Renal Artery Dopplers in Twin Twin Transfusion Syndrome

Study Overview
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Brief Summary
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Twin-twin transfusion syndrome (TTTS) is a complication affecting 10-15% of monochorionic, diamniotic (MCDA) twin pregnancies. Unevenly distributed blood flow across a shared placental circulation results in a volume-restricted donor twin and a volume-overloaded recipient twin, and TTTS has high perinatal morbidity and mortality without treatment. Differential donor and recipient findings in TTTS can be observed upon ultrasound evaluation. TTTS is classified according to the Quintero staging system, which evaluates amniotic fluid volumes, fetal bladders, Doppler study of the umbilical artery and ductus venosus, and for the presence of hydrops or death. However, due to seemingly complex and variable disease pathophysiology, the Quintero system cannot predict outcomes on a case-by-case basis. Prior studies have associated fetal renal artery Doppler ultrasound measurements with amniotic fluid volume in singleton pregnancies. In fetuses with placental insufficiency, adaptive circulatory changes maintain adequate oxygen delivery to vital organs such as the heart, brain, and adrenals, with a consequent deprivation to splanchnic organs. In the fetal kidney, as vascular resistance increases during hypoxia, renal perfusion decreases proportionately. These changes are reflected in renal artery Doppler findings. As these same adaptations are believed to occur in donor twins, renal artery Doppler studies may also be of value in the TTTS evaluation. This study plans to perform renal artery Doppler assessments in MCDA twins complicated by TTTS, and compare them to measurements in gestational-age equivalent MCDA twins without TTTS. If findings differ significantly, it would support further investigation into the use of renal artery Doppler studies for the evaluation of complicated MCDA twins.

Detailed Description
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TTTS, which complicates 10-15% of MCDA twin pregnancies, is characterized by a net imbalance of volume between twins, mediated through abnormal placental blood vessel anastomoses that connect the two placental circulations. Clinically, the donor twin develops features of anemia and hypovolemia, while the recipient twin shows signs of hypervolemia and hypertensive fluid overload. If untreated, the syndrome has a perinatal mortality rate as high as 80-100%. Although modern intrauterine therapies have improved the rates of fetal death, significant risks of morbidity and mortality remain even after treatment. Twin-twin transfusion syndrome is most commonly classified according to a staging system developed by Quintero et al in 1999, which is based on discrete, categorical ultrasound findings (amniotic fluid volume, presence/absence of a fetal bladder, umbilical artery Doppler studies, fetal hydrops, and death). The system includes 5 stages ranging from mild disease with isolated discordant amniotic fluid volumes, to severe disease with demise of one or both twins. Although this system has some prognostic value, it also has significant limitations due to the highly complex physiologic conditions that are involved in the disease. For example, some criteria in the staging system are not consistently representative of fetal physiology. Additionally, the stages do not correlate well with overall perinatal survival or with outcomes following intrauterine therapies. Recent work has demonstrated that the complex pathophysiology of twin-twin transfusion syndrome involves a discordant activation of the renin angiotensin system (RAS). RAS is normally important in fluid and salt regulation in both the adult and the fetus, and TTTS in marked hypovolemia and hypervolemia in monozygous fetuses within the same maternal environment. The renal RAS in the donor is up-regulated, presumably as a consequence of hypovolemia. The recipient is also exposed to high levels or RAS components, either due to the transfusion of these components from the donor via anastomoses, or via discordant placental RAS activation, resulting in a hypertensive, hypervolemic state. Multiple studies have identified a correlation between Doppler assessment of the fetal renal artery and the development of oligohydramnios, a hypovolemic state, in singleton pregnancies. However, the use of renal artery Doppler studies has not yet been fully evaluated in twin gestations. In particular, it has not been evaluated in MCDA twin gestations complicated by TTTS, the pathophysiology of which involves significant alterations in fetal volume and fluid status. This project is intended to serve as a single-center study to determine if there is indeed a difference in renal artery Doppler parameters in sets of MCDA twins with TTTS compared to sets of MCDA twins without TTTS. The identification of a significant difference would potentially provide support for further investigation into this measurement as a screening tool or prognostic indicator when applied to MCDA twin pregnancies. Secondary goals of this study include: comparing donor to recipient renal artery Doppler findings among pregnancies with TTTS, evaluating serial renal artery Doppler findings over time per pregnancy, and evaluating pre- and post-therapy renal artery Doppler findings in those pregnancies undergoing therapy for TTTS.

Official Title
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Are Renal Artery Doppler Indices Different Between Monochorionic Diamniotic Twins With Twin-twin Transfusion Syndrome and Monochorionic Diamniotic Twins Without Twin-twin Transfusion Syndrome?

Conditions
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Twin Twin Transfusion Syndrome

Intervention / Treatment
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* Diagnostic Test: Doppler ultrasound of fetal renal artery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: pregnant women with monochorionic / diamniotic (MCDA) twin pregnancies with and without twin-twin transfusion syndrome (TTTS) greater than 14 weeks gestation Exclusion Criteria: higher-order multiple gestation sonographic evidence of a major structural fetal anomaly (exceptions to this structural fetal anomaly exclusion are acquired recipient twin cardiac changes that are known to be associated with TTTS - these cases may be considered for study inclusion)
Sexes Eligible for Study
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Female

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| TTTS Cases<br>Cases of monochorionic / diamniotic twin pregnancies diagnosed with twin-twin transfusion syndrome. | Diagnostic Test: Doppler ultrasound of fetal renal artery<br>* Doppler ultrasound assessment of the proximal fetal renal artery to with measurement of the peak systolic velocity, resistive index, pulsatility index, and systolic/diastolic ratio.<br>|
| MCDA Controls<br>Controls of monochorionic / diamniotic twin pregnancies without a diagnosis of twin-twin transfusion syndrome. | Diagnostic Test: Doppler ultrasound of fetal renal artery<br>* Doppler ultrasound assessment of the proximal fetal renal artery to with measurement of the peak systolic velocity, resistive index, pulsatility index, and systolic/diastolic ratio.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fetal renal artery Doppler PSV for twin A | Doppler ultrasound assessment of the proximal fetal renal artery with measurement of the peak systolic velocity for twin A. | Obtained at the time of enrollment. | 
| Fetal renal artery Doppler RI for twin A | Doppler ultrasound assessment of the proximal fetal renal artery with measurement of the resistive index for twin A. | Obtained at the time of enrollment. | 
| Fetal renal artery Doppler PI for twin A | Doppler ultrasound assessment of the proximal fetal renal artery with measurement of the pulsatility index for twin A. | Obtained at the time of enrollment. | 
| Fetal renal artery Doppler PSV for twin B | Doppler ultrasound assessment of the proximal fetal renal artery with measurement of the peak systolic velocity for twin B. | Obtained at the time of enrollment. | 
| Fetal renal artery Doppler RI for twin B | Doppler ultrasound assessment of the proximal fetal renal artery with measurement of the resistive index for twin B. | Obtained at the time of enrollment. | 
| Fetal renal artery Doppler PI for twin B | Doppler ultrasound assessment of the proximal fetal renal artery with measurement of the pulsatility index for twin B. | Obtained at the time of enrollment. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post-laser fetal renal artery Doppler PSV for twin A | Doppler ultrasound assessment of the proximal fetal renal artery with measurement of the peak systolic velocity for twin A. | Obtained within one week following fetoscopic laser therapy for cases in which this treatment is provided. | 
| Post-laser fetal renal artery Doppler RI for twin A | Doppler ultrasound assessment of the proximal fetal renal artery with measurement of the resistive index for twin A. | Obtained within one week following fetoscopic laser therapy for cases in which this treatment is provided. | 
| Post-laser fetal renal artery Doppler PI for twin A | Doppler ultrasound assessment of the proximal fetal renal artery with measurement of the pulsatility index for twin A. | Obtained within one week following fetoscopic laser therapy for cases in which this treatment is provided. | 
| Post-laser fetal renal artery Doppler PSV for twin B | Doppler ultrasound assessment of the proximal fetal renal artery with measurement of the peak systolic velocity for twin B. | Obtained within one week following fetoscopic laser therapy for cases in which this treatment is provided. | 
| Post-laser fetal renal artery Doppler RI for twin B | Doppler ultrasound assessment of the proximal fetal renal artery with measurement of the resistive index for twin B. | Obtained within one week following fetoscopic laser therapy for cases in which this treatment is provided. | 
| Post-laser fetal renal artery Doppler PI for twin B | Doppler ultrasound assessment of the proximal fetal renal artery with measurement of the pulsatility index for twin B. | Obtained within one week following fetoscopic laser therapy for cases in which this treatment is provided. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Renal Artery Doppler