ISUOG Practice Guidelines: role of ultrasound in twin pregnancy

The International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) is a scientific organization that encourages sound clinical practice, and high-quality teaching and research related to diagnostic imaging in women's healthcare. The ISUOG Clinical Standards Committee (CSC) has a remit to develop Practice Guidelines and Consensus Statements as educational recommendations that provide healthcare practitioners with a consensus-based approach, from experts, for diagnostic imaging. They are intended to reflect what is considered by ISUOG to be the best practice at the time at which they are issued. Although ISUOG has made every effort to ensure that Guidelines are accurate when issued, neither the Society nor any of its employees or members accepts any liability for the consequences of any inaccurate or misleading data, opinions or statements issued by the CSC. The ISUOG CSC documents are not intended to establish a legal standard of care because interpretation of the evidence that underpins the Guidelines may be influenced by individual circumstances, local protocol and available resources. Approved Guidelines can be distributed freely with the permission of ISUOG ([email protected]). The incidence of multiple pregnancy is rising, mainly due to delayed childbirth and advanced maternal age at conception and the resultant widespread use of assisted reproduction techniques1. The twin birth rate increased by just under 70% between 1980 (19 per 1000 live births) and 2006 (32 per 1000 live births)2. Twin pregnancy is associated with a high risk of perinatal mortality and morbidity3-6. In 2009, the associated stillbirth rate was 12 per 1000 twin births and 31 per 1000 triplet and higher-order multiple births, compared with five per 1000 singleton births7, 8. Preterm birth prior to 37 weeks' gestation occurs in up to 60% of multiple pregnancies, contributing to the increased risk of neonatal mortality (65% of neonatal deaths among multiple births are preterm, compared with 43% of neonatal deaths in singletons) and long-term morbidity9-12. Of course, such complications rise with a reduction in gestational age at birth. In addition, compared with singletons, twins are at increased risk of iatrogenic preterm delivery due to the greater incidence of maternal and fetal complications. The risk is significantly higher in monochorionic compared with dichorionic pregnancy3-6. Ultrasound assessment of fetal biometry, anatomy, Doppler velocimetry and amniotic fluid volume is used to identify and monitor twin pregnancies at risk of adverse outcomes such as twin-to-twin transfusion syndrome (TTTS) and fetal growth restriction (FGR). As in singletons, impaired fetal growth can be assessed in twins by comparing biometry and Doppler velocimetry parameters against standards for uncomplicated pregnancy. This guidance will address the role of ultrasound in the care of uncomplicated twin pregnancy and those complicated by TTTS, selective FGR (sFGR), twin anemia–polycythemia sequence (TAPS), twin reversed arterial perfusion (TRAP) sequence, conjoined twins and single intrauterine death (IUD). The document provides guidance on the methods used to determine gestational age and chorionicity, screening for chromosomal and structural abnormalities, and screening for TTTS, TAPS, growth abnormalities and preterm birth. The management of higher-order multiple pregnancy will be covered in a separate document. The Cochrane Library and Cochrane Register of Controlled Trials were searched for relevant randomized controlled trials, systematic reviews and meta-analyses and a search of MEDLINE from 1966 to 2014 was carried out. The date of the last search was 15 November 2014. In addition, relevant conference proceedings and abstracts were searched. Databases were searched using the relevant MeSH terms including all sub-headings. This was combined with a keyword search using ‘twin’, ‘multiple’, ‘pregnancy’, ‘ultrasound’, ‘twin-to-twin transfusion syndrome’, ‘fetal growth restriction’, ‘twin anemia polycythemia sequence’, ‘twin reversed arterial perfusion’, ‘acardiac twin’, ‘monochorionic monoamniotic’, ‘conjoined’, ‘demise’. The National Library for Health and the National Guidelines Clearing House were also searched for relevant guidelines and reviews. Gray (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections and clinical trial registries. The search was limited to the English language. When possible, recommendations are based on, and explicitly linked to, the evidence that supports them, while areas lacking evidence are annotated as ‘good practice points’. Details of the grades of recommendations and levels of evidence used in these Guidelines are given in Appendix 1. Other studies have recommended the use of the smaller CRL or the mean CRL, which takes into account both fetuses13-15. The disadvantage of using the smaller CRL is the potential of the operator believing that the larger twin is large-for-gestational age, and therefore being falsely reassured that the smaller twin is still growing appropriately. The most common practice is to use the larger CRL. If the woman presents after 14 weeks' gestation, the larger head circumference should be used1. Twin pregnancies conceived via in-vitro fertilization should be dated using the oocyte retrieval date or the embryonic age from fertilization (EVIDENCE LEVEL: 2+). Every attempt should be made to determine the chorionicity of a twin pregnancy. Chorionicity should be determined between 11 + 0 and 13 + 6 weeks of gestation using the membrane thickness at the site of insertion of the amniotic membrane into the placenta, identifying the T-sign or lambda sign (Figure 1), and the number of placental masses visualized using ultrasound1. It is important to examine the dividing membrane carefully; in dichorionic diamniotic twin pregnancy, the twins are separated by a thick layer of fused chorionic membranes with two thin amniotic layers, one on each side, giving the appearance of a ‘full lambda’, compared with only two thin amniotic layers separating the two fetuses in monochorionic diamniotic (MCDA) twin pregnancy (the T-sign). In women presenting for the first time after 14 weeks of gestation, chorionicity is best determined using the same ultrasound signs, in particular by counting the membrane layers, and noting discordant fetal sex. The reliability of the number of placental masses is questionable, as dichorionic placentae are commonly adjacent to each other, appearing as a single mass, and 3% of monochorionic twin pregnancies have two placental masses on ultrasound, the presence of which does not preclude the presence of vascular anastomoses16. It is likely that using a combination of ultrasound features, rather than a single one, would be more accurate1. If it is not possible to determine chorionicity by transabdominal ultrasound imaging, this should be attempted using transvaginal sonography. If it is still not possible to determine chorionicity, a second opinion should be sought from a tertiary referral center. If the center is uncertain about the chorionicity, it is safer to classify the pregnancy as monochorionic1 (EVIDENCE LEVEL: 3). At the time at which chorionicity is determined, amnionicity (i.e. whether or not the twins share the same amniotic sac) should be determined and documented. In case of doubt, absence of the intertwin membrane is best confirmed by transvaginal scan. Another useful finding is demonstration of cord entanglement, which is almost universal in MCMA twin pregnancy, using color and pulsed-wave Doppler ultrasound. Using pulsed-wave Doppler, two distinct arterial waveform patterns with different heart rates are seen within the same sampling gate (EVIDENCE LEVEL: 4). All MCMA twin pregnancies should be referred to a tertiary center with expertise in their management1. It is recommended that an ultrasound image demonstrating the chorionicity is stored electronically and that a hard copy is added to the medical records. As determination of chorionicity is most accurate at 11–14 weeks' gestation when the amnion and chorion have not yet fused, the first-trimester scan in twin pregnancy is paramount (EVIDENCE LEVEL: 4). It is important to follow a reliable, consistent strategy for antenatal twin labeling. Options include: labeling according to their site, either left and right, or upper and lower; or mapping in the first trimester according to the insertion of their cords relative to the placental edges and membrane insertion. In some healthcare settings, Twin A is the fetus on the right side, while Twin B is the one on the left. This information should be documented clearly in the woman's notes in order to ensure consistent labeling during follow-up scans17. It is advisable to describe each twin using as many features as possible so as to enable others to identify them accurately; e.g. ‘Twin A (female) is on the maternal right with a posterior placenta and marginal cord insertion’. For pregnancies with discordance, the labeling should be accompanied by a description such as ‘Twin A, potential recipient’. It is important to acknowledge that labeling is less accurate in MCMA twin pregnancy, particularly in the first trimester. It should be borne in mind that the twins labeled as ‘Twin A’ and ‘Twin B’ during antenatal ultrasound scans may not necessarily be delivered in that order, in particular if the mode of delivery is Cesarean section18. It is important to alert parents and healthcare professionals attending the delivery to this fact, particularly in pregnancies in which the twins are discordant for structural abnormalities that are not obvious by external examination, e.g. congenital diaphragmatic hernia or cardiac defects. In such cases, an ultrasound scan should be performed just prior to delivery and also before instigating any specific neonatal intervention. In uncomplicated dichorionic twin pregnancy, ultrasound imaging should be performed in the first trimester, again at around 20 weeks' gestation (second-trimester anomaly scan), and every 4 weeks thereafter (unless a complication is detected which might require more frequent scans) (Figure 2)1. In uncomplicated monochorionic twins, an ultrasound scan should be performed in the first trimester. There should then be scans every 2 weeks from 16 weeks onwards, as timely detection of TTTS and TAPS has been shown to improve perinatal outcome (Figure 3)19, 20 (EVIDENCE LEVEL: 4). At each ultrasound assessment, the following should be assessed: fetal biometry, amniotic fluid volume and umbilical artery Doppler (from 20 weeks' gestation) for both twins. Discordance in estimated fetal weight (EFW) should be calculated and documented at each scan from 20 weeks. In monochorionic twin pregnancy, middle cerebral artery (MCA) peak systolic velocity (PSV) should be recorded from 20 weeks, in order to screen for TAPS. In MCDA twins, the amniotic fluid volume (deepest vertical pocket) should be assessed and documented at each ultrasound scan to screen for TTTS. Cervical length assessment is performed ideally at the same visit as the anomaly scan in the second trimester, in order to identify women at risk of extreme preterm birth (EVIDENCE LEVEL: 2+, 2++). In twin pregnancy, screening for trisomy 21 can be performed in the first trimester using the combined test, which includes maternal age, NT measurement and serum β-hCG and PAPP-A levels. An alternative is the combination of maternal age and the NT recorded between 11 + 0 and 13 + 6 weeks of gestation1. In case of a vanished twin, if there is still a measurable fetal pole, β-hCG and PAPP-A measurements are biased and NT alone should be used for risk estimation. The risk of trisomy 21 in monochorionic twin pregnancy is calculated per pregnancy based on the average risk of both fetuses (because the twins share the same karyotype), whereas in dichorionic twin pregnancy the risk is calculated per fetus (as around 90% are dizygotic so have different karyotypes). The DR for Down syndrome may be lower in twin compared with singleton pregnancy1. However, a recent meta-analysis reported similar performance (89% for singletons, 86% for dichorionic twins and 87% for monochorionic twins, at a false-positive rate (FPR) of 5%)22 (EVIDENCE LEVEL: 2++). The likelihood of being offered invasive testing on the basis of a combined screening result is greater in twin compared with singleton pregnancy1. Moreover, invasive testing carries greater risks in twins23-25. A meta-analysis showed that the overall pregnancy loss rate following chorionic villus sampling (CVS) in twin pregnancy was 3.8%, and following amniocentesis was 3.1%23. Other research has reported lower loss rates: 2% following CVS and 1.5–2% following amniocentesis26. The risk was found to be similar for transabdominal and transcervical approaches, use of a single-needle or double-needle system, and single or double uterine entry23 (EVIDENCE LEVEL: 2++). Screening and diagnostic testing for trisomy is more complex in twin compared with singleton pregnancy. It is important, therefore, that counseling prior to testing is provided by healthcare professionals with expertise in this area1. It is important to inform women and their partners in advance of the potentially complex decisions that they will need to make on the basis of the results of combined screening, bearing in mind the increased risk of invasive testing in twins, the possible discordance between dichorionic twins for fetal aneuploidy, and the risks of selective fetal reduction1 (EVIDENCE LEVEL: 2+). Cell-free DNA (cfDNA) analysis of maternal blood for risk assessment for fetal trisomy 21 is used increasingly in clinical practice. It has the potential to overcome many of these complex issues, because it has a much higher DR and lower FPR than does the combined test27. In a recent meta-analysis, the weighted pooled DR for trisomy 21 in singleton pregnancy was 99% for a FPR of 0.1%28. The corresponding values in twin pregnancy were 94.4% and 0%. However, so far, the reported number of trisomy-21 cases in twin pregnancy diagnosed using cfDNA testing is far smaller than that in singleton pregnancy (EVIDENCE LEVEL: 2++). Invasive testing for chromosomal or genetic analysis of twins should be carried out by a fetal medicine expert. CVS is preferred in dichorionic twin pregnancy because it can be performed earlier than can amniocentesis. Earlier diagnosis of any aneuploidy is particularly important in twin pregnancy, given the lower risk of selective termination in the first compared with the second trimester (7% risk of loss of the entire pregnancy, and 14% risk of delivery before 32 weeks)29. It is important to map carefully the position of the twins within the uterus. During amniocentesis in monochorionic twins, if monochorionicity has been confirmed before 14 weeks' gestation and the fetuses appear concordant for growth and anatomy, it is acceptable to sample only one amniotic sac. Otherwise, both amniotic sacs should be sampled because of the possibility of rare discordant chromosomal anomalies in monochorionic pregnancy. CVS in monochorionic pregnancy will sample only the single placenta so will miss these rare discordant chromosomal anomalies. Discordance for most of the common human aneuploidies (trisomies 13, 18 and 21, Turner syndrome and triploidy) has been reported in monochorionic twin pairs30. In the event of heterokaryotypic monochorionic pregnancy, selective reduction by umbilical cord occlusion can be offered from 16 weeks onwards, with a survival rate of more than 80% for the healthy twin31, 32. When monochorionic twins are discordant for an abnormality, prior to invasive testing a discussion should take place regarding the complexity of selective termination, should it become necessary32 (EVIDENCE LEVEL: 3). Although some studies have reported an association between first-trimester intertwin discordance in NT or CRL, or reversed a-wave in the ductus venosus (DV), and the development of TTTS, their predictive value is poor17, 33-35. NT discordance of ≥ 20% had a sensitivity of 52–64% and a specificity of 78–80%, a positive predictive value of 50% and a negative predictive value of 86% for the development of TTTS36, 37. Discordance in NT of ≥ 20% is found in around 25% of monochorionic twins and the risk of early IUD or development of severe TTTS in this group is more than 30%37. The risk of complications is less than 10% if the NT discordance is < 20%37. An abnormal DV will pick up only 38% of all pregnancies that subsequently develop TTTS, and, of those predicted to be at high risk, only 30% will ultimately develop TTTS35. Similarly, although intertwin discordance in CRL at 11–13 weeks' gestation is significantly associated with the risk of pregnancy loss (area under the receiver–operating characteristics curve (AUC), 0.5), birth-weight discordance (AUC, 0.6), sFGR (AUC, 0.6) and preterm delivery prior to 34 weeks' gestation (AUC, 0.5), again the predictive value is poor (pooled predictive risk of 52%)38, 39. Nevertheless, the management of twin pregnancy with CRL discordance ≥ 10% or NT discordance ≥ 20% should be discussed with a fetal medicine expert and in these pregnancies there should be detailed ultrasound assessment and testing for karyotype abnormalities. The risk of fetal abnormalities was found to be 25% in pregnancies with CRL discordance ≥ 10%, compared with 4% in pregnancies with CRL discordance < 10%40. However, CRL discordance at 7 + 0 to 9 + 6 weeks' gestation is a predictor of the risk of single fetal demise in the first trimester (DR of 74% for a FPR of 5%)41 (EVIDENCE LEVEL: 2++). At the first-trimester scan (between 11 + 0 and 13 + 6 weeks' gestation) the fetuses should be assessed for the presence of any major anomalies42. Routine second-trimester ultrasound screening for anomalies in twins should be performed by an experienced operator at around 20 (18–22) weeks' gestation1, 43. This scan may be more difficult than usual because of the presence of a second fetus, and it is important to allow adequate time (i.e. in the order of 45 min). The risk of fetal anomaly is greater in twin compared with singleton pregnancy44. The rate per fetus in dizygotic twins is probably the same as that in singletons, whereas it is two-to-three times higher in monozygotic twins. In around 1 in 25 dichorionic, 1 in 15 MCDA and 1 in 6 monoamniotic twin pregnancies, there is a major congenital anomaly that typically affects only one twin45, 46. screening for anomalies should be considered in monochorionic twin pregnancy, bearing in mind that and cardiac abnormalities might become more obvious in the trimester. associated with twins abnormalities, cardiac and anomalies. screening cardiac assessment should be performed according to ISUOG including and and It is important to make the woman of the of ultrasound screening, which according to the of The of screening for fetal anomaly in the second trimester giving parents the to for the birth of a with a potential them the of termination, to a center for the and, intrauterine (EVIDENCE LEVEL: 3). to two of twin pregnancies will have an anomaly only one fetus, to the between management and selective termination of the in monozygotic twins, for a structural anomaly is found in than 20% of pregnancies should be referred to a fetal medicine center for management1. In monochorionic twins discordant for a structural abnormality, discordant aneuploidy is rare not In these expert ultrasound assessment in a tertiary with invasive fetal chromosomal or genetic testing if and a discussion of the likely for both the and the twin, are For that are and a high risk of intrauterine management is preferred in dichorionic twins, whereas in monochorionic twin pregnancy this would to the healthy against the adverse of demise of the The of selective termination in twin pregnancy the risk of preterm birth. This is particularly relevant in twin pregnancies discordant for in which selective termination in the second trimester is associated with a higher risk of and preterm compared with that in the first trimester (7% risk of loss of the entire pregnancy, and 14% risk of delivery before 32 weeks)29. When the diagnosis is made in the second trimester, women might for a selective termination in the trimester, if the when the is associated with a risk of preterm birth rather than fetal loss of the The and of each should be considered loss of a fetal medicine to the in the event of preterm and risk of complications associated with the specific (EVIDENCE LEVEL: 2++). in dichorionic twin pregnancy is performed by or of or When selective termination of one twin of a monochorionic is the of is not an because of the risk to the healthy cord or of the twin is This to demise of the twin while the healthy twin against of its blood volume into the twin following its The survival rate of the is 80% and the risk of of the membranes and preterm birth prior to 32 weeks is The risk of adverse in the may also be increased compared with that in uncomplicated (EVIDENCE LEVEL: 2++). and iatrogenic preterm births are more common in twin than in singleton than of twins are before 37 weeks of gestation and of twin births before 37 and 32 weeks of gestation, these rates are and times the rates for singleton pregnancy, women found to have a at the second-trimester ultrasound scan are to be at increased risk of preterm However, the sensitivity of this finding is and the of the length used to increased risk of preterm birth is A length < 25 at weeks' gestation in twin pregnancy is a predictor of preterm birth before 34 weeks, not before 37 In a length 20 at weeks was the most accurate predictor of preterm birth before 32 and before 34 weeks (pooled and positive and negative likelihood were and and and and and A length 25 at weeks had a pooled positive likelihood of for the of preterm birth before The predictive of length for preterm birth was in (EVIDENCE LEVEL: 2++). Moreover, there is strategy to preterm birth in these or not the risk of preterm delivery in these However, might the risk of neonatal and research may management in this in due (EVIDENCE LEVEL: The assessment and management of FGR are among If both twins have an < the fetuses should be sFGR is a to twin pregnancies in which one fetus has an < and the intertwin discordance is The of and a of in the to discordant fetal A of for discordance in birth weight was found to adverse outcome not take into account the intertwin discordance use < in one the discordance most predictive of adverse outcome is likely to with gestational A discordance of 20% a for pregnancies at increased risk of adverse outcome of discordance is calculated by the following of larger twin weight of smaller of larger twin (EVIDENCE LEVEL: 2++). a diagnosis has been a should be This search should a detailed anomaly scan and screening for and may also be to chromosomal abnormalities as a of sFGR in monochorionic twin pregnancy occurs mainly due to of the placental and (EVIDENCE LEVEL: 3). using ultrasound is less accurate in twin than in singleton that a combination of and measurements best in both singleton and twin the used to monitor fetal growth in twin pregnancy are the same as those used for However, there is a reduction in fetal growth in twin compared with singleton pregnancy, particularly in the This is particularly in MCDA This that specific twin growth should be used for and growth in twin However, the use of specific twin growth is due to the that the growth in the trimester in most twin pregnancies might be by some of placental (EVIDENCE LEVEL: 2++). discordance between twins is significantly associated with the risk of perinatal The for the risk of perinatal loss in twins with an discordance ≥ 25% was found to be to the National for Health and discordance should be calculated and documented at every scan from 20 weeks If this discordance 25% or a referral should be made to a fetal medicine for assessment, increased fetal including fetal Doppler, and of delivery when (EVIDENCE LEVEL: 2++). The of sFGR on the of velocity in the umbilical artery (Figure In the umbilical artery Doppler waveform has positive In there is or reversed In there is a of The survival rate in sFGR is greater than 90% mortality rates of up to sFGR is associated with a high risk of IUD of the twin preterm delivery with associated risk of if the twin of either twin in up to and risk of in up to of cases prior to sFGR is associated with a risk of death of the fetus, which is in cases in which ultrasound features have been There is also a high to associated rate of in the larger (EVIDENCE LEVEL: 2++). In dichorionic twin pregnancy complicated by the of delivery should be determined based on a assessment and according to the of the by and neonatal As these twins have separate the pregnancy can be as in singleton pregnancy, for of umbilical and DV Doppler, and of pregnancies should be in with the relevant There is limited evidence to the management of monochorionic twins by Options include: management by early or cord occlusion of the twin order to the (EVIDENCE LEVEL: In monochorionic twin pregnancy complicated by fetal growth should be assessed at every 2 weeks, and fetal Doppler artery and at If the umbilical artery Doppler is assessment of the DV blood should be The in these pregnancies is to the pregnancy at is while at the same time single IUD with its associated consequences for the In dichorionic twin pregnancy complicated by follow-up be less as delivery is not recommended