Doppler or Amniocentesis to Predict Fetal Anemia

May 19, 2006 updated by: University of Toronto

Minimally Invasive Management of Rh Alloimmunization: Can Amniotic Fluid DeltaOD450 Measurements Be Replaced by Doppler Studies?

In pregnancies complicated by Rhesus disease, the mother has developed antibodies which cross the placenta and can cause anemia and death of the fetus. When the anemia is detected on time, the fetus can be saved by giving it blood transfusions during the pregnancy.

The standard test to predict whether the fetus needs a blood transfusion is examination of the amniotic fluid. To obtain this fluid a needle has to be inserted in the womb, which has a risk of preterm delivery, infection, and making the disease worse. This is called amniocentesis.

A new safe test, using Doppler ultrasound, has been developed to possibly replace the amniocentesis.

The aim of this study is to compare the new Doppler test with the standard amniocentesis. If the Doppler test is at least as good, this safe test may replace the amniocentesis in the management of pregnancies with Rhesus disease.

Study Overview

Status

Completed

Conditions

Detailed Description

In pregnancies complicated by red cell alloimmunization, the fetus may suffer from chronic progressive hemolytic anemia. Severe fetal anemia leading to hydrops and fetal demise can occur as early as 17 weeks' gestation, while in other pregnancies the only manifestation of the disease is neonatal hyperbilirubinemia. The standard of care in the management of these pregnancies is to select patients at risk of fetal anemia using information about their obstetric history, and serial maternal serum antibody measurements. The selected patients are followed closely, usually in referral centers with a special interest and expertise in managing this now relatively rare disease. Ultrasound evaluation of fetal condition, with emphasis on signs of fetal hydrops, is performed regularly. In addition, serial amniocentesis is done to assess amniotic fluid bilirubin (deltaOD450) values. This spectrophotometric method estimates the level of bilirubin in the amniotic fluid, which correlates with the severity of the hemolytic process.

Although this diagnostic test, introduced by Liley in 1961, has served fetal medicine specialists well for almost 40 years, the invasive nature of the method is considered a serious disadvantage. Furthermore, its reliability has been questioned, especially when used in the second trimester. In the past decade, noninvasive alternative methods to predict the degree of fetal anemia have been developed.

The most promising of these new diagnostic tests is Doppler measurement of fetal blood flow velocities. Fetal blood flow velocity has been shown to correlate linearly with the degree of anemia. Recently, middle cerebral artery (MCA) peak flow velocity measurements have been reported to reliably predict presence or absence of fetal anemia.

The aim of this study is to compare the performance of this new noninvasive diagnostic test with the standard test, amniocentesis for amniotic fluid deltaOD450 values. In an international multicenter setting, a large cohort of consecutive Rh-alloimmunized pregnancies will be studied prospectively. Both diagnostic tests will be performed simultaneously in all patients, and compared with the "gold standard", fetal blood sampling (FBS) to assess the actual hemoglobin concentration.

Study Type

Interventional

Enrollment

157

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Ontario
      • Toronto, Ontario, Canada, M5G 1X5
        • Mt. Sinai Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Pregnant women with red cell alloimmunization associated with a risk of fetal anemia (D, E, c or Duffy (Fya )antibodies, alone or in combination with other antibodies)
  • Gestational age between 12 and 34 weeks at study entry, viable fetus and accurate dating
  • Maternal serum test-result, above the threshold at which the fetus is considered to be at risk of developing hemolytic anemia and thus a potential candidate for invasive testing.

Exclusion Criteria:

  • Presence of Kell-antibodies
  • Presence of fetal hydrops at first ultrasonographic examination
  • Major fetal congenital or chromosomal anomalies

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Sensitivity Middle Cerebral Artery (MCA) peak velocity Doppler measurement and amniotic fluid deltaOD450 measurements, to predict fetal anemia requiring transfusion.
Specificity of Middle Cerebral Artery (MCA) peak velocity Doppler measurement and amniotic fluid deltaOD450 measurements, to predict fetal anemia requiring transfusion.

Secondary Outcome Measures

Outcome Measure
Comparison of the sensitivity and specificity of the original, linearly extended Liley chart with the Queenan (1993) chart, by plotting the deltaOD450 results found in our study in both charts.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Dick Oepkes, MD, PhD, Leiden University Medical Centre, The Netherlands
  • Principal Investigator: Gareth P Seaward, MB, BCh, MSc, Mt.Sinai Hospital, University of Toronto, Canada

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2000

Study Completion

August 1, 2004

Study Registration Dates

First Submitted

February 22, 2006

First Submitted That Met QC Criteria

February 22, 2006

First Posted (Estimate)

February 23, 2006

Study Record Updates

Last Update Posted (Estimate)

May 24, 2006

Last Update Submitted That Met QC Criteria

May 19, 2006

Last Verified

February 1, 2006

More Information

Terms related to this study

Other Study ID Numbers

  • MSH-REB 01-0266-U
  • PSI Grant Number:01-13

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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