ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

Intrauterine fetal transfusion of red blood cells

Intrauterine fetal transfusion of red blood cells
Literature review current through: Jan 2024.
This topic last updated: Jan 19, 2024.

INTRODUCTION — The infusion of red blood cells (RBCs) into the fetus is one of the most successful in utero therapeutic procedures. Although never studied in randomized trials, observational studies have clearly demonstrated that intrauterine transfusion (IUT) of the severely anemic fetus improves survival. (See 'Outcome in alloimmunized pregnancies' below.)

Universal use of prophylactic anti-D immune globulin has reduced the need for IUT dramatically; however, the procedure continues to be an essential modality for treatment of severe fetal anemia from a variety of causes, such as non-RhD alloimmunization, parvovirus B19 infection, chronic fetomaternal hemorrhage, homozygous alpha thalassemia, and infrequently in twin-twin transfusion syndrome and twin-anemia polycythemia sequence.

This topic will discuss patient selection for IUT, procedural issues, complications, and outcome. Potential indications for IUT are reviewed separately.

(See "RhD alloimmunization in pregnancy: Management".)

(See "Management of non-RhD red blood cell alloantibodies during pregnancy".)

(See "Parvovirus B19 infection during pregnancy", section on 'Management of anemia and hydrops'.)

(See "Spontaneous massive fetomaternal hemorrhage".)

(See "Management of thalassemia".)

(See "Twin-twin transfusion syndrome: Management and outcome", section on 'Management of stage V TTTS' and "Twin anemia-polycythemia sequence (TAPS)", section on 'Pregnancy management'.)

SELECTION OF PATIENTS AND PROCEDURES — Pregnancies with severe fetal anemia at 18 to 35 weeks of gestation are optimal candidates for IUT.

Diagnosis and treatment of severe anemia – These pregnancies are initially identified by measuring the fetal middle cerebral artery peak systolic velocity (MCA-PSV): Moderate to severe anemia should be suspected when MCA-PSV is ≥1.50 multiples of the median (MoM). In these cases, the hematocrit/hemoglobin is determined by obtaining fetal blood via percutaneous umbilical vein sampling. (See "RhD alloimmunization in pregnancy: Management", section on 'Assess for severe anemia using MCA-PSV in fetuses at risk' and "Fetal blood sampling".)

The author of this topic performs a first IUT if the fetal hemoglobin is two standard deviations below the mean value for gestational age (table 1). Intervention at this moderately reduced hemoglobin level results in a better fetal outcome than waiting until development of severe anemia (hemoglobin level more than 7 g/dL below the normal mean for gestational age [1]) or development of fetal hydrops (hemoglobin level typically <5 g/dL [1]) [2]. A hematocrit less than 30 percent can also be used as the threshold for fetal transfusion [3].

Route of transfusion – The intravascular approach to IUT is generally limited to pregnancies between 18 and 35 weeks of gestation. Before 18 weeks, the small size of the relevant anatomic structures presents technical challenges; after 35 weeks, IUT is considered riskier than delivery followed by postnatal transfusion therapy [4]. (See 'Umbilical vein' below.)

Prior to 18 weeks of gestation, intraperitoneal transfusions have been used as bridge therapy until access to the umbilical vein is technically feasible later in gestation [5]. (See 'Peritoneal cavity' below.) However, for the rare patient with very severe alloimmunization and previous second-trimester perinatal loss, the administration of intravenous immunoglobulin G (IVIG) with or without maternal plasma exchange may maintain the fetal hematocrit above life-threatening levels long enough to achieve a gestational age when IUT is technically feasible. This is discussed in detail separately. (See "RhD alloimmunization in pregnancy: Management", section on 'Management of pregnancies with severe fetal anemia before 24 weeks of gestation'.)

BLOOD PREPARATION

Allogenic volunteer donor units — RBCs used for IUT should undergo the same testing that occurs for any RBC donor unit. The units are cross-matched with maternal blood to prevent incompatibility with existing maternal anti-red blood cell antibodies. (See "Blood donor screening: Laboratory testing".)

Additional requirements specific to IUT include:

In cases of RhD alloimmunization, type O RhD negative donor units are transfused. In cases of alloimmunization to other RBC antigens, donor units for transfusion are cross-matched to the pregnant patient. Maternal blood may be the best source of donor RBCs in cases where multiple antibodies or alloimmunization to a low-frequency red blood-cell antigen is present. (See 'Maternal donor units' below.)

In cases of Rhc alloimmunization, RhD-positive donor blood will probably be necessary for IUT since an RhD-negative, Rhc-negative donor is rare.

Some centers undertake an extended cross-match based on the maternal RBC phenotype. In one study, extended matching of units for Duffy, Kidd, and S antigens resulted in a 60 percent reduction in the production of new maternal antibodies to these RBC antigens [6].

Donor units negative for antibody to cytomegalovirus (CMV) are chosen, if available.

Leukodepletion should be routinely performed and reduces the CMV risk if a unit from a CMV-seronegative donor is unavailable.

Donor units should be negative for hemoglobin S [7].

The donation should be relatively fresh (<7 days of age) to enhance the level of 2-3-diphosphoglycerate and thus decrease oxyhemoglobin affinity [7].

Association for the Advancement of Blood & Biotherapies (AABB; formerly the American Association of Blood Banks) standards require that RBC units for IUT undergo irradiation with 25 Gy of gamma radiation to the central portion of the donor bag to prevent a graft-versus-host reaction [7].

Donor units are washed and tightly packed to a final hematocrit of 75 to 85 percent to reduce the volume administered to the fetus. (By comparison, a unit of RBCs for transfusion of adults has a hematocrit of approximately 65 percent.)

Maternal donor units — Maternal blood can be used for fetal transfusion if all of the prerequisites for autologous donation are met; however, the requirement for a predonation hemoglobin above 12.5 g/dL will exclude many pregnant people as potential donors (see "Surgical blood conservation: Preoperative autologous blood donation"). The author advises pregnant people who donate blood to consume a daily prenatal vitamin as well as supplemental iron (325 mg ferrous sulfate every other day) and folic acid (1 mg daily). Parenteral iron is appropriate for patients who do not tolerate oral iron, who do not have the expected increase in hemoglobin level with oral iron, and in whom there would be insufficient time to replete iron orally, as it can fully correct iron deficiency in a single administration. (See "Anemia in pregnancy", section on 'Oral versus IV iron'.)

Advantages – Use of maternal RBCs for IUT has some advantages:

It eliminates the mother's risk of becoming newly sensitized to donor RBC antigens. Observational studies of pregnant people undergoing IUT have reported that approximately 25 percent produce additional RBC antibodies due to fetomaternal transfer of donor RBCs with foreign antigens or fetal blood with foreign paternal antigens [8-10]. The risk is highest when the IUT necessitates passing a needle through the placenta. Matching the donor and mother for D, C, c, E, e, and K antigens does not eliminate the risk of new maternal antibody formation because differences in other minor antigens still exist [9].

The RBCs may have a longer half-life, which would potentially decrease the total number of IUTs needed for fetal treatment. A study comparing 76 IUTs in which maternal RBCs were used with 213 IUTs in which donor RBCs were used reported the rate of decline of the fetal hematocrit between IUT procedures was significantly slower in fetuses that received maternal blood, although this difference was not evident until after 33 weeks of gestation [11]. Neonates that received maternal blood required fewer transfusions than neonates whose transfusion came from other donors. The lower transfusion requirements may have been related to use of blood with a high proportion of young cells (with a longer half-life) as a result of increased maternal reticulocytosis after repeated maternal donations.

The risk of transmission of blood-borne viral infections may be lower, but this has not been studied.

Collection – In contrast to blood donation from the usual blood donor, pregnant blood donors are placed in the left lateral recumbent position during the donation and the donated volume is replaced with isotonic intravenous fluids. Fetal monitoring during maternal blood donation is unnecessary. A standard volume of 450±45 mL is withdrawn, as subsequent washing and packing will markedly reduce the final volume available for IUT. The donated unit can be separated into two smaller aliquots and refrigerated for up to 42 days; however, prolonged refrigeration compromises the advantages of using fresh blood. Blood can be frozen within six days of collection for future use and can be stored for up to ten years.

Processing – A unit donated by the mother for her fetus undergoes additional processing compared with nonmaternal donor units. It is washed several times to remove the problem antibody. Since the mother and fetus share human leukocyte antigens (HLA) at many loci, the possibility of graft-versus-host disease is higher than with use of an unrelated donor unit where HLA mismatch enables the recipient's immune system to destroy the donor lymphocytes. However, the standard practice of preinfusion irradiation of the unit will prevent this complication.

Issues when the mother is CMV seropositive – The use of maternal blood from a CMV-seropositive mother is controversial since dormant CMV can reside in polymorphonuclear leukocytes; however, leukoreduction is typically performed and is an effective mechanism for preventing the transmission of CMV. The known and possible risks and benefits of use of blood from CMV-seropositive mothers should be discussed with the mother in consultation with the blood bank service.

Maternal siblings as donors — The mother's siblings, if ABO compatible with the fetus, can be tested as potential RBC donors. In 25 percent of cases, the sibling's RBCs will be compatible with the mother's serum if their parents are heterozygous for the corresponding low frequency antigen. This approach should be reserved for rare settings of clinically significant alloantibodies where access to compatible allogeneic volunteer donor units is limited.

PROCEDURE

Clinician experience — In an evaluation of the "learning curve" for IUTs at a single center with four operators using cumulative sum analysis, a level of competence was achieved after 34 and 49 procedures [12]. The authors hypothesized that individual maintenance of competence would require at least 10 procedures annually.

Maternal preparation

Forty-eight hours before the initial IUT, a course of antenatal corticosteroids is administered when the fetus is at a gestation age where the patient and their physician agree that emergency cesarean birth would be performed if indicated because of fetal compromise. (See "Antenatal corticosteroid therapy for reduction of neonatal respiratory morbidity and mortality from preterm delivery".)

Many centers will allow the patient to have clear liquids up to two hours before the scheduled procedure. Other types of oral intake should be avoided for six to eight hours before the procedure.

If the fetus has attained a gestational age where emergency cesarean birth would be performed, many centers perform the IUT in an operating room on the Labor and Delivery unit in the event that a serious complication necessitating an emergency delivery occurs.

Intravenous access is obtained.

Some clinicians administer a prophylactic antibiotic such as a first generation cephalosporin (1 to 2 grams within one hour of the start of the procedure); no data are available on the value of antibiotic prophylaxis in this setting.

Maternal sedation (eg, midazolam 1 to 2 mg or fentanyl 25 to 50 mcg intravenously) may be administered, if needed to reduce maternal anxiety. In the operating room, a remifentanil infusion can be used and monitored by an anesthesiologist. It can be easily titrated to the desired effect due to its short half-life.

Choosing a fetal access site — Potential fetal access sites include the umbilical vein, peritoneal cavity, umbilical artery, and heart. The various points of access for IUT have not been compared in randomized trials [13].

Our approach — Intravascular fetal transfusion (IVT) is preferable to intraperitoneal transfusion (IPT) because of higher survival rates, particularly of hydropic fetuses [14-17]. The umbilical vein is the preferred vascular site because of ease of access and greater safety compared with other vascular sites. Umbilical artery puncture results in a higher incidence of bradycardia than umbilical vein puncture, probably due to spasm of the muscularis [18,19]. Direct cardiac puncture is rarely performed because of a higher risk of severe complications, including fetal death [20-22].

Gestational age and fetal ascites are other considerations. IVT early in the second trimester (<22 weeks) is technically challenging, particularly if the mother has obesity. In these cases, use of IPT followed by IVT when technically feasible can be the best approach [23]. However, IPT is ineffective in the setting of fetal ascites due to poor absorption of the intraperitoneal blood; IVT should be performed in these cases if possible. Intracardiac transfusion is an option if IVT is not possible [22]. 

In most patients, the author uses a combined approach (IVT followed by IPT) as it provides a more stable fetal hematocrit between procedures, presumably due to slow absorption of RBCs from the intraperitoneal reservoir. This allows a longer interval between procedures, so fewer IUTs are needed [24,25]. Packed RBCs are administered by IVT to achieve a final fetal hematocrit of 35 to 40 percent, immediately followed by a standard calculated volume of RBCs for the IPT [24] (see 'Calculating transfusion volume' below). The decline in fetal hematocrit between procedures is markedly reduced with this approach when compared with IVT alone (0.1 versus 1 percent decline per day).

Umbilical vein — North American centers typically target the umbilical vein at the placental end of the cord insertion for the site of transfusion, while many European centers target the intrahepatic portion of the umbilical vein. Either target is reasonable.

Umbilical cord at placental insertion site — The author's preference is to puncture the umbilical vein in the portion of umbilical cord near its insertion into the placenta. Puncture of a free-floating middle segment of cord or the cord insertion proximate to the fetal umbilicus is undesirable because manipulation of the cord at these sites is more likely to result in fetal bradycardia [18,19]. Free-floating midsegments of the umbilical cord have the additional problem of readily floating away from the needle when cord penetration is attempted. Cord movement is minimal where the cord is anchored by the placenta.

If the umbilical vein in the portion of umbilical cord near its insertion into the placenta is not accessible due to fetal position and posterior placentation, the intrahepatic portion of the umbilical vein is a reasonable option when the fetus is appropriately positioned.

Intrahepatic umbilical vein — Transfusion into the intrahepatic portion of the umbilical vein is an acceptable alternative to transfusion at the placental insertion site as long as the fetal position is favorable. The procedure-related fetal loss rate appears to be similar to, or less than, that with puncture of the umbilical vein at the placental insertion [19,26].

Two advantages of puncture of the intrahepatic portion of the umbilical vein are (1) a low incidence of fetal bradycardia, probably due to absence of inadvertent umbilical artery puncture at this anatomical level, and (2) blood loss from the cord puncture site is compensated, at least in part, by its subsequent absorption from the peritoneal cavity [26,27].

One concern regarding the intrahepatic umbilical vein site is that it may be more painful for the fetus. The fetal stress hormones noradrenaline, cortisol, and beta-endorphin have been reported to increase with intrahepatic puncture, a response not seen with procedures at the placental insertion site [28]. Another concern is that fetal movement during intrahepatic umbilical vein transfusion places the fetus at higher risk of organ trauma from a dislodged needle than when transfusion is performed at other sites. This can be avoided by administering a drug to induce fetal paralysis or not holding the transfusion needle in a fixed position during the infusion [19,27,29]. (See 'Technique' below.)

Peritoneal cavity — IPT provides indirect access to the fetal circulation. It utilizes the principle that fluid and cells in the peritoneal cavity are absorbed through the subdiaphragmatic lymphatics and thoracic duct. In the hydropic fetus, however, functional blockage of the lymphatic system probably exists and prevents good absorption of RBCs, thus rendering the procedure ineffective in those fetuses who are most severely anemic and in need of treatment. In a study of hydropic and nonhydropic fetuses matched for severity of disease, placental location, and gestational age at the first transfusion, IVT approximately doubled the survival rate in hydropic fetuses and increased survival by 13 percent in nonhydropic fetuses compared with IPT [14].

Given the higher rate of survival with IVT, it is the preferred method for transfusing the anemic fetus. However, IPT remains a viable option when fetal vascular access is difficult because of early gestational age or fetal position [23,30].

Calculating transfusion volume

Intravascular transfusion — The volume of blood transfusion for IVT depends upon the initial fetal hematocrit, fetal size, hematocrit of the transfused RBCs, and target hematocrit. Gestational age affects whether the calculated volume for initial transfusion is administered over one, two, or three procedures.

Formula

The simplest method of calculating the volume of packed RBCs to be infused assumes the donor unit has a hematocrit of approximately 78 percent and uses a series of coefficients for increasing the initial fetal hematocrit by specific increments (table 2) [31]. As an example, to increase the hematocrit of a 1000-gram fetus by 10 percent, one multiplies 1000 (the estimated fetal weight [EFW] in grams) by 0.02 to yield 20 mL (the volume that needs to be transfused to raise the fetal hematocrit by an increment of 10 percent). After obtaining the initial fetal hematocrit, the total volume to be transfused to reach a target hematocrit can then be calculated using this increment.

Another formula for calculating the amount of blood to be transfused is [32]:

Volume transfused (mL) = volume of fetoplacental unit (mL) x (final - initial hematocrit) divided by the hematocrit of the transfused blood.

The fetoplacental volume (mL) is calculated from the ultrasound estimate of the fetal weight according to the formula (1.046 + fetal weight in grams x 0.14).

Influence of gestational age – Fetal hematocrit normally increases linearly across gestation. The normal fetal hematocrit is 37±4 percent at 17 weeks, rising to 43±7 percent at term [33]. However, acute correction of severe fetal anemia is associated with profound hemodynamic changes. For example, cardiac output falls markedly due to the acute increase in afterload and viscosity markedly increases [34]. These abrupt hemodynamic changes are most stressful for fetuses at earlier gestational ages. Therefore, for fetuses under 24 weeks, the target hematocrit for the first transfusion is typically lower than the normal hematocrit for gestational age.

Before 24 weeks of gestation – Before 24 weeks, the author aims for a first post-transfusion hematocrit below 25 percent, or less than a fourfold increase from the pretransfusion value [35]. A second IVT is performed within 48 hours to bring the hematocrit into the normal range, and a third IVT is scheduled 7 to 10 days later.

After 24 weeks of gestation – After 24 weeks of gestation, the author's target hematocrit is 40 to 50 percent, consistent with expert guidelines [36]. Transfusing the fetus to supraphysiologic hematocrit values (50 to 65 percent) should be avoided (although done at some centers) because this level of hematocrit is associated with a marked rise in whole blood viscosity [37], which can lead to complications [38,39].

Intraperitoneal transfusion

Formula – The formula for the volume of IPT was determined decades ago to allow for the maximum infusion of RBCs without compromising umbilical venous blood flow from excessive intraabdominal pressure. The calculation involves subtracting 20 from the gestational age in weeks and multiplying by 10 [40]. Thus, a fetus at 30 weeks would receive 100 mL of blood ([30-20] X10 = 100). Blood in the peritoneal reservoir can be expected to be absorbed over a 7 to 10 day period.

Influence of gestational age – The historic formula does not allow for calculation of IPT volume prior to 20 weeks of gestation. In a series of six patients with a previous history of severe fetal anemia before 20 weeks (including 4 fetal deaths), IPT was performed from 15 to 21 weeks in the subsequent pregnancy using between 5 and 10 mL of donor cells with a hematocrit between 72 and 80 percent in conjunction with weekly maternal IVIG infusions; the fetuses were then transitioned to IVT [23]. Five of the six fetuses in the subsequent pregnancy survived.

Technique

Preparation – The uterus is displaced to the left to avoid aortocaval compression and reduce the risk of maternal supine hypotension. The abdomen is prepared and draped as for a surgical procedure.

Sonographic guidance and needle insertion – One operator provides continuous ultrasound guidance using a transducer covered with a sterile sleeve.

For IVT into the umbilical vein, the operator identifies the access site and infiltrates the maternal skin with a local anesthetic and then directs a 20-gauge six-inch needle into the vein. A 22-gauge needle can be used for pregnancies under 22 weeks due to the small vessel size at these earlier gestational ages.

Fetal blood sample – An initial sample of blood is withdrawn for a complete blood count and reticulocyte count. We use a portable automated hemocytometer that is located near the operating room because it provides results quickly and, in contrast to a spun capillary hematocrit, gives mean corpuscular red cell volume (MCV), which confirms that fetal, as opposed to maternal, blood has been obtained (MCV greater than 100 mL suggests fetal RBCs). This requires coordination with the hospital laboratory service to schedule a technician who will run the required standards prior to analyzing a sample. However, the MCV is not helpful after two transfusions since the fetal RBCs have been replaced by adult RBCs. Injecting saline and seeing turbulence in the umbilical vein is another method of confirming that the needle position is correct.

Fetal paralysis and sedation – After withdrawing a blood sample, a short-acting paralytic agent is administered to minimize fetal movement and, in turn, needle dislodgement. Options include vecuronium (0.1 mg per kg of ultrasound EFW) [41] or atracurium besylate (0.4 mg per kg of EFW) [29,42]. These drugs provide fetal paralysis for up to one to two hours and have minimal cardiovascular effects. Fetal paralysis appears to improve the safety of fetal transfusion and has been reported to prevent 80 percent of procedure-related fetal heart rate (FHR) changes [19].

The author also administers fentanyl (2 mcg per kg of EFW) for fetal sedation (ie, attenuate the fetal physiological stress response and fetal movement); it is mixed in the same syringe as the paralytic agent. The fetal physiological stress response, if not blunted, may have deleterious effects on the developing central nervous system [43,44].

Transfusion – If fetal anemia is confirmed (fetal hemoglobin two standard deviations below the mean value for gestational age (table 1) or hematocrit <30 percent), a second operator infuses packed RBCs using a 20 mL syringe attached to a three-way stopcock connected, via extension tubing, to the blood bag and the procedure needle. A nonluer lock stopcock is used to connect the procedure needle and distal end of the extension tubing to facilitate manipulation of the tubing without disturbing the needle. During the infusion, the transfused blood should be visible streaming away from the needle in the umbilical vein as it mixes with fetal blood.

Fetal heart rate monitoring – The FHR should be monitored periodically using color flow or pulsed Doppler ultrasound. Swirling at the tip of the needle (as opposed to streaming inside the vein away from the tip of the needle) suggests a fall in fetal cardiac output and should prompt FHR assessment for bradycardia.

If a deceleration is noted, the infusion is stopped and then restarted at a slower rate after the FHR recovers. If the deceleration does not resolve after 30 seconds, however, intravenous administration of atropine (20 mcg per kg EFW by ultrasound) should be considered just prior to removal of the procedure needle. To prepare for this possibility, we include two sterile syringes of atropine in the initial procedure set-up. The mother should be turned to the left lateral decubitus position and the FHR is continuously monitored by ultrasound. We perform an emergency cesarean birth when fetal myocardial contractility is severely depressed (ie, no opening and closing of the fetal atrioventricular valves is seen on ultrasound) or a deceleration persists for more than three minutes with no sign of resolution, and the gestational age is above the lower limit of neonatal viability.

Post-transfusion blood sample – When the infusion is completed, another fetal blood sample is obtained to check the post-transfusion hematocrit. After the second and subsequent transfusions, the author also performs a Kleihauer-Betke test or hemoglobin electrophoresis to determine the proportion of adult RBCs or adult hemoglobin, which indicates the extent of suppression of fetal erythropoiesis as a result of transfusion.

Post-transfusion monitoring – The FHR is monitored in a recovery room setting until fetal movement resumes and a reactive nonstress test (as appropriate for gestational age) is documented. The patient can then be discharged.

Follow-up – A follow-up ultrasound examination is scheduled for the following day as most cases of fetal loss occur within the first 24 hours post procedure.

Scheduling subsequent transfusions — The goal is to maintain the fetal hematocrit above 25 percent.

Second, third, and fourth transfusions – The author empirically transfuses again 10 days after the first transfusion, two weeks after the second transfusion, and three weeks after the third transfusion. Another reasonable approach is to base the interval between transfusions on the expected decline in fetal hemoglobin of 0.4 g/dL/day, 0.3 g/dL/day, and 0.2 g/dL/day after the first, second, and third transfusion, respectively [45,46]. However, the immediate post-procedure hemoglobin may not reflect the hemoglobin when the fetus is stable due to fluid shifts from the extravascular to the intravascular compartment and bleeding from the cord puncture site when the needle is removed.

Subsequent transfusions – The interval between subsequent procedures can usually be lengthened to three to four weeks because after three transfusions fetal erythropoiesis is suppressed and the fetal blood volume is composed primarily of donor RBCs, which are not at risk for hemolysis. At this point, it is assumed that the fetal hemoglobin falls by 0.4 g/dL/day and hematocrit falls by an absolute value of 1 percent per day due to aging of RBCs and fetal growth. The lifespan of adult RBCs may be shorter in the fetal circulation [47-49]. In addition, progressive fetal growth results in an increased intravascular space, thereby creating a dilutional anemia when fetal erythropoiesis is suppressed. However, the rate in the fall of hemoglobin is variable, and faster when the fetus is hydropic (approximately 2 percent per day [50]), fetomaternal bleeding is ongoing, or the mother develops antibodies to new RBC antigens.

Role of Doppler — No convincing data support the use of Doppler measurement of fetal middle cerebral artery peak systolic velocity (MCA-PSV >1.5 multiples of the median [MoM]) for timing repeat transfusions. Although MCA-PSV greater than 1.50 MoM is very useful for predicting moderate to severe anemia before the initial fetal transfusion, this threshold performs less well for timing the second and subsequent IUTs because fetal MCA blood flow is different when replaced by adult RBCs [45,46,51]. Adult RBCs are smaller, less rigid, and have different oxygen carrying capacity and oxygen delivery characteristics compared with fetal RBCs. As a result, adult RBCs have different rheological properties than fetal RBCs.

In a multicenter randomized trial of 71 patients that evaluated serial MCA-PSV determinations versus calculated decline in fetal hematocrit (1 percent/day) for determining inter-transfusion intervals, the number of IUTs performed, the incidence of procedure-related complications, and the incidence of adverse infant outcomes were similar for the two approaches [52]. The serial MCA Doppler group had a nonstatistically significant trend towards a lower mean hemoglobin level at birth (10.36 versus 12.03 g/dL) and more frequent need for neonatal exchange transfusion (40.0 versus 26.5 percent). This is concerning and implies that the more cost-effective approach for determining when to perform the next IUT should be based on the predicted decline in fetal hematocrit between procedures, which is the author's practice.

If a clinician chooses to use MCA-PSV for determining when to perform the second transfusion, we suggest a threshold of 1.69 MoM, which correlates with severe anemia in the fetus who has undergone a single IUT [36]. In one study, a threshold value of 1.69 MoM predicted all cases of severe fetal anemia with a false positive rate of 6 percent, and a threshold value of 1.32 MoM predicted all cases of moderate anemia with a false positive rate of 37 percent [51]. We suggest not using MCA-PSV to time subsequent IUTs [53]. After two previous IUTs, 66 to 100 percent of the fetus's RBCs contain adult hemoglobin. In this setting, where most of the fetal RBCs have been replaced by donor cells, MCA-PSV loses its ability to discriminate moderate to severe fetal anemia from mild anemia [45,54]. In a meta-analysis of 12 studies (696 fetuses), the sensitivity of MCA-PSV ≥1.50 MoMs for prediction of moderate to severe anemia after one, two, or three or more transfusions was 78, 74, and 60 percent, respectively, compared with 86 percent in nontransfused fetuses [55]. Therefore, expected decline in fetal hemoglobin of 0.3 g/dL/day is the best way to predict timing of the third and subsequent transfusions [36,56].

When to stop IUTs — IUTs are generally not performed after 35+0 weeks of gestation [22].

Phenobarbital — The author prescribes phenobarbital (30 mg orally three times per day for 10 days prior to the day of planned delivery) for his patients after their last IUT to enhance fetal hepatic maturity. In his series of patients who underwent IUT for fetal hemolytic disease, newborns of the 33 patients who received phenobarbital prior to delivery had significantly fewer exchange transfusions than newborn survivors of the 38 patients who did not receive phenobarbital (3 out of 33 versus 16 out of 31) [57]. However, a randomized trial is needed to demonstrate the potential efficacy of short-term phenobarbital administration in reducing the need for neonatal exchange transfusion.

Timing delivery — Labor is induced approximately three weeks after the last IUT, typically at 37+0 or 38+0 weeks of gestation, or a cesarean birth is scheduled if indicated for standard obstetric indications [22].

Delayed cord clamping — Delayed cord clamping appears to be advantageous for fetuses who have received IUTs because of RBC alloimmunization.

In an observational study (72 pregnancies), delaying cord clamping by 30 seconds compared with immediate cord clamping in this population was associated with higher hemoglobin levels at birth (13.2 versus 10.2 g/dL), a smaller proportion of neonates requiring postnatal exchange transfusions (19 versus 47 percent), and slightly longer duration between birth and first transfusion [58]. The maximum level of bilirubin, rate of intensive phototherapy, and total duration of phototherapy were the same for both groups.

In the only randomized trial evaluating the outcome of delayed versus early cord clamping in Rh-alloimmunized infants (70 infants at 28 to 41 weeks of gestation approximately half of whom had IUTs), delayed clamping improved hematocrit (called packed cell volume in this study) at two hours of life without significantly increasing risks for double volume exchange transfusion, partial exchange transfusion, and duration of phototherapy during the hospital stay, or blood transfusion through 14 weeks of life [59].

Special populations

Multiple gestations — In multiple gestations, using the intrahepatic portion of the umbilical vein for IVT access clearly identifies which fetus is being transfused. In comparison, it can be difficult to determine which fetus is associated with its corresponding umbilical cord at the placental insertion site.

Dichorionic twins – Neither, one, or both of a dichorionic twin pair may be anemic. Since intraplacental anastomoses are rare in dichorionic twins, each fetus is managed in the same way as a singleton pregnancy.

Monochorionic twins – Neither or both twins are affected in monochorionic twins. Because intraplacental anastomoses are almost universal, MCA-PSV is measured in the twin not initially targeted for IUT as a baseline. After the co-twin has been transfused to the usual target hematocrit, a repeat MCA-PSV is performed in the nontargeted twin while the patient is still in the procedure room. Normalization of the previously elevated MCA-PSV indicates that suspected anemia in the nontargeted twin has been corrected through intertwin transfusion. There are no specific guidelines on the total volume to transfuse in these situations.

Reports of IUTs in multiple gestations have been limited to case descriptions of twins. The largest series reported to date included only five pregnancies: four cases of dichorionic twin gestations and one case of monochorionic twins [60]. In the one case of monochorionic gestation, IUT of one fetus was quickly followed by movement of donor RBCs through intraplacental anastomoses, as illustrated by a positive Kleihauer-Betke stain at the time of fetal blood sampling of the second twin. In subsequent IUTs, the transfusion of only one member of the twin pair resulted in adequate levels of hemoglobin in both twins.

COMPLICATIONS

Intravascular transfusion — Fetal bradycardia and bleeding from the puncture site are the most common complications of IUT, but usually resolve. Transient bradycardia occurs in 4 to 5 percent of intravascular transfusions (IVTs), possibly secondary to arterial spasm [61,62]. The rate is higher when the umbilical artery is transfused. Post-procedure bleeding from the puncture site for more than one minute was reported in 5 percent of 135 procedures in one series, but bleeding did not lead to a severe adverse event in six of the seven cases [62].

The rates of serious procedure-related complications of IVT were illustrated in a series of 937 transfusions in 334 fetuses at the national referral center for fetal therapy in Leiden, The Netherlands between 2001 and 2015 [63]:

Any complication – 1.2 percent of procedures

Preterm prelabor rupture of membranes – 0.1 percent of procedures

Infection – 0.1 percent of procedures

Emergency cesarean delivery – 0.4 percent of procedures

Fetal loss – 0.6 percent of procedures

These rates are lower than or similar to those published in an earlier series from the same center [19]. The authors attributed the improvement to experience derived from a high annual procedure volume and to avoiding techniques that may increase the occurrence of complications, such as umbilical arterial puncture, transfusing into a free loop of cord in amniotic fluid, and transfusion without use of fetal paralytic drugs. However, patients in the most recent cohort also had less severe disease at referral (eg, fewer cases of hydrops and fewer transfusions at very early gestational ages). The authors noted that pregnancies less than 20 weeks of gestation remain at higher risk of procedure-related complications. Fetal hydrops was not associated with an increased risk of procedure-related complications, but was associated with a higher risk of adverse outcome.

Other potential complications include fetal cerebral injury, possibly related to changes in intravascular volume, hemodynamics, and/or viscosity; fetal trauma from movement into the needle; bleeding from laceration of a large placental vessel; and fetomaternal hemorrhage, which can potentially increase maternal alloantibody titers as well as severity of hemolytic disease in the index or future pregnancies [38,64,65].

Intraperitoneal transfusion — Most of the complications that can occur with IVT can also occur with intraperitoneal transfusion (IPT).

Procedure-related complications specific to IPT were illustrated in a series describing the outcome of 77 fetal IPTs in 35 pregnancies [66]. Transfusion-related complications occurred in five cases (two fetal colon infusions, two fetal retroperitoneal infusions, one fetal abdominal wall hematoma), but no fetus died, required urgent delivery, or suffered long-term sequelae. These procedures were performed under continuous ultrasound guidance and with intensive perinatal management.

OUTCOME IN ALLOIMMUNIZED PREGNANCIES

Survival — Overall survival after IUT is over 95 percent when transfusion is performed for alloimmunization but varies with center, experience, and gestational age at development of hydrops fetalis [67]. Survival is reduced when severe anemia develops before 20 weeks of gestation [19,68]. The higher rate of fetal loss at early gestational ages reflects the technical difficulties of invasive therapy in a very small fetus, as well as the inability of the very immature fetus to tolerate the hemodynamic changes of severe anemia and the hemodynamic changes following transfusion [5,68,69].

A report from a single treatment center included 645 fetuses receiving 1852 IUTs between 1987 and 2016. Severe hydrops was defined as the presence of moderate ascites with or without the presence of pericardial or pleural effusions or scalp edema; mild hydrops was defined as a thin rim of ascites with or without a pericardial effusion. Survival was 67 percent with severe hydrops, 95 percent with mild hydrops, and 96 percent with no hydrops [67]. The frequency of hydrops fell substantially after 1998. This was attributed to routine first-trimester antibody screening in all pregnant people; the utility of middle cerebral artery peak systolic velocity (MSA-PSV) for early, accurate detection of severe fetal anemia; and timely referral of these fetuses for IUT. Between 2011 and 2016, only 6 of 115 fetuses were hydropic (5 mild, 1 severe) and all survived.

Neonatal transfusion — If the neonatal hematocrit is near normal because of a recent IUT for alloimmunization, neonatal exchange transfusion may not be necessary. With senescence of the transfused RBCs, 88 percent of infants transfused in utero will require a "top-up" transfusion in the first three months of life due to suppression of fetal erythropoiesis from IUT and persistence of maternal antibody not removed by exchange transfusion [70,71]. In some cases, up to four top-up transfusions are necessary before reticulocytosis begins and anti-red cell antibodies disappear [72]. Management of these infants is discussed separately. (See "Alloimmune hemolytic disease of the newborn: Postnatal diagnosis and management".)

Neurologic outcome — One long-term concern of IUT is that advances in treatment techniques have allowed more moribund and hydropic fetuses to survive and these children may be at higher risk of long-term morbidity. Available data are reassuring, but are limited to mostly small series [73-78].

The LOTUS study (long-term follow-up after IUTs) is the largest study to evaluate the incidence of and risk factors for neurodevelopmental impairment in children with hemolytic disease of the fetus/newborn treated with IUT [79]. Alloimmunization was related to RhD in 80 percent of cases, 26 percent of the fetuses were hydropic, the mean gestational age at first transfusion was 26 weeks, the mean number of transfusion was 3, and all of the pregnancies were delivered between 35 and 37 weeks of gestation. Major findings at follow-up at median age 8.2 years (range 2 to 17 years) were:

Isolated severe developmental delay – 5 in 291 (1.7 percent)

Isolated cerebral palsy – 2 in 291 (0.7 percent)

Isolated bilateral deafness – 3 in 291 (1.0 percent)

Cerebral palsy and severe developmental delay – 4 in 291 (1.4 percent)

Composite neurodevelopmental impairment (cerebral palsy, severe development delay, bilateral deafness, or blindness) – 14 in 291 (4.8 percent)

The incidence of severe neurodevelopmental delay (3.1 percent) in this study is similar to that of the general Dutch population (2.3 percent). However, the incidence of cerebral palsy (2.1 percent) was higher than expected in a general population (0.7 percent with delivery between 32 and 36 weeks and 0.2 percent with delivery at ≥37 weeks of gestation).

The major risk factor for neurodevelopmental impairment was hydrops, which affected 9 in 14 (64 percent) children with neurodevelopmental impairment versus 66 in 277 (24 percent) children without impairment. In a multivariate regression model, severe hydrops was a significant independent risk factor, but mild hydrops was not.

High neonatal bilirubin levels due to increased RBC destruction may cause hearing loss. Phototherapy and exchange transfusion are the two major modalities used to prevent complications from hyperbilirubinemia, but hearing loss has been reported rarely despite therapy [74]. The author suggests initial neonatal hearing screening (which is mandated by most states in the United States) followed by hearing screening at one year of age. (See "Unconjugated hyperbilirubinemia in term and late preterm newborns: Initial management" and "Unconjugated hyperbilirubinemia in neonates: Risk factors, clinical manifestations, and neurologic complications", section on 'Chronic bilirubin encephalopathy (kernicterus)'.)

Other outcomes — Pilot studies have suggested that fetal anemia may have long-term effects on cardiovascular development [80,81]. However, the clinical significance of these mild changes in cardiovascular development is unknown.

SUMMARY AND RECOMMENDATIONS

Candidates for fetal transfusion – Pregnancies with severe fetal anemia at 18 to 35 weeks of gestation are optimal candidates for intrauterine transfusion (IUT). We obtain fetal blood for hematocrit/hemoglobin determination when the fetal middle cerebral artery peak systolic velocity (MCA-PSV) is >1.50 multiples of the median (MoM) and perform the first IUT if fetal hemoglobin is two standard deviations below the mean value for gestational age (table 1). (See 'Selection of patients and procedures' above.)

Blood for transfusion – Packed red blood cells (RBCs) from an allogenic volunteer donor or the mother can be used for IUT. Blood for IUT must undergo the same testing that occurs for any red cell donor unit and additional preparations unique to this setting. (See 'Blood preparation' above.)

Transfusion technique

We suggest administering a short-acting paralytic agent to the fetus (Grade 2C). Reduction in fetal movement reduces the risk of complications. (See 'Technique' above.)

For the hydropic fetus, we recommend intravascular transfusion (IVT) rather than intraperitoneal transfusion (IPT) (Grade 1B). IVT results in significantly higher survival rates than IPT in this population.

We also suggest IVT for nonhydropic fetuses (Grade 2C). IVT appears to be more effective in nonhydropic fetuses as well, and its effects are more rapid than IPT, but both procedures are effective and either procedure is reasonable. In most patients, the author uses a combined approach (IVT followed by IPT at the same procedure) as it provides a more stable fetal hematocrit between procedures. (See 'Choosing a fetal access site' above.)

We use the umbilical vein near the placental insertion site for IVT, but using the intrahepatic portion of the umbilical vein is also reasonable. Puncture of the umbilical artery should always be avoided because it can cause spasm. (See 'Umbilical vein' above.)

In cases of severe alloimmunization with suspected fetal anemia before 20 weeks when reasonable access to the umbilical vein cannot be attained, IPT is a reasonable option. Volumes of 5 to 10 mL have been used in these cases. (See 'Intraperitoneal transfusion' above.)

Target hematocrit – We aim for a target hematocrit of 40 to 50 percent. The volume of blood for IUT is calculated from a formula and depends upon the initial fetal hematocrit, size of the fetus, the hematocrit of the transfused RBCs, and the target hematocrit. (See 'Intravascular transfusion' above.)

Transfusion schedule

We empirically transfuse 10 days after the first transfusion, two weeks after the second transfusion, and three weeks after the third transfusion. Another reasonable approach is to base the interval between transfusions on the expected decline in fetal hemoglobin of 0.4 g/dL/day, 0.3 g/dL/day, and 0.2 g/dL/day after the first, second, and third transfusion, respectively. (See 'Scheduling subsequent transfusions' above.)

Although MCA-PSV greater than 1.50 MoM is very useful for predicting moderate to severe anemia before the initial fetal transfusion, this threshold performs less well for timing the second and subsequent IUTs because fetal MCA blood flow is different when replaced by adult RBCs. If a clinician uses MCA-PSV for determining when to perform the second transfusion, we suggest a threshold of 1.32 MoM, which correlates with moderate to severe anemia in the fetus who has undergone a single IUT. We suggest not using MCA-PSV to time IUTs after the second IUT. (See 'Role of Doppler' above.)

Complications – Transient fetal bradycardia is the most common complication of IUT, but usually resolves. The best estimate of risk of procedure-related fetal loss is 1 to 2 percent and the overall risk of procedure-related complications is 3 percent. Fetal bleeding, infection, and preterm birth account for most of the mortality and morbidity. (See 'Complications' above.)

Timing of and preparation for delivery

We do not perform IUT after 35+0 weeks of gestation and induce labor approximately three weeks after the last IUT, or schedule cesarean birth if there is standard obstetric indication. (See 'When to stop IUTs' above and 'Timing delivery' above.)

We prescribe maternal phenobarbital 30 mg orally three times per day for 10 days before the planned day of delivery to enhance fetal hepatic maturity and reduce the need for neonatal exchange transfusion. (See 'Phenobarbital' above.)

Outcome

Overall survival after IUT is over 90 percent, but varies with center, experience, and the presence of hydrops fetalis. Survival of hydropic fetuses is lower than that of fetuses who are not hydropic at first transfusion. (See 'Survival' above.)

Normal neurologic outcome can be expected in over 90 percent of surviving infants, even if hydrops fetalis is noted at the time of the first transfusion. (See 'Neurologic outcome' above.)

  1. Nicolaides KH, Soothill PW, Clewell WH, et al. Fetal haemoglobin measurement in the assessment of red cell isoimmunisation. Lancet 1988; 1:1073.
  2. Mari G, Deter RL, Carpenter RL, et al. Noninvasive diagnosis by Doppler ultrasonography of fetal anemia due to maternal red-cell alloimmunization. Collaborative Group for Doppler Assessment of the Blood Velocity in Anemic Fetuses. N Engl J Med 2000; 342:9.
  3. Moise KJ Jr. Management of rhesus alloimmunization in pregnancy. Obstet Gynecol 2008; 112:164.
  4. Klumper FJ, van Kamp IL, Vandenbussche FP, et al. Benefits and risks of fetal red-cell transfusion after 32 weeks gestation. Eur J Obstet Gynecol Reprod Biol 2000; 92:91.
  5. Yinon Y, Visser J, Kelly EN, et al. Early intrauterine transfusion in severe red blood cell alloimmunization. Ultrasound Obstet Gynecol 2010; 36:601.
  6. Schonewille H, Prinsen-Zander KJ, Reijnart M, et al. Extended matched intrauterine transfusions reduce maternal Duffy, Kidd, and S antibody formation. Transfusion 2015; 55:2912.
  7. Fung MK, Grossman MK, Hillyer CD, Westhoff CM. Technical manual of the American Association of Blood Banks, 18th ed, American Association of Blood Banks, Bethesda, Maryland 2014.
  8. Viëtor HE, Kanhai HH, Brand A. Induction of additional red cell alloantibodies after intrauterine transfusions. Transfusion 1994; 34:970.
  9. Schonewille H, Klumper FJ, van de Watering LM, et al. High additional maternal red cell alloimmunization after Rhesus- and K-matched intrauterine intravascular transfusions for hemolytic disease of the fetus. Am J Obstet Gynecol 2007; 196:143.e1.
  10. Watson WJ, Wax JR, Miller RC, Brost BC. Prevalence of new maternal alloantibodies after intrauterine transfusion for severe Rhesus disease. Am J Perinatol 2006; 23:189.
  11. el-Azeem SA, Samuels P, Rose RL, et al. The effect of the source of transfused blood on the rate of consumption of transfused red blood cells in pregnancies affected by red blood cell alloimmunization. Am J Obstet Gynecol 1997; 177:753.
  12. Lindenburg IT, Wolterbeek R, Oepkes D, et al. Quality control for intravascular intrauterine transfusion using cumulative sum (CUSUM) analysis for the monitoring of individual performance. Fetal Diagn Ther 2011; 29:307.
  13. Dodd JM, Windrim RC, van Kamp IL. Techniques of intrauterine fetal transfusion for women with red-cell isoimmunisation for improving health outcomes. Cochrane Database Syst Rev 2012; :CD007096.
  14. Harman CR, Bowman JM, Manning FA, Menticoglou SM. Intrauterine transfusion--intraperitoneal versus intravascular approach: a case-control comparison. Am J Obstet Gynecol 1990; 162:1053.
  15. Lewis M, Bowman JM, Pollock J, Lowen B. Absorption of red cells from the peritoneal cavity of an hydropic twin. Transfusion 1973; 13:37.
  16. Creasman WT, Duggan ER, Lund CJ. Absorption of transfused chromium-labeled erythrocytes from the fetal peritoneal cavity in hydrops fetalis. Am J Obstet Gynecol 1966; 94:586.
  17. Taylor WW, Scott DE, Pritchard JA. Fate of compatible adult erythrocytes in the fetal peritoneal cavity. Obstet Gynecol 1966; 28:175.
  18. Weiner CP, Wenstrom KD, Sipes SL, Williamson RA. Risk factors for cordocentesis and fetal intravascular transfusion. Am J Obstet Gynecol 1991; 165:1020.
  19. Van Kamp IL, Klumper FJ, Oepkes D, et al. Complications of intrauterine intravascular transfusion for fetal anemia due to maternal red-cell alloimmunization. Am J Obstet Gynecol 2005; 192:171.
  20. Westgren M, Selbing A, Stangenberg M. Fetal intracardiac transfusions in patients with severe rhesus isoimmunisation. Br Med J (Clin Res Ed) 1988; 296:885.
  21. Antsaklis AI, Papantoniou NE, Mesogitis SA, et al. Cardiocentesis: an alternative method of fetal blood sampling for the prenatal diagnosis of hemoglobinopathies. Obstet Gynecol 1992; 79:630.
  22. Donepudi R, Antolin E, Molina F, et al. Practice patterns amongst fetal centers performing intrauterine transfusions (PACT): An international survey study. Eur J Obstet Gynecol Reprod Biol 2022; 274:171.
  23. Fox C, Martin W, Somerset DA, et al. Early intraperitoneal transfusion and adjuvant maternal immunoglobulin therapy in the treatment of severe red cell alloimmunization prior to fetal intravascular transfusion. Fetal Diagn Ther 2008; 23:159.
  24. Moise KJ Jr, Carpenter RJ Jr, Kirshon B, et al. Comparison of four types of intrauterine transfusion: effect on fetal hematocrit. Fetal Ther 1989; 4:126.
  25. Nicolini U, Kochenour NK, Greco P, et al. When to perform the next intra-uterine transfusion in patients with Rh allo-immunization: combined intravascular and intraperitoneal transfusion allows longer intervals. Fetal Ther 1989; 4:14.
  26. Nicolini U, Santolaya J, Ojo OE, et al. The fetal intrahepatic umbilical vein as an alternative to cord needling for prenatal diagnosis and therapy. Prenat Diagn 1988; 8:665.
  27. Nicolini U, Nicolaidis P, Fisk NM, et al. Fetal blood sampling from the intrahepatic vein: analysis of safety and clinical experience with 214 procedures. Obstet Gynecol 1990; 76:47.
  28. Giannakoulopoulos X, Sepulveda W, Kourtis P, et al. Fetal plasma cortisol and beta-endorphin response to intrauterine needling. Lancet 1994; 344:77.
  29. Mouw RJ, Klumper F, Hermans J, et al. Effect of atracurium or pancuronium on the anemic fetus during and directly after intravascular intrauterine transfusion. A double blind randomized study. Acta Obstet Gynecol Scand 1999; 78:763.
  30. Crawford NEH, Parasuraman R, Howe DT. Intraperitoneal transfusion for severe, early-onset rhesus disease requiring treatment before 20 weeks of gestation: A consecutive case series. Eur J Obstet Gynecol Reprod Biol 2020; 244:5.
  31. Giannina G, Moise KJ Jr, Dorman K. A simple method to estimate volume for fetal intravascular transfusions. Fetal Diagn Ther 1998; 13:94.
  32. Mandelbrot L, Daffos F, Forestier F, et al. Assessment of fetal blood volume for computer-assisted management of in utero transfusion. Fetal Ther 1988; 3:60.
  33. Forestier F, Daffos F, Catherine N, et al. Developmental hematopoiesis in normal human fetal blood. Blood 1991; 77:2360.
  34. Moise KJ Jr, Mari G, Fisher DJ, et al. Acute fetal hemodynamic alterations after intrauterine transfusion for treatment of severe red blood cell alloimmunization. Am J Obstet Gynecol 1990; 163:776.
  35. Radunovic N, Lockwood CJ, Alvarez M, et al. The severely anemic and hydropic isoimmune fetus: changes in fetal hematocrit associated with intrauterine death. Obstet Gynecol 1992; 79:390.
  36. Society for Maternal-Fetal Medicine (SMFM). Electronic address: [email protected], Mari G, Norton ME, et al. Society for Maternal-Fetal Medicine (SMFM) Clinical Guideline #8: the fetus at risk for anemia--diagnosis and management. Am J Obstet Gynecol 2015; 212:697.
  37. Welch R, Rampling MW, Anwar A, et al. Changes in hemorheology with fetal intravascular transfusion. Am J Obstet Gynecol 1994; 170:726.
  38. Dildy GA 3rd, Smith LG Jr, Moise KJ Jr, et al. Porencephalic cyst: a complication of fetal intravascular transfusion. Am J Obstet Gynecol 1991; 165:76.
  39. Drew JH, Guaran RL, Cichello M, Hobbs JB. Neonatal whole blood hyperviscosity: the important factor influencing later neurologic function is the viscosity and not the polycythemia. Clin Hemorheol Microcirc 1997; 17:67.
  40. Bowman JM. The management of Rh-Isoimmunization. Obstet Gynecol 1978; 52:1.
  41. Daffos F, Forestier F, Mac Aleese J, et al. Fetal curarization for prenatal magnetic resonance imaging. Prenat Diagn 1988; 8:312.
  42. Bernstein HH, Chitkara U, Plosker H, et al. Use of atracurium besylate to arrest fetal activity during intrauterine intravascular transfusions. Obstet Gynecol 1988; 72:813.
  43. Society for Maternal-Fetal Medicine (SMFM). Electronic address: [email protected], Society of Family Planning (SFP), Norton ME, et al. Society for Maternal-Fetal Medicine Consult Series #59: The use of analgesia and anesthesia for maternal-fetal procedures. Am J Obstet Gynecol 2021; 225:B2.
  44. Chatterjee D, Arendt KW, Moldenhauer JS, et al. Anesthesia for Maternal-Fetal Interventions: A Consensus Statement From the American Society of Anesthesiologists Committees on Obstetric and Pediatric Anesthesiology and the North American Fetal Therapy Network. Anesth Analg 2021; 132:1164.
  45. Scheier M, Hernandez-Andrade E, Fonseca EB, Nicolaides KH. Prediction of severe fetal anemia in red blood cell alloimmunization after previous intrauterine transfusions. Am J Obstet Gynecol 2006; 195:1550.
  46. O'Riordan SL, Ryan GA, Cathcart B, et al. The rate of decline in fetal hemoglobin following intrauterine blood transfusion in the management of red cell alloimmunization. Eur J Obstet Gynecol Reprod Biol 2022; 271:93.
  47. Egberts J, van Kamp IL, Kanhai HH, et al. The disappearance of fetal and donor red blood cells in alloimmunised pregnancies: a reappraisal. Br J Obstet Gynaecol 1997; 104:818.
  48. Lobato G, Soncini CS. Fetal hematocrit decrease after repeated intravascular transfusions in alloimmunized pregnancies. Arch Gynecol Obstet 2007; 276:595.
  49. Mari G, Detti L, Oz U, et al. Accurate prediction of fetal hemoglobin by Doppler ultrasonography. Obstet Gynecol 2002; 99:589.
  50. Lobato G, Soncini CS. Fetal hydrops and other variables associated with the fetal hematocrit decrease after the first intrauterine transfusion for red cell alloimmunization. Fetal Diagn Ther 2008; 24:349.
  51. Detti L, Oz U, Guney I, et al. Doppler ultrasound velocimetry for timing the second intrauterine transfusion in fetuses with anemia from red cell alloimmunization. Am J Obstet Gynecol 2001; 185:1048.
  52. Dodd JM, Andersen C, Dickinson JE, et al. Fetal middle cerebral artery Doppler to time intrauterine transfusion in red-cell alloimmunization: a randomized trial. Ultrasound Obstet Gynecol 2018; 51:306.
  53. Moise KJ Jr. The usefulness of middle cerebral artery Doppler assessment in the treatment of the fetus at risk for anemia. Am J Obstet Gynecol 2008; 198:161.e1.
  54. Mari G, Zimmerman R, Segata M. Am J Obstet Gynecol 2005; 191:S149.
  55. Martinez-Portilla RJ, Lopez-Felix J, Hawkins-Villareal A, et al. Performance of fetal middle cerebral artery peak systolic velocity for prediction of anemia in untransfused and transfused fetuses: systematic review and meta-analysis. Ultrasound Obstet Gynecol 2019; 54:722.
  56. Ghesquière L, Houfflin-Debarge V, Behal H, et al. Should optimal timing between two intrauterine transfusions be based on estimated daily decrease of hemoglobin or on measurement of fetal middle cerebral artery peak systolic velocity? Transfusion 2017; 57:899.
  57. Trevett TN Jr, Dorman K, Lamvu G, Moise KJ Jr. Antenatal maternal administration of phenobarbital for the prevention of exchange transfusion in neonates with hemolytic disease of the fetus and newborn. Am J Obstet Gynecol 2005; 192:478.
  58. Garabedian C, Rakza T, Drumez E, et al. Benefits of Delayed Cord Clamping in Red Blood Cell Alloimmunization. Pediatrics 2016; 137:e20153236.
  59. Sahoo T, Thukral A, Sankar MJ, et al. Delayed cord clamping in Rh-alloimmunised infants: a randomised controlled trial. Eur J Pediatr 2020; 179:881.
  60. Lepercq J, Poissonnier MH, Coutanceau MJ, et al. Management and outcome of fetomaternal Rh alloimmunization in twin pregnancies. Fetal Diagn Ther 1999; 14:26.
  61. Schumacher B, Moise KJ Jr. Fetal transfusion for red blood cell alloimmunization in pregnancy. Obstet Gynecol 1996; 88:137.
  62. Pasman SA, Claes L, Lewi L, et al. Intrauterine transfusion for fetal anemia due to red blood cell alloimmunization: 14 years experience in Leuven. Facts Views Vis Obgyn 2015; 7:129.
  63. Zwiers C, Lindenburg ITM, Klumper FJ, et al. Complications of intrauterine intravascular blood transfusion: lessons learned after 1678 procedures. Ultrasound Obstet Gynecol 2017; 50:180.
  64. Ghi T, Brondelli L, Simonazzi G, et al. Sonographic demonstration of brain injury in fetuses with severe red blood cell alloimmunization undergoing intrauterine transfusions. Ultrasound Obstet Gynecol 2004; 23:428.
  65. Nicolini U, Kochenour NK, Greco P, et al. Consequences of fetomaternal haemorrhage after intrauterine transfusion. BMJ 1988; 297:1379.
  66. Watts DH, Luthy DA, Benedetti TJ, et al. Intraperitoneal fetal transfusion under direct ultrasound guidance. Obstet Gynecol 1988; 71:84.
  67. Zwiers C, Oepkes D, Lopriore E, et al. The near disappearance of fetal hydrops in relation to current state-of-the-art management of red cell alloimmunization. Prenat Diagn 2018; 38:943.
  68. Lindenburg IT, van Kamp IL, van Zwet EW, et al. Increased perinatal loss after intrauterine transfusion for alloimmune anaemia before 20 weeks of gestation. BJOG 2013; 120:847.
  69. Poissonnier MH, Picone O, Brossard Y, Lepercq J. Intravenous fetal exchange transfusion before 22 weeks of gestation in early and severe red-cell fetomaternal alloimmunization. Fetal Diagn Ther 2003; 18:467.
  70. Saade GR, Moise KJ, Belfort MA, et al. Fetal and neonatal hematologic parameters in red cell alloimmunization: predicting the need for late neonatal transfusions. Fetal Diagn Ther 1993; 8:161.
  71. Ree IMC, Lopriore E, Zwiers C, et al. Suppression of compensatory erythropoiesis in hemolytic disease of the fetus and newborn due to intrauterine transfusions. Am J Obstet Gynecol 2020; 223:119.e1.
  72. De Boer IP, Zeestraten EC, Lopriore E, et al. Pediatric outcome in Rhesus hemolytic disease treated with and without intrauterine transfusion. Am J Obstet Gynecol 2008; 198:54.e1.
  73. Janssens HM, de Haan MJ, van Kamp IL, et al. Outcome for children treated with fetal intravascular transfusions because of severe blood group antagonism. J Pediatr 1997; 131:373.
  74. Hudon L, Moise KJ Jr, Hegemier SE, et al. Long-term neurodevelopmental outcome after intrauterine transfusion for the treatment of fetal hemolytic disease. Am J Obstet Gynecol 1998; 179:858.
  75. Dembinski J, Haverkamp F, Maara H, et al. Neurodevelopmental outcome after intrauterine red cell transfusion for parvovirus B19-induced fetal hydrops. BJOG 2002; 109:1232.
  76. Moise KJ, Whitecar PW. Antenatal therapy for haemolytic disease of the fetus and newborn. In: Alloimmune disorders in pregnancy. Anaemia, thrombocytopenia and neutropenia in the fetus and newborn, Hadley A, Soothill P (Eds), Cambridge University Press, Cambridge 2002.
  77. Harper DC, Swingle HM, Weiner CP, et al. Long-term neurodevelopmental outcome and brain volume after treatment for hydrops fetalis by in utero intravascular transfusion. Am J Obstet Gynecol 2006; 195:192.
  78. Grab D, Paulus WE, Bommer A, et al. Treatment of fetal erythroblastosis by intravascular transfusions: outcome at 6 years. Obstet Gynecol 1999; 93:165.
  79. Lindenburg IT, Smits-Wintjens VE, van Klink JM, et al. Long-term neurodevelopmental outcome after intrauterine transfusion for hemolytic disease of the fetus/newborn: the LOTUS study. Am J Obstet Gynecol 2012; 206:141.e1.
  80. Wallace AH, Dalziel SR, Cowan BR, et al. Long-term cardiovascular outcome following fetal anaemia and intrauterine transfusion: a cohort study. Arch Dis Child 2017; 102:40.
  81. Dickinson JE, Sharpe J, Warner TM, et al. Childhood cardiac function after severe maternal red cell isoimmunization. Obstet Gynecol 2010; 116:851.
Topic 5385 Version 44.0

References

آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟