Twin Pregnancy: Prenatal Issues

Twin pregnancy: Prenatal issues - UpToDate 30/03/21 20.
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Twin pregnancy: Prenatal issues

Authors: Stephen T Chasen, MD, Frank A Chervenak, MD
Section Editors: Deborah Levine, MD, Lynn L Simpson, MD
Deputy Editor: Vanessa A Barss, MD, FACOG
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Feb 2021. | This topic last updated: Oct 20, 2020.
INTRODUCTION
Twin pregnancy is associated with higher rates of almost every potential complication of
pregnancy, with the exceptions of postterm pregnancy and macrosomia. The most serious
risk is preterm delivery, which plays a major role in the increased perinatal mortality and
short-term and long-term morbidity observed in these infants. Higher rates of fetal growth
restriction and congenital anomalies also contribute to adverse outcome in twin births. In
addition, monochorionic twins are at risk for complications unique to these pregnancies,
such as twin-twin transfusion syndrome, which can be lethal or associated with serious
morbidity.
This topic will provide an overview of the prenatal care of women with twin pregnancy.
Intrapartum management is reviewed separately. (See "Twin pregnancy: Labor and delivery".)
CLINICAL PRESENTATION
Twin pregnancies are usually first identified when an ultrasound examination is performed in
early pregnancy for indications such as determination of gestational age or viability,
measurement of nuchal translucency, or fetal anatomic survey (see 'Screening and diagnosis'
below). An increased likelihood of twin pregnancy may be suspected based on use of assisted
reproductive technology to conceive, uterine size that is large for dates, family history of
fraternal twins, or hyperemesis gravidarum. (See 'Prevalence and epidemiology' below.)
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ROLE OF EARLY ULTRASOUND EXAMINATION
Screening and diagnosis — Ultrasound examination is the best method for screening for
and definitive diagnosis of twin gestation.
Most women in resource-rich countries undergo one or more routine screening ultrasound
examinations during pregnancy. Randomized trials comparing routine ultrasound
examination with ultrasound performed only for clinical indications have proven that a
significant number of twin pregnancies are not recognized until the third trimester or
delivery in women who do not undergo routine ultrasound examination [1,2]. As an example,
the Routine Antenatal Diagnostic Imaging with Ultrasound Study (RADIUS) of over 15,000
pregnancies found that in women who did not have a routine second-trimester ultrasound
examination, 38 percent of twin pregnancies were not diagnosed until after 26 weeks of
gestation and 13 percent were not diagnosed until delivery [1]. The Helsinki Ultrasound Trial
reported similar findings: Approximately 25 percent of twin pregnancies were not diagnosed
until after 21 weeks of gestation [2]. In both trials, no twin pregnancies were missed on
ultrasound examination.
Prenatal ultrasound screening guidelines vary worldwide. In the United States, the American
College of Obstetricians and Gynecologists recommends ultrasound examination for all
pregnant women, optimally at 18 to 22 weeks of gestation in the absence of specific
indications (eg, size greater than dates) [3].
Determination of gestational age — Early ultrasound assessment provides an accurate

estimation of gestational age, which is important in all pregnancies, but particularly
important in management of twin pregnancies because of the higher frequency of
complications. Accurate gestational age assessment is essential to accurately time the
various screening and diagnostic tests performed in pregnancy, determine whether fetal
growth is normal for gestational age, and accurately time planned late preterm or term
delivery. (See "Prenatal assessment of gestational age, date of delivery, and fetal weight".)
If there is a discrepancy between the twins in biometric measurements used for estimation of
gestational age, the general consensus is that the estimated delivery date should be based
on the measurements for the larger twin [4,5]. This will minimize the risk that a diagnosis of
growth restriction, which is common in multiple gestations, will be missed due to
underestimation of gestational age.
Assessment of chorionicity and amnionicity — Ultrasonography is an effective prenatal
tool for determining amnionicity and chorionicity. This is critical because monochorionic
twins have a shared fetoplacental circulation, which puts them at risk for specific serious
pregnancy complications, such as twin-twin transfusion syndrome (TTTS), twin anemia
polycythemia sequence (TAPS), and selective fetal growth restriction [6-10]. These
complications increase the risk for neurologic morbidity and perinatal mortality in
monochorionic twins compared with dichorionic twins [7,8,11-14]. In addition to the
complications associated with monochorionic twinning, monoamniotic twins are also at risk
for cord entanglement and conjoined twins.
The optimal time for performing the ultrasound examination for chorionicity and amnionicity
is in the first trimester after seven weeks (sensitivity ≥98 percent [15]), with lower but
acceptable accuracy in the early second trimester (sensitivity ≥90 percent [15]) [16-22].
Sonographic assessment of the fetal membranes is more difficult and less accurate in the
third trimester, especially in the setting of oligohydramnios.
Chorionicity and amnionicity are determined in the following ways:
● Identification of two separate placentas is a highly reliable indicator of dichorionic

twins. This indicator is generally only useful in early pregnancy since separate placentas
often appear fused later in gestation. Rarely, a monochorionic placenta that is bilobed or
has a succenturiate lobe gives the appearance of two separate placentas [23].
● The presence/absence of the intertwin membrane and its sonographic characteristics

early in pregnancy indicate chorionicity and amnionicity.
• Monochorionic/monoamniotic – The intertwin membrane is absent in a

monochorionic/monoamniotic twin pregnancy. Visualizing the intertwin membrane
becomes more difficult with advancing gestational age because of fetal crowding,
progressive thinning of the membrane, and, in some cases, development of
oligohydramnios in one or both sacs. These factors may lead to a false diagnosis of
monochorionic/monoamniotic twins. On the other hand,
monochorionic/monoamniotic twins may be misdiagnosed as
monochorionic/diamniotic twins when separation of the amnion and chorion is
mistaken for an intertwin membrane.
• Dichorionic/diamniotic – An intertwin membrane with the "twin peak" or "lambda

(λ)" sign indicates dichorionic twins. The twin peak or lambda sign refers to a
triangular projection of tissue that extends between layers of the intertwin
membrane from a fused dichorionic placenta ( image 1) [24]. It is best seen at 10

to 14 weeks, becomes less prominent after 20 weeks of gestation, and may
disappear.
An additional clue that twins are dichorionic is that the intertwin membrane is
thicker with dichorionic than monochorionic twins since the dichorionic/diamniotic
membrane consists of four layers (ie, two layers of both amnion and chorion) (
image 2), whereas the intertwin membrane in a monochorionic/diamniotic
pregnancy only consists of two layers of amnion ( image 3). There is no consensus
about the cutoff between thin and thick membranes; thresholds of 1.5 to 2 mm in
the first trimester have been suggested [20,25]. The difference in membrane
thickness is less obvious later in pregnancy [26,27].
• Monochorionic/diamniotic – An intertwin membrane with the "T" sign indicates a

monochorionic/diamniotic placenta. This sign refers to the appearance of the thin
intertwin membrane composed of two amnions as it takes off from the placenta at a
90 degree angle.
• The number of chorion and amnion membrane layers in the intertwin membrane
can be counted, but it is technically difficult; therefore, this method is not commonly
employed. It is best accomplished between 16 and 24 weeks of gestation using high
resolution, magnified images with the membrane perpendicular to the ultrasound
beam.
● After the first trimester, identification of fetuses of different sex is a highly reliable
means of confirming a dichorionic pregnancy.
In a study including over 600 twin pregnancies at 11 to 14 weeks of gestation at a tertiary

referral center, use of the T sign, lambda sign, and number of placentas had sensitivity of 100
percent and specificity of 99.8 percent for determining monochorionicity, with only one
dichorionic pregnancy incorrectly assigned as monochorionic [28]. A placental hematoma
precluded diagnosis of the T or lambda sign in the incorrectly assigned pregnancy. Other
smaller studies have reported sensitivity of 90 to 100 percent and specificity of 97.4 to 99.5
percent using these markers and fetal sex. In a 2016 systematic review of the accuracy of the
lambda sign alone (2292 twins, nine studies), sensitivity for predicting dichorionicity was 99
percent (95% CI 98-100) and specificity was 95 percent (95% CI 92-97) [29]. Pooled sensitivity
of the absence of the lambda sign for predicting monochorionicity was 96 percent (95% CI 92-
98) and pooled specificity was 99 percent (95% CI 98-99).
There are numerous reasons for imperfect accuracy, and clinicians should be mindful of the
possibility of an exception to the usual rules for assigning chorionicity and amnionicity. For
example, a monochorionic placenta may be bipartite and appear as two separate placentas
(but careful imaging will reveal that vascular anastomoses between lobes and thus risk for
TTTS are present) and rarely monozygotic twins have discordance in the phenotypic sex. An
extensive review of the diagnosis of and pitfalls in assessing chorionicity and amnionicity is
available elsewhere [30].
It may be possible to determine zygosity with noninvasive prenatal testing (NIPT), and this
could assist in the assessment of chorionicity when ultrasound findings are not clear. A small
prospective blinded study to validate a single-nucleotide polymorphism-based NIPT reported
100 percent accuracy for zygosity for all 29 monozygotic and 64 dizygotic twin samples in
which a result was reported; another two samples were no result [31]. While amnionicity and
chorionicity in monozygotic twins will reflect the timing of zygotic split, dizygotic twins will be
dichorionic in nearly all cases. However, because there are rare cases of monochorionic
dizygotic twins, dizygosity on NIPT alone cannot confirm dichorionicity [32].
Labeling each twin — It is important to use a consistent strategy for identifying and labeling
each twin over serial examinations in the second and third trimesters. This is relatively easy
to do when the twins are of different sexes. In same-sex twins, each twin may be identified
based on its orientation relative to the other twin: left or right lateral for twins positioned
next to each other and top (fundal) or bottom (cervical) for twins positioned vertically. The
presenting twin in laterally oriented twins may appear to change over time, but the bottom
twin of vertically oriented twins is likely to remain the presenting twin throughout pregnancy
[33]. Documentation of the sites of placental implantation (anterior, posterior, lateral) and of
the sites and types of placental cord insertion (eg, marginal versus central; normal versus
velamentous) is also useful.
Twins may not deliver in the order expected from antenatal ultrasound (termed perinatal
switch), especially when delivered by cesarean.
Other significant findings — In addition to assessment of gestational age, number of

fetuses, and chorionicity and amnionicity, first-trimester ultrasound examination may detect
abnormalities associated with adverse outcome. These include congenital anomalies, crown-
rump length discordance (which may be associated with aneuploidy or TTTS), enlarged
nuchal translucency (which may be associated with aneuploidy, congenital anomalies, or
TTTS). (See "Diagnosis and outcome of first-trimester growth delay", section on 'Discordant
first-trimester fetal size in twin pregnancies' and "Increased nuchal translucency and cystic
hygroma".)
Relationship between chorionicity and amnionicity and zygosity — Dizygotic or

"fraternal" twins occur from ovulation and fertilization of two oocytes, which results in
dichorionic/diamniotic placentation and two separate placentas. Rare cases of dizygotic twins
with monochorionic placentation after assisted reproductive technology (ART) have been
reported, with unexplained etiology [34-38]. Rarely, dizygotic twins have also been reported
after single embryo transfer.
Monozygotic or "identical" twins result from ovulation and fertilization of a single oocyte, with
subsequent division of the zygote. Timing of egg division generally determines placentation (
figure 1). Monozygotic twins may have two separate placentas or one placenta that is
monochorionic/monoamniotic or monochorionic/diamniotic. However, case reports of
atypical twinning (eg, chimeric twins, mirror image twins, discordant monozygotic twins,
polar body twins) have prompted hypotheses for other mechanisms of monozygotic twinning
[39]. Sesquizygotic multiple pregnancy is the term used to describe the rare intermediate
between monozygotic and dizygotic twinning. Chimerism arising at the juncture of zygotic
division has been implicated as the likely initial step in sesquizygotic twinning [40].
From an imaging perspective, approximately 80 to 90 percent of dichorionic placentas are

associated with dizygotic twins and the remainder are associated with monozygotic twins.
Thus, if the placenta is dichorionic and the fetuses are the same sex, approximately 10 to 20
percent will be "identical" twins. All monochorionic placentas are associated with
monozygotic twins, with the rare exceptions described above in some pregnancies conceived
by ART.
PREVALENCE AND EPIDEMIOLOGY
Twin births account for approximately 3 percent of live births and 97 percent of multiple
births in the United States [41]. Dizygotic twins are more common than monozygotic twins:
approximately 70 and 30 percent of twins, respectively (in the absence of the use of assisted
reproductive technology [ART]) [42]. The prevalence of dizygotic twins varies among
populations. By contrast, the prevalence of monozygotic twins is relatively stable worldwide
at 3 to 5 per 1000 births and not affected by maternal age, race, geography.
The major factors influencing the prevalence of dizygotic twins are:
● Use of fertility stimulating drugs – Use of fertility enhancing treatments (ART and non-
ART) substantially increases the prevalence of twin pregnancy compared with natural
conception. These therapies account for most of the increase in twin births in recent
years: In the United States, twin births increased from 1/53 infants in 1980 to 1/31 infants
in 2018, with the peak rate in 2014 (1/29 infants) [41]. Over one-third of all twin infants
born in the United States can be attributed to iatrogenic interventions (in vitro
fertilization [IVF], ovulation induction, superovulation plus intrauterine insemination)
[43]. A decrease in the number of embryos transferred per IVF cycle accounts for much of
the decline in twin births. (See "Strategies to control the rate of high order multiple
gestation".)
Dizygotic twins are more common in pregnancies conceived with IVF than in naturally
conceived pregnancies (≥95 versus 70 percent) since over 50 percent of women undergo
double embryo transfer as part of IVF [44]. However, IVF also appears to increase the risk
of embryo cleavage, thus increasing the chance of monozygotic twins. IVF is the only risk
factor for monozygotic twinning. (See "Pregnancy outcome after assisted reproductive
technology", section on 'Monozygotic multiples'.)
Dizygotic twins are also more common in pregnancies conceived with ovulation inducing
agents alone (without IVF) than in naturally conceived pregnancies since these drugs
increase the likelihood of ovulation and fertilization of multiple oocytes.
● Maternal age – Approximately one-third of the increase in multiple births in recent

decades can be attributed to increasing age at childbirth. The frequency of naturally
conceived dizygotic twins increases two- to threefold between age 15 and age 35 [45];
this may be related to increases in follicle stimulating hormone concentration with age
[46]. Older women are also more likely to utilize fertility treatments.
Although maternal age affects the prevalence of twins, it does not appear to affect twin
pregnancy outcome significantly [47-53]. When matched for chorionicity and amnionicity,
women ≥35 years appear to have the same or a lower risk of adverse perinatal outcome
as younger women with twin pregnancies in observational studies [47,48,51,52].
● Race/geographic area – Significant ethnic/racial variations in the prevalence of naturally

conceived dizygotic twins occur worldwide. In one report, naturally conceived dizygotic
twins accounted for 1.3 per 1000 births in Japan, 8 per 1000 births in the United States
and Europe, and 50 per 1000 births in Nigeria [54]. Spontaneous twinning is more
common in Black/African American and Hispanic mothers than in White mothers [55].
● Parity – Increasing parity correlates with an increased likelihood of dizygotic twin birth,
even after adjustment for maternal age [46].
● Family history – Dizygotic twinning appears to have a genetic component that is

expressed in women but can be inherited from either parent [56]. Thus, a woman is at
increased risk of having twins if she has a family history of twin births. The family history
of the biologic father appears to have little or no effect on his partner's risk of having
twins; however, he could pass the familial trait to his daughters. This theory is supported
by gene mapping studies in animals and humans that found that specific genetic variants
expressed by oocytes or ovarian cells were at least partly responsible for twinning
[56,57].
● Maternal weight and height – Obese (body mass index [BMI] ≥30 kg/m2) and tall
women (≥65 inches [164 cm]) are at greater risk for dizygotic twin birth than underweight
(BMI <20 kg/m2) and short women (<61 inches [155 cm]) [58-60].
● Diet – Diet may be an important factor affecting the dizygotic twinning rate in some
geographic areas, among certain races, and in women of particular body habitus
[46,61,62]. As an example, some studies have reported that folic acid supplementation
increased the rate of twinning [63]. However, there were several limitations to these
studies, which could have biased the results.
RISKS AND OUTCOMES
Vanishing twins — Early spontaneous reduction from twin to singleton pregnancy (ie,
vanishing twin) is common, occurring in 7 to 36 percent of in vitro fertilization (IVF) twin
pregnancies [64-66]. It is unclear if the rate is similar in naturally conceived pregnancies,
which are not routinely imaged from the earliest stages of pregnancy. Although some studies
report that a vanishing twin increases the survivor's risk of low birth weight and small for
gestational age infant compared with pregnancies in which a singleton was conceived, others
have reported equivalent risks of adverse outcome [64-73]. The discordance may be related
to differences among studies in the gestational age range of the vanishing twin at demise
and by differences in IVF techniques on perinatal outcomes. The demised twin can affect
results of cell-free DNA testing when used to screen for the common fetal aneuploidies.
Fetal/neonatal death, preterm birth — In pregnancies in which both twins are alive at the
end of the first trimester, the risks for subsequent fetal/neonatal death or preterm birth
depend on chorionicity and amnionicity, as shown in the table ( table 1) [74].
Infant mortality in twins is significantly higher than that of singletons ( table 2) [75].
Fetal complications
All twins — All twin pregnancies have higher rates of the following fetal complications
than singleton pregnancies [76]:
● Growth restriction (see 'Evaluation of fetal growth and growth discordance' below)
● Congenital anomalies (see 'Screening for congenital anomalies' below)
● Preterm delivery (see 'Preterm labor and delivery' below)
However, rates of postterm pregnancy and macrosomia are lower than in singleton
gestations.
Monochorionic twins — The following fetal complications are of particular concern in

monochorionic twin pregnancies and generally derive from the shared placental circulation
[6-10]:
● Twin-twin transfusion syndrome (TTTS) – Unbalanced blood flow in anastomotic

vessels along the equatorial plate of the shared placenta result in TTTS, which is
characterized by oligohydramnios (including anhydramnios) in one amniotic sac and
polyhydramnios in the other sac ( table 3). First-trimester nuchal translucency >95th
centile in one or both fetuses and crown-rump length discordance ≥10 percent in the first
trimester appear to be modest predictors of future TTTS [77]. (See "Twin-twin transfusion
syndrome and twin anemia polycythemia sequence: Screening, prevalence,
pathophysiology, and diagnosis" and "Twin-twin transfusion syndrome: Management
and outcome".)
● Twin anemia polycythemia sequence (TAPS) – TAPS is a variant of TTTS in which one
twin is anemic and the other twin is polycythemic. The prenatal diagnosis is based on the
middle cerebral artery-peak systolic velocity (MCA-PSV) >1.5 multiples of the median
(MoM) in one twin and <0.8 MoM in the other twin without amniotic fluid volume
discordance ( table 3). The disorder is caused by very small arteriovascular placental
anastomoses that allow the slow unidirectional flow of blood from a donor (anemic) twin
to a recipient (plethoric) twin. (See "Twin-twin transfusion syndrome and twin anemia
polycythemia sequence: Screening, prevalence, pathophysiology, and diagnosis", section
on 'Twin anemia polycythemia sequence'.)
● Twin reversed arterial perfusion sequence (TRAP) – TRAP is a rare complication of

monochorionic twins in which a living twin perfuses a nonliving (acardiac) twin through
patent vascular channels. (See "Diagnosis and management of twin reversed arterial
perfusion (TRAP) sequence".)
● Selective fetal growth restriction (sFGR) – Selective growth restriction is variously

defined as estimated weight of one twin below the 10th percentile or discordance in
estimated twin weights greater than 25 percent:
Discordance = weight larger twin – weight smaller twin/weight larger twin
Selective growth restriction has been classified into three types ( table 4). It is often
due to unequal placental sharing (discordance in placental territory), but other factors
can play a role (eg, umbilical cord insertion abnormalities, unequal splitting of the initial
cell mass, imbalance in bidirectional flow between circulations) [78]. Selective growth
restriction shares some features with TTTS and TAPS, but differential diagnosis is
generally readily achieved ( table 3). (See "Selective fetal growth restriction in
monochorionic twin pregnancies".)
● Single fetal demise – The risk of a fetal death in monochorionic twins exceeds that in
singletons and dichorionic twins. Of additional concern, a single fetal demise of one twin
of a monochorionic pair can cause morbidity or mortality in the co-twin due to their
shared placental circulation. In a retrospective series of 1000 consecutive twin
pregnancies ≥24 weeks of gestation, the risk of single antepartum fetal death in
monochorionic diamniotic twins was more than threefold higher than in dichorionic
twins (3.6 versus 1.1 percent of twin pairs), and occurred in apparently normal twins
monitored closely [79]. (See 'Death of one twin' below.)
● Congenital anomalies – Monochorionic twins have a higher rate of congenital

anomalies than dichorionic twins and singletons. The anomalies have a high rate of
concordance, but can be discordant. (See 'Screening for congenital anomalies' below.)
Monoamniotic twins — In addition to the problems of monochorionic diamniotic

placentation described above, the following fetal complications are of particular concern in
monoamniotic twin pregnancies:
● Intertwin cord entanglement – Cord entanglement is common in monoamniotic twins

and can lead to fetal death. (See "Monoamniotic twin pregnancy (including conjoined
twins)", section on 'Cord entanglement'.)
● Conjoined twins – Conjoined twins are classified according to the anatomical site of
union (eg, chest, head) with the suffix "pagus" (meaning fixed [eg, thoracopagus]).
Findings on ultrasound include monoamnionicity, contiguous skin, shared organs, twins
that stay in the same orientation to one another, fetal scoliosis, unusual limb positioning,
and more than three vessels in the cord [80]. Associated congenital defects unrelated to
the area of fusion are common, as is stillbirth. Detailed ultrasonography and
echocardiography, possibly with additional magnetic resonance imaging, are essential to
determine the extent of deformity, to counsel the parents about prognosis, and to
prepare for possible postnatal surgical management [80-83]. Delivery of potentially
viable infants is always by cesarean. (See "Monoamniotic twin pregnancy (including
conjoined twins)", section on 'Conjoined twins'.)
Maternal risks and complications — Although women carrying twins are at higher risk for
some adverse outcomes than women carrying singletons [84], chorionicity and amnionicity
do not appear to impact this risk in most studies [85,86].
● Maternal hemodynamic changes – Twin pregnancy results in greater maternal

hemodynamic changes than singleton pregnancy [87-90]. Women carrying twins have a
20 percent higher cardiac output and 10 to 20 percent greater increase in plasma volume
than women with singleton pregnancy, which increases their risk of pulmonary edema
when other risk factors are also present [87,88]. Physiological anemia is common, even
though red cell mass increases more in twin pregnancy than in singleton pregnancy. (See
"Anemia in pregnancy".)
● Gestational hypertension and preeclampsia – Gestational hypertension and

preeclampsia are more common in women carrying twins [91,92]. In a secondary analysis
of prospective data from women with twin (n = 684) and singleton (n = 2946) gestations
enrolled in multicenter trials of low-dose aspirin for prevention of preeclampsia, rates of
gestational hypertension and preeclampsia were twice as high in twin compared with
singleton pregnancies (13 percent in twins versus 5 to 6 percent in singletons for both
disorders) [91]. Early severe preeclampsia and HELLP syndrome (Hemolysis, Elevated
Liver enzymes, Low Platelets) tended to occur more frequently in multiple gestations.
Zygosity and chorionicity do not appear to impact risk for preeclampsia in twin
pregnancies [92,93].
The diagnosis, management, and course of preeclampsia/gestational hypertension are

not usually affected by the multiple gestation [94], with some exceptions. A number of
studies have reported that maternal uric acid concentration increases with the number of
fetuses in both normotensive and preeclamptic pregnancies, with typical values of 5.2
and 6.4 mg/dL, respectively, in twin pregnancies [95-98]. In addition, case reports have
described resolution of early severe preeclampsia upon death of one twin [99-101]. (See
"Preeclampsia: Clinical features and diagnosis" and "Preeclampsia: Management and
prognosis" and "Gestational hypertension" and "Treatment of hypertension in pregnant
and postpartum women".)
● Gestational diabetes – Whether gestational diabetes is more common in twin

pregnancies is unclear [102-106]. Screening, diagnosis, and management are similar to
that in a singleton pregnancy. (See "Diabetes mellitus in pregnancy: Screening and
diagnosis" and "Gestational diabetes mellitus: Glycemic control and maternal
prognosis".)
● Acute fatty liver of pregnancy – Acute fatty liver of pregnancy is rare but occurs more
frequently in multiple than singleton gestations. Multiple gestation does not affect
diagnosis or management. (See "Acute fatty liver of pregnancy".)
● Other – Other maternal disorders observed more often in women with multiple
gestations include pruritic urticarial papules and plaques of pregnancy (PUPPP),
intrahepatic cholestasis of pregnancy, iron deficiency anemia, hyperemesis gravidarum,
abruption, and thromboembolism [107-109]. The increased risk of thrombosis relates, at
least in part, to the increased prevalence of cesarean delivery and bedrest in these
pregnancies.
• (See "Dermatoses of pregnancy".)

• (See "Intrahepatic cholestasis of pregnancy".)
• (See "Anemia in pregnancy".)
• (See "Nausea and vomiting of pregnancy: Treatment and outcome".)
• (See "Placental abruption: Pathophysiology, clinical features, diagnosis, and
consequences" and "Placental abruption: Management and long-term prognosis".)
• (See "Deep vein thrombosis in pregnancy: Epidemiology, pathogenesis, and
diagnosis".)
Comparative outcomes of singleton, twin, and triplet pregnancy — Comparative

outcomes (other than death) of twin versus singleton and triplet pregnancies are shown in
the table ( table 5).
PREGNANCY COUNSELING AND MANAGEMENT
Our approach to counseling and management of women with twin pregnancies is described
below, and is generally consistent with recommendations of major organizations worldwide
(see 'Society guideline links' below). Clinicians who provide care for these women should be
knowledgeable about the issues involved. Specialized antenatal clinics for women with
multiple gestations have not been proven to improve birth outcomes compared with
standard care, although data from randomized trials are sparse [110].
Gestational weight gain — The National Academy of Medicine (formerly the Institute of
Medicine) recommends the following cumulative weight gain by term for women carrying
twins [111]:
● Body mass index (BMI) <18.5 kg/m2 (underweight) – No recommendation due to

insufficient data.
● BMI 18.5 to 24.9 kg/m2 (normal weight) – Weight gain 37 to 54 lb (16.8 to 24.5 kg).
● BMI 25.0 to 29.9 kg/m2 (overweight) – Weight gain 31 to 50 lb (14.1 to 22.7 kg).
● BMI ≥30.0 kg/m2 (obese) – Weight gain 25 to 42 lb (11.4 to 19.1 kg).
These thresholds represent the 25th through 75th percentile weight gains in women who gave
birth to twins weighing at least 2500 g [112]. In cohort studies, women with normal
prepregnancy BMIs who met these guidelines had fewer preterm births and higher birth
weights compared with women who did not meet the minimum weight gain suggested by
the guidelines [113-115], while exceeding the guideline increased maternal risks of
gestational hypertension/preeclampsia, eclampsia, and cesarean delivery [115]. Poor
gestational weight gain after 20 weeks appears to have a greater impact than poor first-
trimester weight gain [116]; thus, we reassure women in early pregnancy who are unable to
adhere to recommendations for caloric intake or weight gain due to nausea and vomiting or
other reasons.
To achieve appropriate gestational weight gain, a normal weight woman needs to increase
her dietary intake by approximately 300 kcal/day above that for a singleton pregnancy or 600
kcal/day above that of a nonpregnant woman. After 20 weeks of gestation, weight gain
should be approximately 1.75 pounds/week for underweight women and approximately 1.5
pounds/week for normal weight women, with the same or slightly lower weekly weight gain
in overweight and obese women.
Nutrition — The Society for Maternal-Fetal Medicine recommendations for nutrition in

pregnancy are shown in the table ( table 6) [117].
Screening and diagnostic testing for Down syndrome — A monozygotic twin pregnancy is
thought to have the same Down syndrome risk as a maternal age-matched singleton
pregnancy ( table 7); both fetuses will be affected or both fetuses will be unaffected.
However, rarely, these twins have different genotypes due to postzygotic events, including
nondisjunction and mosaicism [118-123]. They can also be discordant for X-inactivation in
females, differential gene imprinting, and smaller scale genetic abnormalities, such as
microdeletions [124]. Therefore, when diagnostic testing is performed, both fetuses of a
monozygotic pair should undergo karyotyping, although this may not be possible if chorionic
villus biopsy rather than genetic amniocentesis is the diagnostic test. In some cases,
amniocytes as well as fetal blood may be needed to make an accurate diagnosis.
For dizygotic twin pregnancies, the risk of at least one affected fetus is assumed to be twice
the risk of a maternal age-matched singleton pregnancy (eg, at age 35: 2 x 1/350 at delivery)
and the risk of two affected fetuses is assumed to be the product of the risk of the maternal
age-matched singleton pregnancy (eg, at age 35: 1/350 x 1/350 at delivery). However,
observed rates of Down syndrome are lower than expected, possibly due to an increased
frequency of early fetal loss [125]. Despite this observation, more data are needed before
Down syndrome risk estimates can be adjusted for women with twin pregnancies.
For women who choose to undergo screening for Down syndrome, we suggest either first-
trimester combined test or noninvasive screening using cell-free DNA in maternal blood.
While the combined test provides early, fetus-specific risk assessment, cell-free fetal DNA has
higher detection rates. Both fetuses should be karyotyped when karyotyping is performed
since even monozygotic twins may be discordant.
● Noninvasive screening using cell-free DNA – Noninvasive prenatal screening for Down
syndrome using cell-free DNA is challenging because the cell-free fetal DNA in the
maternal circulation derives from each fetus, the average fetal fraction for each twin is
less than that for singletons, and the fetal fraction can differ between twins by at least
1.5-fold in 10 percent of cases [55]. Testing is commercially available for trisomies 13, 18,
and 21, although less validation data are available from twin gestations than from
singletons [126-129]. Emerging data suggest that the sensitivity of cell-free DNA for
Down syndrome in twins may be similar to that in singleton pregnancies, though the rate
of test failure is higher in twins [130,131]. An American College of Obstetricians and
Gynecologists (ACOG) practice bulletin states that cell-free DNA screening for Down
syndrome can be done in twin pregnancies, and available performance data are
encouraging, but the total number of reported affected pregnancies is small, thus
preventing an accurate assessment of performance [132]. The International Society for
Prenatal Diagnosis position statement on cell-free DNA screening for Down syndrome in
multiple gestations concluded that cell-free DNA screening for common trisomies in
twins provides higher positive predictive values compared with serum- and nuchal
translucency-based screening tests [55]. Test failures occur in a median 3.6 percent of
cases (range 1.6 to 13.2 percent), which is higher than the rate in singletons and usually
due to a low fetal fraction. (See "Prenatal screening for common aneuploidies using cell-
free DNA", section on 'Twins'.)
● First-trimester combined test – The first-trimester combined test (beta human

chorionic gonadotropin and pregnancy-associated plasma protein A in serum plus
ultrasound measurement of nuchal translucency) can provide fetus-specific risk
assessment. Increased nuchal translucency at 11 to 13 weeks of gestation is a marker for
Down syndrome, other aneuploidies, congenital malformations, and development of
twin-twin transfusion syndrome (TTTS). (See "First-trimester combined test and
integrated tests for screening for Down syndrome and trisomy 18", section on 'First-
trimester combined test'.)
Interpretation of maternal serum biochemical markers is problematic in twin

pregnancies since both twins contribute to the concentration of the markers and marker
levels may be affected by early loss of one or more embryos of a multiple gestation
[133,134]. Measurement of nuchal thickness can improve the detection rate and help
identify which fetus is affected [135,136]. In a 2014 systematic review of first-trimester
combined risk assessment (nuchal translucency and maternal serum biochemical
markers) in twin pregnancies, test sensitivity in dichorionic twins was 86 percent (95% CI
73-94) and test sensitivity in monochorionic twins was 87 percent (95% CI 53-98) [137]. In
our institution, first-trimester combined risk assessment identified all six affected
pregnancies (five discordant and one concordant for Down syndrome) at a screen-
positive rate of 5 percent, while nuchal translucency alone detected five of six affected
fetuses [136]. Although biochemical marker testing enhanced risk assessment, the levels
in affected twin pregnancies were closer to the median levels than in affected singleton
pregnancies.
Of note, the false-positive rate of nuchal translucency screening is higher in

monochorionic than dichorionic twins because increased nuchal translucency can be an
early manifestation of TTTS as well as a marker of aneuploidy [138]. Also, in vitro

fertilization (IVF) affects biochemical marker levels used in Down syndrome screening
and may be considered by some laboratories when calculating screening results in twins
conceived by this method [139]. (See "Laboratory issues related to maternal serum
screening for Down syndrome", section on 'IVF and other assisted reproduction
techniques'.)
Also of note, fetuses with the same genotype may have different phenotypes; as an
example, only one fetus of twins with Down syndrome may have increased nuchal
translucency. In a series of eight monochorionic twin pairs discordant for nuchal
translucency who were karyotyped, discordance was a marker for concordant
chromosome abnormalities in one twin pair and discordant chromosomal abnormalities
in two twin pairs [123].
Issues related to diagnostic genetic testing in twins by chorionic villus sampling and genetic
amniocentesis are discussed separately. (See "Chorionic villus sampling", section on 'Multiple
gestations' and "Diagnostic amniocentesis", section on 'Multiple gestation'.)
Screening for congenital anomalies — An anatomic survey is typically performed at 18 to

22 weeks of gestation in all twin pregnancies [15]. The incidence of congenital anomalies is
three- to fivefold higher in monozygotic twins than in dizygotic twins or singletons and is
higher in monozygotic monochorionic twins than in monozygotic dichorionic twins [42,140-
143]. In one study, the frequency of congenital anomalies in monochorionic twins was
634/10,000 versus 344/10,000 for dichorionic twins versus 238/10,000 for singletons [142].
The concordance rate of major congenital malformations in monozygotic twins is

approximately 20 percent [144]. The concordance rate is low in dizygotic twin pairs and each
dizygotic twin has a similar risk of a congenital anomaly as a singleton.
Twins are not predisposed to any specific type of congenital anomaly, although congenital
heart disease is more prevalent in monochorionic twins, particularly those with TTTS [141]. In
addition to an anatomic survey at 18 to 20 weeks of gestation, we suggest fetal
echocardiography at 18 to 22 weeks for monochorionic but not dichorionic twins because 5.0
to 7.5 percent of monochorionic twins referred for routine fetal echocardiography have
congenital heart disease in at least one twin [145-147]. Although some studies have reported
an increased risk of congenital heart disease in twins conceived by assisted reproductive
technology, particularly IVF, compared with spontaneously conceived twins [148,149], others
do not support this association [150-153]. We generally do not refer twin pregnancies for
fetal echocardiography for the sole indication of conception via IVF, but some experts
consider IVF an indication for echocardiography in all twin pregnancies [154].
The reported accuracy of ultrasound for detection of fetal anomalies in twins varies because
of differences in ascertainment postnatally and at pregnancy termination, criteria for
defining an anomaly, and operator capability. Ultrasound examination can detect the
majority of major malformations in twins, but should be performed by sonographers
experienced in both anomaly detection and assessment of multiple gestation. Sometimes
more than one examination needs to be performed to adequately assess both twins.
Management of discordant anomalies — The diagnosis of a congenital anomaly in one

twin is especially problematic since decisions regarding monitoring, therapy, and delivery
affect both fetuses. Expectant management, in utero therapy, pregnancy termination, and
selective feticide should all be discussed, if appropriate for the type of abnormality and
gestational age. Women who choose to continue the pregnancy should understand how the
anomalous fetus might affect the co-twin's outcome (eg, preterm birth, organ damage),
including the role of chorionicity.
● Dichorionic twins – In dichorionic twins, selective termination of the anomalous fetus is

a safe and effective option in expert hands, although there is a risk of miscarriage or
preterm delivery of the co-twin. Because of these risks, expectant management may be a
safer option if the twin with the anomaly is not expected to have prolonged survival or a
favorable outcome (eg, trisomy 18) [155]. Anencephaly is an exception since it is
associated with polyhydramnios and preterm birth. If polyhydramnios develops in the
anencephalic twin's sac, selective feticide or amniodrainage appears to result in longer
gestation and higher birth weight in the nonanomalous twin than expectant
management [156,157]. In our practice, we suggest selective termination whenever a
fetal anomaly incompatible with survival is identified in one twin if this anomaly is
associated with polyhydramnios. We recommend not performing amnioreduction unless
maternal respiratory compromise is present. Timing and techniques (eg, intracardiac
injection of potassium chloride) are described separately. (See "Multifetal pregnancy
reduction and selective termination", section on 'Dichorionic fetuses'.)
● Monochorionic twins – In monochorionic twins, selective feticide can be performed but

the technique is different from that in dichorionic twins and is more challenging. It
necessitates obstructing one umbilical cord (eg, radiofrequency or laser ablation, bipolar
coagulation, ligation) rather than intravascular injection of potassium chloride or digoxin
in order to reduce risk to the co-twin associated with shared circulations [158,159].
Timing and techniques are described in more detail separately. (See "Multifetal
pregnancy reduction and selective termination", section on 'Monochorionic fetuses'.)
Screening for short cervical length — We do not routinely obtain a transvaginal ultrasound
measurement of cervical length in the second trimester. Although a short cervical length may
predict pregnancies at increased risk of preterm delivery [160,161], the predictive value is low
in asymptomatic patients ( table 8) and we believe no intervention has been clearly proven
to be effective in reducing preterm birth rates in this population. (See 'Preterm labor and
delivery' below.)
However, others [5], including some UpToDate authors, have taken a different approach: they
measure cervical length at the time of the second-trimester fetal anatomy scan and begin
progesterone supplementation if the cervix is short (≤25 mm). (See "Progesterone
supplementation to reduce the risk of spontaneous preterm birth", section on 'Multiple
gestation'.)
Physical activity and exercise — In early pregnancy, women with uncomplicated twin
pregnancies can generally follow the same exercise/physical activity recommendations as
women with singleton pregnancies. The clinician should assess individual risk factors for
preterm birth and counsel the patient accordingly. As pregnancy progresses, physical
changes generally limit the duration and type of exercise performed. Although case reports
describe elite athletes who trained until delivery despite twin pregnancy, some restriction of
activity is generally desired and prudent. Recommendations for individual patients may
depend on factors such as overall state of health, proposed exercise regimen, and
musculoskeletal factors. (See "Exercise during pregnancy and the postpartum period".)
Monitoring in the second/third trimesters
Evaluation of the placenta — Sonographic evaluation of the placenta is particularly

important in twin pregnancies because they are at increased risk of placental findings
associated with adverse outcome. Identification and appropriate management of affected
pregnancies can improve pregnancy outcome.
These findings include:
● Placenta previa – The incidence of placenta previa in twin pregnancy is higher than in
singletons (3.9 per 1000 live births versus 2.8 per 1000 live births) [162]. This has been
attributed to the larger total area of twin placentas, especially dichorionic twin placentas.
(See "Placenta previa: Epidemiology, clinical features, diagnosis, morbidity and mortality"
and "Placenta previa: Management".)
● Vasa previa – A systematic review of cohort and case control studies identified 438 cases
of vasa previa and reported 11 percent were in twin pregnancies, suggesting a higher
risk in twins compared with the general obstetric population [163]. Transvaginal
examination with color Doppler mapping will detect vasa previa. (See "Velamentous
umbilical cord insertion and vasa previa".)
● Velamentous cord insertion – Velamentous cord insertion, which is associated with an

increased risk for fetal growth restriction and cord compression, has been reported in 12
percent of monochorionic twin pregnancies, 7 percent of dichorionic twin pregnancies,
and 2 percent of singleton pregnancies [164]. (See "Velamentous umbilical cord insertion
and vasa previa".)
Evaluation of fetal growth and growth discordance — Evaluation of fetal growth is

particularly important in twin gestations because growth restriction and preterm birth are
major causes of the higher morbidity/mortality rates in twin compared with singleton
gestations [8,165-172]. Neurologic morbidity is a major concern, and has several etiologies
(eg, preterm birth, hemodynamic effects from death of one twin, growth restriction, TTTS)
[173].
In the first and second trimesters, the growth rate of twins is not significantly different from
that of singletons [174]. In the third trimester, particularly after 30 to 32 weeks of gestation,
most studies have described slower fetal growth in uncomplicated twin gestations than in
uncomplicated singleton gestations [174,175]. A prospective cohort study reported that
almost 40 percent of dichorionic twins near term would be classified as small for gestational
age if a singleton growth standard is used [175]. The slower growth rate has been attributed
to anomalous umbilical cord insertion and to placental crowding (poor early development
due to placental proximity).
Growth curves have been derived specifically for twins but are of limited usefulness since
they were derived from small populations and did not consider chorionicity and amnionicity
or outcome. We and other experts feel that singleton growth curves are the best predictor of
adverse outcome in twin gestations and should be used for evaluating twins for growth
abnormalities [176].
We recommend serial ultrasound examinations of twin pregnancies in the second and third
trimesters to screen for fetal growth restriction and growth discordance, given the risk of
adverse outcome associated with these conditions and the insensitivity of symphysis-fundal
height measurement for identifying fetal growth abnormalities in twins [177-179]. Impaired
growth in one twin can be related to any of several etiologies that only or disproportionately
affect that twin, including anatomic anomalies, chromosomal abnormalities, genetic
syndromes, congenital infection, and placental issues (eg, abruption, unequal sharing,
unfavorable cord insertion [eg, marginal, velamentous]).
Although growth monitoring is typically performed in the second and third trimesters,
discordance in crown-rump length may be observed as early as the first trimester and is
predictive of later weight discordance (see "Diagnosis and outcome of first-trimester growth
delay", section on 'Discordant first-trimester fetal size in twin pregnancies'). Discordance in
other biometric measurements subsequently associated with adverse obstetric and neonatal
outcome may be noted as early as approximately 18 weeks of gestation [180,181]. Either
estimated fetal weight or abdominal circumference can be used to monitor growth in the
second half of pregnancy. An intertwin abdominal circumference difference ≥20 mm,
irrespective of gestational age, has been reported to have 83 percent positive predictive value
to detect a difference in birth weight ≥20 percent [182]. (See "Prenatal assessment of
gestational age, date of delivery, and fetal weight", section on 'Sonographic assessment of
fetal weight'.)
Despite routine use of ultrasound to monitor fetal growth, its ability to accurately identify
discordant twins and adverse perinatal outcome is limited. In a systematic review, estimated
fetal weight discordance ≥20 percent had sensitivity and specificity of 65 and 91 percent,
respectively, for predicting birth weight discordance ≥20 percent [183]. If ultrasound
examination identifies growth discordance or growth restriction in either twin, then more
intensive fetal monitoring is initiated, as in singletons. (See "Selective fetal growth restriction
in monochorionic twin pregnancies".)
Growth abnormalities manifest in three ways: (1) one twin can be small for gestational age
(called selective fetal growth restriction), (2) both twins can be small for gestational age, or (3)
one twin can be significantly smaller than the other twin (ie, growth discordance) although
neither is small for gestational age. In almost two-thirds of discordant twin pairs, the smaller
twin has a birth weight <10th percentile [167]. There is no consensus regarding the optimum
threshold for defining discordance in twins. Discordance in birth weight ranging from 15 to
40 percent has been considered predictive of adverse outcome [166,168-170,184-188]. We
use an estimated weight difference ≥20 percent as the threshold for defining discordance,
but ≥25 percent is also commonly used. Approximately 15 percent of twins are ≥20 percent
discordant in weight [171].
A systematic review (22 studies including over 10,800 twin pregnancies) analyzed the
association between birth weight discordance and perinatal mortality in twin pregnancy and
noted the following [189]:
● In dichorionic twins, the risk of fetal demise increased with increasing discordance: ≥15
percent (odds ratio [OR] 9.8, 95% CI 3.9-29.4), ≥20 percent (OR 7.0, 95% CI 4.15-11.8), ≥25
percent (OR 17.4, 95% CI 8.3-36.7), ≥30 percent (OR 22.9, 95% CI 10.2-51.6) compared
with no discordance. The smaller twin was at higher risk of fetal demise than the larger
twin.
● In monochorionic twins without TTTS, the risk of fetal demise by level of discordance
was: ≥20 percent (OR 2.8, 95% CI 1.3-5.8), ≥25 percent (OR 3.2, 95% CI 1.5-6.7). The
smaller twin was not at higher risk of fetal demise than the larger twin.
● Importantly, the risk of fetal demise was not increased when the weights of the
discordant twins remained appropriate for gestational age (AGA), although the small
number of cases may have underestimated this association.
There were several limitations of these observational studies, such as differences in

definitions, populations, and use of estimated fetal weight versus birth weight, as well as lack
of standardized criteria for the antenatal management. Therefore, AGA but discordant twins
should still be considered at risk of adverse perinatal outcome and be followed closely.
There is no convincing evidence that Doppler velocimetry has benefits for detection of
growth restriction over the use of ultrasound alone; therefore, routine use of Doppler
velocimetry in twin gestations is not recommended [190,191]. However, Doppler ultrasound
is useful for monitoring pregnancies in which the diagnosis of growth restriction,
discordance, or fetal anemia has been made. (See "Selective fetal growth restriction in
monochorionic twin pregnancies", section on 'Stage-based management'.)
Management — The management of growth restriction depends on chorionicity and

amnionicity:
● In dichorionic twins, growth restriction is generally managed as in singletons. (See "Fetal

growth restriction: Evaluation and management".)
● In monochorionic twins, management of growth restriction depends on whether it is

related to selective intrauterine growth restriction, TTTS, or twin anemia polycythemia
sequence (TAPS), and is reviewed separately. (See "Twin-twin transfusion syndrome:

Management and outcome" and "Selective fetal growth restriction in monochorionic twin
pregnancies", section on 'Stage-based management'.)
Assessment of fetal well-being — Routine use of antepartum fetal testing (nonstress test
[NST], biophysical profile [BPP], amniotic fluid volume determination, or Doppler velocimetry)
has no proven benefit in uncomplicated twin pregnancies. However, antepartum fetal
monitoring in twins is widely practiced beginning at approximately 32 weeks of gestation
because of the increased risk of stillbirth in twins, particularly monochorionic twins [192]. The
exact timing of initiation of testing varies among centers, depending on factors such as
chorionicity and amnionicity and underlying complications.
We routinely perform weekly testing in all twin pregnancies beginning at 32 weeks of

gestation, except those that are monochorionic monoamniotic, which are followed more
closely (see "Monoamniotic twin pregnancy (including conjoined twins)"). If complications
such as fetal growth restriction develop, then testing would be initiated earlier and/or
performed more frequently. Some others limit routine testing to those that are
monochorionic diamniotic and may begin testing at 28 to 32 weeks and may perform testing
twice weekly [193]. In dichorionic twin pregnancies, ACOG suggests reserving antenatal
testing for gestations complicated by maternal or fetal disorders that require antepartum
testing, such as fetal growth restriction [194]. They state monochorionic twins should be
followed more closely than dichorionic twins, but have not provided a specific protocol.
Both NSTs and BPPs are reliable in twin gestations [195-197]. (See "Nonstress test and
contraction stress test" and "Biophysical profile test for antepartum fetal assessment".)
The best technique to assess amniotic fluid volume in diamniotic twin gestations is uncertain.
Subjective assessment of the volume of amniotic fluid in each sac appears to be as accurate
as quantitative assessment. (See "Assessment of amniotic fluid volume", section on 'Multifetal
pregnancy'.)
Chorionicity- and amnionicity-based follow-up — Because monochorionic twin

gestations are associated with greater and different risks than dichorionic twin gestations (
table 1), monitoring is based, in part, on chorionicity and amnionicity, and protocols for
monochorionic twins have involved more intensive surveillance than protocols for dichorionic
twins, as described below.
Monochorionic monoamniotic twins are at highest risk of adverse outcome; management of
these pregnancies is reviewed separately. (See "Monoamniotic twin pregnancy (including

conjoined twins)".)
Monochorionic twins — Our approach to monitoring monochorionic twins is outlined

in the algorithm ( algorithm 1). We suggest monitoring monochorionic/diamniotic
pregnancies beginning at 16 to 18 weeks by assessment of amniotic fluid volume and fetal
bladder in both twins for early detection of TTTS; we begin measurement of middle cerebral
artery peak systolic velocity (MCA-PSV) in both fetuses at 26 to 28 weeks for early detection of
TAPS [198,199], although there is no consensus about routine performance of MCA Doppler
to assess for TAPS [15,200]. There are inadequate data to determine the optimal frequency of
monitoring, but measurement every two to three weeks is reasonable, with more frequent
monitoring if abnormalities are detected (eg, discordant amniotic fluid volumes that do not
yet meet criteria for stage I TTTS [201]).
● The diagnosis of TTTS is based on the sonographic finding of oligohydramnios (maximal

vertical pocket <2 cm) and polyhydramnios (maximal vertical pocket >8 cm). (See "Twin-
twin transfusion syndrome and twin anemia polycythemia sequence: Screening,
prevalence, pathophysiology, and diagnosis".)
● The diagnosis of TAPS is based on MCA-PSV >1.5 multiples of the median (MoM) in one
twin and <0.8 MoM in the other twin. (See "Twin-twin transfusion syndrome and twin
anemia polycythemia sequence: Screening, prevalence, pathophysiology, and diagnosis",
section on 'Twin anemia polycythemia sequence'.)
Early detection of TTTS or TAPS can improve perinatal outcome [202,203].
Fetal growth is evaluated every two to four weeks when ultrasound is performed to monitor
for TTTS and TAPS. Monochorionic placentation is a significant risk factor for discordant
growth due to unequal sharing of the placenta or TTTS [11,204-206] (see 'Evaluation of fetal
growth and growth discordance' above). Monochorionic placentation also appears to have a
small independent adverse effect on intrauterine growth compared with dichorionic
placentation [207].
Other UpToDate authors monitor monochorionic twins for TTTS and TAPS similarly, but with
slight differences. (See "Twin-twin transfusion syndrome and twin anemia polycythemia
sequence: Screening, prevalence, pathophysiology, and diagnosis", section on 'Monitoring
monochorionic pregnancies for development of TTTS and TAPS'.)
Dichorionic twins — Close fetal monitoring for TTTS and TAPS is unnecessary in
dichorionic twins. We perform an ultrasound examination every four to six weeks after 20
weeks of gestation to monitor fetal growth, as fetal growth deceleration leading to
discordancy is optimally detected between 20 and 28 weeks of gestation [204]. Many twin
fetuses with growth abnormalities can be identified by 20 to 24 weeks, so if there is no
evidence of growth abnormality at that time, then repeated scanning might not be necessary
[208]; however, we continue serial ultrasound assessment until delivery. Routinely scanning
every two to four weeks has been recommended by some groups [5] and detected more
abnormalities that prompted early delivery in one study, but whether this resulted in better
perinatal outcomes was not determined [209].
APPROACH TO SELECTED PREGNANCY COMPLICATIONS
Death of one twin — Single fetal death in twin pregnancies is not rare. In one study in which
both twins were alive at 11 to 13 weeks of gestation, approximately 3 percent of 4896
dichorionic twin pregnancies and 11 percent of 1329 monochorionic twin pregnancies
experienced a fetal death before 34 weeks [210]. Obviously, the frequency of single fetal
demise is higher if losses before 11 to 13 weeks are included.
Because of the placental vascular anastomoses between monochorionic twins, the

intrauterine death of one twin in a monochorionic pregnancy can cause acute hypotension,
anemia, and ischemia in the co-twin due to exsanguination into the low pressure vascular
system of the deceased twin, resulting in morbidity or death of the co-twin. In a dichorionic
pregnancy, death of one twin may reflect an adverse intrauterine environment that could also
place the co-twin at risk, but the risk is much lower.
The type and magnitude of these risks were illustrated in a 2019 systematic review of studies
that evaluated the prognosis of the co-twin following a single twin death after 14 weeks in
diamniotic twin pregnancies [211]. Following intrauterine demise of one twin:
● The rates of fetal demise of the co-twin in monochorionic and dichorionic pregnancies
were 41 and 22 percent, respectively (comparing monochorionic versus dichorionic: odds
ratio [OR] 2.06, 95% CI 1.14-3.71).
● In monochorionic pregnancies, 20 percent of co-twin survivors had abnormal antenatal

cranial imaging.
● The rates of preterm birth in monochorionic and dichorionic pregnancies were 59 and 54
percent, respectively (comparing monochorionic versus dichorionic: OR 1.42, 95% CI
0.67-2.99).
● The rates of abnormal postnatal cranial imaging in monochorionic and dichorionic

pregnancies were 43 and 12 percent, respectively (comparing monochorionic versus
dichorionic: OR 5.41, 95% CI 1.03-28.56).
● The rates of neurodevelopmental impairment of the co-twin in monochorionic and

dichorionic pregnancies were 29 and 10 percent, respectively (comparing monochorionic
versus dichorionic: OR 3.06, 95% CI 0.88-10.61).
● The rates of neonatal death of the co-twin in monochorionic and dichorionic pregnancies
were 28 and 21 percent, respectively (comparing monochorionic versus dichorionic: OR
1.95, 95% CI 1.00-3.79).
In monochorionic twins, single intrauterine fetal death before 28 weeks of gestation

increased the rate of co-twin fetal and neonatal death compared with single intrauterine fetal
death after 28 weeks.
While the risk to the surviving co-twin in a monochorionic pregnancy is clear when the death
of one twin occurs in the second or third trimester, the risk with death of one twin in the first
trimester is unclear. It has been hypothesized that congenital anomalies and cerebral palsy
may be attributable to early fetal loss of one conceptus in a twin gestation [212]. A
retrospective study using data from the population-based Northern Multiple Pregnancy
Register and Northern Congenital Abnormality Survey in the United Kingdom provided
support for this theory. The risk of a congenital anomaly in the survivor following loss of a co-
conceptus before 16 weeks of gestation was more than twice that in twin births [213]. These
data may reflect, at least in part, the known increased risk of concordant and discordant
congenital anomalies in monozygotic twins, which may lead to early in utero death of one
twin if the anomaly is severe. Prospective studies are needed to clarify these relationships.
Compared with pregnancies conceived as singletons, additional risks to the survivor after
demise of one twin include a 120 g reduction in mean birth weight, an increased risk of small
for gestational age birth, and an increased risk of preterm birth [54].
Management — The optimal management of pregnancies in which one twin is likely to

die or has died is unclear.
● Dichorionic twins – In dichorionic twins, death of one twin is not, by itself, a strong
indication for delivery of the surviving twin. However, if a condition affecting both twins is
present (eg, preeclampsia, chorioamnionitis), then close surveillance and timely delivery
of the surviving twin are indicated to prevent a second fetal loss.
● Monochorionic twins – As discussed above, death of one twin of a monochorionic pair

may have direct harmful effects on the survivor because of intertwin vascular
anastomoses. The hemodynamic changes that occur upon death of one twin are
immediate; therefore, prompt delivery after death to prevent damage to the survivor
appears to be futile [214]. When one twin dies prior to viability, our practice is to discuss
the option of pregnancy termination, although, as stated above, the risk to the co-twin is
not clear when the death occurs in the first trimester. Ultrasound and magnetic
resonance imaging evaluation of the surviving co-twin can identify signs of brain injury,
such as white matter lesions or intracranial hemorrhage, which develop over time and
may be helpful in predicting prognosis if abnormal. However, the performance of
imaging studies to predict or exclude fetal brain injury in this setting is unknown.
If fetal assessment after 26 weeks of gestation suggests impending death rather than
demise of one twin of a monochorionic pair, we suggest prompt delivery of both twins
rather than expectant management given the high risk of neurologic impairment in the
surviving co-twin.
It is not necessary to monitor for maternal coagulopathy in these cases since it is rare.
Maternal hypofibrinogenemia or disseminated intravascular coagulation following death
of one fetus of a multiple gestation has been described in only a few case reports [215-
219]. Although some experts have treated these women with a short course of heparin,
spontaneous resolution of hypofibrinogenemia occurs without therapy. We would only
consider heparin therapy if there is active hypofibrinogenemia-related bleeding,
hypofibrinogenemia in a patient at high risk of hemorrhage such as with placental previa
or abruptio placenta, or if there are thrombotic complications. We have not seen clinical
bleeding with hypofibrinogenemia in this setting. (See "Disseminated intravascular
coagulation (DIC) in adults: Evaluation and management".)
Anti-D immune globulin prophylaxis is recommended for RhD-negative women. (See "RhD
alloimmunization: Prevention in pregnant and postpartum patients", section on 'Prophylaxis
after pregnancy complications associated with fetomaternal bleeding'.)
Preterm labor and delivery — The major source of perinatal morbidity and mortality in twin
gestations is preterm birth. The increased risk is related, in part, to complications related to
monochorionicity and monoamnionicity. In addition, the increased risk of spontaneous
preterm birth (sPTB) may be related, at least in part, to increased myometrial distension
leading to more frequent and greater myometrial contractility compared with singleton
pregnancies [220,221].
In the United States, the preterm delivery rate in twins is 60 percent before 37 completed
weeks of gestation and 20 percent before 34 completed weeks (56 percent low birth weight
[<2500 g] and 9 percent very low birth weight [<1500 g]), although not all of the preterm
deliveries are spontaneous [41]. Interestingly, male-male twin pairs seem to be at highest risk
of preterm birth [222-224]. Risk factors for preterm birth, including the relationship between
prior preterm birth and preterm birth in the current pregnancy, are reviewed separately.
Interestingly, a preceding spontaneous singleton "early term" birth has been reported to be a
risk factor for sPTB in the subsequent twin pregnancy (OR 3.5) [225]. (See "Preterm birth: Risk
factors, interventions for risk reduction, and maternal prognosis", section on 'History of
spontaneous preterm birth'.)
Several studies have reported that neonatal outcome is similar for singletons, twins, and
triplets who are matched for gestational age [226,227]. However, actual outcomes are not
equivalent because the average length of gestation for singletons, twins, and triplets is
approximately 39, 35, and 32 weeks of gestation, respectively.
Multiple gestations that experience spontaneous reduction deliver earlier than nonreduced
pregnancies with the same number of fetuses. In one large series, triplet pregnancies that
spontaneously reduced to twins had significantly more preterm births <32 weeks than twins
that did not originate from a triplet pregnancy (27 versus 12 percent, OR 3.09, 95% CI 1.63-
5.87), and the length of gestation was on average 1.5 weeks shorter [228]. The difference
between groups in delivery <37 weeks was not statistically significant (83 percent versus 73
percent in twins without spontaneous reduction).
As discussed above, we do not routinely perform any tests in an attempt to identify

asymptomatic twin pregnancies at highest risk for preterm labor and delivery. Although an
elevated fetal fibronectin level [229-231] may predict pregnancies at particularly increased
risk of preterm delivery, we do not perform this test in asymptomatic patients since the
predictive value is low in asymptomatic patients and we believe that no intervention has been
clearly proven to be effective in reducing preterm birth rates in this population. The same is
true for screening for a short cervix (see 'Screening for short cervical length' above). Home
uterine activity monitoring (HUAM) effectively detects contractions; however, there are no
convincing data that use of HUAM results in an improvement any measure of neonatal
outcome [232].
Potential interventions — We do not use any of the following interventions in the routine
management of twin pregnancies as none has been proven to be effective. All have been
evaluated as potential methods for reducing the risk of preterm delivery in asymptomatic
twin gestations. However, we use some interventions in selected clinical circumstances, such
hydroxyprogesterone caproate for women with a previous spontaneous singleton preterm
birth or tocolytic drugs for inhibition of acute preterm labor. These clinical scenarios, and
alternative points of view, are reviewed below.
● Tocolytic therapy
• Prophylactic – A 2015 systematic review of randomized, placebo-controlled trials

concluded there was no convincing evidence that prophylactic oral betamimetics
reduced preterm birth in asymptomatic women with twin pregnancies (<37 weeks:
risk ratio [RR] 0.85, 95% CI 0.65-1.10; <34 weeks: RR 0.47, 95% CI 0.15-1.50) [233].
• Therapeutic – Although not evaluated in large randomized trials of twin pregnancies

alone, a brief course of tocolysis in women with acute preterm labor is reasonable to
allow a course of corticosteroids [194]. Women with twin pregnancies appear to be at
higher risk of pulmonary edema after administration of beta-adrenergic agents
because they have a higher blood volume and lower colloid osmotic pressure than
women carrying singletons. Therefore, these drugs should be used judiciously in
women with multiple gestations; calcium channel blockers or indomethacin is
preferred [194]. Use of tocolytic drugs for inhibition of symptomatic preterm labor
and is discussed separately. (See "Inhibition of acute preterm labor".)
● Pessary
• Unselected pregnancies – In two multicenter, randomized trials that included

approximately 2000 unselected women with multiple gestations, prophylactic
placement of a cervical pessary between 16 and 20 weeks [234] or 20 and 25 weeks
[235] of gestation did not reduce preterm birth or poor perinatal outcome compared
with no pessary use. In another randomized trial of twin gestations with a
midtrimester cervical length ≤30 mm, cervical pessary did not reduce the risk of
preterm birth, but the trial was underpowered to detect a modest benefit [236].
• Pregnancies with a short cervix – Use of a pessary may prolong pregnancy in twin
pregnancies with a short cervix, and more prospective data are available to support
use of a pessary than use of a cerclage. The most common definition of a short
cervix in twins is the same as in singletons: ≤25 mm [237]. Based on results from the
randomized trials described below, use of a cervical pessary may be considered in
twin pregnancies with a short cervix; however, we are not advising our patients to
use a pessary because no consistent benefit in composite neonatal morbidity has
been documented for any cervical length cutoff. We feel that further study
demonstrating a consistent benefit is needed before recommending cervical pessary
for a short cervix in asymptomatic patients or following threatened preterm labor.
- In a multicenter randomized trial in Spain, placement of a pessary in 137

asymptomatic women with twin pregnancies and a short cervix (≤25 mm) at 18
to 22 weeks reduced the rate of sPTB <34 weeks: 16.2 (11/68) versus 39.4
percent (26/66) with expectant management (RR 0.41, 95% CI 0.22-0.76) [238].
However, this reduction was not associated with a statistical reduction in
neonatal morbidity (composite adverse neonatal outcomes: 5.9 [8/68] versus 9.1
percent [12/66], RR 0.64, 95% CI 0.27-1.50).
In a subsequent randomized trial by the same investigators including 132

women with twin pregnancies who remained undelivered 48 hours after
threatened preterm labor and had a short cervix (≤20 mm), use of a pessary
reduced preterm birth <34 weeks (11/67 [16.4 percent] versus 21/65 [32.3
percent] with routine care) but not before 28 or 37 weeks [239]. There was also a
reduction in the number of neonates <2500 g at birth (24/134 [17.9 percent]
versus 92/130 [70.8 percent], RR 0.25, 95% CI 0.15-0.43).
- In a randomized trial in Vietnam comparing the effectiveness of cervical pessary

with vaginal progesterone for the prevention of preterm birth in asymptomatic
women with twin pregnancies and short cervix (≤28 mm), the pessary reduced
preterm birth <34 weeks of gestation by 53 percent (21 [10/47] versus 46 [16/35]
percent, RR 0.47, 95% CI 0.24-0.90) and a composite of poor perinatal outcome
by 62 percent (19 versus 50 percent, RR 0.38, 95% CI 0.12-0.47) [240]. For cervical
length <38 mm, the reduction in the composite of poor perinatal outcomes was
statistically significant, but the reduction in preterm birth <34 weeks was not.
● Cerclage
• Prophylactic cerclage (history indicated or based on twin pregnancy alone) – In

the absence of prospective data demonstrating a clear benefit, we do not perform
history-indicated or prophylactic cerclage in twins. A 2019 meta-analysis of
randomized trials and cohort studies (two randomized trials and four cohort studies)
comparing cervical cerclage with no cervical cerclage in twin gestations with normal
cervical length did not provide convincing evidence that prophylactic cerclage is an
effective intervention for preventing preterm birth and reducing perinatal death in
this population, even in women with a past history of preterm birth [241]. Because of
the small number of preterm deliveries in the analysis (n = 45, <34 weeks; n = 25, <28
weeks) and divergent results in a single small cohort study, a modest effect cannot
be excluded.
Given the low quality of available evidence, another reasonable approach is to

individualize this decision based on the patient's history and perform a history-
indicated cerclage if the patient has a classic history for cervical insufficiency in a
previous singleton pregnancy (second-trimester pregnancy loss associated with no
or minimal mild symptoms) and then presents with twins.
• Ultrasound-indicated cerclage – In the absence of prospective data demonstrating

a benefit, we recommend not performing ultrasound-indicated cerclage in twins. The
2019 meta-analysis described above also assessed the benefit of ultrasound-
indicated cerclage at cervical lengths ≤15 mm and 16 to 24 mm (three randomized
trials and three cohort studies) [241]. In twin pregnancies with cervical length ≤15
mm, cerclage placement was associated with prolongation of pregnancy (mean
difference 3.89 weeks of gestation, 95% CI 2.19-5.59) and a reduction in preterm
birth <37 weeks of gestation (RR 0.86, 95% CI 0.74-0.99), <34 weeks (RR 0.57, 95% CI
0.43-0.75), and <32 weeks (RR 0.61, 95% CI 0.41-0.90) compared with no cerclage. No
benefit was observed for women with cervical lengths of 16 to 24 mm, and no
improvement in neonatal outcome was demonstrated.
Most patients in the overall analysis were in retrospective cohort studies.

Importantly, when only patients in randomized trials were analyzed, ultrasound-
indicated cerclage was associated with higher risks of birth weight <1500 g and
<2500 g, although the number of pregnancies in these trials was small. Since there is
a divergence in results based on study type (cohort study versus randomized trial),
we await appropriately powered clinical trials demonstrating a benefit before
offering ultrasound-indicated cerclage to our patients.
• Physical examination-indicated cerclage – The only randomized trial of physical

examination-indicated cerclage in twin pregnancies found a reduction in sPTB and
perinatal mortality [242], in agreement with previous observational data [241]. In this
trial, 30 twin pregnancies with asymptomatic cervical dilation of 1 to 5 cm at 16+0 to

23+6 weeks of gestation were randomly assigned to receive cerclage or no cerclage.
All women who underwent cerclage received prophylactic antibiotics and
indomethacin. Before randomization, patients with vaginitis or urinary tract infection
were treated, and subclinical chorioamnionitis was excluded by either amniocentesis
or 12 hours of observation for signs of labor or infection. The cerclage group had
reductions in:
- sPTB <24 weeks (29 versus 85 percent, RR 0.35, 95% CI 0.16-0.75)

- Perinatal mortality (18 versus 77 percent, RR 0.23, 95% CI 0.10-0.49, number
needed to treat 1.7)
Cerclage increased the mean gestational age at delivery (29 versus 22.5 weeks).
There were no intraoperative complications. The trial was terminated early by the
data safety monitoring board because of the significant decrease in perinatal
mortality in the cerclage group. Because of this, subanalysis based on the degree of
cervical dilation, gestational age at placement, and use of progesterone or surgical
techniques was not performed. Though this trial was small, with only 30 patients
enrolled in eight sites over four years, the data suggest a clear benefit in
appropriately selected patients. In the authors' practice, physical examination-
indicated cerclage is offered after performing amniocentesis to rule out evidence of
subclinical infection. The section editor performs cerclage after a period of
observation to exclude signs of developing infection, rather than performing an
amniocentesis.
● Supplemental progesterone
• Routine use – The evidence does not support routine use of progesterone
supplementation to reduce the risk of preterm delivery or death in twin pregnancies
in the absence of a previous sPTB. These data are reviewed separately. (See
"Progesterone supplementation to reduce the risk of spontaneous preterm birth",
section on 'Multiple gestation'.)
• Short cervix – Whether progesterone supplementation improves pregnancy

outcome in selected twin pregnancies, such as those with a short cervix, is under
investigation. In a 2017 meta-analysis of individual patient data from six randomized

trials of women with twin gestations and midtrimester cervical length ≤25 mm,
vaginal progesterone reduced preterm birth <33 weeks compared with no
treatment/placebo (RR 0.69, 95% CI 0.51-0.93; 50/159 [31 percent] versus 62/144 [43
percent]) [237]. The relative risks of neonatal death, respiratory distress syndrome,
and birth weight <1500 g were also reduced significantly, on average by 30 to 50
percent. Because appropriately powered randomized trials frequently do not confirm
the findings of meta-analysis of small trials [243], we would like to see results from a
large clinical trial focusing on twin pregnancies before changing clinical practice. If
these findings are confirmed in large randomized trials focused on this population,
we would consider routine cervical length screening in twin pregnancies and
progesterone supplementation in those with a short cervix. Other UpToDate authors
have taken a different approach and both screen and offer progesterone to women
with twin pregnancies and a short cervix. (See "Progesterone supplementation to
reduce the risk of spontaneous preterm birth", section on 'Multiple gestation'.)
• Prior singleton preterm birth – In women with singleton pregnancy and a prior
preterm birth, prophylactic hydroxyprogesterone caproate reduces the rate of
recurrent preterm birth. However, it is not known whether hydroxyprogesterone
caproate is beneficial in women with twin pregnancy and prior spontaneous
singleton preterm birth. We and other UpToDate authors offer these patients
hydroxyprogesterone caproate, and counsel them about the lack of supporting
evidence. (See "Progesterone supplementation to reduce the risk of spontaneous
preterm birth", section on 'Multiple gestation'.)
● Bed rest – Systematic reviews of randomized trials of hospitalization or bed rest in twin
gestations have failed to show that either intervention increases gestational age at
delivery [244-246]. Bed rest may be harmful: A population-based cohort study of
pregnant women reported that antepartum hospitalization (an indirect marker of bed
rest) that was unrelated to delivery was associated with an increased the risk of venous
thromboembolism during hospitalization and in the 28 days after discharge [247].
Preterm prelabor rupture of membranes — Prelabor rupture of membranes typically

occurs in the presenting sac but can develop in the nonpresenting twin, especially after
invasive uterine procedures (eg, amniocentesis). Several studies have looked at perinatal
outcome after preterm prelabor rupture of membranes (PPROM) in twin versus singleton
gestations [248-250]. The largest of these was a retrospective cohort study of 116 twin
pregnancies with PPROM ≤36 weeks of gestation and 116 matched singleton pregnancies
[248]. Perinatal and neonatal outcomes were similar in the two groups; however, the median
latency period was statistically shorter in twins (11.4 versus 19.5 hours). In our series of twin
pregnancies with PPROM, 53 percent of twins with PPROM ≥30 weeks of gestation delivered
within two days, compared with only 29 percent of patients with PPROM <30 weeks [251].
Another study compared the frequency of chorioamnionitis in the nonpresenting and

presenting twins and by placentation [252]. Chorioamnionitis in the nonpresenting twin was
significantly less common in dichorionic than in monochorionic twins. Advanced
inflammation (defined as chorioamnionitis with funisitis) was significantly less common in the
nonpresenting twin than in the presenting twin, but only when the placentas were
dichorionic and separate.
General issues in management of PPROM and PROM are discussed separately. (See "Preterm
prelabor rupture of membranes: Clinical manifestations and diagnosis" and "Management of
prelabor rupture of the fetal membranes at term".)
TTTS and TAPS — (See "Twin-twin transfusion syndrome and twin anemia polycythemia
sequence: Screening, prevalence, pathophysiology, and diagnosis" and "Twin-twin
transfusion syndrome: Management and outcome".)
Selective growth restriction — (See "Selective fetal growth restriction in monochorionic twin
pregnancies".)
USE OF ANTENATAL CORTICOSTEROIDS AND MAGNESIUM SULFATE IN

PREGNANCIES AT RISK FOR PRETERM BIRTH
Antenatal corticosteroids for pregnancies at risk for preterm birth — We use a standard
dosing schedule for antenatal corticosteroids for both singleton and multiple gestations
believed to be at increased risk for preterm delivery within seven days. (See "Antenatal
corticosteroid therapy for reduction of neonatal respiratory morbidity and mortality from
preterm delivery", section on 'Multiple gestation'.)
Routine prophylactic administration to all twin pregnancies should be avoided and may have
adverse effects [253].
Magnesium sulfate for neuroprotection — Magnesium sulfate appears to reduce the

severity and risk of cerebral palsy in infants if administered before preterm birth <32 weeks
of gestation, regardless of fetal number [194]. (See "Neuroprotective effects of in utero

exposure to magnesium sulfate".)
SOCIETY GUIDELINE LINKS
Links to society and government-sponsored guidelines from selected countries and regions
around the world are provided separately. (See "Society guideline links: Multiple gestation".)
INFORMATION FOR PATIENTS
UpToDate offers two types of patient education materials, "The Basics" and "Beyond the
Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th
grade reading level, and they answer the four or five key questions a patient might have
about a given condition. These articles are best for patients who want a general overview and
who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are
longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th
grade reading level and are best for patients who want in-depth information and are
comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to
print or e-mail these topics to your patients. (You can also locate patient education articles on
a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
● Basics topics (see "Patient education: Having twins (The Basics)")
SUMMARY AND RECOMMENDATIONS
● Routine ultrasound examination in the first or early second trimester is the best method
to ensure early diagnosis of a twin pregnancy, establish an accurate gestational age, and
determine chorionicity. (See 'Role of early ultrasound examination' above.)
● The most reliable indicators of dichorionic twins are identification of two separate
placentas and male and female fetuses. If there is a single placental mass, chorionicity
and amnionicity are determined by identification of an intertwin membrane and
examination of this membrane for the twin peak or lambda sign, T sign, thickness, and
number of layers. (See 'Assessment of chorionicity and amnionicity' above.)
● Dizygotic (fraternal) twins are more common than monozygotic (identical) twins,
approximately 70 and 30 percent of twins, respectively (in the absence of use of assisted
reproductive technology). The prevalence of dizygotic twins varies among populations
whereas the prevalence of monozygotic twins is relatively stable worldwide at 3 to 5 per
1000 births. (See 'Relationship between chorionicity and amnionicity and zygosity' above
and 'Prevalence and epidemiology' above.)
● Early spontaneous reduction of one sac ("vanishing twin") has been reported in 15 to 36
percent of pregnancies conceived by in vitro fertilization. Rates of late fetal and infant
death are shown in the table ( table 1). Morbidity and mortality in twins is significantly
higher than in singletons ( table 2). (See 'Vanishing twins' above and 'Fetal/neonatal
death, preterm birth' above and 'Comparative outcomes of singleton, twin, and triplet
pregnancy' above.)
● All twin pregnancies are at increased risk of preterm delivery, congenital anomalies, and
growth restriction compared with singleton pregnancies, though twins are associated
with lower rates of postterm pregnancy and macrosomia. Monochorionic twins are at
significantly higher risk of adverse perinatal outcome than dichorionic twins ( table 1).
They are also at risk for unique pregnancy complications, such as twin-twin transfusion
syndrome, twin anemia polycythemia sequence, twin reversed arterial perfusion
sequence, and selective intrauterine growth restriction. Monoamniotic twins are at risk
for cord entanglement and conjoined twins. (See 'Fetal complications' above.)
● The National Academy of Medicine (formerly the Institute of Medicine) recommends 25

to 54 pounds total weight gain at term for women carrying twins. The lower end of this
range is appropriate for obese women, the middle of the range is appropriate for
overweight women, and the upper end of the range is appropriate for women of normal
weight. (See 'Gestational weight gain' above.)
● For women who choose to undergo screening for Down syndrome, we suggest either
first-trimester combined test or noninvasive screening using cell-free DNA in maternal
blood. While the combined test provides early, fetus-specific risk assessment, cell-free
fetal DNA has higher detection rates. Both fetuses should be karyotyped when
karyotyping is performed since even monozygotic twins may be discordant. (See
'Screening and diagnostic testing for Down syndrome' above.)
● The concordance rate of major congenital malformations in monozygotic twins is

approximately 20 percent. In addition to a sonographic anatomic survey, fetal
echocardiography is suggested at 18 to 22 weeks in monochorionic twins because of

their increased risk of congenital heart disease. Each twin of a dizygotic pair has a similar
congenital anomaly rate as a singleton and anomalies, if present, have a low
concordance rate. (See 'Screening for congenital anomalies' above.)
● Growth restriction is more common in twin than in singleton pregnancy and can be
defined in either of two ways (see 'Evaluation of fetal growth and growth discordance'
above):
• Estimated fetal weight below the 10th percentile using singleton growth curves.
or
• Presence of ≥20 percent discordance in estimated fetal weight between the lighter
and heavier twin.
● Our approach to monitoring monochorionic twin pregnancies is described in the

algorithm ( algorithm 1). (See 'Monochorionic twins' above.)
In dichorionic twin pregnancies, we perform an ultrasound examination every four to six

weeks after 20 weeks of gestation as fetal growth deceleration leading to discordancy is
optimally detected between 20 and 28 weeks of gestation. (See 'Dichorionic twins'
above.)
● We perform weekly testing with nonstress tests and amniotic fluid evaluation or
biophysical profile scoring starting at 32 weeks in almost all twin pregnancies (excludes
monochorionic monoamniotic twins). Testing is performed earlier and/or more
frequently if complications, such as fetal growth restriction, develop. Some providers
begin antepartum monitoring earlier (28 to 32 weeks) in monochorionic pregnancies.
(See 'Assessment of fetal well-being' above.)
● Single fetal death after 20 weeks of gestation occurs in approximately 5 percent of twin
pregnancies. Because of placental vascular anastomoses between monochorionic twins,
the intrauterine death of one twin in a monochorionic twin pregnancy can cause acute
hypotension, anemia, and ischemia in its co-twin, resulting in morbidity or death of the
co-twin. For this reason, if fetal assessment after 26 weeks of gestation suggests
impending death of one twin, we suggest prompt delivery of monochorionic twins rather
than expectant management (Grade 2C). Prompt delivery is unlikely to benefit the
survivor after death of one twin of a dichorionic or monochorionic gestation. (See 'Death
of one twin' above.)
● An elevated fetal fibronectin level or short cervical length on ultrasound examination

may predict women at particularly increased risk of preterm delivery; however, the
predictive value is low in asymptomatic patients. No intervention has been proven to be
effective in reducing preterm birth rates in twin pregnancies. (See 'Preterm labor and
delivery' above.)
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REFERENCES
1. Ewigman BG, Crane JP, Frigoletto FD, et al. Effect of prenatal ultrasound screening on
perinatal outcome. RADIUS Study Group. N Engl J Med 1993; 329:821.
2. Saari-Kemppainen A, Karjalainen O, Ylöstalo P, Heinonen OP. Ultrasound screening and
perinatal mortality: controlled trial of systematic one-stage screening in pregnancy. The
Helsinki Ultrasound Trial. Lancet 1990; 336:387.
3. Committee on Practice Bulletins—Obstetrics and the American Institute of Ultrasound in
Medicine. Practice Bulletin No. 175: Ultrasound in Pregnancy. Obstet Gynecol 2016;
128:e241.
4. Morin L, Lim K, DIAGNOSTIC IMAGING COMMITTEE, et al. Ultrasound in twin

pregnancies. J Obstet Gynaecol Can 2011; 33:643.
5. Khalil A, Rodgers M, Baschat A, et al. ISUOG Practice Guidelines: role of ultrasound in
twin pregnancy. Ultrasound Obstet Gynecol 2016; 47:247.
6. Dubé J, Dodds L, Armson BA. Does chorionicity or zygosity predict adverse perinatal
outcomes in twins? Am J Obstet Gynecol 2002; 186:579.
7. Sebire NJ, Snijders RJ, Hughes K, et al. The hidden mortality of monochorionic twin
pregnancies. Br J Obstet Gynaecol 1997; 104:1203.
8. Adegbite AL, Castille S, Ward S, Bajoria R. Neuromorbidity in preterm twins in relation to
chorionicity and discordant birth weight. Am J Obstet Gynecol 2004; 190:156.
9. Leduc L, Takser L, Rinfret D. Persistance of adverse obstetric and neonatal outcomes in
monochorionic twins after exclusion of disorders unique to monochorionic placentation.
Am J Obstet Gynecol 2005; 193:1670.
10. Hack KE, Derks JB, Elias SG, et al. Increased perinatal mortality and morbidity in
monochorionic versus dichorionic twin pregnancies: clinical implications of a large Dutch
cohort study. BJOG 2008; 115:58.

11. Ortibus E, Lopriore E, Deprest J, et al. The pregnancy and long-term neurodevelopmental
outcome of monochorionic diamniotic twin gestations: a multicenter prospective cohort
study from the first trimester onward. Am J Obstet Gynecol 2009; 200:494.e1.
12. Acosta-Rojas R, Becker J, Munoz-Abellana B, et al. Twin chorionicity and the risk of
adverse perinatal outcome. Int J Gynaecol Obstet 2007; 96:98.
13. Glinianaia SV, Obeysekera MA, Sturgiss S, Bell R. Stillbirth and neonatal mortality in
monochorionic and dichorionic twins: a population-based study. Hum Reprod 2011;
26:2549.
14. McPherson JA, Odibo AO, Shanks AL, et al. Impact of chorionicity on risk and timing of
intrauterine fetal demise in twin pregnancies. Am J Obstet Gynecol 2012; 207:190.e1.
15. Emery SP, Bahtiyar MO, Dashe JS, et al. The North American Fetal Therapy Network
Consensus Statement: prenatal management of uncomplicated monochorionic
gestations. Obstet Gynecol 2015; 125:1236.
16. Lee YM, Cleary-Goldman J, Thaker HM, Simpson LL. Antenatal sonographic prediction of
twin chorionicity. Am J Obstet Gynecol 2006; 195:863.
17. Wan JJ, Schrimmer D, Taché V, et al. Current practices in determining amnionicity and
chorionicity in multiple gestations. Prenat Diagn 2011; 31:125.
18. Blumenfeld YJ, Momirova V, Rouse DJ, et al. Accuracy of sonographic chorionicity
classification in twin gestations. J Ultrasound Med 2014; 33:2187.
19. Stenhouse E, Hardwick C, Maharaj S, et al. Chorionicity determination in twin
pregnancies: how accurate are we? Ultrasound Obstet Gynecol 2002; 19:350.
20. Carroll SG, Soothill PW, Abdel-Fattah SA, et al. Prediction of chorionicity in twin
pregnancies at 10-14 weeks of gestation. BJOG 2002; 109:182.
21. Scardo JA, Ellings JM, Newman RB. Prospective determination of chorionicity, amnionicity,
and zygosity in twin gestations. Am J Obstet Gynecol 1995; 173:1376.
22. Bora SA, Papageorghiou AT, Bottomley C, et al. Reliability of transvaginal
ultrasonography at 7-9 weeks' gestation in the determination of chorionicity and
amnionicity in twin pregnancies. Ultrasound Obstet Gynecol 2008; 32:618.
23. Lopriore E, Sueters M, Middeldorp JM, et al. Twin pregnancies with two separate
placental masses can still be monochorionic and have vascular anastomoses. Am J
Obstet Gynecol 2006; 194:804.
24. Wood SL, St Onge R, Connors G, Elliot PD. Evaluation of the twin peak or lambda sign in
determining chorionicity in multiple pregnancy. Obstet Gynecol 1996; 88:6.

25. Kurtz AB, Wapner RJ, Mata J, et al. Twin pregnancies: accuracy of first-trimester
abdominal US in predicting chorionicity and amnionicity. Radiology 1992; 185:759.
26. Townsend RR, Simpson GF, Filly RA. Membrane thickness in ultrasound prediction of
chorionicity of twin gestations. J Ultrasound Med 1988; 7:327.
27. D'Alton ME, Dudley DK. The ultrasonographic prediction of chorionicity in twin gestation.
28. Dias T, Arcangeli T, Bhide A, et al. First-trimester ultrasound determination of chorionicity
in twin pregnancy. Ultrasound Obstet Gynecol 2011; 38:530.
29. Maruotti GM, Saccone G, Morlando M, Martinelli P. First-trimester ultrasound
determination of chorionicity in twin gestations using the lambda sign: a systematic
review and meta-analysis. Eur J Obstet Gynecol Reprod Biol 2016; 202:66.
30. Lu J, Cheng YKY, Ting YH, et al. Pitfalls in assessing chorioamnionicity: novel observations
and literature review. Am J Obstet Gynecol 2018; 219:242.
31. Norwitz ER, McNeill G, Kalyan A, et al. Validation of a Single-Nucleotide Polymorphism-

Based Non-Invasive Prenatal Test in Twin Gestations: Determination of Zygosity,
Individual Fetal Sex, and Fetal Aneuploidy. J Clin Med 2019; 8.
32. Peters HE, König TE, Verhoeven MO, et al. Unusual Twinning Resulting in Chimerism: A
Systematic Review on Monochorionic Dizygotic Twins. Twin Res Hum Genet 2017; 20:161.
33. Dias T, Ladd S, Mahsud-Dornan S, et al. Systematic labeling of twin pregnancies on
ultrasound. Ultrasound Obstet Gynecol 2011; 38:130.
34. Souter VL, Kapur RP, Nyholt DR, et al. A report of dizygous monochorionic twins. N Engl J
Med 2003; 349:154.
35. Yoon G, Beischel LS, Johnson JP, Jones MC. Dizygotic twin pregnancy conceived with
assisted reproductive technology associated with chromosomal anomaly, imprinting
disorder, and monochorionic placentation. J Pediatr 2005; 146:565.
36. Miura K, Niikawa N. Do monochorionic dizygotic twins increase after pregnancy by
assisted reproductive technology? J Hum Genet 2005; 50:1.
37. Schiewe MC, Whitney JB, Anderson RE. Potential risk of monochorionic dizygotic twin
blastocyst formation associated with early laser zona dissection of group cultured
embryos. Fertil Steril 2015; 103:417.
38. Zou Z, Huang L, Lin S, et al. Unusual twinning: Additional findings during prenatal
diagnosis of twin zygosity by single nucleotide polymorphism (SNP) array. Prenat Diagn
2018; 38:428.
39. McNamara HC, Kane SC, Craig JM, et al. A review of the mechanisms and evidence for
typical and atypical twinning. Am J Obstet Gynecol 2016; 214:172.
40. Gabbett MT, Laporte J, Sekar R, et al. Molecular Support for Heterogonesis Resulting in
Sesquizygotic Twinning. N Engl J Med 2019; 380:842.
41. Martin JA, Hamilton BE, Osterman MJK, Driscoll AK. Births: Final Data for 2018. Natl Vital
Stat Rep 2019; 68:1.
42. Cameron AH, Edwards JH, Derom R, et al. The value of twin surveys in the study of
malformations. Eur J Obstet Gynecol Reprod Biol 1983; 14:347.
43. Adashi EY. Seeing double: a nation of twins from sea to shining sea. Am J Obstet Gynecol
2016; 214:311.
44. https://nccd.cdc.gov/drh_art/rdPage.aspx?rdReport=DRH_ART.ClinicInfo&rdRequestForw
ard=True&ClinicId=9999&ShowNational=1 (Accessed on September 07, 2018).
45. Adashi EY, Gutman R. Delayed Childbearing as a Growing, Previously Unrecognized
Contributor to the National Plural Birth Excess. Obstet Gynecol 2018; 132:999.
46. Bulmer MG. The Biology of Twinning in Man, Clarendon Press, Oxford 1970.
47. Lisonkova S, Joseph KS, Bell R, Glinianaia SV. Effect of advanced maternal age on
perinatal outcomes in twins: the impact of chorionicity. Ann Epidemiol 2013; 23:428.
48. Mullins E, Kumar S. Older mothers do not confer greater perinatal risk to dichorionic
diamniotic twins. Acta Obstet Gynecol Scand 2012; 91:152.
49. Kathiresan AS, Roca LE 2nd, Istwan N, et al. The influence of maternal age on pregnancy
outcome in nulliparous women with twin gestation. Am J Perinatol 2011; 28:355.
50. Fox NS, Rebarber A, Dunham SM, Saltzman DH. Outcomes of multiple gestations with
advanced maternal age. J Matern Fetal Neonatal Med 2009; 22:593.
51. Delbaere I, Verstraelen H, Goetgeluk S, et al. Perinatal outcome of twin pregnancies in
women of advanced age. Hum Reprod 2008; 23:2145.
52. Suzuki S. Obstetric outcomes in nulliparous women aged 35 and over with dichorionic
twin pregnancy. Arch Gynecol Obstet 2007; 276:573.
53. McLennan AS, Gyamfi-Bannerman C, Ananth CV, et al. The role of maternal age in twin
pregnancy outcomes. Am J Obstet Gynecol 2017; 217:80.e1.
54. Practice Committee of American Society for Reproductive Medicine. Multiple gestation
associated with infertility therapy: an American Society for Reproductive Medicine
Practice Committee opinion. Fertil Steril 2012; 97:825.

55. Palomaki GE, Chiu RWK, Pertile MD, et al. International Society for Prenatal Diagnosis
Position Statement: cell free (cf)DNA screening for Down syndrome in multiple
pregnancies. Prenat Diagn 2020.
56. Hoekstra C, Zhao ZZ, Lambalk CB, et al. Dizygotic twinning. Hum Reprod Update 2008;
14:37.
57. Moore RK, Erickson GF, Shimasaki S. Are BMP-15 and GDF-9 primary determinants of
ovulation quota in mammals? Trends Endocrinol Metab 2004; 15:356.
58. Nylander PP. The factors that influence twinning rates. Acta Genet Med Gemellol (Roma)
1981; 30:189.
59. Reddy UM, Branum AM, Klebanoff MA. Relationship of maternal body mass index and
height to twinning. Obstet Gynecol 2005; 105:593.
60. Basso O, Nohr EA, Christensen K, Olsen J. Risk of twinning as a function of maternal
height and body mass index. JAMA 2004; 291:1564.
61. Steinman G. Can the chance of having twins be modified by diet? Lancet 2006; 367:1461.
62. Khamsi F, Roberge S, Wong J. Novel demonstration of a physiologic/pharmacologic role
of insulin-like growth factor-1 in ovulation in rats and action on cumulus oophorus.
Endocrine 2001; 14:175.
63. Muggli EE, Halliday JL. Folic acid and risk of twinning: a systematic review of the recent
literature, July 1994 to July 2006. Med J Aust 2007; 186:243.
64. Romanski PA, Carusi DA, Farland LV, et al. Perinatal and Peripartum Outcomes in
Vanishing Twin Pregnancies Achieved by In Vitro Fertilization. Obstet Gynecol 2018;
131:1011.
65. Harris AL, Sacha CR, Basnet KM, et al. Vanishing Twins Conceived Through Fresh In Vitro
Fertilization: Obstetric Outcomes and Placental Pathology. Obstet Gynecol 2020;
135:1426.
66. Seong JS, Han YJ, Kim MH, et al. The risk of preterm birth in vanishing twin: A multicenter
prospective cohort study. PLoS One 2020; 15:e0233097.
67. Evron E, Sheiner E, Friger M, et al. Vanishing twin syndrome: is it associated with adverse
perinatal outcome? Fertil Steril 2015; 103:1209.
68. Pinborg A, Lidegaard O, la Cour Freiesleben N, Andersen AN. Consequences of vanishing

twins in IVF/ICSI pregnancies. Hum Reprod 2005; 20:2821.
69. Almog B, Levin I, Wagman I, et al. Adverse obstetric outcome for the vanishing twin
syndrome. Reprod Biomed Online 2010; 20:256.
70. Chasen ST, Luo G, Perni SC, Kalish RB. Are in vitro fertilization pregnancies with early
spontaneous reduction high risk? Am J Obstet Gynecol 2006; 195:814.
71. Shebl O, Ebner T, Sommergruber M, et al. Birth weight is lower for survivors of the
vanishing twin syndrome: a case-control study. Fertil Steril 2008; 90:310.
72. La Sala GB, Villani MT, Nicoli A, et al. Effect of the mode of assisted reproductive
technology conception on obstetric outcomes for survivors of the vanishing twin
syndrome. Fertil Steril 2006; 86:247.
73. Zhou L, Gao X, Wu Y, Zhang Z. Analysis of pregnancy outcomes for survivors of the
vanishing twin syndrome after in vitro fertilization and embryo transfer. Eur J Obstet
Gynecol Reprod Biol 2016; 203:35.
74. Litwinska E, Syngelaki A, Cimpoca B, et al. Outcome of twin pregnancy with two live
fetuses at 11-13 weeks' gestation. Ultrasound Obstet Gynecol 2020; 55:32.
75. Misra DP, Ananth CV. Infant mortality among singletons and twins in the United States
during 2 decades: effects of maternal age. Pediatrics 2002; 110:1163.
76. Chauhan SP, Scardo JA, Hayes E, et al. Twins: prevalence, problems, and preterm births.
77. Mackie FL, Hall MJ, Morris RK, Kilby MD. Early prognostic factors of outcomes in
monochorionic twin pregnancy: systematic review and meta-analysis. Am J Obstet
Gynecol 2018; 219:436.
78. Sebire NJ, D'Ercole C, Soares W, et al. Intertwin disparity in fetal size in monochorionic
and dichorionic pregnancies. Obstet Gynecol 1998; 91:82.
79. Lee YM, Wylie BJ, Simpson LL, D'Alton ME. Twin chorionicity and the risk of stillbirth.
80. Winkler N, Kennedy A, Byrne J, Woodward P. The imaging spectrum of conjoined twins.
Ultrasound Q 2008; 24:249.
81. Spitz L. Conjoined twins. Prenat Diagn 2005; 25:814.
82. Mackenzie TC, Crombleholme TM, Johnson MP, et al. The natural history of prenatally
diagnosed conjoined twins. J Pediatr Surg 2002; 37:303.
83. Brizot ML, Liao AW, Lopes LM, et al. Conjoined twins pregnancies: experience with 36
cases from a single center. Prenat Diagn 2011; 31:1120.
84. Santana DS, Cecatti JG, Surita FG, et al. Twin Pregnancy and Severe Maternal Outcomes:
The World Health Organization Multicountry Survey on Maternal and Newborn Health.
85. Carter EB, Bishop KC, Goetzinger KR, et al. The impact of chorionicity on maternal
pregnancy outcomes. Am J Obstet Gynecol 2015; 213:390.e1.
86. Witteveen T, Van Den Akker T, Zwart JJ, et al. Severe acute maternal morbidity in multiple
pregnancies: a nationwide cohort study. Am J Obstet Gynecol 2016; 214:641.e1.
87. Kametas NA, McAuliffe F, Krampl E, et al. Maternal cardiac function in twin pregnancy.
88. Rao A, Sairam S, Shehata H. Obstetric complications of twin pregnancies. Best Pract Res
Clin Obstet Gynaecol 2004; 18:557.
89. Kuleva M, Youssef A, Maroni E, et al. Maternal cardiac function in normal twin pregnancy:
a longitudinal study. Ultrasound Obstet Gynecol 2011; 38:575.
90. Ghi T, degli Esposti D, Montaguti E, et al. Maternal cardiac evaluation during
uncomplicated twin pregnancy with emphasis on the diastolic function. Am J Obstet
Gynecol 2015; 213:376.e1.
91. Sibai BM, Hauth J, Caritis S, et al. Hypertensive disorders in twin versus singleton
gestations. National Institute of Child Health and Human Development Network of
Maternal-Fetal Medicine Units. Am J Obstet Gynecol 2000; 182:938.
92. Francisco C, Wright D, Benkő Z, et al. Hidden high rate of pre-eclampsia in twin
compared with singleton pregnancy. Ultrasound Obstet Gynecol 2017; 50:88.
93. Lučovnik M, Blickstein I, Lasič M, et al. Hypertensive disorders during monozygotic and
dizygotic twin gestations: A population-based study. Hypertens Pregnancy 2016; 35:542.
94. Krotz S, Fajardo J, Ghandi S, et al. Hypertensive disease in twin pregnancies: a review.
Twin Res 2002; 5:8.
95. Fischer RL, Bianculli KW, Hediger ML, Scholl TO. Maternal serum uric acid levels in twin
gestations. Obstet Gynecol 1995; 85:60.
96. Hsu CD, Chung YK, Lee IS, et al. Maternal serum uric acid levels in preeclamptic women
with multiple gestations. Am J Perinatol 1997; 14:613.
97. Fischer RL, Weisberg LS, Hediger ML. Etiology of third-trimester maternal hyperuricemia
in nonpreeclamptic twin gestations. Obstet Gynecol 2001; 97:62.
98. Cohen SB, Kreiser D, Erez I, et al. Effect of fetal number on maternal serum uric acid
concentration. Am J Perinatol 2002; 19:291.
99. Sarhanis P, Pugh DH. Resolution of pre-eclampsia following intrauterine death of one
twin. Br J Obstet Gynaecol 1992; 99:159.
100. Hagay ZJ, Levy R, Zalel Y, Weissman A. Single fetal demise in twin gestation resulting in
the resolution of severe pre-eclampsia. Eur J Obstet Gynecol Reprod Biol 1994; 56:137.
101. Audibert F, Salomon LJ, Castaigne-Meary V, et al. Selective termination of a twin

pregnancy as a treatment of severe pre-eclampsia. BJOG 2003; 110:68.
102. Schwartz DB, Daoud Y, Zazula P, et al. Gestational diabetes mellitus: metabolic and blood
glucose parameters in singleton versus twin pregnancies. Am J Obstet Gynecol 1999;
181:912.
103. Sivan E, Maman E, Homko CJ, et al. Impact of fetal reduction on the incidence of
gestational diabetes. Obstet Gynecol 2002; 99:91.
104. Roach VJ, Lau TK, Wilson D, Rogers MS. The incidence of gestational diabetes in multiple
pregnancy. Aust N Z J Obstet Gynaecol 1998; 38:56.
105. Buhling KJ, Henrich W, Starr E, et al. Risk for gestational diabetes and hypertension for
women with twin pregnancy compared to singleton pregnancy. Arch Gynecol Obstet
2003; 269:33.
106. Henderson CE, Scarpelli S, LaRosa D, Divon MY. Assessing the risk of gestational diabetes
in twin gestation. J Natl Med Assoc 1995; 87:757.
107. Gonzalez MC, Reyes H, Arrese M, et al. Intrahepatic cholestasis of pregnancy in twin
pregnancies. J Hepatol 1989; 9:84.
108. Hall MH, Campbell DM, Davidson RJ. Anaemia in twin pregnancy. Acta Genet Med
Gemellol (Roma) 1979; 28:279.
109. Campbell DM, Templeton A. Maternal complications of twin pregnancy. Int J Gynaecol
Obstet 2004; 84:71.
110. Dodd JM, Crowther CA. Specialised antenatal clinics for women with a multiple
pregnancy for improving maternal and infant outcomes. Cochrane Database Syst Rev
2012; :CD005300.
111. http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2009/Weight-Gai
n-During-Pregnancy-Reexamining-the-Guidelines/Report%20Brief%20-%20Weight%20Ga
in%20During%20Pregnancy.pdf (Accessed on September 07, 2018).
112. www.iom.edu/CMS/3788/48191/68004/68230.aspx (Accessed on May 29, 2009).
113. Fox NS, Rebarber A, Roman AS, et al. Weight gain in twin pregnancies and adverse
outcomes: examining the 2009 Institute of Medicine guidelines. Obstet Gynecol 2010;
116:100.
114. Fox NS, Saltzman DH, Kurtz H, Rebarber A. Excessive weight gain in term twin
pregnancies: examining the 2009 Institute of Medicine definitions. Obstet Gynecol 2011;
118:1000.
115. Shamshirsaz AA, Haeri S, Ravangard SF, et al. Perinatal outcomes based on the institute
of medicine guidelines for weight gain in twin pregnancies. J Matern Fetal Neonatal Med
2014; 27:552.
116. Pettit KE, Lacoursiere DY, Schrimmer DB, et al. The association of inadequate mid-
pregnancy weight gain and preterm birth in twin pregnancies. J Perinatol 2015; 35:85.
117. Goodnight W, Newman R, Society of Maternal-Fetal Medicine. Optimal nutrition for

improved twin pregnancy outcome. Obstet Gynecol 2009; 114:1121.
118. Bermúdez C, Becerra CH, Bornick PW, et al. Placental types and twin-twin transfusion
syndrome. Am J Obstet Gynecol 2002; 187:489.
119. O'Donnell CP, Pertile MD, Sheffield LJ, Sampson A. Monozygotic twins with discordant
karyotypes: a case report. J Pediatr 2004; 145:406.
120. Nieuwint A, Van Zalen-Sprock R, Hummel P, et al. 'Identical' twins with discordant
karyotypes. Prenat Diagn 1999; 19:72.
121. Beattie RB, Manson IW, Whittle MJ. Identical twins with trisomy 21 discordant for
exomphalos. Prenat Diagn 1993; 13:1067.
122. Rogers JG, Voullaire L, Gold H. Monozygotic twins discordant for trisomy 21. Am J Med
Genet 1982; 11:143.
123. Edlow AG, Reiss R, Benson CB, et al. Monochorionic diamniotic twin gestations
discordant for markedly enlarged nuchal translucency. Prenat Diagn 2011; 31:299.
124. Peng R, Zhou Y, Xie HN, et al. MCDA twins with discordant malformations:
submicroscopic chromosomal anomalies detected by chromosomal microarray analysis
and clinical outcomes. Prenat Diagn 2016; 36:766.
125. Sparks TN, Norton ME, Flessel M, et al. Observed Rate of Down Syndrome in Twin
Pregnancies. Obstet Gynecol 2016; 128:1127.
126. Lau TK, Jiang F, Chan MK, et al. Non-invasive prenatal screening of fetal Down syndrome
by maternal plasma DNA sequencing in twin pregnancies. J Matern Fetal Neonatal Med
2013; 26:434.
127. Leung TY, Qu JZ, Liao GJ, et al. Noninvasive twin zygosity assessment and aneuploidy
detection by maternal plasma DNA sequencing. Prenat Diagn 2013; 33:675.
128. Canick JA, Kloza EM, Lambert-Messerlian GM, et al. DNA sequencing of maternal plasma
to identify Down syndrome and other trisomies in multiple gestations. Prenat Diagn
2012; 32:730.
129. Huang X, Zheng J, Chen M, et al. Noninvasive prenatal testing of trisomies 21 and 18 by
massively parallel sequencing of maternal plasma DNA in twin pregnancies. Prenat
Diagn 2014; 34:335.
130. Gil MM, Galeva S, Jani J, et al. Screening for trisomies by cfDNA testing of maternal blood
in twin pregnancy: update of The Fetal Medicine Foundation results and meta-analysis.
Ultrasound Obstet Gynecol 2019; 53:734.
131. Galeva S, Gil MM, Konstantinidou L, et al. First-trimester screening for trisomies by cfDNA
testing of maternal blood in singleton and twin pregnancies: factors affecting test
failure. Ultrasound Obstet Gynecol 2019; 53:804.
132. American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins—
Obstetrics, Committee on Genetics, Society for Maternal-Fetal Medicine. Screening for
Fetal Chromosomal Abnormalities: ACOG Practice Bulletin, Number 226. Obstet Gynecol
2020; 136:e48.
133. Spencer K, Staboulidou I, Nicolaides KH. First trimester aneuploidy screening in the
presence of a vanishing twin: implications for maternal serum markers. Prenat Diagn
2010; 30:235.
134. Chasen ST, Perni SC, Predanic M, et al. Does a "vanishing twin" affect first-trimester
biochemistry in Down syndrome risk assessment? Am J Obstet Gynecol 2006; 195:236.
135. Spencer K, Nicolaides KH. Screening for trisomy 21 in twins using first trimester
ultrasound and maternal serum biochemistry in a one-stop clinic: a review of three years
experience. BJOG 2003; 110:276.
136. Chasen ST, Perni SC, Kalish RB, Chervenak FA. First-trimester risk assessment for
trisomies 21 and 18 in twin pregnancy. Am J Obstet Gynecol 2007; 197:374.e1.
137. Prats P, Rodríguez I, Comas C, Puerto B. Systematic review of screening for trisomy 21 in
twin pregnancies in first trimester combining nuchal translucency and biochemical
markers: a meta-analysis. Prenat Diagn 2014; 34:1077.
138. Stagnati V, Zanardini C, Fichera A, et al. Early prediction of twin-to-twin transfusion
syndrome: systematic review and meta-analysis. Ultrasound Obstet Gynecol 2017;
49:573.
139. Maymon R, Neeman O, Shulman A, et al. Current concepts of Down syndrome screening
tests in assisted reproduction twin pregnancies: another double trouble. Prenat Diagn
2005; 25:746.
140. Sperling L, Kiil C, Larsen LU, et al. Detection of chromosomal abnormalities, congenital
abnormalities and transfusion syndrome in twins. Ultrasound Obstet Gynecol 2007;
29:517.
141. Bahtiyar MO, Dulay AT, Weeks BP, et al. Prevalence of congenital heart defects in
monochorionic/diamniotic twin gestations: a systematic literature review. J Ultrasound
Med 2007; 26:1491.
142. Glinianaia SV, Rankin J, Wright C. Congenital anomalies in twins: a register-based study.
Hum Reprod 2008; 23:1306.
143. Weber MA, Sebire NJ. Genetics and developmental pathology of twinning. Semin Fetal
Neonatal Med 2010; 15:313.
144. Chen CJ, Wang CJ, Yu MW, Lee TK. Perinatal mortality and prevalence of major congenital
malformations of twins in Taipei city. Acta Genet Med Gemellol (Roma) 1992; 41:197.
145. American Institute of Ultrasound in Medicine. AIUM practice guideline for the
performance of obstetric ultrasound examinations. J Ultrasound Med 2013; 32:1083.
146. Bahtiyar MO, Emery SP, Dashe JS, et al. The North American Fetal Therapy Network
consensus statement: prenatal surveillance of uncomplicated monochorionic gestations.
147. Pettit KE, Merchant M, Machin GA, et al. Congenital heart defects in a large, unselected
cohort of monochorionic twins. J Perinatol 2013; 33:457.
148. Tararbit K, Houyel L, Bonnet D, et al. Risk of congenital heart defects associated with
assisted reproductive technologies: a population-based evaluation. Eur Heart J 2011;
32:500.
149. Panagiotopoulou O, Fouzas S, Sinopidis X, et al. Congenital heart disease in twins: The
contribution of type of conception and chorionicity. Int J Cardiol 2016; 218:144.
150. Bahtiyar MO, Campbell K, Dulay AT, et al. Is the rate of congenital heart defects detected
by fetal echocardiography among pregnancies conceived by in vitro fertilization really
increased?: a case-historical control study. J Ultrasound Med 2010; 29:917.
151. Iwashima S, Ishikawa T, Itoh H. Reproductive technologies and the risk of congenital
heart defects. Hum Fertil (Camb) 2017; 20:14.
152. Davies MJ, Moore VM, Willson KJ, et al. Reproductive technologies and the risk of birth
defects. N Engl J Med 2012; 366:1803.
153. Schofield SJ, Doughty VL, van Stiphout N, et al. Assisted conception and the risk of CHD: a
case-control study. Cardiol Young 2017; 27:473.
154. AIUM Practice Parameter for the Performance of Fetal Echocardiograph https://www.aiu
m.org/resources/guidelines/fetalecho.pdf (Accessed on July 02, 2018).
155. Rustico MA, Baietti MG, Coviello D, et al. Managing twins discordant for fetal anomaly.
Prenat Diagn 2005; 25:766.
156. Vandecruys H, Avgidou K, Surerus E, et al. Dilemmas in the management of twins
discordant for anencephaly diagnosed at 11 + 0 to 13 + 6 weeks of gestation. Ultrasound
157. Lust A, De Catte L, Lewi L, et al. Monochorionic and dichorionic twin pregnancies
discordant for fetal anencephaly: a systematic review of prenatal management options.
Prenat Diagn 2008; 28:275.
158. Diehl W, Hecher K. Selective cord coagulation in acardiac twins. Semin Fetal Neonatal
Med 2007; 12:458.
159. Evans MI, Goldberg JD, Horenstein J, et al. Selective termination for structural,
chromosomal, and mendelian anomalies: international experience. Am J Obstet Gynecol
1999; 181:893.
160. Conde-Agudelo A, Romero R, Hassan SS, Yeo L. Transvaginal sonographic cervical length
for the prediction of spontaneous preterm birth in twin pregnancies: a systematic review
and metaanalysis. Am J Obstet Gynecol 2010; 203:128.e1.
161. Lim AC, Hegeman MA, Huis In 'T Veld MA, et al. Cervical length measurement for the
prediction of preterm birth in multiple pregnancies: a systematic review and bivariate
meta-analysis. Ultrasound Obstet Gynecol 2011; 38:10.
162. Ananth CV, Demissie K, Smulian JC, Vintzileos AM. Placenta previa in singleton and twin
births in the United States, 1989 through 1998: a comparison of risk factor profiles and
associated conditions. Am J Obstet Gynecol 2003; 188:275.
163. Jauniaux E, Melcer Y, Maymon R. Prenatal diagnosis and management of vasa previa in
twin pregnancies: a case series and systematic review. Am J Obstet Gynecol 2017;
216:568.
164. Kalafat E, Thilaganathan B, Papageorghiou A, et al. Significance of placental cord
insertion site in twin pregnancy. Ultrasound Obstet Gynecol 2018; 52:378.
165. Garite TJ, Clark RH, Elliott JP, Thorp JA. Twins and triplets: the effect of plurality and
growth on neonatal outcome compared with singleton infants. Am J Obstet Gynecol
2004; 191:700.
166. Hartley RS, Hitti J, Emanuel I. Size-discordant twin pairs have higher perinatal mortality
rates than nondiscordant pairs. Am J Obstet Gynecol 2002; 187:1173.

167. Blickstein I, Keith LG. Neonatal mortality rates among growth-discordant twins, classified
according to the birth weight of the smaller twin. Am J Obstet Gynecol 2004; 190:170.
168. Amaru RC, Bush MC, Berkowitz RL, et al. Is discordant growth in twins an independent
risk factor for adverse neonatal outcome? Obstet Gynecol 2004; 103:71.
169. Branum AM, Schoendorf KC. The effect of birth weight discordance on twin neonatal
mortality. Obstet Gynecol 2003; 101:570.
170. Yinon Y, Mazkereth R, Rosentzweig N, et al. Growth restriction as a determinant of
outcome in preterm discordant twins. Obstet Gynecol 2005; 105:80.
171. Demissie K, Ananth CV, Martin J, et al. Fetal and neonatal mortality among twin
gestations in the United States: the role of intrapair birth weight discordance. Obstet
Gynecol 2002; 100:474.
172. Kingdom JC, Nevo O, Murphy KE. Discordant growth in twins. Prenat Diagn 2005; 25:759.
173. Inklaar MJ, van Klink JM, Stolk TT, et al. Cerebral injury in monochorionic twins with
selective intrauterine growth restriction: a systematic review. Prenat Diagn 2014; 34:205.
174. Alexander GR, Kogan M, Martin J, Papiernik E. What are the fetal growth patterns of
singletons, twins, and triplets in the United States? Clin Obstet Gynecol 1998; 41:114.
175. Grantz KL, Grewal J, Albert PS, et al. Dichorionic twin trajectories: the NICHD Fetal Growth
Studies. Am J Obstet Gynecol 2016; 215:221.e1.
176. Hamilton EF, Platt RW, Morin L, et al. How small is too small in a twin pregnancy? Am J
177. Lynch L, Lapinski R, Alvarez M, Lockwood CJ. Accuracy of ultrasound estimation of fetal
weight in multiple pregnancies. Ultrasound Obstet Gynecol 1995; 6:349.
178. Jensen OH, Jenssen H. Prediction of fetal weights in twins. Acta Obstet Gynecol Scand
1995; 74:177.
179. Hill LM, Guzick D, Chenevey P, et al. The sonographic assessment of twin growth
discordancy. Obstet Gynecol 1994; 84:501.
180. Allaf MB, Campbell WA, Vintzileos AM, et al. Does early second-trimester sonography
predict adverse perinatal outcomes in monochorionic diamniotic twin pregnancies? J
Ultrasound Med 2014; 33:1573.
181. Fox NS, Saltzman DH, Schwartz R, et al. Second-trimester estimated fetal weight and
discordance in twin pregnancies: association with fetal growth restriction. J Ultrasound
Med 2011; 30:1095.
182. Sperling L, Tabor A. Twin pregnancy: the role of ultrasound in management. Acta Obstet
Gynecol Scand 2001; 80:287.
183. Leombroni M, Liberati M, Fanfani F, et al. Diagnostic accuracy of ultrasound in predicting
birth-weight discordance in twin pregnancy: systematic review and meta-analysis.
184. Cameron AH. The Birmingham twin survey. Proc R Soc Med 1968; 61:229.
185. Breathnach FM, McAuliffe FM, Geary M, et al. Definition of intertwin birth weight
discordance. Obstet Gynecol 2011; 118:94.
186. D'Antonio F, Khalil A, Dias T, et al. Weight discordance and perinatal mortality in twins:
analysis of the Southwest Thames Obstetric Research Collaborative (STORK) multiple
pregnancy cohort. Ultrasound Obstet Gynecol 2013; 41:643.
187. Jahanfar S, Lim K, Oviedo-Joekes E. Optimal threshold for birth weight discordance: Does
knowledge of chorionicity matter? J Perinatol 2016; 36:704.
188. Di Mascio D, Acharya G, Khalil A, et al. Birthweight discordance and neonatal morbidity in
twin pregnancies: A systematic review and meta-analysis. Acta Obstet Gynecol Scand
2019; 98:1245.
189. D'Antonio F, Odibo AO, Prefumo F, et al. Weight discordance and perinatal mortality in
twin pregnancy: systematic review and meta-analysis. Ultrasound Obstet Gynecol 2018;
52:11.
190. Chittacharoen A, Leelapattana P, Rangsiprakarn R. Prediction of discordant twins by real-

time ultrasonography combined with umbilical artery velocimetry. Ultrasound Obstet
Gynecol 2000; 15:118.
191. Giles W, Bisits A, O'Callaghan S, et al. The Doppler assessment in multiple pregnancy
randomised controlled trial of ultrasound biometry versus umbilical artery Doppler
ultrasound and biometry in twin pregnancy. BJOG 2003; 110:593.
192. Barigye O, Pasquini L, Galea P, et al. High risk of unexpected late fetal death in
monochorionic twins despite intensive ultrasound surveillance: a cohort study. PLoS Med
2005; 2:e172.
193. Gil P, Van Hook JW. Pregnancy, Twins. Stat Pearls Publishing. 2018. https://www-ncbi-nlm-
nih-gov.ezp-prod1.hul.harvard.edu/books/NBK493200/ (Accessed on July 06, 2018).
194. Committee on Practice Bulletins—Obstetrics, Society for Maternal–Fetal Medicine.
Practice Bulletin No. 169: Multifetal Gestations: Twin, Triplet, and Higher-Order Multifetal
Pregnancies. Obstet Gynecol 2016; 128:e131. Reaffirmed 2019.
195. Patkos P, Boucher M, Broussard PM, et al. Factors influencing nonstress test results in
multiple gestations. Am J Obstet Gynecol 1986; 154:1107.
196. Lodeiro JG, Vintzileos AM, Feinstein SJ, et al. Fetal biophysical profile in twin gestations.
197. Booker W, Fox NS, Gupta S, et al. Antenatal Surveillance in Twin Pregnancies Using the
Biophysical Profile. J Ultrasound Med 2015; 34:2071.
198. Weingertner AS, Kohler A, Kohler M, et al. Clinical and placental characteristics in four
new cases of twin anemia-polycythemia sequence. Ultrasound Obstet Gynecol 2010;
35:490.
199. Baud D, Windrim R, Van Mieghem T, et al. Twin-twin transfusion syndrome: a frequently
missed diagnosis with important consequences. Ultrasound Obstet Gynecol 2014;
44:205.
200. Pessel C, Merriam A, Vani K, et al. Do Doppler studies enhance surveillance of
uncomplicated monochorionic diamniotic twins? J Ultrasound Med 2015; 34:569.
201. Hinch E, Henry A, Wilson I, Welsh AW. Outcomes of stage I TTTS or liquor discordant
twins: a single-centre review. Prenat Diagn 2016; 36:507.
202. Sueters M, Middeldorp JM, Lopriore E, et al. Timely diagnosis of twin-to-twin transfusion
syndrome in monochorionic twin pregnancies by biweekly sonography combined with
patient instruction to report onset of symptoms. Ultrasound Obstet Gynecol 2006;
28:659.
203. de Villiers SF, Slaghekke F, Middeldorp JM, et al. Placental characteristics in
monochorionic twins with spontaneous versus post-laser twin anemia-polycythemia
sequence. Placenta 2013; 34:456.
204. González-Quintero VH, Luke B, O'sullivan MJ, et al. Antenatal factors associated with
significant birth weight discordancy in twin gestations. Am J Obstet Gynecol 2003;
189:813.
205. Fick AL, Feldstein VA, Norton ME, et al. Unequal placental sharing and birth weight
discordance in monochorionic diamniotic twins. Am J Obstet Gynecol 2006; 195:178.
206. Russell Z, Quintero RA, Kontopoulos EV. Intrauterine growth restriction in monochorionic
twins. Semin Fetal Neonatal Med 2007; 12:439.
207. Papageorghiou AT, Bakoulas V, Sebire NJ, Nicolaides KH. Intrauterine growth in multiple
pregnancies in relation to fetal number, chorionicity and gestational age. Ultrasound
208. Grobman WA, Parilla BV. Positive predictive value of suspected growth aberration in twin
gestations. Am J Obstet Gynecol 1999; 181:1139.
209. Corcoran S, Breathnach F, Burke G, et al. Dichorionic twin ultrasound surveillance:
sonography every 4 weeks significantly underperforms sonography every 2 weeks:
results of the Prospective Multicenter ESPRiT Study. Am J Obstet Gynecol 2015;
213:551.e1.
210. Cimpoca B, Syngelaki A, Chi Mu A, et al. Twin pregnancy with two live fetuses at 11-13
weeks: effect of one fetal death on pregnancy outcome. Ultrasound Obstet Gynecol
2020; 55:482.
211. Mackie FL, Rigby A, Morris RK, Kilby MD. Prognosis of the co-twin following spontaneous
single intrauterine fetal death in twin pregnancies: a systematic review and meta-
analysis. BJOG 2019; 126:569.
212. Pharoah PO. Causal hypothesis for some congenital anomalies. Twin Res Hum Genet
2005; 8:543.
213. Pharoah PO, Glinianaia SV, Rankin J. Congenital anomalies in multiple births after early
loss of a conceptus. Hum Reprod 2009; 24:726.
214. Karageyim Karsidag AY, Kars B, Dansuk R, et al. Brain damage to the survivor within 30
min of co-twin demise in monochorionic twins. Fetal Diagn Ther 2005; 20:91.
215. Mitra AG, Chescheir NC, Cefalo RC, Tatum BS. Spontaneous resolution of
hypofibrinogenemia in a triplet gestation associated with second trimester in utero
death of two fetuses. Am J Perinatol 1993; 10:448.
216. Hasbún J, Muñoz H, von Mühlenbrock R, et al. [The successful prolongation of a twin
preterm pregnancy complicated by a dead fetus and disseminated intravascular
coagulation]. Rev Chil Obstet Ginecol 1992; 57:293.
217. Chescheir NC, Seeds JW. Spontaneous resolution of hypofibrinogenemia associated with
death of a twin in utero: a case report. Am J Obstet Gynecol 1988; 159:1183.
218. Romero R, Duffy TP, Berkowitz RL, et al. Prolongation of a preterm pregnancy
complicated by death of a single twin in utero and disseminated intravascular
coagulation. Effects of treatment with heparin. N Engl J Med 1984; 310:772.
219. Skelly H, Marivate M, Norman R, et al. Consumptive coagulopathy following fetal death
in a triplet pregnancy. Am J Obstet Gynecol 1982; 142:595.
220. Turton P, Arrowsmith S, Prescott J, et al. A comparison of the contractile properties of
myometrium from singleton and twin pregnancies. PLoS One 2013; 8:e63800.
221. Lyall F, Lye S, Teoh T, et al. Expression of Gsalpha, connexin-43, connexin-26, and EP1, 3,
and 4 receptors in myometrium of prelabor singleton versus multiple gestations and the
effects of mechanical stretch and steroids on Gsalpha. J Soc Gynecol Investig 2002; 9:299.
222. Tan H, Wen SW, Walker M, et al. The association between fetal sex and preterm birth in
twin pregnancies. Obstet Gynecol 2004; 103:327.
223. Dailey TL, Jayakrishnan A, Phipps M, et al. The contribution of maternal race/ethnicity
and fetal sex to prematurity in twins. Am J Obstet Gynecol 2009; 201:68.e1.
224. Melamed N, Yogev Y, Glezerman M. Effect of fetal sex on pregnancy outcome in twin
pregnancies. Obstet Gynecol 2009; 114:1085.
225. Berveiller P, Rousseau A, Rousseau M, et al. Risk of preterm birth in a twin pregnancy
after an early-term birth in the preceding singleton pregnancy: a retrospective cohort
study. BJOG 2020; 127:591.
226. Jacquemyn Y, Martens G, Ruyssinck G, et al. A matched cohort comparison of the

outcome of twin versus singleton pregnancies in Flanders, Belgium. Twin Res 2003; 6:7.
227. Ballabh P, Kumari J, AlKouatly HB, et al. Neonatal outcome of triplet versus twin and
singleton pregnancies: a matched case control study. Eur J Obstet Gynecol Reprod Biol
2003; 107:28.
228. Barton SE, Missmer SA, Hornstein MD. Twin pregnancies with a 'vanished' embryo: a
higher risk multiple gestation group? Hum Reprod 2011; 26:2750.
229. Gibson JL, Macara LM, Owen P, et al. Prediction of preterm delivery in twin pregnancy: a
prospective, observational study of cervical length and fetal fibronectin testing.
230. Goldenberg RL, Iams JD, Miodovnik M, et al. The preterm prediction study: risk factors in
twin gestations. National Institute of Child Health and Human Development Maternal-
Fetal Medicine Units Network. Am J Obstet Gynecol 1996; 175:1047.
231. Singer E, Pilpel S, Bsat F, et al. Accuracy of fetal fibronectin to predict preterm birth in
twin gestations with symptoms of labor. Obstet Gynecol 2007; 109:1083.
232. Urquhart C, Currell R, Harlow F, Callow L. Home uterine monitoring for detecting preterm
labour. Cochrane Database Syst Rev 2017; 2:CD006172.
233. Yamasmit W, Chaithongwongwatthana S, Tolosa JE, et al. Prophylactic oral betamimetics
for reducing preterm birth in women with a twin pregnancy. Cochrane Database Syst Rev
2015; :CD004733.
234. Liem S, Schuit E, Hegeman M, et al. Cervical pessaries for prevention of preterm birth in
women with a multiple pregnancy (ProTWIN): a multicentre, open-label randomised

controlled trial. Lancet 2013; 382:1341.
235. Nicolaides KH, Syngelaki A, Poon LC, et al. Cervical pessary placement for prevention of
preterm birth in unselected twin pregnancies: a randomized controlled trial. Am J Obstet
Gynecol 2016; 214:3.e1.
236. Berghella V, Dugoff L, Ludmir J. Prevention of preterm birth with pessary in twins
(PoPPT): a randomized controlled trial. Ultrasound Obstet Gynecol 2017; 49:567.
237. Romero R, Conde-Agudelo A, El-Refaie W, et al. Vaginal progesterone decreases preterm
birth and neonatal morbidity and mortality in women with a twin gestation and a short
cervix: an updated meta-analysis of individual patient data. Ultrasound Obstet Gynecol
2017; 49:303.
238. Goya M, de la Calle M, Pratcorona L, et al. Cervical pessary to prevent preterm birth in
women with twin gestation and sonographic short cervix: a multicenter randomized
controlled trial (PECEP-Twins). Am J Obstet Gynecol 2016; 214:145.
239. Merced C, Goya M, Pratcorona L, et al. Cervical pessary for preventing preterm birth in
twin pregnancies with maternal short cervix after an episode of threatened preterm
labor: randomised controlled trial. Am J Obstet Gynecol 2019; 221:55.e1.
240. Dang VQ, Nguyen LK, Pham TD, et al. Pessary Compared With Vaginal Progesterone for
the Prevention of Preterm Birth in Women With Twin Pregnancies and Cervical Length
Less Than 38 mm: A Randomized Controlled Trial. Obstet Gynecol 2019; 133:459.
241. Li C, Shen J, Hua K. Cerclage for women with twin pregnancies: a systematic review and
metaanalysis. Am J Obstet Gynecol 2019; 220:543.
242. Roman A, Zork N, Haeri S, et al. Physical examination-indicated cerclage in twin

pregnancy: a randomized controlled trial. Am J Obstet Gynecol 2020; 223:902.e1.
243. LeLorier J, Grégoire G, Benhaddad A, et al. Discrepancies between meta-analyses and
subsequent large randomized, controlled trials. N Engl J Med 1997; 337:536.
244. Crowther CA, Han S. Hospitalisation and bed rest for multiple pregnancy. Cochrane
Database Syst Rev 2010; :CD000110.
245. Sciscione AC. Maternal activity restriction and the prevention of preterm birth. Am J
Obstet Gynecol 2010; 202:232.e1.
246. da Silva Lopes K, Takemoto Y, Ota E, et al. Bed rest with and without hospitalisation in
multiple pregnancy for improving perinatal outcomes. Cochrane Database Syst Rev 2017;
3:CD012031.
247. Abdul Sultan A, West J, Tata LJ, et al. Risk of first venous thromboembolism in pregnant
women in hospital: population based cohort study from England. BMJ 2013; 347:f6099.
248. Bianco AT, Stone J, Lapinski R, et al. The clinical outcome of preterm premature rupture
of membranes in twin versus singleton pregnancies. Am J Perinatol 1996; 13:135.
249. Mercer BM, Crocker LG, Pierce WF, Sibai BM. Clinical characteristics and outcome of twin
gestation complicated by preterm premature rupture of the membranes. Am J Obstet
Gynecol 1993; 168:1467.
250. Jacquemyn Y, Noelmans L, Mahieu L, Buytaert P. Twin versus singleton pregnancy and
preterm prelabour rupture of the membranes. Clin Exp Obstet Gynecol 2003; 30:99.
251. Trentacoste SV, Jean-Pierre C, Baergen R, Chasen ST. Outcomes of preterm premature
rupture of membranes in twin pregnancies. J Matern Fetal Neonatal Med 2008; 21:555.
252. Phung DT, Blickstein I, Goldman RD, et al. The Northwestern Twin Chorionicity Study: I.
Discordant inflammatory findings that are related to chorionicity in presenting versus
nonpresenting twins. Am J Obstet Gynecol 2002; 186:1041.
253. Murphy DJ, Caukwell S, Joels LA, Wardle P. Cohort study of the neonatal outcome of twin
pregnancies that were treated with prophylactic or rescue antenatal corticosteroids. Am J
Topic 6821 Version 146.0
GRAPHICS
Twin peak or lambda sign
The arrow points to a triangular projection of chorionic tissue emanating from

fused dichorionic placentas and extending between layers of the intertwin
membrane. This is characteristic of a dichorionic diamniotic twin pregnancy.
Graphic 79928 Version 3.0
Thick intertwin membrane
The arrow points to a thick intertwin membrane characteristic of a dichorionic twin

pregnancy in the first trimester. A and B refer to the two twin sacs.
Monochorionic diamniotic pregnancy
The arrow points to a thin intertwin membrane characteristic of monochorionic

diamniotic twin pregnancy dividing sac A and sac B.
Placenta and membranes in twin pregnancies
(A) Two placentas, 2 amnions, 2 chorions (from either dizygotic twins or monozygotic twins with
cleavage of zygote during first 3 days after fertilization).
(B) One placenta, 1 chorion, 2 amnions (monozygotic twins with cleavage of zygote from the 4 th to
the 8 th day after fertilization).
(C) One placenta, 1 chorion, 1 amnion (monozygotic twins with cleavage of zygote from the 8 th to
the 12 th day after fertilization).
Fetal and infant death rates in twin gestations (both fetuses alive at 20 weeks of gestation, n =
150,386)
Preterm Preterm
Fetal or
Pregnancy birth <37 birth <32 Small for
neonatal
Chorioamnionicity loss <24 weeks with weeks with gestational
death ≥24
weeks (%) at least one at least one age birth (%)
weeks (%)
live birth (%) live birth (%)
DC 2.3 1.0 48.6 7.4 31.2
MCDA* 7.7 2.5 88.5 14.2 37.8
MCMA 21.8 9.3 100 26.8 33.2
Pregnancy outcome data for 6225 twin pregnancies with two live fetuses at 11 to 13 weeks of gestation with no major
abnormalities: 4896 DC pregnancies, 1274 MCDA pregnancies, and 55 MCMA pregnancies.
DC: dichorionic; MCDA: monochorionic diamniotic; MCMA: monochorionic monoamniotic

* 10% of these pregnancies underwent fetoscopic laser ablation for twin-twin transfusion syndrome or selective growth
restriction; outcome data would have been poorer without this intervention.
Data from: Litwinska E, Syngelaki A, Cimpoca B. Outcome of twin pregnancy with two live fetuses at 11-13 weeks' gestation. Ultrasound
Infant, neonatal, postnatal mortality per 1000 live births by plurality
Infant deaths Neonatal deaths Postneonatal

(birth to 1 year) (birth to day 28) (day 29 to 1 year)
Singletons 11.2 7.8 3.4
Twins 66.4 55.9 10.5
Triplets* 190.4 168.8 21.6
* Triplets and higher order multiple gestations.

Calculated from US Vital Statistics, 1998 and from US Public Health Service. Healthy People 2000: National Health Promotion and
Disease Prevention Objectives, DHHS Pub. No. (PHS)90-50212. Washington, DC: US Department of Health and Human Services,
Public Health Service; 1990.
Reproduced with permission from: Oleszczuk JJ, Oleszczuk AK, Keith LG. Twin and triplet birth: facts, figures, and costs. Female patient
2003; 28:11. Copyright © 2003 Jaroslaw J Oleszczuk, MD, PhD.
Similarities and differences among TTTS, TAPS, and sFGR on ultrasound examination of both
twins
Ultrasound finding TTTS TAPS sFGR
Fluid discordance +++++ – ++

Oligohydramnios in one sac Oligohydramnios in the sac
and polyhydramnios in the of the intrauterine growth
other sac restricted twin, normal
amniotic fluid volume in the
AGA twin
Growth discordance ++ + +++++

(>25% difference between 50% will have estimated fetal 100% will have estimated
twins) weight <10 th percentile fetal weight <10 th percentile
MCA Doppler discordance ++ +++++ +

(>1.5 MoM in donor/anemic
AND <0.8 MoM in
recipient/plethoric)
Fetal bladder discordance Small donor bladder – –

and/or enlarged recipient
bladder
Ductus venosus +++++ ++ ++

abnormalities
Fetal hydrops +++++ + –
Placental appearance: ++ +++++ -

Donor side hyperechoic
and thickened, recipient
side normal
"+" signifies the prominence of the ultrasound finding. "–" signifies that the ultrasound finding is not associated with
the diagnosis.
TTTS: twin-twin transfusion syndrome; TAPS: twin anemia polycythemia sequence; sFGR: selective fetal growth restriction; AGA:
appropriate for gestational age; MCA: middle cerebral artery; MoM: multiples of the median.
Diagnosis and classification of selective fetal growth restriction in monochorionic twins
Diagnosis: Estimated weight of one twin below the 10 th percentile or discordance in estimated twin weights greater than
25 percent
Type 1: Normal/positive Doppler flow in the umbilical artery

Mild intertwin weight discordance
Usually favorable outcome for both twins: Very low risk of fetal demise of growth-restricted twin
Type 2: Absent/reversed end-diastolic flow in the umbilical artery

Poorest prognosis: High risk of fetal demise of growth-restricted twin
Mean gestational age at delivery: 29 weeks of gestation
Type 3: Intermittent absent/reversed end-diastolic flow in the umbilical artery

Intermediate prognosis: 10 to 15 percent risk of fetal demise of growth-restricted twin
Commonly survive to 32 weeks or more of gestation
Data from: Gratacos E, Ortiz JU, Martinez JM. A systematic approach to the differential diagnosis and management of the complications of
monochorionic twin pregnancies. Fetal Diagn Ther 2012; 32:145.
Gestational age and birthweight characteristics of United States singleton, twin, and triplet
live births, 2006
Singletons Twins Triplets
No. of births 4,121,930 137,085 6118
Mean gestational age 38.7 35.2 32.0

(weeks)
Percent very preterm (<32 1.6 12.1 36.3

weeks)
Percent preterm (<37 11.1 60.4 92.6

weeks)
Birthweight (grams) 3298 2323 1655
Percent very low 1.1 10.2 34.8

birthweight (<1500 grams)
Percent low birthweight 6.5 57.5 95.4

(<2500 grams)
Adapted from: Martin JA, Hamilton BE, Sutton PD, et al. Births: final data for 2006. Natl Vital Stat Rep 2009; 57:1.
Twin pregnancy nutritional recommendations
Intervention First trimester Second trimester Third trimester
Maternal weight/weight gain Assess maternal pregravid Assess/counsel regarding Assess/counsel regarding
BMI, determine BMI-specific maternal BMI-specific maternal BMI-specific
weight gain goals weight gain (each prenatal weight gain (each prenatal
care visit) care visit)
Caloric requirements (kcal × kg –1 × d –1)
Normal BMI 40 to 45 Alter as necessary for weight Alter as necessary for weight
gain goal gain goal
Underweight 42 to 50
Overweight 30 to 35
Micronutrient supplement (daily total intake)
MVI with iron (30 mg 1 2 2

elemental tablets)
Calcium (mg) 1500 2500 2500
Vitamin D (international 1000 1000 1000

units)
Magnesium (mg) 400 800 800
Zinc (mg) 15 30 30
DHA/EPA (mg) 300 to 500 300 to 500 300 to 500
Folic acid (mg) 1 1 1
Vitamin C/E 500 to 1000/400 500 to 1000/400 500 to 1000/400

(mg/international units)
Nutritional consultation Yes Repeat if not at weight gain Repeat if not at weight gain
goal, anemia, GDM goal, anemia, GDM
Laboratory nutritional Hemoglobin ferritin Follow up abnormalities Hemoglobin ferritin GDM

assessment folate/B12 early screen for from first trimester screen with or without
GDM (risk factors) vitamin D vitamin D
Risk factor-appropriate Screen Screen Screen

exercise or reduction in
activity
Daily energy intake is divided over three meals and three snacks, with 20% of calories from protein, 40% of calories
from low-glycemic index carbohydrates, and 40% of calories from fat.
BMI: body mass index; MVI: multivitamin; DHA: docosahexaenoic acid; EPA: eicosapentaenoic acid; GDM: gestational diabetes
mellitus.
From: Goodnight W, Newman R. Optimal nutrition for improved twin pregnancy outcome. Obstet Gynecol 2009; 114:1121. DOI:
10.1097/AOG.0b013e3181bb14c8. Copyright © 2009 American College of Obstetricians and Gynecologists. Reproduced with permission
from Lippincott Williams & Wilkins. Unauthorized reproduction of this material is prohibited.
Maternal age-related risk for common fetal trisomies across pregnancy
Down Edwards Patau Combined

Maternal syndrome/trisomy syndrome/trisomy syndrome/trisomy trisomy 21/18/13
age 21 risk (1:n) 18 risk (1:n) 13 risk (1:n) risk (1:n)
(years)
CVS Amnio Term CVS Amnio Term CVS Amnio Term CVS Amnio Term
18 1150 1210 1495 2520 3150 9010 6985 7945 13,700 710 790 1175
19 1145 1205 1490 2515 3145 8985 6970 7930 13,670 705 785 1165
20 1135 1200 1475 2510 3135 8960 6955 7905 13,635 705 780 1160
21 1125 1185 1460 2500 3125 8930 6925 7875 13,580 695 775 1150
22 1110 1165 1440 2490 3110 8885 6890 7835 13,510 690 765 1135
23 1090 1150 1415 2470 3090 8825 6840 7780 13,410 680 755 1115
24 1065 1120 1380 2450 3060 8745 6770 7700 13,275 670 740 1095
25 1030 1085 1340 2415 3020 8630 6675 7590 13,090 650 720 1065
26 975 1030 1285 2375 2970 8480 6545 7445 12,840 625 690 1025
27 925 975 1220 2320 2900 8280 6375 7250 12,500 600 660 980
28 855 900 1140 2245 2805 8010 6145 6990 12,050 560 620 920
29 770 825 1045 2145 2680 7660 5850 6655 11,470 515 575 850
30 685 730 935 2020 2525 7215 5475 6225 10,735 465 520 770
31 590 630 815 1865 2330 6655 5015 5700 9830 410 455 675
32 490 535 695 1675 2095 5990 4475 5085 8770 350 390 580
33 400 430 570 1460 1825 5220 3870 4400 7585 290 325 480
34 310 345 455 1225 1535 4380 3235 3680 6345 230 260 385
35 240 260 350 990 1235 3530 2615 2975 5130 180 200 300
36 180 195 265 765 955 2725 2055 2335 4030 135 150 225
37 130 145 195 565 710 2025 1580 1800 3100 99 115 170
38 95 105 145 410 510 1455 1210 1375 2370 72 83 125
39 71 79 110 290 360 1035 930 1060 1825 53 61 94
40 52 60 85 205 255 735 730 830 1430 39 45 72
41 40 46 66 150 185 530 590 670 1160 30 35 56
42 32 38 54 110 140 395 495 560 970 23 28 45
43 27 31 45 87 110 310 425 485 840 19 23 37
44 22 26 39 70 88 250 380 435 745 16 19 32
45 19 23 34 60 74 215 350 395 685 14 16 28
46 18 21 31 52 65 185 325 370 640 12 15 25
47 16 19 29 47 59 170 310 355 610 11 14 24
48 15 18 27 44 55 155 300 340 590 11 13 22
49 15 18 26 41 52 150 290 330 570 10 12 21
The table shows the expected prevalence of 3 common autosomal trisomies (21, 18, and 13) individually (first 3 boxed
columns) and together (last boxed column). Within each of these groups, the prevalence is shown at 3 different times in
gestation. These include at the time of CVS at approximately 11 to 13 weeks of gestation, amniocentesis at
approximately 15 to 18 weeks of gestation, and at term. Each row of the table shows these results for a given maternal
age (eg, the row "35 years" includes women age 35.0 through 35.9, average 35.5 years) at the expected date of delivery.
For example, consider a 32.4-year-old woman being counseled prior to a CVS procedure who has no specific indications
of an abnormality other than age (eg, no abnormal ultrasound findings or pregnancy history of aneuploidy). The
chance that the CVS will identify a fetus with Down syndrome is 1:490, with trisomy 18 is 1:1675, and with trisomy 13 is
1:4475. Together, these pose a current combined risk of 1:350. However, her chance of having a term birth with Down
syndrome (1:696), trisomy 18 (1:5990), or trisomy 13 (1:8770) is lower. Together, these pose a term risk of 1:580.
CVS: chorionic villus sampling; amnio: amniocentesis.
References:
1. Morris JK, Savva GM. The risk of fetal loss following a prenatal diagnosis of trisomy 13 or trisomy 18. Am J Med Genet 2008;
146A:827.
2. Morris JK, Mutton DE, Alberman E. Revised estimates of the maternal age specific live birth prevalence of Down's syndrome. J Med
Screen 2002; 9:2.
3. Savva GM, Morris JK, Mutton DE, Alberman E. Maternal age-specific fetal loss rates in Down syndrome pregnancies. Prenat Diagn
2006; 26:499.
4. Savva GM, Walker K, Morris JK. The maternal age-specific live birth prevalence of trisomies 13 and 18 compared to trisomy 21
(Down syndrome). Prenat Diagn 2010; 30:57.
Prediction of preterm birth before 32 weeks of gestation in twins by sonographically

determined cervical length
Cutoff for cervical length Sensitivity Specificity PPV NPV

(mm) (percent) (percent) (percent) (percent)
Assessment at 21 to 24 weeks of gestation
20 42 85 22 94
25 54 86 27 95
30 46 89 19 97
Assessment at 25 to 28 weeks of gestation
20 56 76 16 95
25 63 to 100 70 to 84 13 to 18 96 to 100
PPV: positive predictive value; NPV: negative predictive value.
Data adapted from:

1. Goldenberg RL, Iams JD, Miodovnik M, et al. The preterm prediction study: risk factors in twin gestations. National Institute of Child
Health and Human Development Maternal-Fetal Medicine Units Network. Am J Obstet Gynecol 1996; 175:1047.
2. Guzman ER, Walters C, O'Reilly-Green C, et al. Use of cervical ultrasonography in prediction of spontaneous preterm birth in twin
gestations. Am J Obstet Gynecol 2000; 183:1103.
3. Vayssiere C, Favre R, Audibert F, et al. Cervical length and funneling at 22 and 27 weeks to predict spontaneous birth before 32
weeks in twin pregnancies: a French prospective multicenter study. Am J Obstet Gynecol 2002; 187:1596.
Suggested algorithm for follow-up of monochorionic twins
This algorithm illustrates the authors' approach for monitoring and timing delivery of monochorionic
diamniotic twin pregnancies.
* Routine use of MCA-PSV in the third trimester is controversial. Twin-twin transfusion syndrome, twin anemia
polycythemia sequence, and selective fetal growth restriction are managed differently (refer to separate topic reviews
on each disorder).
Contributor Disclosures
Stephen T Chasen, MD Nothing to disclose Frank A Chervenak, MD Nothing to disclose Deborah
Levine, MD Nothing to disclose Lynn L Simpson, MD Nothing to disclose Vanessa A Barss, MD,
FACOG Nothing to disclose
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must
conform to UpToDate standards of evidence.
Conflict of interest policy

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ROLE OF EARLY ULTRASOUND EXAMINATION

Determination of gestational age — Early ultrasound assessment provides an accurate

Assessment of chorionicity and amnionicity — Ultrasonography is an effective prenatal

Chorionicity and amnionicity are determined in the following ways:

● Identification of two separate placentas is a highly reliable indicator of dichorionic

● The presence/absence of the intertwin membrane and its sonographic characteristics

• Monochorionic/monoamniotic – The intertwin membrane is absent in a

• Dichorionic/diamniotic – An intertwin membrane with the "twin peak" or "lambda

membrane from a fused dichorionic placenta ( image 1) [24]. It is best seen at 10

• Monochorionic/diamniotic – An intertwin membrane with the "T" sign indicates a

In a study including over 600 twin pregnancies at 11 to 14 weeks of gestation at a tertiary

Other significant findings — In addition to assessment of gestational age, number of

Relationship between chorionicity and amnionicity and zygosity — Dizygotic or

From an imaging perspective, approximately 80 to 90 percent of dichorionic placentas are

PREVALENCE AND EPIDEMIOLOGY

The major factors influencing the prevalence of dizygotic twins are:

● Maternal age – Approximately one-third of the increase in multiple births in recent

● Race/geographic area – Significant ethnic/racial variations in the prevalence of naturally

● Family history – Dizygotic twinning appears to have a genetic component that is

RISKS AND OUTCOMES

depend on chorionicity and amnionicity, as shown in the table ( table 1) [74].

Monochorionic twins — The following fetal complications are of particular concern in

● Twin-twin transfusion syndrome (TTTS) – Unbalanced blood flow in anastomotic

● Twin reversed arterial perfusion sequence (TRAP) – TRAP is a rare complication of

● Selective fetal growth restriction (sFGR) – Selective growth restriction is variously

Discordance = weight larger twin – weight smaller twin/weight larger twin

● Congenital anomalies – Monochorionic twins have a higher rate of congenital

Monoamniotic twins — In addition to the problems of monochorionic diamniotic

● Intertwin cord entanglement – Cord entanglement is common in monoamniotic twins

● Maternal hemodynamic changes – Twin pregnancy results in greater maternal

● Gestational hypertension and preeclampsia – Gestational hypertension and

The diagnosis, management, and course of preeclampsia/gestational hypertension are

● Gestational diabetes – Whether gestational diabetes is more common in twin

• (See "Dermatoses of pregnancy".)

Comparative outcomes of singleton, twin, and triplet pregnancy — Comparative

PREGNANCY COUNSELING AND MANAGEMENT

● Body mass index (BMI) <18.5 kg/m2 (underweight) – No recommendation due to

● BMI ≥30.0 kg/m2 (obese) – Weight gain 25 to 42 lb (11.4 to 19.1 kg).

Nutrition — The Society for Maternal-Fetal Medicine recommendations for nutrition in

● First-trimester combined test – The first-trimester combined test (beta human

Interpretation of maternal serum biochemical markers is problematic in twin

Of note, the false-positive rate of nuchal translucency screening is higher in

early manifestation of TTTS as well as a marker of aneuploidy [138]. Also, in vitro

Screening for congenital anomalies — An anatomic survey is typically performed at 18 to

The concordance rate of major congenital malformations in monozygotic twins is

Management of discordant anomalies — The diagnosis of a congenital anomaly in one

● Dichorionic twins – In dichorionic twins, selective termination of the anomalous fetus is

● Monochorionic twins – In monochorionic twins, selective feticide can be performed but

Monitoring in the second/third trimesters

Evaluation of the placenta — Sonographic evaluation of the placenta is particularly

These findings include:

and "Placenta previa: Management".)

● Velamentous cord insertion – Velamentous cord insertion, which is associated with an

Evaluation of fetal growth and growth discordance — Evaluation of fetal growth is

discordant in weight [171].

There were several limitations of these observational studies, such as differences in

Management — The management of growth restriction depends on chorionicity and

● In dichorionic twins, growth restriction is generally managed as in singletons. (See "Fetal

● In monochorionic twins, management of growth restriction depends on whether it is

sequence (TAPS), and is reviewed separately. (See "Twin-twin transfusion syndrome: