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ISUOG Practice Guidelines (updated): role of ultrasound in twin pregnancy

2025; Wiley; Linguagem: Inglês

10.1002/uog.29166

1469-0705

A. Khalil, Alexandros Sotiriadis, Ahmet Baschat, A. Bhide, E. Gratacós, Kurt Hecher, Liesbeth Lewi, Laurence Salomon, B. Thilaganathan, Y. Ville,

Ectopic Pregnancy Diagnosis and Management

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 the 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 has increased over the years, mainly due to delayed childbirth and advanced maternal age at conception and the resultant widespread use of assisted reproduction techniques1. In addition to often involving the transfer of more than one embryo, in-vitro fertilization increases the frequency of monozygotic twinning2. The twin birth rate was reported to have increased in the USA by just under 70% between 1980 (19 per 1000 live births) and 2020 (31 per 1000 live births)3, though other reports demonstrated a decline in the twin birth between 2014 and 2018 in both the USA and UK4. Twin pregnancy is associated with a high risk of perinatal mortality and morbidity5-8. There is also an increased risk of maternal complications, such as hypertensive disorders of pregnancy9. In 2019, the stillbirth rate was 7.6 per 1000 twin births compared with 3.8 per 1000 singleton births10. Preterm birth prior to 37 weeks' gestation occurs in up to 60% of multiple pregnancies, while the risk of very preterm birth prior to 32 weeks is 10 times higher in twin compared with singleton pregnancies (10% vs 1%), contributing to the increased risk of neonatal mortality and long-term morbidity11-14. Compared with singleton pregnancies, twin pregnancies are at increased risk of iatrogenic preterm birth due to the greater incidence of maternal and fetal complications. This risk is significantly higher in monochorionic compared with dichorionic pregnancy5-8. Yet, multiple pregnancies are often excluded from research studies, with only 8% of trials on fetal growth restriction (FGR), 17% of those on pre-eclampsia and 2% of those on diabetes including multiple pregnancies15. Moreover, the majority of recommendations in national and international guidelines for the management of multiple pregnancy lack high-quality robust supporting evidence16. Ultrasound assessment of chorionicity, 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 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 pregnancies 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, TRAP sequence, growth abnormalities and the risk of 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 (RCTs), systematic reviews and meta-analyses, and a search of MEDLINE from 1966 to 2022 was carried out. The date of the last search was 31 December 2022. In addition, relevant conference proceedings and abstracts were searched. Databases were searched using the relevant MeSH terms, including all subheadings. 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' and '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 recommendation and levels of evidence used in these Guidelines are given in Appendix 1. The most common practice for dating twin pregnancies is to use the CRL of the larger twin in the first trimester. Some studies have recommended the use of the smaller CRL or the mean CRL, which takes into account both fetuses17-20, as studies of pregnancies conceived via assisted reproductive technology have shown that the CRL of the smaller twin correlates best with the known gestational age. The disadvantage of using the smaller CRL is the potential for the operator to believe that, in CRL-discordant pairs, the larger twin is large-for-gestational age, therefore being falsely reassured that the smaller twin is growing appropriately. One study showed that using the larger CRL did not increase the proportion of neonates classified as small-for-gestational age (SGA)20. Recommending the use of the smaller CRL would entail a significant change in practice. Generally, it would alter the due date by only a few days, and it is uncertain whether this would result in any improvement in clinical outcomes. Therefore, pending further evidence to inform this question, the recommendation is to continue with the current practice of using the CRL of the larger twin to date twin pregnancies in the first trimester. If the woman presents after 14 weeks' gestation, the head circumference of the larger twin should be used to date the pregnancy. Every effort should be made to determine the chorionicity of a twin pregnancy. Chorionicity should be determined before 13 + 6 weeks of gestation using the ultrasound features of the intertwin septum (Figure 1). It is important to examine the entire intertwin septum carefully. In dichorionic diamniotic (DCDA) 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' or 'twin peak sign', compared with only two thin amniotic layers separating the two fetuses in monochorionic diamniotic (MCDA) twin pregnancy (T-sign or empty lambda 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 whether the fetal sex is discordant. 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 anastomoses21. Conversely, approximately 5% of apparently monochorionic twins were reported to be dizygotic in a Danish series22, and this phenomenon is more common in conceptions after assisted reproduction23. It is likely that using a combination of ultrasound features, rather than a single feature, 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 safest to classify the pregnancy as monochorionic1 (EVIDENCE LEVEL: 3). In monochorionic twin pregnancies, amnionicity (i.e. whether or not the twins share the same amniotic sac) can be determined from 8 weeks onwards, when the amniotic sac becomes visible on ultrasound scan. 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). Pseudo- or partial monoamnionicity is a term used to describe MCDA twin pregnancy in which the intertwin membrane has ruptured spontaneously. The term iatrogenic monoamnionicity is used when the intertwin septum in MCDA twin pregnancy is disrupted as a complication of amniocentesis or other invasive fetal procedure24, 25. All MCMA twin pregnancies should be referred to a tertiary center with expertise in their management1. It is recommended that an ultrasound image of the intertwin septum demonstrating the chorionicity is stored electronically and that a hard copy is added to the medical records. As determination of chorionicity and amnionicity is most accurate in the first trimester, when the amnion and chorion have not yet fused, the first-trimester scan is paramount in twin pregnancy (EVIDENCE LEVEL: 4). It is important to follow a reliable, consistent strategy for antenatal twin labeling. Options include: labeling according to their site, either right and left, or lower and upper; 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. Categorical information, i.e. different sex or discordance for structural anomalies, can also be used when present, as they are not likely to change with advancing gestation. This information should be documented clearly in the woman's notes in order to ensure consistent labeling during follow-up scans26. Overall, 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 (or not possible) in MCMA twin pregnancy, particularly in the absence of discordance. 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, particularly if the mode of delivery is Cesarean section27. It is important to alert parents and healthcare professionals attending the birth to this fact, especially in pregnancies in which the twins are discordant for structural abnormalities that are not obvious on external examination, for example 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 an 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 an uncomplicated monochorionic twin pregnancy, an ultrasound scan should be performed in the first trimester, followed by scans every 2 weeks from 16 weeks onwards, as timely detection of TTTS has been shown to improve perinatal outcome (Figure 3)28, 29 (EVIDENCE LEVEL: 4). Currently, the optimal gestational age for delivery of uncomplicated dichorionic twins is considered to be between 37 + 0 and 37 + 6 weeks, and that for uncomplicated monochorionic twins between 36 + 0 and 36 + 6 weeks, as prolongation of pregnancy beyond this stage may increase the risk of perinatal mortality30. At each ultrasound assessment, the following should be evaluated: fetal biometry, amniotic fluid volume and umbilical artery (UA) Doppler (the latter from 20 weeks' gestation in monochorionic and from 24 weeks' gestation in dichorionic twin pregnancies) for both twins. Discordance in estimated fetal weight (EFW) should be calculated and documented at each scan from 20 weeks onwards. In monochorionic twin pregnancy, middle cerebral artery (MCA) peak systolic velocity (PSV) should be recorded from 20 weeks onwards, in order to screen for TAPS. In MCDA twins, the amniotic fluid volume (deepest vertical pocket (DVP)) should be assessed and documented at each ultrasound scan, to screen for TTTS. 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 free β-hCG and PAPP-A levels1. An alternative is the combination of maternal age and the NT recorded between 11 + 0 and 13 + 6 weeks of gestation, depending on the clinical context and/or healthcare setting. The phenomenon of a vanishing twin occurs in around one in five of all twin pregnancies and is more common in those conceived via assisted reproductive technology31, 32. In a retrospective study comparing maternal serum free β-hCG and PAPP-A levels at 11–13 weeks' gestation in dichorionic pregnancies with a vanishing twin (an empty gestational sac or a dead embryo) with those in normal singleton pregnancies matched for method of conception and gestational age at examination, the levels of maternal serum free β-hCG were similar, while the PAPP-A levels were higher33. Using a modeling approach, similar performance of screening for trisomy 21 could be achieved in pregnancies with, compared to those without, a vanishing twin, provided that appropriate adjustments were made to the level of PAPP-A to account for the interval between embryonic demise and blood sampling. The researchers proposed that screening in twin pregnancies with a vanishing twin could potentially rely on a combination of maternal age, NT measurement and serum free β-hCG, as in singleton pregnancy, without the use of serum PAPP-A, and that maternal serum PAPP-A level could be included only after appropriate adjustment for the interval between embryonic demise and blood sampling33. Prospective validation of this approach is needed before its routine implementation in clinical practice. The risk of trisomy 21 in monochorionic and thus monozygotic twin pregnancy is calculated per pregnancy based on the average risk of both fetuses, whereas in dichorionic twin pregnancy the risk is calculated per fetus, because around 90% are dizygotic. It has been assumed previously that monochorionic twins would have the same chance of having Down syndrome as singletons, and dichorionic twins would have double the risk of at least one twin being affected34. However, this does not appear to be the case. It has been found that the observed-to-expected ratio of Down syndrome in twins is lower than that in singletons: 33.6% for monozygotic, 75.2% for dizygotic and 70.0% for all twins35, 36 (EVIDENCE LEVEL: 2++). The DR of the combined first-trimester test for Down syndrome may be lower in twin compared with singleton pregnancy1. However, a 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%)37 (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 may carry a greater risk in twins38-40. A meta-analysis showed that the overall procedure-related loss rate following chorionic villus sampling (CVS) in twin pregnancy was 3.8%, and following amniocentesis it was 3.1%38. Other reports have cited lower loss rates: 2% following CVS and 1.5–2% following amniocentesis41. The risk was found to be similar for transabdominal vs transcervical approaches, use of a single-needle vs double-needle system, and single vs double uterine entry23, and may be attributable more to background risk factors rather than to the procedure itself42, 43 (See also 'Invasive prenatal diagnosis in twin pregnancy' section, below.) (EVIDENCE LEVEL: 2++). Screening and diagnostic testing for trisomies 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 in advance women and their partners regarding 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. NIPT of fetal cfDNA in maternal blood for risk assessment for fetal trisomy 21 is now commonly used 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 test44. In singletons, NIPT has a DR of > 99% for trisomy 21, with a FPR of 0.04%45. Several factors can affect the use of NIPT in twin pregnancy. First, in dichorionic twins, aneuploidy is usually discordant; if the normal twin contributes a greater fetal fraction to the cfDNA in the maternal blood, this can lead to a false-negative result46, 47. Second, NIPT has a higher failure rate in twin pregnancy, with dichorionicity, conception by in-vitro fertilization and greater maternal weight having been identified as significant predictors of failure of NIPT46, 48. Third, single-twin demise can render unreliable the results of NIPT. These early deaths are more likely to occur in an aneuploid fetus, and this can lead to unreliable results due to the continued release of cfDNA from the demised twin into the maternal circulation49, 50. Several studies have investigated the performance of NIPT in twin pregnancy. For trisomy 21, the reported DR ranges from 94% to 100%, with a failure rate of 2.9% to 9.4%45-47, 51. For trisomies 18 and 13, the DR was 60% in twins47, compared with 97.9% and 99%, respectively, in singletons45. A recent study that recruited over 1000 twin pregnancies concluded that NIPT using cfDNA testing is the most accurate screening test for trisomy 21 in twin pregnancy, with a DR of 100% and a FPR of 0%, and a low failure rate of 0.3% (lower than that reported in other studies)52. However, the performance of this test for trisomies 18 and 13 was less accurate52. An updated meta-analysis on this topic included 137 twin pregnancies with trisomy 21, 50 with trisomy 18 and 11 with trisomy 13, and over 7500 twin pregnancies unaffected by these three trisomies53. The pooled weighted DR and FPR for trisomy 21 were 99.0% and 0.02%, respectively; the equivalent figures for trisomy 18 were 93% and 0.01%, respectively, and those for trisomy 13 were 95% and 0.10%, respectively. In summary, NIPT using cfDNA is the most accurate screening test for trisomies in twin pregnancy. Nevertheless, the number of reported cases of a trisomy in twin pregnancy diagnosed using cfDNA testing remains low, and further evidence is needed (EVIDENCE LEVEL: 2++). When invasive testing for chromosomal or genetic analysis of twins is indicated or desired, it should be carried out by a fetal medicine expert. CVS is preferred in dichorionic twin pregnancy because it can be performed earlier than amniocentesis. Earlier diagnosis of any aneuploidy is particularly important in dichorionic twin pregnancy, given the lower risk of selective termination in the first compared with the second trimester54, 55. 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 pairs56. 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 twin57, 58. When monochorionic twins are discordant for an abnormality, prior to invasive testing a discussion should take place regarding the complexity of selective termination, should this become necessary58 (EVIDENCE LEVEL: 3). A 2012 meta-analysis38 of amniocentesis in twin pregnancies reported a pooled 3.07% pregnancy loss rate, and a 2.54% loss rate before 24 weeks; for case–control studies, the pooled loss rates for twin pregnancies undergoing amniocentesis and for control twins were 2.59% vs 1.53% (relative risk, 1.81 (95% CI, 1.02–3.19)). No difference was found between single vs double uterine entry (EVIDENCE LEVEL: 2+). The same meta-analysis38, albeit with limited data for CVS, reported a pooled loss rate of 3.84% after CVS in twins. There were no significant differences between the transabdominal and transcervical approach, use of a single-needle system vs a double-needle system, or single uterine entry vs double uterine entry (EVIDENCE LEVEL: 2+). No significant differences in loss rates have been reported between CVS and amniocentesis in retrospective studies comparing the two methods. A study including twin pregnancy data from the years 1984–1990 reported a 3.2% loss rate after CVS vs 2.9% after amniocentesis59 (EVIDENCE LEVEL 2+). A more recent study found a non-significant difference, reporting loss rates of 3.85% and 4.0% after CVS and amniocentesis, respectively60 (EVIDENCE LEVEL: 2+). There are insufficient data to compare the loss rate related to CVS with the background risk in twins. A meta-analysis published in 202061 compared directly outcomes between women with twin pregnancy undergoing amniocentesis and those not undergoing amniocentesis, and between women undergoing CVS and those not undergoing CVS. It was found that, compared to the background rate of fetal loss, in pregnancies undergoing amniocentesis, there was no significant difference in the rate of fetal loss before 24 weeks of gestation (odds ratio (OR), 1.59; P = 0.06) or within 4 weeks after the procedure (OR, 1.38, P = 0.3). Overall, the pooled rate of fetal loss was 2.4% (95% CI, 1.4–3.6%) in twin pregnancies undergoing amniocentesis compared with 2.4% (95% CI, 0.9–4.6%) in those not undergoing amniocentesis. Similarly, there was no significant difference compared with the background rate in either overall fetal loss (OR, 1.61; P = 0.5) or fetal loss before 24 weeks of gestation (OR, 1.61; P = 0.5) following CVS. Overall, the pooled rate of fetal loss was 2.0% (95% CI, 0.0–6.5%) in twin pregnancies undergoing CVS compared with 1.8% (95% CI, 0.3–4.2%) in those not undergoing CVS. Those undergoing invasive testing may represent a selected population already at increased risk of miscarriage; two recent multicenter studies attempted to control for this while assessing the CVS procedure-related risk of miscarriage in twin pregnancy42, 43. The first study42 used multivariable logistic regression analysis with backward stepwise elimination, adjusting for maternal and pregnancy characteristics, including maternal age, racial origin and weight, method of conception, smoking status, parity, chorionicity, intertwin discordance in CRL, fetal NT ≥ 95th percentile and free β-hCG and PAPP-A multiples of the median (MoM). The authors reported that, after adjustment for maternal and pregnancy characteristics, CVS did not contribute significantly to the risk of fetal loss. They also found no significant association between fetal loss and the number of intrauterine needle insertions or needle size (LEVEL OF EVIDENCE 2++). The second of these studies43, from the same group, assessed the risk of death of at least one fetus in twin pregnancies that had CVS and those that did not, after propensity score matching (1:1 ratio) which created two comparable groups by balancing the maternal and pregnancy characteristics that led to CVS being performed. The authors reported that there was at least one fetal loss in 29 (11.2%) cases in the CVS group and in 35 (13.6%) cases in the matched non-CVS group (OR, 0.81; 95% CI, 0.48–1.35; P = 0.415). However, there was a significant interaction between the risk of fetal loss after CVS and the background risk of fetal loss: when the background risk was higher, the risk of fetal loss after CVS was lower (OR, 0.46; 95% CI, 0.23–0.90), while, in pregnancies with a lower background risk of fetal loss, the risk of fetal loss after CVS was higher (OR 2.45; 95% CI, 0.95–7.13) (LEVEL OF EVIDENCE 2++). In summary, the current evidence suggests that the contribution of amniocentesis or CVS to the risk of fetal loss in twin pregnancy is likely to be small, with procedure-related loss rates of less than 1% (though, paradoxically, the risk might be a little greater in pregnancies at lower background risk of fetal loss). The technique for amniocentesis and CVS in twin pregnancies is described in more detail in the ISUOG Practice Guidelines for invasive procedures for prenatal diagnosis62. In a dichorionic twin pregnancy, sampling of both amniotic sacs is recommended. There is a small (1.8%) risk of sampling the same sac twice with the two-puncture technique (one per sac). Using the single-puncture technique with intertwin membrane passage, the first 1–2 mL of amniotic fluid sampled after intertwin membrane passage should be discarded to avoid contamination from the first twin. If sampling of two sacs is clinically indicated, as in the case of monochorionic twin pregnancy, the two-puncture technique is recommended to avoid iatrogenic monoamnionicity (EVIDENCE LEVEL: 4). When performing CVS, it is recommended to sample the placenta near the cord insertion and to avoid the area around the dividing membrane in order to avoid unreliable or inaccurate results (which have been reported in 3–4% of cases) (EVIDENCE LEVEL: 4). A single-sampling approach around the amniotic equator is a reasonable option in monochorionic twin pregnancy (EVIDENCE LEVEL: 4). Determination of zygosity should be recommended for the laboratory analysis. It is preferred that the same operator performs the invasive diagnosis and the selective termination procedure, if needed, taking into account local protocols and the resources available. 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 poor26, 63-66. NT discordance of 20% had a sensitivity of 52–64%, specificity of 78–80%, positive predictive value of 50% and negative predictive value of 86% for the development of TTTS67, 68. Discordance in NT of ≥ 20% is found in around 25% of monochorionic twin pregnancies, and the risk of early IUD or development of severe TTTS in these cases is more than 30%68. The risk of complications is less than 10% if the NT discordance is <20%68. An abnormal DV (reversed a-wave in at least one of the fetuses) will pick up only 38% of all monochorionic twin pregnancies that will subsequently develop TTTS, and, of those predicted to be at high risk, only 30% will ultimately develop TTTS65. Similarly, although intertwin discordance in CRL at 11–13 weeks' gestation is significantly associated with the risk of pregnancy loss ≥ 24 weeks, birth-weight discordance and preterm birth prior to 34 weeks' gestation, again, the predictive value is poor69, 70. Nevertheless, the management of twin pregnancy with CRL discordance ≥ 10% or NT discordance ≥ 20% should be discussed with a fetal medicine expert in accordance with local guidelines and depending on resource availability, and in these pregnancies there should be detailed ultrasound assessment and possibly testing for aneuploidy if fetal abnormalities are identified. The risk of fetal abnormality was found to be 25% in dichorionic twin pregnancies with CRL discordance ≥ 10%, compared with 4% in pregnancies with CRL discordance < 10%71. Also, 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, 74% for a FPR of 5%)72 (EVIDENCE LEVEL: 2++). At the first-trimester scan (between 11 + 0 and 13 + 6 weeks' gestation), twin fetuses should be assessed for the presence of a