Amniocentesis

Amniocentesis may be performed for both diagnostic and therapeutic reasons. Diagnostic indications Genetic diagnosis The American College of Obstetricians and Gynecologists recommends that all women be offered prenatal assessment for aneuploidy by either genetic screening or diagnostic testing independent of maternal age or risk factors. Assessment of fetal lung maturity Amniocentesis has traditionally been performed to assess the extent of fetal lung development in the context of medical and obstetrical complications, with the intention of delivering the fetus if fetal lung maturity is demonstrated. Lack of fetal lung maturity increases the risk of infant respiratory distress syndrome. Fetal lung development can be tested by sampling the amount of surfactant in the amniotic fluid obtained via amniocentesis. The efficacy of performing amniocentesis for the assessment of fetal lung maturity has been called into question. Based on this rationale, the risks associated with amniocentesis, and the limited indications, performing amniocenteses for assessing fetal lung maturity may become obsolete except in instances where gestational age is unknown. The gold standard for diagnosing chorioamnionitis is via a gram stain, glucose level, or culture of the amniotic fluid obtained via amniocentesis. Amniocentesis can be used to detect other congenital infections such as cytomegalovirus, hepatitis B, parvovirus B19, and toxoplasmosis. Assessment of severity of Rh isoimmunization The Rh factor is an inherited protein found on the surface of red blood cells. If the mother is Rh negative and the father is Rh positive, a fetus has at least a 50% chance of being Rh positive. Rh sensitization typically does not cause problems during the first pregnancy of an Rh negative woman. Physicians have used the process of inserting a needle transabdominally into the uterus to extract excess amniotic fluid, also known as a reductive amniocentesis or decompression, for the management of polyhydramnios as early as the late 1800s. This process can result in polyhydramnios in one twin and oligohydramnios in the other twin. A potential benefit of using amniotic stem cells over those obtained from embryos is that they address the ethical concerns among anti-abortion activists by obtaining pluripotent lines of undifferentiated cells without harm to a fetus or destruction of an embryo. In addition, the use of embryonic cells has been shown to develop into tumors such as teratocarcinomas and frequently acquire chromosomal errors, underscoring the benefits of utilizing amniotic stem cells. Research has shown that cells from second trimester amniotic fluid are successful at differentiating into various cell lines. Artificial heart valves, working tracheas, as well as muscle, fat, bone, heart, neural and liver cells have all been engineered through use of amniotic stem cells. Tissues obtained from amniotic cell lines show significant promise for patients with congenital diseases/malformations of the heart, liver, lungs, kidneys, and cerebral tissue. The first amniotic stem cells bank in the US is active in Boston, Massachusetts. == Contraindications ==

There are no absolute contraindications to amniocentesis. Relative contraindications to the procedure include failure to discontinue anticoagulation therapy 48–72 hours prior to amniocentesis, infections such as hepatitis B, hepatitis C, or human immunodeficiency virus (HIV), and oligohydramnios. There is an increased risk of mother-to-child (vertical) transmission of bloodborne infections in patients with hepatitis B, hepatitis C, or HIV after amniocentesis. While not a contraindication, an amniocentesis may be postponed if fusion of the amnion and chorion has not yet occurred. Performing an amniocentesis prior to the fusion of the amnion and chorion is more likely to lead to procedure failure that may require further sampling attempts. == Risks and complications ==

Amniocentesis performed for the purpose of prenatal diagnostic testing for genetic disorders has been established as a safe and accurate procedure. A serious risk of amniocentesis is pregnancy loss. The American College of Obstetricians and Gynecologists note that the pregnancy loss rates attributable to amniocentesis are very low. Studies from 2000 to 2006 estimated the procedure-related pregnancy loss at 0.6-0.86%. The most recent systematic review of the literature and updated meta-analysis on the risk of pregnancy loss following amniocentesis was published in 2019. This study cites the amniocentesis-related pregnancy loss to be 0.30% (95% CI, 0.11–0.49%). The incidence of amniocentesis-related complications, including pregnancy loss and procedure failure, may be mitigated when performed by experienced practitioners who complete 100 or more amniocenteses per year. Experienced practitioners are more likely to complete the procedure with only one puncture attempt. Past literature has shown that twin pregnancies increase the background risk of fetal loss following amniocentesis before 24 weeks' gestation by 1%. The study also found no significant difference in rates of pregnancy loss between twin pregnancies that underwent amniocentesis and those that did not before 24 weeks of gestation. • Active vaginal infection • Maternal body-mass index greater than 40 kg/m2 • Multiparity, or 3 or more childbirths • History of 3 or more pregnancy losses • Carrying a fetus with structural malformations Undergoing amniocentesis in the third trimester has been associated with an increased risk of preterm labor, as defined as the onset of labor between 20 and 37 weeks' gestation, and preterm delivery. When compared to cases of spontaneous PPROM, patients with amniocentesis-related PPROM experience better outcomes and lower rates of pregnancy loss. Therefore, possible consequences of oligohydramnios include infant respiratory distress and small, underdeveloped lungs known as fetal lung hypoplasia. In subsequent pregnancies with RhD positive fetuses, maternal presence of these antibodies can attack and destroy fetal red blood cells, a process called Rh isoimmunization that can result in a condition known as Rhesus disease or hemolytic disease of the fetus and newborn. Maternal blood type is assessed prior to undergoing amniocentesis and RhD immune globulin (RhoGam) is typically administered within 72 hours of the procedure to prevent maternal Rh sensitization in RhD negative patients that are non-sensitized to RhD antigens. Amniotic fluid embolism, a condition in which amniotic fluid or other fetal debris enters the maternal circulation, is an extremely rare and catastrophic complication of amniocentesis. However, amniotic fluid embolism following amniocentesis has been reported infrequently in the literature in the last 60 years, mostly in the context of case-reports. Chorioamnionitis and uterine and maternal skin infections are potential complications of amniocentesis that can occur as a result of bacterial introduction throughout the course of the procedure. The procedure-related risk of fetomaternal hemorrhage attributable to amniocentesis is 2.6%. Amniotic fluid cell culture after amniocentesis has a failure rate of 0.1%. Later gestational ages at the time of the procedure and amniotic fluid samples contaminated with blood increase the risk of amniocyte culture failure. While recognizing the aforementioned risks, the American College of Obstetricians and Gynecologists recommend that prenatal screening, or diagnostic testing for aneuploidy via procedures like amniocentesis or chorionic villus sampling, be discussed with and offered to all patients regardless of maternal age or risk profile. ==Procedure and technique==

An amniocentesis is typically performed in the second trimester between the 15th and 20th week of gestation; however, it can be done at any later gestational age. 18-20 mL of amniotic fluid is slowly aspirated, with the first 1-2 mL typically discarded due to higher risk of maternal cell contamination. The types of tests performed on the sample will be determined by the patient's indications for undergoing amniocentesis. Fluorescent in-situ hybridization (FISH) and quantitative fluorescence polymerase chain reaction (QF-PCR) are two tests commonly performed on uncultured cells after amniocentesis, with results available within two days. These tests can accurately identify trisomy 13, trisomy 18, and trisomy 21. FISH is capable of providing a limited karyotype and, along with the aforementioned trisomies, can also detect aneuploidies in the X and Y sex chromosomes. Abnormal results from FISH studies should be confirmed with other cytogenetic testing, as false positives and negatives are possible Karyotypes are another common test performed on amniotic fluid to visualize chromosome number and characteristics, with a result turnaround of up to three weeks. Another test that may be performed is a chromosomal microarray, which can detect chromosomal imbalances, such as small- and large-scale deletions and duplications. Chromosomal microarray can be performed on cultured or uncultured fetal tissue, with results available as early as 3 days. The American College of Obstetricians and Gynecologist recommends that patients who choose to undergo invasive diagnostic testing have access to chromosomal microarray analysis. == Recovery ==

After an amniocentesis, patients may resume their routine activity level while withholding from strenuous exercise. Follow-up one week after the procedure is recommended to undergo ultrasound evaluation for fetal viability and assess healing of the puncture site. The provider may also administer a RhoGAM injection depending on the patient's and fetus' blood types to prevent reactions to differing Rh proteins. Home care post-procedure Common side effects It is common for patients to experience mild cramping, abdominal pain, or pain at the insertion site. It is also common for patients to experience spotting or mild vaginal bleeding. Patients may feel fatigued and want to rest following the procedure. Recommendations Upon returning home from the procedure, it is recommended that the patient rests at home for 24 hours, avoiding strenuous activity such as exercising, running, heavy lifting, etcetera. It is also important to avoid sexual intercourse during this time. Practitioners often recommend acetaminophen, or Tylenol, to help alleviate any discomfort following the procedure. 650-1,000 mg every 4 hours is standard. Do not exceed 4,000 mg in 24 hours. == History ==

Physicians have used the process of inserting a needle transabdominally into the uterus to extract amniotic fluid for the management of hydramnios, or excess amniotic fluid, as early as the late 1800s. In 1930, needle insertion into the amniotic sac was used to inject contrast dye for the purposes of amniography, or radiographic visualization of the fetal, placental, and uterine outlines. Beginning in the 1950s, amniocentesis was used to diagnose and determine the severity of Rhesus disease. In the mid-1950s, Fritz Fuchs and Povl Riis used fetal cells cultured from extracted amniotic fluid to determine fetal sex based on the presence of Barr Bodies. They postulated that this technique could provide information on the risk for X-linked disease in fetuses with carrier mothers. By the 1960s, this technology was being applied to X-linked conditions such as Duchenne muscular dystrophy and hemophilia. In 1966, M. W Steele and W. R Breg Jr. were able to culture amniocytes that could undergo karyotyping. Their work opened the door to the prenatal diagnosis of aneuploidies. In 1972, R. G. Sutcliffe and D. J. H. Brock found that higher amniotic alpha-fetoprotein levels were associated with neural tube defects. In 1972, ultrasound-guided amniocenteses began replacing free-handed taps following J. Bang and A. Northeved's initiative to employ ultrasound technology to improve amniocentesis. Up until the 1980s, static B-scan ultrasound-guidance was used for the procedure, a process that did not permit visualization of the needle in the amniotic cavity. Eventually, real-time ultrasound scanners improved the ultrasound-assisted amniocentesis. Given its prenatal diagnostic accuracy for a range of fetal conditions and its relative safety profile, amniocentesis has become the most common invasive fetal testing procedure. == Society and culture ==

Prenatal sex discernment and sex-selective abortion As stated in the history section, amniocentesis can be used to determine the sex of a fetus. This can be medically relevant in families that carry X-linked genetic conditions, since parents may want further genetic testing if the fetus is determined to be male (XY), and therefore has a higher likelihood of having the inherited disease. However, sex discernment is also used for social and cultural reasons. In some cultures, male children are more desirable than female children. This leads some parents to use amniocentesis and other forms of prenatal genetic testing (like chorionic villus sampling and preimplantation genetic diagnosis) to determine the sex of the child with the intent of terminating the pregnancy if the fetus is determined to have two X chromosomes. Sex-selective abortion is particularly common in countries such as China or India, among others. Sex-selective abortion is one of the causes for low child sex ratios in countries in Asia, Africa, and Eastern Europe. There are also significantly skewed child sex ratios in the Caucasus region. Naturally, the human sex ratio is approximately 105 males for every 100 females, and any significant deviations from these values is usually considered evidence for sex selective abortion. India and China have made prenatal sex determination illegal in an effort to prevent sex-selective abortion. In India, this happened through the 1994 Pre-Conception and Pre-Natal Diagnostic Techniques (Prohibition Of Sex Selection) Act (PCPNDT Act). However, this has not necessarily affected the widespread practice of sex-selective abortion as abortion is generally legal, and this law has been inconsistently enforced. In China, the societal preference for male children was exacerbated by the historical one-child policy, where in many regions of China, parents were limited to having only one child. As with India, prenatal sex determination is banned in China but remains a widespread practice, with enforcement also proving to be difficult. == See also ==