- Email: [email protected]
Three-dimensional Ultrasound Measurement of the Placental Volume in Early Pregnancy: Method and Correlation with Biochemical Placenta Parameters
Placenta (2001), 22, 602–605 doi:10.1053/plac.2001.0684, available online at http://www.idealibrary.com on
Three-dimensional Ultrasound Measurement of the Placental Volume in Early Pregnancy: Method and Correlation with Biochemical Placenta Parameters M. Metzenbauera,c, E. Hafnera, D. Hoefingera, K. Schuchtera, G. Stanglb, E. Ogrisb and K. Philippa a
Ludwig-Boltzmann-Institute of Clinical Obstetrics and Gynaecology, Department of Obstetrics and Gynaecology, Donauspital am SMZ-Ost, Langobardenstrasse 122, A-1220 Vienna and b Department of Nuclear Medicine, Donauspital am SMZ-Ost, Langobardenstrasse 122, A-1220 Vienna, Austria Paper accepted 2 March 2001
Placental size has been an interesting topic of research for many years. The main aim of this study was to investigate the feasibility of measuring the placental volume at the end of the first trimester using three-dimensional (3D) ultrasound and to correlate these volumes to known placental functional indices and to factors affecting the placenta. Women with singleton pregnancies at the end of the first trimester were included into this study. The volume data of the placentae were correlated to the crown–rump length (CRL), placenta-associated plasma protein A (PAPP-A), free beta-human chroangiogonadotropin (f--hCG) and other factors that may affect the placental size or function. A total of 1462 pregnancies could be evaluated. Comparison between CRL and placental volume proved a significant correlation (r=0.43, P<0.001). Due to the observed proportional growth of CRL and placental volume, a quotient (placental volume/CRL) was calculated for each case. There were no differences between placenta/CRLquotients in relation to gravidity, parity or smoking. Correlations could be established between the placental volume and PAPP-A and f--hCG (PAPP-A: r=0.28, P<0.001, f--hCG: r=0.10, P<0.001). The measurement of the placenta in the first trimester can be performed in a high percentage of cases. The placenta/CRL quotient represents a simple method to compare placentae from different gestational days. The correlation between placental volume and maternal serum screening parameters might provide a chance to refine first trimester Down’s syndrome serum screening. Future studies will be needed to evaluate the possible clinical use of first trimester placental volume measurements. 2001 Harcourt Publishers Ltd Placenta (2001), 22, 602–605
INTRODUCTION It is known that intrauterine growth restriction is often associated with a smaller placenta (Aherne, 1966; Aherne and Dunnill, 1966; Ruckhaberle et al., 1977; Molteni, Stys and Battaglia, 1978; Senecal et al., 1980). Therefore, measurements of placental size using ultrasound for the early detection of potential risk pregnancies have been a topic of some previous studies. Back in 1980, Hoogland and colleagues found that the rate of small-for-gestational-age (SGA) birthweight was higher in pregnancies with smaller placental areas in mid-trimester (Hoogland, de Haan and Martin, 1980). Wolf et al. concluded that small placental volumes, which were estimated by using two-dimensional ultrasound, were more common in cases of adverse pregnancy outcome (Wolf, Oosting and Treffers, 1989). After the introduction of three-dimensional (3D) c To whom correspondence should be addressed at: LudwigBoltzmann-Institute of Clinical Obstetrics and Gynaecology, Department of Obstetrics and Gynaecology, Donauspital am SMZ-Ost, Langobardenstrasse 122, A-1220 Vienna, Austria. Fax: 0043-1-288023880; E-mail: [email protected]
0143–4004/01/060602+04 $35.00/0
ultrasound, placental volumes could be measured more precisely. Hafner et al. found a dependency of birthweight on placental volume in mid-trimester (Hafner et al., 1998). Until now, no data has been published about placental volumetry in the first trimester. In this study, the feasibility of such measurements was first examined. Second, information about the size of the placenta at this stage of pregnancy was obtained. Third, possible correlations were investigated between placental volume and placenta-dependent parameters such as placenta-associated plasma protein A (PAPP-A) and free beta-human chorangiogonadotropin (f--hCG)—which are used in biochemical Down’s syndrome serum screening. Finally, the influence of gravidity, parity and smoking habits was explored.
METHODS All women with singleton pregnancies who visited the department for routine nuchal translucency measurement (which is offered free of charge) over a 10-month period and whose fetal 2001 Harcourt Publishers Ltd
M. Metzenbauer et al.: Three-dimensional Ultrasound Measurement
603
Table 1. Study population
Recruited Excluded Exclusion because of insufficient image quality Exclusion because of diagnosed fetal aneuploidy, intrauterine death before 24 weeks, severe fetal malformations Included Gravidity
1 >1 0 >0 <20 20–29 30–39 >39
Parity Maternal age at the estimated date of delivery
crown–rump length (CRL) was 35 to 64 mm (inclusive) were included in this study. Fetuses with smaller or larger CRLs were not included because of the small number. We excluded pregnancies with diagnosed aneuploidies, intrauterine fetal death or major malformations and cases where ultrasound volume data were insufficient. Insufficient data referred to those in which the entire placenta and/or clear sonographic separation of the placenta was/were not obtained. Gravidity, parity and smoking habits were also noted. Assessment of placental volume was carried out after the routine ultrasound examination during which fetal CRL and nuchal translucency were measured. A Voluson 530D MT of Kretztechnik was used. This machine is equipped with special 3D probes that can ascertain volumes by automatic movements of the transducer around adjustable angles. Routinely, an abdominal probe was used. If the quality was insufficient—as in women who were obese or had a retroverted uterus—a transvaginal transducer was used. Scanned volume datasets were stored on hard disk for later analysis. The measurements were performed in such a way that parallel slices were identified at different parts of the placenta—from one end to the other. Each of these circumferences was marked manually around the boundary between the placenta and surrounding tissues. On average, approx 2 min are needed to mark one placental volume. The volume was calculated by a computer using the formula:
(A=area, d=distance between two areas) All measurements were performed by one of two observers (MM, DH). As previously described, this method has a low intra- and interobserver variability (Hafner et al., 1998). From preliminary data we got the impression that the average placental size grows considerably between the first and second trimester. Therefore, we expected the median placental
Number
Percentage
1513
100.0
51 30
2.3 2.0
21
1.4
1462 573 889 769 693 48 695 680 39
96.6 39.2 60.8 52.6 47.4 3.3 47.5 46.5 2.7
volume to change distinctly during the observed gestational stage. The initial data suggested that this change occurs in line with CRL values, so a quotient placental volume/CRL was considered. To estimate the usefulness of this formula, three groups were formed (fetuses with CRLs from 35 to 44, from 45 to 54 and from 55 to 64) and their median placental volumes were then determined. Finally, the anticipated median for the placental volume/CRL ratio of approx 1 was evaluated from the available data. A free first trimester screening for Down’s syndrome was offered to all women (‘combined test’: nuchal translucency measurements and detection of PAPP-A and f--hCG in maternal serum). Serum samples were taken on the day 3D placental volume and nuchal translucency was measured. Serum analysis was performed with radio immunoassay (Ortho-Clinical Diagnostics, Johnson & Johnson, NJ, USA). Then the concentrations of the parameters were converted into Multiple of Median (MoM) values using Alpha software (Logical Medical Systems, UK). Next PAPP-A and f--hCG were compared to placental volume. Statistical evaluation was carried out with a descriptive analysis, Pearson’s correlation and median tests for an estimation of differences between the groups studied.
RESULTS During the 10-month period 1513 pregnant women were recruited for this study (there was a total of 1518 women but five refused to take part). Image quality was insufficient in 30 cases (consequently, 98 per cent of the volumes could be measured). Twenty-one further pregnancies were eliminated due to diagnosed aneuploidies, intrauterine fetal death or major malformations. In total, the results of 1462 women were evaluated. Population characteristics are shown in Table 1. Pearson’s coefficient showed a significant correlation between CRL and placental volume (r=0.43, 95 per cent CI:
Placenta (2001), Vol. 22
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parameters (PAPP-A: r=0.28, 95 per cent CI: 0.23–0.33, P<0.001, f--hCG: r=0.10, 95 per cent CI: 0.05–0.16, P<0.001, Pearson’s correlation, t approximation)
100
DISCUSSION
Placental volume
140
80 60 40 20 0 30
40
50 CRL
60
Figure 1. Correlation between crown–rump length and placental volume in millilitres (r=0.43, 95 per cent CI: 0.39–0.47, P<0.001, Pearson correlation, t-approximation).
0.39–0.47, P<0.001, Pearson’s correlation, t-approximation, Figure 1). The median of the placental volume was 41.3 ml in pregnancies with a CRL from 35 to 44 mm (n=442), 48.5 ml in pregnancies with a CRL from 45 to 54 mm (n=739) and 59.2 ml in pregnancies with a CRL from 55 to 64 mm (n=281). Due to the parallel development of CRL and placental volume, a quotient (placental volume/CRL) was subsequently calculated for each measurement. The median for this quotient was similar in all three groups: 1.02 ml/mm for the first, 0.99 ml/ mm for the second, and 1.03 ml/mm for the third group. As there is a dependency on the placenta/CRL quotient in all three groups, no test was performed. There were no differences in the placenta/CRL quotient between primi- and multigravidae (0.99 versus 1.01 ml/mm, P=n.s., median test), between nulli- and multiparae (1.00 versus 1.01 ml/mm, P=n.s., median test) and between smokers and non-smokers (0.99 versus 1.01 ml/mm, P=n.s., median test). PAPP-A and f--hCG were taken from 1378 women (94.3 per cent). A significant correlation could be established between the placenta/CRL-quotient and both serum
Previous studies have only described placental volume measurements at advanced stages of pregnancy. This is the first time that a large number of such assessments have been made during the first trimester. Three main conclusions can be made. First, volumetry of the placenta can be carried out in a high percentage of late first trimester pregnancies. The examinations are simple to perform and the measurements can be acquired quickly and easily. Second, a correlation between the CRL and the placental volume could be found—although the relatively small r value indicates that the spread is quite high. Future studies have to demonstrate if these differences have any diagnostic value; for example, if a relatively small placenta is associated with an impaired pregnancy outcome (e.g. SGA birthweight). The placenta/CRL quotient represents a straightforward method for comparing placentae between different gestational days. It can be employed as a method for ‘normalizing’ or correcting discrepances due to growth. Furthermore, no differences in placenta/CRL-quotient were found between women with different gravidity, parity and smoking habit. Finally, the discovery of some weak correlation between placental volume and maternal serum screening markers might provide an opportunity to refine first trimester Down’s syndrome serum screening. For example, a pregnancy with a relatively small placenta and low PAPP-A might be less at risk than a larger placenta and low PAPP-A. Further studies need to be undertaken to estimate this hypothesis. If first trimester placental volumetry proves to be a reasonable method for determining risk pregnancies, then the potential for the prevention of pregnancy complications would be considerable. Studies that have used medications like acetyl salicylic acid when second trimester uterine artery Doppler velocimetry was impaired showed, if any, only relatively small advantages (CLASP, 1994). Volumetry of the placenta during the first trimester could be helpful because of the less advanced state of placentation. As previously mentioned, larger studies are needed to provide answers to all of these questions.
ACKNOWLEDGEMENTS We would like to thank Mrs Brigitte Dillinger-Paller, Mr Thomas Kratochwil and Mr David Nunez for their valuable contributions. This study was supported by the Austrian Science Fund (project number P 13847).
REFERENCES Aherne W (1966) A weight relationship between the human foetus and placenta. Biol Neonat, 10, 113–118. Aherne W & Dunnill MS (1966) Quantitative aspects of placental structure. J Pathol Bacteriol, 91, 123–139. CLASP (Collaborative Low-dose Aspirin Study in Pregnancy) (1994) CLASP: a randomized trial of low-dose aspirin for the prevention and treatment of pre-eclampsia among 9364 pregnant women. Lancet, 343, 619–629.
Hafner E, Philipp T, Schuchter K, Dillinger-Paller B, Philipp K & Bauer P (1998) Second-trimester measurements of placental volume by three-dimensional ultrasound to predict small-for-gestational-age infants. Ultrasound Obstet Gynecol, 12, 97–102. Hoogland HJ, de Haan J & Martin CB (1980) Placental size during early pregnancy and fetal outcome: A preliminary report of a sequential ultrasonographic study. Am J Obstet Gynecol, 138, 441–443. Molteni RA, Stys SJ & Battaglia FC (1978) Relationship of fetal and placental weight in human beings: fetal/placental weight ratios at various
M. Metzenbauer et al.: Three-dimensional Ultrasound Measurement gestational ages and birth weight distributions. J Reprod Med, 21, 327–334. Ruckhaberle KE, Viehweg B, Ruckhaberle B, Schlegel C, Leistner B, Ebert S & Schulz S (1977) Macroscopically determined placentary conditions in the case of underweight neonates. Zentralbl Gynakol, 99, 1323–1330.
605 Senecal J, Kerisit J, Defawe G, Lefrancois MC, Fisselier MP, Grall JY & Le Marec B (1980) A study of the weight of the placenta in normal and pathological pregnancies. J Gynecol Obstet Biol Reprod (Paris), 9, 531–536. Wolf H, Oosting H & Treffers PE (1989) Second-trimester placental volume measured by ultrasound: Prediction of fetal outcome. Am J Obstet Gynecol, 160, 121–126.
Three-dimensional Ultrasound Measurement of the Placental Volume in Early Pregnancy: Method and Correlation with Biochemical Placenta Parameters M. Metzenbauera,c, E. Hafnera, D. Hoefingera, K. Schuchtera, G. Stanglb, E. Ogrisb and K. Philippa a
Ludwig-Boltzmann-Institute of Clinical Obstetrics and Gynaecology, Department of Obstetrics and Gynaecology, Donauspital am SMZ-Ost, Langobardenstrasse 122, A-1220 Vienna and b Department of Nuclear Medicine, Donauspital am SMZ-Ost, Langobardenstrasse 122, A-1220 Vienna, Austria Paper accepted 2 March 2001
Placental size has been an interesting topic of research for many years. The main aim of this study was to investigate the feasibility of measuring the placental volume at the end of the first trimester using three-dimensional (3D) ultrasound and to correlate these volumes to known placental functional indices and to factors affecting the placenta. Women with singleton pregnancies at the end of the first trimester were included into this study. The volume data of the placentae were correlated to the crown–rump length (CRL), placenta-associated plasma protein A (PAPP-A), free beta-human chroangiogonadotropin (f--hCG) and other factors that may affect the placental size or function. A total of 1462 pregnancies could be evaluated. Comparison between CRL and placental volume proved a significant correlation (r=0.43, P<0.001). Due to the observed proportional growth of CRL and placental volume, a quotient (placental volume/CRL) was calculated for each case. There were no differences between placenta/CRLquotients in relation to gravidity, parity or smoking. Correlations could be established between the placental volume and PAPP-A and f--hCG (PAPP-A: r=0.28, P<0.001, f--hCG: r=0.10, P<0.001). The measurement of the placenta in the first trimester can be performed in a high percentage of cases. The placenta/CRL quotient represents a simple method to compare placentae from different gestational days. The correlation between placental volume and maternal serum screening parameters might provide a chance to refine first trimester Down’s syndrome serum screening. Future studies will be needed to evaluate the possible clinical use of first trimester placental volume measurements. 2001 Harcourt Publishers Ltd Placenta (2001), 22, 602–605
INTRODUCTION It is known that intrauterine growth restriction is often associated with a smaller placenta (Aherne, 1966; Aherne and Dunnill, 1966; Ruckhaberle et al., 1977; Molteni, Stys and Battaglia, 1978; Senecal et al., 1980). Therefore, measurements of placental size using ultrasound for the early detection of potential risk pregnancies have been a topic of some previous studies. Back in 1980, Hoogland and colleagues found that the rate of small-for-gestational-age (SGA) birthweight was higher in pregnancies with smaller placental areas in mid-trimester (Hoogland, de Haan and Martin, 1980). Wolf et al. concluded that small placental volumes, which were estimated by using two-dimensional ultrasound, were more common in cases of adverse pregnancy outcome (Wolf, Oosting and Treffers, 1989). After the introduction of three-dimensional (3D) c To whom correspondence should be addressed at: LudwigBoltzmann-Institute of Clinical Obstetrics and Gynaecology, Department of Obstetrics and Gynaecology, Donauspital am SMZ-Ost, Langobardenstrasse 122, A-1220 Vienna, Austria. Fax: 0043-1-288023880; E-mail: [email protected]
0143–4004/01/060602+04 $35.00/0
ultrasound, placental volumes could be measured more precisely. Hafner et al. found a dependency of birthweight on placental volume in mid-trimester (Hafner et al., 1998). Until now, no data has been published about placental volumetry in the first trimester. In this study, the feasibility of such measurements was first examined. Second, information about the size of the placenta at this stage of pregnancy was obtained. Third, possible correlations were investigated between placental volume and placenta-dependent parameters such as placenta-associated plasma protein A (PAPP-A) and free beta-human chorangiogonadotropin (f--hCG)—which are used in biochemical Down’s syndrome serum screening. Finally, the influence of gravidity, parity and smoking habits was explored.
METHODS All women with singleton pregnancies who visited the department for routine nuchal translucency measurement (which is offered free of charge) over a 10-month period and whose fetal 2001 Harcourt Publishers Ltd
M. Metzenbauer et al.: Three-dimensional Ultrasound Measurement
603
Table 1. Study population
Recruited Excluded Exclusion because of insufficient image quality Exclusion because of diagnosed fetal aneuploidy, intrauterine death before 24 weeks, severe fetal malformations Included Gravidity
1 >1 0 >0 <20 20–29 30–39 >39
Parity Maternal age at the estimated date of delivery
crown–rump length (CRL) was 35 to 64 mm (inclusive) were included in this study. Fetuses with smaller or larger CRLs were not included because of the small number. We excluded pregnancies with diagnosed aneuploidies, intrauterine fetal death or major malformations and cases where ultrasound volume data were insufficient. Insufficient data referred to those in which the entire placenta and/or clear sonographic separation of the placenta was/were not obtained. Gravidity, parity and smoking habits were also noted. Assessment of placental volume was carried out after the routine ultrasound examination during which fetal CRL and nuchal translucency were measured. A Voluson 530D MT of Kretztechnik was used. This machine is equipped with special 3D probes that can ascertain volumes by automatic movements of the transducer around adjustable angles. Routinely, an abdominal probe was used. If the quality was insufficient—as in women who were obese or had a retroverted uterus—a transvaginal transducer was used. Scanned volume datasets were stored on hard disk for later analysis. The measurements were performed in such a way that parallel slices were identified at different parts of the placenta—from one end to the other. Each of these circumferences was marked manually around the boundary between the placenta and surrounding tissues. On average, approx 2 min are needed to mark one placental volume. The volume was calculated by a computer using the formula:
(A=area, d=distance between two areas) All measurements were performed by one of two observers (MM, DH). As previously described, this method has a low intra- and interobserver variability (Hafner et al., 1998). From preliminary data we got the impression that the average placental size grows considerably between the first and second trimester. Therefore, we expected the median placental
Number
Percentage
1513
100.0
51 30
2.3 2.0
21
1.4
1462 573 889 769 693 48 695 680 39
96.6 39.2 60.8 52.6 47.4 3.3 47.5 46.5 2.7
volume to change distinctly during the observed gestational stage. The initial data suggested that this change occurs in line with CRL values, so a quotient placental volume/CRL was considered. To estimate the usefulness of this formula, three groups were formed (fetuses with CRLs from 35 to 44, from 45 to 54 and from 55 to 64) and their median placental volumes were then determined. Finally, the anticipated median for the placental volume/CRL ratio of approx 1 was evaluated from the available data. A free first trimester screening for Down’s syndrome was offered to all women (‘combined test’: nuchal translucency measurements and detection of PAPP-A and f--hCG in maternal serum). Serum samples were taken on the day 3D placental volume and nuchal translucency was measured. Serum analysis was performed with radio immunoassay (Ortho-Clinical Diagnostics, Johnson & Johnson, NJ, USA). Then the concentrations of the parameters were converted into Multiple of Median (MoM) values using Alpha software (Logical Medical Systems, UK). Next PAPP-A and f--hCG were compared to placental volume. Statistical evaluation was carried out with a descriptive analysis, Pearson’s correlation and median tests for an estimation of differences between the groups studied.
RESULTS During the 10-month period 1513 pregnant women were recruited for this study (there was a total of 1518 women but five refused to take part). Image quality was insufficient in 30 cases (consequently, 98 per cent of the volumes could be measured). Twenty-one further pregnancies were eliminated due to diagnosed aneuploidies, intrauterine fetal death or major malformations. In total, the results of 1462 women were evaluated. Population characteristics are shown in Table 1. Pearson’s coefficient showed a significant correlation between CRL and placental volume (r=0.43, 95 per cent CI:
Placenta (2001), Vol. 22
604
120
parameters (PAPP-A: r=0.28, 95 per cent CI: 0.23–0.33, P<0.001, f--hCG: r=0.10, 95 per cent CI: 0.05–0.16, P<0.001, Pearson’s correlation, t approximation)
100
DISCUSSION
Placental volume
140
80 60 40 20 0 30
40
50 CRL
60
Figure 1. Correlation between crown–rump length and placental volume in millilitres (r=0.43, 95 per cent CI: 0.39–0.47, P<0.001, Pearson correlation, t-approximation).
0.39–0.47, P<0.001, Pearson’s correlation, t-approximation, Figure 1). The median of the placental volume was 41.3 ml in pregnancies with a CRL from 35 to 44 mm (n=442), 48.5 ml in pregnancies with a CRL from 45 to 54 mm (n=739) and 59.2 ml in pregnancies with a CRL from 55 to 64 mm (n=281). Due to the parallel development of CRL and placental volume, a quotient (placental volume/CRL) was subsequently calculated for each measurement. The median for this quotient was similar in all three groups: 1.02 ml/mm for the first, 0.99 ml/ mm for the second, and 1.03 ml/mm for the third group. As there is a dependency on the placenta/CRL quotient in all three groups, no test was performed. There were no differences in the placenta/CRL quotient between primi- and multigravidae (0.99 versus 1.01 ml/mm, P=n.s., median test), between nulli- and multiparae (1.00 versus 1.01 ml/mm, P=n.s., median test) and between smokers and non-smokers (0.99 versus 1.01 ml/mm, P=n.s., median test). PAPP-A and f--hCG were taken from 1378 women (94.3 per cent). A significant correlation could be established between the placenta/CRL-quotient and both serum
Previous studies have only described placental volume measurements at advanced stages of pregnancy. This is the first time that a large number of such assessments have been made during the first trimester. Three main conclusions can be made. First, volumetry of the placenta can be carried out in a high percentage of late first trimester pregnancies. The examinations are simple to perform and the measurements can be acquired quickly and easily. Second, a correlation between the CRL and the placental volume could be found—although the relatively small r value indicates that the spread is quite high. Future studies have to demonstrate if these differences have any diagnostic value; for example, if a relatively small placenta is associated with an impaired pregnancy outcome (e.g. SGA birthweight). The placenta/CRL quotient represents a straightforward method for comparing placentae between different gestational days. It can be employed as a method for ‘normalizing’ or correcting discrepances due to growth. Furthermore, no differences in placenta/CRL-quotient were found between women with different gravidity, parity and smoking habit. Finally, the discovery of some weak correlation between placental volume and maternal serum screening markers might provide an opportunity to refine first trimester Down’s syndrome serum screening. For example, a pregnancy with a relatively small placenta and low PAPP-A might be less at risk than a larger placenta and low PAPP-A. Further studies need to be undertaken to estimate this hypothesis. If first trimester placental volumetry proves to be a reasonable method for determining risk pregnancies, then the potential for the prevention of pregnancy complications would be considerable. Studies that have used medications like acetyl salicylic acid when second trimester uterine artery Doppler velocimetry was impaired showed, if any, only relatively small advantages (CLASP, 1994). Volumetry of the placenta during the first trimester could be helpful because of the less advanced state of placentation. As previously mentioned, larger studies are needed to provide answers to all of these questions.
ACKNOWLEDGEMENTS We would like to thank Mrs Brigitte Dillinger-Paller, Mr Thomas Kratochwil and Mr David Nunez for their valuable contributions. This study was supported by the Austrian Science Fund (project number P 13847).
REFERENCES Aherne W (1966) A weight relationship between the human foetus and placenta. Biol Neonat, 10, 113–118. Aherne W & Dunnill MS (1966) Quantitative aspects of placental structure. J Pathol Bacteriol, 91, 123–139. CLASP (Collaborative Low-dose Aspirin Study in Pregnancy) (1994) CLASP: a randomized trial of low-dose aspirin for the prevention and treatment of pre-eclampsia among 9364 pregnant women. Lancet, 343, 619–629.
Hafner E, Philipp T, Schuchter K, Dillinger-Paller B, Philipp K & Bauer P (1998) Second-trimester measurements of placental volume by three-dimensional ultrasound to predict small-for-gestational-age infants. Ultrasound Obstet Gynecol, 12, 97–102. Hoogland HJ, de Haan J & Martin CB (1980) Placental size during early pregnancy and fetal outcome: A preliminary report of a sequential ultrasonographic study. Am J Obstet Gynecol, 138, 441–443. Molteni RA, Stys SJ & Battaglia FC (1978) Relationship of fetal and placental weight in human beings: fetal/placental weight ratios at various
M. Metzenbauer et al.: Three-dimensional Ultrasound Measurement gestational ages and birth weight distributions. J Reprod Med, 21, 327–334. Ruckhaberle KE, Viehweg B, Ruckhaberle B, Schlegel C, Leistner B, Ebert S & Schulz S (1977) Macroscopically determined placentary conditions in the case of underweight neonates. Zentralbl Gynakol, 99, 1323–1330.
605 Senecal J, Kerisit J, Defawe G, Lefrancois MC, Fisselier MP, Grall JY & Le Marec B (1980) A study of the weight of the placenta in normal and pathological pregnancies. J Gynecol Obstet Biol Reprod (Paris), 9, 531–536. Wolf H, Oosting H & Treffers PE (1989) Second-trimester placental volume measured by ultrasound: Prediction of fetal outcome. Am J Obstet Gynecol, 160, 121–126.