Multifetal gestations twin, triplet, and higher order multifetal pregnancies

MS NO: ONG-21-658

INTERIM UPDATE

Downloaded from by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0h ACOG PRACTICE BULLETIN
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Clinical Management Guidelines for Obstetrician–Gynecologists

NUMBER 231 (Replaces Practice Bulletin Number 169, October 2016)

Committee on Practice Bulletins—Obstetrics and the Society for Maternal-Fetal Medicine. This Practice Bulletin was developed
by the Committee on Practice Bulletins—Obstetrics and the Society for Maternal-Fetal Medicine with the assistance of Edward
J. Hayes, MD, MSCP.

INTERIM UPDATE: The content in this Practice Bulletin has been updated as highlighted (or removed as necessary) to reflect
a limited, focused change to align with ACOG Committee Opinion 828, Indications for Outpatient Antenatal Fetal Surveil-
lance, and to provide additional information on screening for fetal chromosomal abnormalities in a multifetal gestation.

Multifetal Gestations: Twin, Triplet, and
Higher-Order Multifetal Pregnancies

The incidence of multifetal gestations in the United States has increased dramatically over the past several decades.
For example, the rate of twin births increased 76% between 1980 and 2009, from 18.9 to 33.3 per 1,000 births (1).
However, after more than three decades of increases, the twin birth rate declined 4% during 2014-2018 to 32.6 twins
per 1,000 total births in 2018 (2). The rate of triplet and higher-order multifetal gestations increased more than 400%
during the 1980s and 1990s, peaking at 193.5 per 100,000 births in 1998, followed by a modest decrease to 153.4 per
100,000 births by 2009 (3). The triplet and higher-order multiple birth rate was 93.0 per 100,000 births for 2018, an
8% decline from 2017 (101.6) and a 52% decline from the 1998 peak (193.5) (4). The long-term changes in the
incidence of multifetal gestations has been attributed to two main factors: 1) a shift toward an older maternal age at
conception, when multifetal gestations are more likely to occur naturally, and 2) an increased use of assisted
reproductive technology (ART), which is more likely to result in a multifetal gestation (5).

A number of perinatal complications are increased with multiple gestations, including fetal anomalies, preeclamp-
sia, and gestational diabetes. One of the most consequential complications encountered with multifetal gestations is
preterm birth and the resultant infant morbidity and mortality. Although multiple interventions have been evaluated in
the hope of prolonging these gestations and improving outcomes, none has had a substantial effect. The purpose of this
document is to review the issues and complications associated with twin, triplet, and higher-order multifetal gestations
and present an evidence-based approach to management.

Background multifetal gestations are six times more likely to give birth
preterm and 13 times more likely to give birth before 32
Fetal and Infant Morbidity and weeks of gestation than women with singleton gestations (3).
Mortality
An increase in short-term and long-term neonatal
Multifetal gestations are associated with increased risk of and infant morbidity also is associated with multifetal
fetal and infant morbidity and mortality (Table 1). There is gestations. Twins born preterm (less than 32 weeks of
an approximate fivefold increased risk of stillbirth and a gestation) are at twice the risk of a high-grade intraven-
sevenfold increased risk of neonatal death, which primarily tricular hemorrhage and periventricular leukomalacia
is due to complications of prematurity (6). Women with when compared with singletons of the same gestational

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Table 1. Morbidity and Mortality in Multifetal Gestations

Characteristic Singleton Twins Triplets Quadruplets

Mean birth weight* 3, 285 g 2, 345 g 1,6 80 g 1, 419 g
Mean gestational age*† 38. 5 weeks 35. 0 weeks 31. 7 weeks 30.3 weeks

Downloaded from by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0h Percentage less than 34 weeks of gestation z 2.1 19.5 63.1 82.6
CywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC1y0abggQZXdtwnfKZBYtws= on 03/05/2024
Percentage less than 37 weeks of gestation z 8.2 60.3 9 8.3 9 7.4
7 28 —
Rate of cerebral palsy (per 1,000 live births)§ 1.6 52.5
23.6 96.3¶
Infant mortality rate (per 1,000 live births) k 5.4

* National Center for Health Statistics, Division of Vital Statistics. Natality public-use data 2016-2019, on CDC WONDER Online
Database, October 2020. Available at: Retrieved December 10, 2020.

† Average obstetric estimate gestational age (weeks).

z Martin JA, Hamilton BE, Osterman MJ, Driscoll AK. Births: final data for 2018. Natl Vital Stat Rep 2019;68(13):1-47.

§Petterson B, Nelson KB, Watson L, Stanley F. Twins, triplets and cerebral palsy in births in Western Australia in the 1980s. BMJ
1993;307:1239–43.

k Luke B, Brown M. The changing risk of infant mortality by gestation, plurality, and race: 1989-1991 versus 1999-2001. Pediatrics,
2006;118:2488–97.

¶ Quadruplet and quintuplet data combined.

age (7). This, in part, explains the increased prevalence of for increased screening and potential for interventions,
cerebral palsy in multifetal gestations (8). determination of chorionicity in the first trimester or
early second trimester in pregnancy is important for
Multifetal gestations are associated with signifi- counseling and management of women with multifetal

cantly higher costs, in the antenatal and neonatal periods, gestations.
in large part because of the costs associated with
prematurity (9). The average first-year medical costs, Maternal Morbidity and Mortality
including inpatient and outpatient care, are up to 10 times
greater for preterm infants than for term infants (10). Medical complications are more common in women with
multifetal gestations than with singleton gestations.
Chorionicity These include hyperemesis, gestational diabetes mellitus,
hypertensive disorders of pregnancy, anemia, hemor-
Ultrasonography can be used to determine fetal number, rhage, cesarean delivery, and postpartum depression
estimated gestational age, chorionicity, and amnionicity. (15–21). Although these complications are more com-
The determination of chorionicity in multifetal gestations mon in women with multifetal gestations, the manage-
is clinically important because of the increased risk of ment of these complications follows the same strategies
complications in monochorionic pregnancies. Assess- as with a singleton gestation.
ment of chorionicity is most accurate early in gestation,
and its determination is optimal when ultrasonography is Women with multifetal gestations have an increased
performed in the first trimester or early second trimester. incidence of hypertensive conditions associated with
pregnancy. The occurrence of hypertensive complica-
Compared with dichorionic twins, monochorionic tions is proportional to the total fetal number, with
twins have a higher frequency of fetal and neonatal singletons at 6.5%, twins at 12.7%, and triplets at 20.0%
mortality, as well as morbidities, such as fetal and (22). One study found that ART pregnancies were at
congenital anomalies, prematurity, and fetal growth increased risk (relative risk [RR], 2.1) of developing mild
restriction (11, 12). This trend also is seen in higher- or severe preeclampsia, even after controlling for mater-
order multifetal gestations; for example, a triplet gesta- nal age and parity (23).
tion that is fully monochorionic or has a monochorionic
twin pair is at higher risk of complications than a triplet Preeclampsia not only occurs more frequently in
gestation that is trichorionic (13, 14). women with twin pregnancies than in women with sin-
gleton gestations, it tends to occur earlier in pregnancy.
Because of the increased rate of complications This results in a higher likelihood of complications, such
associated with monochorionicity, as well as the need

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Downloaded from by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0h as preterm delivery at less than 35 weeks of gestation have lower frequencies of pregnancy loss, antenatal
CywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC1y0abggQZXdtwnfKZBYtws= on 03/05/2024 (34.5% twins versus 6.3% in singletons) and abruptio pla- complications, preterm birth, low-birth-weight infants,
centae (4.7% twins versus 0.7% singletons) (17). Multifetal cesarean delivery, and neonatal deaths, with rates similar
gestation is considered a high risk factor for preeclampsia. to those observed in women with spontaneously con-
Therefore, low dose aspirin (81 mg/day) prophylaxis is ceived twin gestations (29). Multifetal reduction may
recommended and should be initiated between 12 and 28 decrease the risk of preeclampsia in women with
weeks of gestation (optimally before 16 weeks of gestation) higher-order multifetal gestations. One study reported
and continued daily until delivery (24). Women with that only 14% of 59 women with twin pregnancies re-
higher-order multifetal gestations are more likely to develop maining after multifetal reduction developed preeclamp-
preeclampsia but also to present in an atypical manner (25). sia compared with 30% of women with triplet
If hemolysis, elevated liver enzymes, and low platelet count pregnancies (30). A meta-analysis of six retrospective
(HELLP) syndrome develops before term, transfer to a ter- cohort studies including 7,398 participants (530 under-
tiary care center may improve the outcome for the woman going multifetal reduction and 6,868 controls) showed
and her fetus (26). that multifetal reduction from twins to a singleton before
15 weeks of gestation was associated with a lower risk of
The likelihood of a multifetal gestation increases preterm birth and a higher birth weight when compared
with maternal age, even outside of ART use. The with expectant management (31).
multiple birth ratio increases from 16.3 per 1,000 live
births for women younger than 20 years to 71.1 per 1,000 In multifetal pregnancy reduction, the fetus(es) to be
live births for women 40 years and older (3). Older reduced are chosen on the basis of technical consider-
women also are more likely to have obstetric complica- ations, such as which is most accessible to intervention
tions irrespective of fetal number, including gestational and chorionicity. Monochorionicity can complicate the
hypertension, gestational diabetes mellitus, and abruptio reduction procedure; if one fetus of a monochorionic

placentae. twin pair is reduced, the negative effects on the
development of the other are unknown. For this reason,
Contribution of Assisted it is usually recommended that both fetuses of a
Reproductive Technology monochorionic pair be reduced.

Over the past several decades, the increased use of ART Selective fetal termination is the application of the
has led to a dramatic increase in the incidence of fetal reduction technique to an abnormal fetus that is part
multifetal births (27). The specific ART techniques that of a multifetal gestation. The risks of the procedure are
may have the most significant effect on the increase of higher than those associated with multifetal reduction,
multifetal pregnancies are IVF and controlled ovarian largely because of a later gestational age at the time of the
hyperstimulation with gonadotropins. According to the procedure (i.e., 18–22 weeks of gestation after diagnosis
most recent data available from cycles completed in of an anomaly compared with 10–12 weeks of gestation
2017, 25.5% of pregnancies conceived with ART are based on fetal number alone) (32). The unintended loss
twins and 0.9% are higher-order multifetal pregnancies rate of the pregnancy is increased when women with
(28). Only recently has there been a decrease in the higher-order multifetal gestations undergo selective fetal
higher-order multiple birth rate (1). Data from 2017 termination in comparison with women with twin gesta-
showed substantial variations in single embryo transfer tions who undergo the procedure (11.1 % versus 2.4%,
rates among states and territories, reflecting variations in respectively) (33). Despite the procedure-related loss
embryo-transfer practices among fertility clinics, which rate, pregnancy prolongation also has been observed in
might in part account for higher multiple birth from ART women who undergo selective fetal termination (34, 35).
observed in some states and territories (28).
Clinical Considerations
Multifetal Reduction and Selective and Recommendations
Fetal Termination
< How is chorionicity determined?
Multifetal reduction reduces the likelihood of spontane-
ous preterm delivery and other neonatal and obstetric Fetal risk is largely dependent on chorionicity. Therefore,
complications by decreasing the number of fetuses. A the chorionicity of a multifetal pregnancy should be
Cochrane review found that women who underwent established as early in pregnancy as possible, and the
pregnancy reduction from triplets to twins, as compared optimal timing for determination of chorionicity by

with those who continued with triplets, were observed to

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Downloaded from by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0h ultrasonography is in the first trimester or early second < Are there routine prophylactic interventions
CywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC1y0abggQZXdtwnfKZBYtws= on 03/05/2024 trimester. In one series, the reported sensitivity, specific-
ity, and positive and negative predictive values for that can prolong pregnancy in women with
prediction of chorionicity by ultrasonography at 14 multifetal gestations?
weeks of gestation or less was shown to be 89.8%,
99.5%, 97.8%, and 97.5%, respectively (36). Overall, Routine prophylactic interventions including cerclage,
chorionicity was determined correctly in 95% of cases. hospitalization, bedrest, tocolytics, and pessary have
not been proved to decrease neonatal morbidity or mor-
When ultrasound assessment clearly shows two pla- tality, and therefore should not be used based solely on
centas or differing fetal sex, the pregnancy is dichorionic. If the indication of multifetal gestation. Recommendations
only one placenta is visualized, the best ultrasonographic regarding potential interventions for women with a multi-
characteristic to distinguish chorionicity is the twin peak fetal gestation and a short cervix or other risk factors for
sign. The twin peak sign (also called the lambda or delta preterm birth can be found in ACOG Practice Bulletin
sign) is a triangular projection of tissue with the same No. 130, Prediction and Prevention of Preterm Birth.
echogenicity as the placenta that extends beyond the
chorionic surface of the placenta and is indicative of a Prophylactic Cerclage
dichorionic gestation (37). The management of complica-
tions related to monochorionicity (eg, twin–twin transfusion Prophylactic cerclage placement in women with a twin
syndrome, single fetal death, and monoamniotic gestation) gestation or a triplet gestation without a history of
and timing of delivery are discussed in “Clinical Consider- cervical insufficiency has not been shown to be benefi-
ations and Recommendations” later in this document. cial (45–47).

< Can adjunctive tests be used to predict spon- Routine Hospitalization and Bed Rest

taneous preterm birth in women with multi- The use of bed rest with or without hospitalization has
fetal gestations? been commonly recommended to women with multifetal
gestations. However, a Cochrane review demonstrated no
Asymptomatic Women benefit from routine hospitalization or bed rest for women
with an uncomplicated twin pregnancy (48). Thus, bed
Several methods have been used in an attempt to further rest with or without hospitalization in women with multi-
quantify the risk of spontaneous preterm birth when fetal pregnancies is not recommended because of the lack
screening asymptomatic women with multifetal gesta- of benefit and the risk of thrombosis and deconditioning
tions, including transvaginal ultrasonographic cervical associated with prolonged bed rest in pregnancy.
length, digital examination, fetal fibronectin screening,
and home uterine monitoring. There are no interventions Prophylactic Tocolytics
that have been shown to prevent spontaneous preterm
delivery in asymptomatic women with multifetal gesta- There is no role for the prophylactic use of any tocolytic
tions identified to be at risk based on these screening agent in women with multifetal gestations, including the
methods. The routine use of these screening methods in prolonged use of betamimetics for this indication. The
asymptomatic women with multifetal pregnancies is not use of tocolytics to inhibit preterm labor in multifetal
recommended (38). gestations has been associated with a greater risk of
maternal complications, such as pulmonary edema (49,
Symptomatic Women 50). In addition, prophylactic tocolytics have not been
shown to reduce the risk of preterm birth or improve
In symptomatic women, the positive predictive value of a neonatal outcomes in women with multifetal gestations
fetal fibronectin test result or of a short cervical length (51–53). The administration of oral betamimetics, specif-
alone is poor, and they should not be used exclusively to ically, did not reduce the incidence of preterm birth, low-
direct management in the setting of acute symptoms (39). birth-weight newborns, or neonatal mortality in women
Although several observational studies have suggested with multifetal gestations when compared with placebo
that knowledge of fetal fibronectin status or cervical (54). Oral betamimetics have been associated with
length in women with singleton gestations who present increased maternal and fetal cardiac stress and gestational

with symptoms of preterm labor may help health care diabetes mellitus (55, 56). Recently, prolonged use of
providers reduce the use of unnecessary resources, these betamimetics also has been associated with increased
findings have not been consistently confirmed by ran- adverse maternal cardiovascular events, including death
domized trials for use in singleton or in multiple gesta- (57). Based on the available evidence, prophylactic to-
tions (40–44). colysis in women with multifetal gestations is not
recommended.

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Downloaded from by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0h Prophylactic Pessary antiinflammatory drugs should be first-line treatment.
CywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC1y0abggQZXdtwnfKZBYtws= on 03/05/2024 Although there is a dearth of large-scale randomized
There is at present no high-quality evidence that pro- trials of multifetal gestations alone, data supporting these
phylactic cervical pessary use in unselected multifetal conclusions come from trials that have included singleton
pregnancies reduces the frequency of spontaneous pre- and multifetal gestations (67). Thus, in multifetal gesta-
term birth or perinatal morbidity. In a multicenter tions a brief course of tocolysis may be considered for up
randomized trial, 813 women with twins between 16 to 48 hours in the setting of acute preterm labor, in order
weeks and 20 weeks of gestation were randomized to an to allow corticosteroids to be administered. Maternal
Arabin cervical pessary or no pessary (58). In the pessary risks associated with tocolytic use include pulmonary
group, at least one child of 53 women (13%) had poor edema.
perinatal outcome (defined as either stillbirth, periven-
tricular leukomalacia, severe respiratory distress syn- Corticosteroids
drome, bronchopulmonary dysplasia, intraventricular
hemorrhage, necrotizing enterocolitis, proven sepsis, or Administration of antenatal corticosteroids to women
neonatal death) compared with at least one child of 55 with singleton gestations at risk of delivery between 24
women (14%) in the control group (RR, 0.98; 95% CI, weeks and 34 weeks of gestation has been shown to

0.69–1.39). A meta-analysis that included this study as decrease the incidence of neonatal death, respiratory
well as other studies of asymptomatic women with mul- distress syndrome, intraventricular hemorrhage, and
tiple gestations at various cervical length cutoffs con- necrotizing enterocolitis (68). A Cochrane review con-
cluded that prophylactic cervical pessary is not an cluded that although antenatal corticosteroids are benefi-
effective intervention for reducing preterm birth and cial in singleton gestations, further research is required to
adverse perinatal outcomes (59). Thus, based on avail- demonstrate an improvement in outcomes for multifetal
able evidence, the use of prophylactic cervical pessary is gestations (68). However, based on the improved out-
not recommended in multifetal pregnancies (58). comes reported in singleton gestations, the National Insti-
tutes of Health recommends that, unless a
< Does progesterone treatment decrease the risk contraindication exists, a course of antenatal corticoste-
roids should be administered to all patients who are at
of preterm birth in women with multifetal risk of delivery within 7 days and who are between 24
gestations? weeks and 34 weeks of gestation, irrespective of the fetal
number (69). For information on administration of ante-
Progesterone treatment does not reduce the incidence of natal steroids at the threshold of viability, see Obstetrics
spontaneous preterm birth in unselected women with Care Consensus 6, Periviable Birth. Administration of
twin or triplet gestations and, therefore, is not recom- corticosteroids to pregnant women during the periviable
mended (60–66). The administration of 17a-hydroxypro- period who are at risk of preterm delivery within 7 days
gesterone caproate to women with triplet gestations did is linked to a family’s decision regarding resuscitation
not reduce neonatal morbidity or prolong gestation (64). and should be considered in that context (70).
In addition, another randomized trial found that its use in
women with triplet gestations was associated with a sig- Regularly scheduled repeat courses or serial courses
nificantly increased rate of midtrimester fetal loss (63). (more than two) are not recommended. A single repeat
Recommendations regarding vaginal progesterone for course of antenatal corticosteroids should be considered
women with a multifetal gestation and a short cervix in women with a gestation of less than 34 weeks, who
can be found in ACOG Practice Bulletin No. 130, Pre- have an imminent risk of preterm delivery within the next
diction and Prevention of Preterm Birth. 7 days, and whose prior course of antenatal corticoste-
roids was administered more than 14 days previously.
< How is preterm labor managed in women with Rescue-course corticosteroids could be provided as early
as 7 days from the prior dose, if indicated by the clinical

multifetal gestations? scenario.

Tocolytics Magnesium Sulfate for
Fetal Neuroprotection
Tocolytic therapy may provide short-term prolongation
of pregnancy, which enables the administration of Several large studies have been performed to examine
antenatal corticosteroids as well as transport to a tertiary whether intravenous magnesium sulfate administered
care facility, if indicated. The overall evidence suggests before preterm delivery would decrease the incidence
that when tocolysis is used for short-term pregnancy of death and cerebral palsy (71–73). Although none of
prolongation, calcium channel blockers or nonsteroidal these studies showed improvement in the primary

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Downloaded from by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0h combined outcome, several meta-analyses of these ran- individual fetus. The distribution of NT measurements
CywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC1y0abggQZXdtwnfKZBYtws= on 03/05/2024 domized trials concluded that prenatal administration of does not differ significantly between singletons and
magnesium sulfate reduced the occurrence of cerebral twins, and standard cutoffs used in singleton gestations
palsy (74–76). The accumulated available evidence sug- can also be used in twin gestations (84). Experience is
gests that magnesium sulfate reduces the severity and limited with triplet gestations, but studies suggest that
risk of cerebral palsy in surviving infants if administered nuchal translucency measurement is feasible, and screen-
when birth is anticipated before 32 weeks of gestation, ing using only maternal age and nuchal translucency has
regardless of fetal number. Hospitals that elect to use been validated for the detection of Down syndrome and
magnesium sulfate for fetal neuroprotection should trisomy 18 (85). Of note, in one study of monochorionic
develop uniform and specific guidelines for their depart- twin pregnancies, a nuchal translucency value above the
ments regarding inclusion criteria, treatment regimens, 95th percentile had a 38% positive predictive value for
concurrent tocolysis, and monitoring in accordance with later development of severe twin–twin transfusion syn-

one of the larger trials (71–73, 77). drome, further complicating first-trimester genetic
screening in monochorionic gestations (86).
< How is prenatal screening for fetal chromo-
Cell-free DNA screening can be performed in twin
somal abnormalities in women with multifetal pregnancies (78). Overall, performance of screening for
gestations different than for singleton trisomy 21 by cell-free DNA in twin pregnancies is
pregnancies? encouraging, but the total number of reported affected
cases is smaller than in singleton pregnancies. Given
All women with multifetal gestations, regardless of age, the small number of affected cases, it is difficult to deter-
are candidates for routine screening for fetal chromo- mine an accurate detection rate for trisomy 18 and 13.
somal abnormalities. No method of fetal chromosomal Twin fetuses in a single pregnancy each contribute dif-
abnormality screening that includes a serum sample is ferent amounts of cell-free DNA into the maternal circu-
as accurate in twin gestations as it is in singleton preg- lation. It is possible that a fetus with a chromosomal
nancies; this information should be incorporated into pre- abnormality would contribute less fetal DNA, therefore
test counseling for patients with multiple gestations. masking the aneuploid test result. Recent studies have
Further, there are no data available for serum screening suggested that sensitivity for trisomy 21 with cell-free
for higher-order multiple gestations such as triplets and DNA in twin pregnancies may be similar to singletons
quadruplets. Analysis of the risks and benefits of screen- when a test result is returned; however, there is a higher
ing or diagnostic testing in patients carrying multiple rate of test failure (87, 88).
fetuses is complex, given the lower effectiveness of
screening and how the prenatal identification of a single In multifetal gestations, if a fetal demise, vanishing
aneuploid fetus might affect the pregnancy management twin, or anomaly is identified in one fetus, there is a
(78). significant risk of an inaccurate test result if serum-
based aneuploidy screening or cell-free DNA is used.
Presumably, monozygotic twins have the same This information should be reviewed with the patient
genetic information in both fetuses and will reflect a and diagnostic testing should be offered.
single test result, although monozygotic twins discordant
for karyotype have been described (79, 80). In a dizy- < What issues arise in prenatal diagnosis of fetal
gotic twin pregnancy, a screen positive test infers that at
least one of two fetuses is at increased risk of a chromo- chromosomal abnormalities in women with

somal abnormality. multifetal gestations?

First-trimester, quad, and sequential or integrated Amniocentesis and CVS can be performed in women
screening are options available to screen twin gestations, with a multifetal gestation who desire definitive testing
although few data on test performance are available from for genetic anomalies. The procedure-associated preg-
prospective studies (81). Second-trimester serum screen- nancy loss rates for both tests are similar (reported at 1–
ing of twin gestations can identify approximately 60% of 1.8%) and are slightly increased compared with loss rates
fetuses affected with trisomy 21 at a 5% screen positive reported in women with singleton gestations (89–91).
rate (82). A meta-analysis suggests that first trimester Chorionic villus sampling has the advantage that it can
combined screening in twin gestations has a detection be performed earlier in gestation.
rate of 89% with a false-positive rate of 5.4%, which is
similar to singleton gestations (83). However, there are technical difficulties that may be
encountered when performing amniocentesis and CVS in
Although serum screening evaluates the pregnancy women with multifetal gestations. There is a risk of
as a whole, the NT measurement directly evaluates the sampling error of approximately 1% in women with

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Downloaded from by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0h multifetal gestations who undergo CVS (92). Genetic increases with the number of gestational sacs: 36% for
CywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC1y0abggQZXdtwnfKZBYtws= on 03/05/2024 amniocentesis, which typically is performed at 15 weeks twins, 53% for triplets, and 65% for quadruplets (102).
of gestation or beyond, has a lower chance of this com-
plication. A complex counseling issue arises in the pres- In the second trimester and third trimester, up to 5%
ence of a monochorionic twin gestation, in which case of twins and 17% of triplets undergo death of one or
the likelihood of discordance in the karyotype is low, and more fetuses (103). Chorionicity influences the rate of
patients may opt for having a karyotype analysis per- loss, predicts outcome in the survivor, and guides man-

formed on a single fetus. In this situation, it is important agement. Monochorionic–diamniotic twins have an
to discuss the accuracy of determining chorionicity by increased risk of stillbirth compared with dichorionic–
ultrasonography. diamniotic twins (104–106). Subsequent to the demise
of one twin after 14 weeks of gestation, the risk of death
When a chromosomal abnormality is diagnosed, in the co-twin is 15% in monochorionic gestations and
counseling should include a discussion of options for 3% for dichorionic gestations (106). The risk of neuro-
pregnancy management if only one fetus is found to be logic abnormality in the surviving twin is greater in
affected. These options include terminating the entire monochorionic gestations (18%) versus dichorionic ges-
pregnancy; selective reduction of the affected fetus; and tations (1%) (107, 108). Although death of a co-twin in a
continuing the pregnancy without any intervention. monochorionic pregnancy in the late second trimester or
early third trimester is associated with significant mor-
< Are multifetal gestations with discordant fetal bidity and mortality in the other fetus, immediate deliv-
ery of the co-twin has not been demonstrated to be of
growth at risk of adverse outcomes? benefit (109). Therefore, in monochorionic twin gesta-
tions in which death of one fetus is identified before 34
Discordant fetal growth in women with multifetal weeks of gestation, management should be based on the
gestations is most commonly defined as a 20% difference condition of the mother or surviving fetus. In the absence
in estimated fetal weight between the larger and smaller of another indication, delivery before 34 weeks of gesta-
fetus (93, 94). This growth discordance ratio is calculated tion is not recommended (110). Care should be individ-
by determining the difference in the estimated fetal ualized for each patient, and consultation with a
weight between the two fetuses, divided by the weight physician with training in maternal–fetal medicine is
of the larger fetus. recommended. In the event that a twin pregnancy is
diagnosed late enough that chorionicity cannot be es-
Whether growth-discordant multifetal gestations— tablished, management should be guided by individual-
without a structural anomaly, aneuploidy, discordant ized assessment of fetal growth, growth discordance, and
infection, oligohydramnios, or fetal growth restriction— other indicators of fetal well-being.
are at increased risk of adverse outcomes is debatable.
Several studies that examined this population have < What is the role of antepartum fetal surveil-
shown that multifetal gestations with discordant but
appropriate-for-gestational-age growth are not at lance in dichorionic pregnancies?

increased risk of fetal or neonatal morbidity and mortality
(95–98). However, multifetal gestations with discordant Once chorionicity has been established in the first or
growth and pregnancies with at least one growth- early second trimester, ultrasound examination between
restricted fetus have been observed to be associated with 18 weeks and 22 weeks of gestation allows for a survey
a 7.7-fold increased risk of major neonatal morbidity of fetal anatomy, amniotic fluid, placentation, and
(99). Moreover, growth-restricted twins have higher peri- growth. Fetal growth in uncomplicated twin pregnancies
natal mortality and morbidity rates when compared with occurs at a similar rate as singletons until approximately
age-matched singletons (100). Thus, although there is no 28–32 weeks of gestation, when the growth rate of twins
clear evidence of increased neonatal morbidity or mor- slows (111). For women with dichorionic twin gesta-
tality with twin discordance alone, fetal growth restric- tions, there are no evidence-based recommendations on
tion (or other abnormalities, such as fetal anomalies or the frequency of fetal growth scans after 20 weeks of
oligohydramnios) in the setting of discordance may be a gestation; however, it seems reasonable that serial ultra-
risk factor for adverse perinatal outcomes. sonographic surveillance be performed every 4 weeks in
the absence of evidence of fetal growth restriction or
< How is the death of one fetus managed? other pregnancy complications (112).

In the first trimester, a substantial number of women with A recent systematic review by the Global Obstetrics
multifetal gestations undergo spontaneous reduction of Network (GONet) Collaboration provided weekly still-
one or more fetuses, commonly referred to as the “van- birth data for twins managed expectantly after 34 weeks
ishing twin” (101). The probability of this reduction

VOL. 137, NO. 6, JUNE 2021 Practice Bulletin Multifetal Gestations e151

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Downloaded from by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0h of gestation (113). The risk of stillbirth increased in all The criterion for diagnosis of twin–twin transfusion
CywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC1y0abggQZXdtwnfKZBYtws= on 03/05/2024 twins with advancing gestational age, and it was signif- syndrome with ultrasonography is a monochorionic–

icantly greater in monochorionic than dichorionic twins. diamniotic twin gestation with oligohydramnios (maxi-
In dichorionic twins, stillbirth rates were as follows: mum vertical pocket less than 2 cm) in one sac and
polyhydramnios (maximum vertical pocket greater than 8
c 0.8 per 1,000 at 35 0/7 to 35 6/7 weeks cm) in the other sac. It is essential to rule out other eti-
ologies, such as selective fetal growth restriction or fetal
c 1.5 per 1,000 at 36 0/7 to 36 6/7 weeks discordance for structural, genetic, or infectious disor-
ders. There is no evidence that routine assessment with
c 3.4 per 1,000 at 37 0/7 to 37 6/7 weeks umbilical artery Doppler is beneficial in the absence of
growth or fluid discordance. Once the diagnosis of twin–
c 10.6 per 1,000 at 38 0/7 to 38 6/7 weeks twin transfusion syndrome has been made, the prognosis
depends on gestational age and severity of the syndrome.
In monochorionic diamniotic twins the stillbirth Staging is commonly performed via the Quintero staging
rates were as follows: system, and interventions including laser coagulation,
amnioreduction, or selective reduction by radiofrequency
c 0.9 per 1,000 at 34 0/7 to 34 6/7 weeks ablation may be considered in collaboration with a cli-
c 2.8 per 1,000 at 35 0/7 to 35 6/7 weeks nician with expertise in twin–twin transfusion syndrome
c 4.5 per 1,000 at 36 0/7 to 36 6/7 weeks diagnosis and management (125, 126).
c 9.6 per 1,000 at 37 0/7 to 37 6/7 weeks
Because of higher stillbirth risks in monochorionic-
The optimal gestational age for initiation of surveil- diamniotic twins and the potential for severe clinical
lance in pregnant individuals with uncomplicated dichor- consequences for the surviving twin, initiation of antena-
ionic twins is not known. However, for patients with tal fetal surveillance is typically recommended at 32 0/7
uncomplicated dichorionic twin pregnancies, weekly ante- weeks of gestation (114–116).
natal fetal surveillance may be considered at 36 0/7 weeks
of gestation (114–116). For patients with a dichorionic Monoamniotic Twins
twin pregnancy complicated by maternal or fetal disorders
such as fetal growth restriction, antenatal fetal surveillance The “natural” incidence of monoamniotic twins is 1 in
should be individualized and may be considered upon 10,000. However, the incidence may be increased for
diagnosis, or at a gestational age after which delivery women who undergo in vitro fertilization using zona
would be considered for abnormal testing (117). manipulation (127). Perinatal mortality is increased in

monoamniotic twins with estimates ranging from 12%
< How are the complications caused by mono- to 23% (128, 129). For patients with monoamniotic twin
pregnancies, antenatal fetal surveillance should be indi-
chorionic placentation managed? vidualized in consultation with maternal–fetal medicine.
Although many clinicians offer early inpatient manage-
Women with monochorionic pregnancies are followed ment (beginning at 24–28 weeks of gestation) with daily
more closely than those with dichorionic pregnancies fetal surveillance, regular assessment of fetal growth, and
because of the higher risk of developing complications in delivery between 32 weeks and 34 weeks of gestation,
pregnancy, including twin–twin transfusion syndrome, twin the optimal management of these patients remains uncer-
anemia-polycythemia syndrome, fetal anomalies, and still- tain (130–132).
birth (106, 118). The Society for Maternal-Fetal Medicine
has developed checklists to assist in management of mono- Rare Complications
chorionic gestations (119). Because of the increased risk of
congenital cardiac disease, fetal echocardiogram is recom- Acardiac twin pregnancy is a complication unique to a
mended at 18–22 weeks in monochorionic pregnancies monochorionic gestation that is characterized by a fetus
(119, 120). Twin to twin transfusion syndrome occurs in lacking a normally developed heart and head. It occurs in
approximately 10–15% of monochorionic–diamniotic approximately 1% of monochorionic twins (133). The
pregnancies and results from the presence of arteriove- acardiac fetus is able to survive in utero because of pla-
nous anastomoses in a monochorionic placenta. In the cental anastomoses shunting blood flow from the “pump
affected pregnancy, there is an imbalance in the fetal– twin.” The pump twin can develop a high cardiac output
placental circulations, whereby one twin transfuses the state and subsequent cardiac failure, which results in
other. It usually presents in the second trimester. Serial intrauterine or neonatal demise in approximately 50%
ultrasonographic evaluation is recommended approximately of cases (134). These rare conditions can be managed
every 2 weeks beginning at approximately 16 weeks of in collaboration with a clinician with expertise in
gestation in monochorionic gestations to monitor for twin-
to-twin transfusion syndrome (121–124).

e152 Practice Bulletin Multifetal Gestations OBSTETRICS & GYNECOLOGY

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Downloaded from by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0h complicated twin gestation management, such as a cesarean delivery did not significantly decrease the risk
CywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC1y0abggQZXdtwnfKZBYtws= on 03/05/2024 maternal–fetal medicine specialist. of fetal or neonatal death or serious neonatal morbidity,
as compared with planned vaginal delivery (2.2% and
Conjoined twinning is a rare anomaly, with an 1.9%, respectively; OR [with planned cesarean delivery],
incidence of 1 in 50,000 to 1 in 100,000 births (135). 1.16; 95% CI, 0.77–1.74; P5.49) (142). Therefore, in
Once the diagnosis is reached, it is imperative that a diamniotic twin pregnancies at 32 0/7 weeks of gestation
complete workup be undertaken to determine shared or later with a presenting fetus that is vertex, regardless
anatomy, which guides management and determines of the presentation of the second twin, vaginal delivery is
prognosis (136). Even with many reports in the lay press a reasonable option and should be considered, provided
of successful separations, of those conjoined twinning that an obstetrician with experience in managing a non-
cases diagnosed in utero, there is only an 18% survival vertex presenting second twin is available (143).
rate of one twin from ultrasonographic diagnosis to suc-
cessful separation (137). The optimal route of delivery for women with higher-
order multifetal gestations remains unknown. Small obser-
< Are there special considerations for timing vational studies have suggested that similar perinatal out-
comes can be obtained for women (with uncomplicated
and route of delivery in women with multifetal triplet pregnancies and a presenting fetus that is vertex) who
gestations? undergo planned trial of labor compared with those who
undergo planned cesarean delivery. Thus, in the presence of
Although, on average, women with twin pregnancies obstetricians with experience in vaginal delivery of multiple
give birth at approximately 36 weeks of gestation, gestations, a planned vaginal delivery of triplets can be
preterm fetuses remain at significant risk of complica- considered (144–146).
tions of prematurity (138). The risk of perinatal mor-
tality begins to increase again in twin pregnancies at Women with one previous low transverse cesarean
approximately 38 weeks of gestation (139). Based on delivery, who are otherwise appropriate candidates for
these data, and in the absence of large randomized twin vaginal delivery, may be considered candidates

trials that demonstrate a clearly optimal time for deliv- for trial of labor after cesarean delivery (147–151).
ery, the following recommendations for timing of Delivery may be complicated by the need for internal
delivery seem reasonable for women with uncompli- fetal manipulation or emergent cesarean delivery.
cated twin gestations (109, 140): Women with multifetal gestations also are at increased
risk of uterine atony, postpartum hemorrhage, and
c Women with uncomplicated dichorionic–diamniotic emergent hysterectomy (152). The administration of
twin gestations can undergo delivery at 38 0/7–38 6/7 neuraxial analgesia in women with multifetal gesta-
weeks of gestation. tions facilitates operative vaginal delivery, external
or internal cephalic version, and total breech extraction
c Women with uncomplicated monochorionic–diamniotic (143).
twin gestations can undergo delivery between 34 0/7
weeks and 37 6/7 weeks of gestation. Summary of
Recommendations
c Women with uncomplicated monochorionic–mono- and Conclusions
amniotic twin gestations can undergo delivery at
32 0/7–34 0/7 weeks of gestation. The following recommendations and conclusions are based
on good and consistent scientific evidence (Level A):
The optimal route of delivery in women with twin
gestations depends on the type of twins, fetal presenta- < There is no role for the prophylactic use of any to-
tions, gestational age, and experience of the clinician
performing the delivery. A twin gestation in and of itself colytic agent in women with multifetal gestations,
is not an indication for cesarean delivery. Women with including the prolonged use of betamimetics for this
monoamniotic twin gestations should be delivered by indication.
cesarean birth to avoid an umbilical cord complication
of the non-presenting twin at the time of the initial twin’s < Progesterone treatment does not reduce the incidence
delivery (130).
of spontaneous preterm birth in unselected women
Women with diamniotic twin gestations whose with twin or triplet gestations and, therefore, is not
presenting fetus is in a vertex position are candidates recommended.
for a vaginal birth (141). A randomized trial of women

with uncomplicated diamniotic twin pregnancies
between 32 0/7 weeks and 38 6/7 weeks of gestation
with a vertex presenting fetus demonstrated that planned

VOL. 137, NO. 6, JUNE 2021 Practice Bulletin Multifetal Gestations e153

© 2021 by the American College of Obstetricians
and Gynecologists. Published by Wolters Kluwer Health, Inc.

Unauthorized reproduction of this article is prohibited.

Downloaded from by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0h < Serial ultrasonographic evaluation is recommended < For patients with a dichorionic twin pregnancy com-
CywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC1y0abggQZXdtwnfKZBYtws= on 03/05/2024
approximately every 2 weeks beginning at approxi- plicated by maternal or fetal disorders such as fetal
mately 16 weeks of gestation in monochorionic ges- growth restriction, antenatal fetal surveillance should
tations to monitor for twin-to-twin transfusion be individualized and may be considered upon
syndrome. diagnosis, or at a gestational age after which delivery
would be considered for abnormal testing.
The following recommendations and conclusions are
based on limited or inconsistent scientific evidence < Women with uncomplicated monochorionic–
(Level B):
monoamniotic twin gestations can undergo delivery
< Women who underwent pregnancy reduction from at 32 0/7–34 0/7 weeks of gestation.

triplets to twins, as compared with those who continued < Women with monoamniotic twin gestations should be
with triplets, were observed to have lower frequencies
of pregnancy loss, antenatal complications, preterm delivered by cesarean birth to avoid an umbilical cord
birth, low-birth-weight infants, cesarean delivery, and complication of the non-presenting twin at the time of
neonatal deaths, with rates similar to those observed in the initial twin’s delivery.
women with spontaneously conceived twin gestations.

< In diamniotic twin pregnancies at 32 0/7 weeks of
< The chorionicity of a multifetal pregnancy should be
gestation or later with a presenting fetus that is vertex,
established as early in pregnancy as possible, and the regardless of the presentation of the second twin,
optimal timing for determination of chorionicity by vaginal delivery is a reasonable option and should be
ultrasonography is in the first trimester or early sec- considered, provided that an obstetrician with expe-
ond trimester. rience in managing a nonvertex presenting second
twin is available.
< Routine prophylactic interventions including cerclage,
< The administration of neuraxial analgesia in women
hospitalization, bedrest, tocolytics, and pessary have
not been proved to decrease neonatal morbidity or with multifetal gestations facilitates operative vaginal
mortality, and therefore should not be used based delivery, external or internal cephalic version, and
solely on the indication of multifetal gestation. total breech extraction.

< Unless a contraindication exists, a course of antenatal References

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reporting results of original research, although review without prior written permission from the publisher.
articles and commentaries also were consulted.
Abstracts of research presented at symposia and American College of Obstetricians and Gynecologists
scientific conferences were not considered adequate for 409 12th Street SW, Washington, DC 20024-2188
inclusion in this document. Guidelines published by
organizations or institutions such as the National Multifetal gestations: twin, triplet, and higher-order multifetal
Institutes of Health and the American College of pregnancies. ACOG Practice Bulletin No. 231. American
Obstetricians and Gynecologists were reviewed, and College of Obstetricians and Gynecologists. Obstet Gynecol
additional studies were located by reviewing 2021;137:e145–62.
bibliographies of identified articles. When reliable
research was not available, expert opinions from
obstetrician–gynecologists were used.

Studies were reviewed and evaluated for quality
according to the method outlined by the U.S.
Preventive Services Task Force:

I Evidence obtained from at least one properly de-
signed randomized controlled trial.

II-1 Evidence obtained from well-designed controlled
trials without randomization.

II-2 Evidence obtained from well-designed cohort or
case–control analytic studies, preferably from
more than one center or research group.

II-3 Evidence obtained from multiple time series with
or without the intervention. Dramatic results in
uncontrolled experiments also could be regarded
as this type of evidence.

III Opinions of respected authorities, based on clinical
experience, descriptive studies, or reports of expert
committees.

Based on the highest level of evidence found in the data,
recommendations are provided and graded according to
the following categories:

Level A—Recommendations are based on good and
consistent scientific evidence.

Level B—Recommendations are based on limited or
inconsistent scientific evidence.

Level C—Recommendations are based primarily on

consensus and expert opinion.

VOL. 137, NO. 6, JUNE 2021 Practice Bulletin Multifetal Gestations e161

© 2021 by the American College of Obstetricians
and Gynecologists. Published by Wolters Kluwer Health, Inc.

Unauthorized reproduction of this article is prohibited.

Downloaded from by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0h This information is designed as an educational resource to aid clinicians in providing obstetric and gynecologic care, and use
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e162 Practice Bulletin Multifetal Gestations OBSTETRICS & GYNECOLOGY

© 2021 by the American College of Obstetricians
and Gynecologists. Published by Wolters Kluwer Health, Inc.

Unauthorized reproduction of this article is prohibited.