Monochorionic twin pregnancies are well known to be at risk for a variety of severe complications, a true challenge for the maternal–fetal medicine specialist. With current standards of care, monochorionicity should be established in the first trimester. Subsequently, frequent monitoring using the appropriate diagnostic tools, and in-depth knowledge about the pathophysiology of all possible clinical presentations of monochorionic twin abnormalities, should lead to timely recognition, and appropriate management. Virtually all unique diseases found in monochorionic twins are directly related to placental angio-architecture. This, however, cannot be established reliably before birth. The clinician needs to be aware of the definitions and symptoms of twin-to twin transfusion syndrome, selective fetal growth restriction, twin anaemia–polycythaemia sequence, and twin reversed arterial perfusion sequence, to be able to recognise each disease and take the required action.
In this chapter, we address current standards on correct and timely diagnoses of severe complications of monochorionic twin pregnancies.
Introduction
Monochorionic twin pregnancies are associated with a variety of serious complications, unique to this group. The underlying pathophysiology of most of these complications seems to be related, directly or indirectly, to the unique angio-architecture of the monochorionic placenta . Imbalanced blood flow, with net transfer of blood and likely of numerous regulating factors, is the accepted cause of twin-twin transfusion syndrome (TTTS) and twin anaemia–polycythemia sequence (TAPS). Although the accepted cause of selective fetal growth restriction (sFGR) is an unequally shared placenta, and the reversed blood flow in the cord and the body of the acardiac twin explains its features, the underlying pathophysiology may start with imbalanced blood flow through particular types of vascular anastomoses. With current imaging technology, we cannot reliably visualise these anastomoses. Ultrasound and Doppler examinations enable us to detect early signs and symptoms of the various pathologic conditions in monochorionic twins. As for some, treatment options exist, timely diagnosis and referral is of vital importance. In this chapter, we aim to discuss the clinically relevant diagnostic tools that can and should apply in the management of monochorionic twin pregnancies.
Twin-to-twin transfusion syndrome
Monochorionic twins share a single placenta with vascular anastomoses that connect the fetal circulations, allowing inter-twin blood transfusion. This is a physiological phenomenon as long as blood flow between the fetuses is balanced. Unbalanced net inter-twin blood transfusion, however, may lead to various forms of serious pathology. The best-known clinical syndrome is TTTS, which is a chronic form of feto–fetal transfusion and affects about 9% of monochorionic twins .
In the past, TTTS was diagnosed at the time of birth based on neonatal criteria that included a growth discordance of 15–20% associated with discordant cord or neonatal haemoglobin concentration of ≥5 g/dl . A subsequent study by Wenstrom et al. showed that any combination of weight and haemoglobin discordance could be seen with equal frequency. The investigators concluded that the historical paediatric parameters should be abandoned for the diagnosis of TTTS.
Nowadays, TTTS is diagnosed prenatally by ultrasound examination. It typically presents in the second trimester of pregnancy, and the diagnosis is based on the presence of a twin oligo–polyhydramnios sequence (TOPS). The following ultrasound criteria are required to diagnose TTTS: (1) the twin gestation is diagnosed as monochorionic (ideally with a scan carried out in the first trimester showing a T-sign); and (2) a combination of oligohydramnios exists in one twin’s amniotic cavity, with polyhydramnios in the other twin’s amniotic cavity. Oligohydramnios is defined as a maximum vertical pocket (MVP) of ≤2 cm. This twin is commonly called the donor twin. Polyhydramnios was originally defined as a MVP of ≥8 cm . Subsequent studies in Europe have proposed to increase the threshold to 10 cm or more for the MVP after 20 weeks’ gestation . This twin is described as the recipient twin.
A twin gestation that meets the above criteria is classified as TTTS. Quintero et al. , in 1999, described a classification of TTTS ( Table 1 ), which has been widely adopted and used throughout the world.
| Stage | Oligo/polyhydramnios a | Absent bladder filling in donor | Critically abnormal Doppler studies b | Hydrops of either fetus | Intrauterine fetal demise of either fetus |
|---|---|---|---|---|---|
| I | + | – | – | – | – |
| II | + | + | – | – | – |
| III | + | + | + | – | – |
| IV | + | + | + | + | – |
| V | + | + | + | + | + |
a Oligohydramnios: maximum vertical pocket of 2 cm or less; polyhydramnios: maximum vertical pocket of 8 cm or over (or ≥10 cm at >20 weeks’ gestation).
b Absent or reversed diastolic velocity in the umbilical artery or ductus venosus or pulsatile umbilical venous velocity.
Quintero Stage I is defined as an oligo–polyhydramnios sequence with MVP of amniotic fluid of the donor and recipient twin of 2 or less and 8 cm or more (or ≥10 cm at >20 weeks’ gestation), respectively.
Stage II is a more progressive stage, including no visualisation of bladder filling in the donor twin. Some investigators have argued that the presence of a small bladder that fails to fill during prolonged ultrasound examination should also qualify as stage II disease . Stage III disease is diagnosed when the Doppler results are critically abnormal, including absent ( Fig. 1 ) or reversed ( Fig. 2 ) diastolic velocity in the umbilical artery or in the ductus venosus ( Fig. 3 ), or pulsatile umbilical venous velocity ( Fig. 4 ) in either the donor, recipient twin, or both. Therefore, many combinations of Doppler abnormalities are possible. Typically, umbilical artery flow abnormalities are seen in donor twins, whereas recipients more often show abnormal ductus venous or pulsatile umbilical venous Doppler studies, indicative of imminent cardiac failure. Subdividing stage III into stage III-D, III-R, or III-DR, to indicate which twin experiences Doppler abnormalities, is advocated by several centres.
Stage IV disease is present when fetal hydrops (e.g. ascites, pericardial effusion, or both, pleural effusions, or scalp oedema) is diagnosed in either twin. Typically this is first seen in the recipient twin. Fetal demise of either fetus is named stage V disease.
Several studies have shown that disease severity defined by Quintero stage at presentation is one the determinants of fetal outcome . Progression to a higher stage is associated with a poorer prognosis . Therefore, early diagnosis of TTTS is important. Essential for optimal outcome is timely diagnosis and timely referral. Despite all the publications and even complete textbooks on TTTS, late referrals with women already in labour, or hydropic fetuses, do still occur. Essential, therefore, is to adhere to, at least, fortnightly ultrasound examination, and in particular combined with patient instruction to report onset of symptoms . It is advised that these fortnightly scans are carried out during the whole pregnancy, starting from 14 weeks gestation. As TTTS usually occurs between 16 and 24 weeks , it is of great importance that the fortnightly scans that are carried out at this time period should specifically focus on (early) signs to detect TTTS, as stated in the National Institute of Health and Clinical Excellence guidelines . Although less common, TTTS can occur up to 30 weeks or beyond, and some centres have shown feasibility of fetoscopic laser surgery beyond the common 26-week limit . Continuation of the fortnightly scans throughout the pregnancy, therefore, seems to be logical advice.
Fetal biometry should not be used to diagnose TTTS. Although estimated fetal weight differences have long been abandoned in diagnosing TTTS, a general belief still exists that donor twins should be smaller than recipients. Typically, a growth discordance of 20% or more or 25% has been used as a diagnostic criterion for selective growth restriction in one of the twin fetuses. Such a birth weight difference, however, is as frequently seen in monochorionic as in dichorionic twins . In a study of 270 patients with TTTS, only 20% met the criteria for selective growth restriction in the donor twin . Consequently, a difference in estimated fetal weight is not considered a mandatory feature of TTTS.
It may, however, be a challenge to distinguish monochorionic twins with single growth restriction from TTTS. The growth-restricted twin may mimic the donor twin presenting with oligohydramnios, a small bladder, and abnormal flow in the umbilical artery. The lack of polyhydramnios in the other amniotic cavity, however, rules out the diagnosis of TTTS.
The finding of polyhydramnios without visualisation of an inter-twin membrane may lead to the false diagnosis of a monoamniotic twin pregnancy. Although TTTS may occur in monoamniotic pregnancies, it is more likely that the donor twin has anhydramnios, with its amniotic membrane tightly wrapped around its body. This is called the ‘stuck’ twin phenomenon ( Fig. 5 ). In most cases, the donor twin is fixed to the uterine wall. A variant of this classic stuck twin occurs when dividing membranes envelops the donor twin with severe oligohydramnios and connected to the uterine wall by a laminar stalk of these membranes, the so-called ‘cocoon-sign’ or intrauterine sling . It may seem ‘unstuck’ and free floating in the recipient’s amniotic cavity with polyhydramnios, and can therefore be misdiagnosed as being surrounded by a normal amount of amniotic fluid. Other causes of stuck twins, not associated with TTTS that have been identified are viral infections, renal disease, and agenesis of the ductus venosus .
In conclusion, the diagnosis and evaluation of stage and severity requires careful history taking, complete detailed evaluation of both twins, their anatomy and functional assessment, placenta and amniotic fluid, with an open mind to rare but important alternative diagnoses. Once the diagnosis is confirmed or at least extremely likely, determining the optimal time and method for intervention becomes the next challenge, which will be discussed elsewhere in this issue of Best Practice and Research Clinical Obstetrics and Gynaecology .
Twin-to-twin transfusion syndrome
Monochorionic twins share a single placenta with vascular anastomoses that connect the fetal circulations, allowing inter-twin blood transfusion. This is a physiological phenomenon as long as blood flow between the fetuses is balanced. Unbalanced net inter-twin blood transfusion, however, may lead to various forms of serious pathology. The best-known clinical syndrome is TTTS, which is a chronic form of feto–fetal transfusion and affects about 9% of monochorionic twins .
In the past, TTTS was diagnosed at the time of birth based on neonatal criteria that included a growth discordance of 15–20% associated with discordant cord or neonatal haemoglobin concentration of ≥5 g/dl . A subsequent study by Wenstrom et al. showed that any combination of weight and haemoglobin discordance could be seen with equal frequency. The investigators concluded that the historical paediatric parameters should be abandoned for the diagnosis of TTTS.
Nowadays, TTTS is diagnosed prenatally by ultrasound examination. It typically presents in the second trimester of pregnancy, and the diagnosis is based on the presence of a twin oligo–polyhydramnios sequence (TOPS). The following ultrasound criteria are required to diagnose TTTS: (1) the twin gestation is diagnosed as monochorionic (ideally with a scan carried out in the first trimester showing a T-sign); and (2) a combination of oligohydramnios exists in one twin’s amniotic cavity, with polyhydramnios in the other twin’s amniotic cavity. Oligohydramnios is defined as a maximum vertical pocket (MVP) of ≤2 cm. This twin is commonly called the donor twin. Polyhydramnios was originally defined as a MVP of ≥8 cm . Subsequent studies in Europe have proposed to increase the threshold to 10 cm or more for the MVP after 20 weeks’ gestation . This twin is described as the recipient twin.
A twin gestation that meets the above criteria is classified as TTTS. Quintero et al. , in 1999, described a classification of TTTS ( Table 1 ), which has been widely adopted and used throughout the world.
| Stage | Oligo/polyhydramnios a | Absent bladder filling in donor | Critically abnormal Doppler studies b | Hydrops of either fetus | Intrauterine fetal demise of either fetus |
|---|---|---|---|---|---|
| I | + | – | – | – | – |
| II | + | + | – | – | – |
| III | + | + | + | – | – |
| IV | + | + | + | + | – |
| V | + | + | + | + | + |
a Oligohydramnios: maximum vertical pocket of 2 cm or less; polyhydramnios: maximum vertical pocket of 8 cm or over (or ≥10 cm at >20 weeks’ gestation).
b Absent or reversed diastolic velocity in the umbilical artery or ductus venosus or pulsatile umbilical venous velocity.
Quintero Stage I is defined as an oligo–polyhydramnios sequence with MVP of amniotic fluid of the donor and recipient twin of 2 or less and 8 cm or more (or ≥10 cm at >20 weeks’ gestation), respectively.
Stage II is a more progressive stage, including no visualisation of bladder filling in the donor twin. Some investigators have argued that the presence of a small bladder that fails to fill during prolonged ultrasound examination should also qualify as stage II disease . Stage III disease is diagnosed when the Doppler results are critically abnormal, including absent ( Fig. 1 ) or reversed ( Fig. 2 ) diastolic velocity in the umbilical artery or in the ductus venosus ( Fig. 3 ), or pulsatile umbilical venous velocity ( Fig. 4 ) in either the donor, recipient twin, or both. Therefore, many combinations of Doppler abnormalities are possible. Typically, umbilical artery flow abnormalities are seen in donor twins, whereas recipients more often show abnormal ductus venous or pulsatile umbilical venous Doppler studies, indicative of imminent cardiac failure. Subdividing stage III into stage III-D, III-R, or III-DR, to indicate which twin experiences Doppler abnormalities, is advocated by several centres.
Stage IV disease is present when fetal hydrops (e.g. ascites, pericardial effusion, or both, pleural effusions, or scalp oedema) is diagnosed in either twin. Typically this is first seen in the recipient twin. Fetal demise of either fetus is named stage V disease.
Several studies have shown that disease severity defined by Quintero stage at presentation is one the determinants of fetal outcome . Progression to a higher stage is associated with a poorer prognosis . Therefore, early diagnosis of TTTS is important. Essential for optimal outcome is timely diagnosis and timely referral. Despite all the publications and even complete textbooks on TTTS, late referrals with women already in labour, or hydropic fetuses, do still occur. Essential, therefore, is to adhere to, at least, fortnightly ultrasound examination, and in particular combined with patient instruction to report onset of symptoms . It is advised that these fortnightly scans are carried out during the whole pregnancy, starting from 14 weeks gestation. As TTTS usually occurs between 16 and 24 weeks , it is of great importance that the fortnightly scans that are carried out at this time period should specifically focus on (early) signs to detect TTTS, as stated in the National Institute of Health and Clinical Excellence guidelines . Although less common, TTTS can occur up to 30 weeks or beyond, and some centres have shown feasibility of fetoscopic laser surgery beyond the common 26-week limit . Continuation of the fortnightly scans throughout the pregnancy, therefore, seems to be logical advice.
Fetal biometry should not be used to diagnose TTTS. Although estimated fetal weight differences have long been abandoned in diagnosing TTTS, a general belief still exists that donor twins should be smaller than recipients. Typically, a growth discordance of 20% or more or 25% has been used as a diagnostic criterion for selective growth restriction in one of the twin fetuses. Such a birth weight difference, however, is as frequently seen in monochorionic as in dichorionic twins . In a study of 270 patients with TTTS, only 20% met the criteria for selective growth restriction in the donor twin . Consequently, a difference in estimated fetal weight is not considered a mandatory feature of TTTS.
It may, however, be a challenge to distinguish monochorionic twins with single growth restriction from TTTS. The growth-restricted twin may mimic the donor twin presenting with oligohydramnios, a small bladder, and abnormal flow in the umbilical artery. The lack of polyhydramnios in the other amniotic cavity, however, rules out the diagnosis of TTTS.
The finding of polyhydramnios without visualisation of an inter-twin membrane may lead to the false diagnosis of a monoamniotic twin pregnancy. Although TTTS may occur in monoamniotic pregnancies, it is more likely that the donor twin has anhydramnios, with its amniotic membrane tightly wrapped around its body. This is called the ‘stuck’ twin phenomenon ( Fig. 5 ). In most cases, the donor twin is fixed to the uterine wall. A variant of this classic stuck twin occurs when dividing membranes envelops the donor twin with severe oligohydramnios and connected to the uterine wall by a laminar stalk of these membranes, the so-called ‘cocoon-sign’ or intrauterine sling . It may seem ‘unstuck’ and free floating in the recipient’s amniotic cavity with polyhydramnios, and can therefore be misdiagnosed as being surrounded by a normal amount of amniotic fluid. Other causes of stuck twins, not associated with TTTS that have been identified are viral infections, renal disease, and agenesis of the ductus venosus .
