26 Legal Considerations

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26

Legal Considerations

1001 Numerous litigations against hospitals and obstetricians

take place in which the placental ﬁndings become an important participant in advising the disputing parties on perinatal circumstances. These litigations are initiated most often on behalf of children with cerebral palsy, occasionally with malformations, stillbirth, or with other less than optimal or expected outcomes (Rosenblatt & Hurst, 1989; Richards & Thomasson, 1992). Record keeping of the clinical circumstances and a professional placental study prove to be of great importance in many cases.

Weinstein (1988), who wrote a concise review on the topic, asserted that such litigation is principally the result of the following:

1. Society’s belief that all wrongs must have a reason and that the wrongs must be put right

2. The pervasive lottery mentality

3. The inability of many individuals to accept responsibil- ity for themselves or their actions

4. An increasing incidence of true medical negligence Many physicians who have become involved in this legal process in one way or another have witnessed that Weinstein’s third point is now common reality. Physicians frequently take care of pregnant patients who continue the use of alcohol and tobacco during pregnancy despite many personal or public warnings against it. Other pregnant patients abuse themselves with cocaine, crack, and other agents and thus endanger their fetuses simultane- ously. This aspect of modern society was discussed in an incisive paper on wrongful births by Fleischer (1987).

Unfortunately, these facts are rarely taken into serious consideration when malpractice claims are litigated, or they are casually dismissed as not likely to be contribu- tory. Other physicians argue that the fourth of the above statements is incorrect; they believe that there has been no true increase of medical malpractice—only the law- suits that claim it to be true have increased. Sandmire (1989) provided cogent evidence for this view. No doubt, there has been an increase in the overall incidence of

cerebral palsy as a result of the increasingly smaller babies for whom care is provided (Anonymous, 1989;

Kuban & Leviton, 1994). Moreover, with increased usage of fertility assistance, more multiple births occur prematurely, and older woman have children, factors that are of importance in the determination of palsy. Conversely, older causes of cerebral palsy-like conditions, such as kernicterus, have all but disappeared, and fewer term babies now suffer this fate. But the oversimplified allegations of intrapartum hypoxia and its blanket alleged relationship to neonatal pH or Apgar score and the ultimate infant performance are often incorrectly assessed, and assumption of negligence or guilt on the part of a perina- tologist is frequently not justified. The understanding of how cerebral palsy develops is still imperfect, but it is under intense scrutiny in important studies by Depp (1995) and Marin-Padilla (1997). Some aspects have been reviewed by Nelson and Leviton (1991), and others by Kuban and Leviton (1994), but cases such as the one described by Lopez-Zeno et al. (1990) should always be remembered before hasty conclusions on etiology are drawn. These authors observed the survival of a normal child, delivered by cesarean section 22 minutes after maternal cardiac arrest had occurred, which was 45 minutes after the fatal shooting occurred. Follow-up failed to show neurologic damage; the placenta was not described. This complete anoxia that was incurred by this fetus is much longer and certainly more severe than is the case for many alleged cerebral palsy hypoxia cases. Thus, careful evaluation is indicated. In a thoughtful review, Perkins (1987) examined this very complex field. It should be required reading before unwarranted conclusions are drawn. It is especially noteworthy that Perkins concluded that “the number of infants injured before labor is highly underestimated,” whereas that “of infants injured during labor is highly overestimated.” The placental record can help materially in sorting out these discrepancies.

“The examination of the placenta may be viewed as a diary of the pregnancy,” as Gillan (1992) has aptly stated,

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and the placenta, therefore, has become an increasingly important organ in adjudicating medicolegal allegations (Benirschke, 1990, 1996; Kaplan, 1995). The recognition that placental examination can be of material help in adjudicating perinatal asphyxia litigations has even been recognized by the legal profession. Schindler (1991) concluded that defense verdicts were issued in the 12 cases in which both the placenta and the cord were available for presentation at court. A monograph by Fisher (1996) on risk management techniques in perinatal and neonatal practice asserts the same view. Regrettably, this aspect was not considered in the last review on cerebral palsy by Kuban and Leviton (1994). Even now, the principal reason for submitting a placenta to the scrutiny of the pathologist remains that it comes from a surgical intervention (Booth et al., 1997). This makes little sense in that a large number of such interventions are routine repeat cesarean section deliveries, not the potentially fetus-endangering gestations. Altshuler and Herman (1989) reviewed the specific needs to be addressed by pathologists, and they also considered some of the epidemiologic principles in an incisive review of this medicolegal topic. Of particular interest is their capsular review of relevant pathologic features of the placenta and the possible correlations of lesions with fetal hypoxic states. They were correct in reiterating that the placenta “is an objective diary, related to the outcome of pregnancy.” Later, Altshuler (1993a,b, 1999) wrote three incisive reviews of the principal lesions of the placenta that may be of paramount importance in reflecting a prenatal onset of hypoxic insults. These papers suggested that the presence of nucleated red blood cells at term, chronic villitis, meconium damage, excessive fibrin deposits, chorioamnionitis, chorangiosis, and “placental dysmaturity” are the most important aspects to be considered in this context. These papers also provide a triage for placental study, and the third paper (Altshuler, 1999) is directed to nonpathologists as well. Furthermore, an important meeting of pathologists, perinatologists, and the legal profession resulted in a volume that attempts to address the complexity of the medicolegal aspects of placental pathology (Travers & Schmidt, 1991; Langston et al., 1997). More quantitative data to ensure that pathologic interpretations by different pathologists are meaningful can be found in Beebe et al. (2000).

The pathologist is often consulted to render specific advice on pathologic findings and on other perinatal aspects of pregnancies with poor outcomes. This consultation prominently includes considerations of findings made at placental examinations. All too often, however, the placental material available is insufficient for an expert opinion. Recommendations are made here about how to collect placentas for such possible need of the future. Altshuler and Herman (1989) suggested that one should briefly record findings from placental examination of all deliveries because cerebral palsy may also occur

with entirely normal deliveries. We agree with this view but found it to be an impractical task for most hospitals.

To have placental material available for possible future study, the authors also suggested that formalin-ﬁxed samples be embedded in parafﬁn and archived as uncut specimens. In our view, the value accruing to the child and pediatrician from an examination of the placenta at the time of delivery supersedes the storage of unexamined material.

It is particularly regrettable, as happens occasionally, that erroneous testimony is given in best faith because the consultants have not properly evaluated the entire facts of a given case. They may have reviewed only the slides without knowing the gross ﬁndings of the placenta, for instance, and may have based their opinions solely on those histologic ﬁndings that were available, whereas detailed study of perinatal circumstances might have provided a more educated judgment. Pathologists should not be put into the position of making judgments on monitor strips and the like. They must, however, have a general idea of the entirety of these complex cases before the placental examination can be meaningfully interpreted.

Even more unfortunate still is testimony by “experts”

who have little experience in placental pathology. Like- wise, pathologists must be mindful not to render expert opinions on areas that are outside of their ﬁeld of com- petence, for instance regarding the ﬁndings of heart rate monitoring.

Litigation has had an impact on the practice of perinatal medicine, without having much improved our knowledge of the cause(s) of cerebral palsy. But because the placental study often provides signiﬁcant insight into prenatal life, it has become apparent to many health care providers that, when caring for problematic neonates or when difﬁculties in labor and delivery are encountered, the placenta should be examined professionally.

The notion that it is imperative to examine the placenta, if only to establish the cause of perinatal deaths, is not new. For instance, in efforts to understand the causes of fetal demise, Davies and Arroyo (1985) were able to ascertain the cause of perinatal death by autopsy alone in 47.6% of their cases. For the purpose of ascribing a cause of death, however, placental study was necessary in an additional 34% of their cases. We have reviewed our material of perinatal autopsies over 2 years and found that the true cause of perinatal death could not be established in 15.6% of the cases (Fig. 26.1). Thrombosis of vessels (Kraus, 1997), maternal ﬂoor infarct, villitis, and abruptio placentae are major reasons in singletons why the placenta must be studied. Driscoll (1965) found it also to be true for 16% of her case material; Salaﬁa and Vintz- ileos (1990) were equally emphatic about the need to examine all placentas.

If the cause of perinatal mortality is strongly corrobo- rated by placental ﬁndings, the same is likely to be true

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of possible perinatal fetal or neonatal damage, making the examination of this organ all the more mandatory. So that one may have the placentas of neonates with developing problems available for study, suggestions were made in Chapter 1 how best to store placentas. This triage for the selection and other related aspects of placental study were well detailed in tabular form by Altshuler (1993a,b). Aside from the aspect of placental storage, to facilitate examination of the placenta in cases of possible neonatal difﬁculties, it is our opinion that all placentas of twins, those of premature infants, and of deliveries in which meconium staining or other obvious perinatal problems are apparent should be studied by the pathologist. It is imperative that these ﬁndings then also become an entry in the patient’s record. This practice is not only desirable for adjudicating many legal cases in which placental pathology can be helpful, but it may materially assist the obstetrician when counseling about future pregnancies and in the accumulation of data that may ultimately help our understanding of perinatal problems.

We have often wished in legal consults that a photo- graph of the placenta was available, particularly when confronted with the record of a poorly described or inad- equately studied placenta. This desire has been made light of in litigations, but photography can be easily accomplished on delivery ﬂoors, where pictures of neonates are taken routinely. This has also been advocated for regions where pathologic support is inadequate (Ward, 1991). If photography is impractical, a drawing of salient ﬁndings, for example, to indicate the insertion of the umbilical cord or the presence of twin vascular anastomoses, is often more helpful than a poor description of the gross features. Ideally, all placentas would have an examination by a knowledgeable pathologist, but this is not likely to happen routinely. Those placentas that are studied, however, must be adequately sampled for histology. At least three sections of villous tissue plus at least one of cord and at least one membrane roll are optimal.

When selecting the villous tissue, it is important that

more than the obviously infarcted or pathologic areas are sampled; most infarcts look alike microscopically. An estimate of the percentage of the villous tissue involved with a gross lesion or lesions is most helpful. For an appreciation of the placental status, for example, for the identifica- tion of Tenney-Parker changes in preeclampsia or chorangiosis and villitis, the more normal-appearing villous tissue is usually more informative than are sections of infarcts. In the membrane roll, the decidua cap- sularis must be included, as it is the best site for an analysis of maternal vessel pathology and for the appreciation of inflammatory processes. Formalin fixation of placentas before examination provides much less valuable information than the examination of a fresh organ. The sooner the placenta is studied, the better the results; however, storage in a refrigerator preserves the salient feature for many days. There is little autolysis when the placenta is refrigerated; it only loses some weight during storage by extrusion of villous water, particularly edematous organs.

The pathologist must also become familiar with the arti- facts produced by ﬁxation, especially being cognizant of changes in weight after ﬁxation (the weight increases).

As stated earlier, litigation has involved, most im- portantly, deliveries in which cerebral palsy became a problem in the future development of an infant. This is, in general, much more common in prematurely born infants, in multiple pregnancy, and in infants who come from prolonged pregnancies. The study of the causes of cerebral palsy is a difﬁcult aspect of medicine, as no single etiology can possibly be assigned, despite the efforts expended in the large, prospective Collaborative Perina- tal Study. Rosen and Dickinson (1992) estimated that 2.7 per 1000 children age 5 to 7 years suffered a form of this illness. Nearly 36% occurred in children with birth weights of less than 2500 g, and the authors suggested that 70%

had an antenatal onset. Interestingly, Rosen and Dickin- son (1993) provided evidence that electronic fetal monitoring was unable to predict the development of cerebral palsy, even though this had been the original intent for Figure 26.1. Perinatal autopsy ﬁndings in 122

consecutive cases (University of California, San Diego, 1981 to 1982). Placental examination was necessary in 19 (16%) to provide the cause of death. In many others, especially the premature infants and anomalies, there were abnormal placental ﬁndings such as inﬂammation and single umbilical artery, but these were not the cause of death. HMS, hyaline membrane syndrome.

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this technology. Nelson et al. (1996) also examined in a very large population whether heart rate abnormalities correlated with the development of cerebral palsy. They also found a high degree of unreliability of this procedure and indicated that, were reliance principally based on irregular heart monitor ﬁndings, an excessive and unwarranted cesarean section rate would follow. Other authors have related similar views, although employing different criteria (Yudkin et al., 1994; Depp, 1995; Goodlin, 1995;

Lien et al., 1995). Because they have little relation to placental pathology, they are not discussed here, but the interested reader will want to review these contributions as well. Naeye and Peters (1987) examined the 7-year outcome of children from the aforementioned large Collaborative Perinatal Study of 56,000 pregnancies.

Their overriding conclusion was that chronic, rather than acute, hypoxia has a greater inﬂuence in causing abnormal brain development (see comments by Harkavy, 1987, and those by Durant and Woodward, 1987). This study, as many others, well demonstrated how complex is the topic of the cause of cerebral palsy (see also Naeye et al., 1989;

Naeye, 1992). The two reviews of Altshuler (1993a,b) cited many additional studies that should be consulted by the reader who wishes to obtain a well-rounded appreciation of this complex topic. At the same time, cerebral palsy also has great social and medical importance; the disease often represents a major tragedy to the families involved and to the child. One of the most thoughtful reviews of this complexity was provided by Perkins (1987). Additional studies from Australia were summarized in the Collaborative Perinatal Study involving 608 children reported by Aylward et al. (1989). These authors also found only weak correlations to perinatal variables.

Their instructive tables showed impressively that many time-honored indicators of asphyxia have little or no bearing on cerebral outcome of the neonate. Regrettably, items such as meconium staining and many more conditions of concern were not studied. Grant et al. (1989) also concluded from their randomized study of the beneﬁts possibly coming from intrapartum monitoring that pre- vention of cerebral palsy is difﬁcult. This study and others have been succinctly annotated in editorial comments (Anonymous, 1989; Freeman, 1990).

The ﬁndings made during a competent placental examination, including histologic study frequently identify abnormal prenatal circumstances that had not been recognized clinically. Grafe (1994) made the same point after correlating placental pathology with central nervous system (CNS) necrosis, hemorrhage, and gliosis. In a large study that correlated placental features with perinatal asphyxia, Beebe et al. (1996) sought to identify speciﬁc features that were more important. Villous ischemic changes, meconium damage, and chorioamnionitis stood out as most important. Nevertheless, the authors urged that long-term follow-up is needed to ascertain precisely

what the impact of certain lesions may have been. Thus, results from placental studies have often materially aided in advising the legal profession accurately. For the purpose of this chapter, we will summarize salient points that have come from our experience in this arena. More details on the conditions to be described are to be found in the relevant sections of this book. It must be reemphasized that an interpretation of the placenta alone is often insuffi - cient to arrive at a full appreciation of the complexity of individual cases. It is frequently necessary to know many other factors than only the placental findings in order to render appropriate advice. For instance, one may need to know the identity of microorganisms in infectious cases, etc. The social history may be of considerable importance, and an accurate estimation of the length of gestation, the complications known to have occurred during pregnancy, and so on must all be weighed in the context of the placental findings. These items give valuable information with which one is in a better position to interpret subtle placental findings. Reviewed here are only some of the more common placental problems that we have encountered, and observations we have made in litigation proceedings.

Twinning Problems

Placentas from twins provide the pathologist with the unique opportunity to compare different placental features with neonatal outcome. Thus, the fetus accompanied by a velamentous insertion of the umbilical cord is usually more growth-restricted than one with a normal cord and is thus uniquely exposed also to the prenatal hazards of anomalous cord insertion. Multiple births also have not only a much higher incidence of prematurity but they also suffer a manifold increased frequency of cerebral palsy compared with singletons. Studies have suggested that some of these cerebral lesions may have a prenatal onset because cystic areas of former white matter necrosis can be evident at birth (Bejar et al., 1990).

Larroche (1986) described a case that also demonstrated these prenatal lesions; she found other cases of prenatal encephalopathies with trauma and other prenatal events.

Central nervous system damage of prenatal onset appears to be commoner in monozygotic, monochorionic twins than in dizygotic multiples. It is therefore imperative that the membrane relation of all twins be ﬁrmly established at the time of delivery or during placental study, if one wants to understand the origin of the lesions. This point is particularly important when one twin has died prena- tally. Coagulative, destructive events in the survivor are then especially common and these are usually conﬁned to monochorionic twins. They generally have a prenatal onset, as sonographic studies have clearly shown (Patten et al., 1989), and commence soon after the death of one

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fetus (Liu et al., 1992; Benirschke, 1993). A particularly illustrative case with which we have had personal con- nection demonstrates clearly how such problems may be inaccurately adjudicated. It was superbly summarized in a book by Werth (1998).

As stated earlier, monochorionic twins not only have a higher rate of prematurity but they suffer perinatal mortality more frequently (Baldwin, 1994). The highest mortality attends monoamnionic twins. Monoamnionic/

monochorionic (MoMo) twins entangle their cords frequently and this may cause restrictions to venous return from the placenta. This complication often kills one or both fetuses; in others one can infer venous return problems from existing thrombi. Further, vascular anastomoses between twins may allow rapid shifts of blood from one twin to the other, which may lead to acute anemia and hypotension in utero. Neonatal anemia seen in one of twins, where the other had recently died in utero has been difﬁcult to interpret prior to detailed placental studies. It goes without saying that the umbilical cords of twins must be labeled at delivery, so that it becomes possible to assign speciﬁc placental lesions to individual infants. It is also necessary to identify and record the presence of a fetus papyraceus, as it may have great relevance in affecting the development of the surviving twin through interplacental vascular anastomoses. Perhaps the cause of the death of one twin was sublethal to the other.

Inﬂammatory processes also have an important impact on fetal well-being and they are frequently correlated with cerebral palsy. As was discussed in some detail in the consideration of infections (Chapter 20), in twins, chorioamnionitis much more often affects twin A, that is to say the twin closest to the cervical os. When one has knowledge of the location of twins in utero, this may lead to a better appreciation of possible aspiration pneumonia and other fetal effects.

Twins have a high frequency of velamentous and marginal insertion of their umbilical cords, and these inser- tional abnormalities are often correlated with single umbilical artery. The membranous vessels may have rup- tured during delivery and have caused acute anemia, or they may be thrombosed, which often produces dire fetal sequelae. Cords with a single umbilical artery are more common in twins, and not only when the cords are margin- ally inserted. When twins are delivered by cesarean section, the twin located in the lower uterine segment may actually be delivered as the second twin. Therefore, recording the distance of membrane rupture from the edge of the placenta aids in assigning the correct position of twins in utero when labeling of cords is inadequate. This point has particular relevance with respect to inﬂamma- tion and to the possible rupture of velamentous vessels.

Twins with velamentous insertion of the umbilical cord are usually smaller than those with more normal cord

position. Such discrepancy in size does not automatically affirm the diagnosis of the transfusion syndrome, as is all too readily done; that diagnosis requires the demonstra- tion of the responsible arteriovenous (AV) shunts in the monochorionic twin placenta. The twin-to-twin transfusion syndrome (TTTS) is a most important aspect of monozygotic twinning. It is largely responsible for the frequent occurrence of hydramnios in twin pregnancy that leads to the high frequency of premature delivery of monochorionic twins. Although anemia and plethora of the neonatal twins may be obvious, this finding alone does not accurately attest to the underlying cause, the presence of an AV fistula in the placenta. Plethora can occur in one twin when for instance the first-born twin has been allowed to drain blood into the second, while this one was still in utero. This is sometimes referred to as acute rather than chronic twin-to-twin transfusion. A surviving twin also may partially and acutely exsangui- nate into a stillborn twin while in utero, with resulting acute hypotension. Knowledge of the time when clamping of the cords was done may also be important when interpreting discordant hemoglobin values of twins. When one twin is small for gestational age, possibly because it had a velamentous insertion of the cord, large surface anastomoses may drain blood from the larger twin into the smaller member while still in situ, an apparent paradox to the findings of the transfusion syndrome. But this is not the equivalent of the classical transfusion syndrome.

For all these reasons, it is important that the nature of interfetal placental blood vessel anastomoses be ascer- tained, possibly by injection of the placental vasculature.

The ﬁndings are best recorded by making a drawing of these connections; they cannot otherwise be readily reconstructed.

Inﬂammation

As with the cause of some premature monochorionic twins, chorioamnionitis (membranitis) and funisitis are much overrepresented in children who develop cerebral palsy (Redline et al., 1998). These pathologic changes are now clearly established as being the result of ascending infection. They cannot be explained by hypoxia occurring during labor or be assigned to changes in amnionic pH, as had been previously suggested. Infections not only are much more common in premature deliveries, but also are indeed probably a main reason for most premature births before 30 weeks’ gestation (see Ornoy et al., 1976, for a consideration of its importance in stillbirths). Ascending infection also correlates with prenatal cystic changes in the brain. Studies have suggested that the hypoxia may be the result of vasoconstriction, engendered by the release of prostaglandins, tumor necrosis factor, or other vasoactive agents that come either from the inﬂamma-

Inﬂammation 1005

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tory exudate or from bacterial products suspended in the amnionic cavity. Indeed, the current suspicion exists that some cytokines may be the direct cause of cerebral degenerative changes (Yoon et al., 1996).

Culturing the surface of the placenta is usually not so helpful for studying the cause of chorioamnionitis as is a meticulous histologic study. The causative organisms of chorioamnionitis frequently do not grow readily in the laboratory, or they require special microbiologic attention that is not always available. Moreover, the placenta is frequently contaminated by the birth process, making most routine cultures worthless, or the patient has received antibiotics before delivery. It may be more prac- tical to obtain material for culture from underneath the chorionic plate or to make touch preparations of the placental surface for the identiﬁcation of organisms. Cho- rioamnionitis is also an occasional cause of thrombosis in fetal surface vessels, which can be identiﬁed macroscopically by the appearance of white-yellow streaks on the surfaces of blood vessels. Altshuler and Herman (1989) referred to the mural thrombi as “cushions,” following De Sa’s (1984) lead (see Chapter 12, Fig. 12.24). They must be sampled for histologic study. Their relevance to medicolegal issues has been well described by Kraus (1997).

When thrombi have developed in large fetal surface vessels, the distal fetal villous vascular bed degenerates, leading to defoliation of vascular endothelium, dispersion of blood, and disorganization of the vessels. It produces the appearance of hemorrhagic endovasculitis (HEV), which we consider to be not an inflammatory process but rather a degenerative one. It is commonly found in the main stem placental vessels of stillborn infants, but this endothelial degeneration has then usually occurred after the fetus’s death. Unfortunately, much inappropriate testimony has been given in the past with this confusing entity of HEV, supposedly indicating the existence of an undiagnosed virus infection before birth. Perhaps the most informative finding for an understanding of HEV has come from finding the lesion confined to the placental portion of only the dead MZ twin of a diamnionic/monochorionic (DiMo) twin placenta. The fact that the surviving twin’s placental bed did not have HEV nearly invalidates the possible inference that HEV is a specific pathologic finding of prenatal infection. In his study of placentas from stillborn fetuses, Genest (1992) depicted these changes and placed a time frame on their occurrence (see Chapter 12).

Villous tissue should be sampled for microscopy in all cases of a suspected virus infection because it must be admitted that many virus infections are difficult to identify precisely by histopathologic study alone. For instance, the immunodeficiency virus that is responsible for the acquired immunodeficiency syndrome (AIDS) leaves no characteristic alterations in the placenta. Hepatitis, Coxsackie virus infection, and other virus-caused diseases

cannot be reliably diagnosed histologically from placental material alone. Therefore, these diseases cannot always be ruled out by placental study alone. Cytomegalovirus (CMV) infection is perhaps the most common prenatal virus infection of relevance to cerebral palsy-type lesions.

Significant damage to fetal brain and other organs occurs frequently from CMV infection, and the placenta often shows characteristic alterations. But these changes are frequently widely scattered in the placenta, sometimes affecting only a few villi, and they may be difficult to find.

It is one of the reasons why several blocks of villous tissue should be prepared for histologic study. It is probably best to obtain five blocks so as to optimally sample the suspect material. Of considerable importance is the prenatal infection with herpes virus, as it may be responsible for porencephaly and neonatal death. It is commonly assumed that the infection is only acquired during the delivery process and thus cesarean section is often prac- ticed when genital blisters exist. Less well known is that a number of cases have been described in which the infection was acquired before birth and where neonates had blisters from herpes simplex virus (HSV) infection with positive cultures (see Chapter 20). These infants may progress to destructive encephalopathy, and when they come to autopsy, neither culture nor electron microscopy identifies the now vanished agent. For that reason, Schwartz and Caldwell (1991) proposed that in situ DNA hybridization studies be done on placental tissue for the correct diagnosis. Few absolutely specific placental changes of this virus infection exist, although Robb et al.

(1986a,b) identiﬁed suggestive features.

Premature infants delivered because of chorioamnionitis are often associated with decidual hemorrhage that clinically may give the appearance of an abruptio placentae. This hemorrhage, however, is usually due to bleeding from deciduitis with thrombosis of decidual veins at the placental margins and cannot be compared with the classic abruptio placentae seen with toxemia and trauma.

Villitis of unknown etiology (VUE) is a severe altera- tion of villi that includes infiltration with T lymphocytes and macrophages but only rarely with plasma cells; it usually leads to destruction of villi. It may be indistin- guishable from CMV-induced villitis. Considerable experience may be required to differentiate the two and it may occasionally be impossible without the use of CMV probes. Villitis of unknown etiology definitely reduces the area of placental exchange and is also often associated with fetal death and with growth restriction. The etiology of VUE is unknown at this time, but the dire significance of the entity cannot be in doubt. There are, however, also cases of VUE that have no apparent effect on fetal development. Villitis of unknown etiology has a tendency to recur in future pregnancies. Evaluation of the significance of finding VUE in the placenta of a retarded

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child may be difﬁcult, and it requires much experience with placental study.

The Green Placenta

The presence of meconium at birth was a frequent reason for alleging that birth was delayed or inappropriately handled in the British examination of obstetrical malpractice claims (Capstick & Edwards, 1990). These authors doubted that preventive measures could avoid the alleged accidents and recommended that attention be paid to the immediate handling of incidents. Interestingly, meconium staining of the placental surface is not only a frequent ﬁnding in mature placentas, it is usually not associated with fetal distress or cerebral palsy. In our experience, meconium staining/discharge occurs in about 17% of all births, most often when they occur after 40 weeks’ gestation. Almost all neonates are normal. One should also consider the possibility that, when a meconium-stained placenta has been standing unrefrigerated for very many hours, some of the meconium pigment may actually travel slightly into the amnion and it may perhaps even mini- mally discolor the chorion. Usually, however, this is then also associated with some autolysis of tissues and is thus recognizable by the pathologist as having been artifactu- ally caused. Refrigeration minimizes this problem, an important point, as the legal profession often disputes the age of meconium presence in placental sections. Because of the nature of the hormonal control of the propulsion of intestinal content, meconium staining is more common in postmature organs and it is extremely rare in immature placentas. Some of the legal guidelines pertaining to meconium staining have been examined by Sepkowitz (1987). In his 8-year experience, 4.3% of newborns (1368) were meconium-stained. His further data suggested that, because of legal negotiations, from 1982 to 1985 there was a marked increase in the reported incidence (14.4%) of meconium staining. Therapeutic measures such as laryn- goscopy and oxygen administration to the neonate were increased as a consequence of these interventions, but they did not guarantee an overall improvement of the neonatal outcome. The author concluded, “While the issuance of medical guidelines alone had little effect on the incidence and care of the meconium-stained newborn, the combination of the legal imperative with medical guidelines had a profound and corruptive effect.”

Prolonged pregnancy is signiﬁcantly correlated with meconium discharge, as are the complications from its aspiration and other hazards of prolonged pregnancy (Arias, 1987). The results of Arias’ study suggested that

“the increased incidence of complications in pregnancy prolonged beyond 40 weeks cannot be adequately predicted with antepartum electronic monitoring, and ultrasound evaluation of fetal size, placental grade, and

amniotic fluid volume.” It is also noteworthy that not all meconium-stained placentas are accompanied by fetal meconium aspiration (Altshuler & Herman, 1989). Sunoo and his colleagues (1989) clearly identified that meconium discharge and aspiration may occur before labor and without evidence of fetal distress. They made a detailed study of 75 cases of meconium aspiration (among 14,527 deliveries) and identified four infants in whom the aspiration occurred during early labor and in whom it was accompanied by normal fetal heart tracings. Postmaturity in itself is also often a reason for litigation when it is associated with a cerebral palsied offspring. Whether these are truly related events remains to be established. But the oligohydramnios and meconium discharge that so often occur after 40 weeks’ gestation are often considered to be signs of placental insufficiency, a concept espoused by Vorherr (1975). We have not been impressed that good evidence for placental dysfunction has been identified, and Naeye (1978) agreed with this notion. Thus, a defini- tive deleterious influence of postmaturity on placental growth and function needs yet to be established.

When a placenta from a premature infant has a green surface, one must consider the possibility that this discoloration is not due to meconium but represents hemosiderin and related precursor pigments. Hemosiderin deposits most frequently accompany the peripheral hem- orrhages of circumvallate placentas, but retromembra- nous hematomas, thromboses, marginal hemorrhage, and fetal hemolysis (after demise) can cause hemosiderin deposits on the placental surface because of hemolysis.

An iron stain of the placenta quickly reveals the nature of the pigment when doubt exists. Other discolorations, from brown to green, may be the result of other insults, for instance the infection with fusobacteria. The nature of those pigments is not always understood. Finally, it must be cautioned that the bilirubin pigment of meconium-laden macrophages will bleach when slides lie in sunlight or ﬂuorescent light.

Because meconium is gradually processed in macrophages, moving from the amnionic surface toward the chorion, a rough estimate of the minimum time elapsed between discharge and delivery may be available from microscopic examination of the placental surface; or when the amnion is stripped and the underlying chorion is examined and found to be green at gross examination, an approximate time frame is indicated by the depth of staining. It must be emphasized, however, that this evaluation is subject to a few errors that must be borne in mind when, as is so frequent in giving testimony, one is asked what the probability is for the meconium to have been discharged at such and such a time. And in our estimation these parameters are not really decisive in understanding cerebral palsy anyway; rather, it may be the consequences of meconium discharge that are relevant. Furthermore, meconium may have been discharged days before

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delivery, and most of it may already have been trans- ported away from the fetal surface when the placenta becomes available for study. It is also probable that repeated meconium discharge can occur in utero, which would be most difﬁcult to discern from placental examination alone. Thus, an estimate of time, based on the only in vitro study of meconium transport, may be misleading (Miller et al., 1985). But that is the best estimate we have at present. It is our opinion that the legal profession is overemphasizing the importance of meconium discharge, without appreciating the complexity of this process and the complex etiology of spastic quadriplegia and other features of cerebral palsy. At the same time, when a damaged infant, even a stillborn, is under consideration and its birth had not been accompanied by meconium discharge, the question why this dead baby was not meco- nium-stained is never asked. Interestingly, most stillbirths we see have no meconium staining, even though, ultimately, anoxia was the cause of their death.

Meconium may be otherwise injurious to the fetal well- being, in part because of its effect on the umbilical circulation. It also causes severe degenerative changes in the vascular walls of the placenta and cord, as it does in the amnionic epithelium. Some evidence now exists to show that vasoconstriction is a consequence of meconium exposure rather than its cause (Altshuler & Hyde, 1989).

Thus, although meconium discharge has become the “red flag” in legal cases, in which it is usually suggested that the passage of meconium alone must be evidence of fetal distress, it is more likely that it is the meconium that damages the fetus by acting as a vasoconstrictive agent on the umbilical and superficial placental vessels. In so doing it perhaps reduces the venous return of oxygenated blood from the placenta; of course, there could also be constriction of arteries with reduced blood flow to the placenta (Naeye, 1995). These avenues are now being explored experimentally, but the courtroom treats the association of meconium and cerebral palsy as being causally related as given facts, unjustly in our opinion.

Similar suggestions of umbilical cord vessel constriction by bacterial products in the amnionic sac infection syndrome have come from experimental studies by Hyde et al. (1989), and Mazor et al. (1995) found meconium staining and bacterial infection with poor outcomes to be linked. Finally, we speculate that the real damage of the

“meconium aspiration syndrome” of neonates may be a chemical injury to the alveolar epithelium, similar to its effect on amnion and cord vessels.

Vascular Abnormalities

Abnormalities of the umbilical cord and placental surface vessels are important ﬁndings in placental examinations.

It has long been obvious that it is important to record the

absence of one umbilical artery, as this frequent ﬁnding correlates well with a variety of fetal congenital anomalies and with growth restriction. But it is particularly important also to look for thromboses in the fetal surface vessels of every placenta. Most surface vascular thrombi are evident macroscopically by the yellow-white streak that then accompanies a chorionic vessel, but may not be appreciated by the inexperienced observer. Thrombi are more difﬁcult to spot in the umbilical cord unless the cord is routinely sectioned in areas of discoloration that were not caused by clamping. Thromboses have many causes.

They develop usually over a long period, although we have seen fresh, occlusive thrombi in cases of recent cord entanglement with stillbirth. The thrombi definitely point to significant prenatal fetal problems. We find thrombi most frequently to be associated with excessively long and heavily spiraled umbilical cords, less often in association with maternal lupus anticoagulant, and often with chorioamnionitis. Cytomegalovirus infection also has the propensity to affect endothelium and to produce thrombi.

Thrombosis of surface vessels may be a feature of diabe- tes complicating pregnancy and of toxoplasmosis. In banal chorioamnionitis one often ﬁnds mural thrombi and occasionally organized thrombi, the so-called cushions. We have reported that thrombi may embolize to the fetus and there they may cause infarcts. However, unless such an infant comes to autopsy, embolic sequelae are usually not evident.

Complete vascular obliteration leads to atrophy of the villous district subserved by the vessel. It is the frequent cause of avascular, apparently hyalinized villi, which may thus reduce the quantity of available “exchange membrane”; for this reason, chronic thrombosis correlates with growth restriction and hypoxia. Some fetal thrombi are found in association with lupus anticoagulant, a condition that must be actively investigated, as it may produce few maternal symptoms. There are additionally many placentas with, at times, extensive thrombosis, in which the etiology of the thrombi remains obscure. Some may well be the result of inherited coagulation disorders and then be associated with CNS damage. This was well delineated by Thorarensen et al. (1990) and speculated upon by Kraus (1997). Relevant studies are now feasible but rarely undertaken. An unknown etiology is particularly true for the arterial thrombi. For the purpose of legal adjudica- tion, it is important to recognize this point and to acknowl- edge that thrombosis is a long-standing event and that it can usually not be anticipated before birth. We have seen a child with cerebral palsy in whom one umbilical artery was nearly completely occluded by an inﬂammatory thrombus. The pregnancy was not complicated in any way and, upon arrival at the hospital, a cesarean section was performed for fetal distress immediately. Still, the jury was led to believe that this tragedy could have been averted by better prenatal care, despite having knowl-

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edge of the placental findings. Redline (2005) has recently summarized his findings in the pathology of placental vascular lesions (thrombosis, VUE, inflammation, meconium damage) in 125 legal cases and compared these with random placentas. He found a remarkably good correlation of these lesions with neurologic impairment.

Umbilical Cord

Aside from the cord accidents that occur with monoamnionic twins, the cord displays lesions that often have a signiﬁcant impact on fetal well-being. Green discoloration of the entire Wharton’s jelly can be observed only macroscopically, as the relatively small number of cord macrophages in the umbilical cord does not stain prominently. The cord is also often discolored from hemolysis, especially when thrombi are present or when prenatal bleeding has occurred. At the site where the cord has been clamped, hemorrhage is frequent, but it can be dis- tinguished from spontaneous hemorrhage by the marks of the serrated clamps that are left embedded on the cord’s surface. We have seen in a child with cerebral palsy that a true cord hematoma had histologic features of an angioma, presumably secondary to its “organization.”

The mother had been traumatized during pregnancy. The surface of the cord may have tiny granular protuberances from candidal infection. The compression from knots or prolapsed cords may be seen macroscopically. When it is present, there may be marked distention of blood vessels on one side but not the other, betraying the prenatal compromise of the circulation. The presence of knots in the umbilical cord may be of great significance. It may be the cause of death but it also betrays the possibly long existence of an impediment to venous return. Such has at least once been clearly demonstrated in a Doppler flow study of a 23-week fetus whose cord was also wound about its neck (Gembruch & Baschat, 1996). Edematous cords occur in edematous as well as in immature infants, whereas thin cords often accompany growth-restricted infants. Angiomas are rare, but when present they are of great significance. Usually the cord is spiraled. When the twists are especially numerous, the cord is also usually excessively long. That such excessive spiraling can lead to fetal death is not in doubt. Indeed, the remarkable twist- ing on the fetus’s abdominal surface in some abortuses testifies to this lethal effect of twists. More problematic is the chronic effect that may ensue from excessive cord twists. They are often associated with fetal surface vessel (venous) thrombi, and a reduced venous return (with oxygenated blood) from the placenta can be deduced.

Future Doppler velocimetry and cordocentesis observations will have to clarify the hemodynamic aspects of cord twists. It is important, however, to be mindful of the correlation of fetal problems with excessively long umbilical

cords; thus, an accurate assessment of the complete length of the cord is essential in all placental studies.

Placental Villous Color

Aside from the meconium staining of the fetal surface, the color of the villous tissue is an important notation at placental delivery, especially in problematical cases. The villous tissue is red because of its fetal hemoglobin content.

Placentas of diabetic mothers are darker because of fetal plethora, and those of immature infants are lighter. Once a number of normal placentas have been examined with this fact in mind, the observer should be able to identify those placentas that are unusually light-colored. They may be from infants with hydrops or, more often, they are associated with infants that had a fetomaternal hemorrhage. In that case, immediate Kleihauer-Betke stains on maternal blood are mandatory. This test is important so that one may estimate the amount of fetal blood loss;

it also provides information needed for the therapeutic transfusion that may have to be instituted. Although intervillous thrombi may be noted in these cases, they are not invariably present.

In hydropic infants, the cause of hydrops should be studied as best as possible. The protocol includes mandatory examination of the Rh status plus a search for nucleated red blood cells, for parvovirus inclusions in red blood cell precursors, and for the existence of other fetal infections, such as CMV. There are many other causes of fetal anemia and hydrops. For instance, cardiac arrhythmias often produce hydrops that the pathologist cannot detect at autopsy. These causes are detailed in Chapter 15. Here it is important to stress that the appreciation of an unusually light-colored placenta has relevance for legal pur- poses as well. Occasional hydropic infants are the result of high-output cardiac failure of the fetus that results from large placental chorioangiomas. They are readily apparent when the placenta is palpated and then sectioned. Neonatal anemia is obvious when a low hemoglobin value is found at neonatal examination. The adjustment of the fetal hematocrit may take some time after fetal blood loss but we have only the most superﬁcial knowledge of how quickly the hematocrits adjust after fetal bleeding—information that would be useful in adjudicating the timing of fetal hemorrhage.

In patients with hepatitis and jaundice, the villous tissue may be a deep golden color, which is often difﬁcult to visualize microscopically and is thus an important mac- roscopic descriptor. This discoloration also tends to bleach in the histologic slides from ofﬁce lighting alone.

The maternal surface may be yellow and ﬁrmer than normal in a condition known as maternal ﬂoor infarction.

This condition is strongly correlated with diffuse ﬁbrinoid deposition throughout the placenta and with fetal growth

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restriction. Some observers have suggested that an increased fibrinoid deposition confirms the diagnosis of prolonged placental perfusion problems, but the maternal floor infarction syndrome has an unknown etiology, although it is a frequent cause of stillbirth. Appropriate histologic study verifies the existence of this condition.

Such excessive ﬁbrinoid deposits are frequently a repeti- tive event in subsequent pregnancies. It has also been associated with adverse perinatal outcome (Adams- Chapman et al., 2002). Contrary to opinions expressed in the literature, this condition is not caused by fetal death.

Color changes on the maternal surface and behind the membranes may disclose an unrecognized abruptio placentae. Most cases of placental separation are clinically silent and can be observed only when the maternal surface is carefully scrutinized. A fresh retroplacental hematoma with indentation of the villous tissue is obvious, however, if the hematoma is formed within an hour or so of delivery; the placenta may then appear unaffected. The clot may have dried (in contrast to the “currant jelly” clot of normal retroplacental blood), and it may be stringy and compacted. When placental separation is focal and has occurred long before delivery, the clot may have largely disappeared, or it is replaced by a brown, ﬁlmy material.

Still older clots leave a greenish (hemosiderin) residue.

Infarcts at the edge of the placenta are common and, when small, they are of little significance. Their age can be approximated from their initially red, then yellow, and eventually white color. Infarcts that are scattered throughout the placenta, however, signify maternal disease of some sort. This finding assumes particular importance in prematurely delivered infants in whom infarcts are generally rare. Most commonly, the cause of such infarcts is preeclampsia, but the lesions due to lupus anticoagulant have a similar appearance; and when infarcts are found in the absence of signs of pregnancy toxemia, their cause requires further study. Moreover, for the understanding of the fetal impact of infarcts, it is probably beneficial that a percentage estimate of the amount of infarcted villous tissue be recorded. Altshuler suggested that most infarcts are not associated with fetal CNS changes (Altshuler &

Herman, 1989).

Chorangiosis, on the other hand, is correlated with prolonged fetal oxygen deprivation. Just how the placenta is able to adapt to changing oxygen supply was considered in detail by Kaufmann and his colleagues (1993) and in earlier chapters of this book. Vascular proliferation, medi- ated through a complex system, is one important feature.

Chorangiosis, one such outcome, is a highly abnormal condition that must be recognized as being associated with many perinatal problems. Although minor forms of chorangiosis are reasonably common, its value for our understanding of the fetal/placental/maternal relations has so far been underestimated. Altshuler (1984, 1993a,b) found chorangiosis in about 5% of neonates admitted to

his intensive care unit—much more commonly than occurs in cases with “routine” placentas. Chorangiosis is never found in normal cases, and Altshuler made the point that chorangiosis is significantly different from con- gestion, and that it probably relates to chronic low-grade hypoxia. That suggestion is supported by the finding of chorangiosis in women gestating at very high altitude (Reshetnikova et al., 1996). Chorangiosis if also often seen with VUE, and we find it peripheral to atrophying villi when old vascular thrombi have occluded the fetal vascular bed. Other correlations exist to fetal death, dia- betes, umbilical cord problems, etc. The recognition of chorangiosis is an important feature of placental study.

Whether “grading” the degree of chorangiosis as pro- moted by Altshuler (1984) is truly helpful remains to be confirmed by new studies. From a legal perspective it must be emphasized that the development of chorangiosis takes time to develop. Scheffen et al. (1990) provided beautiful evidence of the capillary adaptation in the guinea pig placenta following long-standing hypoxia and indicated temporal aspects. Although this system may differ from the histology of human adaptation processes, the underlying mechanism is the same and confirms the clinical findings. Other adaptations to low oxygen satura- tion were discussed in the context of preeclampsia in Chapter 19. They included cytotrophoblast proliferation with syncytial excess, reduction of villous length, and the possible mediation of these processes through cytokines.

Other Types of Pathology

The fetal circulation of the placenta normally contains very few nucleated red blood cells (NRBCs). When they are found in sections of the placenta, the pathologist must seek an explanation for their presence. It may be obvious from hematologic study that there is evidence of hemo- lytic disease, or that transplacental bleeding or chronic infection existed, but often the cause of an excessive number of NRBCs in the fetal vessels is not immediately evident. Fox (1967) suggested that NRBCs are often found in the fetal circulation because of acute hypoxia.

Presumably, the human fetus reacts to oxygen deﬁciency, as it does to anemia, by secreting NRBCs from the hepatic or bone marrow stores. How acutely this reaction occurs and whether it reﬂects a quantitative response to certain levels of oxygen deprivation is unknown. But this relationship to fetal hypoxia has now been shown to have led to elevated NRBC counts in numerous studies of which only a few recent investigations will be cited here. Thus, Baschat et al. (1999, 2003, 2004) found that elevated NRBCs at birth, and especially the persistence of these cells into neonatal life, correlate well with major neonatal complication. Phelan et al. (1995) looked upon the presence of NRBCs in term neonates as evidence of prenatal

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asphyxia. These investigators, as well as Minior et al.

(2000a,b) also found it to accompany fetal growth restriction as the result of “placental insufﬁciency” (Baschat &

Hecher, 2004). The finding of NRBCs in the fetal vessels merely signals to the pathologist that a careful review of the record is needed to explain this important observa- tion that may otherwise be overlooked. As stated, how quickly such a response occurs is unknown, for which reason Shields et al. (1993) attempted to elucidate the blood replacement by experimental hemorrhage in ovine fetuses. Despite an initial increase in fetal erythropoietin (EPO) levels, a significant hemorrhage (40%) was not followed by a significant rise in the fetal reticulocyte count, nor were the former blood volume and hematocrit restored before birth. Thus, the ovine model may not be appropriate to settle this important question. Older studies have suggested that sheep fetuses marshal some response; the current understanding of all of these aspects is discussed in admirable detail in Altshuler’s review (1993a). It cites the study by Ruth et al. (1988), which determined the EPO levels at birth in preeclamptic pregnancies and those of severe asphyxia. The EPO levels were elevated in most pregnancy-induced hypertension (PIH)-derived neonates, irrespective of CNS damage; the significant finding was the marked elevation of EPO levels in those infants who ultimately had CNS damage but not in others. Ferber et al. (2004) later clearly showed that the EPO levels correlate well with the neonatal NRBC counts. We can personally relate two experiences from our files that help in understanding the time course in human fetuses to some extent: One patient was at term and had a major gush of bright red blood (later identified as fetal blood from disrupted velamentous vessels) upon insertion of an intrauterine pressure catheter. She was delivered by cesarean section 48 minutes later; the infant was pale, the placenta otherwise entirely normal. The cord arterial pH was 7.05, hemoglobin 14.6 g, hematocrit 44.8%, white blood count (WBC) 28,000, and platelets 120,000 and falling to 71,000. Three transfusions of packed red blood cells were given and the hemoglobin level was then only 10.3 g, and hematocrit 29.9%. The first enu- meration of NRBCs occurred 1½ hours after delivery and showed 19 NRBC/100 WBC; 6 hours later it was 32 NRBC/100 WBC. Thus, there was a continued hematologic response after the delivery of the anemic child, and some degree of an initial NRBC response was detectable within an hour. This is contrary to the rapid decline of NRBCs postnatally when the hypoxic event has been more remote; under those circumstances most NRBCs are gone on the second day. Another case that is relevant came as a consultation: the mother had a car accident with lap belt injury at 28 weeks’ pregnancy. Approxi- mately 12 hours later the fetus was born with a hematocrit of 25%. Kleihauer stains gave an estimated 40 to 50 mL fetal blood in the maternal circulation; 45

NRBCs/100 WBC were found and there was villous edema. It is entirely possible that the acute blood loss as shown in these two cases initiated a stronger response than would gradual hypoxia. This is consistent with Altshuler’s (1993b) comment that “acute fetal blood loss and congenital septic hemolysis reduce the time it takes fetal hypoxia to cause fetal erythropoiesis and increased nucleated red blood cells.” In another child, the 102 cm long umbilical cord had prolapsed and was hemorrhagic for half of its length. The neonate had 53 NRBCs/100 WBC, but the placenta showed chorangiosis and mural thrombi in large vessels. The latter observations indicate very long-standing fetal hypoxia, a more frequent ﬁnding in this complex situation that prevents adequate assessment of the temporal response of the fetal system. We do not know the complete answers to these questions at present, and encourage colleagues to collect case material in order to gain a better understanding of the time course of the NRBC response. It should also be cautioned that fetal growth restriction is known to be associated with an increased number of NRBCs in their circulation (Nicolini et al., 1990). These authors deduced from the blood studies by cordocentesis that the only reasonable explanation for intrauterine growth restriction with the presence of NRBCs is long-standing hypoxia. Korst et al.

(1996) studied NRBCs in asphyxiated and normal neonates. They found that normal infants have 3.4 (±3.0) NRBCs/100 WBC, but that asphyxiated and neurologi- cally damaged newborns had signiﬁcantly elevated counts (30.3 ± 77.5/100 WBC). The most elevated NRBC counts were explicable only by assuming hypoxia to have occurred long before birth. More discussion of the control of NRBCs in the fetal circulation is to be found at the end of Chapter 8. It should also be related here that Korst et al. (1999) found that neonates with encephalopathy had statistically reduced platelet counts, yet another means of evaluating neonates with CNS problems.

During legal proceedings the pathologist is frequently asked to specify a time frame for the lesion under discussion (e.g., Naeye & Localio, 1995, who enumerated NRBCs and lymphocytes). He or she may be required to specify how quickly villi can become atrophic following thrombosis, or what is the exact temporal evolution of thrombi. How long has a significant phlebitis been present, and is it correlated with the length of time from rupture of membranes? These and other probing questions are often difficult to adjudicate, and the answers (with respect to best medical judgment) may present problems for a conscientious witness. It requires experience, and it may be better to state the lack of our knowledge than to express unwarranted opinions that are contradicted in the courtroom or by other experts. This uncertainty is also an indication for the pathologist to seek new information from appropriate cases in which clinical data corroborate a particular finding. It is the reason why the meticulous

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study of twin placentas can be so useful as it often provides a “control,” a fetus who has shared the same intrauterine environment as the case under litigation but who may be normal.

Another relevant feature found in the study of abnormal infants is villous dysmaturity, the discrepancy of villous maturation with the chronologic age. This is not to say that this placenta is merely an immature one, rather that the placenta shows abnormalities, often irregularly distrib- uted, such as an increase in ﬁbrin, villous size, and stromal cells; decreased syncytial knots; and frequently an increased vascularity. Irregularly matured villi are frequent in the placentas of a variety of chromosomal abnormalities, for instance. Similar villous changes are found in other placental disturbances, as shown in Figure 26.2, and they may be difﬁcult to explain. In this case, they probably resulted

from partial venous thrombosis of surface vessels (Fig.

26.3) in a child whose outcome was cerebral palsy, and which involved litigation. The ultimate cause of these lesions was not apparent, but it is clear that they were long- standing prenatal deviations from normal. Similar thromboses and degenerative changes may have taken place in the organs of the surviving fetus. We will never know.

Tenney-Parker changes of villi (increased syncytial knot- ting) signify deficient uteroplacental blood flow of some duration, and focal villous edema may all be associated with premature delivery and neonatal hypoxia. These notations are all microscopic findings, however, that cannot be anticipated macroscopically. Their frequent presence with abnormal fetal outcomes signifies the importance of placental examination by a competent pathologist and knowledge of the spectrum of what is “normal.”

Figure 26.2. Mural thrombus in a placental surface vein (“cushion”) of a child with unex- plained cerebral palsy. Note that the vein wall is partially degenerated. The lesion was not recognized, macroscopically or microscopically, by the pathologist who signed off on the case. H&E ¥ 160.

Figure 26.3. Irregular villous maturation and adjacent chorangiosis of the placenta in a cerebral palsy case (see Fig. 26.3). The vascularity of the central group of villi is apparent. It is presumed that this focal villous vascular loss is due to the same abnormality that was responsible for the mural thrombus. H&E ¥ 60.

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References 1013

It may be pertinent to review the presence of villous edema in this context. Edema of villi has been associated with poor fetal outcome and has also played a role in the litigation process. Naeye et al. (1983) suggested that villous edema was frequent and severe in the immature placentas (more than 32 weeks) of pregnancy complications. It was believed to correlate with fetal hypoxia, and the authors postulated that the hypoxia was the result of compression of fetal villous capillaries by edema. We find villous edema exceedingly difficult to quantitate, especially when the placenta has been stored and has lost some of its fluid. Moreover, many mildly hydropic fetuses with marked villous edema have not had a hypoxic deficit from compression of villous vessels, making us uneasy to use this criterion in our evaluation of abnormal placentas.

No additional studies of this topic were published until the report by Shen-Schwarz et al. (1989). These investigators found villous edema in 13% of singleton placentas during the second half of pregnancy. In 11% of term placentas, edema was associated with fetal and neonatal deaths. They also detected edema more often in prematurely delivered placentas but were unable to relate villous edema to chorioamnionitis. Altshuler (1993a,b) was also uncertain that villous edema was a cause of fetal hypoxia, as resulting from compressing the villous capillaries. Further studies are needed to clarify the importance of villous edema as a correlate of fetal well-being and to delineate its precise pathogenesis.

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