Cordocentesis and Fetal Transfusion




Abstract


Cordocentesis, or percutaneous umbilical blood sampling, is a procedure that can be used for both diagnostic and therapeutic purposes. The most common indications are isoimmunization and nonimmune hydrops; less common is directly administering drugs to the fetus. In cases of neonatal autoimmune thrombocytopenia, cordocentesis was historically used to diagnosis and assess fetal response to maternal therapy. However, enormous progress has been made in the prophylactic maternal management of that disorder with intravenous immunoglobulin and prednisone; serial cordocentesis is no longer recommended. Fetal blood sampling may be used to confirm that fetal platelet count is high enough for a safe vaginal delivery in patients wishing to avoid cesarean delivery. Cordocentesis and intrauterine transfusion are still commonly used in cases of suspected fetal anemia. Fetal blood sampling should be performed to confirm the diagnosis before intrauterine transfusion and should be done in an ultrasound unit, or if the fetus is viable, in a setting where urgent cesarean delivery can be performed if necessary. During the procedure the needle may be introduced at the placental cord insertion site, a free loop of cord, the intrahepatic umbilical vein, or the peritoneal cavity. Risks associated with the procedure include infection, preterm premature rupture of membranes, preterm labor, placental abruption, maternal-fetal hemorrhage, fetal bradycardia, need for emergent cesarean delivery, and fetal demise. Early gestational age and maternal infection are relative contraindications to cordocentesis. Fetal and neonatal outcomes depend on the etiology of the fetal anemia, gestational age at first transfusion, and the presence of hydrops fetalis.




Keywords

intrauterine transfusion, cordocentesis, fetal anemia, neonatal alloimmune, thrombocytopenia

 




Introduction


Cordocentesis is a procedure that has both diagnostic and therapeutic value in fetal medicine, and is used for fetal blood sampling (FBS) and administration of fetal transfusions. Sir William Liley described the first successful intraperitoneal transfusion in 1963 with x-ray assistance. Almost 20 years later, Rodeck et al. reported using a fetoscopic approach to gain direct fetal vascular access. Ultrasound (US) guided percutaneous umbilical sampling (PUBS) was then described by Daffos et al. in 1983 and was subsequently used for testing karyotype, genetic disorders, blood/antigen typing, infectious testing, and to give direct intravascular fetal therapy. However, the development of less invasive diagnostic techniques has led to a decreased need for FBS. In a single center in Italy, the reported use of cordocentesis for prenatal diagnosis of karyotype analysis decreased from 26.4% (372 of 1408) during 1982–1985 to 2.2% (213 of 9341) during 2000–2004.




Procedure


Setting


Early cordocentesis is performed in a US unit because emergent cesarean delivery is not indicated for the previable fetus if there is evidence of fetal distress during or following the procedure. Once the fetus is viable, the procedure should be performed in a setting where an urgent cesarean delivery can take place if a complication occurs. It is useful to have the patient evaluated by the anesthesia team and prepared for a possible emergent delivery in that setting. Before the procedure, consideration should be given to administering prenatal steroids for fetal lung maturity.


Counseling


All cordocentesis procedures should be preceded by an extensive counseling session in which the indication, risks, benefits, and alternatives to the procedure are discussed.


Indications


Currently, the most common indication for FBS and cordocentesis is diagnosis and management of isoimmunization (56%) and nonimmune hydrops (18%). Cordocentesis is occasionally performed for other diagnostic purposes or therapeutic indications, which may include fetal drug administration for fetal thyrotoxicosis or fetal arrhythmia unresponsive to maternal therapy.


Fetal Anemia


Fetal anemia is defined as hemoglobin levels less than two standard deviations below the mean and can lead to high-output cardiac failure, hydrops fetalis, and fetal demise. This condition used to be common, with most cases resulting from Rhesus-D sensitization. This, however, has become much less prevalent with the development and widespread use of anti-D immune globulin. Nevertheless, alloimmune fetal anemia may still occur if there is inadequate anti-D immune globulin administration or if sensitization develops to other red blood cell antigens (e.g., Kell, c, C, e, Duffy, etc.). As alloimmune anemia and subsequent hydrops has decreased, nonimmune hydrops now accounts for 90% to 99% of hydrops fetalis cases. Nonimmune causes of fetal anemia include infection, fetal-maternal hemorrhage, and hematologic disorders, such as thalassemia. Parvovirus is the most common infectious cause of anemia. In one case series, hydrops fetalis occurred in 4% of patients with acute parvovirus infection.


Doppler velocimetry measuring the peak systolic velocity (PSV) of the middle cerebral artery (MCA) is used to screen pregnancies at risk for fetal anemia. When the PSV is >1.5 multiples of the median (MoM) or there is evidence of hydrops fetalis, severe anemia is suspected and IUT or delivery is indicated. FBS remains the gold standard for definitive diagnosis of severe anemia and should be performed immediately before any IUT.


Serial transfusions may be necessary to prolong the gestation, especially if anemia is diagnosed early in pregnancy. However, after transfusion, MCA Dopplers may not be as predictive of severe anemia since the introduction of the smaller, less rigid adult red blood cells may alter fetal blood flow. One study reported that MCA Doppler >1.5 MoM was a good predictor of severe anemia before the first transfusion, but was associated with a false-positive rate of 37% after the first, and 90% after the second transfusion. The false-positive rate decreased and negative predictive value increased when a higher MoM threshold for severe anemia was used. Another approach to predicting anemia following transfusion is to use the expected daily decline of hemoglobin to determine the interval to the next transfusion. The reported daily decline in hemoglobin was 0.45 g/dL after the first transfusion, 0.35 g/dL after the second, and 0.32 g/dL after the third. This study also reported the median time to subsequent transfusion was 13, 25, and 27 days after the first, second, and third transfusion, respectively. After the first transfusion, the Society of Maternal Fetal Medicine recommends the use of 1.69 MoM as the threshold for further cordocentesis/IUT to decrease the frequency of unnecessary procedures.


Neonatal Alloimmune Thrombocytopenia


Neonatal alloimmune thrombocytopenia (NAIT) is fetal thrombocytopenia that occurs in 1 : 1000 to 2 : 1000 live births in the United States and is caused by maternal sensitization to fetal platelet antigens that are discordant from her own. This process is similar to fetal anemia caused by erythrocyte alloimmunization, and has a high recurrence rate and likelihood for earlier and more severe disease with future pregnancies. Unlike fetal anemia from alloimmunization, significant fetal thrombocytopenia may occur in the first pregnancy. NAIT can cause a spectrum of outcomes ranging from mild, asymptomatic thrombocytopenia to severe thrombocytopenia and may lead to intracranial hemorrhage (ICH) in 20% to 30% of affected cases. This condition should be suspected if there is ICH in the current pregnancy or there is a personal or family history suggestive of NAIT in prior pregnancies (unexplained neonatal thrombocytopenia, intracranial hemorrhage). While maternal antibody evaluation and fetal antigen typing can be done with serum testing and amniocentesis, definitive diagnosis requires FBS to confirm fetal thrombocytopenia. To date, no noninvasive biomarker is available for assessment of fetal platelet count or genotype. The goal of NAIT management is to prevent intracranial bleeding by preventing the development of severe thrombocytopenia in utero. The role of cordocentesis in the management of this disorder has evolved over time and is now used judiciously under specific circumstances.


During the early investigations on NAIT, cordocentesis was used frequently to determine the baseline platelet count, evaluate the effectiveness of therapies in utero, and to determine if the platelet count was high enough for a safe vaginal delivery. As the number of indications for performing cordocentesis in general decreased, there was a concomitant reduction in the number of individuals with substantial experience performing the procedure. As a consequence, the number of patients with procedure-related complications increased, including emergent cesarean delivery and fetal loss. Enormous progress has been made toward reducing the need for cordocentesis in this disorder over the past 3 decades, and it is now possible to avoid dangerously low platelet counts in most affected fetuses with prophylactic maternal management with intravenous immunoglobulin and prednisone. Cordocentesis, previously done to assess the fetal response to maternal therapy at fixed intervals, has been eliminated in favor of empiric increases in therapies based on the risk of developing severe fetal thrombocytopenia. Early-term delivery by cesarean section is recommended. FBS should currently only be performed close to delivery to verify that the fetal platelet count is high enough to permit a safe vaginal delivery in women who would like to avoid abdominal surgery.


Contraindications


While there are no absolute contraindications to cordocentesis, certain maternal viral infections and early gestational age are considered relative contraindications. There is a theoretic risk of vertical transmission of blood-borne diseases, such as human immunodeficiency virus and hepatitis. The risk is likely elevated with a higher viral load, but there is little data on the rates of transmission with this procedure. Early gestational age is associated with increased complication rates and technical difficulty. In one study, the procedure-related fetal loss rate was 5.6% when FBS was performed at less than 20 weeks’ gestation, and 0.8% to 2.2% when performed at greater than 20 weeks’ gestation. A recent single-center study reported that, in their institution, cordocentesis was rarely performed before 18 weeks (accounting for only 3.5% of their cordocentesis cases), but was not associated with an increased risk of fetal loss when compared to FBS performed after 18 weeks’ gestation (2.9% versus 1.8%, P = .40). The overall fetal loss rate in this study was 1.9%. Therefore early gestational age may be considered a relative contraindication for FBS, as there is conflicting data on whether this is associated with a higher rate of fetal loss. However, FBS should be considered if no alternative exists to prevent an imminent demise in utero.


Risks


The risks for this procedure include: infection, preterm premature rupture of membranes, placental abruption, preterm labor, maternal-fetal hemorrhage, alloimmunization, fetal bradycardia, and loss of the pregnancy. Fetal bradycardia occurs during or immediately after the procedure in 5% of patients with decreasing prevalence as gestational age increased. This can occur with vasospasm of the umbilical artery because of contraction of the muscularis, so umbilical vein entry is recommended. Streaming from the needle insertion site into the fetal vessel occurs in 20% to 30% of cases and is often transient, but rarely may cause fetal exsanguination. This occurs less frequently with an intrahepatic vein approach (9%) compared with needle insertion into a cord vessel (26%). Iatrogenic umbilical cord hematoma may cause cord compression and fetal bradycardia ( Fig. 112.1 ). This is often asymptomatic or transient, but may require delivery if there is persistent evidence of nonreassuring fetal status, such as prolonged fetal bleeding or bradycardia. One series reported an emergency cesarean delivery incidence of 2.4%, which was associated with birth asphyxia in 73% and neonatal demise in 33%. In another series, emergent cesarean delivery was performed in 5% of patients with alloimmune thrombocytopenia (NAIT) who underwent diagnostic cordocentesis. Others report the fetal loss rate is 1.4% to 1.9% after cordocentesis.


Jul 7, 2019 | Posted by in OBSTETRICS & GYNAECOLOGY IMAGING | Comments Off on Cordocentesis and Fetal Transfusion
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