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Obstentrics_Williams. Voltolini C, Battersby S, Novembri R, et al: Urocortin 2 role in placental and myometrial inflammatory mechanisms at parturition. Endocrinology 156(2):670, 2015 Wadhwa PO, Porto M, Garite TJ, et al: Maternal corticotropin-releasing hormone levels in the early third trimester predict length of gestation in human pregnancy. Am J Obstet GynecoIs179:1079, 1998 Walker WH, Fitzpatrick SL, Barrera-Saldana HA, et al: he human placental lactogen genes: structure, function, evolution and transcriptional regulation. Endocr Rev 12:316, 1991 Wallace EM, Swanston A, McNeilly AS, et al: Second trimester screening for Down's syndrome using maternal serum dimeric inhibin A. Clin Endocrinol (Ox) 44(1):17,s1996 Warren W, Silverman A: Cellular localization of corticotrophin releasing hormone in the human placenta, fetal membranes and decidua. Placenta ,1995


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Obstentrics_Williams. Warren W, Silverman A: Cellular localization of corticotrophin releasing hormone in the human placenta, fetal membranes and decidua. Placenta ,1995 Weetman AP: he immunology of pregnancy. Thyroid 9:643, 1999 Wehmann RE, Nisula BC: Renal clearance rates of the subunits of human chorionic gonadotropin in man. J Clin Endocrinol Metab 50:674, 1980 Whittle WL, Gibb W, Challis JR: he characterization of human amnion epithelial and mesenchymal cells: the cellular expression, activity and glucocorticoid regulation of ptostaglandin output. Placenta 21 :394, 2000 Williams PJ, Searle F, Robson Sc, et al: Decidual leucocyte populations in early to late gestation normal human pregnancy. J Reprod Immunol 82(1):24, 2009 Winger EE, Reed JL: The multiple faces of the decidual natural killer cell. Am J Reprod Immunol 70:1, 2013


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Obstentrics_Williams. Winger EE, Reed JL: The multiple faces of the decidual natural killer cell. Am J Reprod Immunol 70:1, 2013 Wislocki GB, Dempsey EW: Electron microscopy of the human placenta. Anat Rec 123:133, 1955 Wolfahrt S, Kleine B, Rossmanith WG: Detection of gonadotrophin releasing hormone and its receptor mRNA in human placental trophoblasts using in situ reverse transcription-polymerase chain reaction. Mol Hum Reprod 4:999, 1998 Wu Z, Horgan CE, Carr 0, et al: Biglycan and decorin diferentially regulate signaling in the fetal membranes. Matrix Bioi 34:266, 2014 Xie L, Sadovsky Y: he function of miR-519d in cell migration, invasion, and proliferation suggests a role in early placentation. Placenta 48:34, 2016 Yan C, Wang P, DeMayo J, et al: Synergistic roles of bone morphogenetic Protein 15 and growth diferentiation Factor 9 in ovarian function. Mol Endocrinol 15:854, 2001


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Obstentrics_Williams. Yan C, Wang P, DeMayo J, et al: Synergistic roles of bone morphogenetic Protein 15 and growth diferentiation Factor 9 in ovarian function. Mol Endocrinol 15:854, 2001 Yoshimura M, Pekary AE, Pang XP, et al: hyrotropic activity of basic isoelectric forms of human chorionic gonadotropin extracted from hydatidiform mole tissues. J Ciin Endocrinol Metab 78:862, 1994 Zhang M, Muralimanoharan S, Wortman AC, et al: Primate-speciic miR-515 family members inhibit key genes in human trophoblast differentiation and are up regulated in preeclampsia. Proc Natl Acad Sci USsA 113(45):E7069, 2016 NORMAL PLACENTA . . . . . . . . . . . . . . . . . . . . . . . . . . .. 111 SHAPE AND SIZE VARIANTS . . . . . . . . . . . . . . . . . . . . .. 112 EXTRACHORIAL PLACENTATION . . . . . . . . . . . . . . . . .. 113 CIRCULATORY DISTURBANCES . . . . . . . . . . . . . . . . . .. 113 PLACENTAL CALCIFICATION. . . . . . . . . . . . . . . . . . . . .. 115 PLACENTAL TUMORS ........................... 115


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Obstentrics_Williams. CIRCULATORY DISTURBANCES . . . . . . . . . . . . . . . . . .. 113 PLACENTAL CALCIFICATION. . . . . . . . . . . . . . . . . . . . .. 115 PLACENTAL TUMORS ........................... 115 AMNIOCHORION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 116 UMBILICAL CORD. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 117 The placenta, as a rule, presents more or less rounded outlines, but now and again when inserted in the neighbourhood of the internal os it may take on a horseshoe-like appearance, its two branches running partialy around the oriice. -J. Whitridge Williams (1903) he placenta is a fantastic organ in its own right. As discussed in Chapter 5 (p. 88), it provides the indispensable interface between mother and fetus. Indeed, placental anatomy, ogy, and molecular structure remain some of the most intriguing and understudied topics in obstetrics.


Obstentrics_Williams

Obstentrics_Williams. Although a placental examination by the obstetrician is recommended, by consensus, routine pathological examination is not mandatory. Indeed, speciic conditions that merit submission for detailed inspection are still debated. By way of example, the College of American Pathologists has recommended placental examination for an extensive list of indications (Langston, 1997). Data, however, are insuicient to support all of these. At minimum, the placenta and cord should be inspected in the delivery room. he decision to request pathological examination should be based on clinical and placental findings (Redline, 2008; Roberts, 2008). Listed in Table 6-1 are some of the indications at Parkland Hospital for placental anatomical and histopathological examination.


Obstentrics_Williams

Obstentrics_Williams. At term, the typical placenta weighs 470 g, is round to oval with a 22-cm diameter, and has a central thickness of 2.5 cm (Benirschke, 2012). It is composed of a placental disc, extraplacental membranes, and three-vessel umbilical cord. The disc surface that lies against the uterine wall is the basal plate, which is divided by clefts into portions-termed cotyledons. he fetal surface is the chorionic plate, into which the umbilical cord inserts, typically in the center. Large fetal vessels that originate from the cord vessels then spread and branch across the chorionic plate before entering stem villi of the placenta parenchyma. In tracing these, fetal arteries almost invariably cross over veins. he chorionic plate and its vessels are covered by thin amnion, which can be easily peeled away from a postdelivery specimen.


Obstentrics_Williams

Obstentrics_Williams. As recommended by the American Institute of Ultrasound in Medicine (2013), placental location and relationship to the internal cervical os are recorded during prenatal sonographic examinations. As visualized ultrasonically, the normal placenta is homogenous and 2 to 4 cm thick, lies against the myometrium, and indents into the amnionic sac. The retroplacental space is a hypoechoic area that separates the myometrium from the basal plate and measures less than 1 to 2 cm. The umbilical cord is also imaged, its fetal and placental insertion sites examined, and its vessels counted. Many placental lesions can be identiied grossly or sonographically, but other abnormalities require histopathological examination for clariication. A detailed description of these Antepartum infection with fetal risks Anti-CDE alloimmunization Cesarean hysterectomy Oligohydramnios or hydramnios Peripartum fever or infection Preterm delivery Postterm delivery


Obstentrics_Williams

Obstentrics_Williams. Antepartum infection with fetal risks Anti-CDE alloimmunization Cesarean hysterectomy Oligohydramnios or hydramnios Peripartum fever or infection Preterm delivery Postterm delivery Systemic disorders with known effects Thick or viscid meconium Unexplained late pregnancy bleeding Admission to an acute care nursery Birth weight � 10th or �95th percentile Feta! anemia Vanishing twin beyond the first trimester alndications are organized alphabetically. is beyond the scope of this chapter, and interested readers are referred to textbooks by Benirschke (2012), Fox (2007), and Faye-Petersen (2006) and their colleagues. Moreover, the placenta accrete syndrome and gestational trophoblastic disease are presented in detail in Chapters 20 and 41, respectively.


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Obstentrics_Williams. Of variants, placentas may infrequently form as separate, nearly equally sized discs. his bilobate placenta may also be called bipartite placenta or placenta duplex. In these, the cord inserts between the two placental lobes-either into a connecting chorionic bridge or into intervening membranes. A placenta containing three or more equivalently sized lobes is rare and termed multilobate. Unlike this equal distribution, one or more TABLE 6-1. Some Indications for Placental Pathological Examinationa


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Obstentrics_Williams. TABLE 6-1. Some Indications for Placental Pathological Examinationa FIGURE 6-1 Succenturiate lobe. A. Vessels extend from the main placental disc to supply the small round succenturiate lobe located beneath it. (Used with permission from Dr. Jaya George.) B. Sonographic imaging with color Doppler shows the main placental disc implanted posteriorly (asterisk). The succenturiate lobe is located on the anterior uterine wall across the amnionic cavity. Vessels are identified as the long red and blue crossing tubular structures that travel within the membranes to connect these two portions of placenta.


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Obstentrics_Williams. disparately smaller accessory lobes-succenturiate lobes-may develop in the membranes at a distance from the main placenta (Fig. 6-1). hese lobes have vessels that course through the membranes. Of clinical importance, if these vessels overlie the cervix to create a vasa previa, dangerous fetal hemorrhage can follow vessel laceration (p. 118). n accessory lobe can also be retained in the uterus after delivery to cause postpartum uterine atony and hemorrhage or later endometritis.


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Obstentrics_Williams. Rarely, the placental surface area varies from the norm. With placenta membranacea, villi cover all or nearly all the uterine cavity. This may occasionally give rise to serious hemorrhage because of associated placenta previa or accreta (Greenberg, 1991; Pereira, 2013). A ring-shaped placenta may be a variant of placenta membranacea. his placenta is annular, and a partial or complete ring of placental tissue is present. hese abnormalities appear to be associated with a greater likelihood of tion (Faye-Petersen, 2006; Steemers, 1995). With placenta fenestrata, the central portion of a placental disc is missing. In some instances, there is an actual hole in the placenta, but more often, the defect involves only villous tissue, and the chorionic plate remains intact. Clinically, it may erroneously prompt a search for a retained placental cotyledon.


Obstentrics_Williams

Obstentrics_Williams. During pregnancy, the normal placenta increases its thickness at a rate of approximately 1 mm per week. lthough not measured as a component of routine sonographic evaluation, this thickness typically does not exceed 40 mm (Hoddick, 1985). Placentomegay deines those thicker than 40 mm and commonly results from striking villous enlargement. his may be secondary to maternal diabetes or severe maternal anemia, or to fetal hydrops, anemia, or infection caused by syphilis, toxoplasmosis, parvovirus, or cytomegalovirus. In these conditions, the placenta is homogeneously thickened. Less commonly with placentomegaly, fetal parts are present, but villi are edematous and appear as small placental cysts, such as in cases of partial mole (Chap. 20, p. 391). Cystic vesicles are also seen with placental mesenchymal dysplasia. Vesicles in this rare condition correspond to enlarged stem villi, but unlike molar pregnancy, trophoblast proliferation is not excessive (Woo, 2011).


Obstentrics_Williams

Obstentrics_Williams. Rather than villous enlargement, placentomegaly often may result from collections of blood or ibrin, which impart heterogeneity to the placenta. Examples of this are discussed on page 114 and include massive perivillous fibrin deposition, intervillous or subchorionic thromboses, and large retroplacental hematomas.


Obstentrics_Williams

Obstentrics_Williams. he chorionic plate normally extends to the periphery of the placenta and has a diameter similar to that of the basal plate. With extrachorial placentation, however, the chorionic plate fails to extend to this periphery and leads to a chorionic plate that is smaller than the basal plate (Fig. 6-2). Circummarginate and circumvallate placentas are the two types. In a circummarginate placenta, ibrin and old hemorrhage lie between the placenta and the overlying sheer amniochorion. In contrast, with a circumvallate placenta, the chorion periphery is a thickened, opaque, gray-white circular ridge composed of a double fold of chorion and amnion. Sonographically, the double fold can be seen as a thick, linear band of echoes extending from one placental edge to the other. On cross section, however, it appears as two "shelves," with each lying above an opposing placental margin (see Fig. 6-2). his anatomy can help diferentiate this shelf from amnionic bands and amnionic sheets, which are


Obstentrics_Williams

Obstentrics_Williams. it appears as two "shelves," with each lying above an opposing placental margin (see Fig. 6-2). his anatomy can help diferentiate this shelf from amnionic bands and amnionic sheets, which are described on page 116.


Obstentrics_Williams

Obstentrics_Williams. In relatively small observational studies of circumvallate placenta diagnosed postpartum, it was associated with increased risk for antepartum bleeding, abruption, fetal demise, and preterm birth (Lademacher, 1981; Suzuki, 2008; Taniguchi, 2014). In a prospective sonographic investigation of 17 cases, however, Shen and associates (2007a) found most circumvallate placentas to be transient. Persistent cases were benign. In general, most otherwise uncomplicated pregnancies with either type of extrachorial placentation have normal outcomes, and no increased surveillance is usually required.


Obstentrics_Williams

Obstentrics_Williams. Functionally, placental perfusion disorders can be grouped into: (1) those in which maternal blood low to or within the intervillous space is disrupted, and (2) those with disturbed fetal blood flow through the villi. These lesions are frequently identiied in the normal, mature placenta. Although they can limit maximal placental blood flow, functional reserve within the placental prevents harm in most cases. Indeed, some estimate that up to 30 percent of placental villi can be lost without untoward fetal efects (Fox, 2007). If extensive, however, these lesions can profoundly limit fetal growth. Lesions that disrupt perfusion are frequently seen grossly or sonographically, whereas smaller lesions are seen only histologically. With sonography, many of these, such as subchorionic fibrin deposition, perivillous ibrin deposition, and intervillous thrombosis, appear as focal sonolucencies within the placenta. Importantly, in the absence of maternal or fetal


Obstentrics_Williams

Obstentrics_Williams. FIGURE 6-2 A. In this illustration, circummarginate (left) and circumvallate (right) varieties of extrachorial placentation are shown. Double fold of amnion & chorion A circummarginate placenta is covered by a single layer of amniochorion. B. This transabdominal gray-scale sonographic image shows a circumvallate placenta. The double fold of amnion and chorion creates a broad, opaque white ring and ridge on the fetal surface. complications, isolated placental sonolucencies are considered incidental indings. These collections are caused by slowing of maternal blood low within the intervillous space. In the portion of this space near the chorionic plate, blood stasis is prominent and leads to subsequent ibrin deposition. In viewing the placental fetal surface, subchorionic lesions are commonly seen as white or yellow, firm, round, elevated plaques just beneath the chorionic plate.


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Obstentrics_Williams. Stasis of maternal blood flow around an individual villus also results in fibrin deposition and can lead to diminished villous oxygenation and necrosis of syncytiotrophoblast (Fig. 6-3). These small yellow-white placental nodules are grossly visible within the parenchyma of a sectioned placenta. Within limits, these relect normal placental aging.


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Obstentrics_Williams. Maternal Floor Infarction. his extreme variant of perivillous fibrin deposition is a dense ibrinoid layer within the placental basal plate and is erroneously termed an infarction. Maternal loor inarction has a thick, yellow or white, irm corrugated surface that impedes normal maternal blood low into the intervillous space. In specific cases that extend beyond the basal plate to entrap villi and obliterate the intervillous space, the term massive perivillous ibrin deposition is used. The etiopathogenesis is unclear, but maternal auto-or alloimmunity appears contributory (Faye-Peterson, 2017; Romero, 2013). Antiphospholipid antibody syndrome and angiogenic factors involved with preeclampsia have also been implicated (Sebire, 2002, 2003; Whitten, 2013).


Obstentrics_Williams

Obstentrics_Williams. These lesions are not reliably imaged with prenatal sonography, but they may create a thicker basal plate. Afected pregnancies are associated with miscarriage, fetal-growth restriction, preterm delivery, and stillbirth (Andres, 1990; Mandsager, 1994). Importantly, these adverse outcomes can recur in subsequent pregnancies. This is a collection of coagulated maternal blood normally found in the intervillous space mixed with fetal blood from a break in a villus. Grossly, these round or oval collections vary in size up to several centimeters. hey appear red if recent or white-yellow if older, and they develop at any placental depth. Intervillous thrombi are common and typically not associated with adverse fetal sequelae. Because there is potential for a communication between maternal and fetal circulations, large lesions can cause elevated maternal serum alpha-fetoprotein levels (Salaia, 1988).


Obstentrics_Williams

Obstentrics_Williams. Chorionic villi themselves receive oxygen solely from maternal circulation supplied to the intervillous space. Any uteroplacental disease that diminishes or obstructs this supply can result in infarction of an individual villus. These are common lesions in mature placentas and are benign in limited numbers. If numerous, however, placental insuiciency can develop. When they are thick, centrally located, and randomly distributed, they may be associated with preeclampsia or lupus anticoagulant. As depicted in Figure 6-3, the maternal-placental-fetal unit can develop several hematoma types. These include: (1) retroplacental hematoma-between the placenta and its adjacent decidua; (2) marginal hematoma-between the chorion and


Obstentrics_Williams

Obstentrics_Williams. FIGURE 6-3 Potential sites of maternally and fetally related placental circulatory disturbances. (Adapted from Faye-Petersen, 2006.) decidua at the placental periphery-known clinically as sub chorionic hemorrhage; (3) subamnionic hematoma-these are of fetal vessel origin and found beneath the amnion but above the chorionic plate, and (4) subchorial thrombus along the roof of the intervillous space and beneath the chorionic plate. With this last type, massive subchorionic hematomas are also known as a Breus mole.


Obstentrics_Williams

Obstentrics_Williams. Sonographically, hematomas evolve with time and appear hyperechoic to isoechoic in the irst week after hemorrhage, hypoechoic at 1 to 2 weeks, and inally, anechoic after 2 weeks. Most subchorionic hematomas visible sonographically are fairly small and of no clinical consequence. However, extensive retroplacental, marginal, and subchorial collections have been associated with higher rates of miscarriage, stillbirth, placental abruption, and preterm delivery (Ball, 1996; Fung, 2010; vladu, 2006; Tuuli, 2011). In essence, placental abruption is a large, clinically signiicant retroplacental hematoma.


Obstentrics_Williams

Obstentrics_Williams. Placental lesions that arise from fetal circulatory disturbances are also depicted in Figure 6-3. Deoxygenated fetal blood lows from the two umbilical arteries into arteries within the chorionic plate that divide and send branches out across the placental surface. hese eventually supply individual stem villi, and their thrombosis will obstruct fetal blood low. Distal to the obstruction, afected portions of the villus become nonfunctional. Thrombi in limited numbers are normally found in mature placentas. If many villi are afected, which can be seen with preeclampsia, the fetus may sufer growth restriction, stillbirth, or nonreassuring fetal heart rate patterns (Chisholm, 2015; Lepais, 2014; Saleemuddin, 2010).


Obstentrics_Williams

Obstentrics_Williams. here is a spectrum of villous capillary lesions. Chorangiosis describes an increased number of capillaries within terminal villi. Its deinition requires :::10 capillaries to be present in :::10 villi in :::10 ields viewed through a lOx microscope lens (Altshuler, 1984). Clinically, long-standing hypoperfusion or hypoxia is thought to be causative (Stanek, 2016). It is often associated with maternal diabetes mellitus (Ogino, 2000). Chorangiomatosis describes increased capillary number in stem villi, but terminal villi are spared. his inding has been linked with fetal-growth restriction and anomalies (Bagby, 2011). Despite these associations, the clinical signiicance of both vascular conditions remains unclear. Chorioangiomas are described subsequently. As indicated earlier, these hematomas lie between the chorionic plate and amnion. They most often are acute events during third-stage labor when cord traction ruptures a vessel near the cord insertion.


Obstentrics_Williams

Obstentrics_Williams. Large chronic antepartum lesions may cause fetomaternal hemorrhage or fetal-growth restriction (Deans, 1998). They also may be confused with other placental masses such as chorio angioma. In most cases, Doppler interrogation will show absent internal blood low within a hematoma and permit differentiation (Sepulveda, 2000). Calcium salts can be deposited throughout the placenta but are most common on the basal plate. Calciication accrues with advancing gestation, and greater degrees are associated (Bedir Findik, 2015; Klesges, 1998; McKenna, 2005). These hyperechoic deposits can easily be seen sonographically, and a grading scale from 0 to 3 relects increasing calciication with increasing numerical grade (Grannum, 1979). Following this scheme, a grade 0 placenta is homogeneous, lacks calciication, and displays a smooth, lat chorionic plate. A grade 1 placenta lations. Grade 2 shows echogenic stippling at the basal plate.


Obstentrics_Williams

Obstentrics_Williams. Large, echogenic comma shapes originate from an indented chorionic plate, bur their curve falls short of the basal plate. Last, a grade 3 placenta has echogenic indentations extending from the chorionic plate to the basal plate, which create discrete components that resemble cotyledons. Basal plate densities also increase. As a predictor, this grading scale is not useful for neona tal outcome near term (Hill, 1983; McKenna, 2005; Montan, 1986). However, data from two small studies link grade 3 pla centa prior to 32 weeks with stillbirth and some other adverse pregnancy outcomes (Chen, 2011, 2015).


Obstentrics_Williams

Obstentrics_Williams. These benign tumors have components similar to blood vessels and stroma of the chorionic villus. lso called chorangiomas, these placental tumors occur with an incidence of approximately 1 percent (Guschmann, 2003). In some cases, fetal-to-maternal hemorrhage across tumor capillaries leads to elevated levels of maternal serum alpha-fetoprotein (MSAFP), prompting sonographic evaluation. heir characteristic sonographic appearance shows a well-circumscribed, rounded, predominantly hypoechoic lesion lying near the chorionic plate and protruding into the amnionic cavity (Fig. 6-4). Documenting increased blood low by color Doppler helps to distinguish these lesions from other placental masses such as hematoma, partial hydatidiform mole, teratoma, metastases, and leiomyoma (Prapas, 2000). Although rare, chorangiocarcinoma tumors clinically mirror chorangiomas (Huang, 2015).


Obstentrics_Williams

Obstentrics_Williams. Small chorioangiomas are usually asymptomatic. Large tumors, typically those measuring >4 em, can create signiicant arteriovenous shunting within the placenta to cause high-output heart failure, hydrops, and fetal death (l Wattar, 2014). Compression of fetal erythrocytes within tumor vessels can lead to hemolysis and microangiopathic anemia (Bauer, 1978). Hydramnios, pre term delivery, and fetal-growth restriction are other sequelae. Rare cases include tumor vessel rupture, hemorrhage, and fetal death (Batukan, 2001). At the other extreme, rare rumor infarction can lead to symptom reversal (Zalel, 2002). FIGURE 6�4 Placental chorioangioma. A. Color Doppler imaging displays blood flow through a large chorioangioma with its border outlined by white arrows. B. Grossly, the chorioangioma is a round, well-circumcised mass protruding from the fetal surface.


Obstentrics_Williams

Obstentrics_Williams. Gray-scale and color Doppler interrogation of the placenta and amnionic fluid volume are used to identiy these tumors. Diagnostic tools that can airm associated fetomaternal hemorrhage include MSAFP level and Kleihauer-Betke stain. With fetal concern, echocardiography assesses cardiac function, whereas middle cerebral artery interrogation is used to identiy fetal anemia. Several fetal therapies interfere with the vascular supply to the tumor and reverse fetal heart failure. At specialized perinatal centers, endoscopic laser ablation of feeder vessels to the tumor is most frequently used and is associated with favorable fetal outcomes (Hosseinzadeh, 2015). Of other therapy, fetal transfusion can treat serious anemia, amnioreduction can temporize hydramnios, and digoxin therapy can assist fetal heart failure.


Obstentrics_Williams

Obstentrics_Williams. Maternal malignant tumors rarely metastasize to the placenta. Of those that do, melanomas, leukemias and lymphomas, and breast cancer are the most common (Al-Adnani, 2007). Tumor cells usually are confined within the intervillous space. As a result, metastasis to the fetus is uncommon but is most often seen with melanoma (lexander, 2003). Similarly, cases in which fetal malignancy metastasizes to the placenta are rare (Reif, 2014). hese are predominantly fetal neuroectodermal tumors, and only one case in the literature describes transplantation of tumor to the maternal uterus (Nath, 1995).


Obstentrics_Williams

Obstentrics_Williams. Normal genital-tract flora can colonize and infect the membranes, umbilical cord, and eventually the fetus. Bacteria most commonly ascend after prolonged membrane rupture and during labor to cause infection. Organisms initially infect the chorion and adjacent decidua in the area overlying the internal os. Subsequently, progression leads to full-thickness involvement of the membranes-chorioamnionitis. Organisms often then spread along the chorioamnionic surface to colonize and replicate in amnionic luid. Inlammation of the chorionic plate and of the umbilical cord-unisitis-may follow (Kim, 2015; Redline, 2012).


Obstentrics_Williams

Obstentrics_Williams. Most commonly, there is microscopic or occult chorioamnionitis, which is caused by a wide variety of microorganisms. his is frequently cited as a possible explanation for many otherwise unexplained cases of ruptured membranes, preterm labor, or both as discussed in Chapter 42 (p. 810). In some cases, gross infection is characterized by membrane clouding and is sometimes accompanied by a foul odor that depends on bacterial species. Amnion nodosum is a condition characterized by numerous small, light-tan nodules on the amnion overlying the chorionic plate. hese may be scraped of the fetal surface and contain deposits of fetal squames and fibrin that relect prolonged and severe oligohydramnios (Adeniran, 2007).


Obstentrics_Williams

Obstentrics_Williams. Two notable bandlike structures can be formed by the fetal membranes. Of these, amnionic band sequence is an anatomical disruption sequence in which amnion bands tether, constrict, or amputate fetal parts. Amnionic bands commonly cause limb-reduction defects, facial clefts, or encephalocele (Barzilay, 2015; Guzman-Huerta, 2013). Umbilical cord compromise is another sequela (Barros, 2014; Heifetz, 1984b). Severe defects of the spine or ventral wall that accompany amnionic bands suggest a limb-body wall complex, described in Chapter 10 (p. 206). Clinically, sonography often irst identiies the sequelae of this sequence rather than the bands themselves. As with any fetal anomaly, targeted sonography is indicated. Identiication of a limb-reduction defect, an encephalocele in an atypical location, or an extremity with edema or positional deformity should prompt careful evaluation for amnionic bands. Management depends on the degree of anatomic deformity.


Obstentrics_Williams

Obstentrics_Williams. Management depends on the degree of anatomic deformity. Fetoscopic laser interruption of the band may be suitable in highly selected antepartum cases Qavadian, 2013; Mathis, 2015). In contrast, an amnionic sheet is formed by normal amniochorion draped over a preexisting uterine synechia. Generally, these sheets pose little fetal risk, although slightly higher rates of preterm membrane rupture and placental abruption have been described (Korbin, 1998; Nelson, 2010; Tuuli, 2012). Most umbilical cords at delivery are 40 to 70 cm long, and very few measure <30 cm or > 100 cm. Cord length is inluenced positively by both amnionic luid volume and fetal mobility (Miller, 1982). In retrospective studies, short cords have been linked with congenital malformations and intrapartum distress (Baergen, 2001; Krakowiak, 2004; Yamamoto, 2016). Excessively long cords are linked with cord entanglement or prolapse and with fetal anomalies (Olaya-C, 2015; Rayburn, 1981).


Obstentrics_Williams

Obstentrics_Williams. Because antenatal determination of cord length is technically limited, cord diameter has been evaluated as a predictive marker for fetal outcomes. Some have linked lean cords with poor fetal growth and large-diameter cords with macrosomia (Proctor, 2013). However, the clinical utility of this parameter is still unclear (Barbieri, 2008; Cromi, 2007; Raio, 1999b, 2003).


Obstentrics_Williams

Obstentrics_Williams. Cord coiling characteristics have been reported but are not currently part of standard sonographic evaluation. Usually the umbilical vessels spiral through the cord in a sinistral, that is, let-twisting direction (Fletcher, 1993; Lacro, 1987). he number of complete coils per centimeter of cord length is termed the umbilical coiling index-Uel (Strong, 1994). A normal, antepartum, sonographically derived UCI is 0.4, and this contrasts with a normal, postpartum, physically measured value of 0.2 (Sebire, 2007). UCls < 10th percentile are considered hypocoile, and those > 90th percentile are hypercoiled. Clinically, the signiicance of coiling extremes is controversial. Some studies evaluating large, unselected cohorts ind no associations between UCI values and poor neonatal outcome Qessop, 2014; Pathak, 2010). In others, extremes are linked with various adverse outcomes but most consistently with intrapartum fetal heart rate abnormalities, preterm labor, or fetal-growth restriction


Obstentrics_Williams

Obstentrics_Williams. 2014; Pathak, 2010). In others, extremes are linked with various adverse outcomes but most consistently with intrapartum fetal heart rate abnormalities, preterm labor, or fetal-growth restriction (Chitra, 2012; de Laat, 2006; Predanic, 2005; Rana, 1995).


Obstentrics_Williams

Obstentrics_Williams. Counting cord vessel number is a standard component of anatomical evaluation during fetal sonographic examination and immediately after delivery (Fig. 6-5). Embryos initially have two sonographically in the second trimester. They encircle the fetal bladder (asterisk) as extensions of the superior vesical arteries. In this color Doppler sonographic image, a single umbilical artery, shown in red, runs along the bladder wall before joining the umbilical vein (blue) in the cord. Below this, the two vessels of the cord, seen as a larger red and smaller blue circle, are also seen floating in a cross section of a cord segment. umbilical veins. In the irst trimester, the right vein typically atrophies to leave one large vein to accompany the two, thick-walled umbilical arteries. Four-vessel cords are rare and often associated with congenital anomalies (Puvabanditsin, 2011). If it is an isolated inding, however, prognosis can be good (Avnet, 2011).


Obstentrics_Williams

Obstentrics_Williams. The most common aberration is that of a single umbilical artery (SUA), with a cited incidence of 0.63 percent in liveborn neonates, 1.92 percent with perinatal deaths, and 3 percent in twins (Heifetz, 1984a). Fetuses with major malformations frequently have a single artery. Thus, its identiication often prompts consideration for targeted sonography and possibly fetal echocardiography. The most frequent anomalies are cardiovascular and genitourinary (Hua, 2010; Murphy-Kaulbeck, 2010). In an anomalous fetus, a single artery greatly increases the aneuploidy risk, and amniocentesis is recommended (Dagklis, 2010; Lubusky, 2007).


Obstentrics_Williams

Obstentrics_Williams. If target sonography inds otherwise normal anatomy, an isolated single artery in an otherwise low-risk pregnancy does not significantly increase the fetal aneuploidy risk. However, as in isolated inding, it has been associated with fetal-growth restriction and perinatal death in some but not all studies (ChettyJohn, 2010; Gutvirtz, 2016; Hua, 2010; Murphy-Kaulbeck, 2010; Voskamp, 2013). hus, while clinical monitoring of growth is reasonable, the value of sonographic surveillance is unclear. A rare anomaly is that of a fused umbilical artery with a shared lumen. It arises from failure of the two arteries to split during embryological development. The common lumen may extend through the entire cord, but, if partial, it is typically found near the placental insertion site (Yamada, 2005). In one report, these were associated with a higher incidence of marginal or velamentous cord insertion, but not congenital fetal anomalies (Fujikura, 2003).


Obstentrics_Williams

Obstentrics_Williams. Found in most placentas, the Hyrtl anastomosis is a connection between the two umbilical arteries and lies near the cord insertion into the placenta. This anastomosis acts as a pressureequalizing system between the arteries (Gordon, 2007). As a result, redistribution of pressure gradients and blood flow improves placental perfusion, especially during uterine contractions or during compression of one umbilical artery. Fetuses with a single umbilical artery lack this safety valve (Raio, 1999a, 2001). Several structures are housed in the umbilical cord during fetal development, and their remnants may be seen when the mature cord is viewed transversely. Indeed, J auniaux and colleagues (1989) sectioned 1000 cords, and in one fourth of the specimens, they found remnants of vitelline duct, allantoic duct, and embryonic vessels. These were not associated with congenital malformations or perinatal complications. Cysts occasionally are found along the course of the cord.


Obstentrics_Williams

Obstentrics_Williams. Cysts occasionally are found along the course of the cord. They are designated according to their origin. True cysts are epithelium-lined remnants of the allantoic or vitelline ducts and tend to be located closer to the fetal insertion site. In contrast, the more common pseudocysts form from local degeneration of Wharton jelly and occur anywhere along the cord. Both have a similar sonographic appearance. Single umbilical cord cysts identified in the irst trimester tend to resolve completely, however, multiple cysts may portend miscarriage or aneuploidy (Ghezzi, 2003; Hannaford, 2013). Cysts persisting beyond this time are associated wi th a risk for structural defects and chromosomal anomalies (Bonilla, 2010; Zangen, 2010).


Obstentrics_Williams

Obstentrics_Williams. The cord normally inserts centrally into the placental disc, but eccentric, marginal, or velamentous insertions are variants. Of these, eccentric insertions in general pose no identifiable fetal risk. Marginal insertion is a common variant-sometimes referred to as a battledore placenta-in which the cord anchors at the placental margin. In one population-based study, the rate was 6 percent in singleton gestations and 11 percent in twins (Ebbing, 20l3). This common insertion variant rarely causes problems, but it and velamentous insertion occasionally result in the cord being pulled of during delivery of the placenta (Ebbing, 2015; Luo, 20l3). In monochorionic twins, this insertion may be associated with weight discordance (Kent, 2011).


Obstentrics_Williams

Obstentrics_Williams. With velamentous insertion, the umbilical vessels characteristically travel within the membranes before reaching the placental margin (Fig. 6-6) The incidence of velamentous insertion approximates 1 percent but is 6 percent with twins (Ebbing, 2013). It is more commonly seen with placenta previa (Papinniemi, 2007; Raisanen, 2012). Antenatal diagnosis is possible sonographically, and with velamentous insertion, cord vessels are seen traveling along the uterine wall before entering the placental disc. Clinically, vessels are vulnerable to compression, which may lead to fetal hypoperfusion and acidemia. Higher associated rates of low Apgar scores, stillbirth, preterm delivery, and small for gestational age have been noted (Ebbing, 2017; Esakof, 2015; Heinonen, 1996; Vahanian, 2015). Accordingly, monitoring of fetal growth is reasonable either clinically or sonographically (Vintzileos, 2015).


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Obstentrics_Williams. Last, with the very uncommon furcate insertion, umbilical vessels lose their protective Wharton jelly shortly before they insert. As a result, they are covered only by an amnion sheath and prone to compression, twisting, and thrombosis. With this condition, vessels travel within the membranes and overlie the cervical os. here, they can be torn with cervical dilatation or membrane rupture, and laceration can lead to rapid fetal exsanguination. Over the cervix, vessels can also be compressed by a presenting fetal part. Fortunately, vasa previa is uncommon and has an incidence of 2 to 6 per 10,000 pregnancies


Obstentrics_Williams

Obstentrics_Williams. FIGURE 6-6 Velamentous cord insertion. A.The umbilical cord inserts into the membranes. From here, the cord vessels branch and are supported only by membrane until they reach the placental disc. B. When viewed sonographically and using color Doppler, the cord vessels appear to lie against the myometrium as they travel to insert marginally into the placental disc, which lies at the top of this image. (Ruiter, 2016; Sullivan, 2017). Vasa previa is classiied as type 1, in which vessels are part of a velamentous cord insertion, and type 2, in which involved vessels span between portions of a bilobate or a succenturiate placenta (Catanzarite, 2001). Two other risks are conception with in vitro fertilization and second-trimester placenta previa, with or without later migra tion (Baulies, 2007; Schachter, 2003).


Obstentrics_Williams

Obstentrics_Williams. Compared with intrapartum diagnosis, antepartum diagnosis greatly improves the perinatal survival rate, which ranges from 97 to 100 percent (Oyelese, 2004; Rebarber, 2014; Swank, 2016). Thus, vasa previa is ideally identiied early, although this is not always possible. Clinically, an examiner is occasionally able to palpate or directly see a tubular fetal vessel in the membranes overlying the presenting part. Efective screening for vasa previa begins during scheduled midtrimester sonographic examination. In suspicious cases, transvaginal sonography is added and shows cord vessels inserting into the membranes-rather than directly into the placenta-and vessels running above the cervical internal os (Fig. 6-7). Routine color Doppler interrogation of the placental cord insertion site, particularly in cases of placenta previa or low-lying placenta, may aid its detection. With this, the vessel waveform relects the fetal heart rate. In one systematic review, the median prenatal detection


Obstentrics_Williams

Obstentrics_Williams. in cases of placenta previa or low-lying placenta, may aid its detection. With this, the vessel waveform relects the fetal heart rate. In one systematic review, the median prenatal detection rate was 93 percent (Ruiter, 2015).


Obstentrics_Williams

Obstentrics_Williams. Once vasa previa is identiied, subsequent imaging is reasonable because 6 to 17 percent of cases ultimately resolve (Rebarber, 2015; Swank, 2016). Bed rest apparently has no added advantage. Antenatal corticosteroids can be provided as indicated or given prophylactically at 28 to 32 weeks' gestation to cover possible urgent preterm delivery. Antenatal hospitalization may be considered at 30 to 34 weeks to permit surveillance and expedited delivery for labor, bleeding, or rupture of membranes. Data supporting is limited, and admission may best serve women with risk factors that portend early delivery (Society for Maternal-Fetal Medicine, 2015). A few cases FIGURE 6-7 Vasa previa. Using color Doppler, an umbilical vessel (red circle) is seen overlying the internal os. At the bottom, the Doppler waveform seen with this vasa previa has the typical appearance of an umbilical artery, with a pulse rate of 141 beats per minute.


Obstentrics_Williams

Obstentrics_Williams. of antepartum fetoscopic surgery with vessel laser ablation are described (Hosseinzadeh, 2015; Johnston, 2014). However, current practice is early scheduled cesarean delivery. Robinson mend elective cesarean delivery at 34 to 35 weeks' gestation to balance the risks of perinatal exsanguination versus preterm birth morbidity. he Society for Maternal-Fetal Medicine (2015) considers planned cesarean delivery at 34 to 37 weeks' gestation reasonable. At delivery, the fetus is expeditiously delivered after the hys terotomy incision in case a vessel is lacerated during uterine entry. Delayed cord clamping is not encouraged.


Obstentrics_Williams

Obstentrics_Williams. At delivery, the fetus is expeditiously delivered after the hys terotomy incision in case a vessel is lacerated during uterine entry. Delayed cord clamping is not encouraged. In all pregnancies, otherwise unexplained vaginal bleeding of vasa previa and a lacerated fetal vessel. In many cases, bleed ing is rapidly fatal, and infant salvage is not possible. With less hemorrhage, however, it may be possible to distinguish fetal ver sus maternal bleeding. Various tests may be used, and each relies on the increased resistance of fetal hemoglobin to denaturing by alkaline or acid reagents (Odunsi, 1996; Oyelese, 1999). • Knots, Strictures, and Loops


Obstentrics_Williams

Obstentrics_Williams. • Knots, Strictures, and Loops Various mechanical abnormalities in the cord can impede blood low and sometimes cause fetal harm. Of these, true knots are found in approximately 1 percent of births. hese form from fetal movement, and associated risks include hydramnios and diabetes (Hershkovitz, 2001; Raisanen, 2013). Knots are especially common and dangerous in monoamnionic twins, which are discussed in Chapter 45 (p. 874). When true knots are associated with singleton fetuses, the stillbirth risk is increased four-to tenfold (Airas, 2002; S0rnes, 2000).


Obstentrics_Williams

Obstentrics_Williams. Knots can be found incidentally during antepartum sonography, and a "hanging noose" sign is suggestive (Ramon y Cajal, 2006). hree-dimensional and color Doppler aid diagnostic accuracy (Hasbun, 2007). With these knots, optimal fetal surveillance is unclear but may include umbilical artery Doppler velocimetry, nons tress testing, or subjective fetal movement monitoring (Rodriguez, 2012; Scioscia, 201l). Allowing vaginal delivery is suitable, but abnormal intrapartum fetal heart rate tracings are more often encountered. hat said, cesarean delivery rates are not increased, and cord blood acid-base values are usually normal (Airas, 2002; Maher, 1996). In contrast,alse knots form from focal redundancy and folding of an umbilical cord vessel. hese lack clinical signiicance.


Obstentrics_Williams

Obstentrics_Williams. In contrast,alse knots form from focal redundancy and folding of an umbilical cord vessel. hese lack clinical signiicance. Cord strictures are focal narrowings of the diameter that usually develop near the fetal cord insertion site (Peng, 2006). Characteristic pathological features include an absence of Wharton jelly and stenosis or obliteration of cord vessels at the narrow segment (Sun, 1995). In most instances, the fetus is stillborn (French, 2005). Even less common is a cord stricture caused by an amnionic band. Cord loops are frequently encountered and are caused by coiling around various fetal parts during movement. A cord around the neck-a nuchal cord-is common, and vaginal delivery is suitable. One loop is reported in 20 to 34 percent of deliveries; two loops in 2.5 to 5 percent; and three loops in 0.2 to 0.5 percent (Kan, 1957; S0rnes, 1995; Spellacy, 1966).


Obstentrics_Williams

Obstentrics_Williams. During labor, up to 20 percent of fetuses with a nuchal cord have moderate to severe variable heart rate decelerations, and these are associated with a lower umbilical artery pH (Hankins, 1987). Cords wrapped around the body can have similar efects (Kobayashi, 2015). Despite their frequency, nuchal cords are not associated with greater rates of adverse perinatal outcome (Henry, 2013; Sheiner, 2006). Last, a unic presentation describes when the umbilical cord is the presenting part in labor. These are uncommon and most often are associated with fetal malpresentation (Kinugasa, 2007). A funic presentation in some cases is identiied with placental sonography and color low Doppler (Ezra, 2003). Overt or occult cord prolapse can complicate labor. hus, once identiied at term, cesarean delivery is typically recommended.


Obstentrics_Williams

Obstentrics_Williams. Cord hematomas are rare and generally follow rupture of an umbilical vessel, usually the vein, and bleeding into the Wharton jelly. Hematomas have been associated with abnormal cord length, umbilical vessel aneurysm, trauma, entanglement, umbilical vessel venipuncture, and funisitis (Gualandri, 2008). Most are identiied postpartum, but hematomas are recognized so no graphically as hypoechoic masses that lack blood low (Chou, 2003). Sequelae include stillbirth or intrapartum abnormal fetal heart rate pattern (Abraham, 2015; Barbati, 2009; Sepulveda, 2005; Towers, 2009).


Obstentrics_Williams

Obstentrics_Williams. Umbilical cord vessel thromboses are rare in utero events and seldom diagnosed antepartum. Approximately 70 percent are venous, 20 percent are venous and arterial, and 10 percent are arterial thromboses (Heifetz, 1988). hese all have high associated rates of stillbirth, fetal-growth restriction, and intrapartum fetal distress (Minakami, 2001; Sato, 2006; Shilling, 2014). If these are identiied antepartum as hypoechoic masses without blood low, data from case reports support consideration of prompt delivery if of viable age (Kanenishi, 2013).


Obstentrics_Williams

Obstentrics_Williams. n umbilical vein varix can complicate either the intraamnionic or fetal intraabdominal portion of the umbilical vein. So no graphically and complemented by color Doppler, rare intraamnionic varices show cystic dilatation of the umbilical vein that is contiguous with a normal-caliber portion. Of complications, an intraamnionic varix may compress an adjacent umbilical artery or can rupture or thrombose. In cases without these, White and colleagues (1994) recommend fetal surveillance and delivery once fetal maturity is confirmed. However, data are limited and derived from case reports.


Obstentrics_Williams

Obstentrics_Williams. he rare umbilical artey aneuysm is caused by congenital thinning of the vessel wall with diminished support from Wharton jelly. Indeed, most form at or near the cord placental insertion site, where this support is absent. These are associated with single umbilical artery, trisomy 18, amnionic luid volume extremes, fetal-growth restriction, and stillbirth (Hill, 2010; Vyas, 2016). At least theoretically, these aneurysms could cause fetal compromise and death by compression of the umbilical vein. These aneurysms may appear sonographically as a cyst with a hyperechoic rim. Within the aneurysm, color low and spectral Doppler interrogation demonstrate either lowvelocity or turbulent nonpulsatile flow (Olog, 2011; Sepulveda, 2003; Shen, 2007b). Although not codified, management may include fetal karyotyping, antenatal fetal surveillance, and early delivery to prevent stillbirth (Doehrman, 2014).


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Obstentrics_Williams. Abraham A, Rathore S, Gupta M, et al: Umbilical cord haematoma causing still birth-a case report. J Clin Diagn Res 9(12):QD01, 2015 Adeniran AJ, Stanek J: Amnion nodosum revisited: clinicopathologic and placental correlations. Arch Pathol Lab Med 131: 1829, 2007 Airas U, Heinonen S: Clinical signiicance of true umbilical knots: a population-based analysis. Am J PerinatoIs19:127, 2002 Al-Adnani M, Kiho L, Scheimberg I: Maternal pancreatic carcinoma metastatic to the placenta: a case report and literature review. Pediatr Dev Pathol 10:61,s2007 Alexander A, Samlowski E, Grossman D, et al: Metastatic melanoma in pregnancy: risk of transplacental metastases in the infant. J Clin Oncol 21:2179,s2003 Altshuler G. Chorangiosis: An important placental sign of neonatal morbidity and mortality. Arch Pathol Lab Med 108(1):71, 1984 Al Wattar BH, Hillman SC, Marton T, et al: Placenta chorioangioma: a rare case and systematic review of literature. J Matern Fetal Neonatal Med 27(10):1055,s2014


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Obstentrics_Williams. Al Wattar BH, Hillman SC, Marton T, et al: Placenta chorioangioma: a rare case and systematic review of literature. J Matern Fetal Neonatal Med 27(10):1055,s2014 American Institute of Ultrasound in Medicine: AlUM practice guideline for the performance of obstetric ultrasound examinations. J Ultrasound Med 32(6):1083,s2013 Andres RL, Kuyper W, Resnik R, et al: The association of maternal floor infarction of the placenta with adverse perinatal outcome. Am J Obstet Gynecol 163:935, 1990 Avnet H, Shen 0, Mazaki E, et al: Four-vessel umbilical cord. Ultrasound Obstet Gynecol 38:604, 2011 Baergen RN, Malicki D, Behling C, et al: Morbidity, mortality, and placental pathology in excessively long umbilical cords: retrospective study. Pediatr Dev PathoIs4(2):144, 2001 Bagby C, Redline RW: Multifocal chorangiomatosis. Pediatr Dev Pathol 14(1):38,s2011


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Obstentrics_Williams. Bagby C, Redline RW: Multifocal chorangiomatosis. Pediatr Dev Pathol 14(1):38,s2011 Ball RH, Ade CM, Schoenborn JA, et al: The clinical significance of ultrasonographically detected subchorionic hemorrhages. Am J Obstet Gynecol 174:996,s1996 Barbati A, Cacace MG, Fratini D, et al: Umbilical cord haematoma with altered fetal heart rate. J Obstet Gynaecol 29(2): 150, 2009 Barbieri C, Cecatti JG, Krupa F, et al: Validation study of the capacity of the reference curves of ultrasonographic measurements of the umbilical cord to identiy deviations in estimated fetal weight. Acta Obstet Gynecol Scand 87:286, 2008 Barros M, Gorgal G, Machado AP, et al: Revisiting amniotic band sequence: a wide spectrum of manifestations. Fetal Diagn Ther 35(1):51, 2014 Barzilay E, Harel Y, Haas J, et al: Prenatal diagnosis of amniotic band syndrome-risk factors and ultrasonic signs. J Matern Fetal Neonatal Med 28(3):281,s2015


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Obstentrics_Williams. Barzilay E, Harel Y, Haas J, et al: Prenatal diagnosis of amniotic band syndrome-risk factors and ultrasonic signs. J Matern Fetal Neonatal Med 28(3):281,s2015 Batukan C, Holzgreve W, Danzer E, et al: Large placental chorioangioma as a cause of sudden intrauterine fetal death. A case report. Fetal Diagn her 16:394, 2001 Bauer CR, Fojaco M, Bancalari E, et al: Microangiopathic hemolytic anemia and thrombocytopenia in a neonate associated with a large placental chorioangioma. Pediatrics 62(4):574, 1978 Baulies S, Maiz N, Munoz A, et al: Prenatal ultrasound diagnosis of vasa praevia and analysis of risk factors. Prenat Diagn 27:595, 2007 Bedir Findik R, Ersoy AO, Fidanci V, et al: Vitamin D deficiency and placental calciication in low-risk obstetric population: are they related? J Matern Fetal Neonatal Med 29(19):3189, 2015 Benirschke K, Burton GJ, Baergen R: Pathology of the Human Placenta, 6th ed. New York, Springer, 2012, p 908


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Obstentrics_Williams. Benirschke K, Burton GJ, Baergen R: Pathology of the Human Placenta, 6th ed. New York, Springer, 2012, p 908 Bonilla F Jr, Raga F, Villalaiz E, et al: Umbilical cord cysts: evaluation with different 3-dimensional sonographic modes. J Ultrasound Med 29(2):281, 2010 Catanzarite V, Maida C, Thomas W, et al: Prenatal sonographic diagnosis of vasa previa: ultrasound indings and obstetric outcome in ten cases. Ultrasound Obstet GynecoIs18:109, 2001 Chen KH, Chen LR, Lee H: Exploring the relationship berween preterm placental calciication and adverse maternal and fetal outcome. Ultrasound Obstet GynecoIs37(3):328, 2011 Chen KH, Seow M, Chen LR: The role of preterm placental calciication on assessing risks of stillbirth. Placenta 36(9): 1039, 2015 Chetty-John S, Zhang J, Chen Z, et al: Long-term physical and neurologic development in newborn infants with isolated single umbilical artery. Am J Obstet GynecoI203(4):368.el, 2010


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Obstentrics_Williams. Chetty-John S, Zhang J, Chen Z, et al: Long-term physical and neurologic development in newborn infants with isolated single umbilical artery. Am J Obstet GynecoI203(4):368.el, 2010 Chisholm M, Heerema-McKenney A: Fetal thrombotic vasculopathy: signiicance in live born children using proposed society for pediatric pathology diagnostic criteria. Am J Surg PathoIs39(2):274, 2015 Chitra T, Sushanth YS, Raghavan S: Umbilical coiling index as a marker of perinatal outcome: an analytical study. Obstet Gynecol Int 2012:213689, 2012 Chou SY, Chen YR, Wu CF, et al: Spontaneous umbilical cord hematoma diagnosed antenatally with ultrasonography. Acta Obstet Gynecol Scand 82(11): 1056, 2003 Cromi A, Ghezzi F, Di Naro E, et al: Large cross-sectional area of the umbilical cord as a predictor of fetal macrosomia. Ultrasound Obstet Gynecol 30:804, 2007 Dagklis T, Deigueiredo 0, Staboulidou I, et al: Isolated single umbilical artery and fetal karyotype. Ultrasound Obstet Gynecol 36(3):291, 2010


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Obstentrics_Williams. Dagklis T, Deigueiredo 0, Staboulidou I, et al: Isolated single umbilical artery and fetal karyotype. Ultrasound Obstet Gynecol 36(3):291, 2010 Deans A, Jauniaux E: Prenatal diagnosis and outcome of subamniotic hematomas. Ultrasound Obstet Gynecol 11:319, 1998 de Laat MW, Franx A, Bots ML, et al: Umbilical coiling index in normal and complicated pregnancies. Obstet Gynecol 107:1049,s2006 Doehrman P, Derksen BJ, Perlow JH, et al: Umbilical artery aneurysm: a case report, literature review, and management recommendations. Obstet Gynecol Surv 69(3):159,s2014 Ebbing C, Johnsen SL, Albrechtsen S, et al: Velamentous or marginal cord insertion and the risk of spontaneous preterm birth, prelabor rupture of the membranes, and anomalous cord length, a population-based study. Acta Obstet Gynecol Scand 96(1):78, 2017


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Obstentrics_Williams. Ebbing C, Kiserud T, Johnsen SL, et al: Prevalence, risk factors and outcomes of velamentous and marginal cord insertions: a population-based study of 634,741 pregnancies. PLoS One 8(7):e70380, 2013 Ebbing C, Kiserud T, Johnsen SL, et al: Third stage of labor risks in velamentous and marginal cord insertion: a population-based study. Acta Obstet Gynecol Scand 94(8):878, 2015 EsakofTF, Cheng W, Snowden JM, et al: Velamentous cord insertion: is it associated with adverse perinatal outcomes? J Matern Fetal Neonatal Med 28(4):409,s2015 Ezra Y, Strasberg SR, Farine 0: Does cord presentation on ultrasound predict cord prolapse? Gynecol Obstet Invest 56:6, 2003 Faye-Petersen 0, Sauder A, Estrella Y, et al: Dichorionic twins discordant for massive perivillous ibrinoid deposition: report of a case and review of the literature. Int J Surg Pathol July 1, 2017 [Epub ahead of print]


Obstentrics_Williams

Obstentrics_Williams. Faye-Petersen OM, Heller OS, Joshi VV: Handbook of Placental Pathology, 2nd ed. London, Taylor & Francis, 2006, pp 27, 83 Fletcher S: Chirality in the umbilical cord. BJOG 100(3):234, 1993 Fox H, Sebire NJ: Pathology of the Placenta, 3rd ed. Philadelphia, Saunders, 2007, pp 99, 133, 484 French AE, Gregg VH, Newberry Y, et al: Umbilical cord stricture: a cause of recurrent fetal death. Obstet Gynecol 105: 1235,s2005 Fujikura T: Fused umbilical arteries near placental cord insertion. Am J Obstet Gynecol 188:765, 2003 Fung Y, To KF, Sahota OS, et al: Massive subchorionic thrombohematoma: a series of 10 cases. Acta Obstet Gynecol Scand 89(10):1357, 2010 Ghezzi F, Raio L, Di Naro E, et al: Single and multiple umbilical cord cysts in early gestation: two diferent entities. Ulrrasound Obstet Gynecol 21:213, 2003 Gordon Z, Eytan 0, Jafa AJ, et al: Hemodynamic analysis of Hyrtl anastomosis in human placenta. Am J Physiol Regul Integra Comp PhysioI292:R977, 2007


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Obstentrics_Williams. Gordon Z, Eytan 0, Jafa AJ, et al: Hemodynamic analysis of Hyrtl anastomosis in human placenta. Am J Physiol Regul Integra Comp PhysioI292:R977, 2007 Grannum PA, Berkowitz RL, Hobbins JC: he ultrasonic changes in the maturing placenta and their relation to fetal pulmonic maturity. Am J Obstet Gynecol 133:915, 1979 Greenberg JA, Sorem A, Shifren JL, et al: Placenta membranacea with placenta increta: a case report and literature review. Obstet Gynecol 78:512, 1991 Gualandri G, Rivasi F, Santunione AL, et al: Spontaneous umbilical cord hematoma: an unusual cause of fetal mortality: a report of 3 cases and review of the literature. Am J Forensic Med Pathol 29(2): 185, 2008 Guschmann M, Henrich W, Entezami M, et al: Chorioangioma-new insights into a well-known problem. I. Results of a clinical and morphological study of 136 cases. J Perinat Med 31: 163, 2003


Obstentrics_Williams

Obstentrics_Williams. Guschmann M, Henrich W, Entezami M, et al: Chorioangioma-new insights into a well-known problem. I. Results of a clinical and morphological study of 136 cases. J Perinat Med 31: 163, 2003 Gutvirtz G, Walisch A, Beharier 0, et al: Isolated single umbilical artery is an independent risk factor for perinatal mortality and adverse outcomes in term neonates. Arch Gynecol Obstet 294(5):931,s2016 Guzman-Huerta ME, Muro-Barragan SA, Acevedo-Gallegos S, et al: Amniotic band sequence: prenatal diagnosis, phenotype descriptions, and a proposal of a new classiication based on morphologic indings. Rev Invest Clin 65(4):300,s2013 Hankins GO, Snyder R, Hauth JC, et al: Nuchal cords and neonatal outcome. Obstet Gynecol 70:68 , 1987 Hannaford K, Reeves S, Wegner E: Umbilical cord cysts in the irst trimester: are they associated with pregnancy complications? J Ultrasound Med 32(5):801,s2013


Obstentrics_Williams

Obstentrics_Williams. Hannaford K, Reeves S, Wegner E: Umbilical cord cysts in the irst trimester: are they associated with pregnancy complications? J Ultrasound Med 32(5):801,s2013 Hasbun J, Alcalde JL, Sepulveda W: hree-dimensional power Doppler sonography in the prenatal diagnosis of a true knot of the umbilical cord: value and limitations. J Ultrasound Med 26(9):1215,s2007 Heifetz SA: Single umbilical artery: a statistical analysis of 237 autopsy cases and a review of the literature. Perspect Pediatr Pathol 8:345, 1984a Heifetz SA: Strangulation of the umbilical cord by amniotic bands: report of 6 cases and literature review. Pediatr PathoIs2:285, 1984b Heifetz SA: hrombosis of the umbilical cord: analysis of 52 cases and literature review. Pediatr Pathol 8:37, 1988 Heinonen S, Ryynanen M, Kirkinen P, et al: Perinatal diagnostic evaluation of velamentous umbilical cord insertion: clinical, Doppler, and ultrasonic indings. Obstet GynecoI87(l):112, 1996


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Obstentrics_Williams. Heinonen S, Ryynanen M, Kirkinen P, et al: Perinatal diagnostic evaluation of velamentous umbilical cord insertion: clinical, Doppler, and ultrasonic indings. Obstet GynecoI87(l):112, 1996 Henry E, Andres L, Christensen D: Neonatal outcomes following a tight nuchal cord. J PerinatoIs33(3):231, 2013 Hershkovitz R, Silberstein T, Sheiner E, et al: Risk factors associated with true knots of the umbilical cord. Eur J Obstet Gynecol Reprod Bioi 98(1):36, 200s1 Hill AJ, Strong TH Jr, Elliott JP, et al: Umbilical artery aneurysm. Obstet Gynecol 116(Suppl 2):559, 2010 Hill LM, Breckle R, Ragozzino MW, et al: Grade 3 placentation: incidence and neonatal outcome. Obstet Gynecol 61: 728, 1983 Hoddick K, Mahony BS, Callen PW, et al: Placental thickness. J Ultrasound Med 4(9):479, 1985 Hosseinzadeh P, Shamshirsaz A, Cass DL, et al: Fetoscopic laser ablation of vasa previa for a fetus with a giant cervical lymphatic malformation. Ultrasound Obstet GynecoIs46(4):507, 2015


Obstentrics_Williams

Obstentrics_Williams. Hosseinzadeh P, Shamshirsaz A, Cass DL, et al: Fetoscopic laser ablation of vasa previa for a fetus with a giant cervical lymphatic malformation. Ultrasound Obstet GynecoIs46(4):507, 2015 Hua M, Odibo AO, Macones GA, et al: Single umbilical artery and its associated indings. Obstet GynecoIs115(5):930, 2010 Huang B, Zhang P, Yuan OF, et al: Chorangiocarcinoma: a case report and clinical review. Int J Clin Exp Med 8(9): 16798, 2015 Jauniaux E, De Munter C, Vanesse M, et al: Embryonic remnants of the umbilical cord: morphologic and clinical aspects. Hum Pathol 20(5):458, 1989 Javadian P, Shamshirsaz A, Haeri S, et al: Perinatal outcome after fetoscopic release of amniotic bands: a single-center experience and review of the literature. Ultrasound Obstet GynecoIs42(4):449, 2013 Jessop FA, Lees Cc, Pathak S, et al: Umbilical cord coiling: clinical outcomes in an unselected population and systematic review. Virchows Arch 464(1):105,s2014


Obstentrics_Williams

Obstentrics_Williams. Jessop FA, Lees Cc, Pathak S, et al: Umbilical cord coiling: clinical outcomes in an unselected population and systematic review. Virchows Arch 464(1):105,s2014 Johnston R, Shrivastava K, Chmait RH: Term vaginal delivery following fetoscopic laser photocoagulation of rype II vasa previa. Fetal Diagn Ther 35(1):62,s2014 Kan PS, Eastman NJ: Coiling of the umbilical cord around the foetal neck. BJOG 64:227, 1957 Kanenishi K, Nitta E, Mashima M, et al: HDlive imaging of intra-amniotic umbilical vein varix with thrombosis. Placenta 34(11): 111 0, 2013 Kent EM, Breathnach FM, Gillan JE, et al: Placental cord insertion and birthweight discordance in twin pregnancies: results of the national prospective ESPRiT Study. Am J Obstet Gynecol 205(4):376.el, 201s1 Kim CJ, Romero R, Chaemsaithong P, et al: Acute chorioamnionitis and funisitis: deinition, pathologic features, and clinical signiicance. Am J Obstet Gynecols213(4 Suppl):S29, 2015


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Obstentrics_Williams. Kim CJ, Romero R, Chaemsaithong P, et al: Acute chorioamnionitis and funisitis: deinition, pathologic features, and clinical signiicance. Am J Obstet Gynecols213(4 Suppl):S29, 2015 Kinugasa M, Sato T, Tamura M, et al: Antepartum detection of cord presentation by transvaginal ultrasonography for term breech presentation: potential prediction and prevention of cord prolapse. J Obstet Gynaecol Res 33(5):612,s2007 Klesges LM, Murray OM, Brown JE, et al: Relations of cigarette smoking and dietary antioxidants with placental calciication. Am J Epidemiol 147(2):127, 1998 Kobayashi N, Aoki S, Oba MS, et al: Efect of umbilical cord entanglement and position on pregnancy outcomes. Obstet Gynecol Int 2015:342065, 2015 Korbin CD, Benson CB, Doubilet PM: Placental implantation on the amni otic sheer: efect on pregnancy outcome. Radiology 206(3):773, 1998 Krakowiak P, Smith EN, de Bruyn G, et al: Risk factors and outcomes associated with a short umbilical cord. Obstet Gynecol 103: 119, 2004


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Obstentrics_Williams. Lacro RV, Jones KL, Benirschke K: he umbilical cord twist: origin, direction, and relevance. Am J Obstet Gynecol 157(4 Pt 1):833, 1987 Lademacher OS, Vermeulen RC, Hartens]J, et al: Circumvallate placenta and congenital malformation. Lancet 1:732, 1981 Langston C, Kaplan C, Macpherson T, et al: Practice guideline for examination of the placenta. Arch Pathol Lab Med 121 :449, 1997 Lepais L, Gaillot-Durand L, Boutitie F, et al: Fetal thrombotic vasculopathy is associated with thromboembolic events and adverse perinatal outcome but not with neurologic complications: a retrospective cohort study of 54 cases with a 3-year follow-up of children. Placenta 35(8):611,s2014 Lubusky M, Dhaifalah I, Prochazka M, et al: Single umbilical artery and its siding in the second trimester of pregnancy: relation to chromosomal defects. Prenat Diagn 27:327, 2007 Luo G, Redline RW: Peripheral insertion of umbilical cord. Pediatr Dev Pathol 16(6):399,s2013


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Obstentrics_Williams. Luo G, Redline RW: Peripheral insertion of umbilical cord. Pediatr Dev Pathol 16(6):399,s2013 Madu AE: Breus' mole in pregnancy.] Obstet Gynaecol 26:815, 2006 Maher ]T, Contis]A: A comparison of umbilical cord blood gas values between newborns with and without true knots. Obstet Gynecol 88:863, 1996 Mandsager NT, Bendon R, Mostello D, et al: Maternal floor infarction of the placenta: prenatal diagnosis and clinical signiicance. Obstet Gynecol 83:750, 1994 Mathis], Raio L, Baud D: Fetal laser therapy: applications in the management offetal pathologies. Prenat Diagn 35(7):623, 2015 McKenna D, Tharmaratnam S, Mahsud S, et al: Ultrasonic evidence of placental calciication at 36 weeks' gestation: maternal and fetal outcomes. Acta Obstet Gynecol Scand 84:7, 2005 Miller ME, Jones Me, Smith DW: Tension: the basis of umbilical cord growth.] Pediatr 101(5):844, 1982


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Obstentrics_Williams. Miller ME, Jones Me, Smith DW: Tension: the basis of umbilical cord growth.] Pediatr 101(5):844, 1982 Minakami H, Akahori A, Sakurai S, et al: Umbilical vein thrombosis as a possible cause of perinatal morbidity or mortality: report of two cases. ] Obstet Gynaecol Res 27(2):9 ; 2001 Montan S, Jorgensen C, Svalenius E, et al: Placental grading with ultrasound in hypertensive and normotensive pregnancies: a prospective, consecutive study. Acta Obstet Gynecol Scand 65:477, 1986 Murphy-Kaulbeck L, Dodds L, Joseph KS, et al: Single umbilical artery risk factors and pregnancy outcomes. Obstet Gynecol 116(4):843,2010 Nath ME, Kanbour A, Hu], et al: Transplantation of congenital primitive neuroectodermal tumor of fetus to the uterus of mother: application of biotinlabeled chromosome-speciic probes. lnt] Gynecol Cancer 5(6):459, 1995 Nelson LD, Grobman WA: Obstetric morbidity associated with amniotic sheets. Ultrasound Obstet Gynecol 36(3):324, 2010


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Obstentrics_Williams. Nelson LD, Grobman WA: Obstetric morbidity associated with amniotic sheets. Ultrasound Obstet Gynecol 36(3):324, 2010 Odunsi K, Bullough CH, Henzel], et al: Evaluation of chemical tests for fetal bleeding from vasa previa. Int] Gynaecol Obstet 55(3):20 , 19% Ogino S, Redline RW: Villous capillary lesions of the placenta: distinctions between chorangioma, chorangiomatosis, and chorangiosis. Hum Pathol 31:945,s2000 Olaya-C M, Bernal ]E: Clinical associations to abnormal umbilical cord length in Latin American newbons.s] Neonatal Perinatal Med 8(3):251, 2015 Olog A, homas ]T, Petersen S, et al: Large umbilical artery aneurysm with a live healthy baby delivered at 31 weeks. Fetal Diagn Ther 29(4):331,2011 Oyelese KO, Turner M, Lees e, et al: Vasa previa: an avoidable obstetric tragedy. Obstet Gynecol Surv 54: 138, 1999 Oyelese Y, Catanzarite V, Prefumo F, et al: Vasa previa: the impact of prenatal diagnosis on outcomes. Obstet Gynecol 103:937, 2004


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Obstentrics_Williams. Oyelese Y, Catanzarite V, Prefumo F, et al: Vasa previa: the impact of prenatal diagnosis on outcomes. Obstet Gynecol 103:937, 2004 Papinniemi M, Keski-Nisula L, Heinonen S: Placental ratio and risk of velamentous umbilical cord insertion are increased in women with placenta previa. Ams] Perinatol 24:353, 2007 Pathak S, Hook E, Hackett G, et al: Cord coiling, umbilical cord insertion and placental shape in an unselected cohort delivering at term: relationship with common obstetric outcomes. Placenta 31 (11) :963, 2010 Peng HQ, Levitin-Smith M, Rochelson B, et al: Umbilical cord stricture and over coiling are common causes of fetal demise. Pediatr Dev Pathol 9: 14, 2006 Pereira N, Yao R, Guilfoil DS, et al: Placenta membranacea with placenta accreta: radiologic diagnosis and clinical implications. Prenat Diagn 33(13):1293,s2013


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Obstentrics_Williams. Pereira N, Yao R, Guilfoil DS, et al: Placenta membranacea with placenta accreta: radiologic diagnosis and clinical implications. Prenat Diagn 33(13):1293,s2013 Prapas N, Liang RI, Hunter D, et al: Color Doppler imaging of placental masses: diferential diagnosis and fetal outcome. Ultrasound Obstet Gynecol 16:559,s2000 Predanic M, Perni SC, Chasen ST, et al: Ultrasound evaluation of abnormal umbilical cord coiling in second trimester of gestation in association with adverse pregnancy outcome. Am] Obstet Gynecol 193:387,2005 Proctor LK, Fitzgerald B, Whittle L, et al: Umbilical cord diameter percentile curves and their correlation to birth weight and placental pathology. Placenta 34(1):62, 2013 Puvabanditsin S, Garrow E, Bhatt M, et al: Four-vessel umbilical cord associated with multiple congenital anomalies: a case report and literature review. Fetal Pediatr Pathol 30(2):98, 2011


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Obstentrics_Williams. Puvabanditsin S, Garrow E, Bhatt M, et al: Four-vessel umbilical cord associated with multiple congenital anomalies: a case report and literature review. Fetal Pediatr Pathol 30(2):98, 2011 Raio L, Ghezzi F, Di Naro E, et al: In-utero characterization of the blood flow in the Hyrtl anastomosis. Placenta 22:597,s2001 Raio L, Ghezzi F, Di Naro E, et al: Prenatal assessment of the Hyrtl anastomosis and evaluation of its function: case report. Hum Reprod 14: 1890, 1999a Raio L, Ghezzi F, Di Naro E, et al: Sonographic measurement of the umbilical cord and fetal anthropometric parameters. Eur ] Obstet Gynecol Reprod Bioi 83: 131, 1999b Raio L, Ghezzi F, Di Naro E, et al: Umbilical cord morphologic characteristics and umbilical artery Doppler parameters in intrauterine growth-restricted fetuses. ] Ultrasound Med 22: 1341, 2003


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Obstentrics_Williams. Raio L, Ghezzi F, Di Naro E, et al: Umbilical cord morphologic characteristics and umbilical artery Doppler parameters in intrauterine growth-restricted fetuses. ] Ultrasound Med 22: 1341, 2003 Raisanen S, Georgiadis L, Harju M, et al: Risk factors and adverse pregnancy outcomes among births afected by velamentous umbilical cord insertion: a retrospective population-based register study. Eurs] Obstet Gynecol Reprod BioI 165(2):231, 2012 Raisanen S, Georgiadis L, Harju M, et al: True umbilical cord knot and obstetric outcome. Int] Gynaecol Obstet 122(1):18, 2013 Ramon y Cajal CL, Martinez RO: Four-dimensional ultrasonography of a true knot of the umbilical cord. Am] Obstet Gynecol 195:896, 2006 Ranas], Ebert GA, Kappy A: Adverse perinatal outcome in patients with an abnormal umbilical coiling index. Obstet Gynecol 85(4):573, 1995 Rayburn WF, Beynen A, Brinkman DL: Umbilical cord length and intrapartum complications. Obstet Gynecol 57(4):450, 1981


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Obstentrics_Williams. Rebarber A, Dolin e, Fox NS, et al: Natural history of vasa previa across gestation using a screening protocol.] Ultrasound Med 33(1):141, 2014 Redline RW: Inlammatory response in acute chorioamnionitis. Semin Fetal Neonatal Med 17(1):20,s2012 Redline RW: Placental pathology: a systematic approach with clinical correlations. Placenta 29(Suppl A):S86, 2008 Reif P, Hofer N, Kolovetsiou-Kreiner V, et al: Metastasis of an undiferentiated fetal soft tissue sarcoma to the maternal compartment of the placenta: maternal aspects, pathology indings and review of the literature on fetal malignancies with placenta metastases. Histopathology 65(6):933,s2014 Roberts D]: Placental pathology, a survival guide. Arch Pathol Lab Med 132(4):641, 2008 Robinson BK, Grobman WA: Efectiveness of timing strategies for delivery of individuals with vasa previa. Obstet Gynecol 117(3):542,s201s1


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Obstentrics_Williams. Robinson BK, Grobman WA: Efectiveness of timing strategies for delivery of individuals with vasa previa. Obstet Gynecol 117(3):542,s201s1 Rodriguez N, Angarita M, Casasbuenas A, et al: Three-dimensional highdeinition low imaging in prenatal diagnosis of a true umbilical cord knot. Ultrasound Obstet Gynecol 39(2):245, 2012 Romero R, Whitten A, Korzeniewski S], et al: Maternal Boor infarction/massive perivillous ibrin deposition: a manifestation of maternal antifetal rejection? Am] Reprod Immunol 70(4):285,s2013 Ruiter L, Kok N, Limpens ], et al: Incidence of and risk indicators for vasa praevia: a systematic review. B]OG 123(8):1278,s2016 Ruiter L, Kok N, Limpens J, et al: Systematic review of accuracy of ultrasound in the diagnosis of vasa previa. Ultrasound Obstet Gynecol 45(5):516, 2015


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Obstentrics_Williams. Salaia CM, Silberman L, Herrera NE, et al: Placental pathology at term associated with elevated midtrimester maternal serum alpha-fetoprotein concent·ation. Am ] Obstet Gynecol 158(5): 1 064, 1988 Saleemuddin A, Tantbirojn P, Sirois K, et al: Obstetric and perinatal complications in placentas with fetal thrombotic vasculopathy. Pediatr Dev Pathol 13(6):459,s2010 Sato Y, Benirschke K: Umbilical arterial thrombosis with vascular wall necrosis: clinicopathologic indings of 11 cases. Placenta 27: 15, 2006 Schachter M, Tovbin Y, Arieli S, et al: In vitro fertilization is a risk factor for vasa previa. Fertil Steril 78(3):642, 2003


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Obstentrics_Williams. Scioscia M, Fornale M, Bruni F, et al: Four-dimensional and Doppler sonography in the diagnosis and surveillance of a true cord knot. ] Clin Ultrasound 39(3):157,s2011 Sebire N]: Pathophysiological signiicance of abnormal umbilical cord coiling index. Ultrasound Obstet Gynecol 30(6):804, 2007 Sebire N], Backos M, El Gaddal S, et al: Placental pathology, antiphospholipid antibodies, and pregnancy outcome in recurrent miscarriage patients. Obstet Gynecol 10 1 :258, 2003 Sebire N], Backos M, Goldin RD, et al: Placental massive perivillous ibrin deposition associated with antiphospholipid antibody syndrome. B]OG 109:570,s2002 Sepulveda W, Aviles G, Carstens E, et al: Prenatal diagnosis of solid placental masses: the value of color Bow imaging. Ultrasound Obstet GynecoIs16:554, 2000 Sepulveda W, Corral E, Kottmann C, et al: Umbilical artery aneUlysm: prenatal identiication in three fetuses with trisomy 18. Ultrasound Obstet Gynecol 21:213, 2003 Sepulveda W, Wong AE, Gonzalez R, et al:


Obstentrics_Williams

Obstentrics_Williams. W, Corral E, Kottmann C, et al: Umbilical artery aneUlysm: prenatal identiication in three fetuses with trisomy 18. Ultrasound Obstet Gynecol 21:213, 2003 Sepulveda W, Wong AE, Gonzalez R, et al: Fetal death due to umbilical cord hematoma: a rare complication of umbilical cord cyst. ] Matern-Fetal Neonatal Med 18(6):387,s2005 Sheiner E, Abramowicz ]S, Levy A, et al: Nuchal cord is not associated with adverse perinatal outcome. Arch Gynecol Obstet 274:81, 2006 Shen 0, Golomb E, Lavie 0, et al: Placental shelf-a common, typically transient and benign inding on early second-trimester sonography. Ultrasound Obstet Gynecol 29: 192, a Shen 0, Reinus e, Baranov A, et al: Prenatal diagnosis of umbilical artery aneurysm: a potentially lethal anomaly. ] Ultrasound Med 26(2):251, 2007b Shilling e, Walsh e, Downey P, et al: Umbilical artery thrombosis is a rare but clinically important inding: a series of cases with clinical outcomes. Pediatr Dev PathoIs17(2):89, 2014


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Obstentrics_Williams. Society for Maternal-Fetal (SMFM) Publications Committee, Sinkey RG, Odibo AO, et al: Diagnosis and management of vasa previa. Am J Obstet GynecoIs213(5):615,s2015 S0nes T: Umbilical cord encirclements and fetal growth restriction. Obstet Gynecol 86:725, 1995 S0nes T: Umbilical cord knots. Acta Obstet Gynecol Scand 79: , 2000 Spellacy erN, Gravem H, Fisch RO: The umbilical cord complications of true knots, nuchal coils and cords around the body. Report from the collaborative study of cerebral palsy. Am J Obstet Gynecol 94: 1136, 1966 Stanek J: Chorangiosis of chorionic villi: what does it really mean? Arch Pathol Lab Med 140(6):58,s2016 5teemers NY, De Rop C, Van Assche A: Zonary placenta. Int J Gynaecol Obstet 51(3):251,s1995 Strong TH Jr, Jarles DL, Vega JS, et al: The umbilical coiling index. Am J ObstetsGynecols1700 Pt 1):29, 1994 Sullivan EA, Javid N, Duncombe G, et al: Vasa previa diagnosis, clinical practice, and outcomes in Australia. Obstet Gynecol 130(3):591, 2017


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Obstentrics_Williams. Sullivan EA, Javid N, Duncombe G, et al: Vasa previa diagnosis, clinical practice, and outcomes in Australia. Obstet Gynecol 130(3):591, 2017 Sun Y, Arbuckle S, Hocking G, et al: Umbilical cord stricture and intrauterine fetal death. Pediatr Pathol Lab Med 15:723, 1995 Suzuki S: Clinical signiicance of pregnancies with circumvallate placenta. J Obstet Gynaecol Res 340):51, 2008 Swank ML, Garite TJ, Maurel K, et al: Vasa previa: diagnosis and management. Obstetrix Collaborative Research Network. Am J Obstet Gynecol 215(2):223.e1,s2016 Taniguchi H, Aoki S, Sakamaki K, et al: Circumvallate placenta: associated clinical manifestations and complications-a retrospective study. Obstet Gynecol Int 2014:986230,s2014 Towers CV, Juratsch CE, Garite TJ: The fetal heart monitor tracing in pregnancies complicated by a spontaneous umbilical cord haematoma. J Perinatol 29:517, 2009


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Obstentrics_Williams. Towers CV, Juratsch CE, Garite TJ: The fetal heart monitor tracing in pregnancies complicated by a spontaneous umbilical cord haematoma. J Perinatol 29:517, 2009 Tuuli MG, Norman SM, Odibo AO, et al: Perinatal outcomes in women with subchorionic hematoma: a systematic review and meta-analysis. Obstet GynecoIsI17(5):1205,2011 Tuuli MG, Shanks A, Bernhard L, et al: Uterine synechiae and pregnancy complications. Obstet GynecoIs119(4):810, 2012 Vahanian SA, Lavery JA, Ananth CV, et al: Placental implantation abnormalities and risk of preterm delivery: a systematic review and metaanalysis. Am J Obstet Gynecol213(4 Suppl):S78, 2015 Vintzileos AM, Ananth CV, Smulian JC: Using ultrasound in the clinical management of placental implantation abnormalities. Am J Obstet Gynecol 213(4 Suppl):S70, 2015


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Obstentrics_Williams. Vintzileos AM, Ananth CV, Smulian JC: Using ultrasound in the clinical management of placental implantation abnormalities. Am J Obstet Gynecol 213(4 Suppl):S70, 2015 Voskamp BJ, Fleurke-Rozema H, Oude-Rengerink K, et al: Relationship of isolated single umbilical artery to fetal growth, aneuploidy and perinatal mortality: systematic review and meta-analysis. Ultrasound Obstet Gynecol 42(6):622,s2013 Vyas NM, Manjeera L, Rai S, et al: Prenatal diagnosis of umbilical artery aneurysm with good fetal outcome and review of literature. J Clin Diagn Res 10(l):QDOl,s2016 White SP, Koinas A: Prenatal diagnosis and management of umbilical vein varix of the intra-amniotic portion of the umbilical vein. J Ultrasound Med 13(2):992, 1994


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Obstentrics_Williams. White SP, Koinas A: Prenatal diagnosis and management of umbilical vein varix of the intra-amniotic portion of the umbilical vein. J Ultrasound Med 13(2):992, 1994 Whitten E, Romero R, Korzeniewski SJ, et al: Evidence of an imbalance of angiogeniclantiangiogenic factors in massive perivillous ibrin deposition (maternal Aoor infarction): a placental lesion associated with recurrent miscarriage and fetal death. Am J Obstet GynecoIs208(4):310.el, 2013 Woo GW, Rocha FG, Gaspar-Oishi M, et al: Placental mesenchymal dysplasia. Am J Obstet Gynecol 205(6):e3, 201s1 Yamada S, Hamanishi J, Tanada S, et al: Embryogenesis of fused umbilical arteries in human embryos. Am J Obstet Gynecol 193: 1709, 2005 Yamamoto Y, Aoki S, Oba MS, et al: Relationship between short umbilical cord length and adverse pregnancy outcomes. Fetal Pediatr Pathol 35(2):81, 2016 Zalel Y, Weisz B, Gamzu R, et al: Chorioangiomas of the placenta: sonographic and Doppler low characteristics. Ultrasound Med 21 :909, 2002


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Obstentrics_Williams. Zalel Y, Weisz B, Gamzu R, et al: Chorioangiomas of the placenta: sonographic and Doppler low characteristics. Ultrasound Med 21 :909, 2002 Zangen R, Boldes R, Yafe H, et al: Umbilical cord cysts in the second and third trimesters: signiicance and prenatal approach. Ultrasound Obstet Gynecol 36(3):296, 2010 GESTATIONAL AGE ............................. 124 EMBRYONIC DEVELOPMENT . . . . . . . . . . . . . . . . . . . .. 125 FETAL DEVELOPMENT AND PHYSIOLOGY. . . . . . . . . .. 128 ENERGY AND . . . . . . . . . . . . . . . . . . . . . .. 137 PLACENTAL ROLE IN EMBRYOFETAL DEVELOPMENT. .. 139 Our knowledge concening the physioloy of the oetus has been markedy enriched during recent years; nevertheless, when com pared with the adult, it oers many points concening which we are but slighty inormed or prooundy ignorant. -J. Whitridge Williams (1903)


Obstentrics_Williams

Obstentrics_Williams. -J. Whitridge Williams (1903) Since these words were written by Williams in 1903, great strides in the understanding of fetal organogenesis and physiology have been gained. Contemporary obstetrics incorporates physiology and pathophysiology of the fetus, its development, and its environment. An important result is that fetal status has been elevated to that of a patient who, in large measure, can be given the same meticulous care that obstetricians provide for gravidas. In our 2yh edition, the entirety of Section 5 is dedicated to the fetal patient, as are individual chapters in other sections. Indeed, virtually every aspect of obstetrics can afect the developing fetus.


Obstentrics_Williams

Obstentrics_Williams. Several terms define pregnancy duration and thus fetal age (Fig. 7-1). Gestational age or menstrual age is the time elapsed since the first day of the last menstrual period (LMP), a time that actully precedes conception. This starting time, which is usually approximately 2 weeks before ovulation and fertilization and nearly 3 weeks before blastocyst implantation, has traditionally been used because most women know their approximate last period. Embryologists describe embryofetal development in ovuation age, or the time in days or weeks from ovulation. Another term is postconceptional age, which is nearly identical to ovulation age.


Obstentrics_Williams

Obstentrics_Williams. Until recently, clinicians customarily calculated menstrual age with term pregnancy averaging approximately 280 days, or 40 weeks between the first day of the LMP and birth. This corresponds to 9 and 113 calendar months. However, menstrual cycle length variability among women renders many of these calculations inaccurate. This realization, combined with the frequent use of first-trimester sonography, has led to more accurate gestational age determination (Duryea, 2015). Much of this change hinges on the accuracy of early sonographic measurement. As a result, the American College of Obstetricians and Gynecologists, the American Institute of Ultrasound in Medicine, and the Society for Maternal-Fetal Medicine (Reddy, 2014) together recommend the following: 1. First-trimester sonography is the most accurate method to establish or reairm gestational age. 2. In conceptions achieved with assisted-reproductive technology, this gestational age is used.


Obstentrics_Williams

Obstentrics_Williams. First-trimester sonography is the most accurate method to establish or reairm gestational age. 2. In conceptions achieved with assisted-reproductive technology, this gestational age is used. FIGURE 7-1 Terminology used to describe pregnancy duration. 3. If available, the gestational ages calculated from the LMP and from first-trimester sonography are compared, and the estimated date of coninement (EDC) recorded and discussed with the patient. 4. The best obstetrical estimate of gestational age at delivery is recorded on the birth certiicate. he embryofetal crown-rump length in the first trimester is accurate ±5 to 7 days. hus, if sonographic assessment of gestational age difers by more than 5 days prior to 9 weeks' gestation, or by more than 7 days later in the irst trimester, the estimated delivery date is changed.


Obstentrics_Williams

Obstentrics_Williams. An EDC based on LMP can be quickly estimated as follows: add 7 days to the irst day of the LMP and subtract 3 months. For example, if the irst day of the LMP was October 5, the due date is 10-05 minus 3 (months) plus 7 (days) = 7-12, or July 12 of the following year. This calculation has been termed the Naegele rule. The period of gestation can also be divided into three units of approximately 14 weeks each. These three trimesters are important obstetrical milestones. In addition to estimating the EDC with either Naegele rule or pregnancy "wheels," calculator tools in the electronic medical record and smartphone applications can provide a calculated EDC and gestational age. For example, the American College ofObstetricians and Gynecologists (2016) has developed a calculator application that incorporates sonographic criteria and the LMP or embryo transfer date. This is discussed further in Chapter 10 (p. 183).


Obstentrics_Williams

Obstentrics_Williams. The complexity of embryofetal development is almost beyond comprehension. Figure 7-2 shows a developmental sequence of various organ systems. New information regarding organ development continues to accrue. For example, imaging techniques help unravel the contributions of gene regulation and tissue interaction to eventual three-dimensional organ morphology (Anderson, 2016; Mohun, 2011). Others have described the sequence of gene activation that underlies cardiac development. During the irst 2 weeks after ovulation and then fertilization, the zygote-or preembryo-develops to the blastocyst stage. The blastocyst implants 6 or 7 days following fertilization. The 58-cell blastocyst diferentiates into ive embryo-producing cells-the inner cel mass-and the remaining 53 cells form placental trophoblast. Details of implantation and early development of the blastocyst and placenta are described in Chapter 5 (p. 87). Ears Canals, Diaphragm Transverse septum, diaphragm


Obstentrics_Williams

Obstentrics_Williams. Ears Canals, Diaphragm Transverse septum, diaphragm Lungs Tracheoesophageal septum, bronchi, lobes Heart Primitive tube, great vessels, valves. chambers Intestines Foregut, liver, pancreas, midgut gut chlea. inner ears. ossicles --Yolksac . Developing FIGURE 7-3 Early human embryos. Ovulation ages: A. 19 days (presomite). B. 21 days (7 somites). C. 22 days (1o7 somites). (After drawings and models in the Carnegie Institute.) he conceptus is termed an embryo at the beginning of the third week after ovulation and fertilization. Primitive chorionic villi form, and this coincides with the expected day of menses. he embryonic period, during which time organogenesis takes place, lasts 6 weeks. It begins the third week from the LMP through the eighth week. The embryonic disc is well deined, and most pregnancy tests that measure human chorionic


Obstentrics_Williams

Obstentrics_Williams. FIGURE 7-4 Three-to four-week-old embryos. A, B. Dorsal views of embryos during 22 to 23 days of development showing 8 and 12 somites, gonadotropin (hCG) become positive by this time. As shown in Figure 7-3, the body stalk is now diferentiated. There are villous cores in which angioblastic chorionic mesoderm can be distinguished and a true intervillous space that contains maternal blood. During the third week, fetal blood vessels in the chorionic villi appear. In the fourth week, a cardiovascular system has formed (Fig. 7-4). hereby, a true circulation is established respectively. (-E. Lateral views of embryos during 24 to 28 days, showing 16, 27, and 33 somites, respectively. (Redrawn from Moore KL: The Developing Human: Clinically Oriented Embryology, 4th ed. Philadelphia, Saunders, 1988.)


Obstentrics_Williams

Obstentrics_Williams. FIGURE 7-5 Embyro photographs. A. Dorsal view of an embryo at 24 to 26 days and corresponding to Figure 7-4C. B. Lateral view of an embryo at 28 days and corresponding to Figure 7-40. C. Lateral view of embryofetus at 56 days, which marks the end of the embryonic period and the beginning of the fetal period. The liver is within the white, halo circle. (From Werth B, Tsiaras A: From Conception to Birth:


Obstentrics_Williams

Obstentrics_Williams. A Life Unfolds. New York, Doubleday, 2002.) both within the embryo and between the embryo and the chorionic villi. Partitioning of the primitive heart begins. Also in the fourth week, the neural plate forms, and it subsequently folds to form the neural tube. By the end of the ifth menstrual week, the chorionic sac measures approximately 1 cm in diameter. he embryo is 3 mm long and can be measured sonographically. Arm and leg buds have developed, and the amnion is beginning to ensheathe the body stalk, which thereafter becomes the umbilical cord. At the end of the sixth week, the embryo measures approximately 9 mm long, and the neural tube has closed (Fig. 7-5). Cardiac motion is almost always discern able sonographically (Fig. 7-6). The cranial end of the neural tube closes by 38 days from the LMP, and the caudal end closes by 40 days. Thus, the neural tube has closed by the end of the sixth week. And by the end of the eighth week, the crownrump length approximates 22 mm. Fingers and


Obstentrics_Williams

Obstentrics_Williams. the LMP, and the caudal end closes by 40 days. Thus, the neural tube has closed by the end of the sixth week. And by the end of the eighth week, the crownrump length approximates 22 mm. Fingers and toes are present, and the arms bend at the elbows. The upper lip is complete, and the external ears form definitive elevations on either side of the head. hree-dimensional images and videos of human embryos from the MultiDimensional Human Embryo project are found at: http://embryo.soad. umich.edu/index.html.


Obstentrics_Williams

Obstentrics_Williams. FIGURE 7-6 A. This image of a 6-week, 4-day embryo depicts measurement of the crown-rump length, which is 7.4 mm at this gestational age. B. Despite the early gestational age, M-mode imaging readily demonstrates embryonic cardiac activity. The heart rate in this image is 124 beats per minute. Transition from the embryonic period to the fetal period occurs at 7 weeks after fertilization, corresponding to 9 weeks after onset of the last menses. At this time, the fetus approximates 24 mm in length, most organ systems have developed, and the fetus enters a period of growth and maturation. These phases are outlined in Figure 7-2.


Obstentrics_Williams

Obstentrics_Williams. The uterus usually is just palpable above the symphysis pubis. Fetal growth is rapid, and the fetal crown-rump length is 5 to 6 cm (Fig. 7-7). Centers of ossiication have appeared in most fetal bones, and the fingers and toes have become diferentiated. Skin and nails develop, and scattered rudiments of hair appear. he external genitalia are beginning to show deinitive signs of male or female gender. he fetus begins to make spontaneous movements. Fetal growth slows at this time. The crown-rump length is 12 cm, and the fetal weight approximates 150 g (Hadlock, 1991). Practically speaing, the sonographic crown-rump length is not measured beyond 13 weeks, which corresponds to approximately 8.4 cm. Instead, biparietal diameter, head circumference, abdominal circumference, and femur length are measured. Fetal weight in the second and third trimesters is estimated from a combination of these measurements (Chap. 10, p. 184).


Obstentrics_Williams

Obstentrics_Williams. Eye movements begin at 16 to 18 weeks, coinciding with midbrain maturation. By 18 weeks in the female fetus, the uterus is formed and vaginal canalization begins. By 20 weeks in the male, testicles start to descend. FIGURE 7-7 This image of a 12-week, 3-day embryo depicts measurement of the crown-rump length. The fetal profile, cranium, and a hand and foot are also visible in this image. This is the midpoint of pregnancy as estimated from the LMP. The fetus now weighs somewhat more than 300 g, and weight increases substantially in a linear manner. From this point onward, the fetus moves approximately every minute and is active 10 to 30 percent of the day (DiPietro, 2005). Brown fat forms, and the fetal skin becomes less transparent. Downy lanugo covers its entire body, and some scalp hair can be seen. Cochlear function develops between 22 and 25 weeks, and its maturation continues for 6 months after delivery.


Obstentrics_Williams

Obstentrics_Williams. The fetus now weighs almost 700 g (Duryea, 2014). he skin is characteristically wrinkled, and fat deposition begins. The head is still comparatively large, and eyebrows and eyelashes are usually recognizable. By 24 weeks, the secretory type II pneumocytes have initiated surfactant secretion (Chap. 32, p. 607). The canalicular period of lung development, during which the bronchi and bronchioles enlarge and alveolar ducts develop, is nearly completed. Despite this, a fetus born at this time will attempt to breathe, but many will die because the terminal sacs, required for gas exchange, have not yet formed. The overall survival rate at 24 weeks is barely above 50 percent, and only approximately 30 percent survive without severe morbidity (Rysavy, 2015). By 26 weeks, the eyes open. Nociceptors are present over all the body, and the neural pain system is developed (Kadic, 2012). The fetal liver and spleen are important sites for hemopoiesis.


Obstentrics_Williams

Obstentrics_Williams. The crown-rump length approximates 25 cm, and the fetus weighs about 1100 g. The thin skin is red and covered with vernix caseosa. The pupillary membrane has just disappeared from the eyes. Isolated eye blinking peaks at 28 weeks. The bone marrow becomes the major site of hemopoiesis. he otherwise normal neonate born at this age has a 90-percent chance of survival.without physical or neurological impairment. At 32 weeks, the fetus has attained a crown-rump length approximating 28 cm and a weight of about 1800 g. he skin surface is still red and wrinkled. In contrast, by 36 weeks, the fetal crown-rump length averages about 32 cm, and the weight approximates 2800 g (Duryea, 2014). Because of subcutaneous fat deposition, the body has become more rotund, and the previous wrinkled facies is now fuller. Normal fetuses have nearly 100-percent survival rate.


Obstentrics_Williams

Obstentrics_Williams. This is considered term, and the fetus is now fully developed. The average crown-rump length measures about 36 cm, and the average weight approximates 3500 g.


Obstentrics_Williams

Obstentrics_Williams. The cranial end of the neural tube closes by 38 days from the LMP, and the caudal end closes by 40 days. Hence, folic acid supplementation to prevent neural-tube defects must be in place before this point to be eicacious (Chap. 9, p. 169). The walls of the neural tube form the brain and spinal cord. The lumen becomes the ventricular system of the brain and the central canal of the spinal cord. During the sixth week, the cranial end of the neural tube forms three primary vesicles. In the seventh week, five secondary vesicles develop: the telencephalon-future cerebral hemispheres; diencephalon-thalami; mesencephalon-midbrain; metencephalon-pons and cerebellum; and myelencephalonmedulla. Meanwhile, lexures develop and fold the brain into its typical configuration. The end of the embryonic period signiies completion of primary and secondary neuralization. At 3 to 4 months' gestation, neuronal proleration peaks.


Obstentrics_Williams

Obstentrics_Williams. At 3 to 4 months' gestation, neuronal proleration peaks. As expected, disorders in this cerebral development phase profoundly worsen function (Volpe, 2008). Neuronal migration occurs almost simultaneously and peaks at 3 to 5 months. This process is characterized by movement of millions of neuronal cells from their ventricular and subventricular zones to areas of the brain in which they reside for life (Fig. 7-8). U pregulation of gene expression for neuronal migration has been described (Iruretagoyena, 2014). Noninvasive methods to study fetal neurodevelopment have also been reported (Goetzl, 2016).


Obstentrics_Williams

Obstentrics_Williams. As gestation progresses, the fetal brain appearance steadily changes. Thus, it is possible to identiY fetal age from its external appearance (Volpe, 2008). Neuronal proliferation and migration proceed along with gyral growth and maturation (see Fig. 7-8). Sequential maturation studies by Manganaro (2007) and Dubois (2014) and their colleagues have characterized the developing fetal brain image using magnetic resonance (MR) imaging. Other recent investigations that also used MR imaging have quantiied development of subcortical brain structures from 12 to 22 weeks (Meng, 2012). Myelination of the ventral roots of the cerebrospinal nerves and brainstem begins at approximately 6 months, but most


Obstentrics_Williams

Obstentrics_Williams. Myelination of the ventral roots of the cerebrospinal nerves and brainstem begins at approximately 6 months, but most A B c �. .�. ''' FIGURE 7-8 Neuronal proliferation and migration are complete at 20 to 24 weeks. During the second half of gestation, organizational events proceed with gyral formation and proliferation, diferentiation, and migration of cellular elements. Approximate gestational ages are shown. A. 20 weeks. B. 35 weeks. C.40 weeks. myelination progresses after birth. This lack of myelin and incomplete skull ossiication permit fetal brain structure to be seen sonographically throughout gestation.