Discordant blood flow velocity waveforms in left and right brachial arteries in growth-retarded fetuses

Discordant Blood Flow Velocity Left and Right Brachial Arteries Retarded Fetuses

Waveforms in Growth-

WALDO SEPULVEDA, MD, SARAH BOWER, MD, PETER NICOLAIDIS, MICHAEL DE SWIET, MD, AND NICHOLAS M. FISK, PhD Objective: To determine if the increase in cerebral blood flow (“brain-sparing” effect) with fetal hypoxemia is associated with discordant hemodynamics in the upper extremities. Methods: We studied 12 fetuses with severe growth retardation, absent or reverse end-diastolic blood flow in the umbilical artery, and low pulsatility index (PI) in the middle cerebral artery, and 12 appropriately grown control fetuses with normal fetoplacental Doppler studies. The right and left brachial arteries were identified by high-resolution color Doppler ultrasonography, and the PI was measured in each brachial artery. Results: All growth-retarded fetuses had lower impedance indices in the right than in the left brachial artery (mean API 1.0, 95% confidence interval ICI] 0.7-1.3, P < .OOl). No differences in the brachial artery impedance indices were found in control fetuses matched for gestational age (mean API 0.0, 95% CI -0.2 to 0.2). Conclusions: Left and right brachial artery blood flow velocity waveforms are discordant in fetuses with growth retardation and cerebral vasodilation. Because the right arm receives its blood supply from the same source as the brain (brachiocephalic artery) and given the proximity of the left subclavian artery to the ductus arteriosus, we speculate that this might be the result of increased blood flow into the brachiocephalic circulation and/or functional differences in the distribution of left and right ventricular output within the aortic arch in response to fetal hypoxemia. (Obstet Gynecol

1995,+86:734-S)

It is known from animal studies that fetal hypoxemia is characterized by redistribution of fetal blood flow to maintain flow to vital organs, such as the brain and heart, at the expense of the lungs, kidneys, spleen, gut, From Institute Hospitnl,

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the Centre for Fetnl Care, Royal Postgraduate Medical School, of Obstetrics and Gynaecology, Queen Charlotte’s and Cheha London, United Kingdom; and thy Fetal Medicine Unit, Mitera Hospital, Athms, Greece.

0029-7844/95/$9.50 SSDI 0029-7844(95)00253-N

in

MD,

and carcass.‘-4This “brain-sparing“ effect also occurs in humans, as evidenced by Doppler studies showing decreased downstream resistance and increased blood flow velocity in the cerebral arteries of fetuses shown to be hypoxemic at fetal blood sampling5 and those with increased umbilical artery impedance indices suggestive of hypoxemia.6-‘” Recent human data show that human fingerprint patterns, believed to reflect elevated arterial flow or pressure in utero, differ between the left and right sides, especially in hypertensive adults and those shown at birth to have had impaired fetal growth.‘l Therefore, we speculated that hemodynamic redistribution in growth-retarded fetuses might differentially affect leftand right-sided arterial supply to the upper body. The right subclavian artery arises from the brachiocephalic artery, whose other single branch is the right common carotid, whereas the left arises directly from the aorta separately from the left common carotid (Figure 11.” The right arm thus receives its blood supply from the samesource as the brain, a territory known to undergo vasodilation with increased flow in response to hypoxemia, whereas the left arm blood supply is independent of the cerebral circulation and, therefore, might potentially suffer the same vasoconstrictive effects as other low-priority areas of the body in response to hypoxemia. The aim of this study was to determine if brachial artery flow velocity waveforms differ between the two limbs in fetuses with severe growth retardation.

Materials and Methods During a IO-month period, second-trimester pregnancies with fetal growth retardation, absent or reverse end-diastolic blood flow in the umbilical artery, and low impedance indices in the middle cerebral artery

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RCCA \

IA LCCA

RS\A

Figure 1. Schematic diagram of the fetal aortic arch and its main branches. The right subclavian artery (RSA) and right common carotid artery (RCCA) are branches of the brachiocephalic artery (cur4 arrow). The left subclavian artery (ISA) iq a branch of the aorta (Ao) and therefore independent of the cerebral circulation. LCCA : left common carotid artery.

suggestive of cerebral vasodilation were studied prospectively with high-resolution color Doppler ultrasonography (Acuson 128XP/lO; Acuson, Mountain View, CA). Gestational age was based on certain menstrual dates confirmed by dating ultrasonography before 15 weeks. Fetal growth retardation was defined as an abdominal circumference’” and an estimated fetal weight’” below the fifth percentile for gestational age, and confirmed by a birth weight below the fifth percentile.‘” Absent and reverse end-diastolic blood flow in the umbilical artery were defined as the absence of Doppler shift and the presence of backward flow during diastole, respectively.” Brain-sparing was defined as impedance indices in the middle cerebral artery below the fifth percentile for gestational age.‘O Amniotic fluid (AF) volume was evaluated using the amniotic fluid index (AFI), with oligohydramnios defined as an AFI below the 2.5th percentile for gestational age” and anhydramnios as the absence of AF. A similar number

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of appropriate for gestational age fetuses, matched for gestational age (? 1 week), with normal AF volume and normal Doppler waveforms in the umbilical and middle cerebral arteries comprised the control group. Informed consent was obtained from all patients after review by the local ethics committee. We identified the target vessel by color flow mapping and the corresponding flow velocity waveforms obtained by pulsed-wave Doppler using a 2-mm range gate as follows: 1) umbilical artery, from a free loop of the cord; 2) middle cerebral artery, from the vessel identified in relation to the anterior wing of the sphenoid bone laterally to the circle of Willis; and 3) bra&al artery, at the level of the upper or middle third of the humerus, the left or right sides being carefully identified using the fetal heart, stomach, and gallbladder as landmarks (Figure 2). A high-pass filter of 125 Hz was used. The spatial peak temporal average value for the Doppler transmitting power of the equipment was less than 50 mW/cm’. The impedance index used to measure downstream resistance to flow was the pulsatility index (PI) ([peak systolic velocity minus the lowest diastolic velocityl/mean velocity),‘8 which is the only index that provides quantitative information in vessels with absent or reverse blood flow. For each vessel, the mean value of three consecutive symmetrical waveforms obtained during fetal apnea was used for subsequent analysis. Differences between left and right brachial artery flow velocity waveforms were expressed as 01 (left brachial artery PI minus the right brachial artery PI). Data from Doppler studies of the umbilical and cerebral arteries were used in clinical management decisions; data from the brachial arteries were not made available to the clinicians. Details of pregnancy outcome were obtained by reviewing the medical records or contacting the referring obstetrician. Normality of distribution was checked by histograms and confirmed by normality tests. Student t test for paired and unpaired samples was used as appropriate for comparison between the right and left brachial artery PIs and between groups, with P < .05 considered significant.

Results During the study period, 17 growth-retarded fetuses fulfilled the criteria for the study; five cases were excluded subsequently because of poor recording in one or both brachial arteries or the inability to obtain reproducible waveforms from both brachial arteries. The median gestational age at study in the remaining 12 growth-retarded fetuses was 25 weeks (range 20-28). Pregnancy complications other than fetal growth retardation were present in seven cases, including maternal

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Figure 2. Brachial artery flow velocity waveforms weeks’ gestation.

hypertension (n = 5) and abnormal twin pregnancy (n = 2). All other women were free of medical or obstetric complications. There was absent end-diastolic flow in the umbilical artery in seven cases and reverse flow in the remaining five. Five had normal AF volume, four had oligohydramnios, and three had anhydramnios. Three patients opted for termination of the pregnancy and three fetuses died in utero. Perinatal outcome was poor in the remaining six; median gestational age at delivery was 27 weeks (range 25-31), mean birth weight was 625 g (range 425-845), and two newborns died in the first week of life. In growth-retarded fetuses, the PI in the right brachial artery was always lower than in the left (mean API 1.0, 95% confidence interval [CII 0.7-1.3; P < ,001) (Figure 3). In contrast, in the control group there were no differences between right and left brachial PIs (mean API 0.0, CI -0.2 to 0.2), the brachial artery API being significantly higher in the study group compared with controls (P = .OOl) (Figure 4). The difference in the two groups was attributable to a significant decrease in right brachial artery PI in fetuses with growth retardation compared with controls (mean PI 3.0, CI 2.7-3.3 versus mean PI 3.8, CI 3.4-4.2, respectively; I-’ < .Ol), whereas PIs on the left side were similar (mean PI 4.0 versus mean PI 3.8, respectively; P > .05). In the control group, there was no consistent pattern in relation to right or left side; in seven cases (58%), the right-side brachial artery had a lower PI than the left. There was no

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significant correlation between API and gestational age in either group (R = -0.14 and R = 0.30 in the study and control groups, respectively). However, a significant correlation between API and the PI in the middle cerebral artery was found (R = -0.635, P < .05).

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Fetal Brachial Figure 3. rulsatility in growth-retarded

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index (PI) in the left and right fetal brachial fetuses.

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Figure 4. Fetal brachial artery delta retarded fetuses and in controls. intrauterme growth retardation.

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pulsatility index Lines show the

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(API) in growthmean. IUGlZ =

Discussion This study demonstrates that fetuses with severe growth retardation and Doppler blood flow patterns indicative of hypoxemic brain-sparing have discordant blood flow velocity waveforms in the brachial arteries. Because comparable waveforms in control fetuses were concordant, these findings most likely reflect the effect on fetal circulatory adaptation to hypoxemia of anatomic differences in the origin of arterial supply to the right and left upper limbs. Embryologically, the left subclavian artery arises from the aortic arch distal to the ductus arteriosus, whereas the right, a branch of the brachiocephalic artery, arises proximally.” However, this relationship changes during early fetal growth, such that from about 8 weeks’ gestation, the origin of the left subclavian comes to lie cranial to the insertion of the ductus arteriosus.‘2 Thus, in normal human fetuses, both arms are supplied via the aortic arch with oxygenated blood arising in an anterograde fashion form the left ventricle. However, in the presence of hypoxemia, experimental Doppler studies in fetal sheep” and anecdotal observation of growth-retarded human fetuses’” have shown that flow reverses in the aortic isthmus (ie, between the left subclavian artery and the ductus arteriosus), suggesting that the left subclavian artery is supplied with deoxygenated right ventricular blood ascending in a retrograde fashion from the ductus arteriosus. Therefore, we speculate that discordant blood flow in the fetal arms of hypoxemic fetuses reflects differential origin of left and right ventricular output within the aortic arch. In growth-retarded fetuses, the aortic arch receives oxygenated blood from the umbilical vein, which is

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preferentially streamed within the heart into the left ventricle to supply the coronary arteries, the brachiocephalic artery, and the left carotid artery.12 In contrast, the left subclavian artery’s proximity to the ductus allows it to receive predominantly deoxygenated blood from the right ventricle. However, we do not know if reverse isthmic flow occurred in the fetuses studied here; this technique has yet to be validated in human studies and would seem difficult to document in growth-retarded fetuses with oligohydramnios. Analysis of the results on each side indicates that discordancy between the left and right brachial artery was due to reduced downstream resistance in the right rather than increased downstream resistance in the left. Our failure to demonstrate increased impedance in the left brachial artery is not so surprising, given that femoral artery waveforms in growth-retarded fetuses do not show increased impedance.” In the fetus, femoral and brachial arteries normally have high downstream resistance, and Doppler measurements may not be sufficiently sensitive to detect further increases in vascular impedance. Our finding of a reduction in PI in the right brachial artery of growth-retarded fetuses can be explained by either vasodilation or increased blood flo~~~ to the right arm. The first seems unlikely in that there is no known mechanism by which vascular tone might be affected differentially in the two limbs. In growth-retarded human fetuses, left ventricular cardiac output, which supplies the right brachiocephalic trunk, is known to increase and right ventricular output to decrease.23C24 We did not measure brachial blood flow in this study because of the inherent inaccuracy of angle-dependent compound measurements.” However, we have shown previously that fetuses with single umbilical artery similarly have a reduction in PI in the ipsilateral femoral artery, presumably due to increased flow from the common iliac artery on that side.2” The fact that the API in brachial arteries was higher in those growth-retarded fetuses with lower PIs in the middle cerebral artery also supports a role of increased blood flow through the brachiocephalic artery in the physiopathology of these differences. Fingerprints, which are felt to reflect second-trimester blood flow, are abnormal in hypertensive adults found to have growth retardation in utero; significant differences in fingerprint patterns have been reported between right and left arms.l’ Our finding of differential hemodynamics in the left and right arms suggests a basis for discordant fingerprint patterns, and may have prognostic significance, given the mounting evidence that adult hypertension is initiated in utero and amplified throughout life.”

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17. Moore TR, Cayle JE. The amniotic fluid index in normal human pregnancy. Am J Obstet Gynecol 1990;162:1168-73. 18. Gosling RG, King DH. Ultrasound angiology. In: Marcus AW, Adamson L, eds. Arteries and veins. Edinburgh: Churchill Livingstone, 1975:61-98. 19. Bonnin P, Fouron JC, Teyssier G, Sonesson SE, Skoll A. Quantitative assessment of circulatory changes in the fetal aortic isthmus during progressive increase of resistance to umbilical blood flow. Circulation 1993;88:216-22. 20. Fouron JC, Teyssier G, Shalaby L, Lessard M, van Doesburg NH. Fetal central blood flow alterations in human fetuses with umbilical artery reverse diastolic flow. Am J Perinatol 1993;10:197-207. 21. Mari G. Arterial blood flow velocity waveforms of the pelvis and lower extremities in normal and growth-retarded fetuses. Am J Obstet Gynecol 1991;163:143-51. 22. Spencer JAD, Giussani DA, Moore PJ, Hanson MA. In vitro validation of Doppler indices using blood and water. J Ultrasound Med 1991;10:305-8. W, Chita SK, Chapman MG, Allan LD. Evidence of 23. Al-Ghazali redistribution of cardiac output in asymmetrical growth retardation. Br J Obstet Gynaecol 1989;96:697-704. D. Fetal cardiac function in intrauterine growth 24. Rizzo G, Arduini retardation. Am J Obstet Gynecol 1991;165:876-82. W, Bower S, Flack NJ, Fisk NM. Discordant iliac and 25. Sepulveda femoral artery flow velocity waveforms in fetuses with single umbilical artery. Am J Obstet Gynecol 1994;171:521-5. 26. Law CM, de Swiet M, Osmond C, et al. Initiation of hypertension in utero and its amplification throughout life. BMJ 1993;306:24-7.

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Waldo Sepulveda, MD Harris Birthright Research Centre for Fetal Medicine King’s College Hospital Medical School Denmark Hill London SE5 SRX United Kingdom

Received February 27, 1995. Received in revised form July Accepted July 22, 1995. Copyright 0 1995 by The Gynecologists.

6, 1995.

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