Intrauterine transfusion for fetal anemia due to red blood cell alloimmunization: 14 years experience in Leuven.

OBJECTIVE: The purpose of this study is to report on the pregnancy and neonatal outcome of intrauterine transfusion (IUT) for red blood cell (RBC-)alloimmunization. MATERIAL AND METHODS: Retrospective cohort study of all IUT for RBC-alloimmunization in the University Hospital of Leuven, between January 2000 and January 2014. The influence of hydrops, gestational age and technique of transfusion on procedure related adverse events were examined. RESULTS: 135 IUTs were performed in 56 fetuses. In none of the cases fetal or neonatal death occurred. Mild adverse events were noted in 10% of IUTs, whereas severe adverse events occurred in 1.5%. Hydrops and transfusion in a free loop were associated with an increased risk of adverse events whereas gestational age (GA) at transfusion after 34 weeks was not. Median GA at birth was 35.6 weeks and 9% was born before 34 weeks. Besides phototherapy 65.4% required additional neonatal treatment for alloimmune anemia. Non-hematologic complications occurred in 23.6% and were mainly related to preterm birth. CONCLUSION: In experienced hands, IUT for RBC-alloimmunization is a safe procedure in this era. Patients should be referred to specialist centers prior to the development of hydrops. IUT in a free loop of cord and unnecessary preterm birth are best avoided.

Fluid shift from intravascular compartment during fetal red blood cell transfusion.

OBJECTIVES: Intrauterine transfusion imposes a considerable burden on the fetal circulation by increasing volume and pressure, and a fluid shift from the fetal circulation occurs even during the procedure. The aim of this study was to quantify the intraprocedural fluid shift and to investigate the effect of procedural and fetal characteristics on this fluid shift. METHODS: In 95 alloimmunized pregnancies, we calculated fluid shift at the first intrauterine transfusion by determining initial and final blood volumes. We evaluated the association of the fluid shift with the speed and volume of the transfusion, the severity of anemia and the presence of hydrops. RESULTS: Of the included fetuses, 11 were mildly hydropic and four were severely hydropic. A mean fluid shift of 36% of the transfused volume was found. Fluid shift related positively to transfused volume (P < 0.001). The percentage fluid shift of transfused volume was inversely related to the speed of transfusion (mL/kg/min) (P < 0.041) and was not related to the severity of anemia (P = 0.55) or to hydrops (P = 0.66). It was found that younger fetuses had been unintentionally subject to high volumes and speeds of transfusion relative to their size. CONCLUSIONS: Around one-third of the transfused volume is lost from the intravascular compartment during the procedure of intrauterine transfusion. There is a large variation between fetuses, partly explained by the volume and speed of the transfusion. Neither severity of anemia nor hydrops plays a clear-cut role, and thus other factors may explain the variation in fluid shift. The probability that hematocrit will still increase after transfusion, as a result of a continuing fluid shift, should be considered in transfusion policy. Advice is given on gestational age-adjusted speed of transfusion.

Placental characteristics in growth-discordant monochorionic twins: a matched case-control study.

OBJECTIVE: To compare the placental characteristics in monochorionic (MC) twin pregnancies with and without birth weight discordance (BWD). METHODS: We performed a matched case-control study to compare the placental characteristics of MC placentas from pregnancies with BWD (≥25%) (n = 47) with a control group of MC placentas without BWD (n = 47), matched for gestational age at birth. Placental sharing, angioarchitecture and diameter of the arterio-arterial (AA) anastomosis were assessed by placental injection with colored dye. RESULTS: The rate of velamentous cord insertion in MC placentas with and without BWD was 30% (28/94) and 16% (15/94), respectively (p = 0.036). Placental sharing discordance in MC placentas with and without BWD was 36% and 17%, respectively (p < 0.001). The mean diameter of the AA anastomosis in MC placentas with and without BWD was 2.2 mm and 1.8 mm, respectively (p = 0.024). CONCLUSION: MC placentas from growth-discordant twins are more unequally shared, have a higher rate of velamentous cord insertions and larger diameter of AA anastomosis compared to gestational age matched controls.

Fetal stress hormone changes during intrauterine transfusions.

OBJECTIVE: To document fetal stress hormone and Doppler changes after intrauterine transfusions (IUTs) in either the intrahepatic portion of the umbilical vein (IHV) or the placental cord insertion (PCI). METHOD: Pregnant women scheduled for IUT for fetal anemia (N = 25) were included prospectively. Cortisol, ß-endorphin and noradrenalin concentrations in fetal plasma and middle cerebral artery pulsatility index before and after transfusion were compared. Transfusions were performed through the (IHV), thus puncturing the fetus, or at the PCI. RESULTS: There were no measurable differences between the transfusion sites. CONCLUSION: In anemic fetuses undergoing transfusion, Doppler changes and fetal stress hormone changes were unrelated to the site of needle insertion.

Twin anemia-polycythemia sequence: diagnostic criteria, classification, perinatal management and outcome.

Monochorionic twins share a single placenta with intertwin vascular anastomoses, allowing the transfer of blood from one fetus to the other and vice versa. These anastomoses are the essential anatomical substrate for the development of several complications, including twin-twin transfusion syndrome (TTTS) and twin anemia-polycythemia sequence (TAPS). TTTS and TAPS are both chronic forms of fetofetal transfusion. TTTS is characterized by the twin oligopolyhydramnios sequence, whereas TAPS is characterized by large intertwin hemoglobin differences in the absence of amniotic fluid discordances. TAPS may occur spontaneously in up to 5% of monochorionic twins and may also develop after incomplete laser treatment in TTTS cases. This review focuses on the pathogenesis, incidence, diagnostic criteria, management options and outcome in TAPS. In addition, we propose a classification system for antenatal and postnatal TAPS.

Total blood volume is maintained in nonhydropic fetuses with severe hemolytic anemia.

OBJECTIVE: Fetal alloimmune anemia is associated with increased blood flow velocities and cardiomegaly. In severe cases, hydrops can develop. We investigated whether the decrease of red blood cell volume is associated with a reduction or expansion of plasma volume. METHODS: In 86 alloimmunized fetuses that received a first intrauterine transfusion, we calculated fetal total blood volumes (i.e. fetoplacental blood volumes) using a dilutional principle of fetal hemoglobin with adult hemoglobin. The relation between total blood volume and estimated fetal weight, severity of anemia and hydrops was analyzed. RESULTS: Gestational age ranged from 17 to 35 weeks. Mean hemoglobin deficit was 6.8 standard deviations (range 2.1-11.7) below the normal mean. Fetal total blood volume was significantly related to estimated fetal weight (p < 0.001). Mean total blood volume in nonhydropic fetuses was 123 ml/kg (n = 74) and in hydropic fetuses 144 ml/kg (n = 12). There was a significant relation between total blood volume per kg body weight and hydrops (p = 0.035); however, there was no relation with severity of anemia (p = 0.94). CONCLUSION: In the human nonhydropic fetus with severe hemolytic anemia, total blood volume is maintained: the decrease in red blood cell volume is thus compensated by an increase in plasma volume. In hydropic fetuses, however, total blood volume seems to be increased. This is in accordance with the hypothesis that congestive heart failure plays a role in the pathophysiology of hydrops in anemic fetuses.

Quantification of feto-fetal transfusion rate through a single placental arterio-venous anastomosis in a monochorionic twin pregnancy.

Twin-to-twin transfusion syndrome (TTTS) is due to unbalanced inter-twin blood flow through placental vascular anastomoses. We present a TTTS-case treated with fetoscopic laser surgery that allowed us to calculate the net inter-twin blood flow. In the weeks following laser treatment, the ex-recipient developed severe fetal anemia and was treated with two intrauterine adult red cell transfusions (at 26 and 29 weeks' gestation, respectively). After birth, placental injection with color-latex identified a single residual arterio-venous anastomosis from the ex-recipient to the ex-donor. We measured the fetal and adult hemoglobin concentrations in the anemic fetus before and after both intrauterine transfusions, and in both twins at birth. On the basis of these measurements, we calculated the blood flow across the residual arterio-venous anastomosis and found it to be 5.8+/-1.5 mL/24h after the 1st transfusion and 11.4+/-2.9 mL/24h after the 2nd transfusion.

On the origin of amniotic fluid bilirubin.

We studied the relationship between bilirubin concentrations in amniotic fluid and fetal blood in 68 non-hydropic rhesus d-alloimmunized anemic fetuses at first blood sampling. In these alloimmunized fetuses, the amniotic fluid/fetal blood ratio for bilirubin decreased from 0.09 at 28 weeks to 0.05 at 33 weeks. In normal fetuses, amniotic fluid/fetal blood ratios for bilirubin, and for albumin, are in the same range and show a similar decrease during gestation. We conclude that amniotic fluid bilirubin concentration is determined, firstly, by fetal blood bilirubin concentration and, secondly, by the amniotic fluid/fetal blood ratio of albumin. Among five possible pathways bilirubin could take to build up a concentration in amniotic fluid (fetal kidneys, lungs, skin, bowel, membranes), the intramembranous pathway is the only one that is compatible with the amniotic fluid/fetal blood ratios for bilirubin that we found and must therefore be the most important.