INTRODUCTION — Fetal blood sampling (FBS) refers to three techniques used to gain access to fetal blood: cordocentesis (also known as percutaneous umbilical blood sampling), intrahepatic blood sampling, and cardiocentesis. FBS is riskier than postnatal venipuncture and interpretation of results can be difficult because of the limited availability of normative fetal laboratory values across gestation.
The techniques for FBS can also be used for intravenous administration of medication (eg, digoxin) or blood products (eg, platelets, red blood cells) to the fetus. (See "Intrauterine fetal transfusion of red cells" and "Fetal and neonatal alloimmune thrombocytopenia: Parental evaluation and pregnancy management" and "Fetal arrhythmias".)
INDICATIONS — Fetal blood is sampled to aid in the diagnostic evaluation of fetal disorders. A major difference between FBS and venipuncture in children and adults is the relatively high degree of procedure-related risk: FBS can have lethal complications. Since evaluation of amniocytes or chorionic villi can often provide similar information as fetal blood, FBS should be limited to clinical situations in which use of lower risk diagnostic procedures (ie, amniocentesis, chorionic villus sampling) does not provide adequate or sufficiently timely diagnostic information .
Confirmation of severe fetal anemia suspected because of elevated middle cerebral artery peak systolic velocity (>1.5 multiples of the median for gestational age) is a common indication for FBS . In Southeast Asian countries, FBS is frequently performed for genetic diagnosis of a severe thalassemia (alpha thalassemia major, beta thalassemia major, beta thalassemia/hemoglobin E disease) in at-risk fetuses . (See "Alpha thalassemia major: Prenatal and postnatal management", section on 'Fetal testing'.)
PROCEDURE — The maternal abdomen is prepared with an antibacterial solution and draped. Aseptic technique should be used.
Site — Prior to fetal viability, FBS can be performed in a room used for sonographic examinations or in a labor room. After viability, the procedure should be performed in proximity to an operating room since an emergency cesarean delivery may be required if nonreassuring fetal heart rate patterns develop during or after the procedure.
Antenatal glucocorticoids — Most clinicians administer glucocorticoids at least 24 hours prior to diagnostic and therapeutic procedures in fetuses between 24+0 and 33+6 weeks of gestation to enhance fetal lung maturity. The risk/benefit ratio of this practice has not been studied and may be difficult to assess, given the small risk of procedure-related preterm delivery. (See "Antenatal corticosteroid therapy for reduction of neonatal respiratory morbidity and mortality from preterm delivery".)
Laboratory/imaging — A sample of maternal blood is drawn before the procedure for comparison with the fetal samples that will be obtained. An obstetric ultrasound examination is also performed to confirm fetal viability and to determine fetal position and the location of the placenta.
Intravenous access — Placement of a maternal intravenous catheter allows easy and rapid administration of analgesics, antibiotics, and fluids, as needed, and is prudent preparation in the event of procedure-related complications necessitating emergency cesarean delivery.
Antibiotic prophylaxis — No randomized trials evaluating the efficacy of antibiotic prophylaxis in this setting have been performed. Given that FBS is a "clean" procedure with a low risk of infection, most centers have elected not to use antibiotic prophylaxis .
Maternal local anesthesia and sedation — Local anesthesia is optional for diagnostic procedures. However, it is useful for therapeutic procedures (eg, transfusions) to ease patient discomfort associated with prolonged needle insertion. Maternal sedation is not generally required .
Fetal paralytic drugs — Reducing fetal movement is not routinely necessary for FBS, but can be helpful when movement is likely to dislodge the needle, such as during prolonged procedures (eg, fetal transfusion) or for accessing sites other than a cord insertion on an anterior placenta. It is important to note that a paralyzed fetus that blocks access to the cord insertion site, such as into a posterior placenta, may prevent performance of the FBS procedure. Atracurium (0.4 mg/kg) given intramuscularly provides paralysis for up to an hour with minimal fetal cardiovascular effects .
Needle guide — Most real-time ultrasound machines are equipped with an on-screen template of the needle tract that is used to target the sampling site. A needle-guiding device attached to the transducer may decrease the risk of cord laceration or needle displacement , but it restricts the lateral motion of the needle and hampers the procedure if the needle needs repositioning. This problem can be resolved by removing the guiding device during the procedure, if it becomes necessary. A "free-hand technique" is also commonly employed because it provides flexibility for adjusting the needle path. No trials have been published comparing the two methods, and either technique is acceptable.
Needle — A 20- to 22-gauge spinal needle is generally used for FBS. Smaller bore needles prolong the period of time required to obtain fetal blood and are more difficult to manipulate because they bend. A 22-gauge needle is preferable before 24 weeks of gestation because of the small diameter of the umbilical vessels, and also when thrombocytopenia is suspected because it may reduce the risk of bleeding at the insertion site. An alternative technique involves inserting a 20-gauge needle biopsy guide into the amniotic cavity, followed by threading a 25-gauge needle through the guide and then into the umbilical vein . The needle guide helps prevent bending of the smaller-gauge needle and improves visualization.
The length of the needle should take into account the distance from the skin to the target segment of cord, and the possibility that intervening events, such as uterine contractions, may increase this distance. The standard length of a spinal needle is 8.9 cm (excluding the hub), but longer needles are available (up to 15 cm).
Priming the needle with sodium citrate solution or heparin immediately before the procedure helps to prevent clot formation. Modified needles with silicon coating of the bore have been shown in vitro to result in a significant increase in flow rate and lower clot formation . Needles designed to optimize sonographic visualization (eg, Cook OBGYN) are also available. A clear benefit of these new designs has not been clearly demonstrated.
Assistants — Many operators prefer to insert the needle while holding the transducer themselves. Once the needle tip is in place, an assistant is necessary either to hold the transducer or to draw the blood samples.
Other operators prefer to be guided throughout the procedure by an assistant. A second assistant is useful to adjust the quality and size of the on-screen image during the procedure.
SAMPLING SITE — Sampling site can be individualized based on position of the placenta and fetus, as well as operator experience. Success rates are high with each of the following sampling methods, though cardiocentesis is rarely performed given high rates of fetal loss.
Umbilical cord blood sampling — The first step in sampling the umbilical cord is to identify a fixed segment of the cord, preferably where the cord inserts into the placenta since the stability of the abdominal insertion site is at risk if the fetus moves. A free loop of cord can be used if it can be stabilized by the uterine sidewall to allow piercing; sampling from a free loop of cord avoids the need for confirmation of fetal origin of the blood, but it is a less desirable alternative since stability is precarious and may result in continued bleeding from the puncture site . The major disadvantage of using the placental insertion site is the possibility of contamination by maternal blood.
FBS is easiest when the placenta is anterior and the site is approached transplacentally; however, penetration of the placenta increases the risk of fetomaternal hemorrhage and fetal loss (3.6 versus 1.3 percent ). This is less of an issue when the placenta is posterior, but in these cases, the fetus may hamper access to the target portion of the cord. Manipulation of the maternal abdomen to move the fetus may provide better access to the sampling site under these circumstances. Alternatively, intrahepatic vein access can be attempted. (See 'Intrahepatic vein fetal blood sampling' below.)
It may be necessary to perform a therapeutic amniocentesis to gain access to the cord insertion site in cases complicated by polyhydramnios with a posterior placenta. Oligohydramnios can also interfere with visualization of the insertion site; amnioinfusion or needling of a fixed loop of cord may overcome this difficulty. The following points are some additional insights related to the procedure:
●Doppler color flow mapping can be used to confirm the placental cord insertion site by showing the branching of the cord vessels within the placenta.
●Amniocentesis, if indicated, should be done prior to cordocentesis to avoid blood contamination of the fluid specimen. After aspiration of amniotic fluid, the needle is either advanced into the cord or, in cases with an anterior placenta, withdrawn within the placental mass, reoriented, and advanced into the cord. (See "Diagnostic amniocentesis".)
●It is easier and safer to sample the umbilical vein than an artery; puncture of the artery increases the incidence of bradycardia, postprocedural bleeding, and emergency delivery [9,10]. This is especially important in cases of a single umbilical artery. The vein and artery can be distinguished by the differences in their relative sizes and assessment of waveform analysis with spectral Doppler. Correct identification of the origin of the sample (arterial versus venous) is crucial for accurate interpretation of the acid-base and oxygenation status of the fetus.
●Upon entering the umbilical cord, the stylet is removed, and fetal blood is withdrawn into a syringe attached to the hub of the needle. The syringe may be primed with a small amount of anticoagulant, such as heparin or citrate. Proper positioning of the needle can be confirmed by injection of a small amount of physiological saline solution into the cord and observation of turbulent flow along the vessel. After umbilical blood flow is documented by Doppler color flow, an initial sample should be submitted for red blood cell size determination (ie, mean corpuscular volume) to distinguish fetal from maternal cells, unless the procedure was performed on a free loop of umbilical cord, at the intrahepatic vein, or fetal heart, since no maternal blood contamination is expected at these sites. (See 'Confirmation of fetal blood' below.)
If multiple samples are required, it may be helpful to attach a T-connector extension set to the hub of the needle to minimize the risk of needle dislodgement during attachment of the syringes.
After the desired samples have been obtained, the needle is withdrawn and the puncture site monitored for bleeding. If an intraumbilical vein transfusion is performed after sampling, the fetal heart rate should be monitored intermittently by interrogating an umbilical artery near the transfusion site using Doppler color flow or by assessing blood velocity waveforms by pulse Doppler. (See "Intrauterine fetal transfusion of red cells".)
If the patient has a viable fetus, the fetal heart rate is monitored for one to two hours after the procedure using an external fetal heart rate monitor.
Intrahepatic vein fetal blood sampling — A 20- or 22-gauge needle is introduced into the fetal abdomen and aimed for the intrahepatic portion of the umbilical vein or the left portal vein. The risk of needle dislodgement (8.7 percent of cases ) can be minimized by using longer needles and, after insertion into the target, allowing the needle to move with fetal movements.
This technique has some advantages compared with cordocentesis, including:
●Lack of need for immediate laboratory support to confirm the fetal origin of the sample and certainty of the venous origin of the sample.
●A lower frequency of fetomaternal hemorrhage (therefore, less risk of alloimmunization) because the placenta is avoided.
●Significantly less streaming (bleeding) from the sampling site compared with cordocentesis (0.8 versus 30.8 percent) .
●Ease of access to the sampling site in cases with a posterior placenta or twins.
This procedure is often used as a second-line approach in cases of failed cordocentesis, but some centers have started using it as first-line procedure for the reasons discussed above [11-13]. The negligible risk of streaming from the sampling site makes intrahepatic vein sampling an appealing alternative to cordocentesis in cases at risk for fetal thrombocytopenia. The risk of procedure-related fetal loss ranges from 0 to 6.2 percent [11-13]; because of the small number of series published, the risk of procedure-related fetal loss specifically in low-risk cases is not known.
No significant changes in the concentrations of liver enzymes have been noted following the procedure, which suggests minimal fetal liver injury .
Cardiocentesis — Cardiocentesis has few indications due to a high rate of fetal loss (approximately 5 percent) [13,14]. It is reserved for cases where there is a high probability of a serious fetal disorder and FBS from other sites is technically impossible or has repeatedly failed.
Ideally the needle should be introduced swiftly through the anterior thoracic wall and into the right ventricle, if possible, to prevent fetal movements from interfering with the procedure .
BLOOD SPECIMEN — Fetal blood samples are placed into tubes containing EDTA (ethylenediaminetetraacetic acid) or heparin and mixed well to prevent clotting. The appropriate tubes and minimum volume of blood required for specific studies are listed in the table (table 1). The maximum volume of blood removed should not exceed 6 to 7 percent of the fetoplacental blood volume for the gestational age, which can be calculated as 100 mL/kg of estimated fetal weight .
Use of a point-of-care hemoglobinometer has been proposed to shorten the duration between obtaining a fetal sample and the fetal hemoglobin result .
Confirmation of fetal blood — Contamination with maternal blood or amniotic fluid can alter the diagnostic value of the fetal blood specimen. Confirmation that the sample is fetal blood should be performed when FBS is performed at the placental cord insertion site, but is not necessary at the abdominal cord insertion site or with intrahepatic vein sampling or cardiocentesis since maternal contamination is not relevant concern.
As discussed above, the purity of the fetal blood sample is commonly assessed using the mean corpuscular volume of red blood cells (RBC) since fetal RBCs are larger than maternal RBCs. On occasion, this parameter can be misinterpreted (eg, in the presence of some maternal hematologic disorders [eg, macrocytic anemia] or after repeated fetal transfusions of blood from an adult donor).
Other methods to differentiate maternal from fetal blood include:
●Kleihauer-Betke test – As little as 0.5 percent maternal blood contamination can be detected by this test, which is based on different susceptibilities of fetal and adult hemoglobin to acid elution . The accuracy of the test is decreased during the late third trimester since fetal erythrocytes contain increasing amounts of hemoglobin A near term. (See "Spontaneous massive fetomaternal hemorrhage", section on 'Kleihauer-Betke assay'.)
●Human chorionic gonadotropin (hCG) determination – This is the best marker for detection of maternal blood contamination; however, results are rarely available in real time . Maternal blood contains high concentrations of this hormone, whereas fetal blood is practically devoid of it. The fetal blood to amniotic fluid to maternal blood ratio for hCG is 1:100:400. hCG determination can detect as little as 0.2 percent contamination with maternal blood or 1 percent contamination with amniotic fluid .
●Hemoglobin alkaline denaturation test (Apt test) – 0.1 mL of sampled blood is added to a glass tube containing alkali reagent (5 mL of water and 0.3 mL of 10 percent potassium hydroxide) and the tube is gently shaken for two minutes. The sample is considered contaminated with maternal blood if the color of the mixture changes from red to green-brown [19,20].
●Blood typing – The I antigen is present only on adult RBCs; fetal RBCs do not have this antigen. Monoclonal antibodies for the I antigen can detect as little as a 5 percent maternal blood contamination .
●White blood cell differential count – Lymphocytes are the predominant white blood cell in the fetus, whereas neutrophils are predominant in the mother.
Dilution with amniotic fluid can be inferred by:
●A similarly proportional decrease in the number of RBCs, white blood cells, and platelets in the specimen.
●The presence of an amniotic fluid arborization pattern (ie, ferning) or multiple desquamated epithelial cells on a smear of the fetal blood specimen [21,22].
NORMAL VALUES — The distribution of the most common hematologic and acid-base parameters in fetal blood in relation to the gestational age is listed in the tables (table 2A-G).
COMPLICATIONS — Bleeding, bradycardia, and infection, all of which may be life-threatening, are the major fetal complications associated with cordocentesis. Maternal complications unrelated to the pregnancy are unusual.
Fetal bleeding — Bleeding from the puncture site is the most common complication of cordocentesis, occurring in 20 to 30 percent of cases . Puncture of the umbilical artery is associated with a significantly longer duration of bleeding than venipuncture, where the mean duration of bleeding is 35 seconds [9,10]. Postprocedural bleeding appears to carry a more ominous prognosis when it occurs before 21 weeks of gestation .
Fetuses with defects in platelet number or function are at significant risk for potentially fatal bleeding from the puncture site [24-28]. Thus, it is prudent to slowly transfuse the fetus with concentrated, washed maternal (or compatible donor) platelets while awaiting the fetal platelet count when FBS is performed to diagnose a fetal platelet disorder. These platelets are usually obtained from maternal plateletpheresis to minimize the risks of transfusion-related infections with pooled donor platelets. A transfusion of 15 to 20 mL of platelet concentrate usually increases the fetal platelet count by 70,000 to 90,000, which is adequate to prevent bleeding from the cord puncture site.
Dislodgement of the needle before platelet transfusion can have fatal consequences for the fetus affected with a platelet abnormality. Because of the low risk of bleeding from the sampling site, intrahepatic vein sampling has been proposed as the optimal technique for FBS in cases of suspected fetal thrombocytopenia . (See 'Intrahepatic vein fetal blood sampling' above.)
If prenatal diagnosis is being performed for evaluation of a congenital hemostatic disorder, fresh frozen plasma should be available for fetal transfusion at the time of FBS since excessive bleeding has been reported after sampling in fetuses with bleeding diatheses, such as severe von Willebrand disease and hemophilia [29,30].
If continued bleeding is noted from the puncture site, options include immediate delivery, if considered appropriate based on gestational age, or attempts at fetal volume restoration. (See 'In utero fetal resuscitation' below.)
Cord hematoma — Cord hematoma is generally asymptomatic, but can be associated with a transient or prolonged sudden fetal bradycardia [31-33]. Expectant management is recommended in the presence of reassuring fetal monitoring tests (eg, nonstress test, biophysical profile) and a nonexpanding hematoma. However, delivery is indicated if signs of nonreassuring fetal status persist.
In one series that examined umbilical cords after delivery, hematomas were noted following FBS in 17 percent of cases . No relationship was documented between the size of the hematoma and either transient fetal bradycardia or bleeding from the cord puncture site.
Fetomaternal bleeding — Significant fetomaternal bleeding occurs in approximately 40 percent of cases [34-36]. These fetomaternal bleeds may be defined by either:
●A greater than 50 percent postprocedural increase in maternal serum alpha-fetoprotein concentration from blood taken immediately before and after FBS.
●Kleihauer-Betke staining of the maternal blood showing a calculated fetomaternal hemorrhage of greater than 1 mL of fetal whole blood.
Fetomaternal bleeding is more common with an anterior than a posterior placenta, with procedures lasting longer than three minutes, and with those requiring two or more needle insertions [34-36]. The main consequence of a small fetomaternal bleed is an increase in maternal alloantibody titers when the procedure is performed because of red blood cell alloimmunization [34,35]. New alloimmunization is also possible. A large fetomaternal bleed is rare and can result in severe fetal anemia and death. (See "Spontaneous massive fetomaternal hemorrhage".)
There is no consensus as to the clinical indications for obtaining preprocedural and postprocedural maternal blood samples to quantify the volume of fetomaternal hemorrhage. The author does not order these tests.
Bradycardia — Transient fetal bradycardia is reported in 5 to 10 percent of fetuses undergoing FBS . Most cases resolve without intervention within five minutes. The higher incidence of bradycardia in procedures involving puncture of an umbilical artery suggests that this complication may be due to a vasovagal response caused by local vasospasm .
A higher rate of bradycardia has also been noted among growth restricted fetuses compared with those appropriately grown (17 versus 4 percent). The greatest risk of bradycardia is in the growth restricted fetus with absent diastolic flow in the umbilical artery by Doppler analysis: bradycardia occurred in 21 percent of these fetuses versus 5 percent of those with normal diastolic flow .
Infection — The maternal risk from FBS is minimal and is mainly limited to chorioamnionitis. Infection occurs after fewer than 1 percent of procedures, but is responsible for up to 40 percent of pregnancy losses associated with FBS [10,37-39]. The author administers antibiotic prophylaxis for this reason, although the benefit of this intervention is unproven. (See 'Antibiotic prophylaxis' above.)
Failure rate — Cordocentesis and intrahepatic vein sampling have similar rates of failure to obtain a blood specimen (9 and 5 percent, respectively) . For this reason, it is useful to become familiar with both techniques, so that the appropriate technique may be chosen based upon indications and ease of access to the sampling site.
Fetal loss — The risk of postprocedure pregnancy loss appears to be 1.4 to 1.9 percent [40-42]. This risk was illustrated by a large cohort study in which over 5000 FBS procedures were performed to detect a karyotype abnormality or hemoglobinopathy at 16 to 22 weeks in pregnant patients without medical or obstetric complications or a sonographically evident fetal anomaly . Fetal loss rate in patients with normal results followed until delivery was 0.9 percentage points higher than in controls matched for maternal age, parity, and gestational age at sonogram who did not undergo the procedure (1.9 versus 1.0 percent, relative risk [RR] 1.9, 95% CI 1.4-2.7) .
A similar excess risk (0.6 percent) was reported in another large case-control series including 6650 cases of cordocentesis .
The most important risk factors for procedure-related fetal loss appear to be:
●Abnormal fetus – The risk of fetal loss is substantially higher in the abnormal fetus. In three reports, the total spontaneous pregnancy loss rate within two weeks of the procedure was 1 percent when FBS was performed on a normal-appearing fetus for diagnosis of genetic disorders or karyotyping, 7 to 13 percent in a fetus with structural anomalies, 9 to 14 percent among growth-restricted fetuses, and 25 to 32 percent in fetuses with nonimmune hydrops [39,43,44].
●Inadequate operator experience – Procedures performed by less experienced operators (defined as <40 or <60 procedures) are associated with higher rates of fetal losses compared with procedures performed by experienced operators [2,42]. In the large cohort study described above, the risk of fetal loss was over twofold higher if performed by an inexperienced compared with an experienced operator (3.5 versus 1.7 percent, adjusted odds ratio [OR] 2.16, 95% CI 1.25-3.72) . Undergoing training on a cordocentesis training model may decrease the risk of fetal losses for operators in early practice (ie, <60 procedures) as well as duration of the procedure . This suggests that FBS procedures should be consolidated to a few centers with adequate volume to maintain operators' experience .
●Sampling from the fetal heart – Obtaining the blood sample from the fetal heart rather than from the umbilical vein. (See 'Cardiocentesis' above.)
●Gestational age <24 weeks – The risk of fetal loss is higher in fetuses <24 weeks of gestation ; the lowest gestational age at which FBS has been reported is 16 weeks .
In a case-control study including 1020 patient pairs between 16 and 24 weeks of gestation (average gestational age: 19.7±1.4 weeks) and no evidence of fetal anomalies, those undergoing FBS compared with controls undergoing ultrasound without FBS had an increased risk of fetal loss (3.2 versus 1.8 percent) . Most losses occurred before 28 weeks and 30 percent occurred within two weeks of the procedure.
●Other – Prolonged bleeding from the puncture site (adjusted OR 10.8, 95% CI 5.3-22.4), fetal bradycardia (adjusted OR 3.3, 95% CI 1.8-6), and placental penetration (adjusted OR 2.6, 95% CI 1.7-4.1) also appear to be independent risk factors of fetal loss .
Fetal anomalies — The large cohort study of over 5000 FBS procedures described above (see 'Fetal loss' above) noted three fetuses with late-occurring anomalies in the FBS group (two fetuses with hydranencephaly, one fetus with hydrocephalus) compared with one fetus with hydrocephalus in the no-FBS group . Although biologically plausible that thromboembolism secondary to FBS may lead to such complications, the absolute risk of an anomaly appears small (<1/1000 procedures).
Small for gestational age, preterm birth, and other complications — The large cohort study of over 5000 FBS procedures described above (see 'Fetal loss' above) also reported that patients who underwent FBS and had normal results had significant increases in rates of small for gestational age neonates (6.9 versus 4.6 percent, RR 1.5, 95% CI 1.3-1.8), delivery before 37 weeks of gestation (12.7 versus 7.4 percent, RR 1.7, 95% CI 1.5-1.9), and delivery before 34 weeks of gestation (2.6 versus 1.3 percent, RR 1.9, 95% CI 1.4-2.5) compared with controls who did not undergo the procedure and matched for maternal age, parity, and gestational age at sonogram . Logistic regression analysis showed that low experience level of the operator (ie, having performed <40 cases), prolonged bleeding during the procedure (ie, for longer than one minute), penetration through the placenta, and fetal bradycardia after the procedure were independent predictors of the adverse outcomes.
Rates of premature rupture of membranes, abruption, chorioamnionitis, and hypertensive complications of pregnancy were not different between the two groups.
Vertical transmission of infection — Invasive procedures such as FBS in patients with chronic hepatitis or infection with HIV place the fetus at risk of procedure-related vertical transmission. Based on review of the literature on amniocentesis in these patients, this risk is probably very low and related to viral load . The possibility of vertical transmission should be discussed with these patients.
The risk of transmission may be decreased by administering appropriate antiviral medication to reduce viral load to undetectable levels, if possible, before performing the procedure and avoiding penetration of the placenta during the procedure. No specific guidelines are available; a risk-benefit analysis should be conducted for each case based on the patient's viral load, the indication for the procedure, and urgency.
MULTIPLE GESTATIONS — Access to an optimal site for cordocentesis can be more difficult when multiple fetuses are present, and the risk of complications appears to be increased, as well. In a relatively large study comparing outcomes after midtrimester cordocentesis in 122 twin fetuses and 336 singleton controls matched for maternal age and operator experience, twins had a significantly higher frequency of fetal bradycardia (13 versus 6.0 percent) and transient bleeding from the puncture site (34.8 versus 26.1 percent) . The fetal loss rate within two weeks of cordocentesis, however, was similar for both groups (1.4 versus 1.1 percent) after exclusion of pregnancies undergoing termination or feticide because of abnormal findings.
Other studies have reported an 8 to 12 percent rate of fetal loss in twin gestations undergoing FBS, but are biased by factors such as a small number of cases, inclusion of both fetoscopy and cordocentesis procedures, and different indications for the procedure [47,48].
IN UTERO FETAL RESUSCITATION — In utero treatment of fetal bradycardia during or after FBS can be attempted before viability or to avoid an emergency cesarean delivery in a very preterm infant. The option of emergency abdominal delivery and ex utero resuscitation is preferable in the late-preterm fetus. The following measures should be implemented if bradycardia occurs:
●Improve uterine perfusion and enhance fetal oxygenation by placing the mother in the left-lateral decubitus position and increasing intravenous hydration. Maternal hypotension, if present, may be treated with phenylephrine or ephedrine. The author prefers phenylephrine rather than ephedrine as ephedrine has been associated with a transient decrease in fetal (ie, umbilical) pH when used at the time of cesarean delivery [49,50]. This is discussed in more detail elsewhere. (See "Anesthesia for cesarean delivery", section on 'Vasopressors'.)
●Palpate the uterus to evaluate for tetanic uterine contractions as the cause of the bradycardia. Subcutaneous or intravenous tocolytics (eg, terbutaline 0.25 mg subcutaneously or atosiban 6.75 mg in 4.9 mL saline given intravenously over one minute) can be administered to the mother to relax the uterus and potentially resolve the bradycardia [51,52].
The operator should be aware that titanic contractions in the setting of fetal bradycardia may signal placental abruption, particularly after a technically challenging procedure involving transplacental passage of the needle. (See "Acute placental abruption: Pathophysiology, clinical features, diagnosis, and consequences".)
●Persistent or worsening bradycardia may be secondary to prolonged bleeding or massive fetomaternal bleeding with hypovolemic shock. Fetal volume restoration can be accomplished by injecting maternal whole blood or normal saline at a volume of 15 mL/kg of estimated fetal weight into a fetal umbilical vessel (preferably the vein). If the umbilical vessels cannot be accessed due to hypovolemia and/or vasoconstriction, a cardiocentesis can be performed [29,53].
●If all of the above measures fail, intracardiac administration of the inotropic agent epinephrine (1:10,000 solution at a dose of 0.1 to 0.3 mL/kg of estimated fetal weight) can be attempted. There is no evidence in the neonatal literature to suggest that atropine is useful in the acute phase of resuscitation.
SUMMARY AND RECOMMENDATIONS
●Fetal blood sampling (FBS) uses any of three techniques to gain access to fetal blood: cordocentesis, intrahepatic blood sampling, and cardiocentesis. (See 'Introduction' above.)
●FBS is not indicated when less invasive alternatives (eg, amniocentesis, chorionic villus sampling) are available. (See 'Indications' above.)
●In viable fetuses, we suggest performing the procedure in proximity to an operating room and with intravenous access in place since an emergency cesarean delivery may be required. (See 'Procedure' above.)
●Amniocentesis, if indicated, should be done prior to the procedure to avoid blood contamination of the fluid specimen. (See 'Umbilical cord blood sampling' above.)
●The optimal site for cordocentesis is the umbilical vein in the portion of the cord that inserts in the placenta. Proper positioning of the needle is confirmed by injection of physiological saline solution into the cord and observation of turbulent flow along the vessel. (See 'Umbilical cord blood sampling' above.)
●Intrahepatic vein fetal sampling is generally reserved for cases in which cordocentesis fails, cannot be performed due to fetal position, or FBS is indicated by a suspected fetal platelet disorder. Cardiocentesis has a high rate of fetal loss and is used when there are no other options. (See 'Intrahepatic vein fetal blood sampling' above and 'Cardiocentesis' above.)
●The maximal amount of blood removed should not exceed 6 to 7 percent of the fetoplacental blood volume for the gestational age. (See 'Blood specimen' above.)
●The purity of the fetal blood sample is commonly assessed using the mean corpuscular volume of red blood cells (RBCs) since fetal RBCs are larger than maternal RBCs. On occasion, this parameter can be misinterpreted (eg, in the presence of some maternal hematologic disorders, such as macrocytic anemia, or after repeated fetal transfusions of adult donor blood). (See 'Blood specimen' above.)
●Fetal bleeding, bradycardia, and infection are the major complications; maternal complications are rare. (See 'Complications' above and 'In utero fetal resuscitation' above.)
●FBS procedures are associated with a significant increase in the risk of fetal loss (0.6 to 1.9 percent) and other obstetric complications. Since operator experience is a major determinant of such complications, ideally FBS should be consolidated to a few centers with adequate volume to maintain operators' experience. (See 'Complications' above.)
3 : Effect of atracurium or pancuronium on the anemic fetus during and directly after intravascular intrauterine transfusion. A double blind randomized study.
11 : Fetal blood sampling from the intrahepatic vein: analysis of safety and clinical experience with 214 procedures.
14 : Cardiocentesis: an alternative method of fetal blood sampling for the prenatal diagnosis of hemoglobinopathies.
19 : Application of the 'Apt test' in prenatal diagnosis to evaluate the fetal origin of blood obtained by cordocentesis: results of 30 pregnancies.
20 : Accuracy of the haemoglobin alkaline denaturation test for detecting maternal blood contamination of fetal blood samples for prenatal karyotyping.
28 : False-negative prenatal exclusion of Wiskott-Aldrich syndrome by measurement of fetal platelet count and size.
29 : Diagnosis and treatment of feto-maternal hemorrhage in a fetus with homozygous von Willebrand's disease.
30 : Diagnosis and treatment of feto-maternal hemorrhage in a fetus with homozygous von Willebrand's disease.
35 : Effect of diagnostic and therapeutic cordocentesis on maternal serum alpha-fetoprotein concentration.
38 : Percutaneous fetal umbilical blood sampling: procedure safety and normal fetal hematologic indices.
46 : Comparisons of outcomes after cordocentesis at mid-pregnancy between singleton and twin pregnancies.
49 : Practice Guidelines for Obstetric Anesthesia: An Updated Report by the American Society of Anesthesiologists Task Force on Obstetric Anesthesia and the Society for Obstetric Anesthesia and Perinatology.
50 : Phenylephrine vs ephedrine in cesarean delivery under spinal anesthesia: A systematic literature review and meta-analysis.
52 : A prospective randomised trial of atosiban versus hexoprenaline for acute tocolysis and intrauterine resuscitation.
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