Williams Obstetrics, 24th Edition

CHAPTER 45. Multifetal Pregnancy













Multifetal pregnancies may result from two or more fertilization events, from a single fertilization followed by an “erroneous” splitting of the zygote, or from a combination of both. Such pregnancies are associated with increased risk for both mother and child, and this risk increases with the number of offspring. For example, 60 percent of twins, 90 percent of triplets, and virtually all of quadruplets are born preterm (Martin, 2012). From these observations, it is apparent that women were not intended to concurrently bear more than one offspring. And although they are often viewed as a novelty or miracle, multifetal pregnancies represent a potentially perilous journey for the mother and her unborn children.

Fueled largely by infertility therapy, both the rate and the number of twin and higher-order multifetal births have increased dramatically since 1980. Specifically, the twinning rate rose 76 percent from 18.9 to 32.1 per 1000 live births in 2009 (Martin, 2012). During the same time, the number of higher-order multifetal births increased more than 400 percent to a peak in 1998. Since then, however, evolving infertility management has resulted in decreased rates of higher-order multifetal births to its lowest level in 15 years. Specifically, the rate of triplets or more decreased by 10 percent from 153 per 100,000 births in 2009 to 138 per 100,000 births in 2010 (Martin, 2012).

The overall increase in prevalence of multifetal births is of concern because the corresponding increase in the rate of preterm birth compromises neonatal survival and increases the risk of lifelong disability. For example, in this country, about a fourth of very-low-birthweight neonates—those born weighing < 2500 g—are from multifetal gestations, and 15 percent of infants who die in the first year after birth are from multifetal pregnancies (Martin, 2012). In 2009, the infant mortality rate for multiple births was five times the rate for singletons (Mathews, 2013). A comparison of singleton and twin outcomes from infants delivered at Parkland Hospital is shown in Table 45-1. These risks are magnified further with triplets or quadruplets. In addition to these adverse outcomes, the risks for congenital malformations are increased with multifetal gestation. Importantly, this increased risk is for each fetus and is not simply because there are more fetuses per pregnancy.

TABLE 45-1. Selected Outcomes in Singleton and Twin Pregnancies Delivered at Parkland Hospital from 2002 through 2012


The mother may also experience higher obstetrical morbidity and mortality rates. These also increase with the number of fetuses (Mhyre, 2012; Wen, 2004). In a study of more than 44,000 multifetal pregnancies, Walker and colleagues (2004) reported that, compared with singletons, the risks for preeclampsia, postpartum hemorrhage, and maternal death were increased twofold or more. The risk for peripartum hysterectomy is also increased, and Francois and associates (2005) reported this to be threefold for twins and 24-fold for triplets or quadruplets. Finally, these mothers are at increased risk for depression compared with women with a singleton pregnancy (Choi, 2009).


Twin fetuses usually result from fertilization of two separate ova–dizygotic or fraternal twins. Less often, twins arise from a single fertilized ovum that divides–monozygotic or identical twins. Either or both processes may be involved in the formation of higher numbers. Quadruplets, for example, may arise from as few as one to as many as four ova.

image Dizygotic versus Monozygotic Twinning

Dizygotic twins are not in a strict sense true twins because they result from the maturation and fertilization of two ova during a single ovulatory cycle. Moreover, from a genetic perspective, dizygotic twins are like any other pair of siblings. On the other hand, monozygotic or identical twins, although they have virtually the same genetic heritage, are usually not identical.

As discussed subsequently, the division of one fertilized zygote into two does not necessarily result in equal sharing of protoplasmic material. Monozygotic twins may actually be discordant for genetic mutations because of a postzygotic mutation, or may have the same genetic disease but with marked variability in expression. In female fetuses, skewed lyonization can produce differential expression of X-linked traits or diseases. Furthermore, the process of monozygotic twinning is in a sense a teratogenic event, and monozygotic twins have an increased incidence of often discordant malformations (Glinianaia, 2008). For example, in a study of 926 monozygotic twins, Pettit (2013) reported a 12-fold increase in the prevalence of congenital heart defects, but 68 percent of affected infants had a normal sibling. Accordingly, dizygotic or fraternal twins of the same sex may appear more nearly identical at birth than monozygotic twins.

Genesis of Monozygotic Twins

The developmental mechanisms underlying monozygotic twinning are poorly understood. Minor trauma to the blastocyst during assisted reproductive technology (ART) may lead to the increased incidence of monozygotic twinning observed in pregnancies conceived in this manner (Wenstrom, 1993).

The outcome of the monozygotic twinning process depends on when division occurs. If zygotes divide within the first 72 hours after fertilization, two embryos, two amnions, and two chorions develop, and a diamnionic, dichorionic twin pregnancy evolves (Fig. 45-1). Two distinct placentas or a single, fused placenta may develop. If division occurs between the fourth and eighth day, a diamnionic, monochorionic twin pregnancy results. By approximately 8 days after fertilization, the chorion and the amnion have already differentiated, and division results in two embryos within a common amnionic sac, that is, a monoamnionic, monochorionic twin pregnancy. Conjoined twins result if twinning is initiated later.


FIGURE 45-1 Mechanism of monozygotic twinning. Black boxing and blue arrows in columns A, B, and C indicate timing of division. A. At 0 to 4 days postfertilization, an early conceptus may divide into two. Division at this early stage creates two chorions and two amnions (dichorionic, diamnionic). Placentas may be separate or fused. B. Division between 4 and 8 days leads to formation of a blastocyst with two separate embryoblasts (inner cell masses). Each embryoblast will form its own amnion within a shared chorion (monochorionic, diamnionic). C. Between 8 and 12 days, the amnion and amnionic cavity form above the germinal disc. Embryonic division leads to two embryos with a shared amnion and shared chorion (monochorionic, monoamnionic). D. Differing theories explain conjoined twin development. One describes an incomplete splitting of one embryo into two. The other describes fusion of a portion of one embryo from a monozygotic pair onto the other.

It has long been accepted that monochorionicity incontrovertibly indicated monozygosity. Rarely, however, monochorionic twins may in fact be dizygotic (Hack, 2009). Mechanisms for this are speculative, but Ekelund and coworkers (2008) found in their review of 14 such cases that nearly all have been conceived after ART procedures.

Superfetation and Superfecundation

In superfetation, an interval as long as or longer than a menstrual cycle intervenes between fertilizations. Superfetation requires ovulation and fertilization during the course of an established pregnancy, which is theoretically possible until the uterine cavity is obliterated by fusion of the decidua capsularis to the decidua parietalis. Although known to occur in mares, superfetation is not known to occur spontaneously in humans. Lantieri and colleagues (2010) reported a case after ovarian hyperstimulation and intrauterine insemination in the presence of an undiagnosed tubal pregnancy. Most authorities believe that alleged cases of human superfetation result from markedly unequal growth and development of twin fetuses with the same gestational age.

Superfecundation refers to fertilization of two ova within the same menstrual cycle but not at the same coitus, nor necessarily by sperm from the same male. An instance of superfecundation or heteropaternity, documented by Harris (1982), is demonstrated in Figure 45-2. The mother was sexually assaulted on the 10th day of her menstrual cycle and had intercourse 1 week later with her husband. She was delivered of a black neonate whose blood type was A and a white neonate whose blood type was O. The blood type of the mother and her husband was O.


FIGURE 45-2 An example of dizygotic twin boys as the consequence of superfecundation.

image Frequency of Twinning

Dizygotic twinning is much more common than monozygous splitting of a single oocyte, and its incidence is influenced by race, heredity, maternal age, parity, and, especially, fertility treatment. By contrast, the frequency of monozygotic twin births is relatively constant worldwide—approximately one set per 250 births, and this incidence is generally independent of race, heredity, age, and parity. One exception is that zygotic splitting is increased following ART (Aston, 2008).

The “Vanishing Twin”

The incidence of twins in the first trimester is much greater than the incidence of twins at birth. Studies in which fetuses were evaluated with sonography in the first trimester have shown that one twin is lost or “vanishes” before the second trimester in up to 10 to 40 percent of all twin pregnancies (Brady, 2013). The incidence is higher in the setting of ART.

Monochorionic twins have a significantly greater risk of abortion than dichorionic twins (Sperling, 2006). In some cases, the entire pregnancy aborts. In many cases, however, only one fetus dies, and the remaining fetus delivers as a singleton. Undoubtedly, some threatened abortions have resulted in death and resorption of one embryo from an unrecognized twin gestation. It has been estimated that 1 in 80 births are multifetal, whereas 1 in 8 pregnanciesbegin multifetal followed by spontaneous reduction of one or more embryos or fetuses (Corsello, 2010).

Dickey and associates (2002) described spontaneous reduction in 709 women with a multifetal pregnancy. Before 12 weeks, one or more embryos died in 36 percent of twin pregnancies, 53 percent of triplet pregnancies, and 65 percent of quadruplet pregnancies. Interestingly, pregnancy duration and birthweight were inversely related to the initial gestational sac number regardless of the final number of fetuses at delivery. This effect was most pronounced in twins who started as quadruplets. Chasen and coworkers (2006) reported that spontaneous reduction of an in vitro fertilization (IVF) twin pregnancy to a singleton pregnancy was associated with perinatal outcomes intermediate between IVF singleton pregnancies and IVF twin pregnancies that did not undergo spontaneous reduction.

In one analysis of 41 cases of spontaneous reduction, higher values of pregnancy-associated plasma protein A (PAPP-A) and free β-human chorionic gonadotropin (β-hCG) were identified (Chasen, 2006). Gjerris and colleagues (2009) compared 56 cases of “vanishing twin” to 897 singletons after ART and did not identify any differences in first-trimester serum markers as long as the reduction was identified before 9 weeks. If diagnosed after 9 weeks, the serum markers were higher and less precise than in singleton ART gestations. Therefore, the diagnosis of vanishing twin should be excluded to avoid confusion during maternal serum screening for Down syndrome or neural-tube defects (Chap. 14p. 283).

Factors That Influence Twinning

Race. The frequency of multifetal births varies significantly among different races and ethnic groups (Table 45-2). Abel and Kruger (2012) analyzed more than 8 million births in the United States between 2004 and 2008. These investigators found the highest rate of twinning in African American women (3.5 percent) and lower rates in white (3.0 percent) women. Hispanic, Asian, and Native American women had comparatively lower rates then white women. In one rural community in Nigeria, Knox and Morley (1960) found that twinning occurred once in every 20 births! These marked differences in twinning frequency may be the consequence of racial variations in levels of follicle-stimulating hormone—FSH (Nylander, 1973).

TABLE 45-2. Twinning Rates per 1000 Births by Zygosity


Maternal Age. As depicted in Figure 45-3, maternal age is another important risk factor for multiple births. Dizygotic twinning frequency increases almost fourfold between the ages of 15 and 37 years (Painter, 2010). It is in this age range that maximal FSH stimulation increases the rate of multiple follicles developing (Beemsterboer, 2006). The rate of twinning also increases dramatically with advancing maternal age because the use of ART is more likely in older women (Ananth, 2012). Although paternal age has been linked to frequency of twinning, its affect is felt to be small (Abel, 2012).


FIGURE 45-3 Multifetal birth rates in the United States according to maternal age and race, 2010. (Data from Martin, 2012.)

Parity. Increasing parity has been shown to independently increase the incidence of twinning in all populations studied. Antsaklis and coworkers (2013) noted a progressive increase in multiparity in twinning during a 30-year period, but cautioned that some of this increase is presumably due to ART. In a two-year study from Nigeria, where such technology is not commonly available, Olusanya (2012) calculated an eightfold increase in multiple gestations when parity was 4 or less and a 20-fold increase when parity was 5 or more compared with primiparas.

Heredity. As a determinant of twinning, the family history of the mother is more important than that of the father. In a study of 4000 genealogical records, White and Wyshak (1964) found that women who themselves were a dizygotic twin gave birth to twins at a rate of 1 set per 58 births. Women who were not a twin, but whose husbands were a dizygotic twin, gave birth to twins at a rate of 1 set per 116 pregnancies. Painter and associates (2010) performed genome-wide linkage analyses on more than 500 families of mothers of dizygotic twins and identified four potential linkage peaks. The highest peak was on the long arm of chromosome 6, with other suggestive peaks on chromosomes 7, 9, and 16. That said, the contribution of these variants to the overall incidence of twinning is likely small (Hoekstra, 2008).

Nutritional Factors. In animals, litter size increases in proportion to nutritional sufficiency. Evidence from various sources indicates that this occurs in humans as well. Nylander (1971) showed a definite increasing gradient in the twinning rate related to greater nutritional status as reflected by maternal size. Taller, heavier women had a twinning rate 25 to 30 percent greater than short, nutritionally deprived women. Evidence acquired during and after World War II showed that twinning correlated more with nutrition than body size. Widespread undernourishment in Europe during those years was associated with a marked fall in the dizygotic twinning rate (Bulmer, 1959). Several investigators have reported a 40-percent increase in the prevalence of twinning among women who have taken supplementary folic acid (Ericson, 2001; Haggarty, 2006; Hasbargen, 2000). Conversely, in a systematic review, Muggli and Halliday (2007) were unable to demonstrate a significant association. Analysis of twinning rate in Texas after folic acid fortification of cereal-grain products also did not demonstrate an independent increase in twinning between 1996 and 1998 (Waller, 2003).

Pituitary Gonadotropin. The common factor linking race, age, weight, and fertility to multifetal gestation may be FSH levels (Benirschke, 1973). This theory is supported by the fact that increased fecundity and a higher rate of dizygotic twinning have been reported in women who conceive within 1 month after stopping oral contraceptives, but not during subsequent months (Rothman, 1977). This may be due to the sudden release of pituitary gonadotropin in amounts greater than usual during the first spontaneous cycle after stopping hormonal contraception. Indeed, the paradox of declining fertility but increasing twinning with advancing maternal age can be explained by an exaggerated pituitary release of FSH in response to decreased negative feedback from impending ovarian failure (Beemsterboer, 2006).

Infertility Therapy. Ovulation induction with FSH plus chorionic gonadotropin or clomiphene citrate remarkably enhances the likelihood of multiple ovulations. A mainstay of current infertility therapy and common antecedent to IVF is ovarian stimulation followed by timed intrauterine insemination. In their review of this practice, McClamrock and coworkers (2012) reported rates of twin and higher-order multifetal pregnancies as high as 28.6 percent and 9.3 percent, respectively. Rates this high remain a major concern. There are currently two ongoing multicenter trials—Assessment of Multiple Gestations from Ovarian Stimulation (AMIGOS) and Pregnancy in Polycystic Ovary Syndrome II (PPCOSII)—that are designed to provide guidance on achieving maximum pregnancy rates while minimizing multifetal gestation rates (Diamond, 2011; Legro, 2012).

In general with IVF, the greater the number of embryos that are transferred, the greater the risk of twins and multiple fetuses. In 2005, 1 percent of infants born in the United States were conceived through ART, and these infants accounted for 17 percent of multifetal births (Wright, 2008). The American Society for Reproductive Medicine (2013) recently revised their age-related guidelines on numbers of cleavage-stage embryos or blastocysts to transfer in an effort to reduce the incidence of higher-order multifetal pregnancies. For example, women younger than 35 years with a favorable prognosis should have no more than two embryos transferred. These practices have effectively lowered rates (Kulkarni, 2013).

image Sex Ratios with Multiple Fetuses

In humans, as the number of fetuses per pregnancy increases, the percentage of male conceptuses decreases. Strandskov and coworkers (1946) found the percentage of males in 31 million singleton births in the United States was 51.6 percent. For twins, it was 50.9 percent; for triplets, 49.5 percent; and for quadruplets, 46.5 percent. Swedish birth data spanning 135 years reveals the number of males per 100 female infants born was 106 among singletons, 103 among twins, and 99 among triplets (Fellman, 2010). Females predominate even more in twins from late twinning events. For example, 68 percent of thoracopagus conjoined twins are female (Mutchinick, 2011). Two explanations have been offered. First, beginning in utero and extending throughout the life cycle, mortality rates are lower in females. Second, female zygotes have a greater tendency to divide.

image Determination of Zygosity

Twins of opposite sex are almost always dizygotic. In rare instances, due to somatic mutations or chromosome aberrations, the karyotype or phenotype of a monozygous twin gestation can be different. Most reported cases are related to postzygotic loss of the Y chromosome in one 46,XY twin. This results in a phenotypically female twin due to Turner syndrome (45,X). Zech and colleagues (2008) reported a rare case of a 47,XXY zygote that underwent postzygotic loss of the X chromosome in some cells and loss of the Y chromosome in other cells. The phenotype of the resultant twins was one male and one female. Karyotype analyses revealed both to be 46,XX/46,XY genetic mosaics.

The risk for twin-specific complications varies in relation to zygosity as well as chorionicity—the number of chorions. As shown in Table 45-3, the latter is the more important determinant. Specifically, there are increased rates of perinatal mortality and neurological injury in monochorionic diamnionic twins compared with dichorionic pairs (Hack, 2008; Lee, 2008). In their retrospective analysis of more than 2000 twins, McPherson and associates (2012) reported that the risk of fetal demise in one or both monochorionic twins was twice that in dichorionic multifetal gestations.

TABLE 45-3. Overview of the Incidence of Twin Pregnancy Zygosity and Corresponding Twin-Specific Complications


Sonographic Determination of Chorionicity

Chorionicity can sometimes be identified in the first trimester with sonography. Two separate placentas suggest dizygosity. In pregnancies with a single placental mass, it may be difficult to identify chorionicity. Identification of a thick dividing membrane—generally 2 mm or greater—supports a presumed diagnosis of dichorionicity. Also, the twin peak sign is seen by examining the point of origin of the dividing membrane on the placental surface. The peak appears as a triangular projection of placental tissue extending a short distance between the layers of the dividing membrane (Fig. 45-4).


FIGURE 45-4 A. Sonographic image of the “twin-peak” sign, also termed the “lambda sign,” in a 24-week gestation. At the top of this sonogram, tissue from the anterior placenta is seen extending downward between the amnion layers. This sign confirms dichorionic twinning. B. Schematic diagram of the “twin-peak” sign. A triangular portion of placenta is seen insinuating between the amniochorion layers.

In contrast, monochorionic pregnancies have a dividing membrane that is so thin it may not be seen until the second trimester. The membrane is generally less than 2-mm thick, and magnification reveals only two layers. The right-angle relationship between the membranes and placenta and no apparent extension of placenta between the dividing membranes is called the T sign (Fig. 45-5). Evaluation of the dividing membrane can establish chorionicity in more than 99 percent of pregnancies in the first trimester (Miller, 2012).


FIGURE 45-5 A. Sonographic image of the “T” sign in a monochorionic diamnionic gestation at 30 weeks. B. Schematic diagram of the “T” sign. Twins are separated only by a membrane created by the juxtaposed amnion of each twin. A “T” is formed at the point at which amnions meet the placenta.

Placental Examination

A carefully performed visual examination of the placenta and membranes after delivery serves to establish zygosity and chorionicity promptly in approximately two thirds of cases. The following systematic examination is recommended. As the first neonate is delivered, one clamp is placed on a portion of its cord. Cord blood is generally not collected until after delivery of the other twin. As the second neonate is delivered, two clamps are placed on that cord. Three clamps are used to mark the cord of a third neonate, and so on as necessary. Until the delivery of the last fetus, each cord segment must remain clamped to prevent fetal hypovolemia and anemia caused by blood leaving the placenta via anastomoses and then through an unclamped cord.

The placenta should be carefully delivered to preserve the attachment of the amnion and chorion. With one common amnionic sac, or with juxtaposed amnions not separated by chorion arising between the fetuses, the fetuses are monozygotic. If adjacent amnions are separated by chorion, then the fetuses could be either dizygotic or monozygotic, but dizygosity is more common (see Figs. 45-1 and 45-6). If the neonates are of the same sex, blood typing of cord blood samples may be helpful. Different blood types confirm dizygosity, although demonstrating the same blood type in each fetus does not confirm monozygosity. For definitive diagnosis, more complicated techniques such as DNA fingerprinting can be used, but these tests are generally not performed at birth unless there is a pressing medical indication.


FIGURE 45-6 Dichorionic diamnionic twin placenta. The membrane partition that separated twin fetuses is elevated and consists of chorion (c) between two amnions (a).


image Clinical Evaluation

During examination, accurate fundal height measurement, described in Chapter 9 (p. 176), is essential. With multiple fetuses, uterine size is typically larger during the second trimester than expected. Rouse and associates (1993) reported fundal heights in 336 well-dated twin pregnancies. Between 20 and 30 weeks, fundal heights averaged approximately 5 cm greater than expected for singletons of the same fetal age.

In general, it is difficult to diagnose twins by palpation of fetal parts before the third trimester. Even late in pregnancy, it may be difficult to identify twins by abdominal palpation, especially if one twin overlies the other, if the woman is obese, or if there is hydramnios. Palpating two fetal heads, often in different uterine quadrants, strongly supports a twin diagnosis.

Late in the first trimester, fetal heart action may be detected with Doppler ultrasonic equipment. Thereafter, it becomes possible to identify two fetal heartbeats if their rates are clearly distinct from each other and from that of the mother. Careful examination with an aural fetal stethoscope can identify fetal heart sounds in twins as early as 18 to 20 weeks.

image Sonography

By careful sonographic examination, separate gestational sacs can be identified early in twin pregnancy (Fig. 45-7). Subsequently, each fetal head should be seen in two perpendicular planes so as not to mistake a cross section of the fetal trunk for a second fetal head. Ideally, two fetal heads or two abdomens should be seen in the same image plane, to avoid scanning the same fetus twice and interpreting it as twins. Sonographic examination should detect practically all sets of twins. Given the increased frequency of sonographic examinations during the first trimester, early detection of a twin pregnancy is common. Indeed, one argument in favor of routine first-trimester sonographic screening is earlier detection of multiple fetuses.


FIGURE 45-7 Sonograms of first-trimester twins. A. Dichorionic diamnionic twin pregnancy at 6 weeks’ gestation. Note the thick dividing chorion (yellow arrow). One of the yolk sacs is indicated (blue arrow). B. Monochorionic diamnionic twin pregnancy at 8 weeks’ gestation. Note the thin amnion encircling each embryo, resulting in a thin dividing membrane (blue arrow).

Higher-order multifetal gestations are more difficult to evaluate. Even in the first trimester, it can be difficult to identify the actual number of fetuses and their position. This determination is especially important if pregnancy reduction or selective termination is considered (p. 919).

image Other Diagnostic Aids

Radiography and Magnetic Resonance Imaging

Abdominal radiography can be used if fetal number in a higher-order multifetal gestation is uncertain. However, radiographs generally have limited utility and may lead to an incorrect diagnosis if there is hydramnios, obesity, fetal movement during the exposure, or inappropriate exposure time. Additionally, fetal skeletons before 18 weeks’ gestation are insufficiently radiopaque and may be poorly seen.

Although not typically used to diagnose multifetal pregnancy, magnetic resonance (MR) imaging may help delineate complications in monochorionic twins (Hu, 2006). Bekiesinska-Figatowska and colleagues (2013) reviewed their experience with 17 complicated twin gestations evaluated by both sonographic and MR imaging. They concluded that MR imaging provides a more detailed assessment of pathology in twins and is particularly helpful in cases of conjoined twins.

Biochemical Tests

There is no biochemical test that reliably identifies multiple fetuses. Serum and urine levels of β-hCG and maternal serum alpha-fetoprotein (MSAFP) are generally higher with twins compared with singletons. However, levels may vary considerably and overlap with those of singletons.


The various physiological burdens of pregnancy and the likelihood of serious maternal complications are typically greater with multiple fetuses than with a singleton. This should be considered, especially when counseling a woman whose health is compromised and in whom multifetal gestation is recognized early. Similar consideration is given to a woman who is not pregnant but is considering infertility treatment.

Beginning in the first trimester, and temporarily associated with higher serum β-hCG levels, women with multifetal gestation often have nausea and vomiting in excess of women with a singleton pregnancy. In women with multiple fetuses, blood volume expansion is greater and averages 50 to 60 percent compared with 40 to 50 percent in those with a singleton (Pritchard, 1965). Although the red cell mass also increases, it does so proportionately less in twin pregnancies. Combined with increased iron and folate requirements, this predisposes to anemia. This augmented hypervolemia teleologically offsets blood loss with vaginal delivery of twins, which is twice that with a single fetus.

Women carrying twins also have a typical pattern of arterial blood pressure change. MacDonald-Wallis and coworkers (2012) analyzed serial blood pressures in more than 13,000 singleton and twin pregnancies. As early as 8 weeks’ gestation, the diastolic blood pressure in women with twins was lower than that with singleton pregnancies but generally increased to a greater degree at term. In an earlier study, Campbell (1986) demonstrated that this increase was at least 15 mm Hg in 95 percent of women with twins compared with only 54 percent of women with a singleton.

Hypervolemia along with decreased vascular resistance has an impressive affect on cardiac function. Kametas and associates (2003) assessed function in 119 women with a twin pregnancy. In these women, cardiac output was increased another 20 percent above that in women with a singleton pregnancy. Kuleva and colleagues (2011) compared serial echocardiography results in 20 women with uncomplicated twin pregnancies with those of 10 women with singletons. Similarly, they also demonstrated a greater increase in cardiac output in those with twins. Both studies found the cardiac output rise was predominantly due to greater stroke volume and to a much lesser degree due to increased heart rate. Vascular resistance was significantly lower in twin gestations throughout pregnancy compared with singleton gestations (Kuleva, 2011).

Uterine growth in a multifetal gestation is substantively greater than in a singleton pregnancy. The uterus and its nonfetal contents may achieve a volume of 10 L or more and weigh in excess of 20 pounds. Especially with monozygotic twins, excessive amounts of amnionic fluid may rapidly accumulate. In these circumstances, maternal abdominal viscera and lungs can be appreciably compressed and displaced by the expanding uterus. As a result, the size and weight of the large uterus may preclude more than a sedentary existence for these women.

If hydramnios develops, maternal renal function can become seriously impaired, most likely as the consequence of obstructive uropathy (Quigley, 1977). With severe hydramnios, therapeutic amniocentesis may provide relief for the mother, may improve obstructive uropathy, and possibly may lower the preterm delivery risk that follows preterm labor or prematurely ruptured membranes (Chap. 11p. 236). Unfortunately, hydramnios is often characterized by acute onset remote from term and by rapid reaccumulation following amniocentesis.


image Spontaneous Abortion

Miscarriage is more likely with multiple fetuses. During a 16-year study, Joo and colleagues (2012) demonstrated that the spontaneous abortion rate per live birth in singleton pregnancies was 0.9 percent compared with 7.3 percent in multiple pregnancies. Furthermore, they found that monochorial placentation was more common in multiple gestations ending in miscarriage than in those resulting in a livebirth. Twin pregnancies achieved through ART are at increased risk for abortion compared with those conceived spontaneously (Szymusik, 2012).

image Congenital Malformations

The incidence of congenital malformations is appreciably increased in multifetal gestations compared with singletons. Glinianaia and associates (2008) reported that the rate of congenital malformations was 406 per 10,000 twins versus 238 per 10,000 singletons. In this survey-based study, the malformation rate in monochorionic twins was almost twice that of dichorionic twin gestations. This increase has been attributed to the high incidence of structural defects in monozygotic twins. But from a 30-year European registry of multifetal births, Boyle and coworkers (2013) found a steady increase in structural anomalies from 1987 (2.16 percent) to 2007 (3.26 percent). During this time, the proportion of dizygotic twins increased by 30 percent, while the proportion of monozygotic twins remained stable. This higher risk of congenital malformations in dizygotic twins over time correlates with increased availability of ART. An increase in birth defects related to ART has been reported repeatedly (Talauliker, 2012).

image Low Birthweight

Multifetal gestations are more likely to be low birthweight than singleton pregnancies due to restricted fetal growth and preterm delivery. From 1988 to 2012 at Parkland Hospital, data were collected from 357,205 singleton neonates without malformations and from 3714 normal twins who were both liveborn. Birthweights in twin infants closely paralleled those of singletons until 28 to 30 weeks’ gestation. Thereafter, twin birthweights progressively lagged (Fig. 45-8). Beginning at 35 to 36 weeks, twin birthweights clearly diverge from those of singletons.


FIGURE 45-8 Birthweight percentiles (25th to 75th) for 357,205 singleton neonates compared with the 50th birthweight percentile for 3714 twins, Parkland Hospital 1988—2012. Infants with major malformations, pregnancies complicated by stillbirth, and twin gestations with > 25 percent discordance were excluded. (Data courtesy of Dr. Don McIntire.)

In general, the degree of growth restriction increases with fetal number. The caveat is that this assessment is based on growth curves established for singletons. Several authorities argue that fetal growth in twins is different from that of singleton pregnancies, and thus abnormal growth should be diagnosed only when fetal size is less than expected for multifetal gestation. Accordingly, twin and triplet growth curves have been developed (Kim, 2010; Odibo, 2013; Vora, 2006).

The degree of growth restriction in monozygotic twins is likely to be greater than that in dizygotic pairs (Fig. 45-9). With monochorionic embryos, allocation of blastomeres may not be equal, vascular anastomoses within the placenta may cause unequal distribution of nutrients and oxygen, and discordant structural anomalies resulting from the twinning event itself may affect growth. For example, the quintuplets shown in Figure 45-10 represent three dizygotic and two monozygotic fetuses. When delivered at 31 weeks, the three neonates from separate ova weighed 1420, 1530, and 1440 g, whereas the two derived from the same ovum weighed 990 and 860 g.


FIGURE 45-9 Marked growth discordance in monochorionic twins. (Photograph contributed by Dr. Laura Greer.)


FIGURE 45-10 Davis quintuplets at 3 weeks following delivery. The first, second, and fourth newborns from the left each arose from separate ova, whereas the third and fifth neonates are from the same ovum.

In the third trimester, the larger fetal mass leads to accelerated placental maturation and relative placental insufficiency. In dizygotic pregnancies, marked size discordancy usually results from unequal placentation, with one placental site receiving more perfusion than the other. Size differences may also reflect different genetic fetal-growth potentials. Discordancy can also result from fetal malformations, genetic syndromes, infection, or umbilical cord abnormalities such as velamentous insertion, marginal insertion, or vasa previa (Chap. 6p. 122).

image Hypertension

Hypertensive disorders due to pregnancy are more likely to develop with multiple fetuses. The exact incidence attributable to twin gestation is difficult to determine because twin pregnancies are more likely to deliver preterm before preeclampsia can develop and because women with twin pregnancies are often older and multiparous. The incidence of pregnancy-related hypertension in women with twins is 20 percent at Parkland Hospital. In their analysis of 513 twin pregnancies > 20 weeks’ gestation, Fox and coworkers (2014) also identified 20 percent of parturients with either gestational hypertension or preeclampsia. Case-control analyses suggest that prepregnancy body mass index (BMI) ≥ 30 kg/m2 and egg donation are additional independent risk factors for preeclampsia. Gonzalez and colleagues (2012) compared 257 women with twins and gestational diabetes with 277 nondiabetic women carrying twins. These researchers found a twofold increased risk of preeclampsia in women diagnosed with gestational diabetes. Finally, in the Matched Multiple Birth Dataset for the National Center for Health Statistics, Luke and associates (2008) analyzed 316,696 twin, 12,193 triplet, and 778 quadruple pregnancies. These investigators found that the risk for pregnancy-associated hypertension was significantly increased for triplets and quadruplets (11 and 12 percent, respectively) compared with that for twins (8 percent).

These data suggest that fetal number and placental mass are involved in preeclampsia pathogenesis. Women with twin pregnancies have levels of antiangiogenic soluble fms-like tyrosine kinase-1 (sFlt-1) that are twice that of singletons. Levels are seemingly related to increased placental mass rather than primary placental pathology (Bdolah, 2008; Maynard, 2008). Rana and coworkers (2012) measured antiangiogenic sFlt-1 and proangiogenic placental growth factor (PlGF) in 79 women with twins referred for evaluation of preeclampsia. In the 58 women identified with either gestational hypertension or preeclampsia, there was a stepwise increase in sFlt-1 concentrations, decrease in PlGF levels, and increase in sFlt-1/PlGF ratios compared with normotensive twin pregnancies. With multifetal gestation, hypertension not only develops more often but also tends to develop earlier and be more severe. In the analysis of angiogenic factors mentioned above, more than one half presented before 34 weeks, and in those who did, the sFlt-1/PlGF ratio rise was more striking (Rana, 2012). This relationship is discussed in Chapter 40 (p. 735).

image Preterm Birth

The duration of gestation decreases with increasing fetal number (Fig. 45-11). According to Martin and colleagues (2012), more than five of every 10 twins and nine of 10 triplets born in the United States in 2010 were delivered preterm. Delivery before term is a major reason for increased neonatal morbidity and mortality rates in multifetal pregnancy. Prematurity is increased sixfold and tenfold in twins and triplets, respectively (Giuffre, 2012). In their review, Chauhan and associates (2010) reported that, similar to singleton pregnancies, approximately 60 percent of preterm births in twins are indicated, about a third result from spontaneous labor, and 10 percent follow prematurely ruptured membranes. In their analysis of almost 300,000 live births in Ohio, Pakrashi and DeFranco (2013) found that the proportion of preterm birth associated with premature membrane rupture increased with gestational plurality from 13 percent with singletons to 20 percent with triplets or more.


FIGURE 45-11 Cumulative percent of singleton, twin, and triplet or higher-order multifetal births according to gestational age at delivery in the United States during 1990. (From Luke, 1994, with permission.)

The preterm birth rate among multifetal gestations has increased during the past two decades. In an analysis of nearly 350,000 twin births, Kogan and coworkers (2000) showed that during the 16-year period ending in 1997, the term birth rate among twins declined by 22 percent. Joseph and colleagues (2001) attributed this decline to an increased rate of indicated preterm deliveries. This trend is not necessarily negative, as it was associated with decreased perinatal morbidity and mortality rates among twins that reached 34 weeks. Although the causes of preterm delivery in twins and singletons may be different, neonatal outcome is generally the same at similar gestational ages (Gardner, 1995; Kilpatrick, 1996; Ray, 2009). Importantly, outcomes for preterm twins who are markedly discordant may not be comparable with those for singletons because whatever caused the discordance may have long-lasting effects.

image Prolonged Pregnancy

More than 40 years ago, Bennett and Dunn (1969) suggested that a twin pregnancy of 40 weeks or more should be considered postterm. Twin stillborn neonates delivered at 40 weeks or beyond commonly had features similar to those of postmature singletons (Chap. 43p. 864). From an analysis of almost 300,000 twin births, Kahn and coworkers (2003) calculated that at and beyond 39 weeks, the risk of subsequent stillbirth was greater than the risk of neonatal mortality. At Parkland Hospital, twin gestations have empirically been considered to be prolonged at 40 weeks.

image Long-Term Infant Development

Historically, twins have been considered cognitively delayed compared with singletons (Record, 1970; Ronalds, 2005). However, in cohort studies evaluating normal-birthweight term infants, cognitive outcomes between twins and singletons are similar (Lorenz, 2012). Christensen and associates (2006) found similar national standardized test scores in ninth grade in 3411 twins and 7796 singletons born between 1986 and 1988. In contrast, among normal-birthweight infants, the cerebral palsy risk is higher among twins and higher-order multiples. For example, the cerebral palsy rate has been reported to be 2.3 per 1000 in singletons, 12.6 per 1000 in twins, and 44.8 per 1000 in triplets (Giuffre, 2012). Much of this excess risk is thought to be related to an increased risk of fetal-growth restriction, congenital anomalies, twin-twin transfusion syndrome, and fetal demise of a cotwin (Lorenz, 2012).


Several unique and fascinating complications arise in multifetal pregnancies. These have been best described in twins but can be found in higher-order multifetal gestations. Most fetal complications due to the twinning process itself are seen with monozygotic twins. Their pathogenesis is best understood after reviewing the possibilities shown in Figure 45-1.

image Monoamnionic Twins

Only about 1 percent of all monozygotic twins will share an amnionic sac (Hall, 2003). Said another way, approximately 1 in 20 monochorionic twins are monoamnionic (Lewi, 2013). This configuration is associated with a high fetal death rate from cord entanglement, congenital anomalies, preterm birth, or twin-twin-transfusion syndrome, which is described subsequently. In a comprehensive review, Allen and associates (2001) reported that monoamnionic twins diagnosed antenatally and alive at 20 weeks have approximately a 10-percent risk of subsequent fetal demise. In a Dutch report of 98 monoamnionic twin pregnancies, the perinatal mortality rate was 17 percent (Hack, 2009). Umbilical cord entanglement, a frequent cause of death, is estimated to complicate at least half of cases (Fig. 45-12). Diamnionic twins can become monoamnionic if the dividing membrane ruptures and therefore have similar associated morbidity and mortality rates.


FIGURE 45-12 Monozygotic twins in a single amnionic sac. The smaller fetus apparently died first, and the second subsequently succumbed when umbilical cords entwined.

Unfortunately, there are no management methods that guarantee good outcomes for either or both twins. This is because of the unpredictability of fetal death from cord entanglement and the lack of an effective means of monitoring for it. Quinn and colleagues (2011) retrospectively evaluated the feasibility of inpatient continuous fetal heart monitoring in 17 sets of monoamnionic twins. After review of more than 10,000 hours of fetal tracing, these investigators concluded that this was possible in only 50 percent of cases. Importantly, an abnormal fetal heart rate tracing prompted delivery in only six cases. Morbid cord entanglement appears to occur early, and monoamnionic pregnancies that have successfully reached 30 to 32 weeks are at reduced risk. In the Dutch series described above, the incidence of intrauterine demise dropped from 15 percent after 20 weeks to 4 percent when gestational age exceeded 32 weeks (Hack, 2009).

Although umbilical cords frequently entangle, factors that lead to pathological umbilical vessel constriction are unknown. Color-flow Doppler sonography can be used to diagnose entanglement (Fig. 45-13). However, once identified, evidence to guide management is observational, retrospective, and subject to biased reporting. One proposed management scheme is based on a study by Heyborne and coworkers (2005), who reported no stillbirths in 43 twin pregnancies of women admitted at 26 to 27 weeks’ gestation for daily fetal surveillance. Conversely, there were 13 stillbirths in 44 women who were managed as outpatients and admitted only for an obstetrical indication. Because of this report, women with monoamnionic twins are recommended to undergo 1 hour of daily fetal heart rate monitoring, either as outpatients or as inpatients, beginning at 26 to 28 weeks. With initial testing, a course of betamethasone is given to promote pulmonary maturation (Chap. 42p. 850). If fetal testing remains reassuring, cesarean delivery is performed at 34 weeks and after a second course of betamethasone. This management scheme is used at Parkland Hospital and resulted in the successful 34-week delivery of the twins depicted in Figure 45-13.


FIGURE 45-13 Monochorionic monoamnionic cord entanglement. A. Despite marked knotting of the cords, vigorous twins were delivered by cesarean. B. Preoperative sonogram of this pregnancy shows entwined cords. C. This finding is accentuated with application of color Doppler. (Photographs contributed by Dr. Julie Lo.)

image Aberrant Twinning Mechanisms

Several aberrations in the twinning process result in a spectrum of fetal malformations. These are traditionally ascribed to incomplete splitting of an embryo into two separate twins. However, it is possible that they may result from early secondary fusion of two separate embryos. These separated embryos are either symmetrical or asymmetrical, and the spectrum of anomalies is shown in Figure 45-14.


FIGURE 45-14 Possible outcomes of monozygotic twinning. The asymmetrical category contains twinning types in which one twin complement is substantially smaller and incompletely formed.

Conjoined Twins

In the United States, united or conjoined twins have been referred to as Siamese twins–after Chang and Eng Bunker of Siam (Thailand), who were displayed worldwide by P. T. Barnum. Joining of the twins may begin at either pole and may produce characteristic forms depending on which body parts are joined or shared (Fig. 45-15). Of these, thoracopagus is the most common (Mutchinick, 2011). The frequency of conjoined twins is not well established. At Kandang Kerbau Hospital in Singapore, Tan and coworkers (1971) identified seven cases of conjoined twins among more than 400,000 deliveries–an incidence of 1 in 60,000.


FIGURE 45-15 Types of conjoined twins. (Redrawn from Spencer, 2000.)

As reviewed by McHugh and associates (2006), conjoined twins can frequently be identified using sonography at midpregnancy. This provides an opportunity for parents to decide whether to continue the pregnancy. As shown in Figure 45-16, identification of cases during the first trimester is also possible. A targeted examination, including a careful evaluation of the connection and the organs involved, is necessary before counseling can be provided. As shown in Figure 45-17, MR imaging can play an important adjunctive role in clarifying shared organs. Compared with sonography, MR imaging may provide superior views, especially in later pregnancy when amnionic fluid is diminished and fetal crowding is increased (Hibbeln, 2012).


FIGURE 45-16 Sonogram of a conjoined twin pregnancy at 13 weeks’ gestation. These thoracoomphalopagus twins have two heads but a shared chest and abdomen.


FIGURE 45-17 Magnetic resonance imaging of conjoined twins. This T2-weighted HASTE sagittal image demonstrates fusion from the level of the xiphoid process to just below the level of the umbilicus, that is, omphalopagus twins. Below the fused liver (L), there is a midline cystic mass (arrow) within the tissue connecting the twins. An omphalomesenteric cyst was favored given the location within the shared tissue. (Image contributed by Dr. April Bailey.)

Surgical separation of an almost completely joined twin pair may be successful if essential organs are not shared (Spitz, 2003; Tannuri, 2013). Consultation with a pediatric surgeon often assists parental decision making. Conjoined twins may have discordant structural anomalies that further complicate decisions about whether to continue the pregnancy.

Viable conjoined twins should be delivered by cesarean. For the purpose of pregnancy termination, however, vaginal delivery is possible because the union is most often pliable (Fig. 45-18). Still, dystocia is common, and if the fetuses are mature, vaginal delivery may be traumatic to the uterus or cervix.


FIGURE 45-18 Conjoined twins aborted at 17 weeks’ gestation. (Photograph contributed by Dr. Jonathan Willms.)

External Parasitic Twins

This is a grossly defective fetus or merely fetal parts, attached externally to a relatively normal twin. A parasitic twin usually consists of externally attached supernumerary limbs, often with some viscera. Classically, however, a functional heart or brain is absent. Attachment mirrors those sites described earlier for conjoined twins (see Fig. 45-14). Parasites are believed to result from demise of the defective twin, with its surviving tissues attached to and vascularized by its normal twin (Spencer, 2001). In a worldwide collaborative epidemiological study, parasitic twins were found to account for 3.9 percent of all conjoined twins and to occur more frequently in male fetuses (Mutchinick, 2011).


Early in development, one embryo may be enfolded within its twin. Normal development of this rare parasitic twin usually arrests in the first trimester. As a result, normal spatial arrangement of and presence of many organs is lost. Classically, vertebral or axial bones are found in these fetiform masses, whereas heart and brain are lacking. These masses are typically supported by their host by a few large parasitic vessels (Spencer, 2000). Malignant degeneration is rare (Kaufman, 2007).

image Monochorionic Twins and Vascular Anastomoses

Another group of fascinating fetal syndromes can arise when monozygotic twinning results in two amnionic sacs and a common surrounding chorion. This leads to anatomical sharing of the two fetal circulations through anastomoses of placental arteries and veins. All monochorionic placentas likely share some anastomotic connections. However, there are marked variations in the number, size, and direction of these seemingly haphazard connections (Fig. 45-19). In their analyses of more than 200 monochorionic placentas, Zhao and colleagues (2013) found the median number of anastomoses to be 8 with an interquartile range of 4 to 14. With rare exceptions, anastomoses between twins are unique to monochorionic twin placentas.


FIGURE 45-19 Shared placenta from pregnancy complicated by twin-twin transfusion syndrome. The following color code was applied for injection. Left twin: yellow = artery, blue = vein; right twin: red = artery, green = vein. A.Part of the arterial network of the right twin is filled with yellow dye, due to the presence of a small artery-to-artery anastomosis (arrow). B. Close-up of the lower portion of the placenta displays the yellow dye-filled anastomosis. (From De Paepe, 2005, with permission.)

Artery-to-artery anastomoses are most common and are identified on the chorionic surface of the placenta in up to 75 percent of monochorionic twin placentas. Vein-to-vein and artery-to-vein communications are each found in approximately half. One vessel may have several connections, sometimes to both arteries and veins. In contrast to these superficial vascular connections on the surface of the chorion, deep artery-to-vein communications can extend through the capillary bed of a given villus (Fig. 45-20). These deep arteriovenous anastomoses create a common villous compartment or third circulation that has been identified in approximately half of monochorionic twin placentas.


FIGURE 45-20 Anastomoses between twins may be artery-to-vein (AV), artery-to-artery (AA), or vein-to-vein (VV). Schematic representation of an AV anastomosis in twin-twin transfusion syndrome that forms a “common villous district” or “third circulation” deep within the villous tissue. Blood from a donor twin may be transferred to a recipient twin through this shared circulation. This transfer leads to a growth-restricted discordant donor twin with markedly reduced amnionic fluid, causing it to be “stuck.”

Whether these anastomoses are dangerous to either twin depends on the degree to which they are hemodynamically balanced. In those with significant pressure or flow gradients, a shunt will develop between fetuses. This chronic fetofetal transfusion may result in several clinical syndromes that include twin-twin transfusion syndrome (TTTS), twin anemia polycythemia sequence (TAPS), and acardiac twinning.

Twin-Twin Transfusion Syndrome (TTTS)

The prevalence of this condition is approximately 1 to 3 per 10,000 births (Simpson, 2013). In this syndrome, blood is transfused from a donor twin to its recipient sibling such that the donor may eventually become anemic and its growth may be restricted. In contrast, the recipient becomes polycythemic and may develop circulatory overload manifest as hydrops. The donor twin is pale, and its recipient sibling is plethoric (Fig. 45-21). Similarly, one portion of the placenta often appears pale compared with the remainder.


FIGURE 45-21 Twin-twin transfusion syndrome at 23 weeks. A. Pale donor twin (690 g) also had oligohydramnios. B. The plethoric recipient twin (730 g) had hydramnios. (From Mahone, 1993, with permission.)

The recipient neonate may have circulatory overload from heart failure and severe hypervolemia and hyperviscosity. Occlusive thrombosis is another concern. Finally, polycythemia in the recipient twin may lead to severe hyperbilirubinemia and kernicterus (Chap. 33p. 644).

Pathophysiology. Any of the different types of vascular anastomoses discussed before may be found with monochorionic placentas. Classically, chronic TTTS results from unidirectional flow through arteriovenous anastomoses. Deoxygenated blood from a donor placental artery is pumped into a cotyledon shared by the recipient (see Fig. 45-20). Once oxygen exchange is completed in the chorionic villus, the oxygenated blood leaves the cotyledon via a placental vein of the recipient twin. Unless compensated—typically through arterioarterial anastomoses—this unidirectional flow leads to an imbalance in blood volumes (Lewi, 2013).

Clinically important twin-twin transfusion syndrome frequently is chronic and results from significant vascular volume differences between the twins. Even so, the pathogenesis is more complex than a net transfer of red blood cells from one twin to another. Indeed, in most monochorionic twin pregnancies complicated by the syndrome, there is no difference in hemoglobin concentrations between the donor and recipient twin (Lewi, 2013).

The syndrome typically presents in midpregnancy when the donor fetus becomes oliguric from decreased renal perfusion (Simpson, 2013). This fetus develops oligohydramnios, and the recipient fetus develops severe hydramnios, presumably due to increased urine production. Virtual absence of amnionic fluid in the donor sac prevents fetal motion, giving rise to the descriptive term stuck twin or polyhydramnios-oligohydramnios–syndrome—“poly-oli.” This amnionic fluid imbalance is associated with growth restriction, contractures, and pulmonary hypoplasia in the donor twin, and premature rupture of the membranes and heart failure in the recipient.

Fetal Brain Damage. Cerebral palsy, microcephaly, porencephaly, and multicystic encephalomalacia are serious complications associated with placental vascular anastomoses in multifetal gestation. The exact pathogenesis of neurological damage is not fully understood but is likely caused by ischemic necrosis leading to cavitary brain lesions (Fig. 45-22). In the donor twin, ischemia results from hypotension, anemia, or both. In the recipient, ischemia develops from blood pressure instability and episodes of severe hypotension (Lopriore, 2011). Cerebral lesions may also be due to postnatal injury associated with preterm delivery. Quarello and associates (2007) reviewed data from 315 liveborn fetuses from pregnancies with twin-twin-transfusion syndrome and reported cerebral abnormalities in 8 percent.


FIGURE 45-22 Cranial magnetic resonance imaging study of a diamnionic–monochorionic twin performed on day 2 of life. The subarachnoid space and lateral ventricles are markedly enlarged. There are large cavitary lesions in the white matter adjacent to the ventricles. The bright signals (arrowheads) in the periphery of the cavitary lesions most probably correspond to gliosis. (From Bejar, 1990, with permission.)

If one twin of an affected pregnancy dies, cerebral pathology in the survivor probably results from acute hypotension. A less likely cause is emboli of thromboplastic material originating from the dead fetus. Fusi and coworkers (1990, 1991) observed that with the death of one twin, acute twin-twin anastomotic transfusion from the high-pressure vessels of the living twin to the low-resistance vessels of the dead twin leads rapidly to hypovolemia and ischemic antenatal brain damage in the survivor. In their systematic review of 343 twin pregnancies complicated by single fetal demise, Hillman and colleagues (2011) calculated a 26-percent risk of neurodevelopmental morbidity in monochorionic twins compared with 2 percent in dichorionic twins. They also found that this morbidity was related to gestational age at the death of the cotwin. If the death occurred between 28 and 33 weeks’ gestation, monochorionic twins had an almost eightfold risk of neurodevelopmental morbidity compared with dichorionic twins of the same gestational age. With fetal death after 34 weeks, the likelihood dramatically decreased—odds ratio 1.48.

The acuity of hypotension following the death of one twin with twin-twin-transfusion syndrome makes successful intervention for the survivor nearly impossible. Even with delivery immediately after a cotwin demise is recognized, the hypotension that occurs at the moment of death has likely already caused irreversible brain damage (Langer, 1997; Wada, 1998).

Diagnosis. There have been dramatic changes in the criteria used to diagnose and classify varying severities of twin-twin transfusion syndrome. Previously, weight discordancy and hemoglobin differences in monochorionic twins were calculated. However, it was soon appreciated that in many cases these were late-onset findings. According to the Society for Maternal-Fetal Medicine (2013), TTTS is diagnosed based on two criteria: (1) presence of a monochorionic diamnionic pregnancy, and (2) hydramnios defined if the largest vertical pocket is > 8 cm in one twin and oligohydramnios defined if the largest vertical pocket is < 2 cm in the other twin. Only 15 percent of pregnancies complicated by lesser degrees of fluid imbalance progress to TTTS (Huber, 2006).

Once identified, TTTS is typically staged by the Quintero (1999) staging system:

• Stage I—discordant amnionic fluid volumes as described above, but urine is still visible sonographically within the bladder of the donor twin.

• Stage II—criteria of stage I, but urine is not visible within the donor bladder.

• Stage III—criteria of stage II and abnormal Doppler studies of the umbilical artery, ductus venosus, or umbilical vein.

• Stage IV—ascites or frank hydrops in either twin.

• Stage V—demise of either fetus.

In addition to these criteria, there is evidence that cardiac function of the recipient twin correlates with fetal outcome (Crombleholme, 2007). Although fetal echocardiographic findings are not part of the staging system above, many centers routinely perform fetal echocardiography for TTTS. It has been theorized that early diagnosis of cardiomyopathy in the recipient twin may identify pregnancies that would benefit from early intervention. One system for evaluating cardiac function—the myocardial performance index (MPI) or Tei index—is a Doppler index of ventricular function calculated for each ventricle (Michelfelder, 2007). Although scoring systems that include assessment of cardiac function have been developed, their usefulness in prediction of outcomes remains controversial (Simpson, 2013).

At Parkland Memorial Hospital, evaluation before and during treatment includes anatomical and neurological fetal assessment using echocardiography, MPI calculation, Doppler velocimetry, and MR imaging; genetic counseling and amniocentesis; and placental mapping.

Management and Prognosis. The prognosis for multifetal gestations complicated by TTTS is related to Quintero stage and gestational age at presentation. More than three fourths of stage I cases remain stable or regress without intervention. Conversely, outcomes in those identified at stage III or higher are much worse, and the perinatal loss rate is 70 to 100 percent without intervention (Simpson, 2013). Several therapies are currently used for TTTS, including amnioreduction, laser ablation of vascular anastomoses, selective feticide, and septostomy (intentional creation of a communication in the dividing amnionic membrane). Comparative data from randomized trials for some of these techniques are discussed below.

The Eurofetus trial included 142 women with severe TTTS diagnosed before 26 weeks. Participants were randomly assigned to laser ablation of vascular anastomoses or to serial amnioreduction (Senat, 2004). These investigators reported an increased survival rate to age 6 months for at least one twin with laser ablation compared with serial amnioreduction–76 versus 51 percent, respectively. Moreover, analyses of randomized studies confirm better neonatal outcomes with laser therapy compared with selective amnioreduction (Roberts, 2008; Rossi, 2008, 2009). In contrast, Crombleholme and associates (2007), in a randomized trial of 42 women, found equivalent rates of 30-day survival of one or both twins treated with either amnioreduction or selective fetoscopic laser ablation–75 versus 65 percent, respectively. Furthermore, evaluation of twins from the Eurofetus trial through 6 years of age did not demonstrate any additional survival benefit beyond 6 months or improved neurological outcomes in those treated with laser (Salomon, 2010).

At this time, laser ablation of anastomoses is preferred for severe TTTS (stages II-IV), although optimal therapy for stage I disease is controversial. After laser therapy, close ongoing surveillance is necessary. Robyr and colleagues (2006) reported that a fourth of 101 pregnancies treated with laser required additional invasive therapy because of either recurrent TTTS, or middle cerebral artery Doppler evidence of anemia or polycythemia. Recently, in a comparison of selective laser ablation of individual anastomoses versus ablation of the entire surface of chorionic plate along the vascular equator, Baschat and coworkers (2013) found that equatorial photocoagulation reduced the likelihood of recurrence.

Moise and associates (2005) compared amnioreduction and septostomy in a multicentered randomized trial of 73 women. Repeated procedures were performed for symptoms or if the greatest vertical pocket of amnionic fluid met the original inclusion criteria of 8 to 12 cm, depending on gestational age. Perinatal outcomes were the same in each group, with at least one survivor in 80 percent of pregnancies. The average number of additional procedures was two in each group. Much of this is moot, however, because intentional septostomy has largely been abandoned as treatment (Simpson, 2013).

Selective reduction has generally been considered if severe amnionic fluid and growth disturbances develop before 20 weeks. In such cases, both fetuses typically will die without intervention. Selection of which twin is to be terminated is based on evidence of damage to either fetus and comparison of their prognoses. Any substance injected into one twin may affect the other twin because of shared circulations. Therefore, feticidal techniques include methods to occlude the circulation of the chosen fetal umbilical vein or by umbilical cord occlusion using radiofrequency ablation, fetoscopic ligation, or coagulation with laser, monopolar, or bipolar cauterization (Challis, 1999; Chang, 2009; Donner, 1997). Even after these procedures, however, the risks to the remaining fetus are still appreciable (Rossi, 2009).

Twin Anemia Polycythemia Sequence (TAPS)

This form of chronic fetofetal transfusion is characterized by significant hemoglobin differences between donor and recipient twins without the discrepancies in amnionic fluid volumes typical of twin-twin-transfusion syndrome (Slaghekke, 2010). It is diagnosed antenatally by middle cerebral artery (MCA) peak systolic velocity (PSV) > 1.5 multiples of the median (MoM) in the donor and < 1.0 MoM in the recipient twin (Simpson, 2013). The spontaneous form reportedly complicates 3 to 5 percent of monochorionic pregnancies, and it occurs in up to 13 percent of pregnancies after laser photocoagulation. Spontaneous TAPS usually occurs after 26 weeks and iatrogenic TAPS develops within 5 weeks of a procedure (Lewi, 2013). Although a staging system has been proposed by Slaghekke and colleagues (2010), further studies are necessary to better understand the natural history of TAPS and its management.

Twin-Reversed Arterial Perfusion (TRAP) Sequence

Also known as an acardiac twin, this is a rare—1 in 35,000 births—but serious complication of monochorionic multifetal gestation. In the TRAP sequence, there is usually a normally formed donor twin that has features of heart failure and a recipient twin that lacks a heart (acardius) and other structures. It has been hypothesized that the TRAP sequence is caused by a large artery-to-artery placental shunt, often also accompanied by a vein-to-vein shunt (Fig. 45-23). Within the single, shared placenta, arterial perfusion pressure of the donor twin exceeds that in the recipient twin, who thus receives reverse blood flow of deoxygenated arterial blood from its cotwin (Lewi, 2013). This “used” arterial blood reaches the recipient twin through its umbilical arteries and preferentially goes to its iliac vessels. Thus, only the lower body is perfused, and disrupted growth and development of the upper body results. Failure of head growth is called acardius acephalus; a partially developed head with identifiable limbs is called acardius myelacephalus; and failure of any recognizable structure to form is acardius amorphous, which is shown in Figure 45-24 (Faye-Petersen, 2006). Because of this vascular connection, the normal donor twin must not only support its own circulation but also pump its blood through the underdeveloped acardiac recipient. This may lead to cardiomegaly and high-output heart failure in the normal twin (Fox, 2007).


FIGURE 45-23 Twin reversed-arterial-perfusion sequence. In the TRAP sequence, there is usually a normally formed donor twin that has features of heart failure, and a recipient twin that lacks a heart. It has been hypothesized that the TRAP sequence is caused by a large artery-to-artery placental shunt, often also accompanied by a vein-to-vein shunt. Within the single, shared placenta, perfusion pressure of the donor twin overpowers that in the recipient twin, who thus receives reverse blood flow from its twin sibling. The “used” arterial blood (colored blue) that reaches the recipient twin preferentially goes to its iliac vessels and thus perfuses only the lower body. This disrupts growth and development of the upper body.


FIGURE 45-24 Photograph of an acardiac twin weighing 475 grams. The underdeveloped head is indicated by the black arrow, and its details are shown in the inset. A yellow clamp is seen on its umbilical cord. Its viable donor cotwin was delivered vaginally at 36 weeks and weighed 2325 grams. (Photograph contributed by Dr. Michael D. Hnat.)

Lewi and coworkers (2010) reviewed 26 cases of TRAP sequence identified in the first trimester. In one third, the pump twin died before planned intervention at 16 to 18 weeks. In more than half of all the cases, there was spontaneous cessation of flow to the acardiac twin, and such flow arrest was associated with subsequent death or neurological injury in 85 percent of the normal twins. Quintero and associates (1994, 2006) have reviewed methods of in utero treatment of acardiac twinning in which the goal is interruption of aberrant vascular communication between the twins. Of these methods, Lee (2007), Lewi (2010), Livingston (2007), and their colleagues found an approximate 90-percent survival rate following second-trimester radiofrequency ablation. This method cauterizes umbilical vessels in the malformed recipient twin to terminate blood flow from the donor. In a review of 118 complicated monochorionic twin gestations that underwent bipolar cord coagulation, Lanna and associates (2012) reported a fetal loss rate in those treated before 19 weeks of 45 percent compared with 3 percent in those treated after 19 weeks. Prompted by the high mortality rate of TRAP sequence in the first trimester, small case series of early intervention have been reported (O’Donoghue, 2008; Scheier, 2012). Importantly, efficacy and safety of intervention before fusion of the amnion and chorion has not been demonstrated convincingly (Lewi, 2013).

image Complete Hydatidiform Mole with Coexisting Normal Fetus

Also termed a twin molar pregnancy, this is due to a complete diploid molar pregnancy comprising one conceptus, whereas the cotwin is a normal fetus. Reported prevalence rates range from 1 in 22,000 to 1 in 100,000 pregnancies (Dolapcioglu, 2009). It must be differentiated from a partial molar pregnancy in which an anomalous singleton fetus—usually triploid—is accompanied by molar tissue (Chap. 20p. 398).

Optimal management is not known for this twin gestation. Diagnosis is usually made in the first half of pregnancy, and termination at that time would remove the mole but also the normal fetus. However, pregnancy progression exposes the woman to the later postpartum dangers of persistent trophoblastic disease that requires chemotherapy and may be fatal. Despite this, pregnancy continuation is increasingly being recommended in cases with a karyotypically normal and nonanomalous twin, no early preeclampsia, and declining hCG levels (Sebire, 2002).

If observation and pregnancy progression is chosen, preterm delivery is frequently required because of persistent and heavy bleeding or severe preeclampsia. Dolapcioglu and coworkers (2009) reviewed 159 reported cases and reported a live birth in 35 percent. Preeclampsia and preterm birth each developed in a third. Niemann and colleagues (2007) reported that persistent trophoblastic disease rates following such a twin gestation were not increased compared with those after a singleton complete mole.


Size inequality of twin fetuses, which can be a sign of pathological growth restriction in one fetus, is calculated using the larger twin as the index. Generally, as the weight difference within a twin pair increases, the perinatal mortality rate increases proportionately. Because the single placenta is not always equally shared in monochorionic twins, these twins have greater rates of discordant growth outside of TTTS than dichorionic twins. It develops in approximately 15 percent of twin gestations (Lewi, 2013; Miller, 2012). As discussed further in Chapter 44 (p. 879), restricted growth of one twin fetus usually develops late in the second and early third trimester. Earlier discordancy indicates higher risk for fetal demise in the smaller twin. Specifically, when discordant growth is identified before 20 weeks, fetal death occurs in about 20 percent (Lewi, 2013). Importantly, differences in crown-rump length (CRL) are associated with fetal structural and chromosomal anomalies but are not reliable predictors for birthweight discordance (Miller, 2012).

image Etiopathogenesis

The cause of birthweight inequality in twin fetuses is often unclear, but the etiology in monochorionic twins likely differs from that in dichorionic twins. Discordancy in monochorionic twins is usually attributed to placental vascular anastomoses that cause hemodynamic imbalance between the twins. Reduced pressure and perfusion of the donor twin can cause diminished placental and fetal growth. Even so, unequal placental sharing is probably the most important determinant of discordant growth in monochorionic twins (Lewi, 2013). Occasionally, monochorionic twins are discordant in size because they are discordant for structural anomalies.

Discordancy in dichorionic twins may result from various factors. Dizygotic fetuses may have different genetic growth potential, especially if they are of opposite genders. Alternatively, because the placentas are separate and require more implantation space, one placenta might have a suboptimal implantation site. Bagchi and associates (2006) observed that the incidence of severe discordancy is twice as great in triplets as it is in twins. This finding lends credence to the view that in utero crowding is a factor in fetal-growth restriction. Placental pathology may play a role as well. Kent and coworkers (2012) evaluated placental abnormalities in 668 twin gestations. They observed a strong relationship between histological placental abnormalities and birthweight discordancy with associated growth restriction in dichorionic, but not monochorionic, twin pregnancies.

image Diagnosis

Size discordancy between twins can be determined sonographically in several ways. One common method uses sonographic fetal biometry to compute an estimated weight for each twin (Chap. 10p. 198). The weight of the smaller twin is then compared with that of the larger twin. Thus, percent discordancy = weight of larger twin minus weight of smaller twin, divided by weight of larger twin. Alternatively, considering that growth restriction is the primary concern and that abdominal circumference (AC) reflects fetal nutrition, some use the sonographic AC value of each twin. With these methods, some specify discordance if the AC measurements differ more than 20 mm or if the estimated fetal weight difference is 20 percent or more.

That said, several different weight disparities between twins have been used to define discordancy. Accumulated data suggest that weight discordancy greater than 25 to 30 percent most accurately predicts an adverse perinatal outcome. Hollier and coworkers (1999) retrospectively evaluated 1370 twin pairs delivered at Parkland Hospital and stratified twin weight discordancy in 5-percent increments within a range of 15 to 40 percent. They found that the incidence of respiratory distress, intraventricular hemorrhage, seizures, periventricular leukomalacia, sepsis, and necrotizing enterocolitis increased directly with the degree of weight discordancy. These conditions increased substantially if discordancy was greater than 25 percent. The relative risk of fetal death increased significantly to 5.6 if there was more than 30-percent discordancy. It increased to 18.9 if there was greater than 40-percent discordancy.

image Management

Sonographic monitoring of growth within a twin pair and calculating discordancy has become a mainstay in management. Other sonographic findings, such as oligohydramnios, may be helpful in gauging fetal risk. Monochorionic twins are generally monitored more frequently. This is because their risk of death is higher—3.6 percent versus 1.1 percent—and the risk of neurological damage in the surviving twin is substantial compared with those risks in dichorionic twins (Hillman, 2011; Lee, 2008). Thorson and colleagues (2011) retrospectively analyzed 108 monochorionic twin pregnancies and found that a sonographic surveillance interval of greater than 2 weeks was associated with detection of higher-stage twin-twin transfusion syndrome. These findings have led some to recommend serial sonographic surveillance every 2 weeks in monochorionic twins (Simpson, 2013; Society for Maternal-Fetal Medicine, 2013). However, there have been no randomized trials of the optimal frequency of sonographic surveillance in monochorionic twin pregnancies. At Parkland Hospital, monochorionic twins undergo sonographic evaluation to assess interval growth every 4 weeks. Dichorionic twins are evaluated every 6 weeks. Depending on the degree of discordancy and the gestational age, fetal surveillance may be indicated, especially if one or both fetuses exhibit restricted growth. Nonstress testing, biophysical profile scores, and umbilical artery Doppler assessment have all been recommended in the management of twins, but none have been evaluated in appropriately sized prospective trials (Miller, 2012).

The American College of Obstetricians and Gynecologists (2010) recommends that antepartum testing be performed in multifetal gestations for the same indications as in singleton fetuses (Chap 17p. 345). At Parkland Hospital, all women with twin discordance of 25 percent or greater undergo daily monitoring as an inpatient. There are limited data to establish the optimal timing of delivery of twins. Delivery is usually not prompted by size discordancy alone, except occasionally at advanced gestational ages. The Royal College of Obstetricians and Gynecologists (2008) advocates delivery by 37 weeks’ gestation in monochorionic twins and by 38 weeks in dichorionic twins.


At any time during multifetal pregnancy, one or more fetuses may die, either simultaneously or sequentially. The causes and incidence of fetal death are related to zygosity, chorionicity, and growth concordance.

image Death of One Fetus

In some pregnancies, one fetus dies remote from term, but pregnancy continues with one or more live fetuses. When this occurs early in pregnancy, it may manifest as a vanishing twin discussed on page 892. Fetal death in a slightly more advanced gestation may go undetected until delivery of a normal-appearing live infant along with a dead fetus that is barely identifiable. It may be compressed appreciably–fetus compressus, or it may be flattened remarkably through desiccation—fetus papyraceus (Fig. 45-25).


FIGURE 45-25 This fetus papyraceus is a tan ovoid mass compressed against the fetal membranes. Anatomical parts can be identified as marked. Demise of this twin had been noted during sonographic examination performed at 17 weeks’ gestation. Its viable cotwin delivered at 40 weeks. (Photograph contributed by Dr. Michael V. Zaretsky.)

In a review of 9822 Japanese twin pregnancies, Morikawa and associates (2012) reported that 2.5 percent of monochorionic diamnionic twins greater than 22 weeks’ gestation had a death of one or both twins compared with 1.2 percent of dichorionic twins. As shown in Figure 45-26, the risk of stillbirth is related to gestational age in all twins, but is much higher for monochorionic twin pregnancies before 32 weeks. In this same review, women with monochorionic diamnionic twins who lost one twin were 16 times more likely to experience death of the cotwin than women with dichorionic twins who lost one twin (Morikawa, 2012). Similarly, in their analysis of 1094 twin pregnancies, Mahony and associates (2011) identified a threefold increased risk of death of one or both fetuses in monochorionic twins compared with dichorionic pairs. Last, in their systematic review and metaanalyses, Hillman and colleagues (2011) concluded that after one twin dies, the odds of cotwin demise was five times higher in monochorionic twins compared with dichorionic twins experiencing the same fate. Analyses of 701 triplets identified mortality rates to be 2.1 percent, 3.2 percent, and 5.3 percent in trichorionic triamnionic, dichorionic triamnionic, and monochorionic triamnionic triplets, respectively (Kawaguchi, 2013).


FIGURE 45-26 Prospective risk of stillbirth among women who reached a given gestational week (per 1000 women). (From Morikawa, 2012, with permission.)

Other factors that affect the prognosis for the surviving twin include gestational age at the time of the demise and duration between the demise and delivery of the surviving twin. With demise of the vanishing twin discussed earlier, after the first trimester, the risk of death is not increased for the survivor. However, when one fetus dies in the second trimester or later, the effect of gestational age at the time of death and the mortality risk to the cotwin is less clear. In the analysis by Hillman and colleagues (2011), cotwin demise rates were unaffected regardless of whether the first death occurred at 13 to 27 weeks or at 28 to 34 weeks. In cases with the death of one twin after the first trimester, however, the odds of spontaneous and iatrogenic preterm delivery of the remaining living twin were increased (Hillman, 2011). Preterm birth was five times more likely in monochorionic twin gestations complicated by demise of one twin between 28 and 33 weeks’ gestation. If the fetus died after 34 weeks, preterm delivery rates were similar.

The neurological prognosis for a surviving cotwin depends almost exclusively on chorionicity. In their comprehensive review, Ong and coworkers (2006) found an 18-percent rate of neurological abnormality in twins with monochorionic placentation compared with only 1 percent in those with dichorionic placentation. In another review, in twin pregnancies complicated by a single fetal demise before 34 weeks, a fivefold increased risk of neurodevelopmental morbidity was identified in monochorionic twins compared with dichorionic twins. If the one fetus died after 34 weeks, the likelihood of neurological deficits was essentially the same between monochorionic and dichorionic twin pregnancies (Hillman, 2011).

Later in gestation, the death of one of multiple fetuses could theoretically trigger coagulation defects in the mother. Only a few cases of maternal coagulopathy after a single fetal death in a twin pregnancy have been reported. This is probably because the surviving twin is usually delivered within a few weeks of the demise (Eddib, 2006). That said, we have observed transient, spontaneously corrected consumptive coagulopathy in multifetal gestations in which one fetus died and was retained in utero along with its surviving twin. The plasma fibrinogen concentration initially decreased but then increased spontaneously, and the level of serum fibrinogen-fibrin degradation products increased initially but then returned to normal levels. At delivery, the portions of the placenta that supplied the living fetus appeared normal. In contrast, the part that had once provided for the dead fetus was the site of massive fibrin deposition. This is further discussed and illustrated in Chapter 41 (p. 811).


Decisions should be based on gestational age, the cause of death, and the risk to the surviving fetus. As mentioned previously, if the loss occurs early in the first trimester, a vanishing twin is considered harmless to the survivor. If the loss occurs after the first trimester, the risk of death or damage to the survivor is largely limited to monochorionic twin gestations. Morbidity in the monochorionic twin survivor is almost always due to vascular anastomoses, which often cause the demise of one twin followed by sudden hypotension in the other. If one fetus of a monochorionic twin gestation dies after the first trimester but before viability, pregnancy termination can be considered (Blickstein, 2013). Occasionally, death of one but not all fetuses results from a maternal complication such as diabetic ketoacidosis or severe preeclampsia with abruption. Pregnancy management is based on the diagnosis and the status of both the mother and surviving fetus. If the death of one dichorionic twin is due to a discordant congenital anomaly, its death should not affect its surviving twin.

Single fetal death during late second and early third trimester presents the greatest risk to the surviving twin. Although the risks of subsequent death or neurological damage to the survivor are comparatively increased for monochorionic twins at this gestational age, the risk of preterm birth is equally increased in mono- and dichorionic twins (Ong, 2006). Delivery generally occurs within 3 weeks of diagnosis of fetal demise, thus antenatal corticosteroids for survivor lung maturity should be considered (Blickstein, 2013). Regardless, unless there is a hostile intrauterine environment, the goal should be to prolong pregnancy.

Timing of elective delivery after conservative management of a late second or early third trimester single fetal death is a matter of debate. Dichorionic twins can probably be safely delivered at term. Monochorionic twin gestations are more difficult to manage and are often delivered between 34 and 37 weeks’ gestation (Blickstein, 2013). In cases of single fetal death at term, especially when the etiology is unclear, most opt for delivery instead of expectant management.

image Impending Death of One Fetus

Abnormal antepartum test results of fetal health in one twin fetus, but not the other, pose a particular dilemma. Delivery may be the best option for the compromised fetus yet may result in death from immaturity of the cotwin. If fetal lung maturity is confirmed, salvage of both the healthy fetus and its jeopardized sibling is possible. Unfortunately, ideal management if twins are immature is problematic but should be based on the chances of intact survival for both fetuses. Often the compromised fetus is severely growth restricted or anomalous. Thus, performing amniocentesis for fetal karyotyping in women of advanced maternal age carrying twin pregnancies is advantageous, even for those who would continue their pregnancies regardless of the diagnosis. Aneuploidy identification in one fetus allows rational decisions regarding interventions.


Primary goals of prenatal management of multifetal pregnancy are to provide close observation of the mother and her fetuses to prevent or interdict complications as they develop. A major imperative is to prevent preterm delivery of markedly immature neonates. At Parkland Hospital, women with multifetal gestations are seen every 2 weeks beginning at 22 weeks’ gestation, and a digital cervical examination is performed at each visit. Identification of other unique complications discussed above may also lead to interventions including early delivery. We routinely perform sonographic studies to assess fetal growth and amnionic fluid every 4 weeks in monochorionic twins or 6 weeks in dichorionic pairs.

image Diet

Along with more frequent prenatal visits, it must be ensured that the maternal diet provides additional requirements for calories, protein, minerals, vitamins, and essential fatty acids. Achievement of BMI-specific weight gain goals, supplementation with macro- and micronutrients to meet the increased needs associated with a twin gestation, and carbohydrate-controlled diets have been recommended (Goodnight, 2009). The Institute of Medicine guidelines for twin pregnancy recommend a 37- to 54-lb weight gain for women with a normal BMI. In their extensive review of the topic, Goodnight and Newman (2009) recommend supplementation of micronutrients such as calcium, magnesium, zinc, and vitamins C, D, and E based on upper intake levels from the Food and Nutrition Board of the Institute of Medicine. The daily recommended increased caloric intake for women with twins is 40 to 45 kcal/kg/d, composed of 20 percent protein, 40 percent carbohydrate, and 40 percent fat divided into three meals and three snacks daily.

image Surveillance of Fetal Growth and Health

Because a cornerstone of fetal assessment in twin pregnancy is identification of abnormal fetal growth or discordancy, serial sonographic examinations are usually performed throughout the third trimester. Assessment of amnionic fluid volume is also important. Associated oligohydramnios may indicate uteroplacental pathology and should prompt further evaluation of fetal well-being. That said, quantifying amnionic fluid volume in multifetal gestation is sometimes difficult. Some measure the deepest vertical pocket in each sac or assess the fluid subjectively. Measurement of the amnionic fluid index (AFI) may also be helpful. Using data from 488 diamnionic twins with birthweight between the 10th and 90th percentiles, Hill and associates (2000) described a protocol for measuring the AFI in twin gestations. Each amnionic sac was divided into quadrants that extended along a vertical, horizontal, or oblique axis. The deepest vertical pocket free of umbilical cord in each quadrant was measured. They found a slightly lower median value in twins than singletons. The AFI was highest at 26 to 28 weeks’ gestation and declined until delivery. Magann and coworkers (2000) compared subjective assessment and several objective methods of assessing amnionic fluid in 23 sets of twins. They found all methods to be equally poor in predicting abnormal volumes in diamnionic twins. At Parkland Hospital, the single deepest vertical pocket is measured in each sac. A measurement < 2 cm is considered oligohydramnios and a measurement ≥ 8 cm is considered hydramnios (Hernandez, 2012).

Tests of Fetal Well-Being

As described throughout Chapter 17, there are several methods of assessing fetal health in singleton pregnancies. The nonstress test or biophysical profile is commonly used in management of twin or higher-order multifetal gestations. Because of the complex complications associated with multifetal gestations and the potential technical difficulties in differentiating fetuses during antepartum testing, the usefulness of these methods appears limited. According to DeVoe (2008), the few exclusive studies of nonstress testing in twins suggest that the method performs the same as in singleton pregnancies. Elliott and Finberg (1995) used the biophysical profile as the primary method for monitoring higher-order multifetal gestations. They reported that four of 24 monitored pregnancies had a poor outcome despite reassuring biophysical profile scores. Although biophysical testing is commonly performed in multifetal gestations, there are insufficient data to determine its efficacy (DeVoe, 2008).

In an early study of 272 twin sets, Giles and colleagues (1990) reported that availability of umbilical artery Doppler velocimetry led to a reduced perinatal mortality rate. In a later randomized trial of 526 twin pregnancies by the same group, the addition of umbilical artery Doppler velocimetry to management compared with fetal testing based on fetal-growth parameters alone resulted in no perinatal outcome improvement (Giles, 2003). Hack and associates (2008) investigated the utility of umbilical artery Doppler velocimetry in 67 uncomplicated monochorionic twin gestations. They found similar mortality rates in those with abnormal pulsatility indices of the umbilical artery compared with those with normal indices. Differences in neonatal morbidity were explained by gestational age at delivery.

All testing schemes have high false-positive rates in singletons, and data suggest that testing in multifetal gestations performs no better. In cases of abnormal testing in one twin and normal results in another, iatrogenic preterm delivery remains a major concern.

Pulmonary Maturation

According to Robinson and coworkers (2012), beyond a strategy of planned delivery of uncomplicated monochorionic twins at 38 weeks, a secondary strategy is amniocentesis to verify pulmonary maturity before delivery between 36 and 38 weeks. In cases of complicated twin gestations, amniocentesis may be performed earlier. As measured by determination of the lecithin-sphingomyelin ratio, pulmonary maturation is usually synchronous in twins (Leveno, 1984). Moreover, although this ratio usually does not exceed 2.0 until 36 weeks in singleton pregnancies, it often exceeds this value by approximately 32 weeks in multifetal pregnancies. McElrath and colleagues (2000) reported similar increased values of surfactant in twins after 31 weeks’ gestation. In a comparison of respiratory morbidity in 100 twins and 241 singleton newborns delivered by cesarean before labor, Ghi and associates (2013) found less neonatal respiratory morbidity in twins, especially those delivered ≤ 37 weeks’ gestation. In some cases, however, pulmonary function may be markedly different, and the smallest, most stressed twin fetus is typically more mature.


Preterm labor is common in multifetal pregnancies and may complicate up to 50 percent of twin, 75 percent of triplet, and 90 percent of quadruplet pregnancies (Elliott, 2007). The proportion of preterm births in multifetal gestations, however, varies widely. For example, the preterm birth rate is 42 percent in Ireland but is 68 percent in Austria (Giuffre, 2012). These differences likely reflect different clinical approaches to management. Several techniques have been applied in attempts to prolong these pregnancies. Methods include bed rest—especially through hospitalization, prophylactic administration of β-mimetic drugs or progestins, prophylactic cervical cerclage, and pessary placement.

image Prediction of Preterm Birth

A major goal of multifetal pregnancy prenatal care is accurate prediction of women likely to experience preterm delivery, with prediction followed by prevention. This has been an elusive goal, but some advances have been made. Goldenberg and coworkers (1996) prospectively screened 147 twin pregnancies for more than 50 potential preterm birth risk factors. These investigators found that cervical length and fetal fibronectin concentration in the cervical canal were predictive of preterm birth (Chap. 42p. 843). At 24 weeks, a cervical length ≤ 25 mm was the best predictor of birth before 32 weeks. At 28 weeks, an elevated fetal fibronectin level was the best predictor. Similarly, To and associates (2006) sonographically measured cervical length in 1163 twin pregnancies at 22 to 24 weeks. Rates of preterm delivery before 32 weeks were 66 percent in those with cervical lengths of 10 mm; 24 percent for lengths of 20 mm; 12 percent for 25 mm; and only 1 percent for 40 mm. McMahon and colleagues (2002) found that women with multifetal gestations at 24 weeks who had a closed internal os on digital cervical examination, a normal cervical length by sonographic examination, and a negative fetal fibronectin test result had a low risk to deliver before 32 weeks. Interestingly, a closed internal os by digital examination was as predictive of early delivery as the combination of normal sonographically measured cervical length and negative fetal fibronectin test results.

In a systematic review and metaanalysis of transvaginal cervical length for the prediction of preterm birth, Conde-Agudelo and coworkers (2010) concluded that cervical length between 20 and 24 weeks was a good predictor of spontaneous preterm birth in asymptomatic women with twin pregnancies. These authors found that a cervical length ≤ 20 mm was most accurate for predicting birth < 34 weeks, with a specificity of 97 percent and positive likelihood ratio of 9.0.

image Prevention of Preterm Birth

Several schemes have been evaluated to prevent preterm labor and delivery. In recent years, some have been shown to decrease the risk of preterm delivery in small subgroups of singleton pregnancies. Unfortunately, most have been disappointingly ineffective.

Bed Rest

Most evidence suggests that routine hospitalization is not beneficial in prolonging multifetal pregnancy. In a metaanalysis of seven trials of hospitalization with bed rest, Crowther and Han (2010) concluded that the practice did not reduce the risk of preterm birth or perinatal mortality. Also at Parkland Hospital, elective hospitalization was compared with outpatient management, and no advantages were found (Andrews, 1991). Importantly, however, almost half of the women required admission for specific indications such as hypertension or threatened preterm delivery.

Limited physical activity, early work leave, more frequent health care visits and sonographic examinations, and structured maternal education regarding preterm delivery risks have been advocated to reduce preterm birth rates in women with multiple fetuses. Unfortunately, there is little evidence that these measures substantially change outcome.

Prophylactic Tocolysis

Tocolytic therapy in multifetal pregnancies has not been extensively studied. In a Cochrane review of five randomized trials of prophylactic oral β-mimetic therapy that included 374 twin pregnancies, Yamasmit and coworkers (2012) concluded that treatment did not reduce the rate of twins delivering before 37 or before 34 weeks. Especially in light of the recent Food and Drug Administration warning against the use of oral terbutaline, prophylactic use of β-mimetics in multifetal gestations seems especially unwarranted.

Intramuscular Progesterone Therapy

Although somewhat effective in reducing recurrent preterm birth in women with a singleton pregnancy, weekly injections of 17α-hydroxyprogesterone caproate (17-OHPC) are not effective for multifetal gestations (Caritis, 2009; Rouse, 2007). These results were corroborated in a more recent randomized trial in 240 twin pregnancies (Combs, 2011). Moreover, women carrying twins and identified with a cervical length < 36 mm (25th percentile) did not benefit despite their increased risk for preterm birth (Durnwald, 2010). Senat and colleagues (2013) randomly assigned 165 asymptomatic women with twins and a cervical length < 25 mm to 17-OHPC and also found no reduction in delivery before 37 weeks.

Caritis and associates (2012), in an evaluation of plasma drug concentrations in a Maternal-Fetal Medicine Units (MFMU) Network trial, reported that higher concentrations of 17-OHPC were associated with earlier gestational age at delivery. They concluded that 17-OHPC may adversely lower the gestational age at delivery in women with twin gestations. When taken together, administration of intramuscular 17-OHPC to women with twin pregnancies, even to those with a shortened cervix, does not lower the preterm birth risk.

Vaginal Progesterone Therapy

Micronized progesterone administered vaginally to women with twins is of uncertain benefit. Cetingoz and coworkers (2011) gave 100 mg of micronized progesterone intravaginally daily from 24 to 34 weeks. These authors reported that this practice reduced rates of delivery before 37 weeks from 79 to 51 percent in 67 women with twins. In contrast, several studies have failed to demonstrate any preterm birth rate reduction in women receiving various formulations of vaginal progesterone. Norman and colleagues (2009) randomly assigned 494 women with twins to 10 weeks of daily 90-mg intravaginal progesterone and failed to show reduced rates of delivery before 34 weeks. In the multicenter Prevention of Preterm Delivery in Twin Gestations (PREDICT) trial, Rode and associates (2011) randomly assigned 677 women with twins to receive prophylactic, 200-mg progesterone pessaries or placebo pessaries. These investigators also failed to demonstrate a reduction in delivery rates before 34 weeks. In a subgroup analysis of this trial that included only women with a short cervix or a history of prior preterm birth, Klein and associates (2011) also did not demonstrate a benefit. At Parkland Hospital, management of women with multifetal gestations does not typically include progesterone in any formulation.

Cervical Cerclage

Prophylactic cerclage has not been shown to improve perinatal outcome in women with multifetal pregnancies. Studies have included women who were not specially selected and those who were selected because of a shortened cervix that was identified sonographically (Dor, 1982; Elimian, 1999; Newman, 2002; Rebarber, 2005). In the latter group, cerclage may actually worsen outcomes (Berghella, 2005).


A vaginal pessary that encircles and theoretically compresses the cervix, alters the inclination of the cervical canal, and relieves direct pressure on the internal cervical os has been proposed as an alternative to cerclage. The most popular is the silicone Arabin pessary. In a study of pessary use in women with a short cervix between 18 and 22 weeks, a subgroup analysis of 23 women with twins showed a significant reduction in the delivery rate before 32 weeks compared with the rate in 23 control pregnancies (Arabin, 2003). Liem and coworkers (2013) recently reported on the open-label Pessaries in Multiple Pregnancy as a Prevention of Preterm Birth (ProTWIN) trial completed at 40 centers throughout the Netherlands. These researchers randomized 813 unselected women with twins to receive either the Arabin pessary between 12 and 20 weeks or no treatment. The pessary failed to reduce preterm birth overall but did decrease delivery rates before 32 weeks in a subset of women with a cervical length < 38 mm—29 versus 14 percent. At this time, before such treatment can be recommended, beneficial effects of pessary use in women with a short cervix need to be confirmed.

image Treatment of Preterm Labor

Although many advocate their use, therapy with tocolytic agents to forestall preterm labor in multifetal pregnancy has not resulted in measurably improved neonatal outcomes (Chauhan, 2010; Gyetvai, 1999). They are similarly ineffective in singleton pregnancy as discussed in further detail in Chapter 42 (p. 851). Another caveat is that tocolytic therapy in women with a multifetal pregnancy entails higher risk than in singleton pregnancy. This is in part because of the augmented pregnancy-induced hypervolemia and its increased cardiac demands and susceptibility to iatrogenic pulmonary edema. Gabriel and colleagues (1994) compared outcomes of 26 twin and six triplet pregnancies with those of 51 singletons—all treated with a β-mimetic drug for preterm labor. Women with a multifetal gestation had significantly more cardiovascular complications—43 versus 4 percent—including three with pulmonary edema. In a recent retrospective analysis, Derbent and coworkers (2011) evaluated nifedipine tocolysis in 58 singleton and 32 twin pregnancies. These authors reported higher incidences of side effects such as maternal tachycardia in women with twins—19 versus 9 percent.

Glucocorticoids for Lung Maturation

Administration of corticosteroids to stimulate fetal lung maturation has not been well studied in multifetal gestation. However, these drugs logically should be as beneficial for multiples as they are for singletons (Roberts, 2006). Battista and colleagues (2008) compared the efficacy of betamethasone therapy in 60 preterm twin pregnancies to 60 preterm singleton pregnancies. These researchers found no differences in neonatal morbidity, including respiratory distress. Moreover, Gyamfi and associates (2010) evaluated betamethasone concentrations in maternal and umbilical cord blood in 30 singleton and 15 twin pregnancies receiving weekly antenatal corticosteroids. They found no differences in levels between twins and singletons. These treatments are discussed in Chapter 42 (p. 850). At this time, guidelines for the use of these agents are not different from those for singleton gestations (American College of Obstetricians and Gynecologists, 2010).

image Preterm Premature Membrane Rupture

The frequency of preterm premature rupture of membranes (PPROM) increases with increasing plurality. In a population-based retrospective cohort study of more than 290,000 live births in Ohio, Pakrashi and coworkers (2013) reported the proportion of preterm birth complicated by premature rupture was 13.2 percent in singletons. This rate was compared with 17, 20, 20, and 100 percent in twins, triplets, quadruplets, and higher-order multiples, respectively. Multifetal gestations with PPROM are managed expectantly much like singleton pregnancies (Chap. 42p. 846). Ehsanipoor and colleagues (2012) compared outcomes of 41 twin and 82 singleton pregnancies, both with ruptured membranes between 24 and 32 weeks. They found the median latency was overall shorter for twins—3.6 days compared with 6.2 days for singletons. This difference was significant in pregnancies after 30 weeks—1.7 days and 6.9 days. Importantly, latency beyond 7 days approximated 40 percent in both groups.

image Delayed Delivery of Second Twin

Infrequently, after preterm birth of the presenting fetus, it may be advantageous for undelivered fetus(es) to remain in utero. Trivedi and Gillett (1998) reviewed the English literature and described 45 case reports of asynchronous birth in multifetal gestation. Although likely biased, those pregnancies with a surviving retained twin or triplet continued for an average of 49 days. No advantage was gained by management with tocolytics, prophylactic antimicrobials, or cerclage. In their 10-year experience, Roman and associates (2010) reported a median latency of 16 days in 13 twin and five triplet pregnancies with delivery of the first fetus between 20 and 25 weeks. Survival of the firstborn infant was 16 percent. Although 54 percent of the retained fetuses survived, only 37 percent of survivors did so without major morbidity. Livingston and coworkers (2004) described 14 pregnancies in which an active attempt was made to delay delivery of 19 fetuses after delivery of the first neonate. Only one fetus survived without major sequelae, and one mother developed sepsis syndrome with shock. Arabin and van Eyck (2009) reported better outcomes in a few of the 93 twin and 34 triplet pregnancies that qualified for delayed delivery in their center during a 17-year period.

If asynchronous birth is attempted, there must be careful evaluation for infection, abruption, and congenital anomalies. The mother must be thoroughly counseled, particularly regarding the potential for serious, life-threatening infection. The range of gestational age in which the benefits outweigh the risks for delayed delivery is likely narrow. Avoidance of delivery from 23 to 26 weeks would seem most beneficial. In our experience, good candidates for delayed delivery are rare.


There is a litany of complications that may be encountered during labor and delivery of multiple fetuses. In addition to preterm labor and delivery as already discussed, there are increased rates of uterine contractile dysfunction, abnormal fetal presentation, umbilical cord prolapse, placenta previa, placental abruption, emergent operative delivery, and postpartum hemorrhage from uterine atony. All of these must be anticipated and thus certain precautions and special arrangements are prudent. These should include:

1. An appropriately trained obstetrical attendant should remain with the mother throughout labor. Continuous external electronic monitoring is preferable. If membranes are ruptured and the cervix dilated, the presenting fetus is monitored internally.

2. An intravenous infusion system capable of delivering fluid rapidly is established. In the absence of hemorrhage, lactated Ringer or an aqueous dextrose solution is infused at a rate of 60 to 125 mL/hr.

3. Blood for transfusion is readily available if needed.

4. An obstetrician skilled in intrauterine identification of fetal parts and in intrauterine manipulation of a fetus should be present.

5. A sonography machine is readily available to evaluate the presentation and position of the fetuses during labor and to image the remaining fetus(es) after delivery of the first.

6. An anesthesia team is immediately available in the event that emergent cesarean delivery is necessary or that intrauterine manipulation is required for vaginal delivery.

7. For each fetus, at least one attendant who is skilled in resuscitation and care of newborns and who has been appropriately informed of the case should be immediately available.

8. The delivery area should provide adequate space for the nursing, obstetrical, anesthesia, and pediatric team members to work effectively. Equipment must be on site to provide emergent anesthesia, operative intervention, and maternal and neonatal resuscitation.

image Evaluation upon Admission

Fetal Presentation

In addition to the standard preparations for the conduct of labor and delivery discussed in Chapter 22, there are special considerations for women with a multifetal pregnancy. First, the positions and presentations of fetuses are best confirmed sonographically (American College of Obstetricians and Gynecologists, 2011). Although any possible combination of positions may be encountered, those most common at admission for delivery are cephalic-cephalic, cephalic-breech, and cephalic-transverse. At Parkland Hospital between 2008 and 2013, 71 percent of twin pregnancies had cephalic presentation of the first fetus at the time of admission to labor and delivery. Importantly, with perhaps the exception of cephalic–cephalic presentations, these are all unstable before and during labor and delivery. Accordingly, compound, face, brow, and footling breech presentations are relatively common, and even more so if fetuses are small, amnionic fluid is excessive, or maternal parity is high. Cord prolapse is also frequent in these circumstances.

After this initial evaluation, if active labor is confirmed, then a decision is made to attempt vaginal delivery or to proceed with cesarean delivery. The latter is chosen in many cases because of fetal presentations. Cephalic presentation of the first fetus in a laboring woman with twins may be considered for expectant management. Of the 547 women who presented like this at Parkland Hospital during 5 years, 32 percent delivered spontaneously. Nevertheless, the overall cesarean delivery rate in twin pregnancies during those years was 77 percent. Notably, 5 percent of cesareans performed were for emergent delivery of the second twin following vaginal delivery of the first twin. The desire to avoid this obstetrical dilemma has contributed to the increasing cesarean delivery rate in twin pregnancies across the United States (Antsaklis, 2013; Lee, 2011).

Labor Induction or Stimulation

According to a comparison of 891 twins with more than 100,000 singleton pregnancies included in the Consortium of Safe Labor, Leftwich and colleagues (2013) concluded that both nulliparas and multiparas with twins had slower progression of active labor. Women with twins required between 1 and 3 additional hours to complete first-stage labor. This was despite equivalent rates of labor induction or augmentation. Provided women with twins meet all criteria for oxytocin administration, it may be used as described in Chapter 26 (p. 529). Wolfe and associates (2013) evaluated the success of labor induction in 40 sets of twins compared with 80 singletons and found that protocols for oxytocin alone or in combination with cervical ripening can safely be used in twin gestations. Taylor and coworkers (2012) reported that 100 women with twins undergoing labor induction had similar labor lengths and cesarean delivery rates compared with those of 100 matched women with singleton pregnancies. Still, in an analysis of twin births in the United States between 1995 and 2008, Lee and colleagues (2011) reported that induction rates of twin pregnancies has decreased from a maximum of 13.8 percent in 1999 to 9.9 percent in 2008.

image Analgesia and Anesthesia

During labor and delivery of multiple fetuses, decisions regarding analgesia and anesthesia may be complicated by problems imposed by preterm labor, preeclampsia, desultory labor, need for intrauterine manipulation, and postpartum uterine atony and hemorrhage.

Labor epidural analgesia is ideal because it provides excellent pain relief and can be rapidly extended cephalad if internal podalic version or cesarean delivery is required. There are special considerations for women with severe preeclampsia or with hemorrhage as discussed in their respective chapters. Because of these eventualities, most recommend that continuous epidural analgesia be performed by anesthesia personnel with special expertise in obstetrics.

If general anesthesia becomes necessary for intrauterine manipulation, then uterine relaxation can be accomplished rapidly with one of the halogenated inhalation agents discussed in Chapter 25 (p. 519). Some clinicians use intravenous or sublingual nitroglycerin to achieve uterine relaxation yet avoid the aspiration and hypoxia risks associated with general anesthetics.

image Delivery Route

Regardless of fetal presentation during labor, there must be a readiness to deal with any change of fetal position during delivery and especially following delivery of the first twin. If the first fetus is nonvertex, cesarean delivery is typically performed, whereas cephalic-cephalic twins are commonly considered for vaginal delivery (Peaceman, 2009; Rossi, 2011). Importantly, when comparing neonatal outcomes among all these options, second twins at term as a group have worse composite neonatal outcomes than those of their cotwin regardless of delivery method (Smith, 2007; Thorngren-Jerneck, 2001).

Cephalic-Cephalic Presentation

If the first twin presents cephalic, delivery can usually be accomplished spontaneously or with forceps. According to D’Alton (2010), there is general consensus that a trial of labor is reasonable in women with cephalic-cephalic twins. Hogle and associates (2003) performed an extensive literature review and concluded that planned cesarean delivery does not improve neonatal outcome when both twins are cephalic. The recent randomized trial by Barrett and coworkers (2013) affirms this conclusion. Muleba and colleagues (2005) identified increased rates of respiratory distress in the second twin of preterm pairs regardless of delivery mode or corticosteroid use.

Cephalic-Noncephalic Presentation

The optimal delivery route for cephalic–noncephalic twin pairs remains controversial (D’Alton, 2010). Patient selection is crucial, and options include cesarean delivery of both twins, or less commonly, vaginal delivery with intrapartum external cephalic version of the second twin. Longer intertwin delivery time has been shown in some studies to be associated with poorer second twin outcome (Edris, 2006; Stein, 2008). Thus, breech extraction may be preferable to version. Least desirable, vaginal delivery of the first but cesarean delivery of the second twin may be required due to intrapartum complications such as umbilical cord prolapse, placental abruption, contracting cervix, and fetal distress. Most, but not all, studies show the worst composite fetal outcomes for this scenario (Alexander, 2008; Rossi, 2011; Wen, 2004).

Several reports attest to the safety of vaginal delivery of second noncephalic twins whose birthweight is > 1500 g. Recently, Fox and associates (2014) reported outcomes of 287 diamnionic twin pregnancies between 2005 and 2009. Cesarean delivery was routinely performed for all women with a noncephalic presenting twin fetus, a noncephalic second twin weighing < 1500 g, or a second twin estimated to be 20 percent larger than the presenting twin. All others without contraindications to labor were offered a vaginal delivery and were treated using a strict protocol of second-stage labor management. This included vaginal delivery of a second cephalic twin, breech extraction of a second noncephalic twin, and internal podalic version of an unengaged cephalic second twin followed by breech extraction. Of the 130 who planned a vaginal delivery, only 15 percent underwent cesarean delivery. There was no difference in the rate of 5-minute Apgar score < 7 or of umbilical arterial pH < 7.20 in second twins. The data are less informative concerning vaginal delivery of a second twin whose estimated fetal weight is < 1500 g. That said, however, comparable or even better fetal outcomes with vaginal delivery have been reported with these smaller infants compared with those who weigh > 1500 g (Caukwell, 2002; Davidson, 1992; Rydhström, 1990).

Other investigators advocate cesarean delivery for both members of a cephalic-noncephalic twin pair (Armson, 2006; Hoffmann, 2012). Yang and coworkers (2005a,b) studied 15,185 cephalic-noncephalic twin pairs. The risk of asphyxia-related neonatal deaths and morbidity was increased in the group in which both twins were delivered vaginally compared with the group in which both twins underwent cesarean delivery.

Randomized Trial of Planned Cesarean versus Vaginal Delivery. To add insight into the clinical complexities discussed above, a randomized trial was designed by the Twin Birth Study Collaborative Group from Canada. The study results described by Barrett and colleagues (2013) included 2804 women carrying a presumed diamnionic twin pregnancy with the first fetus presenting cephalic. Women were randomly assigned between 32 and 38 weeks to planned cesarean or vaginal delivery. The time from randomization to delivery—12.4 versus 13.3 days, the mean gestational age at delivery—36.7 versus 36.8 weeks, and use of regional analgesia—92 versus 87 percent was similar in both groups. Salient maternal and perinatal outcomes are shown in Table 45-4. No significant differences in outcomes were noted between the two groups of women. Although there were no increased risks to mother or fetuses with planned vaginal delivery in these circumstances, we agree with Greene (2013) that this trial will moderately affect the cesarean delivery rate of women with twins.

TABLE 45-4. Maternal and Perinatal Outcomes of Women with a Twin Pregnancy Randomized to Planned Cesarean versus Vaginal Delivery


Breech Presentation of First Twin

Problems with the first twin presenting as a breech are similar to those encountered with a singleton breech fetus. Thus, major problems may develop if:

1. The fetus is unusually large, and the aftercoming head is larger than the birth canal.

2. The fetal body is small, and delivery of the extremities and trunk through an inadequately effaced and dilated cervix causes the relatively larger head to become trapped above the cervix. This is more likely when there is disproportion between the fetal buttocks or trunk and the head. This may be seen with preterm or growth-restricted fetuses or with a macrocephalic fetus due to hydrocephaly.

3. The umbilical cord prolapses.

If these problems are anticipated or identified, cesarean delivery is often preferred with a viable-size fetus. But even without these problems, many obstetricians perform cesarean delivery if the first twin presents as breech. This is despite data that support the safety of vaginal delivery. Specifically, Blickstein and associates (2000) reported experiences from 13 European centers with 613 twin pairs and the first twin presenting breech. Vaginal delivery was attempted in 373 of these cases and was successful in 64 percent. Cesarean delivery of the second twin was done in 2.4 percent. There was no difference in the rate of 5-minute Apgar score < 7 or of mortality in breech-presenting first twins who weighed at least 1500 g. Details of techniques for delivery of a breech presentation are described in Chapter 28 (p. 563).

Locked Twins. For twin fetuses to become locked together during delivery, the first must present as breech and the second as cephalic. As the breech of the first twin descends through the birth canal, the chin locks between the neck and chin of the second cephalic-presenting cotwin. This phenomenon is rare, and Cohen and coworkers (1965) described it only once in 817 twin gestations. Cesarean delivery should be considered when the potential for locking is identified.

image Vaginal Delivery of the Second Twin

Following delivery of the first twin, the presenting part of the second twin, its size, and its relationship to the birth canal should be quickly and carefully ascertained by combined abdominal, vaginal, and at times, intrauterine examination. Sonography may be a valuable aid. If the fetal head or the breech is fixed in the birth canal, moderate fundal pressure is applied and membranes are ruptured. Immediately afterward, digital examination of the cervix is repeated to exclude cord prolapse. Labor is allowed to resume. If contractions do not begin within approximately 10 minutes, dilute oxytocin may be used to stimulate contractions.

In the past, the safest interval between delivery of the first and second twins was frequently cited as less than 30 minutes. Rayburn and colleagues (1984), and others, have shown that if continuous fetal monitoring is used, a good outcome is achieved even if this interval is longer. Several investigators have demonstrated a direct correlation between worsening umbilical cord blood gas values and increasing time between delivery of first and second twins (Leung, 2002; Stein, 2008). Gourheux and associates (2007) retrospectively reviewed delivery intervals in 239 twin gestations in France and determined that mean umbilical arterial pH was significantly lower after the interval exceeded 15 minutes. Thus, vigilant monitoring for nonreassuring fetal heart rate or bleeding is required. Hemorrhage may indicate clinically significant placental abruption.

If the occiput or breech presents immediately over the pelvic inlet, but is not fixed in the birth canal, the presenting part can often be guided into the pelvis by one hand in the vagina, while a second hand on the uterine fundus exerts moderate pressure caudally. Alternatively, with abdominal manipulation, an assistant can guide the presenting part into the pelvis. Sonography can aid guidance and allow heart rate monitoring. Intrapartum external version of a noncephalic second twin has also been described.

A presenting shoulder may be gently converted into a cephalic presentation. If the occiput or breech is not over the pelvic inlet and cannot be so positioned by gentle pressure or if appreciable uterine bleeding develops, delivery of the second twin can be problematic.

To obtain a favorable outcome, it is essential to have an obstetrician skilled in intrauterine fetal manipulation and anesthesia personnel skilled in providing anesthesia to effectively relax the uterus for vaginal delivery of a noncephalic second twin (American College of Obstetricians and Gynecologists, 2010). To take maximum advantage of the dilated cervix before the uterus contracts and the cervix retracts, delay must be avoided. Prompt cesarean delivery of the second fetus is preferred if no one present is skilled in the performance of internal podalic version or if anesthesia that will provide effective uterine relaxation is not immediately available.

Internal Podalic Version

With this maneuver, a fetus is turned to a breech presentation using the hand placed into the uterus (Fig. 45-27). The obstetrician grasps the fetal feet to then effect delivery by breech extraction. As mentioned earlier, Fox and colleagues (2010) described a strict protocol for management of the delivery of the second twin, which included internal podalic version. They reported that none of the 110 women who delivered the first twin vaginally underwent a cesarean delivery for the second twin. Chauhan and coworkers (1995) compared outcomes of 23 second twins delivered by podalic version and breech extraction with those of 21 who underwent external cephalic version. Breech extraction was considered superior to external version because less fetal distress developed. The technique of breech extraction is described in Chapter 28 (p. 567).


FIGURE 45-27 Internal podalic version. Upward pressure on the head by an abdominal hand is applied as downward traction is exerted on the feet.

image Vaginal Birth after Cesarean Delivery

Any attempt to deliver twins vaginally in a woman who has previously undergone one or more cesarean deliveries should be carefully considered. As discussed in Chapter 31 (p. 614), some studies support the safety of attempting a vaginal birth after cesarean delivery (VBAC) for selected women with twins (Cahill, 2005; Ford, 2006; Varner, 2005). According to the American College of Obstetricians and Gynecologists (2013b), there currently is no evidence of an increased risk of uterine rupture, and women with twins and one previous cesarean delivery with a low transverse incision may be considered candidates for trial of labor. At Parkland Hospital, such women are generally offered repeat cesarean delivery.

image Cesarean Delivery for Multifetal Gestation

There are several unusual intraoperative problems that can arise during cesarean delivery of twins or higher-order multiples. Supine hypotension is common, and thus these women should be positioned in a left lateral tilt to deflect uterine weight off the aorta (Chap. 4p. 60). A low-transverse hysterotomy is preferable if the incision can be made large enough to allow atraumatic delivery of both fetuses. Piper forceps can be used if the second twin is presenting breech (Fig. 28-13p. 568). In some cases, a vertical hysterotomy beginning as low as possible in the lower uterine segment may be advantageous. For example, if a fetus is transverse with its back down and the arms are inadvertently delivered first, it is much easier and safer to extend a vertical uterine incision upward than to extend a transverse incision laterally or to make a “T” incision vertically.

Cesarean Delivery of the Second Twin

It is not uncommon for cesarean delivery to become necessary for delivery of a second twin after the first has been delivered vaginally. As described earlier, this occurred in 32 of 770 women with twins at Parkland Hospital between 2008 and 2013. In these cases, prompt cesarean delivery is required and is frequently emergently indicated. Indications most often cited are a second fetus that is much larger than the first and is presenting breech or transverse. In other cases, the cervix promptly contracts and thickens after delivery of the first twin. This may be followed by a nonreassuring fetal status or by a cervix that fails to completely dilate again despite adequate uterine contractions.


Fetal heart rate monitoring during labor with triplet pregnancies is challenging. A scalp electrode can be attached to the presenting fetus, but it is difficult to ensure that the other two fetuses are each being monitored separately. With vaginal delivery, the first neonate is usually born with little or no manipulation. Subsequent fetuses, however, are delivered according to the presenting part. This often requires complicated obstetrical maneuvers such as total breech extraction with or without internal podalic version or even cesarean delivery. Associated with malposition of fetuses is an increased incidence of cord prolapse. Moreover, reduced placental perfusion and hemorrhage from separating placentas are more likely during delivery.

For all these reasons, many clinicians believe that pregnancies complicated by three or more fetuses are best delivered by cesarean. Vaginal delivery is reserved for those circumstances in which survival is not expected because fetuses are markedly immature or maternal complications make cesarean delivery hazardous to the mother. Others believe that vaginal delivery is safe under certain circumstances. For example, Alamia and colleagues (1998) evaluated a protocol for vaginal delivery of triplet pregnancies in which the presenting fetus was cephalic. A total of 23 sets of triplets were analyzed, and a third of these were delivered vaginally. Neonatal outcomes were the same in the vaginal and cesarean delivery groups, with no morbidity and 100-percent fetal survival. Grobman and associates (1998) and Alran and coworkers (2004) reported vaginal delivery completion rates of 88 and 84 percent, respectively, in women carrying triplets who underwent a trial of labor. Neonatal outcomes did not differ from those of a matched group of triplet pregnancies delivered by elective cesarean. Conversely, Vintzeleos and colleagues (2005) reviewed more than 7000 triplet pregnancies and found that vaginal delivery was associated with an increased perinatal mortality rate. Importantly, the overall cesarean delivery rate among triplets was 95 percent. At Parkland Hospital, triplet gestations are routinely delivered by cesarean.


In some cases of higher-order multifetal gestation, reduction of the fetal number to two or three improves survival of the remaining fetuses. Selective reduction implies early pregnancy intervention, whereas selective termination is performed later.

image Selective Reduction

Reduction of a selected fetus or fetuses in a multichorionic multifetal gestation may be chosen as a therapeutic intervention to enhance survival of the remaining fetuses (American College of Obstetricians and Gynecologists, 2013a). There are no randomized controlled trials on the effects of such reduction. However, a metaanalysis of nonrandomized prospective studies indicates that pregnancy reduction to twins compared with expectant management is associated with lower rates of maternal complications, preterm birth, and neonatal death (Dodd, 2004, 2012). Pregnancy reduction can be performed transcervically, transvaginally, or transabdominally, but the transabdominal route is usually easiest.

Transabdominal fetal reductions are typically performed between 10 and 13 weeks. This gestational age is chosen because most spontaneous abortions have already occurred, the remaining fetuses are large enough to be evaluated sonographically, the amount of devitalized fetal tissue remaining after the procedure is small, and the risk of aborting the entire pregnancy as a result of the procedure is low. The smallest fetuses and any anomalous fetuses are chosen for reduction. Potassium chloride is then injected under sonographic guidance into the heart or thorax of each selected fetus. Care is used to not enter or traverse the sacs of fetuses selected for retention. In most cases, pregnancies are reduced to twins to increase the chances of delivering at least one viable fetus.

Evans and associates (2005) reported continued improvement in fetal outcomes with this procedure. They analyzed more than 1000 pregnancies managed in 11 centers from 1995 to 1998. The pregnancy loss rate varied from a low of 4.5 percent for triplets who were reduced to twins. The loss rate increased with each addition to the starting number of fetuses and peaked at 15 percent for six or more fetuses (Evans, 2001). Operator skill and experience are believed responsible for the low and declining rates of pregnancy loss.

image Selective Termination

With the identification of multiple fetuses discordant for structural or genetic abnormalities, three options are available: abortion of all fetuses, selective termination of the abnormal fetus, or pregnancy continuation. Because anomalies are typically not discovered until the second trimester, selective termination is performed later in gestation than selective reduction and entails greater risk. This procedure is therefore usually not performed unless the anomaly is severe but not lethal. Thus, a triplet pregnancy in which one fetus has Down syndrome might be a candidate for selective termination, whereas a twin pregnancy in which one fetus has trisomy 18 might not. In some cases, termination is considered because the abnormal fetus may jeopardize the normal one. For example, pathological hydramnios in a twin with esophageal atresia could lead to preterm birth of its sibling.

Prerequisites to selective termination include a precise diagnosis for the anomalous fetus and absolute certainty of fetal location. Thus, if genetic amniocentesis is performed on a multifetal gestation, a map of the uterus with locations of all the fetuses clearly labeled should be made at the time of the diagnostic procedure. Unless a special procedure such as umbilical cord interruption is used, selective termination should be performed only in multichorionic multifetal gestations to avoid damaging the surviving fetuses (Lewi, 2006). Roman and coworkers (2010) compared 40 cases of bipolar umbilical cord coagulation with 20 cases of radiofrequency ablation for treatment of complicated monochorionic multifetal gestations at midpregnancy. They found similar survival rates of 87 and 88 percent, and a median gestational age > 36 weeks at delivery in both. Prefumo and colleagues (2013) reported their preliminary experience with microwave ablation of the umbilical cord for selective termination in two monochorionic twin pregnancies. One pregnancy aborted within 7 days, and the other resulted in a term singleton delivered at 39 weeks’ gestation.

Evans and coworkers (1999) have provided the most comprehensive results to date on second-trimester selective termination for fetal abnormalities. A total of 402 cases were analyzed from eight centers worldwide. Included were 345 twin, 39 triplet, and 18 quadruplet pregnancies. Selective termination using potassium chloride resulted in delivery of a viable neonate or neonates in more than 90 percent of cases, with a mean age of 35.7 weeks at delivery. The entire pregnancy was lost in 7.1 percent of pregnancies reduced to singletons and in 13 percent of those reduced to twins. The gestational age at the time of the procedure did not appear to affect the pregnancy loss rate. Several losses occurred because the pregnancy was actually monochorionic, and potassium chloride also killed the normal fetus through placental vascular anastomoses.

image Ethics

The ethical issues associated with these techniques are almost limitless. There is a beneficence-based justification for offering selective termination in cases in which continuation of the pregnancy poses a threat to the life of coexistent fetuses. The final decision to continue the pregnancy without intervention, to terminate the entire pregnancy, or to elect selective termination is solely the patient’s (Chervenak, 2013). The interested reader is referred to the excellent reviews by Evans and coworkers (1996, 2004) and Simpson and Carson (1996).

image Informed Consent

Before selective termination or reduction, a discussion should include the morbidity and mortality rates expected if the pregnancy is continued; the morbidity and mortality rates expected with surviving twins or triplets; and the risks of the procedure itself.

With couples seeking infertility treatment, the issue of selective reduction should ideally be discussed before conception. Grobman and associates (2001) reported that these couples were generally unaware of the risks associated with multifetal gestation, and they were less desirous of having a multifetal gestation once apprised of the risks.

Specific risks that are common to selective termination or reduction include:

1. Abortion of the remaining fetuses

2. Abortion of the wrong (normal) fetus(es)

3. Retention of genetic or structurally abnormal fetuses after a reduction in number

4. Damage without death to a fetus

5. Preterm labor

6. Discordant or growth-restricted fetuses

7. Maternal infection, hemorrhage, or possible disseminated intravascular coagulopathy because of retained products of conception.

The procedure should be performed by an operator skilled and experienced in sonographically guided procedures.

image Psychological Reaction

Women and their spouses who elect to undergo selective termination or reduction find this decision highly stressful. Schreiner-Engel and colleagues (1995) retrospectively studied the emotional reactions of 100 women following selective reduction. Although 70 percent of the women mourned for their dead fetus(es), most grieved only for 1 month. Persistent depressive symptoms were mild, although moderately severe sadness and guilt continued for many of them. Fortunately, most were reconciled to the termination of some fetuses to preserve the lives of a remaining few. Indeed, 93 percent of the women would have made the same decision again.


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