Determination of Chorionicity

Accurate determination of chorionicity and amnionicity early in pregnancy is vital to optimal obstetric care. A 2010 editorial argued that “there is no diagnosis of twins” but rather any twin gestation must be further classified at diagnosis as either monochorionic or dichorionic. Knowledge of chorionicity is essential in counseling patients on obstetric and neonatal risks because chorionicity is a major determinant of pregnancy outcome. Chorionicity is also crucial in making a surveillance and management plan because monochorionic twin gestations require closer surveillance for complications unique to monochorionic placentation, such as twin-twin transfusion syndrome (TTTS).

Determination of chorionicity is easiest and most reliable when assessed in the first trimester. Between 6 and 10 weeks, counting the number of gestational sacs and evaluating the thickness of the dividing membrane is the most reliable method of determining chorionicity ( Table 32-2 ). Two separate gestational sacs, each containing a fetus, and a thick dividing membrane represent a dichorionic diamniotic pregnancy, whereas one gestational sac with a thin dividing membrane and two fetuses suggests a monochorionic diamniotic pregnancy ( Fig. 32-2 ). For monochorionic gestations, the dividing amniotic membrane may be very difficult to visualize in the first trimester. However, with rare exceptions, the number of amniotic sacs will be the same as the number of yolk sacs, which are relatively easy to count in early gestation.

A, An early first-trimester dichorionic twin gestation. Note the clearly separate gestational sacs, each surrounded by a thick echogenic ring. B, A mid first-trimester monochorionic diamniotic twin pregnancy with a very thin, hairlike dividing membrane (MEM, arrow ). C, An early first-trimester image of a dichorionic triamniotic triplet pregnancy. Note that monochorionic triplets B and C are separated by a very thin membrane, whereas triplet A—with its own placenta—is separated from B and C by a thick membrane.

After 9 weeks, the dividing membranes become progressively thinner, but in dichorionic pregnancies, they remain thicker and easy to identify. 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. The twin peak sign is a triangular projection of tissue that extends beyond the chorionic surface of the placenta ( Fig. 32-3 ). This tissue is insinuated between the layers of the intertwin membrane, is wider at the chorionic surface, and tapers to a point at some distance inward from that surface. This finding is produced by extension of chorionic villi into the potential interchorionic space of the twin membrane where it encounters the placenta of the co-twin; this space exists only in dichorionic pregnancies. The twin peak sign cannot occur in monochorionic placentation because the single continuous chorion does not extend into the potential interamniotic space of the monochorionic diamniotic twin membrane.

Twin peak sign in a dichorionic twin pregnancy. P, fused dichorionic placentae.

After the early second trimester, determination of chorionicity and amnionicity becomes less accurate, and different techniques are used to assess placentation ( Fig. 32-4 ). The sonographic prediction of chorionicity and amnionicity should be systematically approached by determining the number of placentae and the sex of each fetus and then by assessing the membranes that divide the sacs. In our own experience we found that using these criteria, dichorionicity could be determined with 97.3% sensitivity and 91.7% specificity, and monochorionicity with 91.7% sensitivity and 97.3% specificity, in twin gestations first scanned at 22.6 ± 6.9 weeks. In some pregnancies with monochorionic diamniotic placentation, the dividing membranes may not be sonographically visualized because they are very thin. In other cases, they may not be seen because severe oligohydramnios causes them to be closely apposed to the fetus in that sac. This results in a “stuck twin” appearance, in which the trapped fetus remains firmly held against the uterine wall despite changes in maternal position. In many cases, a small portion of the dividing membrane can be seen extending from a fetal edge to the uterine wall ( Fig. 32-5 ). Diagnosis of this condition confirms the presence of a monochorionic diamniotic gestation, which should be distinguished from a monoamniotic gestation, in which dividing amniotic membranes are absent. In the latter situation, free movement of both twins—and entanglement of their umbilical cords—can be demonstrated.

Algorithm for determination of chorionicity and amnionicity in the second and third trimesters.

The donor twin “stuck” against the anterior uterine wall in a case of twin-twin transfusion syndrome. Note the small portion of membrane visible ( arrow ) extending from the edge of the fetus to the uterine wall.

Determination of Zygosity

If a twin set is monochorionic, monozygosity can be inferred. If twins are different genders, with very rare anecdotal exceptions, they can be assumed to be DZ. It is estimated that based on these two findings, about 55% of all twins’ zygosity can be determined by examination of the babies and placentae. Conversely, 45% of all twins (same-sex dichorionic twins) would need further genetic testing to determine zygosity.

Maternal Adaptation to Multifetal Gestation

The degree of maternal physiologic adaptation to pregnancy (see Chapter 3 ) is exaggerated with a multiple gestation. Levels of maternal progesterone, estriol, and human chorionic somatomammotropin (placental lactogen) are higher in multiple gestations than in singletons. This increase in human placental lactogen (hPL) modifies maternal metabolism and is thought to be the cause of the increased risk for gestational diabetes seen in multifetal pregnancies. Increased production of multiple placental proteins such as human chorionic gonadotropin (hCG) may contribute to clinical conditions such as a greater risk for hyperemesis, and it complicates the interpretation of both first- and second-trimester maternal serum screening tests. Cardiovascular adaptations are also greater; both heart rate and stroke volume are increased compared with that of singleton gestations, thus increasing cardiac output. In addition to these cardiac changes, plasma volume expansion and total body water are remarkably increased in twin gestations. Partially as a consequence of increased total body water, colloid oncotic pressure is reduced. Clinical effects of the decreased colloid oncotic pressure are increased dependent edema and a greater propensity for pulmonary edema.

Studies using dye excretion have suggested that hepatic clearance capacity is reduced in pregnancy in general and even more so in twin gestation. As described previously, serum protein concentrations are decreased during pregnancy. Although this is partially due to increased total body water, likely some degree of reduced hepatic contribution of serum proteins is present that is again more exaggerated in multifetal gestation compared with singleton pregnancies. Most obvious to patients, marked uterine changes also occur. By 25 weeks’ gestation, the average twin gestation uterine size is equal to a term singleton pregnancy. By term, the total uterine volume is often 10,000 mL, and the weight of the uterus and its contents can exceed 8 kg. These changes are even more exaggerated with triplets and higher-order gestations.

Maternal Morbidity and Mortality

Virtually every obstetric complication, with the exception of macrosomia and postterm gestation, is more common with multiple gestations, and in general the risk rises proportionally to increasing plurality. Table 32-3 provides the relative risks for various obstetric complications in twin gestations compared with singletons. In addition to the conditions listed in the table, multiples are associated with higher rates of gestational diabetes and rare but life-threatening conditions such as acute fatty liver and peripartum cardiomyopathy. Additionally, women pregnant with multiples not only have higher risks for developing certain conditions but also are more likely to have more severe manifestations of those conditions. For instance, Sibai and associates showed that not only are mothers of twins more likely to develop preeclampsia (relative risk [RR], 2.62; 95% confidence interval [CI], 2.03 to 3.38), but twin mothers with preeclampsia also have higher rates of delivery before 37 weeks and before 35 weeks as well as higher rates of placental abruption and small-for-gestational-age (SGA) infants than singleton mothers with preeclampsia. A large retrospective analysis of 24,781 singleton, 6859 twin, 2545 triplet, and 189 quadruplet pregnancies found an incidence of pregnancy-related hypertensive conditions of 6.5% in singletons, 12.7% in twins, and 20% in triplets and quadruplets. Atypical presentations of preeclampsia are also more common in multifetal gestations, especially triplets and higher-order multiples. One retrospective review of 21 triplet and 8 quadruplet pregnancies found that only half of the women who were delivered for preeclampsia had elevated blood pressures before delivery. Furthermore, proteinuria was present in only 3 of 16 women before delivery. Predominant presentations of preeclampsia in this series were laboratory abnormalities (chiefly elevated liver enzymes) and maternal symptoms. One theory for the higher incidence of atypical preeclampsia in women with triplet and higher-order multiples is that the exaggerated hemodynamic changes found in higher-order multiples will mask the “typical” maternal manifestations of preeclampsia.

These increased maternal risks extend to life-threatening morbidity and even mortality. Multiple gestation has been found to be an independent risk factor for intensive care unit (ICU) admission. Finally, although fortunately still a very rare event, maternal death is also increased in multifetal gestations. A relative risk of 2.9 (95% CI, 1.4 to 6.1) for maternal death in women pregnant with multiples has been reported.

Perinatal Morbidity and Mortality

Multifetal gestations carry significant perinatal risks. Babies who are products of multiple gestations have higher rates of low birthweight (LBW), very low birthweight (VLBW), earlier gestational age at delivery, and higher rates of neonatal and infant death and cerebral palsy ( Table 32-4 ). One in 8 twins and 1 in 3 triplets are born before 32 weeks’ gestation compared with only 2 in 100 singletons. Additionally, the risk for infant death is dramatically higher than in singletons: twins are more than 4 times, triplets 10 times, and quadruplets more than 20 times as likely to die in infancy. Rates of cerebral palsy have been estimated to be 4 to 8 times higher in twins than in singletons and as much as 47 times higher in triplets. Most of this increased risk is attributable to higher rates of early preterm delivery and VLBW in multiple gestations. Notably, although the overall rates of cerebral palsy are higher in twins than in singletons, LBW preterm twins do not have higher rates than similar-weight, gestational age–matched singletons. Interestingly, however, most studies have demonstrated higher rates of cerebral palsy for twins born at term weighing more than 2500 g than for comparable term singletons. This difference is mostly a reflection of the effect of monochorionicity on twin growth and development.

Fetal Anomalies

Fetuses in multiple gestations are known to be at increased risk for anatomic abnormalities, although the exact degree of risk is debated. The largest series available, an international study of more than 260,000 twins, found an increased relative risk for major anomalies of 1.25 (95% CI, 1.21 to 1.28); anomalies were found in all organ systems. This study, however, was not informed on zygosity or chorionicity, and most experts believe that much of the increased risk for structural anomalies in multiple gestation is associated with MZ twinning.

A 2009 population-based study from England found that rates of congenital anomalies were 1.7 times more frequent in twins compared with singletons (95% CI, 1.5 to 2.0) and that the relative risk for monochorionic twins was nearly twice that of dichorionic twins (RR, 1.8; 95% CI, 1.3 to 2.5). A Taiwanese series of 844 twin sets compared with 4573 control singletons found a doubling of the relative risk of major congenital malformations in twins compared with singletons. When broken down by zygosity, the relative risks were 1.7 for DZ twins and 4.6 for MZ twins with an anomaly prevalence of 0.6% for singletons, 1% for DZ twins, and 2.7% for MZ twins. Anomalies were concordant in 18% of the MZ twins but in none of the DZ twins. Older studies have shown somewhat higher overall anomaly rates both for singletons and twins but found similar distributions. Thus the overall evidence supports an approximately twofold increased risk for congenital anomalies in twins versus singletons, with most of this risk occurring in MZ twins.

A strong association has been found between MZ twinning and midline structural defects. Nance has presented evidence that a group of birth defects that involve midline structures—including symmelia, holoprosencephaly, exstrophy of the cloaca, and neural tube defects—may be associated with the MZ twinning process. Nance suggests that the MZ twinning process with its attendant opportunities for asymmetry, cytoplasmic deficiency, and competition in utero may favor the discordant expression of midline defects in these gestations.

“Vanishing Twin”

The so-called vanishing twin is a well-known obstetric phenomenon, and this term refers to the loss of one fetus of a multiple gestation early in pregnancy . This is typically either asymptomatic or associated with spotting or mild bleeding. Landy and colleagues reported on a series of 1000 first-trimester ultrasounds and found an incidence of twinning of just over 3%. After confirming a twin gestation (two embryos with heartbeats), 21.2% ultimately delivered singletons. In general, if two gestational sacs are confirmed by the first-trimester ultrasound, the chance of delivering twins is 63% for women younger than 30 years and 52% for women 30 years or older. If two embryos with cardiac activity are seen in the first trimester, the chance of a twin birth rises to 90% for women younger than 30 years and 84% for women 30 years or older. Other investigators have shown that, not unexpectedly, the earlier the initial ultrasound, the greater the chance of a vanishing twin phenomenon. Additionally, monochorionic twin gestations are at higher risk for either a vanishing twin or a complete pregnancy loss than are dichorionic twins. A vanishing twin phenomenon is even more common in higher-order multiples. Dickey and colleagues performed an ultrasound at 3.5 to 4.5 weeks postovulation and repeated the scan every 2 weeks until 12 weeks to assess the natural history of early pregnancy in higher-order gestations. Spontaneous loss of one or more sacs occurred in 53% of 132 triplets and in 65% of 23 quadruplets. Most of these losses were recognized earlier than 9 weeks’ gestation.

First-Trimester Multifetal Pregnancy Reduction

The increasing use of ovulation induction and assisted reproduction has resulted in a growing number of multifetal pregnancies with three or more fetuses. Because the risk for pregnancy loss, preterm delivery, and long-term physical and neurodevelopmental morbidity for children who are products of multiple gestations is directly proportional to the number of fetuses being carried, first-trimester multifetal pregnancy reduction (MPR) has been advocated as a method to reduce the risks associated with prematurity. Currently, the method of choice is injection of potassium chloride into the thorax of one or more of the fetuses, most commonly performed transabdominally under real-time sonographic guidance. Unless reduction of the entire monochorionic component is planned, the use of this technique is contraindicated in monochorionic pregnancies because of the vascular communications within the placenta.

MPR is an outpatient procedure usually performed between 11 and 13 weeks, and chorionic villus sampling (CVS) can be performed on some or all of the fetuses before the procedure to confirm karyotype if desired. Ultrasound is used to map the location of each fetus, nuchal translucencies should be measured, and prophylactic antibiotics are often administered. Any fetus that appears small for gestational age, anatomically abnormal, abnormal in nuchal translucency measurement, or is known to have a karyotypic abnormality is included among those reduced. If a monochorionic twin component is present in a higher-order multiple gestation, the monochorionic set is generally targeted for reduction. If no abnormalities can be detected, the fetus or fetuses that are technically most accessible are chosen for reduction. In order to minimize the risk for premature rupture of the membranes whenever possible, the fetus whose sac overlies the internal cervical os is not electively reduced. Follow-up ultrasound examinations should be performed to confirm the success of the procedure and to monitor the growth of the remaining fetuses.

In deciding on the appropriateness of MPR for a multifetal pregnancy, the clinician must take into account not only the potential improvement in pregnancy outcome from reducing a higher-order multifetal pregnancy but also the risk of losing the entire desired pregnancy as a result of the procedure. Evans and colleagues published a series of 3513 completed first-trimester MPR procedures from 11 centers in five countries. The overall loss rate was 9.6%, but each of the participating centers showed significant improvement in this parameter as the operators developed more experience. Additionally, loss rates increased steadily from 4.5% to 15.4% as the number of starting fetuses rose from three to six or more.

Stone and colleagues also demonstrated a learning curve evidenced by fewer complications with increasing experience. A 2008 report of the most recent 1000 multifetal reductions (of >2000 procedures performed by their group at that time) found that the overall unintended pregnancy loss rate was 4.7%, a decrease from a 9.5% loss rate in the first 200 procedures at their institution. This 4.7% loss rate is unlikely to drop further because it approximates the baseline risk for pregnancy loss with twins in general. The rates of complete pregnancy loss by starting fetal number were 2.1%, 5.1%, 5.5%, and 11% for twins, triplets, quadruplets, and quintuplets or more, respectively. All patients except two reduced to twins or singletons; complete pregnancy loss rates by finishing fetal number were 3.8% for singletons and 5.3% for twins.

Although perinatal morbidity and mortality are clearly improved when pregnancies with quadruplets or greater are reduced to smaller numbers, the obstetric and perinatal advantages of reducing triplets to twins remain debatable. A 2006 meta-analysis attempted to answer this question. The authors collected 893 pregnancies beginning as triplets, of which 411 were expectantly managed and 482 underwent MPR to twins. The rate of pregnancy loss before 24 weeks was higher in the MPR group (8.1% vs. 4.4%; P = .036). However, this risk was offset by a lower risk for delivery between 24 and 32 weeks in the MPR group (10.4% vs. 26.7%; P < .0001). The authors calculated that 7 reductions are needed to prevent one delivery before 32 weeks, and that 26 reductions would result in one loss before 24 weeks. Thus reducing triplets to twins may be associated with overall improvements in outcome. Since this meta-analysis, several other papers that reported outcomes in triplets reduced to twins have been published. A 2014 retrospective cohort study from the Netherlands compared 86 women with trichorionic triplets reduced to twins with 44 women with ongoing trichorionic triplet pregnancies and 824 women with conceived dichorionic twins. The study found that the median gestational age at delivery for reduced twins was 3 weeks longer than for triplets and 1 week shorter than for primarily conceived twins (36.1 weeks vs. 33.3 weeks vs. 37.1 weeks; P < .001). A significant difference was also found in birthweight (2217 g, 1700 g, and 2422 g in reduced twins, triplets, and primary twins, respectively; P < .001). However, no difference in survival was reported. In addition, no statistically significant reduction was noted in delivery prior to 24 weeks or prior to 32 weeks in the reduced twins compared with the triplets. Another 2014 paper from Iran reported on 115 ART-conceived triplet pregnancies. Of those 115 triplet pregnancies, 57 were reduced to twins and 58 were not. The reduced pregnancies had a lower risk of preterm labor, higher birthweights, more advanced gestational age at delivery (35.1 vs. 32.4 weeks; P = .002), and lower rates of neonatal intensive care unit (NICU) admission. Additionally, they reported lower perinatal mortality in the reduced pregnancies (6% vs. 17.6%; P = .007). Of course, it must be considered that inherent in a reduction procedure from triplets to twins is a one-third mortality rate. Offering the option of a multifetal reduction procedure to patients carrying triplets is medically reasonable, but whether this is perceived as a valuable option by the patient will depend on many factors, including the family’s social, financial, ethical, and religious considerations.

Discordance for Anomalies

When an anomaly is detected in a twin gestation, even in an MZ set, the co-twin is usually normal. The diagnosis of discordance for a major anatomic abnormality places the parents in an extremely difficult position. Management choices include (1) expectant management of both fetuses, (2) termination of the entire pregnancy, or (3) selective termination of the anomalous fetus.

Several issues should be considered when counseling patients about the management of a multiple pregnancy complicated by discordant anomalies. These include (1) severity of the anomaly and certainty of diagnosis, (2) likelihood of survival or intact survival of the anomalous twin, (3) chorionicity, (4) effect of the anomalous fetus on the remaining fetus or fetuses, and (5) the parents’ ethical beliefs. It is important to counsel patients if expectant management could result in adverse outcomes for the healthy twin. In dichorionic twins, the main issue is whether the presence of an anomalous co-twin is associated with a significantly increased risk of preterm delivery (e.g., an anomaly with polyhydramnios). For monochorionic twins, the issues are more complex. In addition to the possibility of preterm birth (PTB) associated with the presence of an anomalous co-twin, intrauterine fetal death (IUFD) of the anomalous fetus clearly has direct implications for the normal co-twin. As discussed elsewhere in this chapter, IUFD of one twin in a monochorionic pair is associated with a high rate of death or neurologic impairment of the co-twin.

Regarding the risk of PTB, the data are conflicting. Several papers have shown an increased risk of preterm delivery compared with twins in which neither fetus has a major structural anomaly. A 2009 population-based study using the 1995 through 1997 United States Matched Multiple Births dataset compared more than 3000 normal co-twins of fetuses with nonchromosomal structural anomalies with more than 12,000 control twins unaffected by structural anomalies. They found higher rates of PTB (both <37 and <32 weeks), LBW, and perinatal mortality in the normal co-twins of affected fetuses. However, the differences in mean gestational age at delivery and mean birthweight, although statistically significant, were small (35.0 vs. 35.8 weeks, P < .0001, and 2265 vs. 2417 g, P < .0001, respectively). A recent smaller paper did not find an increased risk of preterm delivery in twin pregnancies complicated by a major anomaly in one fetus. Harper and colleagues compared 66 twin pregnancies discordant for anomalies with 1911 structurally normal twin pregnancies and found no difference in median gestational age at delivery (36.0 vs. 35.7 weeks for normal vs. anomalous pregnancies, respectively; P = .43).

Some papers have shown a small increased risk of perinatal mortality in normal co-twins of anomalous fetuses. However, it should be noted that one of these papers did not have information on chorionicity, and several of the deaths in the other paper were in monochorionic sets. Consequently, the evidence for an increased risk of perinatal mortality in dichorionic pregnancies discordant for major anomalies is inconclusive. Other studies, even one of the papers that demonstrated a higher risk of preterm delivery, have not detected any differences in perinatal mortality or neonatal outcomes other than hospital length of stay.

Selective Termination

Although multiple techniques have been used to effect selective termination (ST) of a single fetus in a multiple gestation, the most common approach in dichorionic gestations is intracardiac injection of potassium chloride.

Evans and collegues reported the outcomes of 402 ST procedures in dichorionic twins from eight centers in four countries using ultrasound-guided intracardiac injection of potassium chloride. They reported successful ST in 100% of cases and delivery of one or more viable infants in more than 90% of cases. The complete pregnancy loss rate prior to 24 weeks was 7.1%, and no cases of disseminated intravascular coagulation (DIC) or serious maternal complications were reported.

In monochorionic twins, ST is far more challenging. Ablation of the umbilical cord of the anomalous fetus is needed to avoid back-bleeding through communicating vessels, which may precipitate death or neurologic injury in the remaining normal co-twin. Selective termination by cord occlusion can be considered in several circumstances involving monochorionic multiple gestations. These include:

• 1.
  

  Severely discordant anomalies

  
  
• 2.
  

  Severely discordant growth with high risk for IUFD at previable or periviable gestational ages

  
  
• 3.
  

  Twin reversed arterial perfusion (TRAP) sequence

  
  
• 4.
  

  Severe TTTS with associated discordant anomaly or in cases in which laser ablation was precluded by position of the fetus and placenta

Each of the above indications is discussed in more detail in the corresponding sections of this chapter.

Bipolar coagulation of the umbilical cord is probably the most commonly used technique, although radiofrequency ablation (RFA), laser coagulation, and ligation of the cord have also been successful. The site for port insertion is chosen according to the position of the placenta and the amniotic sac of the target fetus and its umbilical cord. Preferentially, the other sac is avoided. Sometimes amnioinfusion is necessary to expand the target sac.

Pregnancy outcomes for the surviving co-twin are relatively favorable after selective cord occlusion. Rossi and D’Addario published a review of the literature regarding umbilical cord occlusion in complicated monochorionic twin pregnancies. They evaluated 12 studies that comprised 345 cases of cord occlusion at median gestational ages between 18 and 24 weeks. The overall survival rate for the remaining twin was 79% and was higher for cases after 18 weeks (89%) than for those undergoing the procedure earlier than 18 weeks (69%) regardless of the indication. Survival rates were 86% after RFA, 82% after bipolar cord coagulation, 72% after laser, and 70% after cord ligation. Long-term follow-up was not available for most studies. However, in one series, the incidence of developmental delay was 8% in 67 infants older than 1 year who underwent evaluation by a pediatrician.

Intrauterine Fetal Demise of One Twin

Intrauterine fetal demise of one twin occurs most commonly during the first trimester. This phenomenon is known as a vanishing twin and was discussed earlier in this chapter. Although it can be associated with vaginal spotting, the loss of one conceptus early in the first trimester is often not clinically recognized, and the prognosis for the surviving twin is generally excellent. IUFD of one fetus in a multiple gestation in the second or third trimester is much less common and complicates about 2.4% to 6.8% of twin pregnancies, but it can have more severe sequelae for the surviving fetus. In triplet pregnancies, studies have reported single IUFD rates between 4.3% and 17%.

The etiology of IUFD in a multiple pregnancy may be similar to that for singletons or may be unique to the twinning process. Death in utero may be caused by conditions that affect only the demised twin, such as chromosomal or structural abnormalities, or by more global conditions such as maternal diseases, which put the entire pregnancy at risk. In diamniotic monochorionic pregnancies, IUFD may result from complications of TTTS or twin anemia-polycythemia sequence (TAPS), whereas cord entanglement is a major contributor to IUFD in monoamniotic monochorionic twins. Just as in singletons, however, the etiology of many IUFDs remains elusive.

Single IUFD in a twin gestation puts the surviving twin in jeopardy. In twin pregnancies complicated by demise of one twin, intrauterine death of the co-twin is reported in 12% to 15% of monochorionic gestations and in 3% to 4% of dichorionic gestations. In a 2006 meta-analysis by Ong and associates of twin pregnancies complicated by a single IUFD, preterm delivery occurred in 68% of monochorionic twins and in 57% of dichorionic twins, figures that include both spontaneous and iatrogenic preterm delivery. A more recent meta-analysis in 2011 by Hillman and colleagues found strikingly similar rates of PTB: 68% for monochorionic and 54% for dichorionic twins. In the Hillman meta-analysis, overall PTB rates did not differ statistically by chorionicity except in the subgroup, in which IUFD occurred between 28 and 33 weeks. In this subgroup, preterm delivery was nearly 5 times more common in monochorionic compared with dichorionic twins (OR, 4.96; 95% CI, 1.6 to 15.8). The authors speculate that this difference may relate to iatrogenic delivery as a result of clinician concern for co-twin demise in monochorionic pregnancies. Neither of these meta-analyses had a control group of twins with two survivors. However, the reported percentages for PTB in the IUFD pregnancies are not markedly different than the 58.8% risk of preterm delivery reported by national vital statistics data for all twin pregnancies. That said, some studies have shown an increased risk of PTB in twin pregnancies complicated by a single IUFD.

Surviving co-twins of pregnancies complicated by a single IUFD are also at risk for brain injury. Pharoah and Adi reported on a large cohort of all registered twin births in England and Wales between 1993 and 1995 and found a 20% risk of cerebral impairment in the surviving twins. That paper provided information on gender but not chorionicity or zygosity. The meta-analysis by Hillman and colleagues reported the rate of abnormal postnatal (<4 weeks of delivery) cranial imaging and neurodevelopmental impairment after a single fetal death. Abnormal cranial imaging was found in 34% of monochorionic twins compared with 16% of dichorionic twins (not significant with OR 3.25; 95% CI, 0.66 to 16.10). Neurodevelopmental impairment followed single fetal death in 26% versus 2% for monochorionic and dichorionic twins, respectively (OR, 4.81; 95% CI, 1.4 to 16.6).

Multicystic encephalomalacia is believed to be a precursor to infant and childhood cerebral impairment in many cases; it results in cystic lesions within the cerebral white matter distributed in areas supplied by the anterior and middle cerebral arteries, and it is associated with profound neurologic handicap ( Fig. 32-6 ). Patients with monochorionic placentation should thus be counseled about the risk of developing this condition and the resultant cerebral palsy or other serious neurodevelopmental handicap in the surviving twin. Ultrasound examination of the fetal brain may be suggestive of multicystic encephalomalacia but is not always definitive. Antenatal magnetic resonance imaging (MRI) of the fetal brain may also be useful in its detection. We currently offer fetal MRI to all patients with monochorionic placentae approximately 2 to 3 weeks after the demise of one fetus has been detected. If a normal MRI does not definitively rule out brain abnormalities, it is a very positive prognostic finding.

Ultrasound of the fetal brain of a monochorionic twin before (A) and after (B, C) intrauterine fetal death of the co-twin at 20 weeks’ gestation. Note the normal brain anatomy in A, the dilation and cystic changes shortly after the co-twin’s demise in B, and the residual irregular hydrocephalus and parenchymal loss 12 weeks later in C. B, twin B; NF, nuchal fold.

The most widely accepted hypothesis as to the cause of neurologic injury in surviving co-twins in a monochorionic pregnancy is that significant hypotension occurs at the time of the demise. After death of the first twin, the resulting low pressure in that twin’s circulatory system causes blood from the survivor to rapidly back-bleed into the dead twin through placental anastomoses. If the resulting hypotension is severe, the surviving twin is at risk for both demise and ischemic damage to vital organs. The brain is at particular risk because of its high oxygen requirements. It should be stressed that, because the injury is coincident with the IUFD, rapid delivery of the co-twin following single IUFD in a monochorionic pregnancy will not improve the outcome.

Until relatively recently, it was thought that intrauterine demise in a monochorionic twin gestation would not cause neurologic injury to its co-twin until at least the mid second trimester. However, in 2003, Weiss and coworkers reported a case of injury to a fetus after IUFD of the co-twin at about 13 weeks. Multicystic encephalomalacia was diagnosed by ultrasound and MRI in the co-twin at 20 weeks. The patient was counseled regarding the likelihood of a poor prognosis and opted for termination. Multicystic encephalomalacia was confirmed pathologically, although the exact timing of the injury could not be determined.

Other maternal risks exist with single IUFD in a multifetal gestation. Cesarean delivery appears to be increased in these patients, often because of nonreassuring fetal status of the surviving twin. However, other adverse maternal outcomes such as hemorrhage, infection, and coagulopathy have not been found to be increased in twin mothers with a single IUFD. It was originally estimated that the incidence of maternal DIC was 25% when a dead fetus was retained in a multiple gestation. However, only a few isolated cases of laboratory changes consistent with a subclinical coagulopathy have been reported under these circumstances. The estimated 25% incidence is certainly a gross overestimation. It is also reassuring to note that no cases of clinically significant coagulopathy have been reported in the extensive literature on selective termination and multifetal pregnancy reduction.

The optimal management for a single IUFD in multiple gestations is not well established, and recommendations are based mainly on expert opinion. Clinical management depends on the gestational age, maternal status, or detection of in utero compromise of the surviving fetus or fetuses. The goal is to optimize the outcome for the survivor while also avoiding unnecessary prematurity. Serial sonographic assessment of the surviving co-twin’s growth is indicated, as is antenatal testing. However, when to initiate antenatal testing and the frequency of testing depends on clinical factors such as gestational age at the time of the IUFD.

The 2011 National Institute of Child Health and Human Development (NICHD) and Society for Maternal-Fetal Medicine (SMFM) workshop on timing of indicated late-preterm and early-term birth addressed the issue of a single IUFD in a twin pregnancy. If the IUFD occurs at 34 weeks or beyond, delivery should be considered. In the 2014 Practice Bulletin on Multifetal Gestation, the American College of Obstetricians and Gynecologists (ACOG) gives a similar recommendation, stating that in the absence of other indications, a single IUFD in a twin pregnancy before 34 weeks should not prompt immediate delivery. In the authors’ practices, a single IUFD in a monochorionic diamniotic pregnancy at or after 34 weeks would be an indication for delivery. In a dichorionic pregnancy, delivery timing would be individualized based on the likely cause of the IUFD, the appropriateness of fetal growth, and fetal testing of the surviving co-twin.

Vaginal delivery is not contraindicated, and cesarean delivery is reserved for routine obstetric indications. Autopsy should be offered for the stillborn fetus but may not be helpful if the demise occurred several weeks earlier. Pathologic examination of the placenta is also recommended. In addition, the pregnancy history should be communicated to the pediatricians caring for the neonate.

Twin-Twin Transfusion Syndrome

Etiology

Twin-twin transfusion syndrome is exclusively a complication of monochorionic multifetal pregnancies. It occurs in 10% to 15% of monochorionic diamniotic gestations and is thus the most common life-threatening complication specific to this type of twinning. TTTS is characterized by an imbalance of fetal blood flow through communicating vessels across a shared placenta, which leads to underperfusion of the donor twin and overperfusion of the recipient ( Fig. 32-7 ). The donor twin develops oligohydramnios, and if it is chronic, intrauterine growth restriction (IUGR) ensues; the recipient twin experiences volume overload , which results in polyhydramnios that leads to uterine overdistension and increased intrauterine pressure, both of which may con­tribute to an increased risk for preterm labor and preterm premature rupture of the membranes (PPROM). On fetal echocardiography, the recipient demonstrates decreased ventricular function, tricuspid regurgitation, and cardiomegaly. Over time, recipient twins can develop functional right ventricular outflow tract obstruction and pulmonic stenosis. These cardiac abnormalities often progress during pregnancy and persist into the neonatal period.

A, The placenta of a pregnancy complicated by twin-twin transfusion syndrome. Milk has been injected into an artery on the donor side of the placenta ( black arrow ). It can be seen returning through the venous circulation on that side but is also evident in the venous circulation of the recipient twin ( white arrow ). B, The arteriovenous shunt shown in A.

TTTS can present at any gestational age, but earlier onset is associated with a poorer prognosis. If untreated, the reported mortality rates can range from 80% to 100%. Furthermore, if one fetus dies in utero, the surviving twin is at risk for death or multiorgan ischemia from acute exsanguination due to back-bleeding into the circulation of the dead co-twin.

All monochorionic twins share vascular anastomoses and thus exist in a state of constant intertwin transfusion. As noted earlier, however, only a minority develop clinical TTTS. The following pathophysiology has been proposed to explain this observation. In monochorionic placentae, three types of vascular communication are possible: (1) arteriovenous (AV), (2) arterioarterial (AA), and (3) venovenous (VV). AA and VV anastomoses are usually superficial bidirectional anastomoses on the surface of the chorionic plate; however, AV anastomoses—referred to as deep anastomoses —involve a shared cotyledon, which receives arterial supply from one twin and drains on the venous side to the other twin. All these anastomoses are identifiable at the chorionic surface. Superficial anastomoses, especially those that are AA, are crucial for maintaining bidirectional flow. According to this hypothesis, an inadequacy of superficial AA and VV anastomoses, which help maintain balanced blood flow, allows TTTS to manifest due to an imbalance of deep AV anastomoses.

Management

When TTTS is diagnosed, five management options are available: (1) expectant management, (2) septostomy, (3) serial amnioreduction, (4) selective termination/cord occlusion, and (5) fetoscopic laser photocoagulation. Selective termination is only offered in extreme cases of advanced TTTS. Expectant management is generally not recommended in stage II or greater TTTS because of the poor perinatal outcomes associated with the disorder if untreated. However, management depends on the gestational age at diagnosis and, despite the previously mentioned limitations of the Quintero staging system, on the severity of the clinical findings.

Septostomy

Septostomy involves intentional perforation of the dividing membrane, usually performed with a 20- or 22-gauge needle under ultrasound guidance. This procedure can, in theory, equalize amniotic fluid volumes (AFVs) between amniotic sacs. The only randomized trial involving this technique compared septostomy with amnioreduction for the treatment of TTTS. The study was terminated early after enrollment of 73 women because the rate of survival of at least one infant was similar in both groups (78% vs. 80%; P = .82). The major advantage seen with septostomy was that women randomized to the septostomy group were more likely to require only a single procedure for treatment (64% vs. 46%; P = .04). Because septostomy could functionally create an iatrogenic monoamniotic pregnancy with its own inherent risks, the procedure has been criticized and infrequently recommended as a therapeutic option for TTTS.

Serial Amnioreduction

In serial reduction amniocentesis, a needle is placed into the polyhydramniotic sac under ultrasound guidance. Amniotic fluid is withdrawn until the fluid volume normalizes (i.e., DVP <8 cm). Because of the large amount of fluid to be removed, attaching the needle to a closed-system vacuum container is more practical than withdrawing fluid manually. Amnioreduction is repeated as often as necessary to maintain a normal or near-normal AFV. The mechanism by which this procedure restores the amniotic fluid balance is unknown. Removing excessive fluid from the sac with polyhydramnios may result in decreased intraamniotic pressure that in turn may result in increased placental perfusion to the twin with oligohydramnios, especially through thin-walled superficial venous anastomoses with secondary improvement in its AFV. Additionally, normalizing the AFV may help prolong pregnancy by relieving uterine overdistension and pressure on the cervix.

Although no prospective studies are available with which to compare serial amnioreduction with conservative management, based on observational data, amnioreduction appears to offer a twofold to threefold increase in overall survival compared with no intervention. The exception may be late-onset (third-trimester) stage I TTTS that remains stable over a 1- to 2-week observation period. A large retrospective cohort study using the International Amnioreduction Registry to analyze 223 sets of twins with TTTS diagnosed prior to 28 weeks’ gestation and treated with serial amnioreduction found a live birth rate of 78%, and 60% were alive 4 weeks after birth. IUFD of at least one twin occurred in 31% of the pregnancies. In 14% of cases, IUFD of both babies occurred. Of those babies alive 4 weeks after birth, 24% of the recipients and 25% of the donors had abnormal findings on cranial imaging. Poor prognostic factors for survival were earlier gestational age at diagnosis, no end-diastolic flow in the umbilical arteries, hydrops, LBW, and earlier gestational age at delivery. Complications within 48 hours of the procedure (spontaneous rupture of the membranes, spontaneous delivery, fetal distress, fetal death, and placental abruption) occurred in 15% of patients.

Laser Therapy

Laser ablation of placental anastomoses is the favored treatment option for early-onset TTTS ( Fig. 32-8 ). In the United States, the use of laser photocoagulation to treat TTTS is restricted to gestations earlier than 26 weeks. Unlike both serial amnioreduction and septostomy, which are considered palliative procedures, laser ablation is the only therapeutic option that corrects the underlying pathophysiologic aberration that causes TTTS. Additionally, because laser ablation interrupts the vascular anastomoses between the fetuses, it has the advantage of being protective of the surviving twin should one twin succumb in utero.

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