the term fetus are mainly linked to the difficulty of interpretation ofabnormal fetal heart rate patterns and to the poor specificity of the technique in identifying threatening hypoxia.Furthermore, twin pregnancy are often complicated by prematurity. Assessment of fetal well being in thepreterm fetus by analysis of the fetal heart rate presents, in addition to the limitations described, further andspecific difficulties. The antepartum non-stress test, of recognised value in the term fetuses, is of less welldefined value in the preterm fetus, due to greater uncertainty in the relationship between baseline heart rate,reactivity and fetal conditions. The interpretation of fetal heart rate patterns of the preterm fetus, is also complicated by the impact of specificdrugs more frequently used in women with threatened or actual preterm labour. It is well known, for example,that the administration of steroids or magnesium sulphate exert a negative effect on fetal heart rate variability,and that administration of beta-receptor agonists affects both fetal heart rate variability and baseline heart rate.The assessment of fetal well being in the preterm fetus by electronic fetal monitoring therefore requires furtherstudies to develop specific interpretative criteria considering the specific physiological aspects of the maturingfetus. Another problem related to cardiotocogrphyc fetal monitoring in twin pregnancy is that linked to the difficultyof obtaining a reliable dual tracing. This difficulty can give rise to errors linked to the double recording of thesame heart rate or in the inadvertent recording of maternal heart rate that can be erroneously interpreted asfetal. When possible it is advisable to record the heart rate of the first twin by a scalp clip.
The ST waveform analysis of the fetal electrocardiogram
ST analysis has emerged not as an alternative to cardiotocography but as a support tool to allow more accurateinterpretation of intrapartum events. The fetal ECG is readily obtainable during labour from the same scalpelectrode used to obtain the fetal heart rate utilizing a dedicated CTG plus fetal ECG monitor (STAN® S 21,Neoventa Medical AB, Gothenburg, Sweden). Numerous experimental animal studies have clarified the pathophysiology of ST waveform changes of the fetalECG during hypoxia. The evidence from experimental work indicate that ST waveform elevation reflects compensated myocardialstress and a switch to anaerobic myocardial metabolism. A progressive rise in T/QRS ratio represents continuing anaerobic metabolism with a risk of eventual decompensation due to depletion of myocardial glycogen stores and a progressive metabolic acidosis. Persistently biphasic and negative waveform changesindicate myocardial decompensation as a result of direct myocardial ischemic hypoxia. Clinical analysis of STwaveform changes is assisted by a specifically developed computerized ST log function that provide directstatements on specific significant ST events, to provide additional user support. This pathophysiological modelof interpretation has lead to the development of specific clinical action guidelines that have been tested in several observational and randomized control studies. These studies demonstrate the high sensitivity ofCTG+ST to predict fetal acidosis, associated with a significant increase in positive predictive values as compared with CTG only. The results from the recent Swedish randomized trial on CTG alone versus CTG+ST analysis (4495 cases)showed in the CTG+ST arm of the trial a 60% reduction in the number of cases with metabolic acidosis (cord artery pH<7,05 and base deficit >12mmol/l) accompanied by a 25% reduction in operative interventionsfor fetal distress as compared with the CTG only arm, with no increase in operative deliveries for other reasons.The trial protocol allowed for an interim analysis after 1600 cases. This analysis showed frequent breaches of protocol as clinical management in the CTG+ST arm was conducted according to the "old" CTG information.The result of this lack of compliance was not only more operative interventions but also babies being exposedto unnecessary intrauterine hypoxia with two babies requiring neonatal intensive care. After retraining and enhanced experience with ST analysis that allowed a more rigorous application of theCTG+ST clinical action protocol, it was possible to obtain in the second half of the trial an even more pronounced reduction in metabolic acidosis (-75%) with no babies admitted to NICU and a decrease of operative delivery rate for fetal distress of 44%. These results confirm the capacity of ST waveform analysis toprovide diagnostic information on developing hypoxia during labour that can lead to a significant improvementin fetal outcome.
The challenge of obstetric surveillance is to identify those fetuses whose physiological defence mechanisms arecompromised so that the obstetrician is able to act before decompensation has occurred. During the antenatalperiod, the evaluation of fetal hemodynamic adaptation to hypoxemia and the assessment of its chronologicalevolution by Doppler technology is crucial. This assists in planning appropriate obstetrical management and inreducing the risks of fetal damage. Inadequate data exists to establish the value of the biophysical profile in multiple gestations. It appears that thebiophysical score cannot differentiate between distressed and non-distressed fetuses in the same pregnancy.Therefore, an equivocal biophysical profile has limited value in predicting fetal distress in multiple pregnanciesdespite a high negative predictive value. Accordingly serial assessment of fetal well being should include allmethods available: the non-stress test, the biophysical profile and Doppler velocimetry. During intrapartum period, the relative inaccessibility of the fetus and the complexity of the pathophysiology of fetal oxygenation make it difficult to obtain and interpret information on fetal response to the stress of labor.Due to the limitations of cardiotocography, additional information is required for an appropriate decision making during labor. The results of clinical randomized studies show the capacity of modern technologyapplied to fetal surveillance, and in particular the analysis of fetal electrocardiogram in term fetuses, to provideuseful additional information that can improve our ability to interpret fetal reactions to labor events. A significant improvement in fetal surveillance, particularly in multiple pregnancies, is related not only to theavailability of more specific information but also on the capacity of making the better use of the informationavailable. This requires clinical skills, knowledge of fetal physiology and understanding of the technical basisand limitations of the methodologies of monitoring used.
1. Greene KR, Rosén KG. Intrapartum asphyxia. In: Fetal and neonatal neurology and neurosurgery. Levene and Lilford ed. ChurchillLivingstone, 1995.
2. MacLennan A. A template for defining a causal relation between acute intrapartum events and cerebral palsy: international consensusstatement. BMJ 1999; 319: 1054-59.
3. Rosén KG, Murphy K. How to assess fetal metabolic acidosis from cord samples. J Perinat Med 1991; 19: 221-226. 4. Jauniaux E., Jurkovic D., Campbell S., Hustin J. Doppler ultrasonographyc features of the developing placental circulation: correlationwith anatomic findings. Am J Obstet Gynecol 1992; 166:585-7.
5. Warwick B.G., Trudinger B.J., Baird P.J. Fetal umbilical artery flow velocity waveforms and placental resistance: pathological correla-tion. Br J Obstet Gynaecol 1985; 92:31-38.
6. Nordenvall M., Ullberg U., Laurin J., Lingman G., Sandstedt B., Ulmsten U. Placental morphology in relation to umbilical arteryblood velocity waveforms. Eur J Obstet Gynecol Rep Biol 1991; 40:179-190.
7. Trudinger B.J., Warwick B.G., Colleen M.C. Utero-placental blood flow velocity-time waveforms in normal and complicated pregnan-cy. Br J Obstet Gynaecol 1985; 92:39-45.
8. Trudinger B.J., Warwick B.G., Colleen M.C. Flow velocity waveforms in maternal utero placental and fetal umbilcal placental circula-tions. Am J Obstet Gynecol 1985; 152:155-63.
9. Trudinger B.J., Warwick B.G., Colleen M.C., Bombardieri J., Collins L. Fetal umbilical artery flow velocity waveforms and placentalresistance: clinical significance. Br J Obstet Gynaecol 1985; 92:23-30.
10. Trudinger B.J., Stevens D., Connelly A., Hales J.R.S., Alexander G., Bradley L., et al. Umbilical artery flow velocity waveforms andplacental resistance: the effects of the embolization of the umbilical circulation. Am J Obstet Gynecol 1987; 157:1443-8.
11. Mari G., Deter R.L. Middle cerebral artery flow velocity waveforms in normal and small-for-gestational-age fetuses. Am J ObstetGynecol 1992; 166: 1262-70.
12. Veille J.C., Penry M. Effect of maternal administration of 3% carbon dioxide on umbilcal artery and fetal renal and middle cerebralartery Doppler waveforms. Am J Obstet Gynecol 1992; 167:1668-71.
13. Luzi G., Coata G., Caserta G., Cosmi E.V., Di Renzo G.C. Doppler velocimetry of different section of the fetal umbilcal artery in relation to perinatal outcome. J Perinat Med 1996; 24:327-34.
14. Clerici G., Luzi G., Di Renzo G.C. Cerebral circulation from healthy to IUGR and distressed fetus: what happens and how we canexplain it. In Kurjak A., Di Renzo G.C. Modern methods of the assessment of fetal and neonatal brain CIC Int eds. 1996: 36-50.
15. Bilardo C.M., Snijders R.M., Campbell S., Nicolaides K.H. Doppler study of fetal circulation during long-term maternal hyperoxigenation for severe early onset intrauterine growth retardation. Ultrasound Obstet Gynecol 1991; 1: 250-57.
16. Scherjon S.A., Smolders-DeHaas H., Kok J.H., Zonderwan H.A. The "brain sparing" effect: Antenatal cerebral Doppler findings inrelation to neurologic outcome in very preterm infants. Am J Obstet Gynecol 1993; 169:169-75.
17. Weiner Z., Farmakides G., Schulman H., Penny B. Central peripheral hemodynamic changes in fetuses with absent end-diastolicvelocity in umbilical artery: Correlation with computerized fetal heart rate pattern. Am J Obstet Gynecol 1994; 170: 509-15.
18. Van Den Wijngaard, Groenenberg I.A.L., Wladimiroff J.W., Hop W.C.J. Cerebral Doppler ultrasound of the human fetus. Br J ObstetGynaecol 1989; 96:845-49.
19. Sepulveda W., Shennan A.H., Peek M.J. Reverse end-diastolic flow in the middle cerebral artery: an agonal pattern in the human fetus.Am J Obstet Gynecol 1996; 174: 1645-7.
20. Greene KR. Intrapartum fetal monitoring: CTG, ECG and fetal blood sampling. In Fetal Medicine: basic science and clinical practice.Rodeck and Whittle ed. Churchill Livingsone, 2000.
21. Cohn HE, Sachs EJ, Heymann MA, Rudolph AM. Cardiovascular responses to hypoxaemia and acidemia in fetal lambs. Am J ObstetGynaecol 1974, 120: 817-824.
22. Rurak DW, Richardson BS, Patrick JE, Carmichael L Homan J. Oxygen consumption in the fetal lamb during sustained hypoxaemiawith progressive acidemia. Am J Physiol 1990; 258: 1108-15.
23. Dawes GS, Mott JC, Shelley HJ. The importance of cardiac glycogen for the maintenance of life in foetal lambs and newborn animalsduring anoxia. J Physiol 1959; 146: 516-538.
24. FIGO guidelines for the use of fetal monitoring. Int J Gynecol Obstet 1987; 25: 159-167.
25. Larsen JF. Why has conventional intrapartum cardiotocography not given the expected results? J Perinat Med 1996; 24: 15-23.
26. Greene KR. Intelligent fetal heart rate computer systems in intrapartum surveillance. Current Opinion in Obstetrics & Gynaecology1996; 8: 123-127.
27. Lindecrantz K, Lilja H, Widmark C, Rosén KG: The fetal ECG during labour. A suggested standard. J Biomed Eng 1988; 10: 351-353.
28. Rosén KG, Isaksson O. Alterations in fetal heart rate and ECG correlated to glycogen, creatine phosphate and ATP levels during graded hypoxia. Biol Neonate 1976; 30: 17-24.
29. Rosén KG, Dagbjartsson A, Henriksson BA, Lagercrantz H, Kjellmer I. The relationship between circulating catecholamines and STwaveform in the fetal lamb electrocardiogram during hypoxia. Am J Obstet Gynaecol 1984; 149:190-195.
30. Widmark C, Jansson T, Lindecrantz K, Rosén KG. ECG waveform, short term heart rate variability and plasma cathecholamine concentrations in response to hypoxia in intrauterine growth retarded guinea pig fetuses. J Develop Physiol 1991; 15: 161-168.
31. Rosén KG,Luzietti R. Intrapartum fetal monitoring: its basis and current developments.Prenat Neonat Med 2000;5:1-4
32. Arulkumaran S, Lilja H, Lindecrantz K, Ratnam SS, Thavarasah AS, Rosén KG Fetal ECG waveform analysis should improve fetasurveillance in labour. J Perinat Med 1990; 18: 13-22.
33. Luzietti R, Erkkola R, Hasbargen U, Mattsson L, Thoulon J-M, Rosén KG. European community multi-center trial "Fetal ECG analysis during labour": ST plus CTG analysis. J Perinat Med 1999; 27: 431-440.
34. Luzietti R, Rosén KG. ST waveform analysis of the fetal ECG and intrapartum hypoxia. XVII European Congress of PerinatalMedicine. Prenat Neonat Med. 2000;5 (2):30.
35. Westgate J, Harris M, Curnow JSH, Greene KR. Plymouth randomised trial of cardiotocogram only versus ST waveform plus cardiotocogram for intrapartum monitoring: 2,400 cases. Am J Obstet Gynecol 1993; 169: 1151-1160.
36. Amer-Wåhlin I, Norén H, Hellsten C et al. Randomised controlled trial of CTG versus CTG+ST analysis of the fetal ECG. Int J Gynecol Obstet 2000; 70: 35.
37. Lodeiro JG, Vintzileos AM, Feinstein SJ, Campbell WA, Nochimson DJ. Fetal biophysical profile in twin gestations. Obstet Gynecol1986,67:824-7.
38. Medina D, Vargas N, Bustos JC, Cadima R, Lavarello C. Biophysical profile in twin pregnancy: prospective study. Rev Chil ObstetGinecol 1994;59:343-8.
39. Zimmer EZ, Goldstein I, Alglay S. Simultaneous recording of fetal breathing movements and body movements in twin pregnancy. J Perinat Med 1988;16:109-12.
40. Elliot JP, Finberg HJ. Biophysical profile testing as an indicator of fetal well-being in high-order multiple gestations. Am J ObstetGynecol 1995;172:508-12.
41. Chau AC, Kjos SL, Kovacs BW. Ultrasonographic measurement of amniotic fluid volume in normal diamniotic twin pregnancies. Am J Obstet Gynecol 1996;174:1003-7
42. Magann EF, Nevils BG, Chauhan SP, Whitworth NS, Klausen JH, Morrison JC. Low amniotic fluid volume is poorly identified in singleton and twin pregnancies using the 2 x 2w cm pocket technique of the biophysical profile. South