Multi Fetal

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Williams Obstetrics, 25e >
CHAPTER 45: Multifetal Pregnancy
In single-ovum twins, there is always a certain area of the placenta in which there is anastomosis between vascular systems which is never present in the fused
placenta of double-ovum twins. Thus, if at an early period the heart of one embryo is considerably stronger than that of the other, a gradually increasing area of
the communicating portion of the placenta is monopolized by the former, so that its heart increases rapidly in size, whilst that of the latter receives less blood and
eventually atrophies.
—J. Whitridge Williams (1903)
INTRODUCTION
In Williams’ time, a great deal concerning the embryological and morphological development of multifetal pregnancies was unknown. These pregnancies may result
from two or more fertilization events, from a single fertilization followed by a splitting of the zygote, or from a combination of both. Multifetal gestations were
problematic during those times and remain so today for both the mother and her fetuses. For example, in this country, approximately a fourth of very-low-
birthweight neonates—those born weighing <1500 g—are from multifetal gestations (Martin, 2017).
Fueled largely by infertility therapy, both the rate and the number of twins and higher-order multifetal births grew dramatically during the 1980s and 1990s in the
United States. National data from Martin and coworkers (2017) presented here is informative. The twinning rate rose 76 percent from 18.9 per 1000 live births in 1980
to 33.2 in 2009. During the same time, the number of higher-order multifetal births peaked in 1998 at a rate of 1.9 per 1000 total births. Since then, however, evolving
infertility management has lowered rates of higher-order multifetal births—especially among non-Hispanic white women. For example, the rate of triplets or more
declined by more than 50 percent from 1998 to 2015 in this demographic group. And, in 2015, the overall multifetal birth rate was 34.5 per 1000, with twins
representing nearly 97 percent of these births.
These rates of multifetal pregnancies have a direct e ect on the rates of preterm birth and its comorbidities. In addition, the risks for congenital malformation and its
consequences are greater with multifetal gestations. Importantly, this increased risk applies to each fetus and is not simply the result of more fetuses. In sum, in 2013
in the United States, multifetal births accounted for 3 percent of all live births but for 15 percent of all infant deaths. Moreover, the risk of infant death rose
proportionally with the number of fetuses in the pregnancy (Matthews, 2015). Specifically, the infant mortality rate for twins was more than four times the rate for
single births. In the same year, the infant mortality rate for triplets was nearly 12 times the rate for singletons, and for quadruplets, it was a staggering 26 times that
for singletons! From Parkland Hospital, a comparison of singleton and twin outcomes is shown in Table 45-1. These risks are magnified further with higher-order
births.
TABLE 45-1
Selected Outcomes in Singleton and Twin Pregnancies Delivered at Parkland Hospital from 1988 through 2016
Outcome Singletons (No.) Twins (No.)
Pregnancies 202,306 2412
Birthsa 202,306 4824
Stillbirths 1011 (5.0) 114 (23.6)
Neonatal deaths 590 (2.9) 92 (19.5)
Perinatal deaths 1601 (7.9) 206 (42.7)
Very low birthweight (<1500 g) 1927 (9.6) 507 (107.6)
aBirth data are represented as number (per 1000).
bDenominator for neonatal deaths and very low birthweight is liveborn infants.
Data from Dr. Don McIntire.
The mother may also experience higher obstetrical morbidity and mortality rates. These rates also rise with the number of fetuses (Mhyre, 2012; Young, 2012). In one
study of more than 44,000 multifetal pregnancies, the risks for preeclampsia, postpartum hemorrhage, and maternal death were twofold higher than these rates in
singleton gestations (Walker, 2004). The risk for peripartum hysterectomy is also greater. Francois and associates (2005) reported this to be threefold for twins and
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24-fold for triplets or quadruplets. Last, compared with women with a singleton pregnancy, these mothers are at increased risk for depression as well as parental
divorce (Choi, 2009; Jenna, 2011).
MECHANISMS OF MULTIFETAL GESTATIONS

Twin fetuses usually result from fertilization of two separate ova, which yields dizygotic or fraternal twins. Less o en, twins arise from a single fertilized ovum that
then divides to create 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. These traditional models of twinning discussed in the next sections have been taught for more than 50 years and
remain the widely accepted theory. More recently, Herranz (2015) o ered a provocative alternative hypothesis, which posits that monozygotic twinning occurs with
splitting at the postzygotic two-cell stage. Notably, data are not robust in support of either the traditional or the newly proposed model (Denker, 2015).
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. Namely, 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 di erential expression of X-linked traits or diseases. Further, the process of monozygotic twinning is in a sense a teratogenic event, and monozygotic twins
have a higher incidence of o en discordant malformations (Glinianaia, 2008). For example, in one study of 926 monozygotic twins, the prevalence of congenital heart
defects was 12-fold greater than the general population rate, but 68 percent of a ected infants had a normal sibling (Pettit, 2013). From any of these mechanisms,
dizygotic 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. The incidence of monozygotic twins is increased two- to fivefold in
pregnancies conceived using assisted reproductive technology (ART). The predisposition to splitting may stem from specimen handling, growth media, or sperm
DNA microinjection or may arise from intrinsic abnormalities associated with infertility (McNamara, 2016).
The outcome of the monozygotic twinning process depends on when division occurs. If zygotes divide within the first 72 hours a er 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 a er fertilization, the
chorion and the amnion have already di erentiated, 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 indicates 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 to 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. Di ering 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.
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It has long been accepted that monochorionicity incontrovertibly indicated monozygosity. Rarely, however, monochorionic twins may in fact be dizygotic (Hackmon,
2009). Mechanisms for this are speculative, but in one review of 14 cases, nearly all had been conceived a er ART procedures (Ekelund, 2008). McNamara and
colleagues (2016) o er an excellent review of the mechanisms and evidence for both typical and atypical twinning.
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 associates (2010) reported a case a er
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 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. More recent cases have been reported in the
setting of paternity lawsuits (Girela, 1997). Given that superfecundation may also occur with ART, women should be advised to consider avoiding intercourse a er
embryo transfer (McNamara, 2016; Peigné, 2011).
FIGURE 45-2
An example of dizygotic twin boys as the consequence of superfecundation.
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Factors A ecting Twinning
Dizygotic twinning is much more common than monozygotic 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 1 set per 250 births, and this
incidence is generally independent of demographic factors. One exception is that rates of zygotic splitting are increased following ART (Aston, 2008).
Demographics
Among di erent races and ethnic groups, the frequency of multifetal births varies significantly. In one analysis of more than 8 million births in the United States
between 2004 and 2008, the rate of twinning was 3.5 percent in black women and 3 percent in whites (Abel, 2012). Hispanic, Asian, and Native American women had
comparatively lower rates than white women. In one rural community in Nigeria, twinning occurred once in every 20 births (Knox, 1960)! These marked di erences in
twinning frequency may be the consequence of racial variations in levels of follicle-stimulating hormone—FSH (Nylander, 1973).
Maternal age is another important risk factor for multifetal pregnancies (Fig. 45-3). Dizygotic twinning frequency rises almost fourfold between the ages of 15 and 37
years (Painter, 2010). As such, there is a paradox of declining fertility but increasing twinning rates with advancing maternal age (Beemsterboer, 2006). Another
explanation for the dramatic rise in twinning with advancing maternal age may be a higher use of ART in older women (Ananth, 2012). Paternal age has also been
linked to twinning frequency, but its e ect is felt to be small (Abel, 2012). Although twin pregnancy is associated with greater risks for most adverse perinatal
outcomes, McLennan and associates (2017) did not find advanced maternal age to be an additional risk factor for fetal and infant death. From this population-based
study of the United States, they concluded that women in their 30s may be counseled that their age is not a major additional risk factor for adverse obstetric
outcomes in the setting of twin pregnancy.
FIGURE 45-3
Multifetal birth rates in the United States according to maternal age and race, 2015. (Data from Martin, 2017.)
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Increasing parity independently raises the incidence of twinning in all populations studied. During a 30-year period, Antsaklis and coworkers (2013) noted a
progressively increasing positive correlation between multiparity and twinning. However, they cautioned that greater use of ART may be partially contributory. In a
two-year study from Nigeria, where such technology is not commonly available, Olusanya (2012) calculated the e ects of multiparity compared with primiparity.
They found an eightfold rise in multifetal gestation rates when parity was ≤4, and a 20-fold rise when parity was ≥5.
Heredity
As a determinant of twinning, the family history of the mother supersedes that of the father. One study of 4000 genealogical records showed that women who
themselves were a dizygotic twin gave birth to twins at a rate of 1 set per 58 births (White, 1964). 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, and other suggestive peaks were on
chromosomes 7, 9, and 16. That said, the contribution of these variants to the overall incidence of twinning is likely small (Hoekstra, 2008).
Nutrition
In animals, the litter size number grows in proportion to nutritional su iciency. Evidence from various sources indicates that this occurs in humans as well. Nylander
(1971) showed an 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. Likewise, Reddy and associates (2005) found an association of maternal weight and dizygotic
twinning in the United States, in the absence of fertility drugs. Indeed, the influence of maternal weight as a factor for twinning will continue to rise in importance as
the percentage of obese women in the United States continues to grow.
Evidence acquired during and a er World War II suggested that twinning correlated more with nutrition than with 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 greater prevalence of
twinning among women who have taken supplementary folic acid (Ericson, 2001; Haggarty, 2006). Conversely, in a systematic review, Muggli and Halliday (2007)
were unable to demonstrate a significant association. Analysis of twinning rate in Texas a er folic acid fortification of cereal-grain products also failed to
demonstrate an independent increase in twinning rates (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
greater fecundity and a higher rate of dizygotic twinning have been reported in women who conceive within 1 month a er 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 a er 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
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Ovulation induction with FSH plus human chorionic gonadotropin (hCG) or clomiphene citrate remarkably enhances the likelihood of multiple concurrent
ovulations. In their review of this practice, McClamrock and coworkers (2012) reported rates of twins and higher-order multifetal pregnancies as high as 28.6 percent
and 9.3 percent, respectively. Rates this high remain a major concern. Two ongoing multicenter trials—Assessment of Multiple Gestations from Ovarian Stimulation
(AMIGOS) and Pregnancy in Polycystic Ovary Syndrome II (PPCOSII)—are designed to provide guidance on achieving maximum pregnancy rates while minimizing
multifetal gestation rates (Diamond, 2015; Legro, 2014).
In general with in vitro fertilization (IVF), the greater the number of embryos that are transferred, the greater the risk of twins and other multifetal gestations. In 2014,
ART contributed to 1.6 percent of all newborns in the United States and to 18.3 percent of all neonates in multifetal gestations (Sunderam, 2017). The American
Society for Reproductive Medicine (2017) recently revised their age-related guidelines regarding the number of cleavage-stage embryos or blastocysts to transfer
during IVF. This e ort aims to reduce the incidence of higher-order multifetal pregnancies. Based on these new recommendations, women younger than 35 years are
encouraged to receive a single-embryo transfer, regardless of embryo stage. These practices have e ectively lowered multifetal rates, and the rate of triplet or higher-
order multifetal pregnancy has declined every year since 2009 (Kulkarni, 2013; Martin, 2017).
Sex Ratios in Multifetal Pregnancies
In humans, as the number of fetuses per pregnancy rises, the percentage of male conceptuses declines. 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 newborns 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 o ered. 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.
Determining 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
monozygotic twin gestation can be di erent (Turpin, 1961). Most reported cases describe postzygotic loss of the Y chromosome in one 46,XY twin resulting in a
phenotypically female twin with Turner syndrome (45,X). Zech and coworkers (2008) found 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.
Determining Chorionicity
The risk for twin-specific complications varies in relation to both zygosity and chorionicity—the number of chorions. Shown in Table 45-2, the latter is the more
important determinant. Specifically, perinatal mortality and neurological injury rates are greater in monochorionic diamnionic twins compared with dichorionic
diamnionic pairs (Hack, 2008; Lee, 2008). In one retrospective analysis of more than 2000 twins, the risk of fetal demise in one or both monochorionic twin(s) was
twice that in dichorionic multifetal gestations (McPherson, 2012). Moreover, the prospective risk of antepartum stillbirth is higher for monochorionic than for
dichorionic twins at all preterm gestational ages. The highest risk is before 28 weeks’ gestation (Glinianaia, 2011). In contrast, chorionicity di erences do not
significantly a ect maternal outcomes (Carter, 2015).
TABLE 45-2
Overview of the Incidence of Twin Pregnancy Zygosity and Corresponding Twin-Specific Complications
Rates of Twin-Specific Complications in Percent
Type of Twinning Twins Fetal-Growth Restriction Preterm Deliverya Placental Vascular Anastomosis Perinatal Mortality
Dizygotic 80 25 40 0 10–12
Monozygotic 20 40 50 15–18
Diamnionic/dichorionic 6–7 30 40 0 18–20
Diamnionic/monochorionic 13–14 50 60 100 30–40
Monoamnionic/monochorionic <1 40 60–70 80–90 58–60
Conjoined 0.002 to 0.008 — 70–80 100 70–90
aDelivery before 37 weeks.
Data from Manning, 1995.
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Sonographic Determination
This has become an integral tool to assist in multifetal pregnancy management. Indeed, the diagnosis and evaluation of a multifetal gestation is now considered a
recognized indication for first-trimester sonography (Reddy, 2014). In addition, the North American Fetal Therapy Network (NAFTNet)—a consortium of 30 medical
institutions in the United States and Canada—have provided recommendations for determination of chorionicity using sonography (Emery, 2015).
Sonographic features used to evaluate chorionicity vary according to gestational age. Accuracy is greatest in the first trimester and diminishes as gestational age
advances. Namely, chorionicity can be determined sonographically with 98-percent accuracy in the first trimester but may be incorrect in up to 10 percent of second-
trimester examinations (Emery, 2015; Lee, 2006). Moreover, for sonographic evaluations between 15 and 20 weeks’ gestation, the odds of chorionicity
misclassification rise by approximately 10 percent for each week of advancing gestational age in pregnancies compared with those completed before 14 weeks
(Blumenfeld, 2014). Overall, chorionicity can be correctly determined with sonography before 24 weeks in approximately 95 percent of cases (Lee, 2006).
Early in the first trimester, the number of chorions equates to the number of gestational sacs. A thick band of chorion separating two gestational sacs signals a
dichorionic pregnancy, whereas monochorionic twins have a single gestational sac. If the gestation is monochorionic diamnionic, it may be di icult to visualize the
thin intervening amnion before 8 weeks’ gestation (Emery, 2015). If the intervening membrane is di icult to visualize, the number of yolk sacs usually correlates with
the number of amnions. However, the number of yolk sacs as a predictor of amnionicity may not always be accurate (Shen, 2006). Although uncommonly seen early,
cord entanglement identifies a monoamnionic gestation. When chorionicity is uncertain, additional later sonographic examinations are performed.
A er 10 to 14 weeks’ gestation, sonographic assessment of chorionicity may be determined using four features. These are the number of placental masses, thickness
of the membrane dividing the sacs, presence of an intervening membrane, and fetal gender (Emery, 2015). First, two separate placentas suggest dichorionicity. The
converse is not necessarily true, such as cases with a single fused placental mass. Second, identification of a thick dividing membrane—generally ≥2 mm—supports a
presumed diagnosis of dichorionicity. In a dichorionic pregnancy, this visualized membrane is composed of a total of four layers—two amnion and two chorion. Also,
the twin peak sign—also called lambda or delta 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. The “twin-peak” sign is seen at the bottom of this schematic
diagram. The triangular portion of placenta insinuates between the amniochorion layers.
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In contrast, monochorionic pregnancies have a dividing membrane that is so thin (generally <2 mm) that it may not be seen until the second trimester. The
relationship between the membranes and placenta without 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). Lack of a dividing
membrane signals a monochorionic monoamnionic gestation.
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.
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Last, twins with di ering gender indicates a dichorionic (and dizygotic) gestation (Emery, 2015). A rare exception to this scenario would be a heterokaryotypic
monochorionic gestation, described earlier (Sex Ratios in Multifetal Pregnancies). If both twins are the same gender, additional measures are necessary.
Placental Examination
A carefully performed visual examination of the placenta and membranes a er 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 a er delivery of the other twin. As the second neonate is delivered, two clamps are placed on that cord, and so on as necessary.
Alternatively, in higher-order deliveries, color-tagged clamps can be simpler. 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. At this time, evidence is insu icient to
recommend for or against delayed umbilical cord clamping in multifetal gestations (American College of Obstetricians and Gynecologists, 2017a). At Parkland
Hospital, we currently do not perform delayed cord clamping in these pregnancies.
The placenta is carefully delivered to preserve the attachment of the amnion and chorion. With one common amnionic sac or with juxtaposed amnions not
separated by chorion, the fetuses are monozygotic (see Fig. 45-1). If adjacent amnions are separated by chorion, the fetuses could be either dizygotic or monozygotic,
but dizygosity is more common (Fig. 45-6). If the neonates are of the same sex, blood typing of cord blood samples may be helpful. Di erent 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. However, these tests are generally not performed at birth unless medical indications dictate a need.
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).
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DIAGNOSIS OF MULTIFETAL GESTATION

Clinical Evaluation
During physical examination, accurate fundal height measurement, described in Chapter 9 (Subsequent Prenatal Visits), is essential. With multifetal pregnancies,
uterine size is typically larger during the second trimester than expected for a singleton. Rouse and associates (1993) reported fundal heights in 336 well-dated twin
pregnancies. Between 20 and 30 weeks’ gestation, fundal heights averaged approximately 5 cm greater than expected for singletons of the same fetal age.
Diagnosing twins by palpation of fetal parts before the third trimester is di icult. Even late in pregnancy, this may be challenging, especially if one twin overlies the
other, if the woman is obese, or if there is hydramnios. Palpating two fetal heads, o en in di erent uterine quadrants, strongly supports a twin diagnosis. Late in the
first trimester, two fetal heartbeats may be di erentiated with Doppler ultrasonic equipment if their rates are clearly distinct from each other and from that of the
mother.
Overall, however, using clinical criteria alone to diagnose multifetal gestations is unreliable. For example, in the Routine Antenatal Diagnostic Imaging with
Ultrasound (RADIUS) trial, for 37 percent of women who did not have a screening ultrasound examination, their twin pregnancies were not diagnosed until 26 weeks’
gestation. And, in 13 percent of unscanned women, their multifetal gestations were only diagnosed during their admission for delivery (American College of
Obstetricians and Gynecologists, 2016; LeFevre, 1993).
Sonography
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Sonographic examination should detect practically all sets of twins. And, given the increased frequency of sonographic examinations during the first trimester, early
detection of a twin pregnancy is common. Sonography can also be used to determine fetal number, estimated gestational age, chorionicity, and amnionicity. With
careful examination, separate gestational sacs, if present, 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.
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 challenging to evaluate. Even in the first trimester, it can be di icult to identify the actual number of fetuses and their
position. This determination is especially important if pregnancy reduction or selective termination is considered (Selective Reduction or Termination).
Other Diagnostic Aids
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 fetuses move during the exposure or if exposure time is inadequate. Additionally, fetal skeletons before 18 weeks’ gestation are
insu iciently 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). In one review of 17 complicated twin gestations evaluated by both sonographic and MR imaging, the latter provided a more detailed assessment of twin
pathology (Bekiesinska-Figatowska, 2013). This was particularly helpful in cases of conjoined twins.
No biochemical test reliably identifies multifetal gestations. Serum and urine levels of β-hCG and maternal serum levels of alpha-fetoprotein (MSAFP) are generally
higher with twins compared with those in singletons. However, levels may vary considerably and overlap with those of singletons.
MATERNAL PHYSIOLOGICAL ADAPTATIONS

The various physiological burdens of pregnancy and the likelihood of serious maternal complications are typically greater with multifetal gestations than with a
singleton pregnancy. This is considered, especially when counseling a woman whose health is compromised and in whom a multifetal gestation is recognized early.
Similar consideration is given to the 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 a multifetal gestation o en have nausea and vomiting in
excess of that with a singleton pregnancy. In women carrying more than one fetus, blood volume expansion is greater and averages 50 to 60 percent compared with
40 to 50 percent in those with a singleton (Pritchard, 1965). This augmented hypervolemia teleologically o sets blood loss with vaginal delivery of twins, which is
twice that with a single fetus. Although red cell mass also accrues, it does so proportionately less in twin pregnancies. Combined with greater iron and folate
requirements, this predisposes to anemia.
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 rose by a greater degree at term. An earlier study demonstrated that this rise was at least 15 mm Hg in 95 percent of women with twins
compared with only 54 percent of women with a singleton (Campbell, 1986).
Hypervolemia along with decreased vascular resistance has an impressive e ect on cardiac function. In one study of 119 women with a twin pregnancy, cardiac
output rose another 20 percent above that in women with a singleton pregnancy (Kametas, 2003). Similarly, Kuleva and coworkers (2011) using serial
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echocardiography found a greater increase in cardiac output in 20 women with uncomplicated twin pregnancies. Both studies found the augmented cardiac output
was predominantly due to greater stroke volume rather than higher heart rate. Vascular resistance was significantly lower in twin gestations throughout pregnancy
compared with singleton ones. In a study of 30 uncomplicated twin pregnancies, this same group of investigators using echocardiography later identified progressive
diastolic dysfunction from the first to third trimester. The dysfunction subsequently normalized a er delivery (Ghi, 2015).
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. Unfortunately, hydramnios is o en characterized by acute onset remote from term and by rapid
reaccumulation despite amniocentesis.
PREGNANCY COMPLICATIONS
Spontaneous Abortion
Miscarriage is more likely with multifetal gestation. In one 16-year study, the spontaneous abortion rate per live birth in singleton pregnancies was 0.9 percent
compared with 7.3 percent in multifetal ones (Joó, 2012). Also, twins achieved through ART are at greater risk for abortion compared with those conceived
spontaneously (Szymusik, 2012).
In some cases, one fetus may be spontaneously lost rather than the entire gestation. As a result, the incidence of twins in the first trimester is much greater than the
incidence of twins at birth. It has been estimated that 1 in 80 births are multifetal, whereas 1 in 8 pregnancies begin multifetal but are spontaneously reduced
(Corsello, 2010). Sonography studies in the first trimester have shown that one twin is spontaneously reduced or “vanishes” before the second trimester in up to 10
to 40 percent of all twin pregnancies (Brady, 2013). The incidence is higher following ART conception. Also, monochorionic twins have a significantly greater risk of
spontaneous reduction than dichorionic twins (Sperling, 2006). Undoubtedly, some threatened abortions are the result of death and resorption of one embryo from
an unrecognized twin gestation.
Dickey and associates (2002) described spontaneous reduction in 709 multifetal pregnancies. Before 12 weeks, one or more embryos died in 36 percent of twin
pregnancies, in 53 percent of triplet pregnancies, and in 65 percent of quadruplet pregnancies. Interestingly, ultimate pregnancy duration and birthweight were
inversely related to the initial gestational sac number regardless of the final number of fetuses at delivery. This e ect was most pronounced in twins who started as
quadruplets. Chasen and coworkers (2006) reported that spontaneous reduction of an IVF twin pregnancy to a singleton pregnancy was associated with perinatal
outcomes intermediate between those for IVF singleton and IVF twin pregnancies that did not undergo spontaneous reduction. Evidence for adverse immediate and
long-term e ects of twin spontaneous reduction on the remaining pregnancy is conflicting (McNamara, 2016).
Notably, spontaneous reduction of a twin gestation may a ect prenatal screening results. In one study of ART-conceived gestations, Gjerris and colleagues (2009)
compared 56 twin pregnancies with a single early demise and 897 singleton gestations. They found no di erences in first-trimester serum marker concentrations as
long as the embryonic loss was identified before 9 weeks’ gestation. If diagnosed a er 9 weeks, the serum markers were higher and less precise in gestations with an
early demise of one twin than in the singleton gestations. With a vanishing twin, first-trimester maternal serum levels of the pregnancy associated plasma protein-A
(PAPP-A) can be elevated. Second-trimester MSAFP and dimeric inhibin A levels can also be higher (Huang, 2015). This phenomenon may also a ect noninvasive
prenatal testing using cell-free DNA (cfDNA). In one report, this e ect was thought to be responsible for 15 percent of the false-positive results from quantitative
counting methods (Futch, 2013). The recent development of single nucleotide polymorphism technology for cfDNA testing appears to hold promise in better
identifying these cases (Curnow, 2015). Regardless, the diagnosis of a spontaneously reduced abortus is ideally excluded to help avoid confusion with results from
aneuploidy and neural-tube defect screening.
Congenital Malformations
As noted earlier, the incidence of congenital malformations is appreciably higher in multifetal gestations compared with that in singleton pregnancies. In one survey-
based study, the congenital malformation rate was 406 per 10,000 twins compared with 238 per 10,000 singletons (Glinianaia, 2008). The malformation rate in
monochorionic twins was almost twice that of dichorionic twin gestations. This increase has been attributed to the higher incidence of structural defects in
monozygotic twins. Indeed, one large population-based study between 1998 and 2010 found that twins had a 73-percent greater risk of congenital heart disease than
singletons. The risk was substantially higher among monochorionic twins (Best, 2015). But, from a 30-year European registry of multifetal births, structural anomaly
rates rose steadily from 2.16 percent in 1987 to 3.26 percent in 2007 (Boyle, 2013). Yet, during this time, the proportion of dizygotic twins grew by 30 percent, whereas
the proportion of monozygotic twins remained stable. This higher risk of congenital malformations in dizygotic twins over time correlated with increased availability
of ART. An increase in rates of birth defects related to ART has been reported repeatedly (Boulet, 2016; Talauliker, 2012).
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
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twins closely paralleled those of singletons until 28 to 30 weeks’ gestation. Therea er, twin birthweights progressively lagged (Fig. 45-8). Beginning at 35 to 36 weeks’
gestation, 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 also excluded. (Data from 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 di erent 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). At Parkland,
we use the standards of birthweight in twin gestations stratified by placental chorionicity for identification of suspected fetal-growth restriction (Ananth, 1998).
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 a ect 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. (Used with permission from Dr. Laura Greer.)
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FIGURE 45-10
Davis quintuplets at 3 weeks following delivery. The first, second, and fourth newborns from the le each arose from separate ova, whereas the third and fi h
neonates are from the same ovum.
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In the third trimester, the larger fetal mass leads to accelerated placental maturation and relative placental insu iciency. In dizygotic pregnancies, marked size
discordancy usually results from unequal placentation, with one placental site receiving more perfusion than the other. Size di erences may also reflect di erent
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. 44, Accelerated Lung Maturation).
Hypertension
Pregnancy-related hypertensive disorders are more likely to develop with multifetal gestations. The exact incidence attributable to twin pregnancy is di icult to
determine because these gestations are more likely to deliver preterm and before preeclampsia usually develops. Also, women with twin pregnancies are o en older
and multiparous, qualities associated with lower rates of preeclampsia (Francisco, 2017). The incidence of pregnancy-related hypertension in women with twins is 20
percent at Parkland Hospital. In their analysis of 513 twin pregnancies, Fox and coworkers (2014) identified 15 percent of parturients with preeclampsia. Another
study compared 257 women with twins and gestational diabetes against 277 nondiabetic women carrying twins. These researchers found a twofold greater risk of
preeclampsia in women diagnosed with gestational diabetes (Gonzalez, 2012). Conversely, no specific zygosity confers a greater rate of hypertensive disorder in twin
pregnancies (Lu ovnik, 2016). Finally, from the National Center for Health Statistics, Luke and associates (2008) analyzed 316,696 twin, 12,193 triplet, and 778
quadruplet pregnancies. These investigators noted 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 greater 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 an incremental rise in
sFlt-1 concentrations, decline in PlGF levels, and increase in sFlt-1/PlGF ratios compared with normotensive twin pregnancies. With multifetal gestation,
hypertension not only develops more o en but also tends to develop earlier and be more severe. In the analysis of angiogenic factors mentioned above, more than
half of a ected women presented before 34 weeks, and their sFlt-1/PlGF ratio rise was more striking (Rana, 2012). This relationship is discussed in Chapter 40
(Endothelial Cell Injury).
Preterm Birth
The duration of gestation shortens with accruing fetal number. More than five of every 10 twins and nine of 10 triplets born in the United States in 2015 were
delivered preterm (Martin, 2017). Prematurity is sixfold and tenfold greater in twins and triplets, respectively (Giu re, 2012). One review showed that approximately
60 percent of preterm births in twins are indicated, about a third result from spontaneous labor, and 10 percent follow prematurely ruptured membranes (Chauhan,
2010). In another analysis of almost 300,000 live births, the proportion of preterm birth associated with premature membrane rupture rose with gestational plurality
from 13 percent with singletons to 20 percent with triplets or more (Pakrashi, 2013).
Although the causes of preterm delivery in twins and singletons may be di erent, neonatal outcome is generally the same at similar gestational ages (Kilpatrick,
1996; Ray, 2009; Salem, 2017). However, 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 e ects (Yinon, 2005).
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 newborns, cognitive outcomes between twins and singletons are similar (Lorenz, 2012). Christensen and associates (2006) found similar national
standardized test scores in the ninth grade in 3411 twins and 7796 singletons born between 1986 and 1988.
In contrast, among normal-birthweight neonates, 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 (Giu re, 2012). Greater risks of fetal-growth restriction, congenital
anomalies, twin-twin transfusion syndrome, and fetal demise of a cotwin are suggested contributors to these di erences (Lorenz, 2012).
UNIQUE FETAL COMPLICATIONS

Several unique complications arise in multifetal pregnancies. These are 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 a er reviewing the possibilities shown in
Figure 45-1.
Monoamnionic Twins
Only about 1 percent of all monozygotic twin gestations will share an amnionic sac, and approximately 1 in 20 monochorionic twin gestations are monoamnionic
(Hall, 2003; Lewi, 2013). Diamnionic twins can become monoamnionic if the dividing membrane spontaneous or iatrogenically ruptures. Their morbidity and
mortality rates then mirror those of monoamnionic twins.
Historical mortality rates in monoamnionic twins were reported to be as high as 70 percent. Contemporary outcomes are improved, yet the demise rate a er viability
remains elevated (Post, 2015). Of those fetuses alive before 16 weeks’ gestation, less than half survive until the neonatal period. Fetal abnormalities and
spontaneous miscarriage contribute to most losses (Prefumo, 2015). A er 20 weeks, the perinatal mortality rate for monoamnionic twin pregnancies approximates
15 percent (Shub, 2015). A high fetal death rate is attributable to preterm birth, congenital anomalies, twin-twin transfusion syndrome, or cord entanglement.
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Congenital anomaly rates in monoamnionic twins reach 18 to 28 percent (Post, 2015). Since concordance of anomalies is found in only approximately one quarter of
cases, the finding of normal anatomy in one twin does not negate the need for a thorough evaluation in the second. Also, because of the higher risk of cardiac
anomalies, fetal echocardiography is indicated in these pregnancies. Of note, monoamnionic twins are by definition monozygotic and thus presumed to be
genetically identical. Consequently, either both or none of the fetuses have chromosomal abnormalities except in rare cases of discordance (Zwijnenburg, 2010).
Indeed, the risk for Down syndrome in each fetus of the monozygotic pair is similar to or lower than the risk in maternal age-matched singletons (Sparks, 2016). The
standard methods for Down syndrome screening in these pregnancies can be applied (Chap. 14, Traditional Aneuploidy Screening Tests).
The rate of twin-twin transfusion syndrome in monoamnionic twins is lower than the rate reported in monochorionic diamnionic pregnancies. This may be due to
the near universal presence in monoamnionic twins of arterioarterial anastomoses, which are presumed to be protective (Hack, 2009b; Post, 2015). Nonetheless,
twin-twin transfusion syndrome surveillance is recommended and described in Diagnosis.
Umbilical cords frequently entangle (Fig. 45-11). Morbid cord entanglement appears to occur early, and monoamnionic pregnancies that have successfully reached
30 to 32 weeks’ gestation are at reduced risk. In one Dutch series, the incidence of intrauterine demise dropped from 15 percent a er 20 weeks to 4 percent at
gestational ages >32 weeks (Hack, 2009a). Although color-flow Doppler sonography is used to diagnose entanglement (Fig. 45-12), factors that lead to pathological
umbilical vessel constriction are unknown. A consequence is that fetal death from cord entanglement is unpredictable. Unfortunately, monitoring for this is relatively
ine ective. In one study, a er analysis of more than 10,000 hours of fetal tracing from 17 sets of monoamnionic twins, Quinn and colleagues (2011) concluded that
monitoring was physically possible in only 50 percent of cases. An abnormal fetal heart rate tracing prompted delivery in only six cases.
FIGURE 45-11
Monozygotic twins in a single amnionic sac. The smaller fetus apparently died first, and the second subsequently succumbed when umbilical cords entwined.
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FIGURE 45-12
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. (Used with permission from Dr. Julie Lo.)
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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. However, in 44 women managed as outpatients and admitted only for obstetrical indications, there were 13
stillbirths. Because of this report, women with monoamnionic twins are recommended to undergo 1 hour of daily fetal heart rate monitoring, either as an outpatient
or inpatient, beginning at 26 to 28 weeks’ gestation. With initial testing, a course of betamethasone is given to promote pulmonary maturation (Chap. 42,
Corticosteroids for Fetal Lung Maturation). If fetal testing remains reassuring and no other intervening indications arise, cesarean delivery is performed at 32 to 34
weeks. A second course of betamethasone can be given before this (American College of Obstetricians and Gynecologists, 2016). This management scheme is used at
Parkland Hospital and resulted in the successful 34-week delivery of the twins depicted in Figure 45-12.
Unique and Aberrant Twinning
Of monoamnionic twins just described, one interesting subset derives from embryonic splitting on postfertilization day 9. These “mirror image twins” are genetically
identical but have mirror image features such as handedness and hair whorls (Post, 2015).
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More seriously, several aberrations in monozygotic twinning 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 45-13.
FIGURE 45-13
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–a er 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 produce characteristic forms depending on which body parts are joined or shared (Fig.
45-14). Of these, thoracopagus is the most common (Mutchinick, 2011). The frequency of conjoined twins is not well established. 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 45-14
Types of conjoined twins. (Modified with permission from Spencer R: Theoretical and analytical embryology of conjoined twins: part I: embryogenesis, Clin Anat.
2000;13(1):36–53.)
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Conjoined twins can frequently be identified using sonography at midpregnancy (McHugh, 2006). This provides an opportunity for parents to decide whether to
continue the pregnancy. As shown in Figure 45-15, identification of cases during the first trimester is also possible. During sonographic interrogation, fetal poles are
closely associated and do not change relative position from one another. A targeted examination, including a careful evaluation of the organs involved, is necessary
before counseling can be provided. As shown in Figure 45-16, MR imaging is a valuable adjunct to clarify shared organs. Compared with sonography, MR imaging can
provide superior views, especially in later pregnancy when amnionic fluid is diminished and fetal crowding is greater (Hibbeln, 2012).
FIGURE 45-15
Sonogram of a conjoined twin pregnancy at 13 weeks’ gestation. These thoracoomphalopagus twins have two heads but a shared chest and abdomen.
FIGURE 45-16
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. (Used with permission from Dr. April Bailey.)
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Surgical separation of an almost completely joined twin pair may be successful if essential organs are not shared (O’Brien, 2015; Tannuri, 2013). Conjoined twins may
have discordant structural anomalies that further complicate decisions about whether to continue the pregnancy. Consultation with a pediatric surgeon o en assists
parental decision making. A recent series in Seminars in Pediatric Surgery with a preface by Spitz (2015) provide an excellent reference regarding postnatal
management.
Viable conjoined twins should be delivered by cesarean. For the purpose of pregnancy termination, however, vaginal delivery is possible because the union is most
o en pliable (Fig. 45-17). Still, dystocia is common, and if the fetuses are mature, vaginal delivery may be traumatic to the uterus or cervix.
FIGURE 45-17
Conjoined twins aborted at 17 weeks’ gestation. (Used with permission from Dr. Jonathan Willms.)
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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, o en 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. Its surviving tissue attaches to and receives vascularity from the
normal cotwin (Spencer, 2001). In one large epidemiological study, parasitic twins accounted for 4 percent of all conjoined twins and occurred more frequently in
male fetuses (Mutchinick, 2011).
Fetus-in-Fetu
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 the fetiform mass, whereas a heart and brain are
absent. These masses are believed to represent a monozygotic, monochorionic diamnionic twin gestation and are typically supported by large parasitic vessels to
the host (McNamara, 2016; Spencer, 2000). Malignant degeneration is rare (Kaufman, 2007).
Monochorionic Twins and Vascular Anastomoses
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All monochorionic placentas likely share some anastomotic connections. And, with rare exceptions, anastomoses between twins are unique to monochorionic twin
placentas. However, the number, size, and direction of these seemingly haphazard connections vary markedly (Fig. 45-18). In one analysis of more than 200
monochorionic placentas, the median number of anastomoses was 8, with an interquartile range of 4 to 14 (Zhao, 2013).
FIGURE 45-18
Shared placenta from pregnancy complicated by twin-twin transfusion syndrome. The following color code was applied for injection. Le 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. (Reproduced with permission from De Paepe ME,
DeKoninck P, Friedman RM: Vascular distribution patterns inmonochorionic twin placentas, Placenta. 2005 Jul;26(6):471–475.)
Artery-to-artery anastomoses are most frequent 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. 45-19). These deep arteriovenous anastomoses create a common villous compartment or “third circulation” that has been identified in
approximately half of monochorionic twin placentas.
FIGURE 45-19
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.”
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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
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. Classically, the donor twin is pale, and its recipient
sibling is plethoric. Similarly, one portion of the placenta o en appears pale compared with the remainder. The recipient neonate may also 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. 33, Polycythemia and Hyperviscosity). The prevalence of TTTS approximates 1 to 3 cases per 10,000 births (Society
for Maternal-Fetal Medicine, 2013).
Chronic TTTS results from unidirectional flow through deep arteriovenous anastomoses. Deoxygenated blood from a donor placental artery is pumped into a
cotyledon shared by the recipient (see Fig. 45-19). 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 superficial arterioarterial anastomoses—this unidirectional flow leads to an imbalance
in blood volumes (Lewi, 2013). Clinically important TTTS frequently is chronic and results from significant vascular volume di erences 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 with the
syndrome, hemoglobin concentrations between the donor and recipient twin do not di er (Lewi, 2013).
TTTS typically presents in midpregnancy when the donor fetus becomes oliguric from decreased renal perfusion (Society for Maternal-Fetal Medicine, 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. 45-20). In the donor twin, ischemia results from hypotension, anemia, or both. In the recipient, ischemia develops from blood pressure instability and episodes
of profound hypotension (Lopriore, 2011). Cerebral lesions may also be due to postnatal injury associated with preterm delivery (Chap. 34, Retinopathy of
Prematurity). In one review of 315 liveborn fetuses from pregnancies with TTTS, cerebral abnormalities were found in 8 percent (Quarello, 2007).
FIGURE 45-20
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These serial sonograms depict an interventricular hemorrhage with parenchymal extension and eventual porencephaly that developed following cotwin demise in a
monochorionic pregnancy. From le to right, these images were obtained 1 week, 5 weeks, and 8 weeks following demise of the cotwin.
If one twin of an a ected 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 one review of 343 twin pregnancies complicated by single fetal demise, the risk of neurodevelopmental morbidity in monochorionic twins was 26 percent
compared with 2 percent in dichorionic twins (Hillman, 2011). This morbidity was related to the 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 a er 34 weeks, the likelihood dramatically decreased—odds ratio 1.48.
The acuity of hypotension following the death of one twin with TTTS makes successful intervention for the survivor nearly impossible. Even with delivery
immediately a er 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). As such, immediate delivery is not considered beneficial in the absence of another indication.
Diagnosis
The criteria used to diagnose and classify varying severities of TTTS have dramatically changed. Previously, weight discordancy and hemoglobin di erences in
monochorionic twins were calculated. However, in many cases, these are late findings. According to the Society for Maternal-Fetal Medicine (2013), TTTS is
diagnosed based on two sonographic criteria. First, a monochorionic diamnionic pregnancy is identified. Second, hydramnios defined by a largest vertical pocket >8
cm in one sac and oligohydramnios defined by a largest vertical pocket <2 cm in the other twin is found. Only 15 percent of pregnancies complicated by lesser
degrees of fluid imbalance progress to TTTS (Huber, 2006). Although growth discordance or growth restriction may be found with TTTS, these per se are not
considered diagnostic criteria.
Organizations that include the American College of Obstetricians and Gynecologists (2016), Society for Maternal–Fetal Medicine (2013), and North American Fetal
Therapy Network (Emery, 2015) recommend sonography surveillance of pregnancies at risk for TTTS. To aid earlier identification of amnionic fluid abnormalities and
other complications of monochorionic twins, these examinations begin at approximately 16 weeks’ gestation, and subsequent studies are considered every 2 weeks.
Once identified, TTTS is typically classified by the Quintero (1999) staging system (Fig. 45-21):
FIGURE 45-21
A. Sonogram of stage I TTTS at 19 weeks’ gestation. Oligohydramnios in the donor twin sac causes the membrane to essentially wrap around the “stuck twin” and
suspend it from the anterior uterine wall. B. In this same pregnancy, hydramnios is seen in the recipient twin sac. The measured pocket exceeds 10 cm. C. Stage II
TTTS in a donor twin at 17 weeks’ gestation. Color Doppler highlights the arteries that outline the fetal bladder, which contains no urine.
Stage I—discordant amnionic fluid volumes as described in the earlier paragraph, 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
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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, evidence suggests that cardiac function of the recipient twin correlates with fetal outcome (Crombleholme, 2007). Although fetal
echocardiographic findings are not part of the Quintero staging system, many centers routinely perform fetal echocardiography for TTTS. Theoretically, earlier
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 to predict outcomes remains controversial (Society for Maternal-Fetal
Medicine, 2013).
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
have been reported to 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 (Society for Maternal-Fetal Medicine, 2013). At Parkland Hospital, among expectantly managed pregnancies with
TTTS, most had early disease at diagnosis, and 50 percent of stage I cases progressed (Duryea, 2016).
Several therapies are available for TTTS and include amnioreduction, laser ablation of vascular placental anastomoses, selective feticide, and septostomy. Described
further in Chapter 11 (Oligohydramnios), amnioreduction describes needle drainage of excess amnionic fluid. Septostomy is intentionally creating a hole in the
dividing amnionic membrane but has largely been abandoned as treatment (Society for Maternal-Fetal Medicine, 2013). Comparative data from randomized trials for
some of these other 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). A higher survival rate to age 6 months for at least one twin was found in pregnancies undergoing laser
ablation–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 an 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). Optimal therapy for stage
I disease is controversial.
A er 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 (MCA) Doppler evidence of anemia or polycythemia. Recently, in a
comparison of selective laser ablation of individual anastomoses versus ablation of the entire surface of the chorionic plate along the vascular equator, Baschat and
coworkers (2013) found that equatorial photocoagulation reduced the likelihood of recurrence.
Selective fetal 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. Any substance injected into one twin may a ect the other twin because of shared circulations. Thus, for the fetus chosen for
reduction, feticidal techniques include methods that occlude the umbilical vein or umbilical cord of using radiofrequency ablation, fetoscopic ligation, or
coagulation with laser, monopolar, or bipolar energy (Challis, 1999; Chang, 2009; Parra-Cordero, 2016). Even a er these procedures, however, the risks to the
remaining fetus are still appreciable (Rossi, 2009). This topic is further discussed in Selective Reduction or Termination.
Twin Anemia–Polycythemia Sequence
This form of chronic fetofetal transfusion, referred to as TAPS, is characterized by significant hemoglobin di erences between donor and recipient twins. However,
TAPS lacks the discrepancies in amnionic fluid volumes typical of TTTS (Slaghekke, 2010). It is diagnosed antenatally by MCA peak systolic velocity (PSV) >1.5
multiples of the median (MoM) in the donor and <1.0 MoM in the recipient twin (Society for Maternal-Fetal Medicine, 2013). The spontaneous form of TAPS reportedly
complicates 3 to 5 percent of monochorionic pregnancies, and it occurs in up to 13 percent of pregnancies a er laser photocoagulation of the placenta. Spontaneous
TAPS usually occurs a er 26 weeks’ gestation, 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 elucidate the natural history of TAPS and its management. In brief, evidence of
fetal compromise or greater di erences in MCA PSV between twins raise the stage.
Twin Reversed-Arterial-Perfusion Sequence
Also known as an acardiac twin, this is a rare but serious complication of monochorionic multifetal gestation. An estimated incidence is 1 case in 35,000 births. In the
classic twin reversed-arterial-perfusion (TRAP) sequence, there is a normally formed donor twin that shows features of heart failure and a recipient twin that lacks a
heart (acardius) and other structures. In one theory, the TRAP sequence is caused by a large artery-to-artery placental shunt, o en also accompanied by a vein-to-
vein shunt (Fig. 45-22). Within the single, shared placenta, arterial perfusion pressure of the donor twin exceeds that in the recipient twin, who thus receives reverse
blood flow containing 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 therefore disrupted growth and development of the upper body results. In these
cases, failed 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 45-23 (Faye-Petersen, 2006). Because of this vascular connection, the normal donor
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twin must not only support its own circulation but also pump blood through the underdeveloped acardiac recipient. This may lead to cardiomegaly and high-output
heart failure in the normal twin (Fox, 2007).
FIGURE 45-22
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, o en 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 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 45-23
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. (Used with permission from Dr. Michael D. Hnat.)
In the past, the mortality rate among the pump twins exceeded 50 percent. This stemmed largely from complications of prematurity or from a prolonged high-output
state leading to cardiac failure (Dashe, 2001). Risk appears to be directly related to size of the acardiac twin. One sonographic method to estimate acardiac twin size
uses the volume of an ellipse: length × width × height ×π/6. When the acardiac twin volume is <50 percent of that of the pump twin, expectant management may be
reasonable given the inherent risks of fetal intervention (Chap. 15, Radiofrequency Ablation)(Jelin, 2010). When the volume of the acardiac twin is large, however,
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treatment has generally been o ered. Radiofrequency ablation (RFA) is the preferred modality of therapy, and contemporary reports now suggest improved perinatal
outcomes. The North American Fetal Therapy Network reviewed their experiences with 98 cases from 1998 to 2008 in which RFA of the umbilical cord was performed
(Lee, 2013). Median gestational age at delivery was 37 weeks, and 80 percent of neonates survived (Lee, 2013). The average gestational age at the time of the RFA was
20 weeks, and the estimated acardius-to-pump twin volume on average was 90 percent. Major complications were prematurely ruptured membranes and preterm
birth.
Interestingly, TRAP sequences can also occur within monoamnionic pregnancies. The perinatal outcomes of such pregnancies appear to be worse than that of
monochorionic diamnionic cases. Sugibayashi and associates (2016) in a review of 40 cases recently reported that pump twin survival following RFA was 88 percent
in monochorionic diamnionic pregnancies but only 67 percent in monoamnionic pregnancies.
Hydatidiform Mole with Coexisting Normal Fetus
This unique gestation contains one normal fetus, and its cotwin is a complete molar pregnancy. Reported prevalence rates range from 1 in 22,000 to 1 in 100,000
pregnancies (Dolapcioglu, 2009). It must be di erentiated from a partial molar pregnancy, in which an anomalous singleton fetus—usually triploid—is accompanied
by molar tissue (Fig. 20-4). At times, a twin pregnancy may occur with a normal twin in one sac and a partial mole in the other sac (McNamara, 2016).
Diagnosis is usually made in the first half of pregnancy. Sonographically, a normal-appearing twin is accompanied by its cotwin, which is a large placenta containing
multiple small anechoic cysts (Fig. 20-4). O en, these pregnancies are terminated, but pregnancy continuation is increasingly adopted. First, the pregnancy
prognosis is not as poor as previously thought, and live birth rates range between 20 and 40 percent (Dolapcioglu, 2009; McNamara, 2016). Second, the risk of
persistent trophoblastic disease is similar whether the pregnancy is terminated or not (Massardier, 2009; Sebire, 2002). That said, given the limited number of cases,
robust data for firm recommendations are lacking. Importantly, complications of expectant management include vaginal bleeding, hyperemesis gravidarum,
thyrotoxicosis, and early-onset preeclampsia (McNamara, 2016). Many of these complications result in preterm birth with its attendant adverse perinatal sequelae as
well as perinatal loss. Logically, close surveillance is needed for those continuing the pregnancy.
DISCORDANT GROWTH OF TWIN FETUSES

Fetal size inequality develops in approximately 15 percent of twin gestations and may reflect pathological growth restriction in one fetus (Lewi, 2013; Miller, 2012).
Generally, as the weight di erence within a twin pair rises, the perinatal mortality rate increases proportionately. If it develops, restricted growth of one twin fetus,
o en termed selective fetal-growth restriction, 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 approximately 20 percent of the growth-restricted
fetuses (Lewi, 2013).
Etiopathogenesis
The cause of birthweight inequality in twin fetuses is o en unclear, but the etiology in monochorionic twins likely di ers from that in dichorionic twins. 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.
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 di erent genetic growth potential, especially if they are of opposite
genders. Second, 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 multifetal growth restriction. Placental pathology may play a role as well. In one study of 668 twin placentas, a strong relationship between
histological placental abnormalities and birthweight discordancy was observed in dichorionic, but not monochorionic, twin pregnancies (Kent, 2012).
Diagnosis
Size discordancy between twins can be determined sonographically. That said, di erences in crown-rump length are not reliable predictors for birthweight
discordance (Miller, 2012). Thus, most begin surveillance for discordancy a er the first trimester. One common method uses sonographic fetal biometry to compute
an estimated weight for each twin (Chap. 10, Gestational Age Assessment). The weight of the smaller twin is then compared with that of the larger twin. Thus,
percent discordancy is calculated as the weight of the larger twin minus the weight of the smaller twin, then divided by the weight of the larger twin. Alternatively,
given that abdominal circumference (AC) reflects fetal nutrition, some use the sonographic AC value of each twin.
With these methods, some diagnose selective fetal-growth restriction if the AC measurements di er more than 20 mm or if the estimated fetal weight di erence is 20
percent or more. That said, several di erent 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. At Parkland, Hollier and coworkers (1999) retrospectively
evaluated 1370 delivered twin pairs 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 syndrome, intraventricular hemorrhage, seizures, periventricular leukomalacia, sepsis, and necrotizing enterocolitis rose directly with the
degree of weight discordancy. Rates of these conditions grew substantially if discordancy exceeded 25 percent. The relative risk of fetal death increased significantly
to 5.6 if discordancy was more than 30 percent and rose to 18.9 if it was greater than 40 percent.
Management
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Serial Sonography
Sonographic monitoring of twin growth has become a mainstay in management. 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 evaluation interval >2 weeks was associated with a higher Quintero stage at the time of TTTS diagnosis. These findings have led some to recommend
serial sonographic examination 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. In addition, a specific ultrasound examination to search for TTTS is completed at each intervening 2-
week mark between these sonograms.
For dichorionic pregnancies, a recent report suggests that sonographic evaluation every 2 weeks would identify more abnormalities prompting delivery (Corcoran,
2015). It has yet to be determined if this practice would improve perinatal outcomes. At our institution, dichorionic twins are sonographically evaluated every 6
weeks.
Fetal Surveillance
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, and umbilical artery Doppler assessment have all been recommended in the management of twins. However, none has been
assessed in appropriately sized prospective trials (Miller, 2012).
If discordancy is identified in a monochorionic twin pregnancy, umbilical artery Doppler studies in the smaller fetus may help guide management (Gratacós, 2007).
Namely, investigators have correlated umbilical artery Doppler results with placental findings and with the degree of selective fetal-growth restriction to predict fetal
outcome (Gratacós, 2012). These correlations have yielded categories of selective fetal-growth restriction. Type I is characterized by positive end-diastolic flow, a
smaller degree of weight discordance, and a relatively benign clinical course. Type II displays persistently absent end-diastolic flow in the smaller twin and carries a
high risk of deterioration and demise. Type III is intermittently absent or reversed end-diastolic flow. Because of large artery-to-artery anastomoses associated with
the placentas in this category, type III is associated with a lower risk of deterioration than type II. In all evaluated cases, unequally shared placenta was noted to some
degree.
With uncomplicated dichorionic multifetal gestations, use of antepartum surveillance has not improved perinatal outcomes. In sum, the American College of
Obstetricians and Gynecologists (2016) recommends that antepartum testing be performed in multifetal gestations for indications similar to those for singleton
fetuses (Chap. 17, Fetal Movements).
At Parkland, all women with twin discordancy ≥25 percent undergo daily monitoring as an inpatient. Data are limited to establish the optimal timing of delivery of
twins for size discordancy alone. For those at advanced gestational ages, delivery can be pursued.
FETAL DEMISE
Death of One Fetus
At any time during multifetal pregnancy, one or more fetuses may die, either simultaneously or sequentially. Causes and incidence of fetal death are related to
zygosity, chorionicity, and growth concordance.
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 in Pregnancy Complications. In a slightly more advanced gestation, fetal death may go undetected until delivery. In this case, delivery
of a normal newborn is followed by expulsion of 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. 45-24).
FIGURE 45-24
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. (Used with permission from Dr. Michael V.
Zaretsky.)
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As shown in Figure 45-25, the risk of stillbirth is related to gestational age in all twins but is much higher for monochorionic twin pregnancies before 32 weeks’
gestation. In a review of 9822 twin pregnancies, Morikawa and associates (2012) reported that 2.5 percent of monochorionic diamnionic twins greater than 22 weeks
had a death of one or both twins. This compared with 1.2 percent of dichorionic twins. 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. Other investigations have found similar
trends (Danon, 2013; Hillman, 2011; Mahony, 2011).
FIGURE 45-25
Prospective risk of stillbirth among women who reached a given gestational week (per 1000 women). (Reproduced with permission from Morikawa M, Yamada T,
Yamada T, et al: Prospective risk of stillbirth: monochorionic diamniotic twins vs dichorionic twins, J Perinat Med. 2012 Jan 10;40(3):245–249.)
Other factors that a ect 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 a vanishing twin, the risk of death a er the first trimester is not increased for the survivor. However, when a fetus dies in the second trimester or
later, the e ect of gestational age at the time of death and the mortality risk to the cotwin are less clear. In an analysis by Hillman and colleagues (2011), cotwin
demise rates were una ected regardless of whether the first death occurred at 13 to 27 weeks’ gestation or at 28 to 34 weeks. In cases with the death of one twin a er
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 a er 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 higher risk of neurodevelopmental morbidity was identified in
monochorionic twins compared with dichorionic twins. If the one fetus died a er 34 weeks, the likelihood of neurological deficits was essentially the same between
monochorionic and dichorionic twin pregnancies (Hillman, 2011).
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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 a er
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.
Management
Decisions should be based on gestational age, the cause of death, and the risk to the surviving fetus. First-trimester losses require no additional surveillance for this
specific indication. If the loss occurs a er 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 o en cause the demise of one twin followed by sudden hypotension in the
other (Twin-Twin Transfusion Syndrome). For this reason, if one fetus of a monochorionic twin gestation dies a er 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 in the first trimester, it should not a ect the surviving twin.
Single fetal death during the late second and early third trimesters presents the greatest risk to the surviving twin. Although the risks of subsequent death or
neurological damage to the survivor are comparatively higher 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 the intrauterine environment is hostile, the goal is to prolong the preterm pregnancy.
Timing of elective delivery a er conservative management of a late second- or early third-trimester single fetal death is debatable. Dichorionic twins can probably be
safely delivered at term. Monochorionic twin gestations are more di icult to manage and are o en 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. The American College of
Obstetricians and Gynecologists (2016) also endorse an individualized approach to such cases.
Impending Death of One Fetus
During antepartum surveillance tests of well-being, abnormal results in one twin, 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.
O en the compromised fetus is severely growth restricted or anomalous. Thus, performing amniocentesis for fetal chromosomal analysis in women of advanced
maternal age carrying twin pregnancies is advantageous, even for those who would continue their pregnancies regardless of the diagnosis. Chromosomal
abnormality identification in one fetus allows rational decisions regarding interventions.
PRENATAL CARE
With prenatal management of multifetal pregnancy, primary goals aim 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. A
digital cervical examination is performed at each visit to screen for cervical shortening or dilation. Identification of other unique complications discussed earlier may
also lead to interventions including admission or early delivery.
Diet
Along with more frequent prenatal visits, the maternal diet should provide additional requirements for calories, protein, minerals, vitamins, and essential fatty acids.
The Institute of Medicine (2009) recommends a 37- to 54-lb weight gain for women with twins and a normal BMI. In their review, Goodnight and Newman (2009)
endorse supplementation of micronutrients such as calcium, magnesium, zinc, and vitamins C, D, and E. This is based on upper intake levels from the Food and
Nutrition Board of the Institute of Medicine. The daily recommended augmented caloric intake for women with twins is 40 to 45 kcal/kg/d. Diets contain 20 percent
protein, 40 percent carbohydrate, and 40 percent fat divided into three meals and three snacks daily.
Sonography
As noted earlier (Fetal Demise), serial sonographic examinations are usually performed throughout the third trimester to search for abnormal fetal growth and assess
amnionic fluid volume. 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 di icult. Some measure the deepest vertical pocket in each sac or assess the fluid
subjectively. Magann and coworkers (2000) compared subjective assessment and several objective methods of assessing amnionic fluid volume 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 (Duryea, 2017; Hernandez, 2012).
Antepartum Fetal Surveillance
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Of surveillance methods, the nonstress test or biophysical profile is o en selected for twin or higher-order multifetal gestations. Because of the complex
complications associated with these gestations and the potential technical di iculties in di erentiating 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 insu icient data to determine its e icacy (DeVoe, 2008).
Similar findings have been reported with the addition of umbilical artery Doppler velocimetry in twins with concordant growth. For example, when umbilical artery
Doppler velocimetry was added to management compared with fetal testing based on fetal-growth parameters alone in the absence of growth discordance,
perinatal outcomes were not improved (Giles, 2003). Likewise, Hack and associates (2008) investigated the utility of umbilical artery Doppler velocimetry in 67
uncomplicated monochorionic twin gestations and did not find di erences in mortality rates using pulsatility indices of the umbilical artery.
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. Options are similar to those described in the management of
impending fetal death (Prenatal Care).
PRETERM BIRTH
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). Similar to singleton preterm labor, intraamnionic infection is documented in approximately one third of twin pregnancy cases (Oh, 2017).
In twins, the proportion of preterm births varies widely from 40 to 70 percent (Giu re, 2012). For example, black women have disparately higher risks for preterm
delivery (Grant, 2017).
Prediction of Preterm Birth
A major goal of multifetal prenatal care is accurate prediction of women likely to experience preterm delivery. Within the past decade, cervical length has been
shown to be a potent predictor of preterm labor and delivery. To and associates (2006) sonographically measured cervical length in 1163 twin pregnancies at 22 to 24
weeks’ gestation. 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; and only 1
percent for 40 mm. In one review, Conde-Agudelo and coworkers (2010) concluded that a cervical length <20 mm was most accurate for predicting birth before 34
weeks, with a specificity of 97 percent and positive likelihood ratio of 9.0. Kindinger and colleagues (2016) noted that prediction depended on both cervical length
and gestational age at ascertainment. One study compared serial cervical length measurements with a single midgestation measurement. These authors found that
multiple assessments were more accurate to determine the risk of preterm twin birth in asymptomatic women (Melamed, 2016a). In another study, a change in
cervical length ≥0.2 cm identified pregnancies at risk for delivery before 35 weeks (Moroz, 2017). Interestingly, a closed internal os by digital examination was found
to be as predictive of postponed delivery as was the combination of a normal sonographically measured cervical length and negative fetal fibronectin test result
(McMahon, 2002). Unfortunately, cervical length assessment in twin pregnancies has not been associated with improved outcomes (Gordon, 2016).
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, but
only in subgroups of singleton pregnancies. In general, most have been disappointingly ine ective for both singleton and multifetal pregnancies (American College
of Obstetricians and Gynecologists, 2016).
Bed Rest
The bulk of evidence suggests that routine hospitalization does not prolong multifetal pregnancy. In one metaanalysis, the practice did not reduce the risk of preterm
birth or perinatal mortality (Crowther, 2010). At Parkland Hospital, elective hospitalization was compared with outpatient management, and no advantages were
found (Andrews, 1991). Importantly, however, almost half of women managed as outpatients 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. However, little evidence suggests that these measures
substantially change outcome.
Prophylactic Tocolysis
This has not been studied extensively in multifetal pregnancies. In one review of prophylactic oral beta-mimetic therapy that included 374 twin pregnancies,
treatment did not reduce the rate of twins delivering before 37 or before 34 weeks’ gestation (Yamasmit, 2015). In light of the Food and Drug Administration warning
against the use of oral terbutaline because of maternal side e ects, the prophylactic use of beta-mimetic drugs in multifetal gestations seems unwarranted.
Intramuscular Progesterone Therapy
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Although somewhat e ective in reducing recurrent preterm birth in women with a singleton pregnancy, weekly injections of 17 alpha-hydroxyprogesterone caproate
(17-OHP-C) are not e ective for multifetal gestations (Caritis, 2009; Rouse, 2007). These results were corroborated in a randomized trial of 240 twin pregnancies
(Combs, 2011). Moreover, women carrying twins and having a cervical length <36 mm (25th percentile) did not benefit despite their greater risk for preterm birth
(Durnwald, 2010). Senat and colleagues (2013) assigned 165 asymptomatic women with twins and a cervical length <25 mm to 17-OHP-C and also found no
reduction in delivery rate before 37 weeks. Last, in an evaluation of plasma drug concentrations, higher concentrations of 17-OHP-C were associated with earlier
gestational age at delivery (Caritis, 2012). The authors concluded that 17-OHP-C may adversely lower the gestational age at delivery in women with twin gestations.
In sum, administration of intramuscular 17-OHP-C 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 to prevent preterm birth has provided conflicting results. Cetingoz and coworkers (2011) gave
100 mg of micronized progesterone intravaginally daily from 24 to 34 weeks’ gestation. 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. In the Prevention of Preterm Delivery in Twin Gestations (PREDICT) trial, 677 women with twins were randomly assigned to receive prophylactic, 200-
mg progesterone pessaries or placebo pessaries (Rode, 2011). Progesterone failed to reduce delivery rates before 34 weeks. In a subgroup analysis that included only
women with a short cervix or a history of prior preterm birth, also no benefit was found (Klein, 2011). Norman and colleagues (2009) also noted no lower rates of
delivery before 34 weeks with progesterone gel treatment.
Romero and colleagues (2017) performed a metaanalysis of individual patient data for 303 women with twin gestation and a short cervix randomized to receive
either vaginal progesterone or no treatment. They reported a significantly reduced risk of preterm birth before 30 weeks’ gestation and improved composite
perinatal outcomes in the treated women. Currently at Parkland Hospital, management of women with multifetal gestations does not typically include progesterone
in any formulation.
The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) is currently enrolling patients into a randomized, placebo-
controlled trial to further evaluate the use of micronized vaginal progesterone or the Arabin pessary, describe subsequently (PROSPECT, 2015). The primary outcome
is delivery prior to 35 weeks or fetal loss.
Cervical Cerclage
Prophylactic cerclage does not improve perinatal outcome in women with multifetal pregnancies. Studies have included women who were not specially selected but
also those who were selected because of a shortened cervix that was identified sonographically (Houlihan, 2016; Newman, 2002; Rebarber, 2005). Indeed, in the
latter group, cerclage may actually worsen outcomes (Berghella, 2005; Roman, 2013).
Rescue cerclage in women with a second-trimester twin gestation and a dilated cervix may be beneficial. Roman and coworkers (2016) reported a retrospective
cohort study in which women undergoing rescue cerclage had significantly better neonatal outcomes than those without cerclage.
Pessary
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. One of the most popular is the silicone Arabin pessary. In a study of its use in women with a short cervix
between 18 and 22 weeks’ gestation, 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). In another randomized trial, women treated with a cervical pessary had significantly fewer births before 34 weeks
(Goya, 2016).
Other studies have been less favorable. In the randomized Pessaries in Multiple Pregnancy as a Prevention of Preterm Birth (ProTWIN) trial, 813 unselected women
with twins received either the Arabin pessary between 12 and 20 weeks or no treatment (Liem, 2013). The pessary failed to reduce preterm birth overall but did
decrease delivery rates before 32 weeks—29 versus 14 percent—in a subset of women with a cervical length <38 mm. Similar results were reported from a
randomized multicenter trial with a total of 1180 twin pregnancies (Nicolaides, 2016). A smaller randomized study using a Bioteque cup pessary showed no
di erence in outcomes (Berghella, 2017). At this time, pessary use is not recommended by the American College of Obstetricians and Gynecologists (2016). As noted
above, results from the ongoing PROSPECT trial are anticipated to provide more data.
Treatment of Preterm Labor
Although many advocate their use, therapy with tocolytic agents to forestall preterm labor in multifetal pregnancy does not result in measurably improved neonatal
outcomes (Chauhan, 2010; Gyetvai, 1999). Another caveat is that tocolytic therapy in women with a multifetal pregnancy entails higher risks than in singleton
pregnancy. This stems in part from augmented pregnancy-induced hypervolemia, which raises cardiac demands and increases the susceptibility to iatrogenic
pulmonary edema (Chap. 47, Acute Pulmonary Edema). Gabriel and colleagues (1994) compared outcomes of 26 twin and six triplet pregnancies with those of 51
singletons—all treated with a beta-mimetic drug for preterm labor. Women with a multifetal gestation had significantly more cardiovascular complications—43
versus 4 percent—including three gravidas with pulmonary edema. In a retrospective analysis, Derbent and coworkers (2011) evaluated nifedipine tocolysis in 58
singleton and 32 twin pregnancies. These authors reported higher incidences of side e ects such as maternal tachycardia in women with twins—19 versus 9 percent.
Glucocorticoids for Lung Maturation
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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). In a large retrospective study evaluating betamethasone therapy e icacy in preterm twin versus
preterm singleton pregnancies, no di erences in neonatal morbidity between the two groups were identified (Melamed, 2016b). Gyamfi and associates (2010)
evaluated betamethasone concentrations in women receiving weekly antenatal corticosteroids and found no di erences in levels between twins and singletons.
Conversely, another study found lower cord/maternal ratios of dexamethasone in twin versus singleton pregnancies (Kim, 2017). These treatments are discussed in
Chapter 42 (Corticosteroids for Fetal Lung Maturation). At this time, guidelines for the use of these agents do not di er from those for singleton gestations (American
College of Obstetricians and Gynecologists, 2016).
Preterm Premature Membrane Rupture
The frequency of preterm premature rupture of membranes (PPROM) rises with increasing plurality. In a population-based study of more than 290,000 live births, the
proportion of preterm birth complicated by premature rupture was 13.2 percent in singletons (Pakrashi, 2013). This rate compared with rates of 17, 20, 20, and 100
percent in twins, triplets, quadruplets, and even higher-order multiples, respectively. Multifetal gestations with PPROM are managed expectantly similar to singleton
pregnancies (Chap. 42, Intentional Delivery). 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 number of days to subsequent delivery was overall shorter for twins—3.6 days compared with 6.2
days for singletons. This latency di erence was significant in pregnancies a er 30 weeks—1.7 days and 6.9 days. Importantly, latency beyond 7 days approximated 40
percent in both groups.
Delayed Delivery of Second Twin
Infrequently, a er preterm birth of the presenting fetus, it may be advantageous for undelivered fetus(es) to remain in utero. Trivedi and Gillett (1998) reviewed 45
case reports of asynchronous birth in multifetal gestations. Although reported outcomes may reflect bias, 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’
gestation. Survival of the firstborn neonate 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 a er 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.
LABOR AND DELIVERY

Preparations
A litany of complications may be encountered during labor and delivery of multiple fetuses. In addition to preterm birth, rates of uterine contractile dysfunction,
abnormal fetal presentation, umbilical cord prolapse, placenta previa, placental abruption, emergent operative delivery, and postpartum hemorrhage from uterine
atony are higher. All of these must be anticipated, and thus certain precautions and special arrangements are prudent. These should include the following.
1. An appropriately trained obstetrical attendant should remain with the mother throughout labor. Continuous 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) a er
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 e ectively. Equipment must be on
site to provide emergent anesthesia, operative intervention, and maternal and neonatal resuscitation.
Timing of Delivery
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Several factors a ect this timing and include gestational age, fetal growth, lung maturity, and presence of maternal complications. 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 o en exceeds this value by approximately 32 weeks in multifetal pregnancies. Similar increased values of surfactant have
been noted in twins a er 31 weeks’ gestation (McElrath, 2000). 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 di erent, and the smallest, most stressed twin fetus is typically more mature.
At the other end of the spectrum, 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. 43, Incidence). From an analysis of almost
300,000 twin births, at and beyond 39 weeks, the risk of subsequent stillbirth was greater than the risk of neonatal mortality (Kahn, 2003).
From their guidelines, the American College of Obstetricians and Gynecologists (2016) recommends delivery at 38 weeks for uncomplicated dichorionic twin
pregnancies. Women with uncomplicated monochorionic diamnionic twin pregnancies can undergo delivery between 34 and 376/7 weeks. And, for women with
monoamnionic twin pregnancies, delivery is recommended at 32 to 34 weeks. At Parkland Hospital, we generally follow these recommendations but do not routinely
deliver monochorionic diamnionic twin pregnancies before 37 weeks unless another obstetrical indication develops.
Evaluation of 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. 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 a 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.
A er 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 usually
chosen because of fetal presentations. In general, cephalic presentation of the first fetus in a laboring woman with twins may be considered for vaginal delivery
(American College of Obstetricians and Gynecologists, 2016). The proportion of women undergoing an attempted vaginal delivery varies greatly depending on the
skills of the delivering physician (de Castro, 2016; Easter, 2017; Schmitz, 2017). Still, the cesarean delivery rate is high. For example, of the 547 women with the first
twin presenting cephalic who were admitted to Parkland Hospital during 5 years, only 32 percent were delivered spontaneously. And, 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 rising cesarean delivery rate in twin pregnancies across the
United States (Antsaklis, 2013).
Labor Induction or Stimulation
A er a comparison of 891 twins with more than 100,000 singleton pregnancies included in the Consortium of Safe Labor, Le wich and colleagues (2013) concluded
that active labor progressed more slowly in both nulliparas and multiparas with twins. Provided women with twins meet all criteria for oxytocin administration, it
may be used as described in Chapter 26 (Oxytocin). Wolfe and associates (2013) evaluated the success of labor induction and concluded that oxytocin alone or in
combination with cervical ripening can safely be used in twin gestations. Taylor and coworkers (2012) reported similar results. Conversely, Razavi and colleagues
(2017) found that maternal morbidity was increased with labor induction. In an analysis of twin births in the United States, induction rates of twin pregnancies have
decreased from a maximum of 13.8 percent in 1999 to 9.9 percent in 2008 (Lee, 2011). Generally, at Parkland Hospital we do not induce or augment labor in women
with a multifetal gestation. In suitable candidates with a strong desire for vaginal birth, amniotomy induction has been one option.
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. If general anesthesia becomes necessary for intrauterine manipulation, uterine relaxation can be accomplished rapidly with one of the halogenated
inhalation agents discussed in Chapter 25 (Inhalational Anesthetics). Some clinicians use intravenous or sublingual nitroglycerin or intravenous terbutaline to
achieve uterine relaxation yet avoid the risks associated with general anesthetics. These agents are usually best administered by the anesthesia team.
Delivery Route
Regardless of fetal presentation during labor, obstetricians must be ready to deal with any change of fetal position during delivery. This is especially true following
delivery of the first twin. Importantly, related to delivery method, second twins at term have worse composite neonatal outcomes compared with outcomes of their
cotwin regardless of delivery method (Muleba, 2005; Smith, 2007; Thorngren-Jerneck, 2001).
Cephalic-Cephalic Presentation
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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. From their review, Hogle and associates (2003) found that planned cesarean delivery does not
improve neonatal outcome when both twins are cephalic. The randomized trial by Barrett and coworkers (2013) a irms this conclusion.
Cephalic-Noncephalic Presentation
The optimal delivery route for cephalic–noncephalic twin pairs remains controversial. 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, or fetal distress. Most but not all studies report 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 >1500g. A French multicenter study of 5915 twin pregnancies
illustrates this (Schmitz, 2017). Of these, 25 percent had a planned cesarean delivery. The other 75 percent with a first twin cephalic and gestational age >32 weeks
had a planned trial of vaginal delivery, which was successful in 80 percent. Interestingly, perinatal mortality and morbidity rates were significantly higher in the
planned cesarean delivery group delivered <37 weeks—5.2 versus 3.0 percent, respectively. Fox and colleagues (2014) reported outcomes in 287 diamnionic twin
pregnancies, of which 130 underwent a planned vaginal delivery. Only 15 percent of the planned vaginal delivery group underwent a cesarean delivery. Perinatal
outcomes were similar in both groups. These two studies included only those fetuses with estimated weights >1500 g. Notably, comparable or even better fetal
outcomes with vaginal delivery have been reported with neonates weighing <1500 g compared with those weighing >1500 g (Caukwell, 2002; Davidson, 1992).
Other investigators advocate cesarean delivery for both members of a cephalic-noncephalic twin pair (Armson, 2006; Ho mann, 2012). Yang and coworkers (2005a,b)
studied 15,185 cephalic-noncephalic twin pairs. The risks of asphyxia-related neonatal deaths and morbidity were higher in the group in which both twins were
delivered vaginally compared with the group in which both twins underwent cesarean delivery.
To add insight into the clinical complexities just discussed, a randomized trial was designed by the Twin Birth Study Collaborative Group from Canada. The study
results described by Barrett and associates (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’ gestation 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, were similar in both groups. Salient
maternal and perinatal outcomes are shown in Table 45-3. No significant di erences in outcomes were noted between the two groups of women. Although risks to
mother or fetuses with planned vaginal delivery in these circumstances were not increased, Greene (2013) posited that this trial would have only modest e ects on
the cesarean delivery rate of women with twins.
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TABLE 45-3
Maternal and Perinatal Outcomes of Women with a Twin Pregnancy Randomized to Planned Cesarean versus Vaginal Delivery
Outcome Planned Cesarean Delivery Planned Vaginal Delivery p value
Maternal (No.) 1393 1393
Cesarean delivery 89.9% 39.6%
Before labor 53.8% 14.1%
Serious morbidity 7.3% 8.5% 0.29
Death (No.) 1 1
Hemorrhage 6.0% 7.8%
Blood transfusion 4.7% 5.4%
Thromboembolism 0.4% 0.1%
Perinatal (No.) 2783 2782
Primary composite outcome 2.2% 1.9% 0.49
Perinatal mortality 9 per 1000 6 per 1000
Serious morbidity 1.3% 1.3%
Possible encephalopathya 0.5% 0.4%
Intubation 1.0% 0.6%
aIncludes coma; stupor; hyperalert, drowsy or lethargic; or ≥2 seizures.
Data from Barrett, 2013.
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 di iculties may develop in the
following settings. First, the fetus may be large, and the a ercoming head is larger than the birth canal. Second, the fetal body can be small, and delivery of the
extremities and trunk through an inadequately e aced and dilated cervix causes the relatively larger head to become trapped above the cervix. This is more likely
when there is significant disproportion between the head and body. Examples are preterm or growth-restricted fetuses or those with macrocephaly from
hydrocephaly. Last, umbilical cord prolapse is an ever-present risk.
If these problems are anticipated or identified, cesarean delivery is o en preferred with a viable-sized 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 di erence in the rate of 5-minute Apgar scores <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 (Partial
Breech Extraction).
Twin fetuses may become locked together during delivery if the first presents breech and the second 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.
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 is 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 a erward, 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.
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In the past, the safest interval between delivery of the first and second twins was frequently cited as <30 minutes. Rayburn and colleagues (1984) and others have
shown that if continuous fetal monitoring is used, a good outcome is usually achieved even if this interval is longer. A direct correlation between worsening umbilical
cord blood gas values and increasing time between delivery of first and second twins has been shown (Leung, 2002; Stein, 2008). From review of 239 twin gestations,
Gourheux and associates (2007) determined that mean umbilical arterial pH was significantly lower a er the delivery interval exceeded 15 minutes. In a study of
more than 175,000 twin pairs, Cheng and colleagues (2017) reached similar conclusions for maternal and perinatal morbidity.
If the occiput or breech presents immediately over the pelvic inlet, but is not fixed in the birth canal, the presenting part can o en be guided into the pelvis by one
hand in the vagina, while a second hand on the uterine fundus exerts moderate pressure caudally. A presenting shoulder may be gently converted into a cephalic
presentation. 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.
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, an obstetrician skilled in intrauterine fetal manipulation and anesthesia personnel skilled in providing
anesthesia to e ectively relax the uterus for vaginal delivery of a noncephalic second twin are essential (American College of Obstetricians and Gynecologists, 2016).
To take maximum advantage of the dilated cervix before the uterus contracts and the cervix retracts, delay should 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 e ective uterine relaxation is not
immediately available.
With internal podalic version, a fetus is turned to a breech presentation using the hand placed into the uterus (Fig. 45-26). The obstetrician grasps the fetal feet to
then e ect delivery by breech extraction (Chap. 28, Total Breech Extraction). As mentioned earlier, Fox and associates (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 internal 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. Additional information and illustrations of this procedure are found in Cunningham and Gilstrap’s Operative Obstetrics, 3rd edition
(Yeomans, 2017).
FIGURE 45-26
Internal podalic version. Upward pressure on the head by an abdominal hand is applied as downward traction is exerted on the feet.
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Vaginal Birth a er Cesarean Delivery
Any attempt to deliver twins vaginally in a woman who has previously undergone one or more cesarean deliveries should be carefully considered. Some studies
support the safety of attempting a vaginal birth a er cesarean delivery (VBAC) for selected women with twins (Cahill, 2005; Ford, 2006; Varner, 2005). According to the
American College of Obstetricians and Gynecologists (2017c), no evidence currently suggests an increased risk of uterine rupture, and women with twins and one
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previous cesarean delivery with a low transverse incision may be considered candidates for trial of labor. At Parkland Hospital, we recommend repeat cesarean
delivery.
Cesarean Delivery for Multifetal Gestation
Several unusual intraoperative problems can arise during cesarean delivery of twins or higher-order multiples. Supine hypotension is common, and thus gravidas are
positioned in a le lateral tilt to deflect uterine weight o the aorta (Chap. 4, Renin, Angiotensin II, and Plasma Volume). 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. 28-11). 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.
Triplet or Higher-Order Gestation
Fetal heart rate monitoring during labor with triplet pregnancies is challenging. A scalp electrode can be attached to the presenting fetus, but it is di icult 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 o en 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 should undergo cesarean delivery (American College of
Obstetricians and Gynecologists, 2016). 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. 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 di er from those of a matched group of triplet pregnancies undergoing elective cesarean delivery. Conversely,
in one review of more than 7000 triplet pregnancies, vaginal delivery was associated with a higher perinatal mortality rate (Vintzeleos, 2005). Lappen and coworkers
(2016) reported similar results from the database of the Consortium on Safe Labor. They recommended prelabor cesarean delivery for triplets. Importantly, the
overall cesarean delivery rate among triplets was 95 percent.
SELECTIVE REDUCTION OR TERMINATION

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. The procedure should be performed by an operator skilled and experienced
in sonographically guided procedures.
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, 2017b). One 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’ gestation. 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 a er 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 avoid entry or traverse the sacs of fetuses selected for
retention.
Evans and associates (2005) analyzed more than 1000 pregnancies from 1995 to 1998. The pregnancy loss rate varied from a low of 4.5 percent for triplets that were
reduced to twins. The loss rate rose with each addition to the starting number of fetuses and peaked at 15 percent for six or more fetuses. Operator skill and
experience are believed responsible for the low and declining rates of pregnancy loss.
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. In some
cases, termination is considered because the abnormal fetus may jeopardize the normal one.
Prerequisites to selective termination include a precise diagnosis for the anomalous fetus and absolute certainty of fetal location. 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
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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 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
a ect the pregnancy loss rate.
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 (American College of Obstetricians and Gynecologists, 2017b). Specific
risks of selective termination or reduction are: (1) abortion of the remaining fetuses; (2) abortion or retention of the wrong fetus(es); (3) damage without death to a
fetus; (4) preterm labor; (5) discordant or growth-restricted fetuses; and (6) maternal complications. The last includes potential infection, hemorrhage, or
disseminated intravascular coagulopathy because of retained products of conception. 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).
REFERENCES
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Alexander JM, Leveno KJ, Rouse D, et al: Cesarean delivery for the second twin. Obstet Gynecol 112(4):748, 2008
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4/11/2018

Williams Obstetrics, 25e >

CHAPTER 45: Multifetal Pregnancy

—J. Whitridge Williams (1903)

Outcome Singletons (No.) Twins (No.)

Pregnancies 202,306 2412

Birthsa 202,306 4824

Stillbirths 1011 (5.0) 114 (23.6)

Neonatal deaths 590 (2.9) 92 (19.5)

Perinatal deaths 1601 (7.9) 206 (42.7)

Very low birthweight (<1500 g) 1927 (9.6) 507 (107.6)

aBirth data are represented as number (per 1000).

Data from Dr. Don McIntire.

MECHANISMS OF MULTIFETAL GESTATIONS

Dizygotic versus Monozygotic Twinning

Genesis of Monozygotic Twins

Superfetation and Superfecundation

Factors A ecting Twinning

Sex Ratios in Multifetal Pregnancies

Rates of Twin-Specific Complications in Percent

Diamnionic/dichorionic 6–7 30 40 0 18–20

Diamnionic/monochorionic 13–14 50 60 100 30–40

Monoamnionic/monochorionic <1 40 60–70 80–90 58–60

Conjoined 0.002 to 0.008 — 70–80 100 70–90

aDelivery before 37 weeks.

Data from Manning, 1995.

DIAGNOSIS OF MULTIFETAL GESTATION

Other Diagnostic Aids

MATERNAL PHYSIOLOGICAL ADAPTATIONS

Long-Term Infant Development

UNIQUE FETAL COMPLICATIONS

Unique and Aberrant Twinning

External Parasitic Twins

Monochorionic Twins and Vascular Anastomoses

Twin-Twin Transfusion Syndrome

Fetal Brain Damage

Stage IV—ascites or frank hydrops in either twin

Stage V—demise of either fetus.

Management and Prognosis

Twin Anemia–Polycythemia Sequence

Twin Reversed-Arterial-Perfusion Sequence

Hydatidiform Mole with Coexisting Normal Fetus

DISCORDANT GROWTH OF TWIN FETUSES

Impending Death of One Fetus

Antepartum Fetal Surveillance

Prediction of Preterm Birth

Prevention of Preterm Birth

Intramuscular Progesterone Therapy

Vaginal Progesterone Therapy

Treatment of Preterm Labor

Glucocorticoids for Lung Maturation

Preterm Premature Membrane Rupture

Delayed Delivery of Second Twin

LABOR AND DELIVERY

3. Blood for transfusion is readily available if needed.

Evaluation of Fetal Presentation

Labor Induction or Stimulation

Analgesia and Anesthesia

Outcome Planned Cesarean Delivery Planned Vaginal Delivery p value

Maternal (No.) 1393 1393

Cesarean delivery 89.9% 39.6%

Before labor 53.8% 14.1%

Serious morbidity 7.3% 8.5% 0.29

Hemorrhage 6.0% 7.8%