First trimester placental and myometrial blood perfusion measured by 3D power Doppler in normal and unfavourable outcome pregnancies
Introduction
The causes for pregnancy-associated problems like pre-eclampsia and intrauterine growth restriction are diverse and elusive, and yet, from a clinical point of view, there seems to be an underlying basis – namely abnormally low blood flow through the placenta [1], [2], [3], [4]. A clinical example which supports this hypothesis is increased uterine artery blood flow impedance in the second trimester of pregnancy measured by 2D ultrasound Doppler. A great number of studies show a strong correlation between this condition of reduced placental blood flow, caused by an impaired trophoblast invasion, and conditions like pre-eclampsia and intrauterine growth restriction [5], [6], [7], [8], [9], [10]. When this connection was detected, it raised hope that women at risk could be treated prophylactically several weeks before the real disease starts, in order to avoid or at least mitigate any pregnancy problems. Nevertheless, it turned out that the detection of increased uterine artery impedance during the second trimester is only of limited use, as prophylactic treatment at this late stage is not sufficiently effective [11], [12], [13], [14]. At best it may lead to better pregnancy surveillance. The next logical step was to perform uterine Doppler measurements in the first trimester to start a possible treatment at this early stage. Increased uterine artery impedance in the first trimester is unfortunately not as helpful as in the second trimester as its correlation with pregnancy problems is considerably weaker [15], [16], [17], [18].
Uterine artery impedance reflects the resistance of blood flow in the decidual and myometrial spiral arteries of the mother. Fetal trophoblasts invade maternal tissue alongside these arteries, destroying their muscle fibres and thus remodelling these vessels into pliant channels, leading to low flow resistance. The activity of this process is only inadequately captured by uterine artery Doppler impedance, as trophoblast invasion starts as early as the first trimester but Doppler studies show the best result many weeks afterwards at approximately 22–24 weeks.
A possible approach to assess trophoblast invasion in the first trimester, i.e. at the time when it actually takes place, could be to measure placental and myometrial vascularization and perfusion. Power Doppler sonography is a method which allows observation of the number and flow of small tissue-vessels. It has been stated that it could be superior to spectral Doppler in low velocity blood flow conditions [19], [20]. 3D methods however can provide this information for the entire placenta and its adjoining myometrium. Some studies have focused on this particular aspect but they were mostly performed relatively late in pregnancy and the methods used were unconvincing as only parts of the placentas were measured [21], [22], [23], [24].
In this study we present data of routine 3D power Doppler measurements of the entire placenta and the neighbouring myometrium, done between 11 and 14 weeks of gestation. We want to ascertain how placental and myometrial blood flow and vascularization behave at this early stage of pregnancy. By comparing these findings with second trimester uterine artery impedance and pregnancy outcome data we want to know whether these indices can be used to assess the trophoblast activity in order to detect risk pregnancies earlier in pregnancy.
Section snippets
Methods
All women who book for delivery in our hospital routinely receive a free nuchal translucency and “combined test” measurement between 11 and 14 weeks when they give their consent. At the same time we routinely measure the placental volume (PV) with 3D ultrasound and form the placental quotient (PQ = placental volume/crown-rump length) which has repeatedly been described [25], [26], [27]. We also examine both uterine arteries at the level of the internal cervical os and calculate the pulsatility
Statistics
Associations were calculated by the non-parametric Spearman’s correlation coefficient in SAS (SAS/STAT User’s Guide, Version 9, Cary, NC 27513: SAS Institute Inc. 2002–2003). A group consisting of PE and PIH-pregnancies was formed and compared with the group of normal outcome pregnancies using the Kruskal–Wallis test. Pair-wise comparisons for all measured parameters between normal versus PE and PIH-pregnancies were done by the Wilcoxon test. P-values for those pair-wise comparisons were
Results
Placental and myometrial vascularization and flow in 423 singleton pregnancies were measured. Six had to be excluded due to fetal aneuploidies or malformations. Four women suffered from abortion between 12 and 22 weeks. 30 women did not show up at the scheduled time of fetal anomaly scan for unknown reasons or pregnancy outcome could not be followed up, which left a total of 383 women for evaluation.
Maternal data are shown in Table 1.
The correlations of the collected data to placental and
Discussion
Many attempts have been made to find first trimester parameters which are able to detect pregnancies at risk for IUGR and PE. According to a common hypothesis, these severe problems are a consequence of low placental blood flow due to impaired trophoblast invasion [1], [2], [3], [4]. Efforts have been made to assess reduced placental blood flow using uterine artery spectral Doppler. Large scale studies, however, show that the sensitivity of this method is limited if used as a screening tool in
References (38)
- et al.
Essai Regional Aspirin Mere-Enfant (ERASME) collaborative group. Randomised comparison of uterine artery Doppler and aspirin (100 mg) with placebo in nulliparous women: the essai regional aspirine mere-enfant study (Part 2)
BJOG
(2003) - et al.
Placental vascular sonobiopsy using three-dimensional power Doppler Ultrasound in normal and growth retarded fetuses
Placenta
(2009) - et al.
Correlation of first trimester placental volume and second trimester uterine artery Doppler flow
Placenta
(2001) - et al.
Factors affecting color Doppler energy ultrasound recordings in an in-vitro model
Ultrasound Med Biol
(1998) - et al.
The physiological response of the vessels of the placental bed to normal pregnancy
J Pathol Bacteriol
(1967) - et al.
Inadequate maternal vascular response to placentation in pregnancies complicated by pre-eclampsia and by small-for-gestational-age infants
Br J Obstet Gynaecol
(1986) - et al.
Placental bed spiral arteries in the hypertensive disorders of pregnancy
Br J Obstet Gynaecol
(1991) - et al.
A study of placental bed spiral arteries and trophoblast invasion in normal and severe pre-eclamptic pregnancies
Br J Obstet Gynaecol
(1994) - et al.
Doppler ultrasound screening as part of routine antenatal scanning: prediction of pre-eclampsia and intrauterine growth retardation
Br J Obstet Gynaecol
(1993) - et al.
Improved prediction of pre-eclampsia by two-stage screening of uterine arteries using the early diastolic notch and color Doppler imaging
Obstet Gynecol
(1993)
The association between increased mean arterial pressure and abnormal uterine artery resistance to blood flow during pregnancy
Obstet Gynecol
Fetomaternal Doppler sonography nomograms
Clin Exp Obstet Gynecol
Assessment of risks for the development of pre-eclampsia by maternal characteristics and uterine artery Doppler
BJOG
Uterine artery Doppler in the prediction of adverse pregnancy outcome
Curr Opin Obstet Gynecol
Fetal Medicine Foundation Second Trimester Screening Group. Randomized controlled trial using low-dose aspirin in the prevention of pre-eclampsia in women with abnormal uterine artery Doppler at 23 weeks’ gestation
Ultrasound Obstet Gynecol
CLASP: a randomised trial of low-dose aspirin for the prevention and treatment of pre-eclampsia among 9364 pregnant women. CLASP (Collaborative Low-dose Aspirin Study in Pregnancy) collaborative group
Lancet
Barbados Low Dose Aspirin Study in Pregnancy (BLASP): a randomised trial for the prevention of pre-eclampsia and its complications
Br J Obstet Gynaecol
Uterine artery Doppler at 11-14 weeks of gestation to screen for hypertensive disorders and associated complications in an unselected population
Ultrasound Obstet Gynecol
Screening for pre-eclampsia and fetal growth restriction by uterine artery Doppler at 11–14 weeks of gestation
Ultrasound Obstet Gynecol
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