Reference ranges for uterine artery mean pulsatility index at weeks of gestation

Transcription

1 Ultrasound Obstet Gynecol 2008; 32: Published online 6 May 2008 in Wiley InterScience ( DOI: /uog.5315 Reference ranges for uterine artery mean pulsatility index at weeks of gestation O. GÓMEZ, F. FIGUERAS, S. FERNÁNDEZ, M. BENNASAR, J. M. MARTÍNEZ,B.PUERTO and E. GRATACÓS Fetal Growth and Pre-eclampsia Unit, Department of Maternal Fetal Medicine, ICGON, Hospital Clínic, University of Barcelona and Center for Biomedical Research on Rare Diseases (CIBERER), Barcelona, Spain KEYWORDS: Doppler ultrasonography parameters; pulsatility index; uterine arteries ABSTRACT Objectives To construct gestational age (GA)-based reference ranges for the uterine artery (UtA) mean pulsatility index (PI) at weeks of pregnancy. Methods A prospective cross-sectional observational study was carried out of 20 consecutive singleton pregnancies for each completed gestational week at weeks. UtAs were examined by color and pulsed Doppler imaging, and the mean PI, as well as the presence or absence of a bilateral protodiastolic notch, were recorded. Polynomials were fitted by means of leastsquare regression to estimate the relationship between the mean UtA-PI and GA. Results A total of 620 women were included. A seconddegree polynomial (Log e mean UtA-PI = GA + GA , with GA measured in days), after a natural logarithmic transformation, was selected to model our data. There was a significant decrease in the mean UtA-PI between 11 weeks (mean PI, 1.79; 95 th centile, 2.70) and 34 weeks (mean PI, 0.70; 95 th centile, 0.99). It then became more stable up until 41 weeks (mean PI, 0.65; 95 th centile, 0.89). Conclusions The mean UtA-PI shows a progressive decrease until the late stages of pregnancy. Reference ranges for mean UtA-PI may have clinical value in screening for placenta-associated diseases in the early stages of pregnancy, and in evaluating patients with pregnancy-induced hypertension and/or small-forgestational age fetuses during the third trimester. Copyright 2008 ISUOG. Published by John Wiley & Sons, Ltd. INTRODUCTION Uterine artery (UtA) Doppler ultrasound examination has become a valuable method for indirectly assessing uteroplacental circulation from early gestation 1 and has been considered as a potential screening tool for the development of pre-eclampsia, fetal growth restriction, placental abruption and stillbirth Another recent area of application is the prognostic value of UtA Doppler velocimetry in patients with pregnancyinduced hypertension and/or in small-for-gestational age (SGA) fetuses The finding of an abnormal UtA Doppler pattern in these high-risk pregnancies strongly correlates with an adverse maternal and/or perinatal outcome 12 15,17,18. The clinical use of UtA Doppler ultrasound imaging requires the existence of reference values, but no such ranges exist despite the common use of UtA Doppler examination during pregnancy. Pulsatility index (PI) is currently the most commonly used index for the evaluation of UtA Doppler waveform patterns. However, previously published studies on UtA Doppler evaluation throughout pregnancy have used a variety of Doppler indices 3,5,6,10,12,14,15,17,19 22 or scoring systems 13,16,18. Gestational age (GA)-based reference ranges for the mean UtA-PI between 11 and 41 weeks of gestation have not been reported previously following validated methodological guidelines 23,24. The purpose of this study was to derive normative new GA-based reference ranges for the mean UtA-PI at weeks of pregnancy in an appropriately selected population. METHODS A cross-sectional study was carried out of 20 consecutive singleton pregnancies for each completed gestational week at weeks. Most of the women included in the study were undergoing routine scans at 11 14, and weeks. We also included early and late bookers, and healthy women participating in other Correspondence to: Dr O. Gómez, Department of Maternal Fetal Medicine, Institut Clinic de Ginecologia, Obstetricia i Neonatologia, Hospital Clínic, c/sabino de Arana 1, Barcelona, Spain ( ogomez@clinic.ub.es) Accepted: 18 January 2008 Copyright 2008 ISUOG. Published by John Wiley & Sons, Ltd. ORIGINAL PAPER

2 Reference ranges for uterine artery Doppler PI 129 research projects. Inclusion criteria were: GA determined before 22 weeks (crown rump length between 11 and 14 weeks 25, and biparietal diameter between 14 and 22 weeks 26 ); absence of risk factors for vascular disease, including pregestational diabetes, immune disease and renal disease; normal fetal growth (> 10 th and < 90 th centile on growth curves according to local standards) 27 ; absence of treatment with aspirin or heparin before enrollment; and normal umbilical artery Doppler pattern at the time of recruitment in pregnancies at > 24 weeks 28. Fetuses with chromosomal or structural abnormalities were excluded from the study. The research protocol was approved by the local ethics committee and all subjects gave their informed consent. UtA Doppler examinations were performed using an Aspen (Siemens Acuson Inc., Mountain View, CA, USA) or a Voluson 730 Pro (GE Healthcare Technologies, Milwaukee, WI, USA) ultrasound machine, both equipped with multifrequency transvaginal and transabdominal transducers. Examinations were carried out by a number of experienced observers. Data were entered into a computer database. In ultrasound examinations performed on pregnancies at weeks a transvaginal transducer was used to obtain a sagittal section of the cervix. The probe was moved laterally until the paracervical vascular plexus was seen. Color Doppler imaging was used to identify the UtA at the level of the cervicocorporeal junction. Measurements were taken at this point before branching of the UtAs into the arcuate arteries. Pregnancies at weeks were examined transabdominally. The probe was placed on the lower quadrant of the abdomen, angled medially, and again color Doppler imaging was used to identify the UtA at the apparent crossover with the external iliac artery. Measurements were taken approximately 1 cm distal to the crossover point. In all cases, once it had been ensured that the angle was less than 30, the pulsed Doppler gate was placed over the whole width of the vessel. Angle correction was then applied and the signal updated until three similar consecutive waveforms had been obtained. The PI of the left and right arteries was measured, and the mean PI was calculated (Figure 1). The presence or absence of a bilateral early protodiastolic notch was noted. A notch was defined as a persistent decrease in blood flow velocity in early diastole, below the diastolic peak velocity. Umbilical artery PI was measured using standard methodology 28. Statistical analysis We used the statistical method described by Royston and Wright to estimate reference intervals 23. In summary, polynomials were fitted by means of least-square regression to estimate the relationship between mean PI and GA. The best fitting model was selected on the basis of the residual SD. Z-scores (measurement mean/sd) were calculated for assessing model fit. Normal distribution of the Z-scores was checked with the Shapiro Francia W- test, and a natural logarithmic transformation of the data was used if appropriate. The SD was also modeled by GA Figure 1 Right (a) and left (b) uterine arteries (UtA) visualized by transabdominal color flow mapping and Doppler velocity waveforms at 38 weeks (mean UtA-PI, 0.64; absence of bilateral protodiastolic notch). from the scaled residuals. Equations of the polynomial regression curves were used to calculate the mean, and 5 th and 95 th centiles for each GA (centiles = estimated mean ± SD). The adjusted correlation between mean UtA-PI and umbilical artery PI was calculated by means of multiple linear regression. Statistical procedures were performed using SPSS version 11.5 (SPSS Inc., Chicago, IL, USA). RESULTS The study population was recruited between January 2002 and December 2004 and comprised 620 women who met all of the inclusion criteria. Clinical characteristics and pregnancy outcomes of these women are shown in Table 1. The prevalence of bilateral notching was 46.3% (37/80 women) between 11 and 14 weeks, 16.5% (33/200 women) between 15 and 24 weeks, and 5% (17/340 women) between 25 and 41 weeks. The latter group included five cases between 25 and 28 weeks, four cases between 28 and 32 weeks, and eight cases between 32 and41weeks(figure2).

3 130 Gómez et al. Table 1 Demographic characteristics and pregnancy outcome of 620 women included in the study Variable Value Maternal age (years, mean ± SD) 30.2 ± 6.11 Ethnicity (%) White 85.3 Black 0.8 Other 15.9 Nulliparous (%) 63 Cigarette smoking > 5/day (%) 17.8 Pregnancy outcome GA at delivery (weeks, mean ± SD) 39.2 ± 2.05 Birth weight at delivery (g, mean ± SD) 3221 ± 513 Umbilical artery ph at delivery (mean ± SD) 7.24 ± 0.07 Umbilical vein ph at delivery (mean ± SD) 7.31 ± 0.06 Gestational hypertension (n (%)) 8 (1.29) Pre-eclampsia (n (%)) 8 (1.29) Birth weight at delivery < 10 th centile (n (%)) 57 (9.19) Preterm delivery (GA < 34 weeks) (n (%)) 16 (2.58) GA, gestational age. Mean PI Gestational age (weeks) Figure 3 Scatterplot of the mean uterine artery pulsatility index (PI) measured by transvaginal ( ) and transabdominal ( ž) ultrasound examination vs. gestational age in our population. Estimated 5 th, 50 th and 95 th centiles are shown. Table 2 Reference intervals for mean uterine artery pulsatility index Presence/absence of notch (%) Gestational age (weeks) Figure 2 Prevalence of bilateral notching ( ) or absence of notch ( ) throughout gestation. Transvaginal and transabdominal ultrasound examinations were performed on pregnancies at weeks and weeks, respectively. When adjusted for GA (by means of linear regression), a significant correlation was found between umbilical artery PI and mean UtA-PI (r = 0.32, P < 0.001). A second-degree polynomial, after natural logarithmic transformation, describing the relationship between mean UtA-PI and GA in days (Log e mean UtA-PI = GA + GA ) resulted in the lowest residual SD (0.256), and was therefore chosen to model our data. According to this model, mean UtA-PI shows a progressive decline from 11 to 34 weeks, and then remains stable until 41 weeks. The SD of log e mean UtA-PI was found to fit linearly with GA measured in days (SD Log e mean UtA-PI = GA ). The Z-scores were normally distributed (Shapiro Francia W = 0.985, P = 0.1). Figure 3 shows a scatterplot of observed mean UtA-PI values against GA, along with calculated reference intervals, which are tabulated in Table 2. GA (weeks) 5 th centile 50 th centile 95 th centile Transvaginal and transabdominal ultrasound examinations were performed on pregnancies at weeks and weeks, respectively. GA, gestational age. DISCUSSION This study describes new GA-based reference ranges of mean UtA-PI between 11 and 41 weeks of gestation in an

4 Reference ranges for uterine artery Doppler PI 131 appropriate large sample of pregnant women. Various Doppler indices 3,5,6,10,12,14,15,17,19 22, including some scoring systems 13,16,18, have been described for evaluation of the UtA velocity waveform during pregnancy. The PI and resistance index, alone or in combination with the presence of an early diastolic notch, have been the most commonly used indices. However, recent large studies on UtA Doppler imaging during pregnancy have uniformly used the PI 5,9,10. Consequently, we evaluated the distribution of UtA-PI measurements instead of the resistance index. The PI describes the shape of the velocity waveform much better, as it includes the area below the curve in the formula. Likewise and for this reason, the PI index indirectly informs about the presence or absence of a protodiastolic notch. Although a previous large study used the transabdominal route to perform the UtA Doppler examination at weeks 5, we routinely use the transvaginal approach for the week scan 1. It offers several advantages for UtA Doppler evaluation: the probe is located closer to the UtA, the angle of insonation is usually closer to 0 and the waveforms obtained have better definition. However, previous data have shown that UtA-PI values and prevalence of bilateral notching are significantly lower when recorded transabdominally 29,30. It is possible, therefore, that at least some of the decrease found in the mean UtA-PI and the prevalence of bilateral notching between the first and second trimesters might be due to the different routes used (Table 2 and Figure 2). We have followed stringent and validated methodological guidelines to construct these reference ranges 23,24. In particular, we did not exclude individuals on the basis of information that was not available at the time of measurement, such as birth weight, GA at delivery and perinatal outcome. A cross-sectional design was used as such studies are easier to perform and to combine with clinical practice. We included the same number of observations at each week of gestation (20 patients for each week between 11 and 41 weeks gestation). Finally, our data were collected by several operators, reflecting the measurements used in clinical practice and improving the external validity. The good interobserver reproducibility noted in a previous study by our group 31 suggests that mean UtA-PI is a reliable parameter in a clinical setting. UtA Doppler examination provides important information on the conversion process of spiral arteries into uteroplacental arteries. Reflecting the underlying process of placentation 1, the UtA resistance indices decline during the first half of pregnancy 3,6. However, there are few data regarding the normal UtA Doppler spectrum during the late second and third trimesters of gestation. This study confirms previous reports 22,32,33 suggesting that mean UtA-PI shows a significant and progressive decline with gestation. Our data also show that, together with the progressive fall in the mean UtA-PI, the prevalence of bilateral notching decreases with increasing GA. Interestingly, the decrease in mean UtA-PI continues throughout the third trimester until 34 weeks, although the prevalence of bilateral notch remains almost stable beyond 25 weeks of gestation. This might be explained by several factors. First, one could speculate that trophoblastic invasion proceeds slowly during the late second and third trimesters. Second, important maternal hemodynamic changes, such an increased cardiac output and reduced blood viscosity and peripheral resistance, also take place during late stages of pregnancy 34. Finally, there is a rise in the diameter of the UtA throughout gestation due to the increasing levels of estrogens, which have a vasodilatory effect 35. This study further demonstrates that late stages of pregnancy are characterized by very low impedance indices in the UtA Doppler examination. Aside from the factors discussed above, this may have been influenced by the fact that women with the highest PI values are more likely to deliver early. Early-onset and severe cases, which are characterized by the highest grade of placental ischemia and show the highest UtA resistance indices, will not contribute to the construction of reference ranges in the last stages of pregnancy. In summary, we have presented new mean UtA-PI charts derived from a cross-sectional study in a population of 620 women between 11 and 41 weeks of gestation. These reference ranges may be clinically useful in two different respects: to screen for pre-eclampsia and/or fetal growth restriction in the early stages of pregnancy and to evaluate patients with pregnancy-induced hypertension and/or SGA age fetuses. Further studies in this second group of complicated pregnancies are necessary to confirm the clinical value of an abnormal UtA Doppler pattern as a prognostic tool. REFERENCES 1. Jurkovic D, Jauniaux E, Kurjak A, Hustin J, Campbell S, Nicolaides KH. Transvaginal color Doppler assessment of the uteroplacental circulation in early pregnancy. Obstet Gynecol 1991; 77: van den Elzen HJ, Cohen-Overbeek TE, Grobbee DE, Quartero RW, Wladimiroff JW. Early uterine artery Doppler velocimetry and the outcome of pregnancy in women aged 35 years and older. Ultrasound Obstet Gynecol 1995; 5: Harrington K, Goldfrad C, Carpenter RG, Campbell S. Transvaginal uterine and umbilical artery Doppler examination of weeks and the subsequent development of pre-eclampsia and intrauterine growth retardation. Ultrasound Obstet Gynecol 1997; 9: Harrington K, Carpenter RG, Goldfrad C, Campbell S. Transvaginal Doppler ultrasound of the uteroplacental circulation in the early prediction of pre-eclampsia and intrauterine growth retardation. BrJObstetGynaecol1997; 104: Martin AM, Bindra R, Curcio P, Cicero S, Nicolaides KH. Screening for pre-eclampsia and fetal growth restriction by uterine artery Doppler at weeks of gestation. Ultrasound Obstet Gynecol 2001; 18: Gómez O, Martínez J, Figueras F, del Río M, Borobio V, Puerto B, Coll O, Cararach V, Vanrell JA. Uterine artery Doppler at weeks of gestation to screen for hypertensive disorders and associated complications in an unselected population. Ultrasound Obstet Gynecol 2005; 26:

5 132 Gómez et al. 7. Harrington K, Cooper D, Lees C, Hecher K, Campbell S. Doppler ultrasound of the uterine arteries: the importance of bilateral notching in the prediction of pre-eclampsia, placental abruption or delivery of a small-for-gestational-age baby. Ultrasound Obstet Gynecol 1996; 7: Kurdi W, Campbell S, Aquilina J, England P, Harrington K. The role of color Doppler imaging of the uterine arteries at 20 weeks gestation in stratifying antenatal care. Ultrasound Obstet Gynecol 1998; 12: Albaiges G, Missfelder-Lobos H, Lees C, Parra M, Nicolaides KH. One-stage screening for pregnancy complications by color Doppler assessment of the uterine arteries at 23 weeks gestation. Obstet Gynecol 2000; 96: Papageorghiou AT, Yu CK, Bindra R, Pandis G, Nicolaides KH. Multicenter screening for pre-eclampsia and fetal growth restriction by transvaginal uterine artery Doppler at 23 weeks of gestation. Ultrasound Obstet Gynecol 2001; 18: Becker R, Vonk R, Vollert W, Entezami M. Doppler sonography of uterine arteries at weeks: risk assessment of adverse pregnancy outcome by quantification of impedance and notch. JPerinatMed2002; 30: Hofstaetter C, Dubiel M, Gudmundsson S, Marsal K. Uterine artery color Doppler assisted velocimetry and perinatal outcome. Acta Obstet Gynecol Scand 1996; 75: Hernandez-Andrade E, Brodszki J, Lingman G, Gudmundsson S, Molin J, Marsál K. Uterine artery score and perinatal outcome. Ultrasound Obstet Gynecol 2002; 19: Vergani P, Roncaglia N, Andreotti C, Arreghini A, Teruzzi M, Pezzullo JC, Ghidini A. Prognostic value of uterine artery Doppler velocimetry in growth-restricted fetuses delivered near term. Am J Obstet Gynecol 2002; 187: Frusca T, Soregaroli M, Platto C, Enterri L, Lojacono A, Valcamonico A. Uterine artery velocimetry in patients with gestational hypertension. Obstet Gynecol 2003; 102: Sekizuka N, Hasewaba I, Takakuwa K, Tanaka K. Scoring of uterine artery flow velocity waveforms in the assessment of fetal growth restriction and/or pregnancy-induced hypertension. J Matern Fetal Invest 1997; 7: Severi FM, Bocchi C, Visentin A, Falco P, Cobellis L, Florio P, Zagonari S, Pilu G. Uterine and fetal cerebral Doppler predict the outcome of third-trimester small-for-gestational age fetuses with normal umbilical artery Doppler. Ultrasound Obstet Gynecol 2002; 19: Gudmundsson S, Korszun P, Olofsson P, Dubiel M. New score indicating placental vascular resistance. Acta Obstet Gynecol Scand 2003; 82: Joern H, Funk A, Goetz M, Kuehlwein H, Klein A, Fendel H. Development of quantitative Doppler indices for uteroplacental and fetal blood flow during the third trimester. Ultrasound Med Biol 1996; 22: Joern H, Rath W. Comparison of Doppler sonographic examinations of the umbilical and uterine arteries in high-risk pregnancies. Fetal Diagn Ther 1998; 13: Park YW, Cho JS, Choi HM, Kim TY, Lee SH, Yu JK, Kim JW. Clinical significance of early diastolic notch depth: uterine artery Doppler velocimetry in the third trimester. Am J Obstet Gynecol 2000; 182: Murakoshi T, Sekizuka N, Takakuwa K, Yoshizawa H, Tanaka K. Uterine and spiral artery flow velocity waveforms in pregnancy-induced hypertension and/or intrauterine growth retardation. Ultrasound Obstet Gynecol 1996; 7: Royston P, Wright EM. How to construct normal ranges for fetal variables. Ultrasound Obstet Gynecol 1998; 11: Altman DG, Chitty LS. Charts of fetal size: 1. Methodology. Br J Obstet Gynaecol 1994; 101: Robinson HP, Fleming JE. A critical evaluation of sonar crown rump length measurements. Br J Obstet Gynaecol 1975; 82: Mul T, Mongelli M, Gardosi J. A comparative analysis of second-trimester ultrasound dating formulae in pregnancies conceived with artificial reproductive techniques. Ultrasound Obstet Gynecol 1996; 8: Figueras F, Torrents M, Muñoz A, Comas C, Antolín E, Echevarría M, Mallafré J, Carrera JM. References intervals for fetal biometrical parameters. Eur J Obstet Gynecol Reprod Biol 2002; 105: Arduini D, Rizzo G. Normal values of pulsatility index from fetal vessels: a cross-sectional study on 1556 healthy fetuses. J Perinat Med 1990; 18: Steer CV, Williams J, Zaidi J, Campbell S, Tan SL. Intraobserver, interobserver, interultrasound transducer and intercycle variation in colour Doppler assessment of uterine artery impedance. Hum Reprod 1995; 10: Jaffa AJ, Weissman A, Har-Toov J, Shoham Z, Peyser RM. Flow velocity waveforms of the uterine artery in pregnancy: transvaginal versus transabdominal approach. Gynecol Obstet Invest 1995; 40: Gómez O, Figueras F, Martínez JM, del Río M, Palacio M, Eixarch E, Puerto B, Coll O, Cararach V, Vanrell JA. Sequential changes in uterine artery blood flow pattern between the first and second trimesters of gestation in relation to pregnancy outcome. Ultrasound Obstet Gynecol 2006; 28: Bower S, Vyas S, Campbell S, Nicolaides KH. Color Doppler imaging of the uterine artery in pregnancy: normal ranges of impedance to blood flow, mean velocity and volume of flow. Ultrasound Obstet Gynecol 1992; 2: Kurmanavicius J, Florio I, Wisser J, Hebisch G, Zimmermann R, Müller R, Huch R, Huch A. Reference resistance indices of the umbilical, fetal middle cerebral and uterine arteries at weeks of gestation. Ultrasound Obstet Gynecol 1997; 10: Lees MM, Taylor SH, Scott DB, Kerr MG. A study of cardiac output at rest throughout pregnancy. J Obstet Gynaecol Br Commonw 1967; 74: Killam AP, Rosenfeld CR, Battaglia FC, Makowski EL, Meschia G. Effect of estrogens on the uterine blood flow of oophorectomized ewes. Am J Obstet Gynecol 1973; 115: