Current Development Ultrasonographic assessment of placental abnormalities Eric Jauniaux, MD,* and Stuart Campbell, FRCOG London, England Current ultrasonographic techniques offer a novel approach for the identification of a wide variety of placental abnormalities usually described postnatally by the pathologist. Placental vascular lesions, placental tumors, and abnormal placentation are potentially associated with perinatal complications and their diagnosis in utero may influence the pregnancy management. An ultrasonographic classification of placental lesions that is based on their location, size, echogenicity, and number is proposed. Repeated ultrasonographic examination, together with biologic investigations, is important for the prenatal differential diagnosis of most of these lesions and for full understanding of their pathophysiologic characteristics and significance. (AM J OBSTET GVNECOL 1990;163:1650-8.)

Key words: Ultrasonography, placenta, prenatal diagnosis

Recognition of normal and abnormal placental features is a prerequisite for the interpretation of ultrasonographic images. However, despite >20 years of experience in examination of the placenta in utero by ultrasonography, controversies still exist regarding the terminology and the significance of different placental ultrasonographic features. The purpose of this work is to review the different placental ultrasonographic abnormalities together with their pathophysiologic and clinical implications.

Placental development and maturation The development of the placenta has always attracted considerable interest from both anatomists and ultrasonographers. Combined studies using transvaginal ultrasonography, hysteroscopy, chorionic villus sampling, and hysterectomy specimens from the first trimester of pregnancy have recently indicated the absence of continuous blood flow in the intervillous space before 12 weeks of gestation. 1•3 During the first trimester of pregnancy, the placenta is bathed by a clear fluid probably composed of maternal plasma and uterine gland secretions. 1•3 • After 12 weeks the trophoblastic plugs in the spiral arteries that are still remaining from the first From the Department of Obstetrics and Gynecology, King's College School of Medicine and Dentistry, University of London. Reprint requests: Eric Jauniaux, MD, Department of Obstetrics and Gynecology, University Hospital Erasme, Free University of Brussels (ULB), 808 Route de Lennik, B-J070 Brussels, Belgium. *Research Fellow from the Free University of Brussels (ULB), Brussels, Belgium, supported by the British Council (Sir Alexander Fleming Award 1989). 611/22989

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extra villous trophoblastic wave no longer obliterate the uteroplacental arteries, and a real circulation is then established. 1 Ultrasonographic evidence of placental textural changes in vivo were reported in early studies during the second and third trimesters,,· 6 A ultrasonographic classification system for grading placentas in utero was developed by Grannum et aI.' The placental maturational changes were determined by use of a contact B-scanner and graded from 0 to III. These placental changes were correlated with fetal pulmonic maturity evaluated in utero by amniotic fluid lecithin/sphingomyelin (LIS) ratios obtained by amniocentesis. An ideal correlation of 100% was found between placental grade III and mature L/S ratios, suggesting that ultrasonographic placental grading might replace amniocentesis as a standard test to assess fetal pulmonic maturity. Other authors 8 • 9 presented similar results using realtime ultrasonography. However, larger studies showed that the sensitivity of the placental grading system as an indicator of pulmonic maturity was poor. 1O· 14 In addition, this system falsely predicted fetal lung maturity in 8% to 42% of the cases and was therefore not accurate enough to replace amniocentesis for this purpose. 10. 14 A modified classification that is based on multiple placental ultrasonographic sections was also proposed, suggesting that placentas should be considered mature only when grade III changes are present in all sections. 15 Various interpretations of the placental structural changes, interobserver variation in scanning technique, and heterogeneity of the study groups are probably

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Table I. Differential diagnosis of principal placental lesions reported in the literature Location

Fetal plate

Placental tissue

Sonographic features

Pathologic classification

Multiple sonolucent areas limited to the placental periphery (Fig. 1, A) Single sonolucent or hypoeehoic area surrounded by a thin membrane (Fig. 1, C and F) Single hyperechoic area surrounded by a thin membrane (Fig. I, E) Well-circumscribed heterogeneous mass protruding into the amniotic cavity (Fig. 2) Small sonolucent area in the center of the cotyledon Large sonolucent area (Fig. 3, A) Large hyperechoic area (Fig. 3, C and E)

Maternal plate

Multiple sonolucent areas of various sizes and shapes (Fig. 4) Large hyperechoic area Large sonolueent or hypoechoic area

responsible for the controversies generated by the placental grading system, Nevertheless, all these studies have highlighted that complicated pregnancies have a different maturation pattern than normal pregnancies. This important clinical finding was confirmed by further selective studies. Pregnancies complicated by chronic hypertension or preeclampsia and/or intrauterine growth retardation present an accelerated placental maturation, whereas diabetes and maternal-fetal rhesus incompatibilities are associated with delayed placental maturation. 16 Earlier maturational changes were also described in twin gestations, as compared with singleton gestations,17 and after exposure to maternal smoking. 18. 19 Pregnant women with mature placental appearance (grade III) on ultrasonography between 34 and 36 weeks' gestation have an increased risk of problems during labor, and their babies have an increased risk of low birth weight, intrapartum distress, and perinatal death." This study also demonstrated that there was a significant decrease in the risk of perinatal death when the grading was known by the clinician responsible for care. 18 Most of the above-mentioned studies refer to placental senescence or aging to explain the placental maturational changes observed by ultrasonography. Light or electron microscopic study of villi from term placenta does not indicate an aging process. 20 Furthermore, the total placental deoxyribonucleic acid levels continue to rise in a linear fashion until, and beyond, the fortieth week of gestation. 21 Therefore the placental ultrasonographic changes should not be considered as the morphologic hallmarks of placental senescence. Several authors have attempted to reproduce in vitro the ultrasonographic morphologic features observed in vivo!' 5. 22 In early studies the placentas were not always fixed immediately and some changes observed

Circumvallate placenta Circummarginate placenta Subamniotie cyst Old subamniotic hematoma Recent subamniotie hematoma Chorioangioma Centrocotyledonary cavity Large avillous zone (cavern) Septal cyst Early stage of thrombosis formation Old thrombosis Infarct H ydatidif(lrm transformations Recent retroplacental hematoma Old retraplacental hematoma

were not found in vitro; furthermore, new features were probably created during placental collapse.1. 5 More satisfactory results were obtained with the use of a perfusion system in vitro, to avoid placental collapse. 22 Sonolucent areas or central echo-free spaces have been correlated with avillous zones, and the peripheral echoes with septal calcification and fibrin deposition.1. 5 III VIVO

Classification of placental ultrasonographic lesions

Many inaccurate and misleading expressions have been used by sonographers to described placental pathologic lesions. This is probably because of the fact that little attempt has been made to compare ultrasonographic and postpartum findings. The location, the shape, and the echogenicity of the lesion and the number of lesions are the principal ultrasonographic features for the prenatal differential diagnosis of placental abnormalities (Table I). Placenta extrachorialis. Placenta extrachorialis is characterized by a transition of membranous to villous chorion within the placental disk at a variable distance from the placental edge!o. 23. 24 Between 18% and 30% of placentas are of the extrachorial variety.20 Two anatomic entities have been described: circummarginate placentas, which have a flat ring of membranes made up only of amnion and chorion, and circumvallate placentas, which have a raised, often rolled ring of membranes, containing amnion, chorion, and decidual tissue. Circummarginate placentas are practically asymptomatic!O In contrast, circumvallate placentas are associated with a relatively high rate of premature rupture of the membranes, antepartum bleeding, and preterm onset of labor.20. 23 These complications are

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Fig.!. A, Transverse scan at 20 weeks of gestation of the marginal zone of the placenta, showing sonolucent areas over the fetal plate (arrow). These abnormalities were found only near the placental edge. B, Pathologic examination demonstrated a circumvallate placenta. C, Transverse and longitudinal scans of a single sonolucent subamniotic area (asterisk) at 32 weeks corresponding to a subamniotic cyst (D) (asterisk). E and F, Longitudinal sonograms at 24 and 32 weeks, respectively, showing hyperechogenic placental lesions on the top of the fetal plate (stars), surrounded by a thin membrane (arrows). The lesion becomes less echogenic as the clot resolves. G, Pathologic examination revealed an old subamniotic hematoma (star).

probably due to a lack of adaptation of the rigid placental edge with tearing of membranes as the uterine wall stretches in the second half of gestation. Multiple subamniotic sonolucent areas of various sizes and shapes, located in the periphery of the placenta (Fig. 1, A and B) are the main ultrasonographic features of this form of placentation. 25 Cytotrophoblastic cysts. Cytotrophoblastic cysts usually have a single, round or oval cavity, containing a gelatinous materiaJ.2o.23.24 They can be divided into septal cysts when they are located within the placental tissue and subchorionic cysts when they are on the fetal surface beneath the chorionic vessels.~"· 24 These cysts are isolated from the placental circulation and appears ultrasonographically as single sonolucent areas (Fig. 1, C and D) showing no blood flow on realtime imaging!6 Cytotrophoblastic cysts are found in

20% of placentas at term.20 Their incidence in increased in pregnancies complicated by diabetes mellitus or maternal-fetal rhesus incompatibility!O Subamniotic hematomas. These lesions are secondary to the rupture of a fetal vessel before or during delivery and are located beneath the amniotic layer covering the fetal plate. 20 Their incidence is unknown but most of them are found in third-trimester placentas and are thought to occur during delivery as a result of excessive traction on the umbilical cord. 20 Subamniotic hematomas that develop during the second or third trimester are sometimes complicated by fetal growth retardation and abnormal Doppler measurements.27. 28 Ultrasonographically, they appear as a single mass protruding from the fetal plate and surrounded by a thin membrane. The newly formed clot is echogenic

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Fig. 2. A, Heterogeneous placental mass at 32 weeks (asterisk), protruding from the fetal plate near the cord insertion (arrow). The pregnancy was complicated by polyhydramnios. B, Pathologic examination demonstrated a chorioangioma (asterisk) showing generalized degenerative changes. C, Longitudinal ultrasonogram of a hypoechoic placental mass (asterisk) at 18 weeks gestation. D, At 30 weeks half of the lesion (aster-ilk) was more echogenic. At delivery the lesion corresponded to a large chorioangioma partly grooved by bands of fibrous tissue. E, Ultrasonographic appearance of a uterine leiomyoma (asterisk) at 20 weeks of gestation, for comparison.

(Fig, 1, E), but the lesion becomes less so as the clot resolves (Fig. 1, F and G). Chorioangiomas. Chorioangiomas occur in 0.5% to 1% of placentas examined at term.n 2:\ Most chorioangiomas are encapsulated, single, small, round, and intraplacental. 2o 23 Large tumors can be of variable shape, divided by fibrous septa, and they often protrude from the fetal surface near the cord insertion. 20 . ,:\ Degenerative changes such as necrosis, calcification, hyalinization, or myxoid changes are frequently present in large tumors. Chorioangiomas are associated with an increased incidence of polyhydramnios and fetal growth retardation.,o.27 Large tumors (>5 cm in diameter) can also be complicated by fetal cardiac failure with hydrops because of the shunting of blood through the tumor. 20 On ultrasonographic, only large chorioangiomas protruding into the amniotic cavity have been documented. They are well circumscribed, have a different echogenicity from the rest of the placental tissue (Fig. 2, A and B), and are easily detectable early in pregnancy by ultrasonographic.27. 29-31 The echogenicity varies according to the degree of degenerative changes present in the tumor (Fig. 2, C and D). Caverns. These lesions may vary from small sonolucent areas to large sonolucent spaces (Fig. 3, A). Small echo-free spaces in the center of the cotyledon have been described in normal third-trimester mature pla-

centas (grade III of Grannum's classification). These small cavities within the cotyledons are secondary to the dispersion of the free-floating terminal villi by maternal arterial jets of blood entering the intervillous space." Larger intra placental sonolucent spaces are found in 67% of the placentas examined by ultrasonography from the first half of pregnancy until delivery.32 They contain turbulent blood flow on real-time imaging and their shape can be modified by maternal position or by uterine contractions.'6 Histologically, these lesions correspond to large avillous areas surrounded by normal villi. They are probably a non pathologic variation of the normal placental anatomic structure that develops from early in pregnancy.26 They have been described by pathologists as hemorrhagic areas'" or as caverns,"'! sometimes containing semifluid or fluid blood. Thrombosis. Placental thrombosis is the result of focal coagulation of blood in the intervillous spaces and usually occurs during the third trimester. 2o . n 21 Intervillous thromboses are found in about 40% of placentas and contain an admixture of fetal and maternal blood. 20 . 21 The incidence of the lesion is increased in pregnancies complicated by rhesus isoimmunization. 20 Large hypoechoic areas with low flow laterally and relatively high flow in the central part on real-time imaging can be observed in the early stages (Fig. 3, A) of the development of an intervillous thrombosis.'" :12.:1:1 Abnormal hemodynamic flow in the intervillous space

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Fig. 3. A, Ultrasonograms at 35 weeks showing small and large placental sonolucent spaces (asterisks), containing turbulent blood flow. Note the increase echogenicity of the surrounding villi (small arrows). B, Histologic section at the level of the large arrow showing a recent intervillous thrombosis (asterisk) and normal villi (arrow). The villi surrounding the lesion at the level of the small arrows were compressed and infarcted. (Hematoxylin and eosin. x 50.) C, Ultrasonograms at 39 weeks showing a large placental lesion (asterisk) corresponding (D) to an organized intervillous thrombosis (asterisk) with extensive fibrin deposition (large arrow) in periphery. (Hematoxylin and eosin. x 50.) E, Large placental hyperechoic area (asterisk) located near the basal plate at 32 weeks of gestation corresponding (F) to a chronic infarct. (Hematoxylin and eosin. x 50.)

may result from the failure of the cotyledon to expand in response to the increasing flow of the corresponding utero placental artery and compression of the surrounding villi with gradual atrophy as fibrin accumulates in the periphery. This process causes a progressive increase in the echogenicity of the lesion (Fig. 3, C and D), thus distinguishing it from a placental cavern. Finally, the maternal blood coagulates in the placental tissue, focally obliterating the intervillous circulation. This failure to accommodate may be secondary to inadequate venous drainage from the cotyledon or to villous damage related to maternal-fetal incompatibility?o.2:{

Intervillous thrombosis must be distinguished from subchorial thrombosis as a result of pooling and stasis of maternal blood beneath the chorionic plate or in the marginal area of the intervillous chamber!6. 34 Ultrasonographically, these lesions appear as sonolucent space of variable size containing turbulent blood flow on real-time imaging. 26 Their appearance may change from one examination to another as progressive fibrin deposition leads to classic subchorial or marginal thrombosis described by the pathologists. 20 , 23 Infarcts. Placental infarcts are the result of obstruction of a utero placental artery leading to focal degeneration of the overlying villous tissue. 2o. 23 They are

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Fig. 4. A, Longitudinal ultrasonogram at 22 weeks of gestation showing an enlarged placenta containing multiple sonolucent spaces (asterisk). The fetus was anatomically normal. B, Pathologic examination demonstrated diffuse mesenchymal hyperplasia with myxoid degeneration of the villous stem and dilatation of the main fetal vessels (arrows). C, Ultrasonogram at 25 weeks of a molar mass (M) and a normal placenta (P) in a twin pregnancy combining a classic mole and a normal placenta and fetus. D, Pathologic examination confirmed the presence of a normal placenta (P) and a complete mole (M). E, Transverse ultrasonograms of an enlarged placenta containing multiple sonolucent spaces of various sizes and shapes (asterisk). The pregnancy was complicated by severe asymmetric fetal growth retardation, oligohydramnios, and early pregnancy-induced hypertension. F, Pathologic and cytogenetic investigations revealed a triploid syndrome with focal swelling of the villous tissue (asterisk) .

usually located near the maternal plate}o. 23 Small infarcts are found in about 25% of placentas from uncomplicated pregnancies}O The incidence of placental infarction is significantly increased in pregnancies complicated by preeclampsia or essential hypertension 20 . 23. 24 and is directly related to the severity of the disease}0,23 In these maternal hypertensive disorders infarction is extensive and involves more than 10% of the placental tissue}O Large placental infarcts are associated with an increase in perinatal mortality and intrauterine growth retardation. 20, 23, 24 Ultrasonographically, placental infarcts appear as large intraplacental areas that are irregular and hyperechoic in the acute stage 26 and isoechoic in more advanced stages (Fig. 3, E and F). Hydatidiform transformation. Molar or hydatidiform transformation of the villous tissue (Fig. 4, A, C, and E) is a common finding in placental trophoblastic tumors. The principal histologic feature of this group

of tumors is trophoblastic hyperplasia. Trophoblastic tumors are classified on a cytogenetic and morphologic basis into complete and partial mole. 35 ,36 Complete or classic hydatidiform moles are characterized by generalized swelling of the villous tissue, trophoblastic hyperplasia, and no embryonic or fetal tissue. 35 ,36 Complete moles are almost always diploid with a 46,XX chromosomal constitution in 90% of cases and a 46,XY karyotype in 10% of cases. 37 About 15% to 20% of complete moles can become invasive and metastasize. 3s Ultrasonographically, the uterus is filled with sonolucent spaces ("snowstorm" appearance) of various sizes and shapes without embryonic or fetal materia!''' However, molar transformation of one ovum in a dizygotic twin pregnancy has been reported. 39 , 40 In these cases ultrasonographic or pathologic examination shows a molar placental mass together with normal placenta and fetus (Figs. 4, C and D). Partial hydatidiform moles are characterized by focal

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Table II. Review of perinatal features of 35 cases of triploid syndromes diagnosed in second and third trimesters of pregnancy (references 43 to 54) A. Maternal data (No. == 20) 25.95 ± 4.91 Mean maternal age (yr) 2.1 ± 0.89 Mean gravidity 0.75 ± 0.83 Mean parity B. Mean gestational age at diagnosis (wk) 21.12 ± 4.31 (No. == 33) 28.6% C. Maternal complications (13 cases) 6 Pregnancy-induced hypertension 4 Bilateral multicystic ovaries 3 Hyperemesis gravidarum 3 Vaginal bleeding D. Ultrasonographic findings Placenta (No. = 34) 44.1% Normal in 15 cases 55.9% Abnormal in 19 cases 4 Hydropic (enlarged) 10 Molar transformations 5 Hydropic and molar transformations Fetus (No. = 33) Normal in 3 cases 9.1% 90.9% Abnormal in 30 cases 18 IUGR 4 Malformations 8 IUGR and malformations Amniotic fluid (No. = 28) 53.6% Normal in 15 cases 46.4% Abnormal in 13 cases 9 Oligohydramnios 4 Polyhydramnios E. Laboratory findings Maternal serum hCG (No. = 10) Elevated in 9 cases and normal in 1 case Maternal serum AFP (No. = 14) Elevated in 13 cases and normal in 1 case Amniotic fluid AFP (No. = 15) Elevated in 6 cases and normal in 9 cases F. Pathologic findings Placenta (No. = 31) 38.7% Normal in 12 cases 61.3% Abnormal in 19 cases 9 Molar transformations 12 Trophoblast hyperplasia and/or scalloped outline Fetus (No. = 26) 7.7% Normal in 2 cases Abnormal in 24 cases 92.3% 21 Small for dates 13 External defects 10 Internal abnormalities G. Cytogenetic findings (No. = 35) 69,XXX (20 cases) 69,XXY (13 cases) 69,XYY (no cases) 70,XXYY (l case) 46,XY/69,XXY (I case) IUGR, Intrauterine growth retardation; No., number of cases among the 35 cases reviewed with the corresponding information; heG, human chorionic gonadotropin; AFP, a-fetoprotein.

swelling of the villous tissue, focal trophoblastic hyperplasia, and embryonic or fetal tissue.'" 36 The most common karyotype found in these cases is triploidy.

November 1990 Am J Obstet Gynecol

This is a common chromosomal anomaly accounting for 1% to 2% of all clinically recognized human conceptions!!. 42 There is a strong correlation between the origin of the extra set of chromosomes, the degree of the placental molar change, and the survival rate of the pregnancies!2 All cases with an extra paternal set (73%) of chromosomes have significant molar changes (Fig. 4, E and F) while only 14% of cases with an extra maternal set (27%) have significant molar changes!2 Placentas with nonmolar changes are associated with a better fetal survival and are more likely to be found near term!2 Table II summarizes the perinatal data of 35 cases of triploidy reported in the literature!3-54 Only triploidy syndromes confirmed by chromosomal analysis were included. This review indicates that 55.8% of the placentas in triploidy have hydropic and/ or molar changes on ultrasonography. The fetus presents severe growth retardation and/or major congenital defects in 90.9% of the cases and the amniotic fluid volume is abnormal in 46.4%. The ultrasonographic features correlated well with the morphologic findings reported in these cases and in more selective pathologic studies!2 This review is not exhaustive and most of these studies are incomplete; in particular, microscopic findings and laboratory investigations were not constantly reported. Nevertheless, published biologic findings indicate that most of the cases of triploidy are first seen with elevated levels of maternal serum human chorionic gonadotropin and a-fetoprotein even when they are not associated with major congenital fetal defects. Cases of diploid partial moles were recently described. They are characterized by diffuse molar placental changes associated with a normal fetus and elevated levels of human chorionic gonadotropin and a-fetoprotein. 55 Pathologically, areas bearing characteristic molar transformation (diploid cytogenetic constitution) interdigitate with unaffected placental areas. 55. 56 Molar changes of the placenta are not always pathognomonic of trophoblastic disorders and can be found in other placental pathologic conditions such as benign diffuse mesenchymal hyperplasia (Fig. 4, A and B) or in prolonged placental retention in utero after fetal death. 26 ,57 Retroplacental hematomas. The diagnosis of abruptio placentae during the second half of pregnancy is based on the clinical triad of pain, uterine rigidity, and vaginal bleeding, and ultrasonographic investigations can be used only in nonacute cases to confirm clinical diagnosis and to exclude presence of placenta previa. 58 Retroplacental hematomas cause a wide spectrum of ultrasonographic features depending on the location of the lesion and on the degree of organization of the blood clot. Acute hemorrhage is hyperechoic to isoechoic, as compared with placental tissue, while resolving hematomas are hypoechoic. 59

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Other placental abnormalities. Unusual placental abnormalities associated with perinatal complications also have been observed by ultrasonography such as placenta membranacea60 or placenta percreta. 61 Comment

Depending on the delay between the development of a lesion in utero and delivery, the ultrasonographic and pathologic findings can be very different. The ultrasonographic features of most placental vascular lesions may undergo major changes within few days. When placental abnormalities that could be associated with perinatal complications are suspected, serial ultrasonographic examinations should be performed. Repeated ultrasonographic examination will also yield interesting pathophysiologic data on the development of placental lesions and may help in the prenatal differential diagnosis. For example, old thromboses are difficult to differentiate from infarcts if serial examinations are not performed. Repeated ultra sonographic examination is necessary to detect the evolution of a simple hypoechoic space into intervillous thrombosis or to differentiate a subamniotic cyst from a subamniotic hematoma. The increasing echogenicity of a chorioangioma with gestation can be related to fibrotic degeneration of a lesion,27 which may indicate a reduced risk of high-output fetal cardiac failure. Placental ultrasonographic examination must be combined with other prenatal investigations, some of which may help in the differential diagnosis. For example, elevated maternal serum levels of human chorionic gonadotropin are suggestive of trophoblastic disorders while elevated o:-fetoprotein levels are less specific of a typical placental lesion 27 , 62, 63 but indicate a breakdown of the maternal barrier such as may occur in infarcts or thrombosis. Various vascular lesions have been found in placentas from pregnancies complicated by abnormal fetal or maternal Doppler indices. 64 , 65 Although it is unlikely that a clinical decision will be made on placental morphologic features alone, the association of abnormal placental features with abnormal Doppler indices will clarify the hemodynamic changes occurring in these cases. Furthermore, the advent of color Doppler imaging may help to differentiate in utero between maternal and fetal vascular placental abnormalities. REFERENCES 1. Hustin j, Schaaps jP. Echographic and anatomic studies of the maternotrophoblastic border during the first trimester of pregnancy. AM j OBSTET GYNECOL 1987; 157: 162-8. 2. Schaaps jP, Hustin J. In vivo aspect of the maternaltrophoblastic border during the first trimester of gestation, Trophoblast Res 1988;3:39-48. 3. Hustin j, Schaaps jP, Anatomical studies of the uteroplacental vascularization in the first trimester of pregnancy, Trophoblast Res 1988;3:49-60. 4. Fisher CC, Garrett W, Kossoff G, Placenta aging moni-

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