What is the definition of pulsatile umbilical venous flow in twin-twin transfusion syndrome?

What is the definition of pulsatile umbilical venous flow in twin-twin transfusion syndrome?

Research www. AJOG.org OBSTETRICS What is the definition of pulsatile umbilical venous flow in twin-twin transfusion syndrome? Zoi Russell, MD; Rub...

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OBSTETRICS

What is the definition of pulsatile umbilical venous flow in twin-twin transfusion syndrome? Zoi Russell, MD; Rubén A. Quintero, MD; Eftichia V. Kontopoulos, MD OBJECTIVE: The aim of the study was to derive an objective definition

of pulsatile umbilical venous flow (PUVF). STUDY DESIGN: Pulsed Doppler waveform analysis of the umbilical vein was performed in stages III and IV twin-twin transfusion syndrome (TTTS) patients. In patients with PUVF, the umbilical vein maximum (Vmax) and the umbilical vein minimum velocity (Vmin) and the resistance index for the umbilical vein (UVRI) ⫽ (100 ⫻ [Vmax ⫺ Vmin]/ Vmax) were assessed. RESULTS: PUVF was noted in 130 of 226 stages III and IV TTTS pa-

tients. Digital images were available for analysis in 65 of 130 patients

(50%). The minimum UVRI associated with PUVF was 16% for stages III and IV TTTS. There was a trend for increasing UVRI with stage (P ⫽ .052). Stage IV patients were more likely to have an UVRI greater than 30% (P ⫽ .02). CONCLUSION: PUVF can be defined as an UVRI greater than 15%. A

scale definition of PUVF may further facilitate assessment of the degree of fetal hemodynamic compromise. Key words: fetus, pulsatile, pulsatility, Quintero staging, resistance index, twin-twin transfusion syndrome, umbilical vein

Cite this article as: Russell Z, Quintero RA, Kontopoulos EV. What is the definition of pulsatile umbilical venous flow in twin-twin transfusion syndrome? Am J Obstet Gynecol 2008;199:634.e1-634.e4.

M

ultivessel Doppler ultrasonography is widely used in the surveillance of high-risk pregnancies of different etiology. Its implementation in the antenatal assessment of growth-restricted fetuses has been shown to improve prediction of fetal compromise.1-3 When used in combination with other antenatal assessment modalities, Doppler ultrasound can assist in the appropriate delivery timing and optimization of the perinatal outcome of growth-restricted fetuses.4-9 Similarly, Doppler investigation of fetal vessels has been

From the Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, University of South Florida, Tampa, FL. Presented at the 17th World Congress on Ultrasound in Obstetrics and Gynecology, Florence, Italy, Oct. 7-11, 2007.

proven useful in the evaluation and treatment of fetal diseases associated with hemodynamic circulatory changes of different pathophysiology, such as nonimmune hydrops10, 11 and twin-twin transfusion syndrome (TTTS). In the latter case, Doppler evaluation of select fetal vessels constitutes an essential aspect of the Quintero staging system.12 Reference ranges have been established for the Doppler parameters of the most commonly investigated arterial13-15 and venous fetal vessels.16-21 In particular, pulsatile umbilical venous flow has been associated with congestive heart failure and increased risk for adverse perinatal outcome.22-24 Although the umbilical vein is 1 of the most accessible and widely used sites, the definition of pulsatile umbilical venous flow (PUVF) remains subjective. The aim of this study was to develop an objective definition of PUVF.

Received Sept. 28, 2007; revised Jan. 7, 2008; accepted May 27, 2008. Reprints: Rubén A. Quintero, MD, Department of Obstetrics and Gynecology, University of South Florida, 2A Columbia Drive, #6053, Tampa, FL 33606. [email protected]. 0002-9378/$34.00 © 2008 Mosby, Inc. All rights reserved. doi: 10.1016/j.ajog.2008.05.025

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M ATERIALS AND M ETHODS All patients referred with the presumed diagnosis of TTTS underwent a comprehensive ultrasound examination including pulse Doppler waveform analysis of the umbilical vein as part of the Quintero staging system. Only patients visually di-

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agnosed as having PUVF were included in the study. PUVF was considered to be present if there was an undulating waveform of the umbilical vein coinciding with the systolic phase of the umbilical artery. Patients with TTTS were offered all management alternatives including laser therapy. The protocol for laser therapy was approved by the institutional review board, and all subjects gave written informed consent. Pulsed-wave Doppler ultrasound studies of the fetal circulation were performed with a color Doppler system (Voluson 730, General Electric, Waukesha, WI). The wall motion filter was set at 100 MHz or less. The recordings were performed on a free umbilical vein (UV) loop during fetal apnea. UV pulsations were evaluated prospectively for maximum velocity (Vmax) and minimum velocity (Vmin) with the autotrace function of the ultrasound Doppler software. Offline digital measurements of the Vmax and Vmin were retrospectively performed in patients with suboptimal tracings using a digital caliper commercially available. The relationship between Vmax and Vmin of the umbilical vein was assessed by the resistance index for veins (RIV).

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TABLE

FIGURE 1

Clinical characteristics of patients with pulsatile umbilical-venous flow by stage (n ⴝ 65)

Stage III pulsatile umbilical flow

Stage III

Stage IV

P value

Mean gestational age at ultrasound (wks)

19.5

20.5

.704a

Mean gestational age at delivery (wks)

32.8

30.6

.046

At least 1 fetus surviving (%)

93.75

93.3

.694

Median UVRI

25

31

.052

UVRI ⬎ 30%

36

68

.02

.............................................................................................................................................................................................................................................. b .............................................................................................................................................................................................................................................. c .............................................................................................................................................................................................................................................. b .............................................................................................................................................................................................................................................. d .............................................................................................................................................................................................................................................. c

Double pulsation

1/49

4/16

.01

.............................................................................................................................................................................................................................................. a

Student t test. Mann-Whitney U test. Fisher’s exact test. ␹ test. b

c

d

2

..............................................................................................................................................................................................................................................

Russell. Definition of pulsatile umbilical venous flow in TTTS. Am J Obstet Gynecol 2008.

The RIV is similar to the resistance index for arteries or the ductus venosus index25 but does not include the terms of systolic and diastolic velocities. The RIV for the umbilical vein (UVRI) was calculated as 100 ⫻ (Vmax ⫺ Vmin)/Vmax, representing the mathematical expression of the UV waveform deflection during 1 cardiac cycle. The minimum UVRI associated with the diagnosis of PUVF was recorded. To determine whether the degree of UV pulsation was affected by disease severity, the UVRI was analyzed by stage. Statistical analysis was performed with SPSS 15 for Windows (Chicago, IL). All continuous variables were tested for normality using the Kolmogorov-Smirnov test. Student t test or Mann-Whitney U test were used for the comparison of continuous variables. Comparison of proportions was performed with ␹2 or Fisher’s exact test where appropriate. P ⬍ .05 was considered statistically significant.

R ESULTS Two hundred twenty-six stages III and IV TTTS patients were assessed between January 2001 and September 2004. Of these, 130 (57%) were classified as having PUVF. Digital images were available for analysis in 65 of 130 (50%) patients, of which 63 were recipient twins and 2 were donor twins. Sixty of the 65 images were obtained preoperatively (58 recipient twins and 2 donor twins). There were 49 patients with stage III and 16 patients with stage IV TTTS. The Table shows the demographic characteristics of the patient popula-

tion. The minimum UVRI was associated with PUVF was 16% for both stages. There was a trend for increasing UVRI of PUVF by stage: the median UVRI for stage III was 25% (range, 16100%) (Figure 1) vs 31% (range, 16100%) for stage IV (Figure 2, A and B) (P ⫽ .052). Moreover, stage IV patients were more likely to have an UVRI greater than 30% than stage III patients (68.8% vs 36.7%, respectively, P ⫽ .02). Five patients had double umbilical vein pulsations, 4 of which were stage IV. This difference was also statistically significant (P ⫽ .01).

Pulsatile umbilical flow in a stage III TTTS patient showing a UVRI of 16%. Russell. Definition of pulsatile umbilical venous flow in TTTS. Am J Obstet Gynecol 2008.

cordocentesis showed an incidence of 100% hypoxemia and 90.9% acidemia in the PUVF group vs 80% and 47.7%, respectively, in the group with linear umbilical venous flow. Baschat et al8 demonstrated that the addition of venous Doppler measurements in the antenatal assessment of IUGR fetuses improves the specificity of the test. In a study of 74 growth-restricted fetuses, PUVF was FIGURE 2

Stage IV pulsatile umbilical flow

C OMMENT Our data suggest that PUVF can be defined as a UVRI greater than 15%. This value represents the minimum deflection of UV waveform characteristics of the subjective definition of PUVF. The use of a scale definition for PUVF should further facilitate assessment of the degree of hemodynamic compromise in fetuses at risk for congestive heart failure. Indeed, our study showed a trend for increasing UVRI by stage and a greater proportion of fetuses with a UVRI greater than 30% in stage IV. The presence of PUVF in intrauterine growth restricted (IUGR) fetuses is associated with an up to 5-fold increase in perinatal mortality rate.4 In a prospective study by Rizzo et al,7 26 pregnancies complicated by IUGR and absent enddiastolic velocity (AEDV), were divided into 2 groups according to the presence or absence of umbilical vein pulsations. Gas analysis of fetal blood obtained via

Pulsatile umbilical flow in stage IV TTTS patients showing an UVRI of A, 29% and B, 100%. Russell. Definition of pulsatile umbilical venous flow in TTTS. Am J Obstet Gynecol 2008.

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found to be the most sensitive parameter for the prediction of perinatal death.3 Venous Dopplers are also useful in the assessment of fetuses at risk for congestive heart failure.10,11,22 Pulsatile umbilical venous flow is 1 of the criteria used to classify TTTS patients as stage III in the Quintero staging system.12 Other criteria include AREDV in the umbilical artery and reverse flow in the ductus venosus.12 Venous Dopplers are also an integral part of the cardiovascular profile score.24 The fetal inferior vena cava and ductus venosus are characterized by a triphasic waveform consisting of a peak forward velocity during systole (S), peak forward velocity during early diastole (D), and lowest velocity during atrial contraction (a). Several authors have defined the degree of pulsatility for these vessels using indices such as S/D ratio, preload index (a/S), or (S/a).16,18,26,27 In 1993 DeVore and Horenstein25 described the ductus venosus index, which was computed from the Doppler waveform of the ductus venosus at points consistent with ventricular and atrial systole (ventricular systole ⫺ atrial systole)/ ventricular systole). In a cross-sectional study of 143 women with singleton gestation, Hecher et al20 established reference ranges throughout gestation for blood flow velocities and indices of pulsatility in the ductus venosus, inferior vena cava, and right hepatic vein. The authors introduced 2 new indices, the peak velocity index for veins, defined as (S-a)/D, and the pulsatility index for veins, defined as (S-a)/time-averaged maximum velocity (Tmax). The authors found that blood velocities increase with advancing gestational age, whereas the degree of pulsatility decreases.20 Recently Acharya et al published longitudinal data on umbilical vein flow parameters for the second half of the pregnancy.28 Despite significant efforts toward standardization of Doppler indices measurements, the diagnosis of PUVF remains subjective. In all studies up to date, waveforms are considered pulsatile either after visual assessment or when they meet an arbitrarily determined criterion for degree of pulsatility. Nakai et 634.e3

www.AJOG.org al29 defined venous pulsation as a transient decrease in venous flow velocity detected for more than 10 seconds in more than 1 of 3 sampling points. In a population of normal pregnancies, the amplitude of the pulsations was reported to be within one third of the maximum Doppler shift; the minimum amplitude required for detection was not specified.29 Van Splunder et al30 studied the Doppler flow velocity waveforms in 50 women with small-for-gestational-age fetuses. Extraabdominal UV pulsations were defined as at least 3 consecutive negative deflections of the waveform, synchronous to the fetal heart rate, each comprising at least 10% of the time averaged velocity.30 In more recent studies, UV pulsations were defined as a diastolic decrease in velocity greater than 15% of the baseline maximum velocity.31,32 Skulstad et al33 assessed pulsatility both visually (present or absent) and by the temporal maximum velocity tracing of the Doppler. The degree of pulsation was calculated as the difference between the Vmax and the Vmin or as the pulsatility index.33 PUVF can occasionally be observed in normal pregnancies with uncompromised fetuses. Rizzo et al34 reported the presence of UV pulsations up to 8 weeks’ gestation and their gradual disappearance between 9 and 12 weeks’ gestational age. Other authors observed them up to 15 weeks.35 Van Splunder et al36 documented the presence of UV pulsations between 34 and 38 weeks in 19.6% of measurements in a free-floating loop of the cord. However, they reported a limited reproducibility of the observation expressed by both large intrapatient coefficients as well as disagreement between 2 observers.36 Nakai et al also reported UV pulsations in a free-floating cord in normal pregnancies up to 40 weeks’ gestation.29 Potential explanations for the finding of PUVF in normal and pathologic pregnancies include contiguous transmission of the arterial pulse through the walls of the umbilical cord or lack of standardization of the definition of PUVF. Hypoxia,37elevated venous pressure,38 increased afterload, and augmented atrial contractions39,40 have been implicated in the pathogenesis of

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PUVF. A mathematical model developed by Hellevik et al41 proposed that PUVF can be explained as a result of decreased UV compliance. In our population, all pregnancies were abnormal, with an advanced degree of TTTS, including hydrops (stage IV), thus the need to develop an objective definition of PUVF. Furthermore, cutoff values for UVRI that could differentiate physiologic from pathologic states may be derived. Our study was limited by unavailability of digital images for review in 50% of the patients. In addition, whereas all patients had pathologic pregnancies, there is no gold standard that can be used in utero against which to assess the diagnosis of PUVF. Nonetheless, the data seem reliable in that the minimum UVRI was the same for both groups and that stage IV patients were more likely to have an UVRI greater than 30%. In conclusion, our data suggest that PUVF can be defined as an UVRI of greater than 15%. This definition should assist in the evaluation of fetuses at risk for congestive heart failure or hypoxia including TTTS, IUGR, and other fetal conditions associated with hemodynamic compromise. Further studies are warranted to corroborate whether the minimum value of UVRI found in our study for the definition of PUVF is also present in other series. The use of a scale definition should also facilitate comparisons of the degree of hemodynamic fetal compromise among differf ent populations. ACKNOWLEDGMENT We thank Patricia Bornick, RN, MSN, for her invaluable assistance with this manuscript.

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