DOI: 10.1002/pd.4263
ORIGINAL ARTICLE
The vertebral artery Doppler might be an alternative to the middle cerebral artery Doppler in the follow-up of the early onset growth-restricted fetus José Morales Roselló1*, David Hervás Marín2 and Alfredo Perales Marín1 1
Servicio de Obstetricia y Ginecología, Hospital Universitario y Politécnico La Fe, Valencia, Spain Unidad de Bioestadística, Instituto de Investigación Sanitaria La Fe, Valencia, Spain *Correspondence to: José Morales Roselló. E-mail: [email protected]
2
ABSTRACT Objective The objective of this article is to show the clinical utility of the vertebral artery Doppler as an alternative to the middle cerebral artery Doppler in the follow-up of fetuses affected with early-onset growth restriction [fetal growth restriction (FGR)]. Methods We present a group of fetuses with early-onset FGR in which the vertebral artery resistance index (VA RI) and pulsatility index (VA PI) were measured and plotted along with their references earlier calculated using 1980 Doppler examinations. In addition, the VA and middle cerebral artery (MCA) performance was compared using values converted into multiples of the median. Results Similar to that of the MCA, VA RI and VA PI percentiles showed curve shapes with higher values at the beginning of the third trimester. The majority of growth-restricted fetuses showed a notorious decrease in the VA impedance, which was not statistically different to that of the MCA.
Conclusion Vertebral artery Doppler values can be obtained throughout the second half of pregnancy. Preliminary data suggest a clinical application in the management of early-onset FGR. © 2013 John Wiley & Sons, Ltd.
Funding sources: None Conflicts of interest: None declared
INTRODUCTION Vascular supply to the fetal brain comes from two vascular gates: the internal carotid artery (ICA) and the vertebral artery (VA). The first derives from the anastomosis between the third branchial artery and the most cranial segments of the aorta, whereas the second originates from the anastomoses of the first six cervical intersegmental arteries.1 From a phylogenetic point of view, VA supplies the older areas of the brain, brain stem, and cerebellum,2,3 which have been shown to present better adaptive mechanisms to hypoxia than the neocortex irrigated by the ICA and its continuation to the middle cerebral artery (MCA).4 These differences, which might be partially the result of different arterial responses to hypoxemia, prompted us to initiate a research line on the fetal VA Doppler.5,6 Our aim in this work was to describe preliminary data concerning its application in the follow-up of fetuses affected with severe growth restriction [fetal growth restriction (FGR)].
PATIENTS AND METHODS Normal VA references were obtained from the 1980 fetal ultrasound examinations, one per fetus, performed at 19 to Prenatal Diagnosis 2014, 34, 109–114
41 weeks’ gestation on 1980 singleton pregnant women whose last menstrual period was accurately determined with a first trimester ultrasound. During each examination, a complete fetal biometry and a Doppler measurement of the VA, MCA, and umbilical artery (UA) resistance index (RI) and pulsatility index (PI) were performed. Data from fetuses with malformations were excluded. However, fetuses with growth disorders and preterm deliveries were included as were considered part of the general population. The 3rd, 5th, 10th, 50th, 90th, 95th, and 97th RI and PI percentiles (P) were subsequently calculated using ‘percentile regression’ and were plotted along with values obtained in 19 fetuses with severe FGR and absent UA diastolic flow. In this group, only one examination (the nearest to labor) was included. Fetuses were followed until the end of pregnancy, and data related with birth were collected. MCA and VA PI measurements were compared with box and whisker diagrams converting values into multiples of the median (MoM), which was calculated dividing the observed value by the 50th P. Statistical significance was determined using Mann–Whitney U tests with a p < 0.05. Finally, a correlation was performed between MCA © 2013 John Wiley & Sons, Ltd.
J. Morales Roselló
110
Table 1 Coefficients for the equations of the vertebral artery resistance index and pulsatility index percentiles Intercept
Coefficient 1 (EW)
Coefficient 2 2 (EW )
0.076169911
0.001370415
Vertebral artery resistance index 3rd
0.334131747
5th
0.386790451
0.080098733
0.001420081
10th
0.271191794
0.072887802
0.001287495
50th
0.098754215
0.065014895
0.00112011
90th
0.220839002
0.044656085
0.000740741
95th
0.310686978
0.039258305
0.000646511
97th
0.364137749
0.036836985
0.000615021
0.186915307
0.00341242
Vertebral artery pulsatility index 3rd
Figure 1 Diagram for the VA Doppler measurement representing the ‘check mark sign’. The VA is always depicted at the tip of the ‘check mark’ or ‘tick mark’ formed by the occipital bone and the cervical vertebrae sliding sideways the ultrasound beam. VA, vertebral artery; SV, occipital sinus venosus and VA PI MoM values and between Doppler values and birth weight (BW), and the correlation coefficients R2 and p-values were obtained.
1.286740402
5th
1.650138406
0.213913783
0.003829008
10th
1.447586389
0.205465007
0.003684269
50th
2.603511444
0.307655383
0.005282338
90th
2.367073345
0.320579129
0.005423017
95th
2.865858582
0.362270751
0.006073891
97th
2.957051056
0.37977292
0.006414686
EW, examination week. General equation: Intercept + coefficient 1 * EW + coefficient 2 * EW2.
The ultrasound examinations were performed with E6 and 730 Voluson ultrasound machines with 2 to 8 MHz convex probes, and Doppler measurements were performed during fetal apnea, in the absence of fetal movements and according to earlier descriptions.6–8 In summary, the VA Doppler signals were obtained in the space between the first cervical vertebra
Figure 2 Vertebral artery Doppler waveforms at the end of pregnancy. The vertebral artery is depicted at the tip of the ‘check mark sign’. The occipital sinus can be seen at the other side of the occipital bone
Prenatal Diagnosis 2014, 34, 109–114
© 2013 John Wiley & Sons, Ltd.
Prenatal Diagnosis 2014, 34, 109–114
9
12
20
10
10
16
21
28
16
17
140
362
135
34
40
59
131
244
385
63
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
100
21
23
126
20
22
2
N
19
Week
0.49
0.52
0.55
0.58
0.61
0.63
0.65
0.67
0.69
0.70
0.71
0.72
0.72
0.72
0.72
0.72
0.71
0.70
0.69
0.68
0.66
0.64
0.62
P3
0.51
0.55
0.58
0.61
0.63
0.66
0.68
0.69
0.71
0.72
0.73
0.74
0.74
0.74
0.74
0.74
0.73
0.72
0.70
0.69
0.67
0.65
0.62
P5
0.55
0.58
0.61
0.64
0.66
0.68
0.70
0.72
0.73
0.74
0.75
0.76
0.76
0.76
0.76
0.75
0.75
0.74
0.72
0.71
0.69
0.67
0.65
P10
0.68
0.71
0.73
0.75
0.77
0.79
0.80
0.82
0.83
0.83
0.84
0.84
0.84
0.84
0.84
0.83
0.83
0.82
0.80
0.79
0.77
0.75
0.73
P50
Resistence index
0.81
0.82
0.84
0.85
0.86
0.87
0.88
0.88
0.89
0.89
0.89
0.89
0.89
0.89
0.89
0.88
0.87
0.87
0.86
0.84
0.83
0.82
0.80
P90
0.83
0.85
0.86
0.87
0.88
0.89
0.89
0.90
0.90
0.90
0.91
0.91
0.91
0.90
0.90
0.89
0.89
0.88
0.87
0.86
0.85
0.84
0.82
P95
0.84
0.85
0.87
0.88
0.89
0.89
0.90
0.91
0.91
0.91
0.92
0.92
0.92
0.91
0.91
0.91
0.90
0.89
0.89
0.88
0.87
0.85
0.84
P97
Table 2 Percentiles for the vertebral artery resistance index and pulsatility index at 19 to 41 weeks’ gestation
0.64
0.73
0.81
0.89
0.96
1.02
1.08
1.12
1.17
1.20
1.23
1.25
1.26
1.27
1.27
1.27
1.25
1.23
1.21
1.17
1.13
1.09
1.03
P3
0.64
0.73
0.81
0.89
0.96
1.02
1.08
1.12
1.17
1.20
1.23
1.25
1.26
1.27
1.27
1.27
1.25
1.23
1.21
1.17
1.13
1.09
1.03
P5
0.78
0.88
0.96
1.04
1.11
1.17
1.23
1.28
1.32
1.35
1.38
1.40
1.41
1.42
1.41
1.40
1.39
1.36
1.33
1.29
1.24
1.19
1.13
P10
1.13
1.25
1.36
1.46
1.55
1.63
1.69
1.75
1.80
1.83
1.86
1.87
1.88
1.87
1.85
1.82
1.79
1.74
1.68
1.61
1.53
1.44
1.34
P50
Pulsatility index
1.66
1.78
1.89
1.98
2.07
2.15
2.21
2.26
2.31
2.34
2.36
2.37
2.37
2.36
2.34
2.30
2.26
2.20
2.14
2.06
1.97
1.88
1.77
P90
1.78
1.91
2.02
2.13
2.22
2.30
2.37
2.43
2.47
2.51
2.53
2.54
2.53
2.52
2.49
2.45
2.39
2.33
2.25
2.16
2.06
1.95
1.82
P95
1.83
1.97
2.10
2.21
2.31
2.40
2.48
2.54
2.59
2.63
2.65
2.66
2.66
2.65
2.62
2.58
2.53
2.46
2.38
2.29
2.19
2.07
1.94
P97
Doppler of the fetal vertebral artery
111
© 2013 John Wiley & Sons, Ltd.
112
and the occipital bone, at the anatomical point where the artery runs nearly perpendicular to its previous direction through the transverse foramen. In that sonographic section, the occipital bone and the cervical vertebrae resembled a ‘check mark sign’, and the VA could be easily depicted at the tip of the triangle sliding sideways the sonographic beam (Figure 1). The MCA Doppler signals were obtained by the sphenoid wing proximal to its branching at the circle of Willis, and the UA Doppler signals were obtained in free loops of cord. Percentiles were obtained using R software version 2.15.1. (http://www.r-project.org/), and charts were generated with ® ® GRAPHPAD PRISM 5a (GraphPad Software Inc., San Diego, CA, USA). The regression technique used to compute the percentile equations was quantile regression, and there was no need for a weighted regression because our data had no heteroscedasticity. In order to build percentiles, different regression models were assessed going from linear up to third-order polynomials. Best model was selected using Akaike information criterion. Approval from the Institution’s Review Board was obtained, and verbal consent was taken before every examination.
RESULTS The percentile group (N = 1980) had a mean maternal age of 31.6 years (SD 5), a mean gestational age at delivery of 39.9 weeks (SD 1.5), and a mean BW of 3261 g (SD 523). The number of patients per week is described in Table 2 and is adequate to establish reference ranges.9 Concerning the VA Doppler examination, specific features were the presence of frequent nicks on its posterior vertical border due to the particular route around the lateral masses of the atlas and the possibility to detect its continuation as the basilar artery at
Figure 3 Vertebral artery resistance index (VA RI) values of fetuses with growth restriction and absent umbilical artery diastolic flow are represented with the vertebral artery resistance index percentiles. Fetuses that did not survive are represented with black dots
Prenatal Diagnosis 2014, 34, 109–114
J. Morales Roselló
Figure 4 Vertebral artery pulsatility index (VA PI) values of fetuses with growth restriction and absent umbilical artery diastolic flow are represented with the vertebral artery pulsatility index percentiles. Fetuses that did not survive are represented with black dots
the level of the brain stem. Occasionally (
ORIGINAL ARTICLE
The vertebral artery Doppler might be an alternative to the middle cerebral artery Doppler in the follow-up of the early onset growth-restricted fetus José Morales Roselló1*, David Hervás Marín2 and Alfredo Perales Marín1 1
Servicio de Obstetricia y Ginecología, Hospital Universitario y Politécnico La Fe, Valencia, Spain Unidad de Bioestadística, Instituto de Investigación Sanitaria La Fe, Valencia, Spain *Correspondence to: José Morales Roselló. E-mail: [email protected]
2
ABSTRACT Objective The objective of this article is to show the clinical utility of the vertebral artery Doppler as an alternative to the middle cerebral artery Doppler in the follow-up of fetuses affected with early-onset growth restriction [fetal growth restriction (FGR)]. Methods We present a group of fetuses with early-onset FGR in which the vertebral artery resistance index (VA RI) and pulsatility index (VA PI) were measured and plotted along with their references earlier calculated using 1980 Doppler examinations. In addition, the VA and middle cerebral artery (MCA) performance was compared using values converted into multiples of the median. Results Similar to that of the MCA, VA RI and VA PI percentiles showed curve shapes with higher values at the beginning of the third trimester. The majority of growth-restricted fetuses showed a notorious decrease in the VA impedance, which was not statistically different to that of the MCA.
Conclusion Vertebral artery Doppler values can be obtained throughout the second half of pregnancy. Preliminary data suggest a clinical application in the management of early-onset FGR. © 2013 John Wiley & Sons, Ltd.
Funding sources: None Conflicts of interest: None declared
INTRODUCTION Vascular supply to the fetal brain comes from two vascular gates: the internal carotid artery (ICA) and the vertebral artery (VA). The first derives from the anastomosis between the third branchial artery and the most cranial segments of the aorta, whereas the second originates from the anastomoses of the first six cervical intersegmental arteries.1 From a phylogenetic point of view, VA supplies the older areas of the brain, brain stem, and cerebellum,2,3 which have been shown to present better adaptive mechanisms to hypoxia than the neocortex irrigated by the ICA and its continuation to the middle cerebral artery (MCA).4 These differences, which might be partially the result of different arterial responses to hypoxemia, prompted us to initiate a research line on the fetal VA Doppler.5,6 Our aim in this work was to describe preliminary data concerning its application in the follow-up of fetuses affected with severe growth restriction [fetal growth restriction (FGR)].
PATIENTS AND METHODS Normal VA references were obtained from the 1980 fetal ultrasound examinations, one per fetus, performed at 19 to Prenatal Diagnosis 2014, 34, 109–114
41 weeks’ gestation on 1980 singleton pregnant women whose last menstrual period was accurately determined with a first trimester ultrasound. During each examination, a complete fetal biometry and a Doppler measurement of the VA, MCA, and umbilical artery (UA) resistance index (RI) and pulsatility index (PI) were performed. Data from fetuses with malformations were excluded. However, fetuses with growth disorders and preterm deliveries were included as were considered part of the general population. The 3rd, 5th, 10th, 50th, 90th, 95th, and 97th RI and PI percentiles (P) were subsequently calculated using ‘percentile regression’ and were plotted along with values obtained in 19 fetuses with severe FGR and absent UA diastolic flow. In this group, only one examination (the nearest to labor) was included. Fetuses were followed until the end of pregnancy, and data related with birth were collected. MCA and VA PI measurements were compared with box and whisker diagrams converting values into multiples of the median (MoM), which was calculated dividing the observed value by the 50th P. Statistical significance was determined using Mann–Whitney U tests with a p < 0.05. Finally, a correlation was performed between MCA © 2013 John Wiley & Sons, Ltd.
J. Morales Roselló
110
Table 1 Coefficients for the equations of the vertebral artery resistance index and pulsatility index percentiles Intercept
Coefficient 1 (EW)
Coefficient 2 2 (EW )
0.076169911
0.001370415
Vertebral artery resistance index 3rd
0.334131747
5th
0.386790451
0.080098733
0.001420081
10th
0.271191794
0.072887802
0.001287495
50th
0.098754215
0.065014895
0.00112011
90th
0.220839002
0.044656085
0.000740741
95th
0.310686978
0.039258305
0.000646511
97th
0.364137749
0.036836985
0.000615021
0.186915307
0.00341242
Vertebral artery pulsatility index 3rd
Figure 1 Diagram for the VA Doppler measurement representing the ‘check mark sign’. The VA is always depicted at the tip of the ‘check mark’ or ‘tick mark’ formed by the occipital bone and the cervical vertebrae sliding sideways the ultrasound beam. VA, vertebral artery; SV, occipital sinus venosus and VA PI MoM values and between Doppler values and birth weight (BW), and the correlation coefficients R2 and p-values were obtained.
1.286740402
5th
1.650138406
0.213913783
0.003829008
10th
1.447586389
0.205465007
0.003684269
50th
2.603511444
0.307655383
0.005282338
90th
2.367073345
0.320579129
0.005423017
95th
2.865858582
0.362270751
0.006073891
97th
2.957051056
0.37977292
0.006414686
EW, examination week. General equation: Intercept + coefficient 1 * EW + coefficient 2 * EW2.
The ultrasound examinations were performed with E6 and 730 Voluson ultrasound machines with 2 to 8 MHz convex probes, and Doppler measurements were performed during fetal apnea, in the absence of fetal movements and according to earlier descriptions.6–8 In summary, the VA Doppler signals were obtained in the space between the first cervical vertebra
Figure 2 Vertebral artery Doppler waveforms at the end of pregnancy. The vertebral artery is depicted at the tip of the ‘check mark sign’. The occipital sinus can be seen at the other side of the occipital bone
Prenatal Diagnosis 2014, 34, 109–114
© 2013 John Wiley & Sons, Ltd.
Prenatal Diagnosis 2014, 34, 109–114
9
12
20
10
10
16
21
28
16
17
140
362
135
34
40
59
131
244
385
63
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
100
21
23
126
20
22
2
N
19
Week
0.49
0.52
0.55
0.58
0.61
0.63
0.65
0.67
0.69
0.70
0.71
0.72
0.72
0.72
0.72
0.72
0.71
0.70
0.69
0.68
0.66
0.64
0.62
P3
0.51
0.55
0.58
0.61
0.63
0.66
0.68
0.69
0.71
0.72
0.73
0.74
0.74
0.74
0.74
0.74
0.73
0.72
0.70
0.69
0.67
0.65
0.62
P5
0.55
0.58
0.61
0.64
0.66
0.68
0.70
0.72
0.73
0.74
0.75
0.76
0.76
0.76
0.76
0.75
0.75
0.74
0.72
0.71
0.69
0.67
0.65
P10
0.68
0.71
0.73
0.75
0.77
0.79
0.80
0.82
0.83
0.83
0.84
0.84
0.84
0.84
0.84
0.83
0.83
0.82
0.80
0.79
0.77
0.75
0.73
P50
Resistence index
0.81
0.82
0.84
0.85
0.86
0.87
0.88
0.88
0.89
0.89
0.89
0.89
0.89
0.89
0.89
0.88
0.87
0.87
0.86
0.84
0.83
0.82
0.80
P90
0.83
0.85
0.86
0.87
0.88
0.89
0.89
0.90
0.90
0.90
0.91
0.91
0.91
0.90
0.90
0.89
0.89
0.88
0.87
0.86
0.85
0.84
0.82
P95
0.84
0.85
0.87
0.88
0.89
0.89
0.90
0.91
0.91
0.91
0.92
0.92
0.92
0.91
0.91
0.91
0.90
0.89
0.89
0.88
0.87
0.85
0.84
P97
Table 2 Percentiles for the vertebral artery resistance index and pulsatility index at 19 to 41 weeks’ gestation
0.64
0.73
0.81
0.89
0.96
1.02
1.08
1.12
1.17
1.20
1.23
1.25
1.26
1.27
1.27
1.27
1.25
1.23
1.21
1.17
1.13
1.09
1.03
P3
0.64
0.73
0.81
0.89
0.96
1.02
1.08
1.12
1.17
1.20
1.23
1.25
1.26
1.27
1.27
1.27
1.25
1.23
1.21
1.17
1.13
1.09
1.03
P5
0.78
0.88
0.96
1.04
1.11
1.17
1.23
1.28
1.32
1.35
1.38
1.40
1.41
1.42
1.41
1.40
1.39
1.36
1.33
1.29
1.24
1.19
1.13
P10
1.13
1.25
1.36
1.46
1.55
1.63
1.69
1.75
1.80
1.83
1.86
1.87
1.88
1.87
1.85
1.82
1.79
1.74
1.68
1.61
1.53
1.44
1.34
P50
Pulsatility index
1.66
1.78
1.89
1.98
2.07
2.15
2.21
2.26
2.31
2.34
2.36
2.37
2.37
2.36
2.34
2.30
2.26
2.20
2.14
2.06
1.97
1.88
1.77
P90
1.78
1.91
2.02
2.13
2.22
2.30
2.37
2.43
2.47
2.51
2.53
2.54
2.53
2.52
2.49
2.45
2.39
2.33
2.25
2.16
2.06
1.95
1.82
P95
1.83
1.97
2.10
2.21
2.31
2.40
2.48
2.54
2.59
2.63
2.65
2.66
2.66
2.65
2.62
2.58
2.53
2.46
2.38
2.29
2.19
2.07
1.94
P97
Doppler of the fetal vertebral artery
111
© 2013 John Wiley & Sons, Ltd.
112
and the occipital bone, at the anatomical point where the artery runs nearly perpendicular to its previous direction through the transverse foramen. In that sonographic section, the occipital bone and the cervical vertebrae resembled a ‘check mark sign’, and the VA could be easily depicted at the tip of the triangle sliding sideways the sonographic beam (Figure 1). The MCA Doppler signals were obtained by the sphenoid wing proximal to its branching at the circle of Willis, and the UA Doppler signals were obtained in free loops of cord. Percentiles were obtained using R software version 2.15.1. (http://www.r-project.org/), and charts were generated with ® ® GRAPHPAD PRISM 5a (GraphPad Software Inc., San Diego, CA, USA). The regression technique used to compute the percentile equations was quantile regression, and there was no need for a weighted regression because our data had no heteroscedasticity. In order to build percentiles, different regression models were assessed going from linear up to third-order polynomials. Best model was selected using Akaike information criterion. Approval from the Institution’s Review Board was obtained, and verbal consent was taken before every examination.
RESULTS The percentile group (N = 1980) had a mean maternal age of 31.6 years (SD 5), a mean gestational age at delivery of 39.9 weeks (SD 1.5), and a mean BW of 3261 g (SD 523). The number of patients per week is described in Table 2 and is adequate to establish reference ranges.9 Concerning the VA Doppler examination, specific features were the presence of frequent nicks on its posterior vertical border due to the particular route around the lateral masses of the atlas and the possibility to detect its continuation as the basilar artery at
Figure 3 Vertebral artery resistance index (VA RI) values of fetuses with growth restriction and absent umbilical artery diastolic flow are represented with the vertebral artery resistance index percentiles. Fetuses that did not survive are represented with black dots
Prenatal Diagnosis 2014, 34, 109–114
J. Morales Roselló
Figure 4 Vertebral artery pulsatility index (VA PI) values of fetuses with growth restriction and absent umbilical artery diastolic flow are represented with the vertebral artery pulsatility index percentiles. Fetuses that did not survive are represented with black dots
the level of the brain stem. Occasionally (
