Renal Artery Dopplers in Twin Twin Transfusion Syndrome

Brief Title

Renal Artery Dopplers in Twin Twin Transfusion Syndrome

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?

Brief Summary

      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

      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

      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.

Study Type


Primary Outcome

Fetal renal artery Doppler PSV for twin A

Secondary Outcome

 Post-laser fetal renal artery Doppler PSV for twin A


Twin Twin Transfusion Syndrome


Doppler ultrasound of fetal renal artery

Study Arms / Comparison Groups

 TTTS Cases
Description:  Cases of monochorionic / diamniotic twin pregnancies diagnosed with twin-twin transfusion syndrome.


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status

Diagnostic Test

Estimated Enrollment


Start Date

September 9, 2016

Completion Date

June 30, 2018

Primary Completion Date

March 21, 2018

Eligibility Criteria

        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




N/A - N/A


Joses Jain, MD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations



Organization ID


Responsible Party

Principal Investigator

Study Sponsor

Columbia University

Study Sponsor

Joses Jain, MD, Study Director, Columbia University

Verification Date

July 2018