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In the United States, between 1980 and 2004, the twin rate climbed 101% with 68,339 twins born in 1980 and 137,085 twins born in 2006. Multiple gestations now comprise 3% of all pregnancies, and twins comprise 25–30% of deliveries resulting from assisted reproductive technologies (ART). Significant maternal and neonatal effects are felt from this increase in multiple births. The financial costs are also staggering, with combined costs of ART plus pregnancy care, delivery, and neonatal care reaching hundreds of thousands of dollars in some cases. Maternal morbidity and mortality rates are much higher in multiple pregnancy than in singleton pregnancy. Compared with singleton pregnancies, twin pregnancies are more likely to be complicated by hypertensive disorders, gestational diabetes mellitus, anemia, preterm birth, ante- and postpartum hemorrhage, and maternal death. Earlier and more precise sonography has revealed the incidence of multiple gestation to be 3.29–5.39% before 12 weeks. However, in over 20% of such cases, one or more of the pregnancies spontaneously disappears (“vanishing twin”). Although this event may be associated with vaginal bleeding, the prognosis remains good for the remaining twin.
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Approximately two-thirds of twin pregnancies end in a singleton birth; the other embryo is lost from bleeding, is absorbed within the first 10 weeks of pregnancy, or is retained and becomes mummified (fetus papyraceous). Fetus papyraceous is a small, blighted, mummified fetus usually discovered at the delivery of a well-developed newborn. This occurs once in 17,000–20,000 pregnancies spontaneously and is also the result of multifetal reduction. The cause is thought to be death of one twin, amniotic fluid loss, or reabsorption and compression of the dead fetus by the surviving twin.
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Twins can be monozygotic or dizygotic. Higher order multiples can result from either or both processes.
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Monozygotic Multiple Gestation
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Monozygotic twins (“identical twins”) are the result of the division of a single fertilized ovum that subsequently divides into 2 separate individuals. Monozygotic twinning occurs in about 4–5 of 1000 pregnancies in all races. The rate is remarkably constant in all populations and is not influenced by heredity, age of the mother, or other factors. Monozygotic twins are always of the same sex. However, the twins may develop differently depending on the time of preimplantation division. Normally, monozygotic twins share the same physical characteristics (skin, hair and eye color, body build) and the same genetic features (blood characteristics: ABO, M, N, haptoglobin, serum group; histocompatible genes), and they are often mirror images of one another (one left-handed, the other right-handed, etc). However, their fingerprints differ.
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The paradox of “identical” twins is that they may be the antithesis of identical. The very earliest splits are sometimes accompanied by a simultaneous chromosomal error, resulting in heterokaryotypic monozygotes, one with Down syndrome and the other normal. Furthermore, monozygotic twins may be discordant for fetal structural malformations.
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Monozygotic triplets result from repeated twinning (also called supertwinning) of a single ovum. Conversely, trizygotic triplets develop by individual fertilization of 3 simultaneously expelled ova. Triplets may also be produced by the twinning of 2 ova and the elimination of 1 of the 4 resulting embryos. Similarly, quadruplets may be monozygotic, paired dizygotic, or quadrizygotic (ie, they may arise from 1 to 4 ova).
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Monoamniotic twins are the rarest form of monozygotic twins, with an incidence of about 1:10,000 pregnancies (1–5% of monozygotic gestations). The perinatal mortality is much higher than that of other monozygotic twins (23%) mostly due to cord entanglement as a result of the absence of a dividing membrane.
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The placenta and membranes of monozygotic twins vary (Fig. 17–1), depending on the time of initial division of the embryonic disk. Variations are noted below.
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Division prior to the morula stage and differentiation of the trophoblast (day 3) results in separate or fused placentas, 2 chorions, and 2 amnions (dichorionic/diamniotic). (This process grossly resembles dizygotic twinning and accounts for almost one-third of monozygotic twinning.) This is clinically relevant since dichorionic twins have a much lower rate of complications.
Division after differentiation of the trophoblast but before the formation of the amnion (days 4–8) yields a single placenta, a common chorion, and 2 amnions (monochorionic/diamniotic). (This accounts for about two-thirds of monozygotic twinning.)
Division after differentiation of the amnion (days 8–13) results in a single placenta, 1 (common) chorion, and 1 (common) amnion (monochorionic/monoamniotic). This is rare.
Division later than day 15 may result in incomplete twinning. Just prior to that time (days 13–15), division may result in conjoined twins.
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At delivery, the membranous T-shaped septum or dividing membrane of the placenta between the twins must be inspected and sectioned for evidence of the probable type of twinning (Fig. 17–2). Monochorionic, diamniotic twins most commonly have a transparent (<2 mm) septum made up of 2 amniotic membranes only (no chorion and no decidua). Dichorionic, diamniotic twins almost always have an opaque (thick) septum made up of 2 chorions, 2 amnions, and intervening decidua.
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A monochorionic placenta can be identified by stripping away the amnion or amnions to reveal a single chorion over a common placenta. In virtually every case of monochorionic placenta, vascular communications between the 2 parts of the placenta can be identified by careful dissection or injection. In contrast, dichorionic placentas (of dizygotic twinning) only rarely have an anastomosis between the fetal blood vessels. All twin placentas are sent for pathologic examination to confirm chorionicity.
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Placental and membrane examination is a certain indicator of zygosity in twins with monochorionic placentas because these are always monozygotic. Overall, approximately 1% of twins are monoamniotic, and these too are monozygotic. Determination of zygosity is clinically significant in case intertwin organ transplantation is needed later in life, as well as for assessing obstetrical risks. Monozygotic twins can rarely be discordant for phenotypic sex when one twin is phenotypically female due to Turner's syndrome (45,XO) and its sibling is male (46,XY).
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Monochorionic placentation is associated with more disease processes as a result of placental vascular problems. Inequities of the placental circulation in one area (marginal insertion, partial infarction, or thinning) may lead to growth discordance between the twins. Due to vascular anastomoses in monochorionic placentation, standard multifetal reduction using intrathoracic potassium chloride can only be performed with dichorionic placentation.
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The most serious problem with monochorionic placentas is local shunting of blood—also called twin–twin transfusion syndrome. This problem affects approximately 15% of monochorionic twin pregnancies and occurs because of vascular anastomoses to each twin that are established early in embryonic life. The possible communications are artery to artery, vein to vein, and combinations of these. Artery-to-vein communication is by far the most serious; it is most likely to cause twin–twin transfusion. In uncompensated cases, the twins, although genetically identical, differ greatly in size and appearance. The recipient twin is plethoric, edematous, and hypertensive. Ascites and kernicterus are likely. The heart, liver, and kidneys are enlarged (glomerulotubal hypertrophy). Hydramnios follows fetal polyuria. Although ruddy and apparently healthy, the recipient twin with hypervolemia may die of heart failure during the first 24 hours after birth. The donor twin is small, pallid, and dehydrated (from growth restriction, malnutrition, and hypovolemia). Oligohydramnios may be present. Severe anemia, due to chronic blood loss to the other twin, may lead to hydrops and heart failure.
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Velamentous insertion of the cord occurs in about 7% of twins but in only 1% of singletons. There is a corresponding increase in the potentially catastrophic vasa previa. The incidence of 2-vessel cord (single umbilical artery) is 4–5 times higher in monozygotic twins than in singletons.
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Monochorionic, monoamniotic twins (1:100 sets of twins) have < a 90% likelihood of both surviving because of cord entanglement that compromises fetal-placental blood flow. Other common complications are congenital anomalies in 26% of monoamniotic twins and discordant birth weights, primarily due to twin–twin transfusion syndrome. Some authors advocate planned caesarean delivery at 32–34 weeks in an attempt to prevent in utero demise due to cord accidents, as well as continuous external fetal monitoring from about 27 weeks until delivery.
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There are several unusual fetal findings that may be seen in the setting of monozygotic twinning. Conjoined twins result from incomplete segmentation of a single fertilized ovum between the 13th and 14th days; if cleavage is further postponed, incomplete twinning (ie, 2 heads, 1 body) may occur. Lesser abnormalities are also noted, but these occur without regard to specific organ systems. Conjoined twins are described by site of union: pyopagus (at the sacrum); thoracopagus (at the chest); craniopagus (at the heads); and omphalopagus (at the abdominal wall). Curiously, conjoined twins usually are female. Numerous conjoined twins have survived separation.
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An acardiac twin is a parasitic monozygotic fetus without a heart. It is thought to develop from reversed circulation, perfused by 1 arterial–arterial and 1 venous–venous anastomosis. This represents the twin reversed arterial perfusion (TRAP) syndrome. The otherwise normal donor twin is at risk for cardiac hypertrophy and failure and has a 35% mortality rate. Various methods of cord occlusion are being studied as in utero therapy.
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Dizygotic Multiple Gestation
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Dizygotic twins (“fraternal twins”) are produced from separately fertilized ova. They bear only the resemblance of brothers or sisters and may or may not have the same blood type. Significant differences usually can be identified over time. Slightly more than 30% of twins are monozygotic; nearly 70% are dizygotic. Twins of different sexes are always dizygotic (fraternal). Twins of the same sex may be monozygotic or dizygotic. Although monozygotism is random—ie, it does not fit any discernible genetic pattern—dizygotism has hereditary determinants.
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In North America, dizygotic twinning occurs about once in 83 conceptions and triplets occur about once in 8000 conceptions. A traditional approximation of the incidence of spontaneous multiple pregnancies is as follows:
- Twins1:80
- Triplets1:802 = 1:6400
- Quadruplets (etc)1:803 = 1:512,000
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About 75% of dizygotic twins are the same sex. Many factors influence dizygotic twinning including age and ethnicity. Race is a factor, with multiple gestations most common in blacks, least common in Asians, and of intermediate occurrence in whites. The incidence of spontaneous dizygotic twinning varies from 1.3 in 1000 in Japan to 49 in 1000 in western Nigeria. The rate in the United States is about 12 in 1000. Spontaneous twinning increases with advancing maternal age. The widespread use of ART has increased the frequency of dizygotic twins with a minimal effect on the incidence of monozygotic twins.
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Dizygotic twinning is more common among women who become pregnant soon after cessation of long-term oral contraception. This may be a reflection of high “rebound” gonadotropin secretion. Induction of ovulation in previously infertile patients has resulted in many multiple pregnancies—even the gestation of septuplets and octuplets. The estrogen analog clomiphene citrate increases the incidence of dizygotic pregnancy to about 5–10%.
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Clinically, zygosity cannot be ascertained prenatally, so chorionicity seen on ultrasound is a useful surrogate marker for stratification of perinatal risk, with increased risks associated with monochorionicity.