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.
None
Miscarriage and terminations of pregnancy for other reasons than severe alloimmunization
Single group
NGS analysis for fetal red cell blood type in maternal plasma
Diagnostic testNGS 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.
Implementation patient safety composite
Patient safety assessment defined as a composite outcome including: 1. Gestational age (days) at blood sampling for fetal antigen test 2. Number of second confirming samples (n) 3. Turn around time for NGS analyses and report to clinicians (days) 4. Numbers and percentage of fetuses negative for the maternal antibody corresponding antigen according to NGS analysis (n, %) 5. Concordance of fetal antigen according to NGS compared to neonatal cord blood analysis (%)
Obstetric and neonatal outcomes.
Obstetric outcomes: 1. Identified red cell antibodies (n) 2. Number of maternal plasma analysis of red cell antibody titer per pregnancy (median (min-max)) 3. Paternal red cell antigen test carried out. Yes/No, (n) 4. Conventional noninvasive prenatal sampling for antigen D, c, or K with PCR analysis carried out. Yes/No, (n) 5. Number of visits at an obstetric unit, excluded fetal ultrasound (mean (min-max)) 6. Number of fetal ultrasounds due to red cell alloimmunization (n) 7. Number of intrauterine blood transfusions (IUT) to the fetus (n) 8. Number of pregnancies with IUT (n) Neonatal outcomes: 1. Gestational age at birth (days) 2. Birth weight (grams) 3. Neonatal hemoglobin (g/L) and bilirubin umol/L) at birth 4. Hyperbilirubinemia treated with phototherapy (n) 5. Total hours of phototherapy (median (min-max) 6. Blood transfusion (n) 7. Exchange transfusion (n) 8. Days at neonatal intensive care (median (min-max))
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Karolinska University Hospital
Lead sponsor
Karolinska Institutet
Collaborator
University Hospital, Umeå
Collaborator
Uppsala University Hospital
Collaborator
Sahlgrenska University Hospital
Collaborator
Skane University Hospital
Collaborator
University Hospital, Linkoeping
Collaborator
Dept of Obstet & Gynecol, University Hospital Oerebro
Collaborator
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