Twin Twin Transfusion Syndrome Clinical Trial
Official title:
Are Renal Artery Doppler Indices Different Between Monochorionic Diamniotic Twins With Twin-twin Transfusion Syndrome and Monochorionic Diamniotic Twins Without Twin-twin Transfusion Syndrome?
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.
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.
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