User:Ecapelle/Bio460Sandbox

This is the group sandbox page for Anam and Beth for research on prenatal diagnosis and preimplantation genetics. We will be editing the article on Percutaneous umbilical cord blood sampling.

Key Points to Address in the Article
1.) Qualifying Risk Factors--why does this type of exam need to be done?

2.) What is the purpose of this test? What do the results mean? what are the benefits of this?

3.) Risks--Can we expand on this section?

Resources
1.) [|Fetal Blood Sampling] This article has details about various fetal blood sampling methods, as well as the risk vs. benefit of each method.  It could be useful in contributing to an introduction, the procedure, and risks sections.

2.) [|Fetal laboratory medicine: on the frontier of maternal-fetal medicine] Risks/Benefits and some general background information.

3.) [| Mayo Clinic] general information

4.) [| PubMed Article] addresses issues of fetuses with only one umbilical artery

5.) [| Wiley Article] general case studies on effects of cordocentesis

6.) [| UMM Article] great information

7.) [| Cordocentesis Uses] discusses risk factors and uses

8.) [| GLOWM Article] addresses procedure and benefits vs. risks

Outline
I. Background Info

II. Qualifying Risk Factors

III. Procedure--add details

IV. Indications/Contraindications and Associated Risks--add details

V. Diagnostic Uses --add more details

Editing from Anam
General (Background) Info

Percutaneous blood cord sampling (PUBS) is a useful procedure for managing the health of a fetus. The method of PUBS is used to identify many conditions, including chromosomal abnormalities, blood disorders, metabolic disorders, structural, and growth problems. It is also useful for fetal blood transfusions, and to provide a direct supply of medications to the fetus. Moreover, the fetal blood can be analyzed for genetic testing by making a karyotype of the fetus. A karyotype would allow determination of any genetic disorders. Typically, this procedure involves the use of a needle, which is guided by an ultrasound. The site of sample extraction is usually the umbilical cord, but it can also be the intrahepatic valve or the fetal heart (usually in cardiocentesis). The risks with this procedure involve loss of pregnancy, bradychardia (slow heart rate), umbilical bleeding, and transmission of maternal infection. Because the potential of serious risk to the health of the fetus, invasive procedures such as PUBS are only done if absolutely necessary. Also, as the umbilical cord of an early fetus is weak, this procedure is done after the fetus is at least 18 weeks or older to decrease the risk of injury to the fetus.

Procedure

If the fetus is viable, the procedure is performed close to an operating room in case an emergency cesarean section is necessary due to complications caused by the procedure. Currently, there is no definite age of viability because this depends on the fetus’ ability to survive outside the womb, which in cases of premature births, can depend on access to medical care and technology needed to keep the fetus alive through the neonatal stage. As an example, in the United States fetal viability typically occurs at about 24 weeks of gestation, and in Portugal it is at about 25 weeks. When the fetus is in between the ages of 24-34 weeks, a glucocorticoid is given to the patient about 24 hours before the procedure to stimulate lung maturity. An ultrasound is performed before the procedure to view the position of the fetus, and may be used during the procedure to help guide the needle. The mother’s blood is drawn for comparison against fetal blood, and intravenous access is established in the mother in order to supply medications as needed. To reduce the risk of intraamniotic infection, antibiotics are supplied through the intravenous access about 30-60 minutes before the procedure. If movement of the fetus is a risk to the success of the procedure, the fetus may be paralyzed using a fetal paralytic drug.

A 20 or 22 gauge spinal needle is typically used in cordocentesis, and may be prepared with an anticoagulant, which helps to reduce the risk of clot formation. During the procedure, the first step is to locate a relatively stable segment of the umbilical cord. A typical sampling site would be where the segment of the umbilical cord is closest to the placenta, however there is a risk of maternal blood contamination at this site. Blood sampling may be achieved with more ease if the placenta is in the anterior position. However, if the placenta is in the posterior position, the fetus might block direct access to the umbilical cord. Once the umbilical cord is reached and the correct position of the needle is confirmed, the fetal blood is drawn. The needle is removed after all necessary samples are taken. The site of puncture is monitored after the procedure for bleeding. Also, if the fetus is viable, fetal heart rate is monitored post-procedure for one to two hours.

Intrahepatic vein fetal blood sampling may be done as an alternative to cordocentesis. It involves the needle being inserted into the intrahepatic part of the umbilical cord in the fetal abdomen. The benefits of this alternative, compared to cordocentesis, are that chances of contamination of the fetal blood are very low, the risk of fetomaternal hemorrhage are reduced, the risk of bleeding from the sampling site is reduced, and access to the sampling site is easy regardless of the position of the placenta. In pregnancies with high risk of fetal thrombocytopenia, this is the preferred method of blood samples due to the very low risk of site bleeding. ,

After the blood samples are obtained, they are placed into tubes containing anticoagulants in order to stop the blood from clotting. If the blood sample was obtained at the site close to the placenta, a fetal blood confirmation test should be done to ensure no mixing of fetal and maternal blood occurred before the diagnostic tests are done on the blood. Fetal red blood cells (RBC) are usually bigger than maternal RBCs, therefore the average volume of RBCs, the mean corpuscular volume (MCV), is one of the methods used to determine whether or not the fetal blood has been contaminated. Another method, human chorionic gonadotropin (hCG) determination, can detect maternal blood because maternal blood has high levels of hCG. The hemoglobin alkaline denaturation test (Apt test) can detect the presence of maternal blood, which is indicated by a color change from red to brown wen the sample is added to alkali reagent. , Blood typing would also detect maternal blood, as the I antigen only occurs in adults. The Kleihauer-Betke test can detect very small amounts of maternal blood before the third trimester of pregnancy by monitoring hemoglobin elution in acid because adult and fetal hemoglobin elute differently in acid. Finally, a white blood cell count can detect maternal blood in the sample, as fetal white blood cells are primarily leukocytes, while maternal white blood cells are mostly neutrophils. If amniotic fluid infiltrated the sample, then there would be a reduction in the volume of RBCs, white blood cells, and platelets in the sample. Also, patterns consistent with amniotic fluid would be visible in the sample. ,

Editing from Beth
Percutaneous umbilical cord blood sampling does not give a general, overall picture of fetal status and environment. Rather, it gives a snapshot of the current condition at the point of sampling. PUBS may give an indication as to what can be expected in the future; however, results do not say with certainty that fetal distress or lack thereof will occur. Percutaneous umbilical cord blood sampling is not indicated for in every pregnancy. PUBS is often suggested for patients who have not received adequate information from ultrasounds, chorionic villi sampling, and amniocentesis. Pregnancies with fetuses younger than 32 weeks or weighing less than 1500 grams along with atypical fetal monitoring could benefit from percutaneous umbilical cord blood sampling. This includes growth-restricted fetuses who are abnormally small for their gestation period which could be caused by a number of factors including smoking, high blood pressure, substance use, and placenta previa. The results from this test could indicate the fetus’ problems in an attempt to set up a treatment and management plan. While PUBS is an invasive procedure that comes with risks, fetal mortality rate associated with this procedure falls within the range of one to two percent. In order to decrease mortality and procedure-related injuries, it is optimal that the fetus is not stressed. Post-PUBS risks include excessive bleeding, cramping, and infection at the site of needle entry.

History

PUBS is a type of fetal blood sampling which was originally developed to determine the presence of hereditary abnormalities Currently, it can detect a number of abnormalities including pH levels, oxygen levels, chromosomal issues, and infections. PUBS dates back to 1964 when Freda and Adamsons reported the removal of a uterus in a fetus who had a buildup of fluid and ended up dying; however, this was one of the first procedures that showed promise for current day PUBS. Valenti hypothesized in 1972 that the procedure he used to obtain fetal tissue could be used to obtain fetal blood, and in 1973, he was able to sample fetal vessels. Fetoscopy was used and refined between 1974 and 1983 as a prenatal test to determine fetal status as well as obtain fetal blood and perform transfusions in some cases. Fetoscopy is a procedure in which a device is inserted through the abdomen of the mother in order to visualize the fetus. The first documented use of PUBS came in 1983 by Daffos and colleagues who sampled blood from an umbilical vein with a needle whose maneuvers were monitored by an ultrasound. PUBS has presented a more successful and less dangerous alternative to fetoscopy, which carried a miscarriage risk of 5-10%.

Indications and Contraindications

PUBS is not a diagnostic test that is indicated in every pregnancy. It is however suggested in pregnancy cases in which the blood gas levels and pH would aid in diagnosis of a condition, such as anemia, or delivery plan, if termination of the pregnancy is being considered or special plans must be made. Severe fetal growth issues in conjunction with low oxygen in the fetus’ blood and high levels in the mother’s blood also indicate the use of PUBS. With more detailed observations and information on fetal tissue perfusion and metabolism, better predictions on development can be made. For pregnancies in which genetic abnormalities may be present, PUBS can be used to construct a karyotype, usually within 48 hours, and detect irregular chromosomal patterns. Karyotypes are able to confirm or detect monosomies, trisomies, or missing portions of chromosomes to give a detailed picture of the severity of the genetic defect as well as predicting developmental future. PUBS is also indicated in the cases of twins with accumulation of amniotic fluid and substantially different growth rates (at least 10%), if the fetus is expected to be breaking down red blood cells improperly, and in the alleviation of hyrops fetalis, a build-up of fluid in at least 2 parts of the fetus. Suspicion of fetal infections, such as rubella and toxoplasmosis, as well as the need to supply medicine or blood transfusions to the fetus are indications for the use of PUBS.

Due to its invasive nature, the contraindications of PUBS must be taken into account in order to ensure the safety of the fetus and the mother. During the first 18 weeks of pregnancy, the umbilical vein from which the blood sample is taken is not very stable which could lead to excessive bleeding ; therefore, PUBS is contraindicated in any fetus under the age of 18 weeks old. While blood gas levels and pH values are able to give parents and medical professionals a snapshot of fetal status, cases of normal or even growth deficient fetuses with a regular heart rate and typical rhythm are contraindications of PUBS. These fetuses can be monitored with less invasive procedures and equipment, such as ultrasounds, cardiotocography, or maternal blood tests. Mothers affected by hepatitis B, hepatitis C, or hepatitis D are not advised to undergo PUBS. In these cases, the fetus would be put at an increased risk of contracting the hepatitis virus from the mother. However, the necessity of the procedure should be considered along with this risk. PUBS should not be performed in mothers testing positive for the human immunodeficiency virus (HIV) due to increased risk of fetal contraction; however, PUBS is used to determine if the fetus has been infected with HIV

Fetuses with a single umbilical artery

The most prevalent defect in about 1% of fetuses is a single umbilical artery. Fetal and maternal blood supply are typically connected in utero with one vein and two arteries to the fetus. The umbilical vein is responsible for delivering oxygen rich blood to the fetus from the mother; the umbilical arteries are responsible for removing oxygen poor blood from the fetus. This allows for the fetus’ tissues to properly perfuse. When a single umbilical artery is found, more tests are run including a detailed ultrasound to detect any other developmental abnormalities that may be the result of the single artery, genetic deviation, or other causes. Fetal developmental abnormalities along with the concern of an abnormal karyotype indicate PUBS; however, fetuses with a single umbilical artery may present a higher risk. In these cases, a single umbilical artery is required to perform the work of two arteries so it is often dilated up to one and a half times its size in order to meet these demands. A documented case of puncturing a single umbilical artery during PUBS resulted in a decrease in the heart rate of the fetus with irregular improvement ; however, it is difficult to conclude that these symptoms were solely the result of the punctured umbilical artery because these fetuses often have preexisting defects and abnormalities. While ultrasounds and color flow mapping can be used to avoid the umbilical artery and sample from the umbilical vein, the dilation makes the single umbilical artery easier to puncture. Blood flow in the umbilical artery is seen to be twice the normal amount from about 20 weeks on so the effects of a punctured umbilical artery during PUBS are more severe.