Comparison of intrauterine transfusion techniques in hemolytic disease of the fetus and newborn

Abstract

Objectives: Intrauterine transfusions (IUTs) are the cornerstone in treatment for hemolytic disease of the fetus and newborn (HDFN). It has been suggested that a non-vascular intraperitoneal blood transfusion used in conjunction with an intravascular IUT can slow the decrease in fetal hemoglobin (Hb) levels, potentially extending the interval between transfusions. Our aim was to evaluate the rate of decline in Hb levels and the interval between transfusions using different IUT techniques, including intrahepatic transfusions with and without intraperitoneal transfusion, and transplacental transfusion at the site of the placental cord insertion.

Methods: We conducted a retrospective cohort study at the Leiden University Medical Center, the national referral center for HDFN, between January 2006 and December 2022. All cases that underwent intrahepatic (with and without intraperitoneal transfusion) and placental cord insertion IUTs during the study period were included. The primary outcome was the decline in Hb levels per week, measured by comparing the Hb level immediately after the IUT with the Hb level before the subsequent IUT or birth. The primary outcome was analyzed using generalized estimating equations with and without adjustment for confounders.

Results: We included 309 fetuses that received a total of 791 IUTs, of which 151 were intrahepatic-only transfusions, 273 were intrahepatic + intraperitoneal transfusions and 367 were placental cord insertion transfusions. We found an adjusted mean difference in the decline in Hb levels of 0.48 (95% CI, 0.29-0.66) g/dL/week between the group that underwent intrahepatic-only transfusion and the group that underwent intrahepatic + intraperitoneal transfusion (P < 0.001). The adjusted mean difference between the intrahepatic-only IUT group and the placental cord insertion IUT group was 0.49 (95% CI, 0.05-0.94) g/dL/week (P = 0.030). The median interval to the next IUT for the total cohort was 21 (interquartile range (IQR), 18-28) days. Similarly, in the intrahepatic-only and placental cord insertion IUT groups, the median interval to the next IUT was 21 (IQR, 19-28) and 21 (IQR, 15-26) days, respectively. In the intrahepatic + intraperitoneal transfusion group, the median interval was slightly higher (26 (IQR, 21-28) days).

Conclusion: Decline in Hb levels was slower when using intrahepatic + intraperitoneal transfusion compared with other IUT techniques and seemed to prolong the interval between IUT procedures. The potential clinical advantages of the intrahepatic + intraperitoneal transfusion technique need to be weighed against the increased complexity and extended duration of the procedure on an individual basis. © 2025 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Keywords: HDFN; anemia; blood transfusion; erythroblastosis; fetal therapies; intrauterine blood transfusion.

Figure 1

Flowchart summarizing inclusion in study of fetuses with hemolytic disease of the fetus and newborn (HDFN) that underwent intrahepatic intrauterine transfusion (IUT), intrahepatic and intraperitoneal IUT and/or placental cord insertion IUT, as well as numbers of cases missing delta hemoglobin (Hb) values.

Figure 2

Box‐and‐whiskers plot showing unadjusted delta hemoglobin (Hb) according to whether intrauterine transfusion technique used was intrahepatic‐only transfusion, intrahepatic + intraperitoneal transfusion or placental cord insertion transfusion. Boxes show median and interquartile range (IQR), and error bars depict 95% CI. Dots () represent outliers. Asterisks () represent extreme outliers, defined as 3× IQR. The two major outliers (one in the intrahepatic‐only group and one in the placental cord insertion group) were not included in the main analysis and are therefore not displayed in this figure.