Management of Monochorionic Twin Pregnancy Green-Top Guideline No. 51 (2024 Partial Update)

Abstract

This guideline provides evidence-based recommendations and advice on best practices for the clinical care of monochorionic twin (and much rarer higher order) pregnancies. The use of ultrasound to determine chorionicity and amnionicity is key to the management of multiple pregnancies and the interpretation of potential risks to the fetuses. This guideline will outline the best evidence to guide clinical care, including fetal surveillance, the screening for, and treatment of complications associated with monochorionic multiple pregnancy. It is important to emphasise that this guideline is focused on the management of monochorionic multiple pregnancies rather than all multiple pregnancies.

It is also recognised that women carrying a monochorionic pregnancy (most commonly twins) may have concerns and anxieties surrounding their pregnancy. This requires accurate and evidence-based information given in a sensitive manner by healthcare professionals and supported by a multidisciplinary team, ideally within a multiple-pregnancy clinic [1, 2]. In the UK, support is also often given in conjunction with the Twins Trust (formally the Twins And Multiple Births Association [TAMBA]) and The Multiple Births Foundation.

A monochorionic pregnancy is a multiple pregnancy, most commonly a twin pregnancy (99% of cases), in which babies are dependent on a single, shared placenta and where there are placental anastomoses conjoining the fetal circulations. Approximately 20% of twin pregnancies in the UK are monochorionic. Monochorionic placentation can also occur in rarer, higher-order multiples, especially triplets (i.e., dichorionic or monochorionic triplets).

There has been an increase in all types of multiple pregnancies with the use of assisted reproductive technology and the choice of individuals to defer pregnancy to a later maternal age (especially pronounced in high/middle-income countries). Although the rates of twining and higher order pregnancies are increased in people of Nigerian ethnicity, the rate of monochorioncity is not significantly increased in this group. Assisted reproductive technology increases the prevalence of both dichorionic and monochorionic twinning. However, using day 5 blastocyst transfers seems to be associated with a significantly higher rate of monozygotic twinning compared with cleavage stage day 3 transfers (adjusted OR 2.04, 95% CI 1.29–4.48) [3-5].

All multiple pregnancies have increased risks of preterm birth, fetal growth restriction (FGR), pre-eclampsia, postpartum haemorrhage, and additional postnatal potentially morbid complications, such as infant feeding difficulties and adverse puerperal mood change [1, 2, 6, 7]. These complications are not addressed further in this guideline as they are not specific to monochorionic placentation.

The challenges of monochorionic pregnancies arise from the single, shared placenta and placental vascular anastomoses that are almost universal and connect the fetal circulations of both twins, rather than monozygosity itself.

Specific complications associated with inter-twin vascular anastomoses are listed in Table 1. Please note that there may occasionally be some challenging diagnostic and clinical overlaps among the definition of these potentially pathologic conditions (e.g., twin-to-twin transfusion syndrome [TTTS] and selective growth restriction [sGR] with reduced liquor around the smaller twin—see section 6.4.3).

Single intrauterine death, although not exclusive to monochorionic twin pregnancy, is more common and has potentially significant morbid consequences for the co-twin, in the form of brain damage (if it survives).

In addition, the consequences of single fetal death and the management of discordant fetal anomalies (i.e., structural and chromosomal anomalies) in monochorionic twins and higher-order pregnancies are important (and are discussed in more detail later in this document).

Monochorionic diamniotic (MCDA) twin pregnancies carry a higher risk of overall fetal and perinatal loss compared with dichorionic pregnancies due to the conjoining of the fetal circulations within the single placenta. Monochorionic monoamniotic (MCMA) pregnancies, where both twins are in a single amniotic sac (1% of monochorionic twins), are associated with an even higher risk of fetal/perinatal loss, most commonly before 24⁺⁰ weeks of gestation (due to discordant fetal anomalies or associated Twin Reverse Arterial Perfusion [TRAP] syndrome). These monochorionic twins though, carry a significant excess risk throughout a pregnancy (even compared to MCDA twins) [1, 2, 6, 8-11].

All monochorionic placentas contain vascular anastomoses running between the two fetal umbilical cords within and on the surface of the placenta. There are of three types: (i) arterial–arterial; (ii) arterial–venous; and (iii) venous–venous. In many cases, the anastomoses are bidirectional (which rarely lead to haemodynamic imbalance between the fetal circulations) but still conjoins the fetal circulations, a situation associated with excess, sudden fetal death (of one or both twins) [12-14].

In TTTS, which complicates between 15%–20% of monochorionic pregnancies [6, 11], the placenta has a predominance of unidirectional, arterial–venous anastomoses. This may predispose to, and cause, a haemodynamic imbalance within the fetal circulations, adversely affecting fetal cardiac function, fetoplacental perfusion and causing secondary, fetal endocrine dysfunction [15, 16].

Postnatal placental perfusion studies have noted unequal placental ‘territories’ shared by the fetuses with associated marginal or ‘velamentous’ cord insertions. Such findings are common both in TTTS and sGR (which is present in 60% of TTTS cases) complicated monochorionic twin pregnancies [13, 17-19].

Very rarely, TTTS complicates MCMA twin pregnancies, as well as dichorionic and monochorionic triplet pregnancies [17, 20].

Twin Anaemia Polycythaemia Sequence (TAPS) is an important and potentially morbid association in monochorionic pregnancies. Spontaneous TAPS is relatively uncommon (~2%) in apparently uncomplicated monochorionic pregnancies (most commonly MCDA twins). However, if it occurs it is associated with a high risk of perinatal morbidity and mortality with the donor fetus particularly at risk [21]. It may complicate TTTS, occurring in up to 13% of cases post-treatment by fetoscopic laser ablation (if the SOLOMON technique is not used) [22]. If TAPS is suspected, then discordance of liquor volumes (measured by ultrasound) in the fetal amniotic sacs must be excluded, as if present would indicate a recurrence of TTTS (most often due to treatment failure).

The pathogenesis of TAPS is evidenced through postnatal placental injection studies demonstrating ‘minuscule’ artery–vein anastomoses (less than 1 mm) allowing the relatively slow transfusion of blood from the donor to the recipient. This may be associated postnatally with highly discordant haemoglobin levels (80 g/L or greater) between fetuses, with a measured reticulocyte count ratio > 1.7 [22-25].

Significant intrauterine fetal size discordance in monochorionic twins (difference in estimated fetal weight [EFW] of greater than 20% and the smaller twin with EFW or abdominal circumference (AC) on ultrasound of < 10th centile for gestation) is associated with marginally increased perinatal risk but is an indication for increased antenatal surveillance, often with ultrasound scans and Doppler measurements more frequently than every 2 weeks [2].

When the selective fetal discordance is greater than 25%, it is termed ‘selective growth restriction’ (sGR)(see Table 1) [2], and complicates 20% of monochorionic twins, in the absence of TTTS. It is also present in up to 60% of monochorionic twins complicated by TTTS (with associated pathologic discordance in amniotic fluid volumes) [29]. sGR is recognised as a pathological entity associated with a significant rise in twin perinatal mortality, and a significantly differing inter-twin placental territory [18].

A Delphi consensus of expert opinion [26] has defined sGR in monochorionic twins and this is used in this document. It is defined as where the estimated EFW of one fetus is less than 3rd centile OR when two of the following three parameters exist: (i) a growth discordance of greater than 25% difference in EFW between the fetuses; (ii) the smaller fetus having an EFW or AC less than 10th centile for gestation; (iii) abnormal umbilical artery (UA) Doppler of the smaller fetus (UA-PI of greater than 95th centile or shows absent or reversed end-diastolic velocity).

The overall incidence of sGR is often greater than in dichorionic pregnancies. This is because it is often a co-pathology in TTTS [27]. The management of discordant growth and sGR requires experience and close fetal surveillance, by a fetal medicine centre. The ubiquitous placental anastomoses conjoining the fetal circulations make this condition associated with high risks of associated single or double miscarriage and stillbirth rates, if managed conservatively.

It is recognised that because of the aforementioned specific risks associated with monochorioncity, parents may have significant anxieties and concerns, even in uncomplicated pregnancies. Accurate information, presented sensitively, is important to allay unnecessary concerns while imparting to parents the importance of appropriate increased prenatal surveillance [1, 2, 9, 10].

This guideline was developed in accordance with standard methodology for producing Royal College of Obstetricians and Gynaecologists (RCOG) Green-top Guidelines. The Cochrane Library (including the Cochrane Database of Systematic Reviews and the Database of Abstracts of Reviews of Effects [DARE]), EMBASE, Trip, MEDLINE and PubMed (electronic databases) were searched for relevant randomised controlled trials, systematic reviews and meta-analyses. The search was restricted to articles published between 1966 and 2020. The databases were searched using the relevant Medical Subject Headings (MeSH) terms, including all subheadings, and were combined with a keyword search. Search words included ‘monochorionic twin’, ‘TTTS’, ‘twin-twin transfusion syndrome’, ‘TRAP syndrome’, ‘amnioreduction’, ‘laser ablation’, ‘septostomy’, and ‘cord occlusion’ and the search was limited to humans and the English language. The National Library for Health and the National Guideline Clearinghouse were also searched for relevant guidelines and reviews. The most important of these is the 2011 National Institute for Health and Care Excellence (NICE) clinical guideline 129 [1, 9], which was based upon an extensive review of the evidence for the antenatal management of twin and triplet pregnancies. This initial NICE guidance (published in 2011), focused on prenatal care. This was further updated and published in 2019 [2]. This provides additional recent, evidence-based clinical guidance on the management of complications in monochorionic twins and clinical guidance on the intrapartum management of both dichorionic and monochorionic twins.

In addition, qualitative information and lay representation have been provided by the Twins Trust (previously TAMBA) and the Multiple Births Foundation (who had representation on both versions of the NICE Guideline groups).

Where possible, recommendations are based on available evidence. In the absence of published evidence, these have been annotated as ‘good practice points’. Further information about the assessment of evidence and the grading of recommendations may be found in Appendix 1.

Timing for an optimal cut-off for planned preterm birth in laser operated TTTS appears not to have a strong evidence base. However, perinatal mortality after 32 ⁺⁰ appears low (although perinatal morbidity may be unpredictable). In monochorionic twin pregnancies, post-fetoscopic laser ablation the twin pregnancy should be delivered by 36 weeks gestation.

Despite significant improvements in the overall prognosis, fetoscopic laser coagulation for TTTS carries a high risk of postoperative complications such as fetal demise, miscarriage, TAPS and/or recurrence. In most cases, these complications occur shortly after surgery and are therefore expected, if not predictable. The consequence of these complications is an overall reduced survival rate compared to uncomplicated monochorionic pregnancies.

In uncomplicated monochorionic pregnancies, high rates of late stillbirths have prompted a policy of elective preterm birth as early as 32 weeks but in the majority by 36 weeks gestation. Following laser surgery for TTTS, the management and timing of birth may consider two opposite options: (i) that these pregnancies are still at high risk up until late gestation because of possible late unpredictable complications; or (ii) that surgery has reduced the likelihood of such late events and that they could be managed as dichorionic pregnancies.

Optimal management, therefore, involves a balance between the risk of intrauterine adverse events and the consequences of planned preterm birth. Moreover, newborns following TTTS have been shown to carry a higher rate of neurological impairment. Therefore, in the absence of relevant decision-making results, one may favour the reduction of unnecessary preterm births or favour the prevention of potential late unpredictable complications. A retrospective study of 602 consecutive monochorionic twin pregnancies complicated by TTTS who underwent laser ablation therapy in Paris were examined using a cumulative risk model analysis. The results did not identify an optimal cut-off for planned preterm birth in laser-operated TTTS. Perinatal mortality was low after 32 completed weeks of gestation but the study concluded that medical history, clinical findings on ultrasound, parental demand, and clinical expert assessment should fashion the timing of birth between 32⁺⁰ and 36⁺⁰ weeks of gestation [125]. In the UK, most fetal medicine subspecialists would attempt prolongation of gestation until 36⁺⁶ weeks of gestation and manage the pregnancies individually.

In monochorionic twin pregnancies complicated or previously complicated by TAPS, selective growth restriction or single fetal demise, the risk of fetal mortality, prematurity and neonatal death are significantly increased. The aim is to prolong gestation until 36⁺⁶ weeks of gestation. However, the timing and mode of birth are to be individualised taking into account the prospective ultrasound findings (including peripheral and central arterial and venous Doppler velocimetry), fetal growth velocity, and the women's obstetric, medical history and preferences. Again, in the context of birth of monochorionic twins, the role of delayed umbilical cord clamping is controversial because of the theoretical risks of feto-fetal transfusion with ‘intact’ placental anastomoses. At present, there is not sufficient evidence to recommend for or against delayed cord clamping in monochorionic pregnancies.

All ultrasonographers who undertake routine ultrasound scans during pregnancy must be trained to establish chorionicity and the correct labelling of twins. [GPP]

All ultrasonographers who undertake mid-trimester (18 ⁺⁰ –20 ⁺⁶ weeks of gestation) and fetal growth scans of monochorionic twins should be made aware of the appearances of TTTS, sGR and TAPS, and the need to refer women on to specialist centres if such features present. [GPP]

Fetal medicine centres undertaking fetal therapy for relatively rare complications of monochorionic twins should have a minimum of two experienced operators and more than 15 cases per year (rolling 3-year average) to maximise perinatal outcomes and minimise long-term morbidity. [D]

Fetal medicine centres should follow the NHS England Specialised Services Clinical Reference Group for Fetal Medicine recommendations for experience [90]. [Evidence level 4]

MK receives royalties for book sales from Cambridge University Press and Taylor and Francis Publishing; payment for medicolegal expert opinions; and travel and accomodation expenses covered to attend the RCOG Genomics Committee meeting as Chair and biannually for the Fetal Medicine Foundation Congress; he is also a member of the Fetal Committee of the British Society of Genetic Medicine; he also received payment from Illumina-Genomics while working with them from. LB receives royalties for book sales from Cambridge University Press.