Prenatal Blood Typing With Next Generation Sequencing (NGS) - an Implementation Study in HDFN (PREFAB)

Summary

Determination of Fetal Blood Group by Next-Generation Sequencing - A Clinical Study in Pregnancies with Maternal Alloantibodies Directed Against Fetal Blood Cells (Alloimmunization During Pregnancy)

Maternal antibodies can cross the placenta and reach the fetus during pregnancy. In some cases, these antibodies are harmful to the fetus. One such condition is alloimmunization against fetal red blood cells or platelets. This occurs in approximately 1% of all pregnancies and, if left undetected, unmonitored, and untreated, may lead to fetal anemia, heart failure, bleeding, or fetal death.

Today, pregnant women are offered screening for antibodies against red blood cells during pregnancy. It is the fetus that may be affected, making the fetus the patient whose risk of disease and complications after birth healthcare aims to identify and minimize. This presents a particular challenge because, until birth, the fetus remains physically connected to and dependent on the pregnant woman.

Methods are available to estimate the fetal blood group and thereby assess the risk to the unborn child. Since the fetus inherits its blood group from both biological parents, some fetuses will carry blood group antigens that are targeted by the mother's antibodies, while others will not. Current methods are imperfect, and in approximately 30% of cases the fetus will not carry the relevant blood group antigen. Consequently, many pregnancies undergo unnecessary monitoring, causing additional healthcare costs as well as anxiety for the pregnant woman and her partner.

Using advanced genetic technology, we aim to investigate whether analysis of a maternal blood sample by Next-Generation Sequencing (NGS) can accurately determine the fetal blood group. This would enable reliable identification of fetuses at risk of being affected by maternal alloantibodies, while also identifying those that are not at risk and therefore do not require unnecessary monitoring. NGS will be used in a study population in Sweden (seven centers) and validated for patient safety, logistic implementation and health economic costs.

Conditions

• Red Blood Cell Alloimmunization in Pregnancy
• HDFN
• Next Generation Sequencing (NGS)

Interventions

DIAGNOSTIC_TEST

NGS analysis for fetal red cell blood type in maternal plasma

NGS of cell free fetal DNA in maternal plasma for all prospective identified red cell alloimmunization in early pregnancy within seven regions in Sweden. None included regions in Sweden will be analyses according to ongoing clinical routine, that is paternal phenotype identification or follow the pregnancy by repeated maternal antibody titers.

Sponsors & Collaborators

• Karolinska Institutet

  collaborator OTHER

• University Hospital, Umeå

  collaborator OTHER

• Uppsala University Hospital

  collaborator OTHER

• Sahlgrenska University Hospital

  collaborator OTHER

• Skane University Hospital

  collaborator OTHER

• University Hospital, Linkoeping

  collaborator OTHER

• Dept of Obstet & Gynecol, University Hospital Oerebro

  collaborator UNKNOWN

• Karolinska University Hospital

  lead OTHER

Principal Investigators

• Gunilla Ajne, PhD, MD · Karolinska Institutet, Clintec, Div of Obstet&Gyne AND Karolinska University Hospital Stockholm Sweden

• Agneta Wikman, Adj prof, MD · Karolinska Institutet, Centre Hematol & Regen Med AND Clin Immunology & Transf Med Karolinska University Hospital

• Tesfai Emahazion, PhD · Karolinska Institutet, Centre Hematol & Regen Med AND Clin Immunology & Transf Med Karolinska University Hospital

Study Design

Allocation

NA

Purpose

DIAGNOSTIC

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Max Age

45 Years

Sex

FEMALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-09-01

Primary Completion

2028-12-31

Completion

2030-12-31