Introduction

Twin-to-twin transfusion syndrome (TTTS) is a rare but serious condition that occurs in pregnancies involving identical twins who share a single placenta. The condition occurs when abnormal blood vessel connections in the placenta cause a blood flow imbalance between the twins. One twin, known as the "donor," receives insufficient blood, leading to growth restriction and organ underdevelopment. Conversely, the "recipient" twin receives excess blood, which can cause complications such as heart failure and organ enlargement. TTTS can significantly affect neonatal outcomes, including preterm birth, organ damage, and long-term developmental issues. Early detection and intervention are crucial in improving survival rates and minimising long-term disabilities. This article explores the stages of TTTS, its impact on neonatal health, available interventions, and the potential for improved outcomes with timely treatment. By understanding these aspects, we can better address the challenges posed by TTTS and work toward better outcomes for affected twins.

Overview of twin-to-twin transfusion syndrome

Twin-to-twin transfusion syndrome (TTTS) is a rare pregnancy condition that affects identical twins within the uterus. It typically develops around the 15-26 week mark of pregnancy and affects 1-3 out of 10,000 births¹. If left untreated, TTTS significantly increases the risk of death for the twins around birth and the likelihood of long-term disabilities in survivors.

TTTS occurs in identical twins who share a single placenta (monochorionic) but have separate amniotic sacs (diamniotic). The shared placenta has interconnected blood vessels, leading to an imbalance in blood distribution between the twins. One twin (the donor) receives less blood than needed, while the other twin (the recipient) receives too much blood.

TTTS is assessed using the Quintero staging system,² where stage 1 is defined as an imbalance in amniotic fluid and stage 5 is defined as death of one or both twins.³ The system uses ultrasound imaging to measure amniotic fluid levels, assess bladder visibility, evaluate blood flow in vessels and identify structural abnormalities. These measurements help determine the severity of TTTS and appropriate treatment and care. 

Prior to their diagnosis of TTTS, expectant mothers could experience symptoms such as sudden weight gain, swelling and pain.⁴ These symptoms could be similar to those of other pregnancy complications, such as preeclampsia.

Impact of TTTS on neonatal health

Outcomes for donor twins 

The reduced blood volume in the donor twin results in low blood flow to the kidneys. This activates the body’s fluid retention mechanism, leading to reduced urine output (oliguria) and thereby low amniotic fluid levels (oligohydramnios). Insufficient blood and nutrients result in intrauterine growth restriction and underdeveloped organs in the donor twin.⁵ Studies have shown that donor twins in TTTS could also present with anaemia.⁶

Donor twins typically have stable cardiac function, partly due to their reduced blood volume and restricted growth.⁷ However, the ability of the arteries to stretch and extend to accommodate increased blood flow is reduced, which could lead to hypertension and kidney damage in the long term.

The lack of blood flow (renal hypoperfusion) and the inability to filter waste result in the donor twin developing kidney injuries, which could lead to kidney failure ⁸ or chronic kidney disease after birth. ⁹

Outcomes for recipient twins 

The high blood flow to the recipient twin increases blood volume, inhibiting the body's ability to retain fluid. This results in excessive urine output(polyuria) and consequently, excess amniotic fluid (polyhydramnios). Recent studies show that recipient twins can develop polycythemia, which is marked by an excess of red blood cells. This thickens the blood and increases the risk of blood clots and related conditions.⁶

TTTS has a significant impact on the cardiac function of recipient twins.^,7,10 Approximately 50% of deaths after the birth of recipient twins can be attributed to cardiac disease.¹¹ The increased cardiac load causes diastolic dysfunction, preventing the recipient twin's heart from relaxing and filling properly with blood. It also causes leakage through the heart valves or impairs their ability to close properly (atrioventricular valve regurgitation). 

The heart muscles enlarge and overwork to accommodate the excess blood. This could progress towards heart enlargement (cardiomegaly) and biventricular hypertrophy, which is the enlargement and thickening of both heart ventricles. The hypertrophy of the right ventricle may develop to impede or completely block the blood flow from the heart to the lungs. If untreated, these could lead to further cardiac complications.

Recipient twins experience high blood pressure due to the excess blood volume, which can overwhelm the kidneys and damage their structures.¹²

Shared outcomes 

Twin births, especially monochorionic, have a high risk of preterm labour, defined as birth before 37 weeks of pregnancy.¹³ Despite interventions, the risk of preterm labour is elevated in pregnancies with TTTS and continues to be a huge factor associated with the morbidity and mortality of a baby at birth or soon after. 

Twins with TTTS have been reported to experience long-term neurodevelopmental impairment, including cerebral palsy, severe developmental delay in motor skills and/or cognition, bilateral blindness, or deafness.¹⁴

Interventions and their role in outcomes 

Fetoscopic laser therapy 

Fetoscopic laser therapy (FLT) is the gold standard treatment for treating TTTS. It is a minimally invasive procedure that uses a laser to seal abnormal blood vessel connections in the placenta. A fetoscope is inserted into the abdomen and then into the amniotic sac of the recipient twin. Ultrasound imaging is used to visualise the placental blood vessels, and a laser is applied to selectively seal abnormal connections one at a time. The procedure uses local anaesthesia when the incision is made. 

This procedure was introduced in the 1980s and has been continuously refined. Originally, all blood vessel connections between the twins in the shared placenta were sealed. Eventually, the process was refined to Selective Fetoscopic Laser Photocoagulation (SFLP), where only those causing TTTS were treated, which prevented unnecessary vessel closures. The Solomon technique is a recent advancement in which a continuous laser line is drawn from one placental edge to the other, connecting all laser dots.. This ensures there are no connections remaining and creates a clear vessel network for both foetuses.¹⁵

The technique carries risks such as premature rupture of the amniotic sac before 37 weeks of pregnancy, placental abruption resulting in miscarriage, accumulation of fluid in the mother’s lungs, bleeding from the uterus during surgery and infection of the amniotic sac necessitating pregnancy termination.

Amnioreduction

Amnioreduction is a procedure that removes excess amniotic fluid from the recipient twin’s sac. The procedure uses ultrasound imaging to assess the best position to insert a long needle. Once the position is determined, a local anaesthetic is administered, after which the needle is introduced into the abdomen and the amniotic sac. Extra care is taken to avoid the placenta and other structures within the bodies of both the mother and the baby. The amniotic fluid is drained, ensuring an appropriate volume remains.¹⁶ The process is repeated whenever an excess of polyhydramnios is detected in the recipient twin.

The removal of excess fluid results in the mitigation of symptoms that arise due to polyhydramnios. It also reduces the risk of preterm labour or membrane rupture of the amniotic sac of the recipient twin. 

Even though amnioreduction is not the ideal treatment in TTTS, it is performed prior to or following laser therapy as an additional step. Studies show that adjusting fluid removal based on achieving stable intra-amniotic pressure, rather than a fixed volume, leads to better outcomes.¹⁷

Septostomy

Septostomy involves creating a small opening between the amniotic sacs of both fetuses to allow fluid to redistribute more evenly. This method carries many risks and hence, is not recommended as a treatment for TTTS.¹⁸

Umbilical cord occlusion

This procedure is offered in severe cases when the survival of both twins is no longer an option. The blood flow to one twin is completely blocked, increasing the chances of survival for the other twin.¹⁹

Long-term neonatal outcomes post-intervention 

Survival rates and growth outcomes

In the case of untreated TTTS that is diagnosed before 26 weeks, 9 out of 10 pregnancies do not survive. Laser therapy improves survival rates, where almost 9 out of 10 pregnancies will have at least one fetus survive, and 5 out of 10 will have both fetuses survive.²⁰ Laser therapy also reduces the risk of preterm births and results in higher gestational ages during birth.²¹ The risk of fetal death is not impacted by the Quintero stage of TTTS for laser therapy. 

Amnioreduction has comparatively lower survival rates, with 66% chance of one foetus surviving.²⁰  The risk of mortality is affected by the Quintero stage of the TTTS case. 

Infants who underwent laser therapy have higher birth weights, with significant differences between donor and recipient twins.²²

Neurological outcomes

The age of the fetus at birth is the most important predictor of neurodevelopmental impairment. Infants born before 28 weeks experience major neurological complications, regardless of FLS treatment.

Fetoscopic Laser Therapy has been determined to be more effective than amnioreduction in reducing cerebral injury and the risk of brain damage.²³ Neurodevelopmental delay at 2 years was also more commonly observed in those treated with amnioreduction, whereas those treated with FLT scored better on fine motor and social skill tests and showed fewer neurological abnormalities at 2 years of age. Neurodevelopmental outcomes in FLS-treated children remain stable between 2-6 years. There were no significant differences between outcomes in donor and recipient twins.

Research and future directions

Advances in interventions, particularly in fetoscopic laser therapy (FLT) and prenatal imaging, continue to enhance the management of TTTS. Innovations aim to refine these procedures, minimising risks and improving the chances of healthy neonatal outcomes. Additionally, long-term outcome studies are crucial in tracking the developmental progress of TTTS-affected twins. These studies not only inform the effectiveness of current treatments but also help optimise care strategies for the future. There is also a growing need for improved parental counselling, resources, and emotional support to help families navigate the complexities of TTTS pregnancies and postnatal care.

Summary and key takeaways

TTTS significantly affects neonatal health, with donor and recipient twins facing distinct complications. The donor twin often suffers from growth restriction and organ damage, while the recipient twin faces cardiovascular stress and polycythemia. Early intervention, such as fetoscopic laser therapy, plays a pivotal role in improving survival rates and reducing complications.
With ongoing advancements in treatment methods and prenatal care, the outlook for TTTS-affected twins continues to improve. Supportive care, early detection, and increased parental education can ensure better outcomes and provide families with the tools needed to navigate this complex condition.