Chapter 10
Multiple Gestation: Twin Variants and Related Conditions
Vanishing Twin and Fetus Papyraceous . . . . 153
Acardiac Twins . . . . 156
Conjoined Twins . . . . 159
Twin Variants . . . . 160
Triplets and Higher Multiple Births . . . . 161
Twin-to-Twin Transfusion . . . . 163
Chronic Twin-to-Twin Transfusion Syndrome . . . . 163
Acute Twin-to-Twin Transfusion . . . . 166
Chimerism and Mosaicism . . . . 167
Heterokaryotypic Monozygotic Twins . . . . 168
Sacrococcygeal Teratoma and Epignathus . . . . 168
Selected References . . . . 169
Vanishing Twin and Fetus Papyraceous
Clinical Features and Implications
The phenomenon of a “vanishing twin” occurs when a multiple preg- nancy is identified sonographically during the first 15 weeks of pregnancy, but the outcome is a single fetus. When the diagnosis of twins is made before 10 weeks, the rate of disappearance is 71%. When the diagnosis is made between 10 and 15 weeks, the disappearance rate is 62%. Twins first diagnosed after 15 weeks more often develop a fetus papyraceous when one twin dies. A clue to the presence of a vanished twin or fetus papyraceous may be an elevation in maternal a-fetoprotein (AFP) or acetylcholinesterase, which occasionally may pose clinical problems.
Pathogenesis
If one twin dies in gestation and the pregnancy continues undisturbed, the fetus may become a fetus compressus or fetus papyraceous. If the fetus is large, it may macerate, lose much of its fluid, and become flat- tened, misshapened, and paper-like, hence the name. This is most common when death occurs during the second trimester. The fetus papyraceous has become quite common due to the practice of “fetal reduction” used after fertilization via assisted reproductive technology.
Pathologic Features
A fetus papyraceous may be so small and compressed that it is diffi- cult to identify on gross inspection. It may appear as a flattened disk of macerated tissue in the membranes of the remaining twin (Figure 10.1).
Occasionally, a pigmented macule representing the eye is the only clue to the diagnosis (Figure 10.2) and radiographs or histologic sections may be necessary to document their nature (Figure 10.3). The associ- ated placenta, which is usually completely infarcted, may also be dif- ficult to identify, as it often persists as only a crescent of atrophied tissue at the periphery of its twin. When maceration is advanced, the fetus may become a lithopedion. This feature is more common when a fetus is retained for months beyond the expected gestation and need not be a twin.
Figure 10.1. Fetus papyraceous (on the left) in the membranes of a twin placenta. Its dichorionic placenta was a flattened mass of atrophied tissue.
Suggestions for Examination and Report: Fetus Papyraceous Gross Examination:Careful examination of membranes is some- times necessary to identify a fetus papyraceous. Dissection of the dividing membranes between the fetus papyraceous and the other placenta(s) should also be undertaken. Histologic sections of the fetus papyraceous and the associated placenta should be submitted to document their presence.
Comment:The final report should contain a comment about the placentation and zygosity (if possible) along with the diagnosis of a fetus papyraceous.
Figure 10.2. Term placenta with a separate embryo in the membranes (arrow), a fetus papyraceous. The ocular pigment is readily seen.
No placental remains could be identified.
Figure 10.3. Membrane roll of fetus papyraceous with macerated embryonic structures. H&E. ¥16.
Figure 10.4. Usual pattern of vascular anastomoses in acardiac twins. A = artery; V = vein.
Acardiac Twins
An acardiac fetus is one of monozygotic (MZ) twins or higher multiples that has absence of the heart or a severely malformed heart. Acardiac twins are the most severely malformed fetuses that one can imagine. They range from a small, teratoma-like mass to large fetuses with a great variety of anomalies. The incidence of acardiac pregnancies is difficult to ascertain, as most are not reported, but an estimation is 1 in 35,000 to 48,000 births. Acardiacs are more common in higher multiple births than in twins. Well over 600 cases have been reported.
Pathogenesis
The acardiac develops due to the presence of two dominant anastomoses in the monochorial placenta. An artery-to-artery anastomosis brings blood from a usually normal co-twin to the monster, and a vein-to-vein anastomo- sis returns the blood (Figure 10.4). The normal twin provides the cardiac flow to the monster but in a reversed fashion. The reversal of blood flow has been proved to exist with the use of Doppler sonography. The presence of the placental anastomoses is the fundamental cause of the acardiac dysmorphism, and therefore dichorionic (and dizygotic, DZ) human twins cannot develop into acardiacs as they lack these com- munications. The fact that vascular reversal nourishes the acardiac is without question and this vascular reversal can lead to suppression of cardiac development. In fact, much of the failure of organ system development is from the deficient circulation, because blood arrives deoxygenated
and at a reduced pressure. The fact that the lower limbs of acardiacs are usually better formed than the arms has been considered to result from preferential perfusion of the legs, as they are closest to incoming reversed arterial flow. The term TRAP (twin reversed arterial perfu- sion)has been applied to this syndrome. We believe that many of the previously described placental teratomas are really acardiac fetuses that lacked the development of a defined or recognizable umbilical cord. The presence of a cord is usually considered a prerequisite for the diagnosis of “acardiac fetus” but the presence of axial skeleton as a criterion is preferred.
Pathologic Features
There is a wide spectrum of appearance of acardiacs, ranging from a total absence of most organs to the presence of well-formed organs includ- ing gonads (Figures 10.5, 10.6). They may appear similar to an inside- out teratoma with little resemblance to a fetus. They may have a relatively well-formed lower trunk and legs with a misshapen upper body or they may even have remnants of a face and arms. The only organ that has not been described in acardiacs is the liver. For the study and diagnosis of acardiacs, it is usually best to obtain a radiograph of the specimen before dissection, as it gives some idea of the complexity of the abnormality, enables better classification, and delineates if a skull
Acardiac Twins 157
Figure 10.5. Acardiac twin with typical plethoric appearance.
is present. Most acardiacs have a monoamnionic-monochorionic (MoMo) placenta, although some with diamnionic-monochorionic (DiMo) placentas have also been described. Most, but not all, acardiac fetuses have a single umbilical artery.
Clinical Features and Implications
Acardiacs occasionally have great mobility, and may die of cord entan- glement (Figure 10.6). In cases of a DiMo placenta, amnion nodosum is usually present in the acardiac because of its deficient or absent urine pro- duction. Acardiacs often develop hydrops, and the pregnancy is thus frequently complicated by polyhydramnios. This problem may result from hypoproteinemia or heart failure of the donor twin. Plethora is also frequently observed in acardiacs and probably represents stagna- tion of blood, transfused by the pale, normal co-twin (Figure 10.5). This is often reflected in the placenta as well.
Figure 10.6. Macerated MoMo twins, one an acardiac (150 and 20 g). The twins died because of entangling of cords. The acardiac had a remnant of heart with calcification in the remaining muscle fibers. H&E. ¥160. (Courtesy Dr. S. Kassel, Fresno, California.)
Conjoined Twins
Pathogenesis
Incompletely separated or conjoined twins (Siamese, x-pagi, double monsters) take their origin after day 13 of embryogenesis. The precise manner of the formation of conjoined twins is uncertain, with theories of incomplete splitting and partial fusion of embryonic precursors being the most popular. Conjoined twins occur in approximately 1 of 50,000 births, or in 1 of 600 twins. They are much more common in the Japanese population, in Nigeria, and in South Africa. For unknown reasons, 70% of conjoined twins are female. Most fused twins are joined at the chest, thoracopagus, and thoracoomphalopagus, representing 28% of the total, but they may be joined in an infinite number of con- figurations (Figure 10.7). Conjoined siblings in higher gestations have also been reported.
Pathologic Features
The placenta of conjoined twins is MoMo; however, separate placental disks have been reported. The structure of the umbilical cords varies widely.
Approximately 6% have two cords. When the cord is fused, it has a variable number of umbilical vessels (Figure 10.8). As few as three and up to eight vessels have been reported; the latter case had six arteries and two veins. Single umbilical artery (SUA) is also found quite commonly in conjoined twins. Some cords are separate in their insertion onto the placental surface but fuse along their length. There is no association of cord vasculature and structure with the type of conjoined twin.
Conjoined Twins 159
Suggestions for Examination and Report: Acardiac Twins Gross Examination:Detailed documentation of the fetal anom- alies of the acardiac should be performed as well as identification of the type placentation and the type of anastomoses (see Chapter 9).
Comment: The vascular anastomoses and fetal anomalies are usually typical of acardiac twinning.
Suggestions for Examination and Report: Conjoined Twins Gross Examination: Documentation of anastomoses and cord abnormalities should be undertaken as with any monochorionic twin placenta. Evaluation of the anomalies and shared structures is usually done by pediatricians concerned with future viability and possible surgical separation.
Comment:No additional comments are usually necessary.
Twin Variants
DZ and MZ twinning are the most common types of twinning, but other unusual variants have been described. In what has been called the third type of twin, the ovum and polar body are fertilized separately by two different sperm. Thus, the twins have the same maternal genetic con- tribution but two different paternal contributions. Therefore, the twins are intermediate in their genetic configuration between MZ and DZ twins. This type of twinning occurs in less than 1% of twins and likely develops in situations when the polar body is of similar size to the oocyte. It has been recognized by the finding of one corpus luteum in cases of presumed DZ twins. The placentation is diamnionic-dichorionic (DiDi) and the placentas will usually be fused. Another unusual variant of twinning occurs in superfecundation where two ova are fertilized by sperm from two different fathers. Superfetation, on the other hand, is when fertilization occurs at different times, resulting in twins of different gestational ages.
Figure 10.7. Conjoined twins with fusion of anterior portion of the head, chest and upper abdomen.
Triplets and Higher Multiple Births
Multiple births are becoming more common and presently nonatuplets hold the record. Triplets and higher plural births are not only smaller than expected for their gestational age; they also commonly deliver much earlier than twins or singletons. Triplets may be any combination of MZ and DZ twins and chorionicity, that is, TriTri (triamnionic-trichorionic), TriDi (triamnionic-dichorionic), TriMo (triamnionic-monochorionic), DiMo, and MoMo. Terminology for the chorionicity of triplets and higher multiples (Figure 10.9) is usually based first on the total number of chorions and amnions. For example, quadramnionic-trichorionic describes quadruplets with four chorions and three amnions. The diagnosis would then read Quadramnionic-trichorionic quadruplet placenta, diamnionic-monochorionic for quadruplets B and C, for example.
Otherwise, examination and reporting are similar to that for twins.
Uneven numbers of monozygotic multiples (such as triplets or quin- tuplets) may be explained by assuming that, on occasion, one embryo
Triplets and Higher Multiple Births 161
Figure 10.8. Conjoined twins (ischiopagi) with a MoMo placenta, a single velamentous umbilical cord, and single umbilical artery (SUA). They were delivered at 40 weeks gestation. One had a cleft face and microcardia. There were two female genital tracts. (Courtesy Dr. S. Sekiya, Tokyo.)
may not have survived. Alternatively, there may be one division ini- tially and then a secondary division occurs, or three or more embry- onic centers might arise simultaneously instead of two. Because plural gestations generally have poor outcomes, their early diagnosis and
“selective reduction” of some is relatively common.
Figure 10.9. Quadruplet placenta (QuaTri), with DiMo MZ twins at bottom left, one having marginal insertion of the umbilical cord (35 weeks, 920 g).
Suggestions for Examination and Report: Triplets and Higher-Order Multiples
Gross Examination:Examination should be along the same lines as that for twins, that is, documentation of the vascular anasto- moses, separation of fused disks along the vascular equator, and separate examination of each placenta. In complex arrangements, a drawing of the relationships may be helpful.
Comment:As noted above, the number of amnions and chorions should be included in the diagnosis. The specifics of individual relationships may be added as in the following example,
“Triamnionic-dichorionic triplet placenta (diamnionic- monochorionic for triplets A and B).”
Twin-to-Twin Transfusion
Chronic Twin-to-Twin Transfusion Syndrome Pathogenesis
The twin-to-twin transfusion syndrome (TTTS) is a specific entity caused by the unidirectional, prenatal transfusion of blood through arteri- ovenous (A-V) anastomoses in the monochorionic twin placenta (Figure 10.10). Thus, one twin is a donor, and the other is the recipient. Usually, there is a discrepancy in size and development of the twins, particularly with respect to amniotic fluid and fetal fluid status. The syndrome is variable in its consequences because the A-V anastomoses may be single or multiple, of varying size, and may or may not be associated with artery-artery (A-A) and/or vein-vein (V-V) anastomoses. When a simultaneous large anastomosis coexists, the most severe aspect of the syndrome is prevented due to equalization of blood flow between the twins. The twins reach greater gestational maturity or may not even develop TTTS. Prenatal diagnosis is usually made when one mono- chorionic twin shows oligohydramnios and the other shows polyhy- dramnios. The twins may also show a significant weight discrepancy.
This has led to use of the term TOPS for “twin oligohydramnios poly- hydramnios sequence,” a practice with which we strongly disagree.
Twin-to-Twin Transfusion 163
Figure 10.10. Vascular anastomoses in chronic twin-to-twin transfusion syndrome (top). The predom- inant anastomosis is an artery-to-vein anastomosis from the donor (A, left) to the recipient (B, right).
Cross section of a monozygotic placenta after injection of shared cotyledon has been injected with water (bottom). Note that the placenta of the donor (A, left) is paler than the placenta on the right.
Use of this term ignores the etiology, which lies in the placental anastomoses.
Pathologic Features
The prenatal unidirectional exchange of blood results in deprivation of nutrients from the donor twin and excessive development of the recip- ient. The twins may be remarkably discordant (Figure 10.11), and there is a high degree of brain-sparing growth restriction in the smaller twin.
Typically, one twin is dehydrated and anemic, possessing organs much smaller than expected. The recipient is often plethoric and has enlarged organs. The discrepancy is particularly striking in the hearts, and this is one of the most important means for the diagnosis of the transfusion syndrome.
After birth or demise of one twin, rapid blood shifts may occur between the twins, which negate the usefulness of hematologic values. The remarkable pallor of the donor twin’s placental portion and congestion of the recipient’s placenta may be quite striking (Figure 10.12). The histologic structure of the villi can differ substantially as well
Figure 10.11. Macerated DiMo twins with chronic transfusion syndrome at 28 weeks gestation. The donor (left) is plethoric; the recipient (right) is edematous and pale. Recipient (twin A) 285 g; 15 cm CR length; heart 3 g; lungs 10 g; liver 17.5 g; kidneys 1.5 g. Donor (twin B) 189 g; 13 cm CR length; heart 0.7 g; lungs 3 g; liver 4 g; kidneys 1 g. The plethora of twin B is thought to be due to this twin’s earlier death, with exsanguination of A into B (acute twin–twin transfusion).
Twin-to-Twin Transfusion 165
Figure 10.12. DiMo placenta at 26 weeks with chronic TTTS (twin-to-twin transfusion syndrome). Both fetuses died in utero. The recipient’s placenta (right) is markedly congested, while the donor’s (left) is markedly pale.
(Figure 10.13), with enlarged, edematous villi in the donor and con- gested villi in the recipient. Both usually contain markedly increased nucleated red blood cells.
Clinical Features and Implications
The frequency of the transfusion syndrome is difficult to determine but it is estimated to occur in 5% to 30% of monochorionic twins. Observa- tions suggest that it may be more common. There is a wide spectrum of severity and so assigning a precise frequency and assessing thera- peutic efficacy is difficult. For unknown reasons the syndrome is much more common in female twins. Typically, the transfusion syndrome is first recognized by the finding of polyhydramnios. It usually develops around midgestation, but has been diagnosed as early as 12 weeks. The donor twin has oligohydramnios and may move much less than the recipient, so the term “stuck twin” has been applied to this feature.
Clinical diagnosis of TTTS is often difficult. In general, the earlier clin- ical manifestations are present, the poorer the prognosis, although overall the prognosis is poor, particularly if untreated. When the con- dition is diagnosed before 28 weeks of gestation, the overall survival rate is as low as 21%.
The hydramnios often leads to preterm labor and premature rupture of the membranes, and delivery often occurs before the 30th week of gestation. Alternatively, one twin may die, in which case the hydram-
nios ceases nearly immediately and the pregnancy may reach term. If one or both of the twins are liveborn, neonatal morbidity and mortality are significant. The donor often succumbs from hypovolemia and heart failure while the recipient may succumb from congestive heart failure.
Other pathophysiologic consequences of the syndrome include poor fetal growth, periventricular encephalomalacia, intracranial hemorrhage, intraventricular hemorrhage, polycythemia in the recipient, anemia in the donor, hypoglycemia, hyperbilirubinemia, skin necrosis resembling aplasia cutis, cardiac dysfunction, cardiac hypertrophy, and thrombosis.
Treatment Considerations
It has now become possible to obliterate the interfetal vascular connections by prenatal laser treatment. This is hoped to result in improved outcome and normalization of the pregnancy. Other modes of treatment include septostomy (of the dividing membranes) and amniocentesis of the twin with polyhydramnios. In the future, mapping not only the anastomoses but also the character and location of ablated vessels is likely to be important in planning future treatment options.
Acute Twin-to-Twin Transfusion Pathogenesis
Acute twin-to-twin transfusion may occur with or without chronic TTTS. It occurs to some degree in all DiMo twins when one twin dies in Figure 10.13. Histologic appearance of DiMo placenta depicted in Figure 10.12. The section has been taken through the vascular equator of the two placental portions. The donor’s placenta is on the left and the recipient’s on the right. Note that the chorionic villi of the donor are larger and more imma- ture appearing with somewhat edematous stroma. The recipient’s villi are smaller, more mature, and much more congested with blood.
utero. If placental anastomoses are small, the placenta of the dead fetus gradually atrophies and becomes completely infarcted. If, on the other hand, there are large interfetal vascular communications, the placental half belonging to the dead fetus will continue to be perfused by the survivor. The vascular bed of the dead twin is devoid of counterpres- sure and becomes a “sink.” The surviving twin may then literally exsanguinate into the dead twin. Therefore, when one twin of a DiMo pair dies, the survivor experiences some degree of acute blood loss into the dead twin’s circulation through superficial large interplacental anastomoses. These acute hypotensive events occur in the surviving twin immediately after one twin dies. Sonographically, reversal of blood flow in the umbilical cord has been observed after death of one twin.
Clinical Features and Implications
Cerebral palsy is five times more common in twins than in singletons and mostly affects MZ twins. When there is intrauterine fetal demise of one twin, cerebral palsy is particularly common in the surviving twin. Death of the surviving twin is also quite common. The presence of cerebral lesions, such as porencephaly, correlates well with the pres- ence of vascular anastomoses in MZ twins. This is thought, in many cases, to be the result of irregular flow through placental anastomoses, particularly V-V anastomoses.
Chimerism and Mosaicism 167
Suggestions for Examination and Report:
Twin-to-Twin Transfusion
Gross Examination: Documentation of vascular anastomoses is essential to the diagnosis of twin transfusion syndromes (see Chapter 9). In addition, careful attention to the color of the villous tissue (pallor of the donor and congestion of the recipient) is recommended.
Comment:The presence of a monochorionic placenta with a dom- inant artery-to-vein anastomosis is consistent with the diagnosis of chronic TTTS. With fetal demise of one twin, acute twin-to-twin transfusion should be considered as it occurs even in the absence of chronic TTTS. Both may lead to significant morbidity and mortality.
Chimerism and Mosaicism
Chimerism and mosaicism are related but different phenomena.
Whole-body chimerismis when an individual is composed of two popu- lations of cells, the origin of which is two genetically different fertilization products. It may develop in very early stages of development, when dizygotic twin embryos fuse to form a single individual. When two sper- matozoa fertilize an ovum and a polar body and then form a single embryo, such individuals represent, genetically speaking, fraternal twins fused into one body. This is a variant of the third type of twin (see above).
These chimeras are not necessarily clinically manifest. Most are dis- covered when the two populations of cells have different sex chromo- somes (XX/XY), resulting in gonadal abnormalities, most common among which is true hermaphroditism. Whole-body chimeras may also be discovered during routine blood grouping tests, because of unusual phenotypic features, such as heterochromia (eyes of different color) or abnormal patches of the skin resulting from the irregular dis- tribution of melanocyte precursors derived from different genotypes.
It is important to distinguish two pathogenetically different types of chimeras: blood chimeras and whole-body chimeras. Blood chimeras develop from fused placentas with connections between the fetal vessels enabling blood exchange between DZ twins. This has long been described in animals, but vascular connections between the placentas of human DZ twins are rare. Study of these individuals shows that they are blood chimeras but not whole-body chimeras.
Mosaicsare different from chimeras as they are individuals composed of different cell lines but derived from a single fertilization product. Because of “lyonization” and X chromosome inactivation, all human females are mosaics. Not only may mosaics have different cell lines with dif- ferent chromosome numbers but, because of mutations, they may also have cell lines with different phenotypic expression.
Heterokaryotypic Monozygotic Twins
Heterokaryotypic MZ twins begin as MZ twins, and then nondisjunc- tion of chromosomes in one twin gives them a different genetic makeup. Most commonly, this occurs with a sex chromosome resulting in karyotypes of 45XO and 46XY and MZ twins of different sex.
Nondisjunction of autosomes may also occur, however. These twins show mosaicism resulting from the simultaneous occurrence of twinning and somatic nondisjunction of chromosomes. If the Y chromosome of a 46 XY embryo is lost by nondisjunction during early development, male and female (45 X0 and 46 XY) MZ twins may be the outcome. Heterokary- otypic MZ twins may have varying degrees and types of mosaicism.
Mosaicism may be present in certain cell types only, such as lympho- cytes, and in this case is directly due to the presence of placental anas- tomoses. Mosaicism of fibroblasts suggests the loss of a chromosome in one twin after splitting has occurred.
Sacrococcygeal Teratoma and Epignathus
Sacrococcygeal teratomaand epignathus (a tumorous mass affixed to the jaw) are, in our opinion, malformed twins that are part of the spectrum of MZ twinning. Some may take exception to this concept. Neverthe- less, findings of perfectly formed extremities, digits, and other struc- tures favor this view. At times, however, an apparently benign sacrococcygeal teratoma eventuates in a malignancy. An alternate etiologic point of view is that sacrococcygeal tumors and epignathi derive from misplaced germ cells.
Placentomegaly has often been described to be a complication of sacrococ- cygeal teratomas and the same is true of the placenta in epignathi. Other ter- atomas and acardiac twins may also be associated with hydramnios and fetal hydrops. These placental changes are likely the result of high output failure. In effect, the teratoma acts as an arteriovenous fistula.
If there is hydrops, the placenta will be exceptionally pale. There may be severe villous edema, and the villi may show increased cellularity and vascu- lar congestion. Numerous Hofbauer cells may be present as well as many nucleated red blood cells (Figure 10.14).
Selected References
PHP4, Chapter 25, pages 801, 804, 827–875.
Bajoria R, Wigglesworth J, Fisk NM. Angioarchitecture of monochorionic placentas in relation to the twin-twin transfusion syndrome. Am J Obstet Gynecol 1995;172:856–863.
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162:1230–1236.
Bendon RW. Twin transfusion syndrome: pathological studies of the mono- chorionic placenta in liveborn twins and of the perinatal autopsy in mono- chorionic twin pairs. Pediatr Pathol Lab Med 1995;15:363–376.
Benirschke K. Chimerism, mosaicism and hybrids. In: Human genetics.
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Amsterdam: Excerpta Medica, 1971:212–231.
Benirschke K. Intrauterine death of a twin: mechanisms, implications for sur- viving twin, and placental pathology. Semin Diagn Pathol 1993;10:222–231.
Selected References 169
Figure 10.14. Villi of immature placenta in a patient with a large sacrococ- cygeal teratoma. Placenta weighed 880 g at 31 weeks. The neonate died with extensive cerebral necrosis. The villi are irregular and patchily edematous, and have distended fetal capillaries. There is focal hemorrhage, and numerous nucleated red blood cells are present. The cytotrophoblast is more prominent than expected at this age. H&E. ¥160.
Bieber FR, Nance WE, Morton CC, et al. Genetic studies of an acardiac monster:
evidence of polar body twinning in man. Science 1981;213:775–777.
Costa T, Lambert M, Teshima I, et al. Monozygotic twins with 45X,46,XY mosaicism discordant for phenotypic sex. Am J Med Genet 1998;75:40–44.
De Lia JE. Surgery of the placenta and umbilical cord. Clin Obstet Gynecol 1996;39:607–625.
Dimmick JE, Kalousek DK. Developmental pathology of the embryo and fetus.
Philadelphia: Lippincott, 1992.
Jauniaux E, Elkazen N, Leroy F, et al. Clinical and morphologic aspects of the vanishing twin phenomenon. Obstet Gynecol 1988;72:577–581.
Kaplan C, Perlmutter S, Molinoff S. Epignathus with placental hydrops. Arch Pathol Lab Med 1980;104:374–375.
Liu S, Benirschke K, Scioscia AL, et al. Intrauterine death in multiple gestation.
Acta Genet Med Gemellol 1992;41:5–26.
Machin GA. Some causes of genotypic and phenotypic discordance in monozy- gotic twin pairs. Am J Med Genet 1996;61:216–228.
Moore TR, Gale SA, Benirschke K. Perinatal outcome of forty-nine pregnancies complicated by acardiac twinning. Am J Obstet Gynecol 1990;163:907–912.
Scheller JM, Nelson KB. Twinning and neurologic morbidity. Am J Dis Child 1992;146:110–113.
Spencer R. Conjoined twins: theoretical embryological basis. Teratology 1992;
45:591–602.
Section IV
Abnormalities of the Placenta
This section covers abnormalities and lesions of the placenta. The first chapter, Chapter 11, discusses abnormalities encountered in the early abortion specimen and the pathologic changes associated with chro- mosomal anomalies. Chapter 12 deals primarily with the abnormalities of the implantation site and uterus that occur in the postpartum period, including uterine atony, endometritis, retained placental tissue, and placenta accreta. Chapter 13 concerns itself with aberrations in placen- tal shape, and as these aberrations are associated with abnormal implantation, theories of pathogenesis are briefly discussed. Placenta previa, as an abnormality in the location of implantation, has charac- teristics in common with these variants and so is discussed as well.
Finally, pathologic lesions of the fetal membranes are presented in Chapter 14 and those of the umbilical cord in Chapter 15.
