Twin-to-twin transfusion syndrome, also known as TTTS, is a condition that affects many twins in utero. Twin-to-twin transfusion syndrome occurs when there is an unequal blood flow between the two fetuses. It can lead to complications for both twins and has been linked to developmental delays and cerebral palsy in some cases. Twins with this disorder are more likely to be born prematurely than normal twin births.
Brief description of Twin to Twin Transfusion Sydndrome (TTTS)
The cause of Twin to Twin transfusion syndrome is not known. Twin to twin transfusion syndrome is not known to be hereditary or genetic.
Twin to Twin transfusion syndrome (TTTS) can affect identical twin pregnancy where the fetuses share a common placenta (called monochorianic).
Twin to twin transfusion syndrome has a high mortality rate – approximately 60-100% mortality rate.
Sharing a common placenta means that the twin fetuses can begin to share blood circulation. Each fetus uses its own side of the placenta, the placenta blood vessels connecting the twins allow blood to pass from one twin to the other twin. Depending on the amount of blood vessels connecting them, this can mean that the blood is not shared equally, blood is transferred from “the donor” to the other twin “the recipient”.
The effect of Twin to Twin transfusion syndrome
The donor to have less blood, which reduces the donor twins development and growth, and it affects it urinary output, leading to lower than normal amniotic fluid.
The increased volume of blood to the recipient puts a strain on the twin’s heart which can lead to heart failure. The higher than normal urinary output can also lead to excessive amniotic fluid.
Twin to twin transfusion syndrome in early twin pregnancy (before 26 weeks) can cause both twin fetuses to die or severe disabilities.
Twin to twin transfusion syndrome if happening after 26 weeks can mean that the fetuses have a greater chance of survival without severe disability.
Treatment for Twin to twin transfusion syndrome
Research into twin to twin transfusion syndrome is ongoing and recommended treatments rapidly change.
Speak to your obstetrician for the most up to date twin to twin transfusion treatment information.
One treatment that I came across on the internet (although there is no formal clinical trials supporting the treatment – so you should ask your obstetrician for their view) was that some doctors recommend complete bed rest for mothers of twin pregnancy coupled with high intakes of protein from protein shakes. There is no common agreement for why this might be of benefit. So again consult your obstetrician for their view.
Also sometimes known as ‘FFTS’ (Feto-Fetal Transfusion Syndrome), and as ‘TOPS’ (Twin Oligohydramnios-Polyhydramnios Sequence), TTTS is a disease of identical twin fetuses caused by abnormal connecting blood vessels in the twins’ placenta, resulting in an imbalanced flow of blood from one twin to another. The implications of this are very serious for the survival and health of both twins. Once thought to be extremely rare, TTTS is now believed to affect as many as 1 in 1000 pregnancies.
A useful explanation first about what happens normally following conception. The following paragraph is from the British Medical Association’s booklet entitled “Understanding Pregnancy”.
“Your baby starts to grow from the moment of fertilisation. But its real development begins about 5 days later, when the fertilised egg, now a cluster of over 100 cells,reaches the uterus and becomes embedded in its spongy lining. Fingers from the outer cells of the cluster start to burrow into the lining like roots, linking with the mother’s blood supply. These will form the placenta, which will supply all the nutrients the baby needs and carry away all its waste products. Some of these outer cells develop into the umbilical cord, a rope of blood vessels which link the baby to the placenta, and others form membranes which protect the baby.”
According to research figures, up to a third of twin & multiple pregnancies involve identical (correctly known as ‘monozygotic’) twins. Two-thirds of these share the same placenta, and TTTS affects from 5-25% of these. Monozygotic twin pregnancies occur when one group of developing cells (known as a ‘blastocyst’), from one fertilised egg, splits shortly after conception to create two identical embryos. In monozygotic twins, it is believed that the later the egg splits the greater the chance of conditions such as TTTS. Nobody quite knows why an egg/blastocyst splits to make monozygotic twins or understands the factors influencing the timing of the splitting. It is also not fully understood why some develop TTTS.
In Chapter 15 – ‘Multiple Pregnancy’ in ‘Dewhurst’s Textbook of Obstetrics & Gyneacology’, Professor Nicholas Fisk of Queen Charlotte’s & Chelsea hospital in London describes three placental configurations for identical twins. He states that if the splitting occurs within 3 days of fertilisation, the twins will have seperate placentas with around half of these appearing to be ‘fused placentas’ because they are so close together. If splitting occurs between 4-7 days the twins will share a single placenta and each a separate amniotic sac. After 7 days the twins will have a shared placenta and a shared amniotic sac. Professor Kypros Nicolaides of The Harris Birthright Centre in London adds in his document ‘Management of severe twin to twin transfusion syndrome’ that splitting after 12 days results in cojoined or ‘siamese’ twins.
In twins that share a common placenta (known as ‘monochorionic’ twins), blood vessels within the shared placenta commonly form a “link” between the developing babies. In most cases of monozygotic twins sharing the same placenta these joined vessels can include artery-to-artery, vein-to-vein, and artery-to-vein connections. One theory is that usually these connections balance each other out and cause no ill effect.
In TTTS cases, however, it is believed that the joined vessels are imbalanced or are caused to become imbalanced. Essentially blood from the “donor” twin is transfused through the placenta into the “recipient” twin. The fetuses themselves are normal, the abnormality is in the placenta.
Several theories have been proposed over the years for the pathological causes of the condition.
TTTS can kick in at any time during the pregnancy, often as early as 4-5 months. TTTS in its worst form,”Chronic TTTS”, occurs well before delivery when the babies are too immature to be delivered and cared for effectively. On the other hand “Acute TTTS” can occur later right up to or during delivery, sometimes causing death or handicaps in the surviving infants.
Acute TTTS can occur in any case of monochorionic twins, who may not have shown any of the clinical symptoms of Chronic TTTS through the pregnancy. The pressures invoked by normal delivery can cause a mass transfusion of blood from one twin to another. Experienced hospitals can combat this by monitoring fetal heart rates during delivery for signs of Acute TTTS. If it is detected, an emergency C-Section will usually be offered.
Chronic TTTS can bring several difficulties.
The recipient twin (often larger) becomes effectively overloaded with the extra blood supply. His or her heart has to work harder to pump the enriched blood around, which can result in heart failure. The recipient also produces far too much amniotic fluid – termed “polyhydramnios”, which causes the mother to appear far further on in the pregnancy than she actually is. This excess fluid is not only extremely uncomfortable for the mother, but can often bring about an early delivery due to cervical pressure and ruptured membranes, and by directly stretching and stimulating the uterine muscles to contract. The recipient twin may also develop hydrops or edema (retained fluid) within his or her body, which in turn can lead to respiratory, digestive, heart, or brain defects.
The donor twin (often smaller) becomes anaemic due to not having enough blood supply, and usually has a small amniotic sac (the bag of fluid in which the baby lives). This lack of amniotic fluid is termed “oligohydramnios”. The sac is often very close to the developing baby’s body, and the baby appears to be almost shrinkwrapped and “stuck” up against the wall of the uterus. When donor babies survive birth, however, they are often the baby that is stronger as their hearts have not had to work so intensely during pregnancy.
If left untreated, TTTS has a mortality rate of over 80% and can be the root cause of severe handicaps for the few survivors..
How is Antenatal TTTS diagnosed?
The mother may well experience the following symptoms from early on and throughout a TTTS pregnancy: Premature contractions, Rapidly expanding tummy, Rapid weight gain, Breathlessness, Tightness of tummy, Incredible pressure on stomach.
The single most important fact that needs to be determined early in a twin pregnancy is whether the twins are monochorionic (sharing the same placenta) or dichorionic.
If monozygotic monochorionic twins are diagnosed ultrasound scans should be performed at regular intervals (weekly, fortnightly, or monthly) by a fetal medicine specialist in an attempt to determine whether or not TTTS is likely to develop.
The onset of TTTS is detected through ultrasound scan, (sonogram), at a local maternity hospital. The tell-tale signs are often different-sized babies, different-sized bladders, and too little fluid in one sac and too much in the other. A special type of scan known as a ‘colour doppler flow’ may also be performed at some hospitals – this can actually track blood flow through the placenta and umbilical cords to better diagnose the condition. An experienced sonographer, radiologist or fetal medicine specialist with the correct equipment may be able to confirm whether or not twins are identical as early as 12-14 weeks. Later on in the pregnancy it may be more difficult to detect a clear image of the separating membranes and the single placenta. Most maternity hospitals are able to diagnose or at least suspect TTTS, but may be unclear as to available treatment. This is understandable as the treatments for TTTS have not been well publicised within the medical profession up till now.
Professor Geoffrey Machin from the Department of Pathology, Permanente Medical Group, Oakland, California, has worked on twin pregnancy problems in Britain, Canada, and the USA. He has written several papers and textbook chapters on particular problems of monochorionic twins.
Professor Machin writes:
“Although the ultrasound diagnosis of well-advanced antenatal TTTS can be made, it is often already too late to plan and carry out treatment that can be fully effective…
If necessary, expectant parents of twins should insist, from earliest stage of pregnancy, that the chorion status of the fetuses be determined accurately, and that they must be given this information.”
Additional and more specific information is available for professionals on the diagnosis of TTTS. Call for details of our publications.
Once TTTS is suspected, it is crucial that the mother is referred to a specialist fetal medicine consultant immediately. Most hospitals will be able to diagnose TTTS at ultrasound scan, but some are not aware of treatments available.
Treatments available are as follows:
Only a few years ago, treatment for TTTS was rare and at best experimental. Many infant fatalities were never diagnosed as TTTS and simply put down to miscarriage. Further to investigation in recent years throughout the world, however, several types of treatment for the condition are now available – all with very positive results.
A mother’s choice of treatment will depend on many things including the exact condition of the twins and her proximity to a treatment centre. Do remember that treatment needs to be a “team effort”, often including the GP, local hospital, treatment centre, as well as family and friends.
Delivery options will be recommended by the specialist in charge.
At twin-2-twin we cannot advise on any particular kind of treatment, that is for the patient to decide for themselves along with their specialist consultant. We can help, however, by providing the latest details on all treatments and where they are available in the UK and abroad.
We are fortunate in the UK to have resident several world-leading specialists on fetal conditions such as TTTS, and many hard-working and understanding consultants at Fetal Medicine Centres. Research into the condition is currently a high priority within the medical profession worldwide and is beginning to attract wider public interest.
This involves the draining of excess amniotic fluid from the sac of the recipient (larger) twin. The process usually takes about an hour, with a varying amount of fluid being removed – often up to 2.5 litres or more in order to return the level of amniotic fluid to normal. This has the immediate effect of giving more space to the smaller (stuck) twin, can stabilise the larger twin, greatly reduces maternal discomfort associated with carrying excess fluid, and can allow the pregnancy to continue more safely by reducing the risk of premature labour. Many specialists prefer an “aggressive amnioreduction” procedure, which simply means taking even more fluid.
More than one drain is often required, as is constant monitoring of the mother. Some hospitals prefer the mother to remain in hospital during the treatment, others will allow the mother home the day after treatment for bedrest.
Overall, the success rates for amnioreduction therapy are positive, with approximately 44% of pregnancies producing two live infants, and 66% producing one. Obviously figures will differ from country to country and between treatment centres. This procedure is performed at well over a dozen specialist centres in the UK, with much research having been performed by Professor Nicholas Fisk and colleagues at Queen Charlotte’s & Chelsea Hospital in London.
This treatment is either undertaken in conjunction with amnioreduction, or is performed as a single procedure. It involves the creation of a small hole in the twins’ intervening amniotic membranes with the amnioreduction needle. This technique was introduced by Dr. George Saade and associates in America.The hole allows the two amniotic sacs to equalise their fluid levels, and early research findings have been positive. Many centres in the UK now perform this treatment.
Pioneered in the USA by Dr. Julian De Lia and associates, and researched in the UK at The Harris Birthright Research Centre by Prof. Kypros Nicolaides, and recently at St. George’s Medical Centre, London, by Dr. Yves Ville (now in Paris). Laser Treatment is the only one which attempts to rectify the source of the problem, ie) the co-joined vessels in the placenta.
During the procedure an endoscope is passed through the tummy into the sac of the recipient twin.The fetoscope and laser are then passed down the endoscope. Using ultrasound and direct video guidance, the laser is used to selectively coagulate or break the joined vessels, often reversing the effects of the syndrome. This is a one-treatment procedure followed by regular monitoring.
Laser treatment has also been shown to help if one twin has died in utero or has a very poor outlook. By sealing the vessels that connect the twins it can prevent a survivor from transfusing its blood to the dead twin.
Most human organs when approached surgically are very similar from one person to the next. The placenta, however, can vary greatly from the location in the uterus, to size, appearance and the number of cord insertions. Suitability for laser procedure can depend on some of these factors.
This treatment involves causing the deliberate demise of one fetus, in the hope of providing a better chance to the other. This is not as callous as it sounds, as sometimes in severe cases it is considered as the only option to prevent the loss of both twins.
One or two drugs have been tried to reduce the urine output of the recipient twin and therefore reduce polyhydramnios (excess amniotic fluid), but do not seem to have proved popular. Some of the latest research concerns the use of high frequency ultrasound therapy (similar to that used to treat kidney stones) on the placenta. More details on this as we have them.
Being treated for TTTS can be an emotional time and some parents know mentally they could not cope with the uncertain outcome and do opt for a termination.
Many parents do beat the tremendous odds stacked against them and their unborn babies and it sometimes takes them a while to appreciate just how fortunate they have been.
Because it has not been possible to adequately compare the different methods, research has been started both for septostomy (coordinated by Dr Kenneth Moise from Baylor), and for laser (coordinated within the Eurofetus research project by Dr Jan Deprest, Leuven, Belgium). A European-wide controlled randomised study of treatment, comparing amniodrainage against laser fetoscopy is about to begin.
Being diagnosed with TTTS can be the beginning of an emotional and confusing time. Many parents go through diagnosis and treatment and end up with healthy twins. It would be wonderful, of course, if this could happen in every single case, but sadly it does not.
Each case of TTTS can be different, and as your consultant will state, there are no guarantees of success when you agree to undergo treatment. But with no treatment around 80% of pregnancies lose both babies.
Sometimes a course of treatment can appear to be progressing well, only for additional problems to manifest themselves.
Your consultant will be available to answer any questions you may have during your treatment, and he or she should be your first contact for any concerns.
Some Common Questions…
My hospital failed to diagnose the condition, what can I do?
At twin-2-twin, we are attempting to rectify this common complaint and ensure that all maternity hospitals are aware of the condition and how to diagnose it. Every hospital has the equipment to suspect a problem and if they have doubts then should refer you to a fetal medicine specialist. Any hospital can instigate an easy protocol to ensure that no cases are missed, and all should do so. If your case of TTTS was missed, then you have the option of making a complaint to your hospital to ensure that future cases are dealt with correctly. We are available to assist you with this procedure.
My hospital diagnosed the condition, but said that no treatment was available, what can I do?
Again, this is all too common, and frankly there is no excuse for it. All parents with TTTS should be given the option to undergo treatment and be told where different treatments are available. Your hospital needs to be told that treatment is available, and where you can be referred.
Which treatment should I have?
This is often determined by where you live or which treatment centre you attend. It can also depend on the condition of your babies. Some offer one treatment only, others offer more. Your consultant will be able to advise on alternative treatments, and will be able to refer you if that is your wish.
I am unhappy with my treatment, what can I do?
You should first voice any concerns with your consultant directly. If you are uncomfortable with the thought of doing this, then you can ask a family member, friend, or your GP to do it for you. Everybody has the right to a second opinion, and any hospital or treatment centre will be able to arrange this if you request it. Remember, however, that time is often of the essence when treating TTTS.
I have a serious complaint against a hospital, what can I do?
Each hospital has a procedure for dealing with complaints, and information will be made available to you about this. Most claims for medical negligence are not successful, and a long drawn out legal process is often not the best way to overcome grief. Questions, however, often need to be answered concerning mistakes you think may have been made. If you need further advice, on the correct way to approach your treatment centre, please contact us, or one of the organisations below.
Other organisations that have excellent advice and support facilities to offer.
You may contact TAMBA, or SANDS, all on our links page.