Multiple births have increased over the last 30 years, with the most recent data from 2016 showing the twin birth rate to be 33.4 twins per 1,000 total births. The rate of twin births has risen 77% from 1980 to 2016 (18.9 to 33.4 per 1,000 births). However, higher-order multiple birth rates have decreased, down 46% from its 1998 peak at 193.5 births per 100,000 to 101.4 births per 100,000 in 2016.¹ The increase in the number of twin births has been associated with delayed childbearing. Both older maternal age at the time of conception and the use of assisted reproductive technologies increase the probability of multifetal gestations.^2–4

Multiple gestations are, unto themselves, one of the most common high-risk conditions in obstetrics. As we continue to see an increase in multiple infant deliveries, it is important that we recognize the higher risk of adverse birth outcomes compared with singletons, with the risk increasing with plurality.

This chapter will concentrate predominantly on twin gestations, given its consistent incidence.

Zygosity refers to the genetic makeup of the multiples, and chorionicity refers to the placental composition. Multiple gestations are either monozygotic or dizygotic. Monozygotic twins (i.e. identical) result from the division of a zygote derived from a single sperm and single ovum. Dizygotic (i.e. fraternal) twins are a result of the fertilization of two separate ova by two separate sperm. Spontaneous dizygotic twins are more common than monozygotic twins, occurring at a rate of 70% and 30%, respectively.⁵

The placental composition, or chorionicity, looks at the chorion and amnion layers surrounding the developing embryo. It is determined by the mechanism of fertilization and by the timing of embryo division. Early ultrasound is recommended to determine chorionicity and amnionicity. Determining chorionicity is critical to pregnancy outcome and management.^6–8 The most reliable identifier of dichorionic twins is the presence of two separate placentas and two different fetal genders.

The optimal time for performing an ultrasound is in the first trimester, after 7 weeks gestation, due to the appearance and ability to detect the amnion inside the gestational sac.⁹ The ultrasonographer evaluates the thickness of the dividing membrane in determining the chorionicity. At 11 to 14 weeks gestation, sonographic examination of the base of the intertwin membrane for the presence or absence of the lambda, or twin peak, sign provides reliable distinction between a fused dichorionic and a monochorionic pregnancy (Fig. 39-1).¹⁰

All dizygotic twins develop dichorionic diamniotic placentation because each blastocyst generates its own chorionic and amniotic sacs. Chorionicity for monozygotic twins depend on the timing of cleavage of the fertilized ovum. Zygosity is ultimately determined by genetic testing and may be of importance to families (Fig. 39-2).

While the cause of monozygosity is not clearly understood, the rate of monozygotic twins is constant, occurring spontaneously at 0.4%.¹¹ This rate increases at least twofold with assisted reproduction.¹² The incidence of dizygotic twins varies among populations. Dizygotic twin rates are increased with in vitro fertilization (IVF) and ovulation-inducing agents, with increasing parity, in more obese women, in taller women, and with a maternal family history of twins.^13–15 With regard to race, there are lower rates of dizygotic twins in Japanese women and higher rates in Nigerian women.¹⁶

When dating twin pregnancies with discrepant crown-rump lengths, there is variability in which crown-rump length to employ. The most common practice is utilizing the larger twin to assign the gestational age because the smaller twin may be growth restricted, with a poorer prognosis.^17,18 However, some clinicians use the average of the two, or the smaller crown-rump length when the discordance is small.¹⁹

GENERAL

As expected, medical complications are more common in women pregnant with multiple gestations than in those with singletons. Some of the maternal morbidities that are increased include hyperemesis gravidarum, gestational diabetes mellitus, hypertension, anemia, hemorrhage, cesarean delivery, and postpartum depression.^20–26

The incidence of hypertension during pregnancy increases with increasing fetal number. The risk of preeclampsia in singletons is 6.5%, and increases to 12.7% in twins and 20% in triplets.²⁷ Women with multifetal gestations are also more likely to develop atypical presentations of preeclampsia. There should be consideration for transferring the patient to a tertiary care center if hemolysis, elevated liver enzymes, or low platelet count (HELLP) syndrome develops to improve maternal and fetal outcomes.^28,29

The foremost increased risk of multiple gestations is preterm delivery. Half of twins deliver preterm. Therefore twins are at high risk of being born with low weight and are subject to the risks of prematurity. Interestingly, twins have worse outcomes, such as respiratory distress syndrome, compared to gestational-age matched singleton pregnancies.^30,31

FETAL GROWTH RESTRICTION OR DISCORDANCE

Serial growth is monitored in multiple gestations, and each twin should be tracked along its independent growth curve. Stillbirth rates rise congruently with increasing birthweight discordance. Growth discordance is usually defined as 20% between gestations. Discordance may be clinically significant in monochorionic pregnancies, such as in twin-twin transfusion syndrome (TTTS), or it may indicate poor placental implantation site or crowding. However, the exact degree of growth discordance that increases risks is debated. Growth discordance without intrauterine growth restriction (IUGR) is not shown to increase perinatal morbidity.⁵⁰ In a retrospective cohort, 7% of dichorionic twins and 9.2% of monochorionic twins were discordant and this was a risk factor for perinatal morbidities (Fig. 39-3).⁵¹

There is no increased risk of adverse perinatal outcomes in dichorionic-diamniotic pregnancies if both fetuses are appropriately grown.⁵² If one fetus is growth restricted, however, consider twice-weekly antenatal testing and weekly umbilical artery Dopplers. Evaluation includes reviewing prenatal exposures, ultrasound anomaly screening, and karyotype testing.

If umbilical artery Dopplers show an elevated systolic-diastolic ratio or absent or reversed diastolic flow, admission to the hospital and delivery is recommended between 34 and 36 weeks, 32 and 34 weeks, and 30 and 32 weeks, respectively.

FETAL ANOMALIES

Congenital anomalies are successively higher in monozygotic, and then monoamniotic twins. In monozygotic pregnancies, screening for aneuploidy becomes complex and genetic counseling is helpful.

Prenatal Diagnosis/Genetic Screening for Chromosomal Abnormalities

Prenatal detection of chromosomal anomalies consists mainly of nuchal translucency (NT) and invasive diagnostic testing with chorionic villus sampling (CVS) or amniocentesis. Sequential screening, with maternal serum analytes, can be used in twin gestations. Ultrasound screening can be technically more difficult, but other markers of aneuploidy such as the nasal bone are used. Co-twin demise after 8 weeks gestation, higher-order multiples, and multifetal reduction makes first- and second-trimester analyte screening and noninvasive prenatal screening inaccurate. Cell-free DNA screening is not currently recommended for women with multiple gestations. Prenatal screening and counseling depend on the a priori risk of a patient, and genetic counseling is encouraged. A full discussion of genetic screening and testing in multiples is beyond the scope of this chapter.

Multifetal reduction and selective reduction should be discussed with patients with higher-order multiples. Nondirective counseling should be provided and tailored to each unique maternal and fetal scenario to discuss the risks of multifetal pregnancies and the benefits and risks of the procedure.³²

In dizygotic pregnancies, the risk of chromosomal anomalies is increased as each twin adds its own independent probability of aneuploidy. Genetic counseling and invasive prenatal testing should be offered to women with multiple gestations at a younger age. A 35-year-old with a singleton has a similar risk assessment for one fetus with Down syndrome as a 32-year-old with dichorionic twins and a 28-year-old with trichorionic triplets.³³

Monozygotic pregnancies have an increased risk of congenital anomalies of approximately 20% and are thus anatomically screened closely by ultrasound. Fetal echocardiography is often performed due to the increased risk of congenital heart disease.^34,35

Twins have a higher rate of birth defects and monozygosity further increases that risk.^36,37 However, the observed-to-expected Down syndrome risk in women aged 25 to 45 was 33.6%, 75.2%, and 70% for monozygotic, dizygotic, and all twins, respectively, and not as high as previously thought, especially in monozygotic twins.³⁸

Screening with maternal analytes is problematic, as each gestation contributes to the concentration in maternal blood. The combination of first-trimester ultrasound and serum analytes, while less sensitive than for singleton pregnancies, is commonly used to screen for and enhance the risk assessment of Down syndrome in twin pregnancies. Nuchal translucency at 10 to 14 weeks gestation can aid in the detection of Down syndrome, aneuploidies, TTTS, and congenital anomalies. Of note, in monochorionic pregnancies, a discrepancy between the nuchal translucency >20% can indicate an early sign of TTTS.^39–41 Discrepancies greater than 10% between the two crown-rump lengths may also indicate structural or chromosomal anomalies in the smaller twin.^18,19

At this time, the American College of Obstetricians and Gynecologists (ACOG) does not recommend using noninvasive prenatal screening in multiple gestations because it has not been sufficiently studied.⁴² Cell-free fetal DNA is an area of active research in multiples and has been used to screen for frequent autosomal trisomy and even to determine zygosity.

Prenatal testing in multiples is complex and unique scenarios such as mosaicism and sampling errors further complicate the issue. The complication rate from CVS and amniocentesis depend on the gestational age at the time of the procedure, the technique employed, and chorionicity of the pregnancy and may be similar or slightly more frequent than for singleton pregnancies. In a systematic review of twins, the complication rate was 1% above that of singletons.⁴³

Single Twin Intrauterine Fetal Demise

In the first trimester, spontaneous loss of a twin is common and has led to the term vanishing twin. In the second and third trimesters, spontaneous loss of one fetus in a multifetal gestation occurs at a rate of 2% to 7% and has profound consequences to the surviving fetus.⁵³

There is an increased risk of preterm birth, co-twin demise, and neurologic morbidities for the surviving fetus. The main reason for these risks is chorionicity due to vascular anastomosis in monochorionic pregnancies. In a systematic review and meta-analysis of twin pregnancies with a single fetal death, monochorionic twins were nearly five times more likely than dichorionic twins to have neurodevelopmental morbidity.⁵³ This is thought to be due to significant hypotension in the surviving fetus. A fetal death of one of the multiple gestations should not mandate immediate delivery, as adverse effects on the remaining fetus have already occurred. Disseminated intravascular coagulation is theoretical and could potentially be screened for with fibrinogen levels at the time of diagnosis, and then at regular intervals.

Considerations in Monochorionic Pregnancies

Monochorionic twins are at additional risk for unique fetal complications, including TTTS, twin anemia-polycythemia sequence (TAPS), and twin reversed arterial perfusion (TRAP) sequence. With the sharing of the placenta and the vascular supply, there is a risk of selective fetal growth restriction and fetal demise of one twin that places the surviving twin at risk. In addition, there is a higher rate of congenital anomalies in monochorionic twins, with less than 25% concordance, than in dichorionic twins.⁵⁴ Monoamniotic twins are at risk of cord entanglement and may, very rarely, be conjoined.

Twin-Twin Transfusion Syndrome

TTTS, also known as chorioangiopagous twins, fetofetal transfusion, stuck-twin syndrome, and twin oligohydramnios-polyhydramnios sequence, occurs due to unbalanced blood flow through abnormal placental vascular communication. The flow of blood typically moves from one twin to the other, termed the donor, to the other twin, termed the recipient. Due to this unbalanced exchange, the donor twin typically develops anemia, growth restriction, and oligohydramnios. The recipient twin generally develops congestive heart failure from the disproportionate blood volume and polyhydramnios. This occurs only in monochorionic twins at a rate of 9% to 15%, and at a lower rate of 2% to 6% in monoamniotic twins.^55–58

Some of the common findings seen with TTTS are same-sex twins with a single placenta (monochorionic), an absent “twin peak” sign, combined oligohydramnios (deepest vertical pocket [DVP] <2 cm), and polyhydramnios (DVP >8 cm), “stuck twin” due to severe oligohydramnios, signs of cardiac failure or hydrops fetalis in either twin, and a significant discrepancy in the size of the twins (Table 39-1).^59–64 Screening with ultrasound for TTTS typically begins at 16 to 18 weeks and occurs every 2 weeks until 28 to 32 weeks gestation.

Twin Anemia-Polycythemia Sequences

TAPS, an atypical variant of TTTS with only an imbalance in blood flow, is defined as significant hemoglobin discordance between twins (>8 g/dl) without other characteristics of TTTS, such as amniotic fluid volume or fetal size differences. The pathogenesis is unknown, but it is thought to derive from a small placental arteriovenous anastomosis spontaneously forming (5%) or occurring post–laser ablation (2%–13%).^66,67 Anastomotic blood vessels within the placenta slowly shunt blood flow toward one twin, causing polycythemia and resultant anemia in the other twin. TAPS is detected antenatally through measuring middle cerebral artery–peak systolic velocity (MCA-PSV). Concern is raised when the MCA-PSV of one twin is >1.5 multiples of the median (MoM) and <0.8 MoM in the co-twin. This diagnostic criterion is not uniform.⁶⁸ There may also be differences in the appearance of the placenta, with the polycythemic recipient having a thinner, hypoechoic placenta and the anemic donor having a thickened, hyperechoic placenta.^69,70 Optimal management and treatment has not been determined.

Twin Reversed Arterial Perfusion Sequence

The TRAP sequence is unique to monochorionic twins and occurs in up to 2.6% of these pregnancies.⁷¹ The viable, anatomically normal “pump twin” shunts blood through vascular placental anastomoses to the poorly developed, nonviable “acardiac twin,” who has either an absent or a nonfunctioning heart. The diagnosis is made by reversed pulsatile umbilical artery Doppler flow toward the acardiac fetus. Acardiac fetuses vary in appearance, ranging from unsymmetrically formed structures to unrecognizable tissue masses as a secondary effect of blood flow and tissue necrosis. Intrauterine and neonatal demise of the viable twin, usually from high-output cardiac failure, occurs approximately 50% of the time.⁷² Minimally invasive laser treatment or radiofrequency ablation (RFA) to interrupt perfusion of the acardiac twin in the second and early third trimester has shown to improve outcomes.⁷³

For continuing pregnancies, growth and hydrops development are serially monitored. Poor prognostic factors include development of cardiac failure or hydrops fetalis in the pump twin, greater relative size of the acardiac twin to the pump twin, and prematurity.^74,75 Management is not well elucidated, but antenatal corticosteroids may be given at viability, and delivery is often preterm and prompted by the status of the pump twin. Cesarean delivery is used for the usual obstetric indications.

Monoamniotic Twins

Monochorionic-monoamniotic twins are very rare and comprise only 1% to 2% of monozygotic twin pregnancies. Monoamniotic twins are formed when the developing embryo splits between day 8 and day 12 after fertilization, resulting in same-sex twins sharing a single placenta and amniotic sac. There is a predisposition to female gender, and the occurrence increases with assisted reproductive techniques. When the intermembrane of a diamniotic pregnancy ruptures (usually iatrogenically during a procedure), the mortality risks are the same as for monoamniotic twins.⁷⁶

Monoamniotic twins have the highest risk for perinatal mortality. They incur the same risks of twins in general, such as prematurity and growth restriction, and the same monozygotic risk of congenital anomalies. In addition, they are uniquely at risk of cord entanglement as the twins intertwine within the same amniotic sac.⁵⁴ Interestingly, they have a lower incidence of TTTS, which is thought to be due to protective, artery-to-artery, placental anastomosis.⁷⁷

Cord entanglement in monoamniotic twins is found antenatally and in nearly all surviving monoamniotic twins at birth.⁷⁸ The concern is for intermittent occlusion of the umbilical cords, causing neurologic sequelae and potential fetal demise. Wide management variation exists in terms of inpatient vs. outpatient surveillance and the initiation of intensive monitoring. Numbers are small, and there is no prospective data for guidance. Patients are typically counseled about anticipated neonatal delivery outcomes at progressing gestational ages, and when the patient desires intervention, starting intensive inpatient monitoring is considered. A cord accident sometimes can be anticipated by previous fetal monitoring, which therefore allows time for the administration of antenatal corticosteroids. One review found that inpatient monitoring was associated with a tenfold reduction in fetal death.⁵⁴ Importantly, there is no consensus on the frequency of monitoring—three times a day vs. continuous monitoring, etc. Some clinicians question the effect of iatrogenic preterm deliveries and the psychological impact of different monitoring regimens.⁷⁹ Delivery is usually by cesarean section (C-section) at 32 to 34 weeks gestation.⁸⁰

Conjoined twins, occurring when the embryo divides after 13 days, are incredibly rare occurring at a rate of 1.5/100,000 births.⁸¹ The portions of fetal bodies that are connected define the type of conjoined twins, such as cephalopagus, thoracopagus, and omphalopagus. When conjoined twin pregnancies are continued, they require highly specialized multidisciplinary teams and are delivered by C-section.

ANTEPARTUM MANAGEMENT

An ultrasound should be performed in the first trimester and again at 18 to 20 weeks gestation to assess viability, dating, chorionicity, cord insertion sites, anatomy, and gender. Management of twins in the second and third trimester varies based on chorionicity. The standard intervals for clinic visits for singleton pregnancies are often applied to multiple pregnancies and are sometimes shortened; however, there is wide variability in clinical practice.

In dichorionic twins, growth is often monitored by ultrasound every 4 weeks to detect growth restriction. The International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) Practice Guidelines and National Institute for Clinical Excellence (NICE) guidelines recommend that the estimated fetal weight discordance be examined in twins beyond 20 weeks gestation, with a referral to a perinatologist if the discordance is 25% or more.^17,44 In uncomplicated dichorionic pregnancies, as in singleton pregnancies, there is no data supporting the use of Doppler surveillance of the umbilical or other arteries.

In monochorionic pregnancies, amniotic fluid is assessed by the maximum, or deepest, vertical pocket of fluid for each twin in the evaluation for TTTS. Parents should be made aware of the risk of developing complications, including growth restriction, TTTS, TAPS, and TRAP, as well as unpredictable fetal death. In uncomplicated monochorionic twins, ultrasound examinations are generally performed every 2 weeks to measure the deepest vertical pockets, perform umbilical artery and MCA Dopplers and subjectively evaluate fetal bladder filling. If an abnormality is detected, it warrants referral for treatment and closer surveillance.

Antepartum fetal testing, with Non-Stress Tests (NSTs) and biophysical profiles (BPPs), is reliable in twins but has been shown to be beneficial only in the setting of complications such as maternal disease or growth restriction. Routine antenatal testing is not endorsed by ACOG in uncomplicated dichorionic-diamniotic twins.⁴⁵ However, given the imperfect predictive ability of ultrasound to detect growth restriction and the increased risk of stillbirth in multiples, antenatal surveillance is often performed.

Multifetal gestations are considered a high-risk factor for the development of hypertensive disorders of pregnancy. Therefore the US Preventative Services Task Force (UPSTF), ACOG, and the Society of Maternal Fetal Medicine (SMFM) recommend the use of low-dose aspirin after 12 weeks gestation for the prevention of preeclampsia.⁴⁶

From a nutrition standpoint, multiple pregnancies are at risk for micronutrient deficiencies. In addition to a prenatal vitamin, patients carrying twins are recommended to supplement with 1 mg folic acid, 30 mg of iron, and at least 1500 mg of calcium.⁴⁷ Weight gain should be tracked throughout pregnancy, with increased weight gain recommended compared to singleton pregnancies (Table 39-2).