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We undertake a number of research projects in relation to twin and multiple pregnancies. Here are some of our most recent studies:
Twin growth charts
Twins are known to be smaller than singleton babies, but up until recent years, routine use of singleton growth charts to plot the growth of twins were still being used. This led to healthy, well-grown twins being misclassified as growth restricted, and often resulted in unnecessary early delivery, exposing these babies to problems of prematurity.
At St George’s, we carried out some large research projects which compared the normal growth of twins to singletons, and have formulated fetal growth charts which are specific to both sharing one placenta (likely to be identical) and those with separate placentas (likely to be non-identical) twins, in order to ensure that the growth of twins were correctly monitored according to their own growth capacity, thereby avoiding unnecessary intervention. This was the first twin-specific growth chart developed in the world, and is now commonly used across many hospitals in the UK.
Twin and multiples Priority Setting Partnership
Multiple pregnancies have been increasing in prevalence over the last 40 years, and are known to carry higher risks of stillbirth, premature birth, cerebral palsy, and risks to the mother. It can also put immense strain on the physical and mental health of the families, as well as pose an economical burden. Current research has however focused mostly on singleton pregnancies.
The Priority Setting Partnership for twins and multiples was therefore created to identify the most important research questions for multiples, with a long-term goal to reduce poor outcomes in multiple births, as well as improve the physical and psychological wellbeing of the families. The process consisted of an initial survey of research questions, collation of the questions and comparing these to existing research, identifying questions which have not been previously answered, prioritising these further in a secondary survey, and finally, identifying the top 10 most important questions in a workshop of parents and healthcare professionals.
This process was overseen by a steering group of experts and parent group leads, and we received an overwhelming response from 1120 people from 31 countries. Having identified the top 10 most important unanswered questions in multiple births, we believe this will provide credible direction for future research in improving the wellbeing of multiples and their families.
Twin-to-twin transfusion syndrome (TTTS)
TTTS is a serious condition that can occur in 10-15% of twins sharing one placenta (identical). In severe cases, it can result in death or handicap in 90% of twins if left untreated. Numerous research projects have been carried out to identify the best therapies and techniques to treat this condition, when the treatments should be performed, and the outcomes of the babies after treatment.
At St George’s, we have carried out research projects to find the best treatment for stage 1 (mild) TTTS, identify the outcomes of babies who share both a placenta and an amniotic sac who develop TTTS, and have established a core set of outcomes to be reported in research for babies following TTTS so that we can compare and improve the value of future research.
Selective fetal growth restriction (sFGR)
sFGR is when one baby is very small, but the other is (often) growing normally. This can occur in identical or non-identical twins, and the cause for this differs between the two types. The smaller twin has a risk of stillbirth if it remains very malnourished, which can have an impact on the other twin (in identical twins), or lead to very early labour. Extensive research has tried to identify the risks involved to the babies, how to diagnose this condition, what treatments are available, and when the best time would be to deliver the babies.
At St George’s, we have developed criteria for accurately diagnosing sFGR, looked into the natural history and outcomes of twins with sFGR depending on diagnostic criteria used, and established a core set of outcomes to be reported in research for babies following sFGR so that we can compare and improve the value of future research.
Twin anaemia polycythaemia sequence (TAPS)
TAPS is an uncommon condition that occurs in identical twins. It results in one twin becoming very anaemic (low blood level), and the other polycythaemic (high blood level). This can occur either on its own, or after laser treatment for TTTS. So far, the best way to treat this condition is still not established, and research is currently underway in order to find this answer.
Due to the rarity of the condition, most research is limited to very small numbers. An international registry has therefore been created that have collected all the cases of TAPS around the world (including cases from our unit), and the outcomes from different methods of treatment established from much larger numbers.
At St George’s, we have also developed criteria for accurately diagnosing TAPS, and have looked into the natural history and outcomes of twins diagnosed with TAPS according to different diagnostic criteria.
Monochorionic monoamniotic twins (MCMA)
This rare type of identical twins not only share a placenta, but also share the same amniotic sac (pocket of fluid). They carry a higher risk of complications, such as miscarriage, stillbirth, fetal anomalies than identical twins, but also have a risk of cord entanglement. Due to the small numbers of these twins, there is insufficient evidence to establish the best way to manage these twins, and that further research is required in this area.
At St George’s, we have collaborated with other centres to produce a larger sample of these twins, in order to analyse their outcomes, complications, as well as the best ways to manage these twins when they are further complicated by selective fetal growth restriction.
Triplets can be non-identical, identical, or mixed chorionicity (e.g. 2 identical and 1 non-identical). They carry higher risks of miscarriage and very early labour than twins, are often smaller than twins, and can also predispose the mother to more risks (pre-eclampsia, bleeding after birth). Identical triplets also carry the risk of TTTS and TAPS. It is now recommended that women pregnant with triplets should be given the option of reducing the pregnancy to twins or a singleton to reduce these risks. Several studies have looked into the outcomes and management of non-identical triplets, but mixed chorionicity and identical triplets are less common.
At St George’s, we have carried out a collaborative study to analyse the outcomes of growth restricted triplets, according to chorionicity (whether or not they are identical). We have also performed several systematic reviews to collate the outcomes of numerous studies looking into perinatal outcomes according to chorionicity, outcomes following laser treatment for TTTS, and miscarriage and preterm birth rates after selective reduction versus no intervention.
Multiple Pregnancy Registry
This is a UK national initiative endorsed by the Royal College of Obstetricians and Gynaecologists (RCOG), British Maternal Fetal Medicine Society (BMFMS) and the Twin and Multiple Births Association (TAMBA). The aims include: • Systematically tracking complicated multiple pregnancies, triplet and uncomplicated monochorionic twin pregnancies to ascertain pregnancy outcomes and address the gaps in knowledge • Improving patient care in clinical practice • Contributing data to quality benchmarking projects, audits and research studies • Facilitating an easier option to meet near future reporting requirements and performance expectations • Establish a platform to allow long-term follow-up of these infants at a national level. The Registry would allow the possibility of following up a large cohort of twins whose pregnancies were complicated, whether they had treatment or not. These long-term data cannot be determined from short-term clinical trials in selected patients. Some of the neurodevelopmental outcomes cannot be assessed in a robust manner during infancy or early childhood, and most of the studies reporting on the neurodevelopmental outcomes have not followed-up these children beyond the age of two years.
Routinely recorded anonymised data related to mutiple pregnancy will be stored on a secured website database (Registry). The inclusion criteria include complicated multiple pregnancies (twin-to-twin transfusion syndrome, selective fetal growth restriction, twin anaemia polycythaemia sequence, twin reversed arterial perfusion, twin discordant anomaly, single intrauterine demise), triplet pregnancies, and uncomplicated Monochorionic twin pregnancies. The exclusion criteria include uncomplicated dichorionic twin pregnancies
The data will be collected by the local team in each centre contributing to the Registry. The team members performing this task hold a valid good clinical practice (GCP) certificate, to ensure their awareness of clinical governance and the Data Protection Act.
Emergency Cerclage in Twin Pregnancies at Imminent Risk of Preterm Birth: an Open-Label Randomised Controlled Trial (ENCIRCLE)
Twin pregnancies are at an increased risk of early delivery. One of the reasons for this may be due to a weakened neck of the womb (cervix). There are 2 main ways to manage a weakened cervix in pregnancy. One option is to do nothing (conservative approach). The other is to strengthen the cervix with a stitch (cerclage) to provide extra support. There is no good quality convincing evidence to suggest which of these has better outcomes for mum and babies in twin pregnancies. This trial aims to determine whether securing the weakened cervix with a cerclage will help to prolong the pregnancy and prevent early delivery. Babies who are born early experience multiple complications including lung, brain and learning difficulties. Therefore, the study will also aim to determine whether prolonging the pregnancy by inserting the cerclage reduces the number of babies affected by these problems. In order to carry out a fair study we aim to perform what is known as a randomised controlled trial. We will include in the trial two major groups: (1) women pregnant with twins, who present with a weakened cervix and no signs of infection between 14 and 26 weeks of pregnancy. This will be diagnosed on an internal examination or ultrasound scan, and (2) women pregnant with identical twins complicated by twin-to-twin transfusion syndrome (TTTS) treated by Laser surgery between 16 and 26 weeks in whom a short cervix (<15mm) is identified. TTTS is rare but potentially devastating condition which occurs in about 10-15% of identical twin pregnancies. If left untreated, 80-90% of these babies will die. Overall, best first-line treatment of TTTS is laser surgery. Cervical length is a strong predictor of preterm delivery in these pregnancies.
Participants will be allocated randomly into the intervention (cerclage) or control (conservative) group. The procedure to insert the cerclage will be performed under an anaesthetic to minimise discomfort and you will be admitted for 2-3 days following the operation to ensure there are no complications or signs of labour. Women in both groups will be followed up in the same manner until they deliver and the pregnancy outcomes will be compared between the 2 groups to determine which management option is best.
Twin pregnancies With complications: Impact on Neurodevelopment Study via Registry Follow up (TWINS-RF)
When identical twins share a placenta (monochorionic) they are at increased risk of neurodevelopmental delay (disability), especially when there are problems in the shared blood supply in the placenta (this includes conditions like twin-to-twin transfusion syndrome, twin anaemia polycythaemia sequence and selective fetal growth restriction).
The incidence of neurodevelopmental delay in the surviving children of these pregnancies and the factors associated with worse long-term neurodevelopmental outcome are yet to be established.
The primary research objective is to establish the incidence of adverse neurodevelopment in normal and complicated monochorionic twin pregnancies. We plan to recruit pregnancies where the delivery occurred at least one year ago.
When possible, the controls will be matched to the gestational age at delivery. When possible, the controls will be matched to the gestational age at delivery of the cases. Eligible women will be identified by research staff from the TAMBA multiple pregnancy registry. All women identified from the registry will be sent an information leaflet about the study and invited to take part. Those who agree to take part will be asked to sign a consent form, will be asked to complete the Age & Stage Questionnaire 3rd edition (ASQ-3) in respect of their child/children. The ASQ-3 is a parent-completed questionnaire which contains 30 developmental items that are divided into five areas: communication, gross motor, fine motor, problem-solving and personal–social.
Twin Reversed Arterial Perfusion Intervention STudy (TRAPIST)
The study main question is whether early intervention (12-14 weeks gestation) improves the survival and the 2-year development of the children compared to late intervention (16-18 weeks gestation) in twin pregnancies complicated by twin reversed arterial perfusion sequence (TRAP).\n TRAP sequence is a complication of a shared circulation in monochorionic twins (share a single placenta), where there is reversed blood flow from the healthy twin (pump twin) towards the abnormal twin. The reverse flow strains the heart of the pump twin and can increase urine output, which can trigger premature birth.\nTRAP is now routinely diagnosed at the 12th week routine ultrasound scan, but treatment has not traditionally been offered until the 16th week. An intervention before that time has been shown with studies of a similar procedure (amniocentesis) to carry a higher risk of membrane rupture and miscarriage. In some cases the reversed blood flow stops by itself, and intervention planned at 16 weeks is not required. However it has also been shown that diagnosis at 12 weeks with treatment delayed until the 16th week is associated with a high pregnancy loss (up to 33%) of the pump twin. Previous studies have also shown that earlier treatment usually results in delivery closer to the expected date of delivery (less risk of prematurity) with improved survival of the baby.\nTo find this out, we need to put people into groups and give each group a different treatment. The results can then be compared to see if one is better than the other. To try to make sure the groups are the same to start with, each patient is put, by a chance using the computer (randomly),.into either the early group, receiving treatment between 12 and 14 weeks or late group, receiving treatment between 16 and 18 weeks.