Doppler or Amniocentesis to Predict Fetal Anemia

NCT ID: NCT00295516

Last Updated: 2006-05-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 157 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2000-10-31
• Study Completion Date: 2004-08-31

Brief Summary

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.

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.

Conditions

Rh Isoimmunization

Keywords

Rhesus; Isoimmunization; Red Cell Alloimmunization; Fetal Hemolytic Anemia; Erythroblastosis fetalis

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Interventions

Fetal Middle Cerebral Artery Doppler measurement

Intervention Type: PROCEDURE

Eligibility Criteria

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

• Minimum Eligible Age: 0 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Physicians' Services Incorporated Foundation

OTHER

Sponsor Role: collaborator

Stichting Oranjekliniek, The Netherlands

UNKNOWN

Sponsor Role: collaborator

University of Toronto

OTHER

Sponsor Role: lead

Principal Investigators

Dick Oepkes, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Leiden University Medical Centre, The Netherlands

Gareth P Seaward, MB, BCh, MSc

Role: PRINCIPAL_INVESTIGATOR

Mt.Sinai Hospital, University of Toronto, Canada

Locations

Mt. Sinai Hospital

Toronto, Ontario, Canada

Countries

Canada

References

Oepkes D, Seaward PG, Vandenbussche FP, Windrim R, Kingdom J, Beyene J, Kanhai HH, Ohlsson A, Ryan G; DIAMOND Study Group. Doppler ultrasonography versus amniocentesis to predict fetal anemia. N Engl J Med. 2006 Jul 13;355(2):156-64. doi: 10.1056/NEJMoa052855.

Reference Type: DERIVED

PMID: 16837679 (View on PubMed)

Other Identifiers

PSI Grant Number:01-13

Identifier Type: -

Identifier Source: secondary_id

MSH-REB 01-0266-U

Identifier Type: -

Identifier Source: org_study_id