CLINICAL OBSTETRICS AND GYNECOLOGY Volume 58, Number 3, 643–653 Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
Managing Monoamniotic Twin Pregnancies ANNALISA POST, MD, and KENT HEYBORNE, MD Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, University of Colorado, Denver Health Hospital, Denver, Colorado
Abstract: Monoamniotic twins comprise a rare but important subset of twins at risk of unique and serious complications, placing them at the highest risk of perinatal mortality of all twin gestations. In addition to risks faced by all twins (prematurity, selective growth restriction), all monochorionic twins (twintwin transfusion syndrome), and all monozygotic twins (congenital anomalies), monoamniotic twins face the unique risk of cord entanglement. Accordingly, early diagnosis, screening for fetal anomalies, surveillance for twin-twin transfusion syndrome, decisions related to monitoring after viability, and timing and route of delivery are all critical. Herein, we present recommendations for optimal management. Key words: monoamniotic twins, management of twin pregnancies, cord entanglement, inpatient, monitoring
Background Monoamniotic twins are a rare subset of twins comprising about 1% to 2% of monozygotic twin pregnancies worldwide; only conjoined twins are rarer. In monozygotic twin pregnancies, twins of varying chorionicity and amnionicity are Correspondence: Kent Heyborne, MD, Denver Health Hospital, 777 Bannock Street, mc 0660, Denver, CO 80204. E-mail: [email protected] The authors declare that they have nothing to disclose CLINICAL OBSTETRICS AND GYNECOLOGY
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created as a single developing embryo splits at progressively later times. Monochorionic monoamniotic twins arise when a developing embryo splits 7 days or later after fertilization; after 9 to 10 days, conjoined twins result1,2 (Fig. 1). The resulting twins share both a chorion and an amnion and, hence, lack a dividing membrane. Several characteristics of monoamniotic twin pregnancies provide fascinating insights into the process of monoamniotic twinning. (The interested reader is referred to the excellent review by Hall2 for a more in depth discussion.) There is a distinct decrease in the male to female ratio among monoamniotic twins (23.1%) as compared with singletons and dizygotic pregnancies (51.4%). This is theorized to be related to the phenomenon of X inactivation, in which every cell in a dividing female embryo must silence one of the X chromosomes to proceed with development. It is hypothesized that this shifts the twinning process in female zygotes slightly later in time, biasing toward monoamnionicity.3,4 Mirror image twins are a subset of twins in which embryonic splitting occurs VOLUME 58
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FIGURE 1. Schematic drawing of human embryonic development with timing of twinning. Reprinted from Hall.2 Copyright 2003, with permission from Elsevier. Copyright [Elsevier], [Kidlington, Oxford, UK]. All permission requests for this image should be made to the copyright holder.
approximately postfertilization day 9. The twins are genetically identical but have mirror image features including handedness, hair whorls, and even in rare cases situs inversus of one twin. As these twins split from the shared zygote after day 7, all are monoamniotic; those that split after day 9 would be expected to be conjoined. Mirror image twinning is likely due to the occurrence of splitting after the embryonic plate begins to lateralize.2 Assisted reproductive technology affects the incidence of twinning events. The increased risk of dizygotic twins with transfer of >1 embryo is obvious. However, the incidence of monozygotic twins after implantation of a single embryo is also significantly increased, 2 to 6 times over baseline.5 This is believed to be related to damage to the zona pellucida during processing or to intracytoplasmic sperm injection, which then leaves the developing embryo vulnerable to separation.6,7 Among monozygotic twins produced by IVF, however, the ratio of
diamniotic twins is higher than usual. This supports the hypothesis that the embryo separates at an early stage, likely before formation of the tight cell junctions that occurs at the 8 cell stage (by day 3). The incidence of monoamniotic twins, therefore, is minimally impacted by assisted reproductive technologies. Finally, a pregnancy complication exclusive to monochorionic twin pregnancies is the twin reversed arterial perfusion sequence (TRAP sequence), in which one twin is acardiac (historically referred to as an acardiac monster) and the second twin becomes a ‘‘pump twin,’’ supplying the acardiac twin in a retrograde manner with deoxygenated blood via placental surface anastomoses. Although 91% of pump twins are not anomalous, the mortality rate is reportedly 50% to 75%, likely related to increased cardiac demands and frequent congestive heart failure. Two criteria seem to be necessary for the development of a TRAP sequence. The first is the presence of an arterioarterial
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Managing Monoamniotic Twin Pregnancies anastomosis and the second a discordant development8 or an intrauterine demise of one of the monochorionic twins,9 allowing for reversal of blood flow. Although TRAP sequence can occur in both monoamniotic and diamniotic monochorionic twin gestations, it is relatively more common in monoamniotic twins due to the universal presence of arteroarterial anastomoses, whereas similar anastomoses are found in only about 80% of diamniotic monochorionic twins.
Prenatal Care The antenatal diagnosis of twin pregnancy type is ideally made during prenatal care on the basis of early ultrasound findings; however, there are many diagnostic pitfalls that can obscure or confound an accurate diagnosis. In early pregnancy, the number of yolk sacs has previously been thought to be a reliable tool for determining amnionicity. The classic teaching has been that if monochorionic twins are seen but only one yolk sac is identified, the pregnancy is monoamniotic.10 However, review of the literature reveals several case reports in which 2 yolk sacs were seen in the first trimester but a later diagnosis of monoamniotic twins was made on ultrasound and confirmed at delivery.11–13 The opposite scenario has also been reported, in which a single yolk sac was seen but an eventual dividing membrane was noted and a diagnosis of diamnionicity subsequently made. In one series, a single yolk sac was seen in 15% of diamniotic pregnancies.14 In short, the finding of a single or double yolk sac is not a reliable indicator of amnionicity. These findings indicate that the timing of the differentiation of the yolk sac and amniotic membranes are close but not simultaneous. The diagnosis of dichorionic versus monochorionic twins is typically fairly straightforward. First, the finding of different genders effectively assures the diagnosis
645
of a dizygotic and, therefore, dichorionic, pregnancy, with extremely rare exceptions. Ultrasound examination of the placenta is not always diagnostic, as a dichorionic pregnancy may have a single fused placenta. In contrast, the finding of 2 placentas generally also confirms a dichorionic pregnancy, although an accessory placental lobe can obfuscate the situation. When there is a fused dichorionic placentation the membrane between the twins has an easily recognizable thick appearance with a ‘‘Lambda’’ or ‘‘twin peak’’ sign at the interface of the fused membranes with the fused placental masses. This is in contrast to the thin dividing membrane of a monochorionic pregnancy, which forms a characteristic ‘‘T’’ sign where the membranes meet the placenta. Distinguishing between diamniotic and monoamniotic monochorionic pregnancies is more difficult. Both have one placenta and both are the same sex. There are several findings that have historically been used to determine amnionicity, with varying reliability. As noted above, monochorionic diamniotic twins are separated by an amniotic membrane that should be visible on ultrasound, with a typical ‘‘T sign.’’ However, the membrane is thin and often difficult to visualize, especially before 12 weeks or late in pregnancy. Therefore, absence of a separating membrane, especially early in pregnancy, should be treated with suspicion, and it is recommended to continue to evaluate for the dividing membrane on subsequent scans. Monoamniotic pregnancies are commonly complicated by an entangled cord. This finding can be noted on ultrasound and also confirms a diagnosis of monoamnionicity. In rare cases, invasive testing can be used to confirm or make a diagnosis of monoamniotic twins. A ‘‘bubble test’’ involves using an amniocentesis needle to withdraw a few milliliters of amniotic fluid. The syringe is capped and vigorously shaken to produce tiny bubbles, www.clinicalobgyn.com
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then reinstilled under ultrasound visualization. If the pregnancy is monoamniotic, the bubbles will disperse throughout the fluid around both twins. This can be performed concordantly with an amniocentesis for other indications, such as karyotype, or solely to help guide management in a later gestation with unclear amnionicity. Monochorionic diamniotic twins with severe twin-twin transfusion syndrome (TTTS) are numerically more common than monoamniotic twins, so the diagnosis of TTTS should always be entertained before diagnosing monoamnionicity. Monoamnionicity can be mistaken for a twin pregnancy complicated by the ‘‘stuck twin’’ syndrome where oligohydramnios in one amniotic sac can result in the amniotic membranes laying in direct apposition to the fetus. The enveloping membranes typically cause the affected fetus to appear ‘‘stuck’’ against the uterine wall restricting fetal movement. Any new diagnosis of suspected monoamniotic twins in the second or third trimester should always be evaluated relatively urgently by an expert sonologist to exclude severe TTTS, which often requires emergent treatment.
Prenatal Complications The rate of congenital anomalies is significantly higher in monozygotic twins as compared with dizygotic twins or singleton pregnancies. One series by Chen et al15 found that the rate of major congenital anomalies was over 4 higher in monozygotic twins as compared with singletons, and nearly 3 higher than that of dizygotic twins. Another large series by Cameron et al16 found a rate of 6% within monozygotic twins, well above the singleton risk of 0.7% to 1% seen in other series. Some of these anomalies may be a consequence of the disruption of normal circulation due to placental connections.
Within monozygotic twin pregnancies, monoamniotic twins have a higher incidence of congenital anomalies as compared with diamniotic twins. Several authors have reported congenital anomaly rates among monoamniotic twins as high as 18% to 28%,17–19 and these anomalies account for substantial mortality in addition to morbidity. For example, in the Heyborne study, the rate of neonatal demise due to lethal congenital anomalies was 2.6%,14 and Van Mieghem and collogues reported a 4.9% incidence of ‘‘major’’ fetal anomalies.20 Because of environmental impacts on embryonic development (variable epigenetic expression, spontaneous mutations) monozygotic twins have a high level of discordance for genetic disorders and anomalies, with one series finding concordance in only 23% of congenital malformations16 and a second case series finding concordance for major anomalies in only 18% of monozygotic twins.15 This discordance persists in monoamniotic twins. Therefore, the finding of normal anatomy in one twin does not negate the need for thorough evaluation of the second twin. Likewise, the finding of an anomalous twin should prompt careful examination of the second twin, although it is more likely to be a normal second twin rather than a shared anomaly. Pregnancies that are found to be discordant for anomalies or genetic syndromes lead to complicated decisions about pregnancy management, as the anomalous twin can put the normal twin at risk of earlier delivery, demise, and other perinatal complications. The option of selective termination is a complex decision in monoamniotic pregnancies because of shared circulation and cord entanglement. If selective termination is performed, cord occlusion (to prevent the complications of single twin demise) and cord transection (to prevent future demise due to cord entanglement) are needed.21,22 Cardiac anomalies in the general population have a 0.55 to 0.8% incidence; in
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Managing Monoamniotic Twin Pregnancies twin pregnancies, this risk is significantly increased.23 As with congenital anomalies, in general, most studies have reflected an increased incidence with monozygotic as compared with dizygotic twins. This may be related to the impact of shared placental connections, which can impact the fetal circulation during cardiac formation.24 There are also data supporting an increased incidence of cardiac anomalies in monoamniotic twins as compared with diamniotic monochorionic twins, with one small study reporting a rate of 57.1% of at least one twin having a cardiac defect.25 A recent study does question this theory, with demonstration of equal rates of cardiac anomalies between the 2 groups of monozygotic twins.26 As a population-based study, it is unclear if lethal cardiac anomalies are accounted for. The rate for twins was still significantly higher than that of singleton gestations (1.4% vs. 0.87%). Clearly, the diagnosis of monoamniotic twins is an appropriate indication for a fetal echocardiogram at the appropriate gestational age. Monitoring for and diagnosis of TTTS is a key part of the antenatal care of all monochorionic twins. TTTS is a consequence of pathologic vascular anastomoses between the 2 fetal placental circulations. These anastomoses result in unequal blood sharing between the twins, with one twin becoming the arterial ‘‘donor twin’’ and the other becoming the venous ‘‘recipient twin.’’ Both twins are at risk for serious complications including intrauterine fetal demise. The incidence of TTTS in monoamniotic pregnancies is lower than that reported in monochorionic diamniotic pregnancies: 2% to 3% versus 15%.27 This may be due to the near universal presence of arterioarterial anastomoses in monoamniotic twins, which are thought to be protective against TTTS.27,28 However, TTTS is still common enough that it is recommended to provide surveillance for TTTS as part of
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the routine monitoring plan for monoamniotic twin pregnancies. As with monochorionic diamniotic twins, a typical surveillance regimen consists of every 2 week ultrasounds to check for the absence of the fetal bladder and for the presence of polyhydramnios. Any suspicious findings should result in more frequent surveillance. Unlike monochorionic diamniotic twin pregnancies, discrepant amniotic fluid volumes cannot be used for surveillance due to the shared amniotic sac; however, polyhydramnios and discordant bladder volumes, as well as discordant growth, are valuable signs that can lead to the diagnosis of TTTS in monoamniotic pregnancies.29
Antepartum Monitoring Strategies The primary cause for twin mortality in monoamniotic pregnancies has been attributed to entanglement and occlusion of the umbilical cords as a consequence of the absent dividing membrane. Historical mortality rates of monoamniotic twin pregnancies have been reported as high as 70%. Although modern reports have demonstrated better outcomes, the rate of demise after viability remains high. Antenatal monitoring and care, therefore, are focused on the identification of warning signs of impending demise to circumvent mortality from this cause. Both inpatient and outpatient monitoring strategies have been studied, but considerable practice variation persists among Maternal-Fetal Medicine specialists.30 Any recommendation regarding frequency and setting of monitoring of a viable monoamniotic twin pregnancy must balance the benefits of reduced fetal morbidity and mortality against the concerns of inconvenience and possible psychologic and financial strain on the mother and her family, costs to the health care system, and the possibility of iatrogenic prematurity or www.clinicalobgyn.com
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other adverse health issue (thromboembolism, anxiety etc.). In 2004, Heyborne et al19 performed a retrospective study to assess the effectiveness of inpatient monitoring of monoamniotic twins. Ninety-six sets of monoamniotic twins were enrolled; only 87 had 2 surviving fetuses at 24 weeks. Forty three were admitted electively for monitoring at an average gestational age of 26.5 weeks, and the remaining 44 were admitted for usual obstetric indications, resulting in an average gestational age at admission of 30.1 weeks. Among the electively admitted group, there were no fetal deaths. Among the indicated admission group, there were 13 fetal deaths (14.8%); all of these deaths occurred before admission. In other words, no fetal deaths occurred in either group after initiation of inpatient monitoring. Two other, smaller cohort studies have come to similar conclusions. DeFalco et al20 studied 23 monoamniotic twin pregnancies with a retrospective chart review from 1991 to 2001. Among the 11 patients admitted electively between 24 to 28 weeks for inpatient monitoring (which in this study was continuous monitoring), there were no fetal deaths. Among the 12 patients who underwent routine outpatient monitoring (at least 3 times per week nonstress testing or biophysical profile), there were 3 fetal deaths (12.5%). In another small retrospective cohort study by Ezra et al31 in 2005, 26 monoamniotic twin pregnancies were chronicled. Among the 16 pregnancies in the inpatient monitoring group, no fetal demises occurred. Twelve fetal demises were found in the outpatient group (which was comprised of 13 total pregnancies) for a fetal death rate of 46%. However, the outpatient group was not undergoing standardized fetal heart rate monitoring; in fact, only 33% were known to be monoamniotic before delivery. Accordingly, this study contributes to the outcomes of monoamniotic twins monitored as inpatients but should not be used to represent the
expected outcomes with outpatient monitoring. Recently, Van Mieghem et al32 also compared inpatient versus outpatient fetal monitoring in a retrospective review of outcomes for monoamniotic twin pregnancies between 2003 and 2012. Outpatient monitoring varied but included an average of 4 times per week fetal heart rate monitoring and 1 to 2 ultrasounds per week. Inpatient monitoring standards also varied among the 8 centers included in the study, with a maximum intensity of ultrasounds every other day and TID fetal heart rate monitoring. Among the patients who had 2 fetuses alive at 26 weeks, 53 underwent outpatient monitoring and 182 patients underwent inpatient monitoring. With respect to the primary outcome, which was defined as intrauterine fetal demise (IUFD) plus nonrespiratory neonatal morbidity, outpatient and inpatient monitoring groups were found to be similar: 13.2% versus 10.5%, P = 0.55. They, therefore, concluded that outpatient and inpatient monitoring yield similar results. However, this makes the assumption that IUFD and neonatal morbidity are equal outcomes. If fetal death rates are directly compared the outpatient group had a ‘‘potentially preventable’’ fetal death rate of 4.7%, compared with a fetal death rate of 2.1% in the inpatient group. So, although the authors conclude that outpatient monitoring may be preferable given a similar rate of preventable fetal death plus neonatal morbidity with less cost and less theoretic risks of iatrogenic maternal morbidities, the interpretive choices made by these authors selectively favor outpatient monitoring despite demonstrably higher IUFD rates. In addition, indicated inpatient admissions were combined with elective inpatient admissions, which could be expected to negatively skew the inpatient results. In 2012, Murata et al33 published a retrospective review of monoamniotic
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Managing Monoamniotic Twin Pregnancies TABLE 1.
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Fetal Death Rates With Inpatient and Outpatient Care, Studies Published Since 2005 Total Fetal Deaths, Outpatient Outpatient (N) Fetuses (N)
Fetal Deaths, Inpatient (N)
Total Inpatient Fetuses (N)
Heyborne Ezra31
13 N/A
88 N/A
0 0
86 20
Defalco20 Murata et al33 Van Mieghem32 Quinn et al8 Pasquini9 Totals Death rate (%)
3 0 5 0 0 21 8.1
24 2 106 0 40 260
0 1 2 0 N/A 3 0.8
22 52 142 34 N/A 356
Study 19
twin pregnancies outcomes following routine admission and inpatient surveillance at 7 tertiary perinatal centers. Although this study did not include an outpatient cohort, the inpatient monitoring results can be compared with the inpatient cohorts of the above studies. A total of 38 pregnancies were initially included, but 8 ended in fetal loss before inpatient admission. Twenty nine of the remaining 30 women were admitted between 24 and 26 weeks gestational age, underwent fetal monitoring at least daily and ultrasound evaluation at least weekly and had a scheduled Cesarean delivery at 32 to 34 weeks or as obstetrically indicated. The final patient refused inpatient admission and did not suffer a fetal demise but her outpatient management strategy was not described. Of the 29 inpatient admissions, there was one fetal death which occurred at 32 weeks (1.7%). Table 1 summarizes available studies comparing inpatient and outpatient monitoring of monoamniotic twins. We include all available studies of inpatient care and contemporary (since 2005) studies of outpatient care to account for improved outpatient surveillance. In conclusion, several studies have been performed to retrospectively analyze the difference between outcomes for inpatient and outpatient monitoring of monoamniotic twin pregnancies. Most have demonstrated a clear
Notes
Table V Outpatient cohort excluded (see text) Table 1 and 2 Table 1
P
Managing Monoamniotic Twin Pregnancies ANNALISA POST, MD, and KENT HEYBORNE, MD Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, University of Colorado, Denver Health Hospital, Denver, Colorado
Abstract: Monoamniotic twins comprise a rare but important subset of twins at risk of unique and serious complications, placing them at the highest risk of perinatal mortality of all twin gestations. In addition to risks faced by all twins (prematurity, selective growth restriction), all monochorionic twins (twintwin transfusion syndrome), and all monozygotic twins (congenital anomalies), monoamniotic twins face the unique risk of cord entanglement. Accordingly, early diagnosis, screening for fetal anomalies, surveillance for twin-twin transfusion syndrome, decisions related to monitoring after viability, and timing and route of delivery are all critical. Herein, we present recommendations for optimal management. Key words: monoamniotic twins, management of twin pregnancies, cord entanglement, inpatient, monitoring
Background Monoamniotic twins are a rare subset of twins comprising about 1% to 2% of monozygotic twin pregnancies worldwide; only conjoined twins are rarer. In monozygotic twin pregnancies, twins of varying chorionicity and amnionicity are Correspondence: Kent Heyborne, MD, Denver Health Hospital, 777 Bannock Street, mc 0660, Denver, CO 80204. E-mail: [email protected] The authors declare that they have nothing to disclose CLINICAL OBSTETRICS AND GYNECOLOGY
/
created as a single developing embryo splits at progressively later times. Monochorionic monoamniotic twins arise when a developing embryo splits 7 days or later after fertilization; after 9 to 10 days, conjoined twins result1,2 (Fig. 1). The resulting twins share both a chorion and an amnion and, hence, lack a dividing membrane. Several characteristics of monoamniotic twin pregnancies provide fascinating insights into the process of monoamniotic twinning. (The interested reader is referred to the excellent review by Hall2 for a more in depth discussion.) There is a distinct decrease in the male to female ratio among monoamniotic twins (23.1%) as compared with singletons and dizygotic pregnancies (51.4%). This is theorized to be related to the phenomenon of X inactivation, in which every cell in a dividing female embryo must silence one of the X chromosomes to proceed with development. It is hypothesized that this shifts the twinning process in female zygotes slightly later in time, biasing toward monoamnionicity.3,4 Mirror image twins are a subset of twins in which embryonic splitting occurs VOLUME 58
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SEPTEMBER 2015
www.clinicalobgyn.com | 643
Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
644
Post and Heyborne
FIGURE 1. Schematic drawing of human embryonic development with timing of twinning. Reprinted from Hall.2 Copyright 2003, with permission from Elsevier. Copyright [Elsevier], [Kidlington, Oxford, UK]. All permission requests for this image should be made to the copyright holder.
approximately postfertilization day 9. The twins are genetically identical but have mirror image features including handedness, hair whorls, and even in rare cases situs inversus of one twin. As these twins split from the shared zygote after day 7, all are monoamniotic; those that split after day 9 would be expected to be conjoined. Mirror image twinning is likely due to the occurrence of splitting after the embryonic plate begins to lateralize.2 Assisted reproductive technology affects the incidence of twinning events. The increased risk of dizygotic twins with transfer of >1 embryo is obvious. However, the incidence of monozygotic twins after implantation of a single embryo is also significantly increased, 2 to 6 times over baseline.5 This is believed to be related to damage to the zona pellucida during processing or to intracytoplasmic sperm injection, which then leaves the developing embryo vulnerable to separation.6,7 Among monozygotic twins produced by IVF, however, the ratio of
diamniotic twins is higher than usual. This supports the hypothesis that the embryo separates at an early stage, likely before formation of the tight cell junctions that occurs at the 8 cell stage (by day 3). The incidence of monoamniotic twins, therefore, is minimally impacted by assisted reproductive technologies. Finally, a pregnancy complication exclusive to monochorionic twin pregnancies is the twin reversed arterial perfusion sequence (TRAP sequence), in which one twin is acardiac (historically referred to as an acardiac monster) and the second twin becomes a ‘‘pump twin,’’ supplying the acardiac twin in a retrograde manner with deoxygenated blood via placental surface anastomoses. Although 91% of pump twins are not anomalous, the mortality rate is reportedly 50% to 75%, likely related to increased cardiac demands and frequent congestive heart failure. Two criteria seem to be necessary for the development of a TRAP sequence. The first is the presence of an arterioarterial
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Managing Monoamniotic Twin Pregnancies anastomosis and the second a discordant development8 or an intrauterine demise of one of the monochorionic twins,9 allowing for reversal of blood flow. Although TRAP sequence can occur in both monoamniotic and diamniotic monochorionic twin gestations, it is relatively more common in monoamniotic twins due to the universal presence of arteroarterial anastomoses, whereas similar anastomoses are found in only about 80% of diamniotic monochorionic twins.
Prenatal Care The antenatal diagnosis of twin pregnancy type is ideally made during prenatal care on the basis of early ultrasound findings; however, there are many diagnostic pitfalls that can obscure or confound an accurate diagnosis. In early pregnancy, the number of yolk sacs has previously been thought to be a reliable tool for determining amnionicity. The classic teaching has been that if monochorionic twins are seen but only one yolk sac is identified, the pregnancy is monoamniotic.10 However, review of the literature reveals several case reports in which 2 yolk sacs were seen in the first trimester but a later diagnosis of monoamniotic twins was made on ultrasound and confirmed at delivery.11–13 The opposite scenario has also been reported, in which a single yolk sac was seen but an eventual dividing membrane was noted and a diagnosis of diamnionicity subsequently made. In one series, a single yolk sac was seen in 15% of diamniotic pregnancies.14 In short, the finding of a single or double yolk sac is not a reliable indicator of amnionicity. These findings indicate that the timing of the differentiation of the yolk sac and amniotic membranes are close but not simultaneous. The diagnosis of dichorionic versus monochorionic twins is typically fairly straightforward. First, the finding of different genders effectively assures the diagnosis
645
of a dizygotic and, therefore, dichorionic, pregnancy, with extremely rare exceptions. Ultrasound examination of the placenta is not always diagnostic, as a dichorionic pregnancy may have a single fused placenta. In contrast, the finding of 2 placentas generally also confirms a dichorionic pregnancy, although an accessory placental lobe can obfuscate the situation. When there is a fused dichorionic placentation the membrane between the twins has an easily recognizable thick appearance with a ‘‘Lambda’’ or ‘‘twin peak’’ sign at the interface of the fused membranes with the fused placental masses. This is in contrast to the thin dividing membrane of a monochorionic pregnancy, which forms a characteristic ‘‘T’’ sign where the membranes meet the placenta. Distinguishing between diamniotic and monoamniotic monochorionic pregnancies is more difficult. Both have one placenta and both are the same sex. There are several findings that have historically been used to determine amnionicity, with varying reliability. As noted above, monochorionic diamniotic twins are separated by an amniotic membrane that should be visible on ultrasound, with a typical ‘‘T sign.’’ However, the membrane is thin and often difficult to visualize, especially before 12 weeks or late in pregnancy. Therefore, absence of a separating membrane, especially early in pregnancy, should be treated with suspicion, and it is recommended to continue to evaluate for the dividing membrane on subsequent scans. Monoamniotic pregnancies are commonly complicated by an entangled cord. This finding can be noted on ultrasound and also confirms a diagnosis of monoamnionicity. In rare cases, invasive testing can be used to confirm or make a diagnosis of monoamniotic twins. A ‘‘bubble test’’ involves using an amniocentesis needle to withdraw a few milliliters of amniotic fluid. The syringe is capped and vigorously shaken to produce tiny bubbles, www.clinicalobgyn.com
Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
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Post and Heyborne
then reinstilled under ultrasound visualization. If the pregnancy is monoamniotic, the bubbles will disperse throughout the fluid around both twins. This can be performed concordantly with an amniocentesis for other indications, such as karyotype, or solely to help guide management in a later gestation with unclear amnionicity. Monochorionic diamniotic twins with severe twin-twin transfusion syndrome (TTTS) are numerically more common than monoamniotic twins, so the diagnosis of TTTS should always be entertained before diagnosing monoamnionicity. Monoamnionicity can be mistaken for a twin pregnancy complicated by the ‘‘stuck twin’’ syndrome where oligohydramnios in one amniotic sac can result in the amniotic membranes laying in direct apposition to the fetus. The enveloping membranes typically cause the affected fetus to appear ‘‘stuck’’ against the uterine wall restricting fetal movement. Any new diagnosis of suspected monoamniotic twins in the second or third trimester should always be evaluated relatively urgently by an expert sonologist to exclude severe TTTS, which often requires emergent treatment.
Prenatal Complications The rate of congenital anomalies is significantly higher in monozygotic twins as compared with dizygotic twins or singleton pregnancies. One series by Chen et al15 found that the rate of major congenital anomalies was over 4 higher in monozygotic twins as compared with singletons, and nearly 3 higher than that of dizygotic twins. Another large series by Cameron et al16 found a rate of 6% within monozygotic twins, well above the singleton risk of 0.7% to 1% seen in other series. Some of these anomalies may be a consequence of the disruption of normal circulation due to placental connections.
Within monozygotic twin pregnancies, monoamniotic twins have a higher incidence of congenital anomalies as compared with diamniotic twins. Several authors have reported congenital anomaly rates among monoamniotic twins as high as 18% to 28%,17–19 and these anomalies account for substantial mortality in addition to morbidity. For example, in the Heyborne study, the rate of neonatal demise due to lethal congenital anomalies was 2.6%,14 and Van Mieghem and collogues reported a 4.9% incidence of ‘‘major’’ fetal anomalies.20 Because of environmental impacts on embryonic development (variable epigenetic expression, spontaneous mutations) monozygotic twins have a high level of discordance for genetic disorders and anomalies, with one series finding concordance in only 23% of congenital malformations16 and a second case series finding concordance for major anomalies in only 18% of monozygotic twins.15 This discordance persists in monoamniotic twins. Therefore, the finding of normal anatomy in one twin does not negate the need for thorough evaluation of the second twin. Likewise, the finding of an anomalous twin should prompt careful examination of the second twin, although it is more likely to be a normal second twin rather than a shared anomaly. Pregnancies that are found to be discordant for anomalies or genetic syndromes lead to complicated decisions about pregnancy management, as the anomalous twin can put the normal twin at risk of earlier delivery, demise, and other perinatal complications. The option of selective termination is a complex decision in monoamniotic pregnancies because of shared circulation and cord entanglement. If selective termination is performed, cord occlusion (to prevent the complications of single twin demise) and cord transection (to prevent future demise due to cord entanglement) are needed.21,22 Cardiac anomalies in the general population have a 0.55 to 0.8% incidence; in
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Managing Monoamniotic Twin Pregnancies twin pregnancies, this risk is significantly increased.23 As with congenital anomalies, in general, most studies have reflected an increased incidence with monozygotic as compared with dizygotic twins. This may be related to the impact of shared placental connections, which can impact the fetal circulation during cardiac formation.24 There are also data supporting an increased incidence of cardiac anomalies in monoamniotic twins as compared with diamniotic monochorionic twins, with one small study reporting a rate of 57.1% of at least one twin having a cardiac defect.25 A recent study does question this theory, with demonstration of equal rates of cardiac anomalies between the 2 groups of monozygotic twins.26 As a population-based study, it is unclear if lethal cardiac anomalies are accounted for. The rate for twins was still significantly higher than that of singleton gestations (1.4% vs. 0.87%). Clearly, the diagnosis of monoamniotic twins is an appropriate indication for a fetal echocardiogram at the appropriate gestational age. Monitoring for and diagnosis of TTTS is a key part of the antenatal care of all monochorionic twins. TTTS is a consequence of pathologic vascular anastomoses between the 2 fetal placental circulations. These anastomoses result in unequal blood sharing between the twins, with one twin becoming the arterial ‘‘donor twin’’ and the other becoming the venous ‘‘recipient twin.’’ Both twins are at risk for serious complications including intrauterine fetal demise. The incidence of TTTS in monoamniotic pregnancies is lower than that reported in monochorionic diamniotic pregnancies: 2% to 3% versus 15%.27 This may be due to the near universal presence of arterioarterial anastomoses in monoamniotic twins, which are thought to be protective against TTTS.27,28 However, TTTS is still common enough that it is recommended to provide surveillance for TTTS as part of
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the routine monitoring plan for monoamniotic twin pregnancies. As with monochorionic diamniotic twins, a typical surveillance regimen consists of every 2 week ultrasounds to check for the absence of the fetal bladder and for the presence of polyhydramnios. Any suspicious findings should result in more frequent surveillance. Unlike monochorionic diamniotic twin pregnancies, discrepant amniotic fluid volumes cannot be used for surveillance due to the shared amniotic sac; however, polyhydramnios and discordant bladder volumes, as well as discordant growth, are valuable signs that can lead to the diagnosis of TTTS in monoamniotic pregnancies.29
Antepartum Monitoring Strategies The primary cause for twin mortality in monoamniotic pregnancies has been attributed to entanglement and occlusion of the umbilical cords as a consequence of the absent dividing membrane. Historical mortality rates of monoamniotic twin pregnancies have been reported as high as 70%. Although modern reports have demonstrated better outcomes, the rate of demise after viability remains high. Antenatal monitoring and care, therefore, are focused on the identification of warning signs of impending demise to circumvent mortality from this cause. Both inpatient and outpatient monitoring strategies have been studied, but considerable practice variation persists among Maternal-Fetal Medicine specialists.30 Any recommendation regarding frequency and setting of monitoring of a viable monoamniotic twin pregnancy must balance the benefits of reduced fetal morbidity and mortality against the concerns of inconvenience and possible psychologic and financial strain on the mother and her family, costs to the health care system, and the possibility of iatrogenic prematurity or www.clinicalobgyn.com
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Post and Heyborne
other adverse health issue (thromboembolism, anxiety etc.). In 2004, Heyborne et al19 performed a retrospective study to assess the effectiveness of inpatient monitoring of monoamniotic twins. Ninety-six sets of monoamniotic twins were enrolled; only 87 had 2 surviving fetuses at 24 weeks. Forty three were admitted electively for monitoring at an average gestational age of 26.5 weeks, and the remaining 44 were admitted for usual obstetric indications, resulting in an average gestational age at admission of 30.1 weeks. Among the electively admitted group, there were no fetal deaths. Among the indicated admission group, there were 13 fetal deaths (14.8%); all of these deaths occurred before admission. In other words, no fetal deaths occurred in either group after initiation of inpatient monitoring. Two other, smaller cohort studies have come to similar conclusions. DeFalco et al20 studied 23 monoamniotic twin pregnancies with a retrospective chart review from 1991 to 2001. Among the 11 patients admitted electively between 24 to 28 weeks for inpatient monitoring (which in this study was continuous monitoring), there were no fetal deaths. Among the 12 patients who underwent routine outpatient monitoring (at least 3 times per week nonstress testing or biophysical profile), there were 3 fetal deaths (12.5%). In another small retrospective cohort study by Ezra et al31 in 2005, 26 monoamniotic twin pregnancies were chronicled. Among the 16 pregnancies in the inpatient monitoring group, no fetal demises occurred. Twelve fetal demises were found in the outpatient group (which was comprised of 13 total pregnancies) for a fetal death rate of 46%. However, the outpatient group was not undergoing standardized fetal heart rate monitoring; in fact, only 33% were known to be monoamniotic before delivery. Accordingly, this study contributes to the outcomes of monoamniotic twins monitored as inpatients but should not be used to represent the
expected outcomes with outpatient monitoring. Recently, Van Mieghem et al32 also compared inpatient versus outpatient fetal monitoring in a retrospective review of outcomes for monoamniotic twin pregnancies between 2003 and 2012. Outpatient monitoring varied but included an average of 4 times per week fetal heart rate monitoring and 1 to 2 ultrasounds per week. Inpatient monitoring standards also varied among the 8 centers included in the study, with a maximum intensity of ultrasounds every other day and TID fetal heart rate monitoring. Among the patients who had 2 fetuses alive at 26 weeks, 53 underwent outpatient monitoring and 182 patients underwent inpatient monitoring. With respect to the primary outcome, which was defined as intrauterine fetal demise (IUFD) plus nonrespiratory neonatal morbidity, outpatient and inpatient monitoring groups were found to be similar: 13.2% versus 10.5%, P = 0.55. They, therefore, concluded that outpatient and inpatient monitoring yield similar results. However, this makes the assumption that IUFD and neonatal morbidity are equal outcomes. If fetal death rates are directly compared the outpatient group had a ‘‘potentially preventable’’ fetal death rate of 4.7%, compared with a fetal death rate of 2.1% in the inpatient group. So, although the authors conclude that outpatient monitoring may be preferable given a similar rate of preventable fetal death plus neonatal morbidity with less cost and less theoretic risks of iatrogenic maternal morbidities, the interpretive choices made by these authors selectively favor outpatient monitoring despite demonstrably higher IUFD rates. In addition, indicated inpatient admissions were combined with elective inpatient admissions, which could be expected to negatively skew the inpatient results. In 2012, Murata et al33 published a retrospective review of monoamniotic
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Managing Monoamniotic Twin Pregnancies TABLE 1.
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Fetal Death Rates With Inpatient and Outpatient Care, Studies Published Since 2005 Total Fetal Deaths, Outpatient Outpatient (N) Fetuses (N)
Fetal Deaths, Inpatient (N)
Total Inpatient Fetuses (N)
Heyborne Ezra31
13 N/A
88 N/A
0 0
86 20
Defalco20 Murata et al33 Van Mieghem32 Quinn et al8 Pasquini9 Totals Death rate (%)
3 0 5 0 0 21 8.1
24 2 106 0 40 260
0 1 2 0 N/A 3 0.8
22 52 142 34 N/A 356
Study 19
twin pregnancies outcomes following routine admission and inpatient surveillance at 7 tertiary perinatal centers. Although this study did not include an outpatient cohort, the inpatient monitoring results can be compared with the inpatient cohorts of the above studies. A total of 38 pregnancies were initially included, but 8 ended in fetal loss before inpatient admission. Twenty nine of the remaining 30 women were admitted between 24 and 26 weeks gestational age, underwent fetal monitoring at least daily and ultrasound evaluation at least weekly and had a scheduled Cesarean delivery at 32 to 34 weeks or as obstetrically indicated. The final patient refused inpatient admission and did not suffer a fetal demise but her outpatient management strategy was not described. Of the 29 inpatient admissions, there was one fetal death which occurred at 32 weeks (1.7%). Table 1 summarizes available studies comparing inpatient and outpatient monitoring of monoamniotic twins. We include all available studies of inpatient care and contemporary (since 2005) studies of outpatient care to account for improved outpatient surveillance. In conclusion, several studies have been performed to retrospectively analyze the difference between outcomes for inpatient and outpatient monitoring of monoamniotic twin pregnancies. Most have demonstrated a clear
Notes
Table V Outpatient cohort excluded (see text) Table 1 and 2 Table 1
P
