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Measurement Techniques and Potential Application in the Prediction of Pregnancy Complications Kwok Yin Leung; Teresa Ma; Betty YT Lau; Min Chen Posted: 07/10/2012; Expert Rev of Obstet Gynecol. 2012;7(4):379-386. 2012 Expert Reviews Ltd.

Abstract and Introduction

Abstract

First-trimester prediction of intrauterine growth restriction (IUGR), preeclampsia (PE), birthweight, aneuploidy, miscarriage, complications in multiple pregnancies and homozygous 0-thalassemia is a challenging and emerging field. Placenta volumes (PV) and embryo volume/fetal volume ratios are correlated with crownrump length (CRL) or gestational age. Measurement of PV or placental quotient (PV/CRL ratio) is an early method to identify impaired trophoblast invasion and predict subsequent development of IUGR or PE. In early-onset IUGR caused by triploidy, or trisomy 13 or 18, a larger deficit in fetal volume than CRL is observed. Fetal and placental volume measurements may be applied to predict other conditions such as aneuploidy, miscarriage or stillbirth. Standardization of the 3D volumetric methodology is needed to improve reproducibility of measurement. Further studies are required to determine the use of first-trimester volumetry alone or in combination with Doppler ultrasound and other parameters to achieve the best predictive models for IUGR and PE.
Introduction

The development of 3D ultrasound has enabled us to measure the volumes of the embryo (EV), fetus (FV),[1,2] placenta (PV),[3,4] gestational sac (GSV)[1,5] and yolk sac (YSV)[1,6] reliably in the first trimester. A strong correlation between EV[7]/FV ratio,[2,8] PV,[4] GSV[9] and crownrump length (CRL) or gestational age (GA) has been shown.[4,810] An increase in FV or PV over gestation was much greater than CRL.[4,9] Several studies have been performed to investigate the use of first-trimester volumetry in the prediction of intrauterine growth restriction (IUGR; failure of the fetus to achieve its growth potential) and preeclampsia (PE; proteinuric hypertension in pregnancy),[1114] birthweight, [15,16] aneuploidy,[1721] miscarriage,[2224] complications in multiple pregnancies,[25,26] homozygous 0-thalassemia[27] and other adverse outcomes. The pathophysiology of both IUGR and PE includes impairment of trophoblastic invasion of the maternal spiral arteries and their conversion from narrow muscular vessels to wide nonmuscular channels. The traditional prediction methods include maternal history, 2D ultrasonography and biochemical markers.[2832] The use of first-trimester uterine artery Doppler (UAD) and placental biochemical markers (including pregnancy-associated plasma protein A, PGF, soluble fms-like tyrosine kinase 1, P-selectin and neutrophil gelatinase-associated lipocalin) can detect 7788.9% of PE at a 10% false-positive rate,[2830] but present biochemical markers or UAD alone are not sufficiently accurate.[335] The sensitivity of UAD in predicting small-for-gestational-age (SGA)/IUGR was low, ranging from 14 to 37%,[32,34] and for late PE was not high, at approximately 57.0%.[30] Measurement of the gestational sac diameter and CRL has been used to determine GA and for the evaluation of miscarriage. However, measuring CRL can be less reliable before 7 and after 10 weeks' gestation because of amorphous embryonic contour and fetal movements, respectively.[35] Sonographically thick placenta at the second or third trimester is associated with SGA or largefor-gestational-age infants at term.[36] Increased placental thickness at the first trimester is a sonographic sign of homozygous 0-thalassemia, but its sensitivity is 72%.[37] In general, the use of 3D ultrasound to measure volumes of regularly or irregularly shaped objects is more accurate than 2D ultrasound, and is sufficiently accurate and reliable for clinical use.[38,39] Volume calculations are commonly performed using the multiplanar method (which is more time consuming) or a rotational method with virtual organ computer-aided analysis (VOCAL) software (GE Medical Systems, Zipf, Austria).[2,4,5,7,33] Newer volumetric tools include a semiautomated virtual reality (VR) system, ISpace VR (Barco, Kortrijk, Holland), which allows the creation of a 'hologram' of the ultrasound image, depth perception and interaction with the rendered objects,[40] an automated tool for fluid-filled spaces, sonography-based automated volume count (SonoAVC; GE Medical Systems),[41] and extended imaging (XI) VOCAL.[11,42] Ideally, 3D volumetry, like 2D parameters, should be measured using a standardized method to give reproducible results. However, different investigators have applied different techniques for 3D volumetry of different structures, and have presented different reference data (Table 1).
Table 1. Reference data of first-trimester volumetry measured by different 3D ultrasound techniques.

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3D parameters

3D measurement techniques

Gestation (weeks) 6 7 8 9 10 11 12

Ref.

EV/FV (cm3)

Multiplanar VOCAL (30) XI VOCAL Virtual reality

0.04 0.07 0.04

0.19 0.40 0.20 0.31

0.74 0.99 1.02

2.31 2.31 2.45

5.84 4.62 5.12 5.35

11.84 8.65 9.71

19.29 14.25 22.20 [51] 114.93 90.8 87.10 0.12 0.12

[1] [2] [10] [40]

VOCAL vs SonoAVC GSV (cm ) Gestational sac fluid volume (cm3)

3

Mean difference of -76.5% with limit of agreement ranging from -159.6 to 6.7% Multiplanar VOCAL VOCAL Virtual reality Multiplanar VOCAL Virtual reality XI VOCAL Multiplanar VOCAL 4.36 3.8 2.18 0.04 0.05 7.52 8.3 3.97 4.86 0.07 0.06 0.08 0.06 12.97 16.2 5.87 9.82 0.10 0.10 0.08 22.38 26.0 13.75 18.20 0.12 0.12 0.10 38.61 47.1 23.33 32.36 0.13 0.16 0.15 0.16 66.61 67.9 53.70 0.13 0.18

[1] [5] [33] [40] [1] [6] [40] [10] [3] [4]

Yolk sac volume (cm )

PV (ml)

Median: 41.3 ml (CRL: 3544 mm), 48.5 ml (CRL: 4554 mm), 59.2 ml (CRL: 5564 mm) PV = 1.73 exp(0.076 CRL)

CRL: Crownrump length; EV: Embryo volume; FV: Fetal volume; GSV: Gestational sac volume; PV: Placental volume; SonoAVC: Sonography-based automated volume count; VOCAL: Virtual organ computer-aided analysis; XI: Extended imaging.

The aim of this article is to review the current measurement techniques for first-trimester volumetry and their potential applications.

Placental Volume
After automatic acquisition of 3D volume, the placenta is defined by the basal and chorionic border with the uterine wall carefully excluded.[43] Common measurement techniques include the VOCAL method with a 30 rotation angle[10,22] or the multiplanar method.[27] Inter- and intra-observer correlations were good, ranging from 0.8 to 0.99 in some studies,[10,22,23] but relatively poor in another study.[27] XI VOCAL cannot be used interchangeably with VOCAL or multiplanar techniques in measuring PV at 1114 weeks' gestation because of inferior reproducibility and in vivo validity.[44] There was a strong correlation between PV and CRL or GA from 7 to 13 + 6 weeks.[4,16,18] PV increased from 1.7 ml at 7 weeks, through 42.6 ml at 10 + 6 weeks, to 91 ml at 13 + 6 weeks.[4,18] While CRL increased only 4.4-times from 9 to 40 mm, the mean PV increased 10.5-times.[4] Placental quotient (PQ) equals PV divided by the fetal CRL,[12] and is a simple first-trimester parameter to indicate whether a placenta is large or small for a given fetus.[3] Neither PV nor PQ are associated with maternal plasma cell-free fetal DNA levels, which may reflect the extent of placental apoptosis[45] or other unknown mechanisms. There are limitations in using placental volumetry for clinical applications because of the physiological variations in placental shape, weight and volume[46] at each stage of gestation,[47] the heterogeneous nature of placental growth,[13] and the reproducibility and accuracy of measuring the volume of the placenta, an irregular structure.[39]

EV or FV
EV/FV can be measured directly[2] or by subtracting the amniotic fluid and yolk sac volumes from the GSV.[48] Using a direct method, the fetus is traced by drawing a contour line along its head and trunk while excluding the limbs, which usually cross over each other or touch the face in the late first trimester.[8,49] However, other investigators have suggested that measurement of FV should include the limbs, which represent a significant proportion (810%) of the size of the embryonic/fetal body.[50] Specialized 3D software that allows the combination of several volume measurements from various anatomical regions of the fetus in the same dataset at the same time is required. The head volume can also be measured separately and then subtracted from the total head and trunk volume to obtain the volume of the fetal

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trunk.[19]

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VOCAL is a commonly used technique,[2,8] but it is more difficult and it is time consuming to measure embryonic limbs, which appear as separate disconnected objects from the trunk in certain planes unless a thin connecting stalk is drawn between the limbs and the trunk. The reproducibility of doing so has not yet been proven. VOCAL with 9 rotation provides the best compromise among validity, reliability and time required for measurements when compared with the 30, 15 and 6 rotation steps.[39] Other described methods include the multiplanar technique and, rarely, the XI VOCAL technique.[42] It appears that 3D ultrasound (using a multiplanar, VOCAL or XI VOCAL technique) can provide a reproducible measurement of the fetal trunk and head volume at 11 + 0 to 13 + 6 weeks' gestation.[42] The interand intra-observer correlations have shown to be very good.[7,10,42] Semiautomated techniques, using both VOCAL and SonoAVC,[51] facilitate the measurement of the embryo without the need to physically define its contour, which is the prime limiting factor in the aforementioned techniques. However, there was a significant difference in the volumetry between this semiautomated technique and the conventional VOCAL technique alone with 9 rotations.[51] There was a significant correlation between EV and GA or CRL,[2,7,16] with a linear association between 11 + 0 weeks and 13 + 6 weeks,[8] or between a CRL of 45 and 84 mm.[8] These findings are consistent with previous 2D sonographic studies on the S-shaped pattern of fetal growth with gestation, with the linear component at 10 and 30 weeks.[52] At between 11 + 0 and 13 + 6 weeks there is a five- to six-fold increase in FV but only a doubling in CRL.[8] This can represent a mathematical relation of quadratic versus cubic measurement. Whether FV is a potential first-trimester marker of IUGR is not clear. There was no difference in EV between male and female embryos.[1] EV was a better predictor of GA than CRL in a study of 30 in vitro fertilization pregnancies between 7 and 10 weeks of gestation.[53] A recent review has shown that a wide discrepancy exists in reported normal volumes of first-trimester embryos, ranging from 0.20.23 cm3 at 7 weeks to 3.915.12 cm3 at 10 weeks.[7,10,54] This wide discrepancy is likely to be due to inconsistencies in 3D volumetric methodology, inadequate assessment of method repeatability and validity, and a diversity of mutually incompatible 3D imaging formats and software measuring tools. Standardization of the 3D volumetric methodology will help to improve quality assurance in fetal volumetry, and then facilitate its clinical use.[54]

Gestational Sac Volume

The gestational sac consists of the amniotic cavity and the exocelomic cavity in the first trimester. GSV is commonly measured using the VOCAL method with a 30 rotation angle.[9,33] Intraobserver variability was excellent, with an average difference between measurements of 0.5 cm3.[9] GSV can be measured with reliably in VR, but the results were on average 19.8% smaller than the GSV calculated using the ellipsoid formula.[55] There was a high correlation between GSV and GA or CRL.[1,9,16] Mean GSV increased from 8.50 cm3 at 7 weeks to 44.35 cm3 at 10 weeks,[15] and 69 ml at 11 weeks to 144 ml at 13 + 6 weeks.[20] GSV increased from 5.00 to 50.28 cm3 for a CRL increase from 0.9 to 4 cm.[9] GSV is closely related to amniotic fluid volume, which is an ultrafiltrate of maternal plasma. GSV may reflect uteroplacental function in the first trimester,[56] and may potentially have predictive value for adverse pregnancy outcomes.[24]

Gestational Sac Fluid Volume

The gestational sac fluid volume (GSFV) is obtained by subtracting the EV from the GSV after measuring them using VOCAL, with a rotational step of 30 rotation.[33] The GSFV can also be measured using the multiplanar method or VR.[55] SonoAVC is automatic, but may significantly underestimate GSFV.[51] There is a significant correlation between GSFV and GA or CRL.[33] Mean GSFV increased by approximately five- to six-fold from 3.97 cm3 at 77+6 weeks to 23.33 cm3 at 1010+6 weeks of pregnancy.[33] However, the corresponding range of GSFV was wide at 1.1710.97 cm3 (~tenfold) and 11.9332.41 cm3 (~threefold), respectively.[33] Mean GSFV increased by approximately six- to seven-fold from 7.81 to 50.28 cm3 for a CRL increase from 12 to 40 mm.[33] The GSFV/EV ratio decreased with GA.[55] In normal pregnancies, there was a progressive increase in amniotic fluid from 8 to 11 weeks of gestation.[57] Abnormal amniotic fluid volumes may indicate a pathology associated with adverse outcomes,[58] and further studies are required.

Yolk Sac Volume

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YSV was measured using the VOCAL method with 30 rotation[6] or XI VOCAL.[59] There was a poor correlation between YSV and GA or CRL.[6] The mean YSV increased from 0.063 cm3 at 7 weeks to 0.164 cm3 at 10 weeks.[6] Similar to another study,[60] the mean YSV increased in a linear fashion up to 10 weeks, then maintained a plateau until 11 weeks, and decreased thereafter.[6] This can probably be explained by the yolk sac degeneration process secondary to vascular depletion.[61] The absence or malformation of a yolk sac outside the normal growth pattern is associated with poor pregnancy outcomes.[62]

Potential Applications
The potential applications of first-trimester volumetry are summarized in Table 2.
Table 2. Potential applications of first-trimester volumetry.

Area

Main findings

Ref.

Birthweight IUGR Preeclampsia

The embryonic volume during the first trimester of pregnancy correlates better with birthweight than the crownrump length Placental quotient at 12 weeks and uterine artery Doppler at 22 weeks have similar sensitivities (27.1 vs 28.1%) for predicting IUGR The detection of preeclampsia had a sensitivity of 38.5% (placental quotient at 12 weeks) versus 44.8% (uterine artery Doppler at 22 weeks) First-trimester volumetry is unlikely to be a useful predictor of major chromosomal defects In early-onset IUGR caused by aneuploidy, a larger deficit in fetal volume than crownrump length was observed Compared with unaffected pregnancies, the placental quotient of affected pregnancies was greater, while fetal volumes were smaller at 914 weeks' gestation Median twin and triplet placental volumes were 1.66 and 2.28 multiples of the median for singletons, respectively. There was no difference in the rate of placental growth between 11 and 13 + 6 weeks among singletons, twins and triplets 3D volumetric assessment does not improve the diagnosis of miscarriage over conventional 2D sonographic measurements

[15,16] [1114] [12]

Aneuploidy Homozygous 0 -thalassemia Multiple pregnancy

[1721]

[27]

[25,26]

Miscarriage

[2224]

IUGR: Intrauterine growth restriction.

Birthweight Prediction

A strong correlation between placental size and birthweight was well demonstrated previously.[15] A recent study has showed that PV multiples of the median were reduced in SGA neonates (0.88), but increased in large-for-gestational-age neonates (1.09) compared with appropriate-for-gestational-age neonates (1.0).[15] A prospective study of 199 singleton low-risk pregnant women showed that EV during the first trimester of pregnancy correlates better with birthweight than CRL, GSV and PV.[16] A 10 mm3 increase in EV corresponds to a mean birthweight increase of 75 g, while a 1-mm increase in CRL corresponds to a birthweight increase of 113 g.[16] Further studies are required to confirm the usefulness of EV in the prediction of pregnancies complicated by macrosomia or low-birthweight fetuses.
Intrauterine Growth Restriction

Antenatal detection of pregnancies at risk of IUGR can reduce perinatal morbidity and mortality by four- to five-fold.[63] Measurement of PV or PQ may be an efficient method for the early and simple identification of impaired first wave of trophoblast invasion, and the subsequent development of IUGR.[11,12] In a prospective study of 1060 women, a small PV or PQ between 11 and 13 weeks was associated with high-resistance uterine perfusion in the second trimester.[11] Unlike uterine artery Doppler, PV and PQ did not show any dependency on age, gravidity, BMI or smoking habits.[11] In a study of 2489 consecutive singleton pregnancies, PQ at 12 weeks and uterine artery Doppler at 22 weeks had similar sensitivities (27.1 vs 28.1%) for predicting IUGR.[12] In a prospective study of 1199 women at 12 weeks' gestation, the PV was smaller in pregnancies subsequently complicated by SGA neonates with or without PE.[13] A PQ 10th centile occurred in 10% of pregnancies and its sensitivity in predicting complications including IUGR, PE or placental abruption was 22%.[14]
Preeclampsia

PE occurs in approximately 2% of pregnancies, but is a major cause of maternal and perinatal morbidity and mortality.[59] In a prospective

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study of 2489 consecutive singleton pregnancies, logistic regression models for the detection of PE had a sensitivity of 38.5% (PQ at 12 weeks) versus 44.8% (uterine artery Doppler at 22 weeks).[12] Taking a PQ that is 10th centile, the sensitivity for PE with and without SGA neonates was 30.8 and 20.0%, respectively. It appears that PQ is marginally less sensitive than uterine artery Doppler for the prediction of PE,[12] but similarly sensitive (~50%) in predicting the most severe complications, in which delivery took place before 34 weeks.[12]
Aneuploidy

An initial study in 2002 showed that the median PQ in a group of mixed chromosomal abnormalities (0.67) was significantly lower than that in normal fetuses (0.98),[17] and suggested that the inclusion of PV measurements as an additional marker to nuchal translucency may improve the sensitivity of first-trimester screening.[17] A subsequent study showed that the mean PV for GA was smaller in conjunction with trisomies 13 and 18 than in normal pregnancies.[18] However, no difference was observed between normal pregnancies and those with trisomy 21 or Turner syndrome.[18] Measurement of the PV, GSV and FV at 1113 + 6 weeks of gestation is unlikely to be a useful predictor of major chromosomal defects.[1821] In early-onset IUGR caused by aneuploidy, a larger deficit in FV than CRL was observed.[21] This discrepancy can be explained by a larger growth rate of FV than CRL (five- to six-fold vs twofold) in normal fetuses at between 11 + 0 and 13 + 6 weeks.[8] FV may be a better firsttrimester marker of IUGR than CRL. Compared with chromosomally normal fetuses, the fetal head volume for CRL was significantly smaller in conjunction with trisomy 21, trisomy 13 and Turner syndrome, but similar in association with trisomy 18 and triploidy.[19] The fetal trunk volume for CRL was significantly smaller in all chromosomal abnormalities except Turner syndrome.[19] It appears that the IUGR was symmetrical, with the head and trunk being equally affected in fetuses with trisomy 21 and Turner syndrome, but asymmetrical, with the trunk being more severely compromised than the head, in those with triploidy and trisomies 18 and 13.[19] The mean GSV for GA was smaller in pregnancies with triploidy and trisomy 13 than in normal pregnancies, probably owing to a reduced amniotic fluid volume.[20]
Thalassemia

Fetal homozygous 0-thalassemia is the most common cause of hydrops fetalis in southeast Asia. Using placental thickness, the sensitivity to predict an affected pregnancy before 12 weeks of gestation was 72% with a specificity of 97%.[37] In a preliminary study including 11 affected fetuses and 94 normal controls, the mean PQ in affected pregnancies was larger than that seen in unaffected pregnancies (1.37 [standard deviation: 0.65] vs 1.13 [standard deviation: 0.39]), although this difference was not significant.[27] More recently, 106 pregnancies with a larger number of affected pregnancies (n = 26) were studied. Compared with unaffected pregnancies, the FV and FV/CRL quotients of affected pregnancies were significantly smaller at 914 weeks' gestation, although their CRLs were similar [Leung KY, Unpublished Data]. In addition, the PVs and PQs of affected pregnancies were significantly greater [Leung KY, Unpublished Data]. Early-onset IUGR and placentomegaly were probably caused by fetal anemia and hypoxia associated with homozygous 0-thalassemia. Consistent with another study,[8] it appears that 3D volumetry is more sensitive than CRL in detecting IUGR in early pregnancy. Further studies using a larger sample size are needed.
Multiple Pregnancy

In a prospective study on 290 consecutive twin and 37 triplet pregnancies at 11 + 0 to 13 + 6 weeks of gestation,[25] median twin and triplet PVs were 1.66 and 2.28 multiples of the median for singletons, respectively. It appears that PV in multiple pregnancies does not depend on chorionicity. There was no difference in the rate of placental growth between 11 and 13 + 6 weeks among singletons, twins and triplets.[25] In a dichorionic twin pregnancy, discordance in growth with a distinctly small PV was associated with an abnormal twin with triploidy of maternal phenotype.[26]
Miscarriage

In a study of 111 pregnancies, including 30 ongoing pregnancy and 81 miscarriages, the correlation between the GSV and CRL or GA was weaker in cases of missed miscarriage than in ongoing pregnancies.[22] The GSV:EV ratio in missed miscarriages was significantly higher than those in ongoing pregnancies.[56] However, in another study on 86 patients, a logistical regression analysis showed no significant correlation between GSV and the outcome of missed miscarriages managed expectantly.[23] In a study of 125 asymptomatic pregnant women, YSV outside the 5th to 95th percentile or GSV less than the 5th percentile were associated with spontaneous miscarriage in univariate but not in regression analysis.[24] It appears that 3D volumetric assessment does not improve the diagnosis of miscarriage over conventional 2D sonographic measurements.[2224]

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Expert Commentary
It is feasible and reproducible to undertake volumetry of the placenta, fetus, gestational sac, gesational sac fluid and york sac in the first trimester using 3D ultrasound.[16,33] Although the traditional prediction method focuses on clinical history, 2D sonographic parameters and biochemical markers,[2832] first-trimester volumetry may represent an important tool for the prediction of birthweight and pregnancy complications.[1127] There was a strong correlation between PV and EV measured by 3D ultrasound, and CRL or GA in the first trimester. [4,7,9,10] Measurement of PV/PQ is an early method to identify impaired trophoblast invasion, and its use can predict the subsequent development of IUGR at a sensitivity of 27.1% or PE at 38.5%.[12] However, this method alone probably cannot predict all cases of at-risk pregnancies. At between 11 + 0 and 13 + 6 weeks, an increase in FV is greater than CRL.[8] In early-onset IUGR caused by aneuploidy[19] or homozygous 0-thalassemia [Leung KY, Unpublished Data],[44] a larger deficit in fetal volume than CRL was observed. Further studies, including pathological examinations, are required to investigate the pathophysiology. The accuracy of volumetry depends on the measurement technique, the object being measured and the observer.[42] A wide discrepancy in reported normal volumes of first-trimester embryo[54] and other structures (Table 1) was probably a result of inconsistencies in the measurement technique used, inadequate assessment of technique repeatability and validity, and a diversity of mutually incompatible 3D imaging formats and software measuring tools. As the placenta is an irregular structure, the influence of measurement error is larger than it is for the fetus, which is relatively regular and symmetrical.[42,44] The clinical use of placental volumetry is further limited by physiological variations in placental shape, weight and volume [46] at each stage of gestation,[47] and the heterogeneity of placental growth.[39]
Table 1. Reference data of first-trimester volumetry measured by different 3D ultrasound techniques.

3D parameters

3D measurement techniques

Gestation (weeks) 6 7 8 9 10 11 12

Ref.

EV/FV (cm )

Multiplanar VOCAL (30) XI VOCAL Virtual reality

0.04 0.07 0.04

0.19 0.40 0.20 0.31

0.74 0.99 1.02

2.31 2.31 2.45

5.84 4.62 5.12 5.35

11.84 8.65 9.71

19.29 14.25 22.20 [51] 114.93 90.8 87.10 0.12 0.12

[1] [2] [10] [40]

VOCAL vs SonoAVC GSV (cm3) Gestational sac fluid 3 volume (cm )

Mean difference of -76.5% with limit of agreement ranging from -159.6 to 6.7% Multiplanar VOCAL VOCAL Virtual reality Multiplanar VOCAL Virtual reality XI VOCAL Multiplanar VOCAL 4.36 3.8 2.18 0.04 0.05 7.52 8.3 3.97 4.86 0.07 0.06 0.08 0.06 12.97 16.2 5.87 9.82 0.10 0.10 0.08 22.38 26.0 13.75 18.20 0.12 0.12 0.10 38.61 47.1 23.33 32.36 0.13 0.16 0.15 0.16 66.61 67.9 53.70 0.13 0.18

[1] [5] [33] [40] [1] [6] [40] [10] [3] [4]

Yolk sac volume (cm3)

PV (ml)

Median: 41.3 ml (CRL: 3544 mm), 48.5 ml (CRL: 4554 mm), 59.2 ml (CRL: 5564 mm) PV = 1.73 exp(0.076 CRL)

CRL: Crownrump length; EV: Embryo volume; FV: Fetal volume; GSV: Gestational sac volume; PV: Placental volume; SonoAVC: Sonography-based automated volume count; VOCAL: Virtual organ computer-aided analysis; XI: Extended imaging.

Five-Year View
The possible applications of 3D volumetry in the first trimester include prediction of IUGR, PE, birthweight, homozygous 0-thalassemia and other adverse pregnancy outcomes. With advances in technology, 3D volumetry will be much simpler and more accurate, and the measurement time will be reduced. Standardization of 3D volumetric methodology and training might improve the quality assurance in first-trimester volumetry, and then facilitate clinical use.[54] Further development of 3D technology may allow a semiautomated or automated measurement of 3D volumetry in a reliable and accurate manner.

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In the future, the prediction of IUGR and PE could be improved, and ideally be incorporated in the same setting as first-trimester screening for Down's syndrome. Combining first-trimester volumetry with other methods including maternal history, 2D sonographic parameters such as uterine artery Doppler and biochemical markers such as placental hormones is promising.[31] With the recent advances in 3D power Doppler ultrasound and histogram analysis, it is feasible to perform assessments of the vascularization and blood flow of the placenta,[64] with good reproducibility of the 3D power Doppler parameters.[65] Altered 3D fetoplacental volumetry and placental Doppler indices are related to subsequent development of IUGR, PE and other adverse pregnancy outcomes.[64,66] Further studies are required to determine the choice of parameters to achieve the best predictive models.

Sidebar
Key Issues

First-trimester volumetry includes measurement of the volume of the placenta (PV), embryo (EV), fetus (FV), gestational sac and yolk sac. PV, EV/FV ratio and gestational sac volume are correlated with crownrump length (CRL) or gestational age. PV or placental quotient (PV/CRL ratio) is an early method used to identify impaired trophoblast invasion, and its use can predict the subsequent development of intrauterine growth restriction at a sensitivity of 27.1% or preeclampsia at 38.5%. At between 11 + 0 and 13 + 6 weeks, an increase in FV (five- to six-fold) is greater than CRL (twofold). The EV during the first trimester of pregnancy correlates better with birthweight than CRL. In early-onset intrauterine growth restriction caused by aneuploidy or homozygous 0-thalassemia, a larger deficit in FV than CRL was observed. First-trimester volumetry is unlikely to be a useful predictor of major chromosomal defects. The accuracy of volumetry depends on the measurement technique used, the object being measured and the observer. Standardization of 3D volumetric methodology and training will help to improve the quality assurance in first-trimester volumetry, as well as facilitate clinical use.
References

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