A Phase 2 interventional study of Intrauterine Transfusion and Intravenous immunoglobulin (IVIG) in Hemolytic Disease of the Newborn, Fetal Anemia and Rhesus Isoimmunization, sponsored by Post Graduate Institute of Medical Education and Research, Chandigarh. Recruiting at 1 site in India. Open to participants aged 20 Weeks and older. Per ClinicalTrials.gov, last updated 2026-10-21.
Sponsored by Post Graduate Institute of Medical Education and Research, Chandigarh · Phase 2, Interventional, and Treatment
The goal of this clinical trial is to learn if giving intravenous immunoglobulin directly to the fetus during intrauterine transfusion can improve newborn outcomes in pregnancies affected by rhesus isoimmunization.
Rhesus isoimmunization happens when a pregnant woman's immune system attacks her baby's red blood cells. This can cause severe anemia (low red blood cell levels) before birth. Doctors treat this condition with intrauterine transfusion, a procedure that gives blood to the fetus before birth. However, this treatment does not stop the immune attack. Many newborns still develop anemia and high bilirubin levels after birth and may need phototherapy or exchange transfusion.
The main questions this study aims to answer are:
Does adding fetal intravenous immunoglobulin increase the baby's blood count at birth? Does it lower the need for phototherapy or exchange transfusion after birth?
Researchers will compare:
Intrauterine transfusion with fetal intravenous immunoglobulin to Intrauterine transfusion alone to see if adding immunoglobulin improves newborn outcomes.
Participants will:
The main outcome is the baby's blood count at birth. Researchers will also measure:
This study will help determine whether treating the immune process before birth can improve health outcomes for newborns affected by rhesus isoimmunization.
Rhesus isoimmunization is an immune-mediated condition in which maternal immunoglobulin G antibodies directed against fetal red blood cell antigens cross the placenta and cause progressive fetal hemolysis. Ongoing antibody-mediated destruction of fetal erythrocytes may result in moderate to severe fetal anemia, hydrops fetalis, intrauterine fetal demise, and significant neonatal morbidity.
Intrauterine transfusion (IUT) remains the standard of care for moderate to severe fetal anemia. IUT rapidly corrects fetal hematocrit by transfusing antigen-negative packed red blood cells directly into the fetal circulation. Although this intervention improves perinatal survival, it does not modify the underlying immune mechanism. Maternal antibodies persist in the fetal circulation and continue to opsonize both native and transfused erythrocytes. As a result, fetal hematocrit typically declines progressively after each transfusion, often necessitating repeated procedures.
Neonates treated antenatally with IUT frequently develop postnatal anemia and hyperbilirubinemia due to continued immune-mediated hemolysis. Many require intensive phototherapy, exchange transfusion, or additional blood transfusions after birth. Therefore, strategies that attenuate immune-mediated hemolysis before delivery may reduce neonatal treatment burden.
Intravenous immunoglobulin (IVIG) exerts immunomodulatory effects through several mechanisms, including Fc gamma receptor blockade on macrophages, modulation of complement activation, and interference with antibody-mediated cellular cytotoxicity. These mechanisms may reduce erythrophagocytosis of antibody-coated red blood cells within the fetal reticuloendothelial system. While postnatal IVIG has shown inconsistent clinical benefit, earlier administration during active fetal hemolysis may provide greater biological impact.
Direct intravascular administration of IVIG into the fetal circulation at the time of IUT allows targeted exposure within the fetal compartment. This approach avoids reliance on placental transfer and permits immediate interaction with antibody-coated erythrocytes and fetal macrophages. Limited pilot data suggest that moderate-to-high dose fetal IVIG may slow the post-transfusion decline in fetal hematocrit, indicating attenuation of ongoing hemolysis. However, available studies are small, non-randomized, and not powered to evaluate clinically meaningful neonatal outcomes.
This study is an individually randomized, controlled, parallel-arm superiority trial conducted at a tertiary referral center with established expertise in fetal transfusion and neonatal intensive care. Eligible mother-fetus dyads undergoing their first clinically indicated intrauterine transfusion will be randomized in a 1:2 allocation ratio to receive:
Standard intrauterine transfusion alone, or
Intrauterine transfusion with adjunctive direct fetal IVIG administration during the same procedure.
Randomization will occur at the time of the first transfusion. IVIG will be administered intravascularly through the same umbilical venous access following completion of red cell transfusion. All other procedural steps, antenatal monitoring, and delivery planning will follow institutional protocols and remain identical between groups.
Participants will be followed prospectively through delivery and the neonatal hospitalization period. The study evaluates both fetal hematologic response and postnatal clinical outcomes. The primary endpoint is cord blood hematocrit at birth. Secondary endpoints include rate of post-transfusion hematocrit decline, postnatal phototherapy requirements, need for exchange transfusion, need for packed red cell transfusions, number and timing of intrauterine transfusions, and procedure-related adverse events.
The trial is designed to determine whether immunomodulation within the fetal compartment can translate into improved neonatal hematologic stability and reduced postnatal intervention. If effective, this strategy may represent a disease-modifying adjunct to intrauterine transfusion rather than a purely corrective intervention.
Post Graduate Institute of Medical Education and Research, Chandigarh is the lead sponsor of 296 studies on the registry; 44 are open to participants now.
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Exclusion Criteria:
Participants will undergo intrauterine transfusion using compatible packed red blood cells as per institutional protocol. No intravenous immunoglobulin will be administered to the fetus.
Procedure: Intrauterine Transfusion
Participants will undergo standard intrauterine transfusion followed by intravascular administration of intravenous immunoglobulin directly into the fetal circulation during the same procedure.
Procedure: Intrauterine Transfusion · Drug: Intravenous immunoglobulin (IVIG)
Ultrasound-guided intravascular transfusion of compatible packed red blood cells into the fetal circulation for treatment of fetal anemia.
Intravenous immunoglobulin administered intravascularly into the fetal circulation during intrauterine transfusion.
Cord Blood Hematocrit at Birth
Hematocrit measured from umbilical cord venous blood immediately after delivery, expressed as percentage of red blood cell volume.
Time frame: At birth (Day 1)
Rate of Post-Transfusion Decline in Fetal Hematocrit
Change in fetal hematocrit per day following intrauterine transfusion, calculated between procedures.
Time frame: From first intrauterine transfusion until delivery
Need for Phototherapy
Proportion of neonates requiring phototherapy for management of hyperbilirubinemia.
Time frame: From birth until 28 days or discharge, whichever is earlier
Duration of Phototherapy
Total duration of phototherapy administered to the neonate, measured in hours.
Time frame: From birth until 28 days or discharge, whichever is earlier
Need for Exchange Transfusion
Proportion of neonates requiring double-volume exchange transfusion.
Time frame: From birth until 28 days or discharge, whichever is earlier
Number of Postnatal Packed Red Blood Cell Transfusions
Number of packed red blood cell transfusions administered to the neonate.
Time frame: From birth until 28 days or discharge, whichever is earlier
Procedure-Related Adverse Events
Occurrence of complications related to intrauterine transfusion or fetal intravenous immunoglobulin administration. This includes fetal bradycardia requiring intervention, cord bleeding or hematoma, procedure-related fetal loss, preterm labor, maternal fever or suspected infection, and any acute hemodynamic instability following fetal intravenous immunoglobulin administration.
Time frame: Periprocedural to upto 1 week after IUT
Plan to share: Yes — De-identified individual participant data underlying the primary and secondary outcome measures, including baseline characteristics, fetal hematologic parameters, intrauterine transfusion details, and neonatal outcome data, will be made available after publication of the primary results. Data will be shared upon reasonable request for secondary analyses or meta-analysis, subject to review of a methodologically sound proposal and execution of a data use agreement.
Supporting information: Study protocol, Statistical analysis plan, Informed consent form, Analytic code
Time frame: Data and supporting documents will be available beginning 6 months after publication of the primary results and will remain available for 5 years.
Access criteria: Access to de-identified data and supporting documents will be provided upon reasonable request to the principal investigator. Requests must include a methodologically sound proposal and will require execution of a data use agreement.
Started May 2026 (actual). Primary completion is estimated for Jun 2027, 13 months after the start.
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From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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