- Email: [email protected]
3D power Doppler ultrasound assessment of placental perfusion during uterine contraction in labor
Accepted Manuscript 3D power Doppler ultrasound assessment of placental perfusion during uterine contraction in labor Miki Sato, Junko Noguchi, Masato Mashima, Hirokazu Tanaka, Toshiyuki Hata PII:
S0143-4004(16)30137-0
DOI:
10.1016/j.placenta.2016.06.018
Reference:
YPLAC 3434
To appear in:
Placenta
Received Date: 23 March 2016 Revised Date:
11 May 2016
Accepted Date: 30 June 2016
Please cite this article as: Sato M, Noguchi J, Mashima M, Tanaka H, Hata T, 3D power Doppler ultrasound assessment of placental perfusion during uterine contraction in labor, Placenta (2016), doi: 10.1016/j.placenta.2016.06.018. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT 1
3D power Doppler ultrasound assessment of placental perfusion
2
during uterine contraction in labor
RI PT
3 Miki Sato, MD1, Junko Noguchi, MS, PhD2, Masato Mashima, MD1, Hirokazu
5
Tanaka, MD, PhD1, Toshiyuki Hata, MD, PhD1
SC
4
M AN U
6
7
1
8
School of Medicine, 1750-1 Ikenobe, Miki, Kagawa 761-0793, Japan
9
2
12
13
TE D
281-1 Murecho-hara, Takamatsu, Kagawa 761-0123, Japan
EP
11
Department of Nursing, Kagawa Prefectural College of Health Sciences,
Running title: Placental perfusion during uterine contraction
AC C
10
Department of Perinatology and Gynecology, Kagawa University Graduate
14
Key words: Placental vascular sonobiopsy, 3D power Doppler ultrasound,
15
placental perfusion, spontaneous uterine contraction, induced uterine
16
contraction, labor
1
ACCEPTED MANUSCRIPT 17
18
Word count: 2,109
RI PT
19
All correspondence to: Toshiyuki Hata, MD, PhD, Department of
21
Perinatology and Gynecology, Kagawa University Graduate School of
22
Medicine, 1750-1 Ikenobe, Miki, Kagawa 761-0793, Japan
23
M AN U
SC
20
TEL. +81-(0)87-891-2174
25
FAX. +81-(0)87-891-2175
26
E-mail: [email protected]
EP
27
TE D
24
Conflict of Interest
29
The authors declare no conflict of interest.
AC C
28
30
2
ACCEPTED MANUSCRIPT 31
ABSTRACT
32
Introduction: To assess placental perfusion during spontaneous or induced
34
uterine contraction in labor at term using placental vascular sonobiopsy
35
(PVS) by 3D power Doppler ultrasound with the VOCAL imaging analysis
36
program.
37
Method: PVS was performed in 50 normal pregnancies (32 in spontaneous
38
labor group [SLG], and 18 in induced labor group with oxytocin or
39
prostaglandin F2 [ILG]) at 37 to 41 weeks of gestation to assess placental
40
perfusion during uterine contraction in labor. Only pregnancies with an
41
entirely visualized anterior placenta were included in the study. Data
42
acquisition was performed before, during (at the peak of contraction), and
43
after uterine contraction. 3D power Doppler indices such as the
44
vascularization index (VI), flow index (FI), and vascularization flow index
45
(VFI) were calculated in each placenta.
AC C
EP
TE D
M AN U
SC
RI PT
33
3
ACCEPTED MANUSCRIPT Results: There were no abnormal fetal heart rate tracings during contraction
47
in either group. VI and VFI values were significantly reduced during uterine
48
contraction in both groups (SLG: median, -30.4% [range, -95.6 − 9.7%], and
49
ILG, -45.1% [-76.0 − 3.5%]), respectively (P < 0.001). The FI value in the
50
ILG group was significantly lower during uterine contraction (P = 0.035),
51
whereas it did not change during uterine contraction in the SLG group. After
52
uterine contraction, all vascular indices returned almost to the same level as
53
that before uterine contraction. However, the FI value in ILG (-8.6%, [-19.7 −
54
16.0%]) was significantly lower than that in SLG (2.4%, [-13.4 − 38.1%]) after
55
uterine contraction (P < 0.05). All 3D power Doppler indices (VI, FI, and VFI)
56
during uterine contraction (at the peak of contraction) showed a correlation
57
greater than 0.7, with good intra- and inter-observer agreements.
58
Discussion: Our findings suggest that uterine contraction in both
59
spontaneous and induced labors causes a significant reduction in placental
60
perfusion. Reduced placental blood flow in induced uterine contraction has a
61
tendency to be marked compared with that in spontaneous uterine
AC C
EP
TE D
M AN U
SC
RI PT
46
4
ACCEPTED MANUSCRIPT contraction. To the best of our knowledge, this is the first study on the non-
63
invasive assessment of placental perfusion during uterine contraction in
64
labor using 3D power Doppler ultrasound. However, the data and their
65
interpretation in the present study should be taken with some degree of
66
caution because of the small number of subjects studied. Further studies
67
involving a larger sample size are needed to assess placental perfusion and
68
vascularity using PVS during normal and abnormal uterine contractions in
69
normal and high-risk pregnancies.
M AN U
SC
RI PT
62
TE D
70
Key words: Placental vascular sonobiopsy, 3D power Doppler ultrasound,
72
placental perfusion, spontaneous uterine contraction, induced uterine
73
contraction, labor
AC C
74
EP
71
5
ACCEPTED MANUSCRIPT 75
1. Introduction
76
In spontaneous uterine contraction, maternal placental blood flow
78
before labor was reported to be 4.5% of the cardiac output, decreasing to
79
2.9% (35.5% decrease) during uterine contraction, and increasing to 7.2%
80
(60% increase) after contraction in pregnant rhesus monkeys [1]. Reduction
81
of placental blood flow during spontaneous uterine contraction was also 30 ±
82
8% in dogs and 35 ± 12% in rabbits [2]. On the contrary, in induced uterine
83
contraction with oxytocin and prostaglandin E2, uterine contraction led to a
84
marked reduction (average: 73%) of the placental blood flow in pregnant
85
rhesus monkeys, and the placental blood flow partially recovered after the
86
uterine contraction [3]. These reductions of placental blood flow on induced
87
uterine contraction with oxytocin were 43 ± 16% in dogs, and 46 ± 13% in
88
rabbits [2]. However, to the best of our knowledge, there are no available
89
data on the change in placental blood flow during uterine contraction in the
90
human placenta.
AC C
EP
TE D
M AN U
SC
RI PT
77
6
ACCEPTED MANUSCRIPT Placental vascular sonobiopsy (PVS) using three-dimensional (3D)
92
power Doppler ultrasound with VOCAL imaging histogram analysis is a
93
novel technique to quantitatively and qualitatively assess the vascularization
94
and blood flow in the placenta [4-6]. Moreover, PVS is a valid alternative for
95
evaluation of the placental vascularity and blood flow when visualization of
96
the entire placenta is not feasible [7]. In the present study, we assessed
97
placental perfusion during spontaneous or induced uterine contraction in
98
labor at term using PVS.
2. Patients and Methods
EP
100
TE D
99
101
103
2.1. Patients
AC C
102
M AN U
SC
RI PT
91
104
In the period from July 2012 to May 2015, 73 women with normal
105
singleton pregnancies in labor at 37 to 41 weeks of gestation were studied
106
cross-sectionally. The women were recruited randomly. The fetal age was
7
ACCEPTED MANUSCRIPT calculated from the first day of the last menstrual period, with confirmation by
108
first-trimester ultrasound. Women with gestational diabetes, chronic
109
hypertension, maternal systemic disease, or taking antihypertensive
110
medications were not enrolled. Of the 73 women, 23 (31.5%) were excluded
111
because of insufficient data acquisition due to severe artifacts caused by
112
uterine contraction or maternal movements. Therefore, 50 women (32 in a
113
spontaneous labor group [SLG], and 18 in an induced labor group with
114
oxytocin or prostaglandin F2
115
Indications of induced labor were a weak labor in 11 women, and post-term
116
pregnancy in 7 women. Clinical characteristics of the subjects in each group
117
are shown in Table 1. The umbilical artery pulsatility index in all subjects was
118
normal at 26 to 29 weeks of gestation. The growth of all fetuses was normal,
119
and there were no abnormalities during pregnancy. This study was approved
120
by the Kagawa University Graduate School of Medicine Ethics Committee,
121
and standardized written informed consent was obtained from all women.
M AN U
SC
RI PT
107
AC C
EP
TE D
[ILG]) underwent further investigation.
122
8
ACCEPTED MANUSCRIPT 123
2.2. Ultrasound examination
124
A single experienced observer (M.S.) performed all 3D power Doppler
126
ultrasound scans using a Voluson E8 A6 2.4 (GE Healthcare Japan, Tokyo,
127
Japan) with a transabdominal 1-4 MHz transducer (RAB2-5-D) at the first
128
stage of labor. At each examination, each placenta was confirmed to be
129
located in an anterior position. 3D power Doppler ultrasound was employed
130
for a representative placental vascular tree volume based on the following
131
procedure, described in detail in our previous investigations [4-6]. The
132
maximal sensitivity was ensured by setting the pulse repetition frequency
133
(PRF) to 0.6 kHz and the wall motion filter to ‘low’. The following constant
134
default instrument settings (corresponding to the manufacturer’s Doppler
135
power setting) were used throughout the examinations: frequency, mid;
136
dynamic, balance, 225; smooth, 4/5; ensemble, 11; line density, 8; power
137
Doppler map, 4; artifact suppression, on; power Doppler line filter, 3; quality,
138
normal. The power Doppler window was placed over the placenta, including
AC C
EP
TE D
M AN U
SC
RI PT
125
9
ACCEPTED MANUSCRIPT its total thickness, from the basal to chorionic plates. The 3D volume box was
140
positioned over the placenta at a fixed 65˚ angle. Volume acquisition was
141
carried out within 16 seconds before (at the start of contraction), during (at the
142
peak of contraction), and after uterine contraction (at the end of contraction)
143
(Figure 1).
SC
RI PT
139
As presented in detail in our previous studies [4-6], the examination of
145
placental perfusion was performed using PVS. In the measurement of PVS,
146
the power Doppler window is placed over the placenta, including its total
147
thickness, from the basal to chorionic plates (excluding both of them). The
148
spherical 3D volume is obtained between the basal and chorionic plates
149
(Figure 1). The VOCAL program automatically calculates color values
150
(vascularization index [VI], flow index [FI], and vascularization flow index
151
[VFI]) from the acquired sphere. A sequence of six placental sections
152
separated by successive rotations of 30° is obtaine d, and 1 to 3 spherical
153
sampling sites are chosen in each plane. Each spherical volume was taken at
154
approximately equidistant intervals along the length of the placental image.
AC C
EP
TE D
M AN U
144
10
ACCEPTED MANUSCRIPT Each index was an average value from those of 6 to 13 spheres in each
156
placenta. A single experienced observer (M.S.) conducted all 3D Doppler
157
ultrasound histogram analyses with the VOCAL program.
RI PT
155
158
2.3. Statistical analysis
SC
159
M AN U
160
All statistical analyses were performed with SPSS statistical software,
162
version 23 for Windows (SPSS Inc., Chicago, IL, USA). Differences in the
163
maternal age, birth age, cervical dilatation, interval of uterine contraction,
164
birth weight, and umbilical artery blood pH between SLG and ILG groups
165
were assessed by the unpaired t-test. Differences in Apgar scores between
166
the groups were investigated with the Mann-Whitney U test. The percent
167
change of each index during uterine contraction was assessed by the
168
Wilcoxon Signed-rank test. Differences in variables at each stage between
169
SLG and ILG groups were investigated with the Mann-Whitney U test. Intra-
170
and inter-class correlation coefficients were used as an expression of
AC C
EP
TE D
161
11
ACCEPTED MANUSCRIPT reliability [8]. Intra- and inter-class correlation coefficients were defined as
172
the correlation between any two measurements from the same data during
173
uterine contraction (at the peak of contraction). Their values ranged from
174
zero to one; the latter indicates maximum reliability. Intra- and inter-observer
175
variability were calculated according to Bland and Altman’s procedure [9] in
176
20 samples (11 in SLG and 9 in ILG). Intra-observer variation was examined
177
by M.S., and inter-observer variation was assessed by M.S. and J.N. This
178
analysis consisted of a graph, in which the difference between the
179
measurements (y-axis) was plotted against their mean value (x-axis). The
180
95% limits of individual agreement between the two measurements were
181
calculated as the mean difference between two measurements ± 2.0
182
standard deviations. Moreover, the difference between the mean difference
183
and zero was assessed by a two-sample t-test. A P-value < 0.05 was
184
considered significant.
AC C
EP
TE D
M AN U
SC
RI PT
171
185
186
3. Results
12
ACCEPTED MANUSCRIPT 187
There were no significant differences in the maternal age, parity, birth
189
age, cervical dilatation at examination (SLG: mean, 6.1 cm [SD: ± 3.1], and
190
ILG, 5.9 cm [± 3.3]), interval of uterine contraction at examination (SLG:
191
mean, 3.8 min [SD: ± 0.9], and ILG, 3.3 min [± 0.6]), birth weight, Apgar
192
scores at 1 and 5 min, or umbilical artery blood pH between the two groups
193
(Table 1). There was no fever-up during delivery. All women had a normal
194
vaginal delivery. Within 24 hours after delivery, an extensive pediatric
195
assessment was performed of each neonate. No neonate was found to have
196
congenital anomalies or genetic disorders.
EP
TE D
M AN U
SC
RI PT
188
There were no abnormal fetal heart rate tracings during contraction in
198
either group. The percent change of each vascular index value during
199
uterine contraction in both groups is shown in Table 2. VI and VFI values
200
were significantly reduced during uterine contraction in both groups (SLG:
201
median, -30.4% [range: -95.6 − 9.7%], and ILG, -45.1% [-76.0 − 3.5%]),
202
respectively (P < 0.001). The FI value in the ILG group was significantly
AC C
197
13
ACCEPTED MANUSCRIPT lower during uterine contraction (P = 0.035), whereas it did not change
204
during uterine contraction in the SLG group. After uterine contraction, all
205
vascular indices returned almost to the same level at that before uterine
206
contraction. However, the FI value in ILG (-8.6%, [-19.7 − 16.0%]) was
207
significantly lower than that in SLG (2.4%, [-13.4 − 38.1%]) after uterine
208
contraction (P < 0.05). There were no significant differences in any vascular
209
index values during uterine contraction, nor any significant differences in VI
210
or VFI values after uterine contraction between SLG and ILG groups.
213
214
SC
M AN U
TE D
3.1. Intra-observer agreement
EP
212
The mean difference between measurements and the limits of
AC C
211
RI PT
203
215
agreement for each of the parameters studied during uterine contraction (at
216
the peak of contraction) are shown in Table 3. The mean difference and 95%
217
limits of intra-observer agreements for VI, FI, and VFI were 0.296% (5.997, -
218
5.404), 1.597 (8.209, -5.016), and 0.567 (4.258, -3.125), respectively. The
14
ACCEPTED MANUSCRIPT difference between the mean difference and zero was not significant for VI
220
or VFI, but was weakly significant for FI (P = 0.048). Intra-class correlation
221
coefficients for each of the parameters studied are also shown in Table 3. VI,
222
FI, and VFI had intra-class correlation coefficients of 0.940, 0.711, and 0.925,
223
respectively (P < 0.0001).
SC
RI PT
219
225
3.2. Inter-observer agreement
226
M AN U
224
The mean difference between the two investigators (M.S. and J.N.)
228
and the limits of agreement for each of the parameters studied during uterine
229
contraction (at the peak of contraction) are shown in Table 4. The mean
230
difference and 95% limits of inter-observer agreements for VI, FI, and VFI
231
were -1.149% (5.644, -7.942), 0.481 (5.813, -4.852), and -0.156 (3.317, -
232
3.628), respectively. The difference between the mean difference and zero
233
was not significant for each 3D power Doppler vascularity index. Inter-class
234
correlation coefficients for each of the parameters studied are also shown in
AC C
EP
TE D
227
15
ACCEPTED MANUSCRIPT 235
Table 4. VI, FI, and VFI had inter-class correlation coefficients of 0.923,
236
0.836, and 0.908, respectively (P < 0.0001).
In this study, good intra- and inter-class correlation coefficients and
238
intra- and inter-observer agreements were confirmed. Therefore, the
239
measurement values from only one examiner (M.S.) were used for statistical
240
analysis.
M AN U
SC
RI PT
237
241
243
4. Discussion
TE D
242
In the present study, uterine contraction in both spontaneous and
245
induced labors led to a significant reduction in placental perfusion. The main
246
reason for this significant reduction in placental perfusion during uterine
247
contraction is that uterine contractions prevent blood flow into the intervillous
248
space [10, 11]. Interestingly, the reduced placental blood flow in induced
249
uterine contraction had a tendency to be more marked compared with that in
250
spontaneous uterine contraction. Similar findings have also been obtained in
AC C
EP
244
16
ACCEPTED MANUSCRIPT 251
animal experiments [1-3]. Moreover, the recovery of placental blood flow
252
after uterine contraction was rapid in spontaneous labor compared with
253
induced
254
spontaneous and induced uterine contractions may be the significantly
255
higher intensity of labor produced by oxytocin and prostaglandins [2, 3].
256
Another explanation is that prostaglandin F2 has a strong vasoconstrictive
257
effect on both uterine and umbilical circulations [12]. This may explain the
258
differences between the groups. Therefore, these results suggest that we
259
may have to pay attention to the use of oxytocin and prostaglandin F2 for
260
the induction of labor due to the significantly higher intensity of uterine
261
contractions produced by these agents.
explanation
for
these
discrepancies
between
EP
TE D
M AN U
SC
RI PT
The
Fetal heart rate tracings during uterine contraction in SLG and ILG
AC C
262
labor.
263
groups showed no decelerations in this study, although there was a
264
significant reduction in placental blood flow during uterine contraction in both
265
groups. Stuart et al. [13] reported that placental vascular resistance to feto-
266
placental blood flow was not altered by uterine contractions nor the infusion
17
ACCEPTED MANUSCRIPT of oxytocin during uncomplicated labor. There was no difference in fetal
268
oxygenation in the intervillous spaces between spontaneous and oxytocin-
269
induced labors [14]. Subjects enrolled in the present study all had normal
270
pregnancies, and normal vaginal deliveries. Moreover, umbilical artery data
271
in all subjects were normal during pregnancy. Neonatal outcomes were also
272
very favorable. Therefore, feto-placental functions in all pregnancies in this
273
study were good, and each fetus was suggested to have a good reserve
274
capacity to compensate for uterine contractions in labor.
M AN U
SC
RI PT
267
In the present study, we only examined an entirely visualized anterior
276
placenta to keep the maximum depth of the placenta constant [4, 5],
277
because there was a significant reduction in each vascular index value
278
assessed by 3D power Doppler as the distance between the transducer and
279
vascular tree volume increased [15]. Zalud and Shaha [16] stated that only
280
anterior placentas should be included in 3D power Doppler studies to avoid
281
the risk of Doppler signal attenuation. This limitation and disadvantage of 3D
AC C
EP
TE D
275
18
ACCEPTED MANUSCRIPT 282
power Doppler histogram analysis will be resolved as further technical
283
advances are made.
To the best of our knowledge, this is the first study on non-invasive
285
assessment of placental perfusion during spontaneous and induced uterine
286
contractions in labor using PVS by 3D power Doppler ultrasound with the
287
VOCAL imaging histogram analysis. However, the data and their
288
interpretation in the present study should be taken with some degree of
289
caution because of the small number of subjects studied. Further studies
290
involving a larger sample size are needed to evaluate placental blood flow
291
and vascularity using PVS during normal and abnormal uterine contractions
292
in normal and high-risk pregnancies.
SC
M AN U
TE D
EP
AC C
293
RI PT
284
19
ACCEPTED MANUSCRIPT Acknowledgements
295
The work reported in this paper was supported by a Grant-in-Aid for
296
scientific Research on Innovative Areas "Constructive Developmental
297
Science" (No.24119004), and a Research Grant (No.25462561) from The
298
Ministry of Education, Culture, Sports, Science and Technology, Japan.
SC
RI PT
294
M AN U
299
Conflict of Interest
301
The authors have no conflict of interest.
EP AC C
302
TE D
300
20
ACCEPTED MANUSCRIPT 303
References
304
1.
Lees MH, Hill J, Ochsner AJ III, Thomas CL, Novy MJ. Maternal
RI PT
305
placental and myometrial blood flow of the rhesus monkey during
307
uterine contractions. Am J Obstet Gynecol 1971;110:68-81.
2.
Hidaka A, Komatani M, Kurosumi K, Shimazu T, Sugawa T. Influence
M AN U
308
SC
306
309
of uterine contraction on maternal and fetoplacental hemodynamics.
310
Nihon Sanka Fujinka Gakkai Zasshi 1976;28:105-112. (Japanese)
3.
Novy MJ, Thomas CL, Lees MH. Uterine contractility and regional
TE D
311
blood flow responses to oxytocin and prostaglandin E2 in pregnant
313
rhesus monkeys. Am J Obstet Gynecol 1975;122:419-433.
4.
using three-dimensional power Doppler ultrasound in normal and
315
growth restricted fetuses. Placenta 2009;30:391-397.
316
317
318
Noguchi J, Hata K, Tanaka H, Hata T. Placental vascular sonobiopsy
AC C
314
EP
312
5.
Hata T, Tanaka H, Noguchi J, Hata K. Three-dimensional ultrasound
evaluation of the placenta. Placenta 2011;32:105-115.
21
ACCEPTED MANUSCRIPT 319
6.
Noguchi J, Tanaka H, Koyanagi A, Miyake K, Hata T. Three-
320
dimensional power Doppler indices at 18-22 weeks’ gestation for
321
prediction
322
hypertension. Arch Gynecol Obstet 2015;292:75-79.
growth
restriction
or
pregnancy-induced
RI PT
fetal
7.
Tuuli MG, Houser M, Odibo L, Huster K, Macones GA, Odibo AO.
Validation
placental
vascular
sonobiopsy
for
obtaining
325
representative placental vascular indices by three-dimensional power
326
Doppler ultrasonography. Placenta 2010;31:192-196.
M AN U
324
8.
Mercé LT, Barco MJ, Bau S. Reproducibility of the study of placental
TE D
327
of
SC
323
of
vascularization by three-dimensional power Doppler. J Perinat Med
329
2004; 32: 228-233.
331
9.
between two methods of clinical measurement. Lancet 1986; 1: 307-
310.
332
333
334
Bland JM, Altman DG. Statistical methods for assessing agreement
AC C
330
EP
328
10.
Ramsey
EM,
Corner
GWJr,
Donner
MW.
Serial
and
cineradioangiographic visualizeation of maternall circulateon in the
22
ACCEPTED MANUSCRIPT 335
primate (hemochorial) placenta. Am J Obstet Gynecol 1963;86:213-
336
225.
11.
Borell U, Fernström I, Ohlson L, Wiqvist N. Effect of uterine
RI PT
337
contractions on the human uteroplacental blood circulateon. Am J
339
Obstet Gynecol 1964;89:881-890.
12.
McLaughlin MK, Brennan SC, Chez RA. Vasoconstrictive effects of
M AN U
340
SC
338
341
prostaglandins in sheep placental circulations. Am J Obstet Gynecol
342
1978;130:408-413.
13.
Stuart B, Drumm J, FitzGerald DE, Duignan NM. Fetal blood velocity
TE D
343
waveforms
345
1981;88:865-869.
347
14.
350
labour.
Br
J
Obstet
Gynaecol
Truppin M, Wolf L. The maternal-fetal oxygen pressure gradient in
spontaneous and oxytocin-induced labors. Am J Obstet Gynecol
1961;82:804-808.
348
349
uncomplicated
AC C
346
in
EP
344
15.
Raine-Fenning NJ, Nordin NM, Ramnarine KV, Campbell BK, Clewes
JS, Perkins A, Johnson IR. Determining the relationship between
23
ACCEPTED MANUSCRIPT three-dimensional
352
characteristics: an in-vitro flow phantom experiment. Ultrasound
353
Obstet Gynecol 2008;32:540-550.
354
16.
power
Doppler
data
and
true
blood
flow
RI PT
351
Zalud I, Shaha S. Three-dimensional sonography of the placental and
uterine spiral vasculature: Influence of maternal age and parity. J Clin
356
Ultrasound 2008;36:391-396.
M AN U
SC
355
AC C
EP
TE D
357
24
ACCEPTED MANUSCRIPT 358
Legend
359
Figure 1
CTG tracing and the timing of placental vascular
361
sonobiopsy examination using 3D power Doppler ultrasound at 38
362
weeks and 6 days of gestation. Each sphere of placental tissue was
363
obtained between the basal and chorionic plates. a, before uterine
364
contraction (at the start of contraction); b, during uterine contraction
365
(at the peak of contraction); c, after uterine contraction (at the end of
366
contraction).
AC C
EP
TE D
M AN U
SC
RI PT
360
25
RI PT
ACCEPTED MANUSCRIPT
Table1 Clinical characteristics of subjects Maternal age (yo)
Parity
Birth age Cervical (weeks) dilatation (cm)
Median (range)
Mean (SD)
Mean (SD)
32
29.9 (5.4)
0 (0-2)
39.5 (0.9) 6.1 (3.1)
Inducced labor 18
29.6 (3.9)
0 (0-2)
Significance
NS
NS
TE D
Mean (SD)
40.5 (0.9) 5.9 (3.3)
EP
AC C
Spontaneous labor
NS
Uterine Birth contraction weight interval (g) (min)
SC
n
M AN U
Subject
NS
Apgar score
1 min
5 min
UApH
Mean (SD)
Mean (SD)
Median (range)
Median (range)
Mean (SD)
3.8 (0.9)
3028.9 (230.3)
8 (7-10)
9 (7-10)
7.31 (0.08)
3.3 (0.6)
3212.7 (295.8)
8 (5-9)
9 (7-10)
7.28 (0.08)
NS
NS
NS
NS
NS
yo, years olds; min, minute; SD, standerd deviation; NS, not significant; UApH, umbilical artery blood pH.
ACCEPTED MANUSCRIPT
Table2 Percent change of each index value during uterine contraction Subject n Parameter Percent change Mean (SD)
Induced labor
32
18
VI
-34.3a (24.8)
8.6 (54.8)
FI
-1.9 (12.7)
5.7c (14.2)
VFI
-33.6a (28.1)
20.6 (74.4)
a
VI
-39.1 (25.6)
-2.8 (36.3)
FI
-9.0b (14.4)
-3.9c (11.6)
VFI
SC
Spontaneous labor
After
RI PT
During
AC C
EP
TE D
M AN U
-7.2 (39.1) -44.6a (25.6) VI, vascularization index; FI, flow index; VFI, vascularization flow index; a, p < 0.001; b, p = 0.035; c, p = 0.014. Data are presented as percent change compared with the value before uterine contraction.
ACCEPTED MANUSCRIPT Table3 Intra-class correlation coefficient and intra-observer agreement for placental vascularity indices Parameter
Mean difference
95% CI
Limits of agreement
P value
VI (%)
0.296
-1.065 to 1.657
5.997 to -5.404
0.654
0.940 < 0.0001
FI
1.597
0.018 to 3.176
8.209 to -5.016
0.048
0.711 < 0.0001
VFI
0.567
-0.315 to 1.448
4.258 to -3.125
0.194
0.925 < 0.0001
RI PT
ICC
P value
AC C
EP
TE D
M AN U
SC
VI, vascularization index; FI, flow index; VFI, vascularization flow index; 95% CI, 95% confidence interval; ICC, intra-class correlation coefficient.
ACCEPTED MANUSCRIPT Table4 Inter-class correlation coefficient and inter-observer agreement for placental vascularity indices Parameter
Mean difference
95% CI
Limits of agreement
P value
VI (%)
-1.149
-2.771 to 0.473
-7.942 to 5.644
0.155
FI
0.481
-0.793 to 1.754
-4.852 to 5.813
0.439
0.836 < 0.0001
VFI
-0.156
-0.985 to 0.673
-3.628 to 3.317
0.698
0.908 < 0.0001
ICC
P value
SC
RI PT
0.923 < 0.0001
AC C
EP
TE D
M AN U
VI, vascularization index; FI, flow index; VFI, vascularization flow index; 95% CI, 95% confidence interval; ICC, intra-class correlation coefficient.
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
ACCEPTED MANUSCRIPT 1
3D power Doppler ultrasound assessment of placental perfusion
2
during uterine contraction in labor
4
RI PT
3
Highlights
We assessed placental perfusion during spontaneous or induced
M AN U
6
SC
5
uterine contraction in labor at term using placental vascular sonobiopsy
8
with 3D power Doppler ultrasound and the VOCAL imaging analysis
9
program.
significant reduction in placental perfusion.
11
12
13
14
Uterine contraction in both spontaneous and induced labors led to a
EP
Reduced placental blood flow in induced uterine contraction has a
AC C
10
TE D
7
tendency to be more marked compared with that in spontaneous uterine
contraction.
1
ACCEPTED MANUSCRIPT 15
This is the first study on the non-invasive assessment of placental
perfusion during spontaneous or induced uterine contraction in labor
17
using 3D power Doppler ultrasound.
AC C
EP
TE D
M AN U
SC
RI PT
16
2
S0143-4004(16)30137-0
DOI:
10.1016/j.placenta.2016.06.018
Reference:
YPLAC 3434
To appear in:
Placenta
Received Date: 23 March 2016 Revised Date:
11 May 2016
Accepted Date: 30 June 2016
Please cite this article as: Sato M, Noguchi J, Mashima M, Tanaka H, Hata T, 3D power Doppler ultrasound assessment of placental perfusion during uterine contraction in labor, Placenta (2016), doi: 10.1016/j.placenta.2016.06.018. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT 1
3D power Doppler ultrasound assessment of placental perfusion
2
during uterine contraction in labor
RI PT
3 Miki Sato, MD1, Junko Noguchi, MS, PhD2, Masato Mashima, MD1, Hirokazu
5
Tanaka, MD, PhD1, Toshiyuki Hata, MD, PhD1
SC
4
M AN U
6
7
1
8
School of Medicine, 1750-1 Ikenobe, Miki, Kagawa 761-0793, Japan
9
2
12
13
TE D
281-1 Murecho-hara, Takamatsu, Kagawa 761-0123, Japan
EP
11
Department of Nursing, Kagawa Prefectural College of Health Sciences,
Running title: Placental perfusion during uterine contraction
AC C
10
Department of Perinatology and Gynecology, Kagawa University Graduate
14
Key words: Placental vascular sonobiopsy, 3D power Doppler ultrasound,
15
placental perfusion, spontaneous uterine contraction, induced uterine
16
contraction, labor
1
ACCEPTED MANUSCRIPT 17
18
Word count: 2,109
RI PT
19
All correspondence to: Toshiyuki Hata, MD, PhD, Department of
21
Perinatology and Gynecology, Kagawa University Graduate School of
22
Medicine, 1750-1 Ikenobe, Miki, Kagawa 761-0793, Japan
23
M AN U
SC
20
TEL. +81-(0)87-891-2174
25
FAX. +81-(0)87-891-2175
26
E-mail: [email protected]
EP
27
TE D
24
Conflict of Interest
29
The authors declare no conflict of interest.
AC C
28
30
2
ACCEPTED MANUSCRIPT 31
ABSTRACT
32
Introduction: To assess placental perfusion during spontaneous or induced
34
uterine contraction in labor at term using placental vascular sonobiopsy
35
(PVS) by 3D power Doppler ultrasound with the VOCAL imaging analysis
36
program.
37
Method: PVS was performed in 50 normal pregnancies (32 in spontaneous
38
labor group [SLG], and 18 in induced labor group with oxytocin or
39
prostaglandin F2 [ILG]) at 37 to 41 weeks of gestation to assess placental
40
perfusion during uterine contraction in labor. Only pregnancies with an
41
entirely visualized anterior placenta were included in the study. Data
42
acquisition was performed before, during (at the peak of contraction), and
43
after uterine contraction. 3D power Doppler indices such as the
44
vascularization index (VI), flow index (FI), and vascularization flow index
45
(VFI) were calculated in each placenta.
AC C
EP
TE D
M AN U
SC
RI PT
33
3
ACCEPTED MANUSCRIPT Results: There were no abnormal fetal heart rate tracings during contraction
47
in either group. VI and VFI values were significantly reduced during uterine
48
contraction in both groups (SLG: median, -30.4% [range, -95.6 − 9.7%], and
49
ILG, -45.1% [-76.0 − 3.5%]), respectively (P < 0.001). The FI value in the
50
ILG group was significantly lower during uterine contraction (P = 0.035),
51
whereas it did not change during uterine contraction in the SLG group. After
52
uterine contraction, all vascular indices returned almost to the same level as
53
that before uterine contraction. However, the FI value in ILG (-8.6%, [-19.7 −
54
16.0%]) was significantly lower than that in SLG (2.4%, [-13.4 − 38.1%]) after
55
uterine contraction (P < 0.05). All 3D power Doppler indices (VI, FI, and VFI)
56
during uterine contraction (at the peak of contraction) showed a correlation
57
greater than 0.7, with good intra- and inter-observer agreements.
58
Discussion: Our findings suggest that uterine contraction in both
59
spontaneous and induced labors causes a significant reduction in placental
60
perfusion. Reduced placental blood flow in induced uterine contraction has a
61
tendency to be marked compared with that in spontaneous uterine
AC C
EP
TE D
M AN U
SC
RI PT
46
4
ACCEPTED MANUSCRIPT contraction. To the best of our knowledge, this is the first study on the non-
63
invasive assessment of placental perfusion during uterine contraction in
64
labor using 3D power Doppler ultrasound. However, the data and their
65
interpretation in the present study should be taken with some degree of
66
caution because of the small number of subjects studied. Further studies
67
involving a larger sample size are needed to assess placental perfusion and
68
vascularity using PVS during normal and abnormal uterine contractions in
69
normal and high-risk pregnancies.
M AN U
SC
RI PT
62
TE D
70
Key words: Placental vascular sonobiopsy, 3D power Doppler ultrasound,
72
placental perfusion, spontaneous uterine contraction, induced uterine
73
contraction, labor
AC C
74
EP
71
5
ACCEPTED MANUSCRIPT 75
1. Introduction
76
In spontaneous uterine contraction, maternal placental blood flow
78
before labor was reported to be 4.5% of the cardiac output, decreasing to
79
2.9% (35.5% decrease) during uterine contraction, and increasing to 7.2%
80
(60% increase) after contraction in pregnant rhesus monkeys [1]. Reduction
81
of placental blood flow during spontaneous uterine contraction was also 30 ±
82
8% in dogs and 35 ± 12% in rabbits [2]. On the contrary, in induced uterine
83
contraction with oxytocin and prostaglandin E2, uterine contraction led to a
84
marked reduction (average: 73%) of the placental blood flow in pregnant
85
rhesus monkeys, and the placental blood flow partially recovered after the
86
uterine contraction [3]. These reductions of placental blood flow on induced
87
uterine contraction with oxytocin were 43 ± 16% in dogs, and 46 ± 13% in
88
rabbits [2]. However, to the best of our knowledge, there are no available
89
data on the change in placental blood flow during uterine contraction in the
90
human placenta.
AC C
EP
TE D
M AN U
SC
RI PT
77
6
ACCEPTED MANUSCRIPT Placental vascular sonobiopsy (PVS) using three-dimensional (3D)
92
power Doppler ultrasound with VOCAL imaging histogram analysis is a
93
novel technique to quantitatively and qualitatively assess the vascularization
94
and blood flow in the placenta [4-6]. Moreover, PVS is a valid alternative for
95
evaluation of the placental vascularity and blood flow when visualization of
96
the entire placenta is not feasible [7]. In the present study, we assessed
97
placental perfusion during spontaneous or induced uterine contraction in
98
labor at term using PVS.
2. Patients and Methods
EP
100
TE D
99
101
103
2.1. Patients
AC C
102
M AN U
SC
RI PT
91
104
In the period from July 2012 to May 2015, 73 women with normal
105
singleton pregnancies in labor at 37 to 41 weeks of gestation were studied
106
cross-sectionally. The women were recruited randomly. The fetal age was
7
ACCEPTED MANUSCRIPT calculated from the first day of the last menstrual period, with confirmation by
108
first-trimester ultrasound. Women with gestational diabetes, chronic
109
hypertension, maternal systemic disease, or taking antihypertensive
110
medications were not enrolled. Of the 73 women, 23 (31.5%) were excluded
111
because of insufficient data acquisition due to severe artifacts caused by
112
uterine contraction or maternal movements. Therefore, 50 women (32 in a
113
spontaneous labor group [SLG], and 18 in an induced labor group with
114
oxytocin or prostaglandin F2
115
Indications of induced labor were a weak labor in 11 women, and post-term
116
pregnancy in 7 women. Clinical characteristics of the subjects in each group
117
are shown in Table 1. The umbilical artery pulsatility index in all subjects was
118
normal at 26 to 29 weeks of gestation. The growth of all fetuses was normal,
119
and there were no abnormalities during pregnancy. This study was approved
120
by the Kagawa University Graduate School of Medicine Ethics Committee,
121
and standardized written informed consent was obtained from all women.
M AN U
SC
RI PT
107
AC C
EP
TE D
[ILG]) underwent further investigation.
122
8
ACCEPTED MANUSCRIPT 123
2.2. Ultrasound examination
124
A single experienced observer (M.S.) performed all 3D power Doppler
126
ultrasound scans using a Voluson E8 A6 2.4 (GE Healthcare Japan, Tokyo,
127
Japan) with a transabdominal 1-4 MHz transducer (RAB2-5-D) at the first
128
stage of labor. At each examination, each placenta was confirmed to be
129
located in an anterior position. 3D power Doppler ultrasound was employed
130
for a representative placental vascular tree volume based on the following
131
procedure, described in detail in our previous investigations [4-6]. The
132
maximal sensitivity was ensured by setting the pulse repetition frequency
133
(PRF) to 0.6 kHz and the wall motion filter to ‘low’. The following constant
134
default instrument settings (corresponding to the manufacturer’s Doppler
135
power setting) were used throughout the examinations: frequency, mid;
136
dynamic, balance, 225; smooth, 4/5; ensemble, 11; line density, 8; power
137
Doppler map, 4; artifact suppression, on; power Doppler line filter, 3; quality,
138
normal. The power Doppler window was placed over the placenta, including
AC C
EP
TE D
M AN U
SC
RI PT
125
9
ACCEPTED MANUSCRIPT its total thickness, from the basal to chorionic plates. The 3D volume box was
140
positioned over the placenta at a fixed 65˚ angle. Volume acquisition was
141
carried out within 16 seconds before (at the start of contraction), during (at the
142
peak of contraction), and after uterine contraction (at the end of contraction)
143
(Figure 1).
SC
RI PT
139
As presented in detail in our previous studies [4-6], the examination of
145
placental perfusion was performed using PVS. In the measurement of PVS,
146
the power Doppler window is placed over the placenta, including its total
147
thickness, from the basal to chorionic plates (excluding both of them). The
148
spherical 3D volume is obtained between the basal and chorionic plates
149
(Figure 1). The VOCAL program automatically calculates color values
150
(vascularization index [VI], flow index [FI], and vascularization flow index
151
[VFI]) from the acquired sphere. A sequence of six placental sections
152
separated by successive rotations of 30° is obtaine d, and 1 to 3 spherical
153
sampling sites are chosen in each plane. Each spherical volume was taken at
154
approximately equidistant intervals along the length of the placental image.
AC C
EP
TE D
M AN U
144
10
ACCEPTED MANUSCRIPT Each index was an average value from those of 6 to 13 spheres in each
156
placenta. A single experienced observer (M.S.) conducted all 3D Doppler
157
ultrasound histogram analyses with the VOCAL program.
RI PT
155
158
2.3. Statistical analysis
SC
159
M AN U
160
All statistical analyses were performed with SPSS statistical software,
162
version 23 for Windows (SPSS Inc., Chicago, IL, USA). Differences in the
163
maternal age, birth age, cervical dilatation, interval of uterine contraction,
164
birth weight, and umbilical artery blood pH between SLG and ILG groups
165
were assessed by the unpaired t-test. Differences in Apgar scores between
166
the groups were investigated with the Mann-Whitney U test. The percent
167
change of each index during uterine contraction was assessed by the
168
Wilcoxon Signed-rank test. Differences in variables at each stage between
169
SLG and ILG groups were investigated with the Mann-Whitney U test. Intra-
170
and inter-class correlation coefficients were used as an expression of
AC C
EP
TE D
161
11
ACCEPTED MANUSCRIPT reliability [8]. Intra- and inter-class correlation coefficients were defined as
172
the correlation between any two measurements from the same data during
173
uterine contraction (at the peak of contraction). Their values ranged from
174
zero to one; the latter indicates maximum reliability. Intra- and inter-observer
175
variability were calculated according to Bland and Altman’s procedure [9] in
176
20 samples (11 in SLG and 9 in ILG). Intra-observer variation was examined
177
by M.S., and inter-observer variation was assessed by M.S. and J.N. This
178
analysis consisted of a graph, in which the difference between the
179
measurements (y-axis) was plotted against their mean value (x-axis). The
180
95% limits of individual agreement between the two measurements were
181
calculated as the mean difference between two measurements ± 2.0
182
standard deviations. Moreover, the difference between the mean difference
183
and zero was assessed by a two-sample t-test. A P-value < 0.05 was
184
considered significant.
AC C
EP
TE D
M AN U
SC
RI PT
171
185
186
3. Results
12
ACCEPTED MANUSCRIPT 187
There were no significant differences in the maternal age, parity, birth
189
age, cervical dilatation at examination (SLG: mean, 6.1 cm [SD: ± 3.1], and
190
ILG, 5.9 cm [± 3.3]), interval of uterine contraction at examination (SLG:
191
mean, 3.8 min [SD: ± 0.9], and ILG, 3.3 min [± 0.6]), birth weight, Apgar
192
scores at 1 and 5 min, or umbilical artery blood pH between the two groups
193
(Table 1). There was no fever-up during delivery. All women had a normal
194
vaginal delivery. Within 24 hours after delivery, an extensive pediatric
195
assessment was performed of each neonate. No neonate was found to have
196
congenital anomalies or genetic disorders.
EP
TE D
M AN U
SC
RI PT
188
There were no abnormal fetal heart rate tracings during contraction in
198
either group. The percent change of each vascular index value during
199
uterine contraction in both groups is shown in Table 2. VI and VFI values
200
were significantly reduced during uterine contraction in both groups (SLG:
201
median, -30.4% [range: -95.6 − 9.7%], and ILG, -45.1% [-76.0 − 3.5%]),
202
respectively (P < 0.001). The FI value in the ILG group was significantly
AC C
197
13
ACCEPTED MANUSCRIPT lower during uterine contraction (P = 0.035), whereas it did not change
204
during uterine contraction in the SLG group. After uterine contraction, all
205
vascular indices returned almost to the same level at that before uterine
206
contraction. However, the FI value in ILG (-8.6%, [-19.7 − 16.0%]) was
207
significantly lower than that in SLG (2.4%, [-13.4 − 38.1%]) after uterine
208
contraction (P < 0.05). There were no significant differences in any vascular
209
index values during uterine contraction, nor any significant differences in VI
210
or VFI values after uterine contraction between SLG and ILG groups.
213
214
SC
M AN U
TE D
3.1. Intra-observer agreement
EP
212
The mean difference between measurements and the limits of
AC C
211
RI PT
203
215
agreement for each of the parameters studied during uterine contraction (at
216
the peak of contraction) are shown in Table 3. The mean difference and 95%
217
limits of intra-observer agreements for VI, FI, and VFI were 0.296% (5.997, -
218
5.404), 1.597 (8.209, -5.016), and 0.567 (4.258, -3.125), respectively. The
14
ACCEPTED MANUSCRIPT difference between the mean difference and zero was not significant for VI
220
or VFI, but was weakly significant for FI (P = 0.048). Intra-class correlation
221
coefficients for each of the parameters studied are also shown in Table 3. VI,
222
FI, and VFI had intra-class correlation coefficients of 0.940, 0.711, and 0.925,
223
respectively (P < 0.0001).
SC
RI PT
219
225
3.2. Inter-observer agreement
226
M AN U
224
The mean difference between the two investigators (M.S. and J.N.)
228
and the limits of agreement for each of the parameters studied during uterine
229
contraction (at the peak of contraction) are shown in Table 4. The mean
230
difference and 95% limits of inter-observer agreements for VI, FI, and VFI
231
were -1.149% (5.644, -7.942), 0.481 (5.813, -4.852), and -0.156 (3.317, -
232
3.628), respectively. The difference between the mean difference and zero
233
was not significant for each 3D power Doppler vascularity index. Inter-class
234
correlation coefficients for each of the parameters studied are also shown in
AC C
EP
TE D
227
15
ACCEPTED MANUSCRIPT 235
Table 4. VI, FI, and VFI had inter-class correlation coefficients of 0.923,
236
0.836, and 0.908, respectively (P < 0.0001).
In this study, good intra- and inter-class correlation coefficients and
238
intra- and inter-observer agreements were confirmed. Therefore, the
239
measurement values from only one examiner (M.S.) were used for statistical
240
analysis.
M AN U
SC
RI PT
237
241
243
4. Discussion
TE D
242
In the present study, uterine contraction in both spontaneous and
245
induced labors led to a significant reduction in placental perfusion. The main
246
reason for this significant reduction in placental perfusion during uterine
247
contraction is that uterine contractions prevent blood flow into the intervillous
248
space [10, 11]. Interestingly, the reduced placental blood flow in induced
249
uterine contraction had a tendency to be more marked compared with that in
250
spontaneous uterine contraction. Similar findings have also been obtained in
AC C
EP
244
16
ACCEPTED MANUSCRIPT 251
animal experiments [1-3]. Moreover, the recovery of placental blood flow
252
after uterine contraction was rapid in spontaneous labor compared with
253
induced
254
spontaneous and induced uterine contractions may be the significantly
255
higher intensity of labor produced by oxytocin and prostaglandins [2, 3].
256
Another explanation is that prostaglandin F2 has a strong vasoconstrictive
257
effect on both uterine and umbilical circulations [12]. This may explain the
258
differences between the groups. Therefore, these results suggest that we
259
may have to pay attention to the use of oxytocin and prostaglandin F2 for
260
the induction of labor due to the significantly higher intensity of uterine
261
contractions produced by these agents.
explanation
for
these
discrepancies
between
EP
TE D
M AN U
SC
RI PT
The
Fetal heart rate tracings during uterine contraction in SLG and ILG
AC C
262
labor.
263
groups showed no decelerations in this study, although there was a
264
significant reduction in placental blood flow during uterine contraction in both
265
groups. Stuart et al. [13] reported that placental vascular resistance to feto-
266
placental blood flow was not altered by uterine contractions nor the infusion
17
ACCEPTED MANUSCRIPT of oxytocin during uncomplicated labor. There was no difference in fetal
268
oxygenation in the intervillous spaces between spontaneous and oxytocin-
269
induced labors [14]. Subjects enrolled in the present study all had normal
270
pregnancies, and normal vaginal deliveries. Moreover, umbilical artery data
271
in all subjects were normal during pregnancy. Neonatal outcomes were also
272
very favorable. Therefore, feto-placental functions in all pregnancies in this
273
study were good, and each fetus was suggested to have a good reserve
274
capacity to compensate for uterine contractions in labor.
M AN U
SC
RI PT
267
In the present study, we only examined an entirely visualized anterior
276
placenta to keep the maximum depth of the placenta constant [4, 5],
277
because there was a significant reduction in each vascular index value
278
assessed by 3D power Doppler as the distance between the transducer and
279
vascular tree volume increased [15]. Zalud and Shaha [16] stated that only
280
anterior placentas should be included in 3D power Doppler studies to avoid
281
the risk of Doppler signal attenuation. This limitation and disadvantage of 3D
AC C
EP
TE D
275
18
ACCEPTED MANUSCRIPT 282
power Doppler histogram analysis will be resolved as further technical
283
advances are made.
To the best of our knowledge, this is the first study on non-invasive
285
assessment of placental perfusion during spontaneous and induced uterine
286
contractions in labor using PVS by 3D power Doppler ultrasound with the
287
VOCAL imaging histogram analysis. However, the data and their
288
interpretation in the present study should be taken with some degree of
289
caution because of the small number of subjects studied. Further studies
290
involving a larger sample size are needed to evaluate placental blood flow
291
and vascularity using PVS during normal and abnormal uterine contractions
292
in normal and high-risk pregnancies.
SC
M AN U
TE D
EP
AC C
293
RI PT
284
19
ACCEPTED MANUSCRIPT Acknowledgements
295
The work reported in this paper was supported by a Grant-in-Aid for
296
scientific Research on Innovative Areas "Constructive Developmental
297
Science" (No.24119004), and a Research Grant (No.25462561) from The
298
Ministry of Education, Culture, Sports, Science and Technology, Japan.
SC
RI PT
294
M AN U
299
Conflict of Interest
301
The authors have no conflict of interest.
EP AC C
302
TE D
300
20
ACCEPTED MANUSCRIPT 303
References
304
1.
Lees MH, Hill J, Ochsner AJ III, Thomas CL, Novy MJ. Maternal
RI PT
305
placental and myometrial blood flow of the rhesus monkey during
307
uterine contractions. Am J Obstet Gynecol 1971;110:68-81.
2.
Hidaka A, Komatani M, Kurosumi K, Shimazu T, Sugawa T. Influence
M AN U
308
SC
306
309
of uterine contraction on maternal and fetoplacental hemodynamics.
310
Nihon Sanka Fujinka Gakkai Zasshi 1976;28:105-112. (Japanese)
3.
Novy MJ, Thomas CL, Lees MH. Uterine contractility and regional
TE D
311
blood flow responses to oxytocin and prostaglandin E2 in pregnant
313
rhesus monkeys. Am J Obstet Gynecol 1975;122:419-433.
4.
using three-dimensional power Doppler ultrasound in normal and
315
growth restricted fetuses. Placenta 2009;30:391-397.
316
317
318
Noguchi J, Hata K, Tanaka H, Hata T. Placental vascular sonobiopsy
AC C
314
EP
312
5.
Hata T, Tanaka H, Noguchi J, Hata K. Three-dimensional ultrasound
evaluation of the placenta. Placenta 2011;32:105-115.
21
ACCEPTED MANUSCRIPT 319
6.
Noguchi J, Tanaka H, Koyanagi A, Miyake K, Hata T. Three-
320
dimensional power Doppler indices at 18-22 weeks’ gestation for
321
prediction
322
hypertension. Arch Gynecol Obstet 2015;292:75-79.
growth
restriction
or
pregnancy-induced
RI PT
fetal
7.
Tuuli MG, Houser M, Odibo L, Huster K, Macones GA, Odibo AO.
Validation
placental
vascular
sonobiopsy
for
obtaining
325
representative placental vascular indices by three-dimensional power
326
Doppler ultrasonography. Placenta 2010;31:192-196.
M AN U
324
8.
Mercé LT, Barco MJ, Bau S. Reproducibility of the study of placental
TE D
327
of
SC
323
of
vascularization by three-dimensional power Doppler. J Perinat Med
329
2004; 32: 228-233.
331
9.
between two methods of clinical measurement. Lancet 1986; 1: 307-
310.
332
333
334
Bland JM, Altman DG. Statistical methods for assessing agreement
AC C
330
EP
328
10.
Ramsey
EM,
Corner
GWJr,
Donner
MW.
Serial
and
cineradioangiographic visualizeation of maternall circulateon in the
22
ACCEPTED MANUSCRIPT 335
primate (hemochorial) placenta. Am J Obstet Gynecol 1963;86:213-
336
225.
11.
Borell U, Fernström I, Ohlson L, Wiqvist N. Effect of uterine
RI PT
337
contractions on the human uteroplacental blood circulateon. Am J
339
Obstet Gynecol 1964;89:881-890.
12.
McLaughlin MK, Brennan SC, Chez RA. Vasoconstrictive effects of
M AN U
340
SC
338
341
prostaglandins in sheep placental circulations. Am J Obstet Gynecol
342
1978;130:408-413.
13.
Stuart B, Drumm J, FitzGerald DE, Duignan NM. Fetal blood velocity
TE D
343
waveforms
345
1981;88:865-869.
347
14.
350
labour.
Br
J
Obstet
Gynaecol
Truppin M, Wolf L. The maternal-fetal oxygen pressure gradient in
spontaneous and oxytocin-induced labors. Am J Obstet Gynecol
1961;82:804-808.
348
349
uncomplicated
AC C
346
in
EP
344
15.
Raine-Fenning NJ, Nordin NM, Ramnarine KV, Campbell BK, Clewes
JS, Perkins A, Johnson IR. Determining the relationship between
23
ACCEPTED MANUSCRIPT three-dimensional
352
characteristics: an in-vitro flow phantom experiment. Ultrasound
353
Obstet Gynecol 2008;32:540-550.
354
16.
power
Doppler
data
and
true
blood
flow
RI PT
351
Zalud I, Shaha S. Three-dimensional sonography of the placental and
uterine spiral vasculature: Influence of maternal age and parity. J Clin
356
Ultrasound 2008;36:391-396.
M AN U
SC
355
AC C
EP
TE D
357
24
ACCEPTED MANUSCRIPT 358
Legend
359
Figure 1
CTG tracing and the timing of placental vascular
361
sonobiopsy examination using 3D power Doppler ultrasound at 38
362
weeks and 6 days of gestation. Each sphere of placental tissue was
363
obtained between the basal and chorionic plates. a, before uterine
364
contraction (at the start of contraction); b, during uterine contraction
365
(at the peak of contraction); c, after uterine contraction (at the end of
366
contraction).
AC C
EP
TE D
M AN U
SC
RI PT
360
25
RI PT
ACCEPTED MANUSCRIPT
Table1 Clinical characteristics of subjects Maternal age (yo)
Parity
Birth age Cervical (weeks) dilatation (cm)
Median (range)
Mean (SD)
Mean (SD)
32
29.9 (5.4)
0 (0-2)
39.5 (0.9) 6.1 (3.1)
Inducced labor 18
29.6 (3.9)
0 (0-2)
Significance
NS
NS
TE D
Mean (SD)
40.5 (0.9) 5.9 (3.3)
EP
AC C
Spontaneous labor
NS
Uterine Birth contraction weight interval (g) (min)
SC
n
M AN U
Subject
NS
Apgar score
1 min
5 min
UApH
Mean (SD)
Mean (SD)
Median (range)
Median (range)
Mean (SD)
3.8 (0.9)
3028.9 (230.3)
8 (7-10)
9 (7-10)
7.31 (0.08)
3.3 (0.6)
3212.7 (295.8)
8 (5-9)
9 (7-10)
7.28 (0.08)
NS
NS
NS
NS
NS
yo, years olds; min, minute; SD, standerd deviation; NS, not significant; UApH, umbilical artery blood pH.
ACCEPTED MANUSCRIPT
Table2 Percent change of each index value during uterine contraction Subject n Parameter Percent change Mean (SD)
Induced labor
32
18
VI
-34.3a (24.8)
8.6 (54.8)
FI
-1.9 (12.7)
5.7c (14.2)
VFI
-33.6a (28.1)
20.6 (74.4)
a
VI
-39.1 (25.6)
-2.8 (36.3)
FI
-9.0b (14.4)
-3.9c (11.6)
VFI
SC
Spontaneous labor
After
RI PT
During
AC C
EP
TE D
M AN U
-7.2 (39.1) -44.6a (25.6) VI, vascularization index; FI, flow index; VFI, vascularization flow index; a, p < 0.001; b, p = 0.035; c, p = 0.014. Data are presented as percent change compared with the value before uterine contraction.
ACCEPTED MANUSCRIPT Table3 Intra-class correlation coefficient and intra-observer agreement for placental vascularity indices Parameter
Mean difference
95% CI
Limits of agreement
P value
VI (%)
0.296
-1.065 to 1.657
5.997 to -5.404
0.654
0.940 < 0.0001
FI
1.597
0.018 to 3.176
8.209 to -5.016
0.048
0.711 < 0.0001
VFI
0.567
-0.315 to 1.448
4.258 to -3.125
0.194
0.925 < 0.0001
RI PT
ICC
P value
AC C
EP
TE D
M AN U
SC
VI, vascularization index; FI, flow index; VFI, vascularization flow index; 95% CI, 95% confidence interval; ICC, intra-class correlation coefficient.
ACCEPTED MANUSCRIPT Table4 Inter-class correlation coefficient and inter-observer agreement for placental vascularity indices Parameter
Mean difference
95% CI
Limits of agreement
P value
VI (%)
-1.149
-2.771 to 0.473
-7.942 to 5.644
0.155
FI
0.481
-0.793 to 1.754
-4.852 to 5.813
0.439
0.836 < 0.0001
VFI
-0.156
-0.985 to 0.673
-3.628 to 3.317
0.698
0.908 < 0.0001
ICC
P value
SC
RI PT
0.923 < 0.0001
AC C
EP
TE D
M AN U
VI, vascularization index; FI, flow index; VFI, vascularization flow index; 95% CI, 95% confidence interval; ICC, intra-class correlation coefficient.
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
ACCEPTED MANUSCRIPT 1
3D power Doppler ultrasound assessment of placental perfusion
2
during uterine contraction in labor
4
RI PT
3
Highlights
We assessed placental perfusion during spontaneous or induced
M AN U
6
SC
5
uterine contraction in labor at term using placental vascular sonobiopsy
8
with 3D power Doppler ultrasound and the VOCAL imaging analysis
9
program.
significant reduction in placental perfusion.
11
12
13
14
Uterine contraction in both spontaneous and induced labors led to a
EP
Reduced placental blood flow in induced uterine contraction has a
AC C
10
TE D
7
tendency to be more marked compared with that in spontaneous uterine
contraction.
1
ACCEPTED MANUSCRIPT 15
This is the first study on the non-invasive assessment of placental
perfusion during spontaneous or induced uterine contraction in labor
17
using 3D power Doppler ultrasound.
AC C
EP
TE D
M AN U
SC
RI PT
16
2