Umbilical artery Doppler velocimetry in fetuses with a single umbilical artery

Umbilical Artery Doppler Velocimetry in Fetuses With a Single Umbilical Artery BARBARA ULM, MD, MARTIN R. ULM, MD, JOSEF DEUTINGER, MD, AND GERHARD BERNASCHEK, MD Objective: Doppler waveform analysis of the umbilical artery is an important tool for the evaluation of high-risk pregnancies. Yet, available data are based on normal values from three-vessel umbilical cords. Our purpose was to evaluate the value of umbilical artery Doppler velocimetry in fetuses with a single umbilical artery. Methods: One hundred thirteen consecutive singleton fetuses with a single umbilical artery between 16 and 40 weeks' gestational age were studied prospectively at a tertiary referral center for prenatal diagnosis and therapy. Complete follow-up was obtained from 103 cases. Results: The systolic-diastolic ratio in the umbilical artery was abnormal in 31 fetuses (30%) and normal in 72 fetuses (70%). Fetuses with abnormal Doppler waveform analysis in the umbilical artery were significantly more likely to be growth restricted (55 compared with 15%), to have complex malformations (58 compared with 1%) or an abnormal karyotype (29 compared with 0%), or not to survive the fetal/ perinatal period (42 compared with 0%) than those with normal Doppler waveform analysis. Conclusion: Fetuses with a single umbilical artery and abnormal umbilical Doppler velocimetry had a significantly increased risk of adverse fetal and neonatal outcome compared with those with a single umbilical artery but normal Doppler studies. (Obstet Gynecol 1997;90:205-9. © 1997 by The American College of Obstetricians and Gynecologists.)

A single umbilical artery is present in one of 150-200 pregnancies, with a high prevalence of additional fetal malformations, chromosomal anomalies, fetal growth restriction, and prematurity. 1-3 Increased fetal and neonatal morbidity and mortality have been observed even in cases of isolated single umbilical artery. 4'5 The clinical significance of Doppler velocimetry in the surveillance of fetuses at risk for unfavorable outcome is well recognized. 6-s Previous reports on umbilical artery Doppler velocimetry in fetuses with a single umbilical artery, including a total of 43 selected cases, From the Department of Obstetrics and Gynecology, Division of Prenatal Diagnosis and Therapy, Vienna, Austria.

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however, failed to show any correlation of Doppler ultrasonography with fetal outcome. 9-11 The aim of this investigation was to evaluate the value of umbilical Doppler velocimetry in a series of 113 consecutive fetuses with a single umbilical artery, including cases with an isolated single umbilical artery, single or multiple additional malformations, fetal aneuploidy, and fetal growth restriction.

Materials and Methods Between April 1, 1994, and December 31, 1995, 113 consecutive singleton fetuses with a single umbilical artery were studied prospectively. Two-dimensional and Doppler ultrasonographic examinations were performed by using Toshiba SSA-270A ultrasound equipment (Toshiba Medical Systems, Wiener Neudorf, Austria) with a 3.75-MHz curved array transducer. Gestational age was based on maternal menstrual dating and ultrasonography in the first trimester. A single umbilical artery was diagnosed by visualizing only two vessels on a cross-section of a free loop of the umbilical cord. We used color flow Doppler imaging of the cord insertion if there was any uncertainty. After detailed sonography, we categorized the fetuses as having no additional anomalies ("isolated single umbilical artery"), one additional anomaly, or complex abnormalities, defined as the presence of anomalies in more than one organ system, excluding the two-vessel umbilical cord. Fetal growth restriction was judged to be present if the biometric data were below the tenth percentile at the time of study. Preterm delivery was defined as delivery before 36 completed weeks of gestation. After identification of a single umbilical artery, Doppler velocimetry was performed. Umbilical artery flow velocity waveforms were obtained from a freefloating loop of the umbilical cord in periods of fetal apnea and lack of fetal movement. Measurements were performed using an angle of between 30 and 60 degrees

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b e t w e e n the Doppler b e a m and the umbilical artery. W h e n three to four Doppler w a v e f o r m s with g o o d quality (identical shape and density) h a d been obtained, w e calculated the systolic-diastolic ratio (S/D). T h r o u g h 30 completed w e e k s ' gestation, an umbilical artery S / D greater than 4 w a s considered abnormal; after 30 completed w e e k s ' gestation, an S / D greater than 3 w a s considered a b n o r m a l (which is in keeping with current practice in our fetal assessment unit; simplified n o m o grams from three-vessel umbilical cords12'13). We p e r f o r m e d prenatal k a r y o t y p i n g in 82 of 103 fetuses: b y amniocentesis in ten cases, b y placental p u n c t u r e in 28 cases, and b y funipuncture in 44 cases. In the 21 remaining cases, k a r y o t y p i n g w a s not performed, for the following reasons: the m o t h e r declined invasive testing in 14; premature labor occurred in four; and the gestational age w a s b e y o n d 36 completed weeks at the time of diagnosis in three. A single umbilical artery was confirmed b y direct or histologic examination of the umbilical cord in each case. All anomalies detected on intrauterine u l t r a s o n o g r a p h y were confirmed postnatally. We p e r f o r m e d statistical analysis b y using the )(2 (Yates correction) a n d the Student t tests, w h e r e appropriate; the probabilities of adverse fetal o u t c o m e variables were estimated b y calculating the relative risks. 14 P < .05 was considered significant.

Results After 113 consecutive fetuses with a single umbilical artery were identified, ten fetuses were lost to followup, and complete data sets were obtained from 103. Initial s o n o g r a m s were obtained for the following indications: routine early-second-trimester a n o m a l y screening in 49; suspicion of single umbilical artery in 15, of other fetal abnormalities in 11, or of fetal g r o w t h restriction in 11 at an outside institution; a b n o r m a l amniotic fluid v o l u m e in six; previous offspring with malformations a n d / o r a b n o r m a l k a r y o t y p e in five; and suspected red blood cell alloimmunization in two. The reason for the initial scan was u n k n o w n in four cases. The S / D in the umbilical artery at the time of diagnosis was a b n o r m a l in 31 fetuses (30%) and n o r m a l in 72 fetuses (70%). Table 1 depicts clinical characteristics of the two s t u d y groups. Gestational age at diagnosis was 1 6 - 4 0 weeks (mean -+- s t a n d a r d deviation: 21.4 + 5.4 weeks), with 72 cases (70%) being discovered before or at 26 weeks' gestation and 31 cases (30%) being discovered after 26 weeks' gestation. The m e a n gestational age at birth w a s 37.8 -+ 1.7 weeks, and the m e a n birth weight was 2681 + 599 g. The associations of Doppler w a v e f o r m analysis with fetal and neonatal variables are s h o w n in Table 2.

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Table 1. Clinical Characteristics of Pregnancies Complicated by a Single Umbilical Artery With Abnormal and Normal Umbilical Artery Doppler Velocimetry Abnormal Doppler (n = 31) Maternal age (y) Cigarette smokers Gestational age at birth (wk) Birth weight (g)

24.8 ± 3.4 [18-36] 4 (13%) 36.2 ± 3.1 [28-42] 2191 +_712 [900-3290]

Normal Doppler (n = 72) 24.2 ± 3.2 [19-37] 12 (16%) 38.6 ± 2.0 [32-42] 2879 -+ 639 [1100-4550]

.2 .3 < .001 < .001

Data are presented as mean ± standard deviation [range] or n (%}.

Fetuses with a b n o r m a l D o p p l e r velocimetry in the single umbilical artery were significantly more likely to be g r o w t h restricted, to have complex malformations or an a b n o r m a l karyotype, or to be delivered preterm. Table 3 s u m m a r i z e s predictive values for a b n o r m a l umbilical artery Doppler studies in the s t u d y p o p u l a tion. In 74 fetuses (72%), a single umbilical artery was the only a n o m a l y detected b y ultrasonography. Eleven of these fetuses (15%) h a d abnormally high S/Ds. Seventeen fetuses (23%) were g r o w t h restricted (7/11 with a b n o r m a l and 10/63 with n o r m a l umbilical Doppler velocimetry). In fetuses with an isolated single umbilical artery, m e a n gestational age at delivery w a s 39,0 +2.1 weeks, and 21 infants (28%) were b o r n p r e m a t u r e l y (6/11 with abnormal and 15/63 with n o r m a l Doppler results). Prenatal k a r y o t y p i n g was p e r f o r m e d in 60 fetuses with an isolated single umbilical artery (81%), and all h a d a n o r m a l k a r y o t y p e (all 74 infants were phenotypically n o r m a l at birth). There were no fetal or neonatal deaths in the g r o u p with isolated single u m bilical artery.

Table 2. Association of Doppler Velocirnetry in the Umbilical Artery with Adverse Fetal and Neonatal Outcome in 103 Fetuses With a Single Umbilical Artery Abnormal Normal Doppler Doppler (n = 31) (n = 72) Fetal growth restriction Associated structural anomalies Absent One anomaly Complex anomalies Aneuploidy Preterm delivery (only survivors) Perinatal mortality RR = relative risk; CI

RR (95%CI)

P

17 (55%) 11 (15%) 3.6 (1.9,6.7)

< .001

11 (35%) 63 (88%) 0.4 (0.3, 0.7) 2 (6%) 8 (11%) 0.6 (0.1, 2.6) 18 (58%) 1 (1%) 41.8(5.8, 299.5) 9 (29%) 0 13 (72%) 19 (26%) 2.7 (1.7,4.4)

< .001 .3 < .001 < .001 < .001

13 (42%) 0 = confidence interval.

< .001

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Table 3. Predictive Values for Abnormal Umbilical Artery Doppler Velocimetry in Fetuses With a Single Umbilical Artery Sensitivity Specificity All fetuses with a single umbilical artery (n = 103) Fetal growth restriction Aneuploidy Preterm delivery (only survivors) Perinatal mortality Fetuses with an isolated single umbilical artery (n = 74) Fetal growth restriction Preterm delivery

PPV

NPV

81.3 76.6 91.4

54.8 29.0 72.2

84.7 100 73.6

80.0

41.9

100

93.0 90.6

63.6 54.5

(%)

(%)

60.7 100 40.6 100

41.2 28.6

(%)

(%)

84.1 76.2

PPV = positive predictive value; NPV = negative predictive value.

One additional congenital anomaly was present in each of ten of 103 fetuses with a single umbilical artery, and another 19 had complex malformations. The anomalies included cardiac defect in ten, hydrocephaly in six, bilateral hydronephrosis in five, dysmelia in four, renal dysplasia in three, facial cleft in three, diaphragmatic defect in three (hernia in two, aplasia in one), microcephaly in two, Dandy-Walker malformation in two, spina bifida in two, hypotelorism in one, arrhinia in one, hygroma colli in one, unilateral pulmonary hypoplasia in one, duodenal atresia in one, gastroschisis in one, ovarian cyst in one, sinus urogenitalis in one, and club feet in one. Eleven of the 29 fetuses with structural anomalies were growth restricted (38%; ten had an abnormal S/D). Cytogenetic abnormalities were found in nine of 103 fetuses (9%), all with additional malformations: three with trisomy 18, two with trisomy 13, two with triploidy, one with 46,XX, del (15)(q25-qter), and one with 45,X/46,X,i(Xq) mosaicism. All aneuploid fetuses had highly abnormal S/Ds (mean 6.9; four with absent or reversed end diastolic velocities). There were no fetal or neonatal deaths among the fetuses with normal umbilical Doppler velocimetry. Perinatal mortality in the group with abnormal umbilical Doppler velocimetry was 42%, including nine terminations of pregnancy (five cytogenetically abnormal and four with complex malformations), two stillbirths, and two early neonatal deaths (all cytogenetically abnormal).

Discussion Three theories for the pathogenesis of a single umbilical artery have been advanced: agenesis of one umbilical artery, secondary atrophy of one of the previously normal umbilical arteries, and persistence of the allan-

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toic artery. Primary agenesis of one umbilical artery between the 13th and the 17th day of gestation and persistence of the allantoic artery seem to be incompatible with a very common and often isolated congenital abnormality. Evidence suggests that secondary atrophy of one previously normal artery is the most common underlying mechanism: remnants of a secondary artery have been identified histologically in the umbilical cord of many cases with a single umbilical artery. This report represents a large prospective series of umbilical artery Doppler velocimetry in pregnancies with a single umbilical artery identified prenatally. Abnormal Doppler findings were associated significantly with fetal growth restriction, presence of complex malformations, aneuploidy, preterm delivery, and perinatal mortality. On the other hand, normal Doppler scores indicated a relatively good prognosis, in particular, a low risk of fetal aneuploidy or perinatal mortality. The association of a single umbilical artery with a high rate of additional fetal malformations and chromosomal abnormalities is well k n o w n . 1"2"5 The significance of prenatal diagnosis of an isolated single umbilical artery in otherwise normal pregnancies is less clear, with several reports indicating an increased fetal and perinatal risk, even in the absence of additional anomalies, 3'4 and others suggesting that an isolated single umbilical artery would not adversely affect clinical outcome. 15 In our series, a single umbilical artery was the only anomaly found on sonographic screening in 72% of fetuses; among these, Doppler studies were normal in 85% and abnormal in 15% fetuses, respectively. Although the rates of growth-restricted and preterm infants were higher than expected for a normal population with three-vessel umbilical cords, fetal outcome was satisfactory in every case of an isolated single umbilical artery. These findings would suggest that when the single umbilical artery is an isolated abnormality, and when results of Doppler waveform analyses are normal, the fetus may not be at an increased risk of adverse outcome. On the other hand, when Doppler studies are abnormal, we would recommend referral to a center for prenatal diagnosis and therapy to obtain targeted ultrasonography, including fetal echocardiography, and the option for prenatal karyotyping. The rate of congenital malformations associated with a single umbilical artery was 28% in our series. Higher rates were reported by Catanzarite et al ( 4 9 % ) , 4 Duerbeck et al (38%), l° and Iaccarino et al (50%). 1~ Different rates of concomitant structural defects in fetuses with a single umbilical artery may reflect, in particular, different detection rates of isolated single umbilical arteries. Identification of the number of umbilical arteries is an integral part of our routine screening program, which

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m a y explain the relatively high rate (72%) of fetuses with an isolated single umbilical artery in our study population. Nevertheless, even in a prospective series of patients, data m a y be skewed toward cases in which associated malformations are present. The prevalence of fetal growth restriction was significantly higher in cases with abnormal than with normal umbilical artery flow velocimetry. Twenty-three percent (17 of 74) of fetuses with an isolated single umbilical artery and 38% (11 of 29) of those with malformations were growth restricted. This corresponds well with the data of Catanzarite et al, 4 w h o found fetal growth restriction rates of 18% for fetuses with an isolated single umbilical artery and 32% for infants with structural defects, respectively. In a Doppler study of fetuses with a single umbilical artery, Duerbeck et aP ° report only one case of 13 (8%) with fetal growth restriction, which had normal flow velocity values and no additional anomalies. It is interesting to note that in previous investigations of Doppler velocimetry in fetuses with a single umbilical artery, none of the fetuses with additional structural or chromosomal anomalies had abnormal umbilical Doppler scores. 1°'1~ In our series, however, 20 of 29 malformed fetuses (69%) and all nine aneuploid fetuses had abnormally high S/Ds. Both the gestational age at diagnosis of a single umbilical artery and the time at which Doppler measurements were performed in the previous studies were similar to those in our study. Perinatal mortality was 13%, including nine fetuses with abnormal karyotype and four pregnancy terminations for severe fetal malformations. All infants w h o died in utero or during the perinatal period had abnormal Doppler scores, whereas all those w h o had normal Doppler scores survived. One possible explanation for the observed association of Doppler velocimetry with fetal outcome is that under normal circumstances, the single umbilical artery m a y maintain fetoplacental circulation to a more or less sufficient degree. In cases in which a single umbilical artery is the only fetal abnormality, fetoplacental blood flow might even be increased as a result of lower peripheral resistance due to compensatory arterial dilation. 9 Yet, umbilical Doppler flow patterns become pathologic w h e n additional malformations or chromosomal abnormalities are present. However, further prospective studies are needed to confirm this hypothesis. We assumed that standardized Doppler n o m o g r a m s from three-vessel umbilical cords are applicable to cases with two-vessel umbilical cords. This was not obvious, because both the caliber of the vessel and the structure of the vessel wall contribute to Doppler velocity measurements. In neoplastic vessels, which frequently show a larger radius and fewer muscular fibers in the vessel

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wall than normal vessels, reduced vascular impedance results in increased diastolic blood flow and thus low resistance index values. 16 The transverse diameter of a single umbilical artery is generally larger than that of an umbilical artery in a normal three-vessel cord. 9'17 Furthermore, atrophy of one umbilical artery m a y be associated with structural alterations in the remaining artery. TM In neonates with a single umbilical artery., c o m m o n iliac arteries on the side that participated in the placental circuit showed early atherosclerotic lesions and anomalous arterial compliance. 19 We are not aware of any other large collection of umbilical artery Doppler data in pregnancies with a single umbilical artery. This report shows a close relationship between umbilical artery Doppler velocimetry and fetal and perinatal outcome. Thirty percent of fetuses with a single umbilical artery had abnormal Doppler studies. Accordingly, they had a significantly increased risk of adverse fetal and perinatal outcome. Despite the presence of a single umbilical artery, when the Doppler studies were normal, neonatal outcomes also were normal in the majority of cases. Pregnancies complicated by the presence of a single umbilical artery should be assessed with Doppler velocimetry to enable appropriate counseling of the parents, to enhance early detection of chromosomal abnormalities and additional malformations, and to optimize further obstetric management. Umbilical artery Doppler w a v e f o r m analysis in fetuses with a single umbilical artery appears to be a useful tool to identify high-risk pregnancies with the greatest risk of perinatal morbidity and mortality.

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17. Persutte WH, Lenke RR. Transverse umbilical arterial diameter: Technique for the prenatal diagnosis of single umbilical artery. J Ultrasound Med 1994;13:763-6. 18. Nadasy GL, Monos E, Mohacsi E, Csepli J, Kovach AG. Effect of increased luminal blood flow on the development of the human arterial wall. Comparison of mechanical properties of double and single umbilical arteries in vitro. Blood Vessels 1981;18:139-43. 19. Berry CL, Gosling RG, Laogun AA, Bryan E. Anomalous iliac compliance in children with single umbilical artery. Br Heart J 1976;38:510-5.

A d d r e s s r e p r i n t r e q u e s t s to:

Barbara Ulm, M D Department of Obstetrics and Gynecology Division of Prenatal Diagnosis and Therapy Wtihringer G~irtel 18-20 A-1090 Vienna Austria

Received December4, 1996. Received in revisedform March 11, 1997. Accepted March 19, 1997. Copyright © 1997 by The American College of Obstetricians and Gynecologists. Published by Elsevier Science Inc.

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