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Amniocentesis

Amniocentesis is a medical procedure used primarily in the prenatal diagnosis of genetic conditions. It has other uses such as in the assessment of infection and fetal lung maturity. Prenatal diagnostic testing, which includes amniocentesis, is necessary to conclusively diagnose the majority of genetic disorders, with amniocentesis being the gold-standard procedure after 15 weeks' gestation.

In this procedure, a thin needle is inserted into the abdomen of the pregnant woman. The needle punctures the amnion, which is the membrane that surrounds the developing fetus. The fluid within the amnion is called amniotic fluid, and because this fluid surrounds the developing fetus, it contains fetal cells. The amniotic fluid is sampled and analyzed via methods such as karyotyping and DNA analysis technology for genetic abnormalities.

An amniocentesis is typically performed in the second trimester between the 15th and 20th week of gestation. Women who choose to have this test are primarily those at increased risk for genetic and chromosomal problems, in part because the test is invasive and carries a small risk of pregnancy loss. However, the American College of Obstetricians and Gynecologists recommend that all women be offered prenatal assessment for aneuploidy, or the presence of an abnormal number of chromosomes, by either genetic screening or diagnostic testing independent of maternal age or risk factors. There are relative contraindications to performing an amniocentesis, however no absolute contraindications have been identified.

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.

Medical uses
Amniocentesis may be performed for both diagnostic and therapeutic reasons.

Genetic diagnosis
The American College of Obstetricians and Gynecologists recommend that all women be offered prenatal assessment for aneuploidy by either genetic screening or diagnostic testing independent of maternal age or risk factors. Prenatal genetic screening is intended to identify patients who are at increased risk of having a fetus with a genetic condition while prenatal genetic diagnostic testing detects whether a specific genetic condition is present in the fetus with high accuracy. Amniocentesis, along with chorionic villus sampling, are examples of prenatal diagnostic tests. Amniocentesis or chorionic villus sampling are necessary to conclusively diagnose the majority of genetic disorders, with amniocentesis being the gold-standard procedure after 15 weeks' gestation. Transabdominal chorionic villus sampling is an alternative to amniocentesis if genetic diagnostic testing is to be performed in the first trimester between 10 and 15 weeks' gestation. It is important to note that prenatal genetic testing cannot identify all possible fetal genetic abnormalities or their outcomes. When deciding on whether to perform invasive genetic diagnostic testing such as amniocentesis, patients and their physicians should participate in a shared-decision-making process that takes into account a patient's individual risk profile and preferences.

Amniocentesis may be offered to certain patients at higher risks of having a fetus with a genetic disorder. Factors that may place patients at increased risk of fetal genetic disorders include older maternal or paternal age, parental carrier of a balanced chromosomal rearrangement, parental aneuploidy or aneuploidy mosaicism, parental carrier of a genetic disorder, prior child with a structural birth defect, previous fetus or child with autosomal trisomy or sex chromosome aneuploidy, ultrasonographic evidence of a fetus with structural abnormalities, and a high-risk genetic screening test result.

Analysis of samples obtained from amniocentesis is accomplished via karyotyping and DNA analysis technology. Examples of conditions that may be detected include chromosomal abnormalities such as common aneuploidies like trisomy 13, trisomy 18, trisomy 21, Turner syndrome, and Klinefelter syndrome. Micro-deletions or micro-duplications, such as DiGeorge syndrome and Cri-du-Chat syndrome, sex-linked disorders, such as hemophilia and Duchenne muscular dystrophy, and specific genetic mutations previously demonstrated to be present in a family or suspected based on fetal ultrasound findings, such as sickle cell disease, Tay–Sachs disease, neurofibromatosis, and cystic fibrosis.

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. Several tests are available, including the lecithin-sphingomyelin ratio ("L/S ratio"), the presence of phosphatidylglycerol (PG), and the surfactant/albumin (S/A) ratio. An L/S ratio of 2.0 is associated with a lower incidence of infant respiratory distress syndrome.

The efficacy of performing amniocentesis for the assessment of fetal lung maturity has been called into question. The Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Society for Maternal-Fetal Medicine's joint statement on the matter states that "if significant maternal or fetal risks exist, delivery should occur regardless of biochemical maturity and if delivery could be deferred owing to absence of pulmonary maturity there is not a stringent indication for prompt delivery." 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.

Assessment and management of infection
Chorioamnionitis, or intraamniotic infection, is an infection of any combination of the amniotic fluid, placenta, fetus, fetal membranes, or decidua. The gold standard for diagnosing chorioamnionitis is via a gram stain, glucose level, or culture of the amniotic fluid obtained via amniocentesis. However, in clinical practice, performing an amniocentesis for the purpose of diagnosing chorioamnionitis is rare and instead diagnosed based on clinical signs to ensure prompt treatment and avoid invasive prenatal testing.

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 incompatibility occurs when a mother has Rh-negative blood and her baby has Rh-positive blood. If the red blood cells of an Rh positive fetus cross into their Rh negative mother's blood flow, the mother is at risk of Rh sensitization, a process in which maternal antibodies form against red blood cell Rh antigens. Events causing fetomaternal hemorrhage, such as miscarriage, trauma to the abdomen during pregnancy, ectopic pregnancy, induced abortion, invasive pregnancy procedures, labor, and birth can lead to fetal Rh positive red blood cells entering the Rh negative maternal circulation. Rh sensitization typically does not cause problems during the first pregnancy of an Rh negative woman. However, in a subsequent pregnancy with an Rh positive fetus, the formed antibodies can cross the placenta and attack the red blood cells of the fetus, a process called Rh isoimmunization that can result in a condition known as Rhesus disease or hemolytic disease of the fetus and newborn.

Hemolytic disease of the fetus and newborn can lead to varying degrees of fetal anemia, which can potentially have devastating consequences including newborn jaundice, kernicterus, hydrops fetalis, and intrauterine fetal demise. RhD immune globulin (RhoGam) is administered to prevent maternal Rh sensitization in Rh negative patients that are non-sensitized to Rh antigens.

In the past, serial amniocenteses has been used to monitor isoimmunized pregnancies by measuring the levels of bilirubin, a byproduct of red blood cell breakdown, present in amniotic fluid using spectrophotometry. However, ultrasound detecting middle cerebral artery peak systolic velocity has now replaced serial amniocenteses for the management of isoimmunized pregnancies.

Amniocentesis is an invasive prenatal test that has the potential to cause maternal and fetal blood cell mixing, which can worsen Rh isoimmunization.

Decompression of polyhydramnios
Polyhydramnios is an excessive accumulation of amniotic fluid that can lead to serious perinatal and maternal outcomes such as intrauterine fetal demise, preterm labor, premature rupture of membranes, and cesarean delivery. 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.

Reductive amniocentesis is currently indicated for severe cases of polyhydramnios only.

Decompression in twin oligohydramnios-polyhydramnios sequence (TOPS)
Twin oligohydramnios-polyhydramnios sequence is a rare condition that may occur when twins sharing a single placenta develop significant vascular cross-connections, known as anastomoses, resulting in blood flowing away from one twin to the other. This process can result in polyhydramnios in one twin and oligohydramnios in the other twin. Amniocentesis has been employed to reduce the volume in the sac with polyhydramnios in order to relieve amniotic fluid pressures, a process that may improving fetal circulation and outcomes.

Stem cells
Amniotic fluid, which is easily collected, cultured, and stored through cryopreservation, can be a rich source of pluripotent and multipotent mesenchymal, hematopoietic, neural, epithelial, and endothelial stem cells. 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. These patients are at a higher risk of complications if they undergo amniocentesis and should be counseled appropriately. In some cases, the advantages of obtaining the results of an amniocentesis may outweigh the increased risk of complications.

Patients on oral anticoagulation therapy have an increased risk of bleeding from the procedure and may be switched to low-molecular-weight heparin, which carries a lower risk for bleeding complications, prior to amniocentesis. 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. Patients with high viral loads are at a greater risk of vertical transmission of hepatitis B compared to patients with low viral loads. In patients living with HIV, amniocentesis should be deferred until a combined antiretroviral therapy (CART) regimen is established and the patient achieves a low or undetectable viral load.

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. The risks and complications associated with amniocentesis include pregnancy loss, preterm labor and delivery, preterm premature rupture of membranes (PPROM), fetal injuries, Rhesus disease, and amniotic fluid embolism. Oligohydramnios, fetomaternal hemorrhage, cell culture failure, multiple amniotic fluid extraction attempts, and infections are also possible complications. Additional maternal complications include vaginal bleeding, hematoma of the skin, damage to surrounding internal organs, procedural pain including stinging, pressure, and cramping, and post-procedure discomfort.

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. The mechanism for pregnancy loss following amniocentesis is unknown but may be a consequence of bleeding, infection, or trauma to the fetus or the amniotic sac as a result of the procedure. 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. Multiple needle insertion attempts are associated with an increased risk of pregnancy loss. Early amniocentesis, defined as performing the procedure between 10 and 13 weeks' gestation, is associated with significantly higher rates of pregnancy loss following amniocentesis. Early amniocentesis also has higher rates of other complications, including membrane rupture, clubfoot, and amniotic fluid culture failure. For these reasons, the American College of Obstetricians and Gynecologists and other similar professional associations recommend against undergoing amniocentesis prior to 14 weeks' gestation.

In the past, twin pregnancies have been noted to have a higher rate of pregnancy loss (estimated at 3.07%) following amniocentesis. Past literature has shown that twin pregnancies increase the background risk of fetal loss following amniocentesis before 24 weeks' gestation by 1%. Although data on complications following amniocentesis in twin pregnancies continues to be limited, the American College of Obstetricians and Gynecologists note that rate of pregnancy loss due to amniocentesis in this population is estimated to be around 2%. A 2020 systematic review and meta-analysis showed similar findings, noting that pregnancy loss following amniocentesis may be lower than previously reported in twin pregnancies. 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.

Maternal factors that may further increase the risk of pregnancy loss following amniocentesis include:

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. Preterm premature rupture of membranes (PPROM) and subsequent leakage of amniotic fluid are additional possible complications, with the procedure-related PPROM rate following amniocentesis estimated to be between 1–2%. When compared to cases of spontaneous PPROM, patients with amniocentesis-related PPROM experience better outcomes and lower rates of pregnancy loss. Leakage of amniotic fluid can result in oligohydramnios, or an amniotic fluid volume that is less than the minimum expected for gestational age. Adequate amniotic fluid volumes are essential for fetal lung development. Therefore, possible consequences of oligohydramnios include infant respiratory distress and small, underdeveloped lungs known as fetal lung hypoplasia.
 * Presence of uterine fibroids
 * Presence of Müllerian anomalies, which are a group of congenital defects affecting the development of the female reproductive tract
 * 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

Needle injuries to the fetus are increasingly rare due to the practice of using continuous ultrasound-guidance, including during needle insertion and amniotic fluid extraction. Reported needle injuries include cord bleeding, ocular injuries, fetal brain and cutaneous injuries, and deformities such as clubfoot. The risk of fetal injury increases with increasing number of puncture attempts.

Maternal and fetal blood cells may mix during an amniocentesis and, as a result, patients with rhesus (RhD) negative blood types carrying a RhD positive fetus are at risk of Rh sensitization. Rh sensitization is a process in which maternal antibodies form against red blood cell RhD antigens. 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. Amniotic fluid embolism can result in cardiovascular collapse and has a poor maternal prognosis. 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 risk of amniocentesis-related chorioamnionitis and uterine infections is less than 0.1%. Performing the procedure using sterile techniques can help prevent infection.

Fetomaternal hemorrhage, or the entrance of fetal blood into the maternal circulation, is another complication of amniocentesis. It can result in anemia that can have consequences of varying severity. 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. It is an outpatient procedure typically performed by an obstetrician-gynecologist with additional amniocentesis training.

Genetic counseling should be provided to the pregnant patient and informed consent should be obtained prior to the procedure.

Prior to the onset of the amniocentesis, the pregnant patient will undergo ultrasound evaluation to assess fetal viability and position, gestational age, amniotic fluid volume, maximum vertical pocket, umbilical cord insertion site, and any obvious fetal deformities. This information is utilized to determine the needle used and how the procedure should be performed. The fetus should be at least 15 weeks' gestation and the chorion and amnion should be fused.

Amniocentesis is a sterile procedure, therefore medical personnel performing and assisting with the procedure will scrub with antiseptic solution, use sterile gloves, clean the maternal abdomen with antiseptic solution, cover the ultrasound probe with a sterile cover, and use sterile ultrasound gel.

Ultrasound guidance is used continuously throughout the course of the procedure so that the needle is always visualized. A sterile 20–22 gauge spinal needle is firmly inserted perpendicular to the maternal abdomen. After puncturing the maternal abdomen, the operator punctures the uterus, gains access into amniotic cavity by puncturing the amniotic membrane while taking care not to cause membrane tenting, and proceeds to advance the needle into the amniotic cavity. The needle should be guided into the region of the maximum vertical pocket, where the single largest area of amniotic fluid devoid of fetal parts, umbilical cord, and placenta is available for sampling. Amniotic fluid is composed of fetal cells, urine, and lung secretions. 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 remaining sample is submitted for laboratory testing. Fetal viability after the procedure should be confirmed by observing adequate fetal cardiac activity. The number of needle puncture attempts should be documented.

There is little scientific data supporting administration of prophylactic antibiotics prior to an amniocentesis and therefore, it is currently not recommended. Similarly, there is little scientific support for the placement of a local anesthetic prior to amniocentesis.

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 isoimmunization in RhD negative patients that are non-sensitized to RhD antigens.

Amniocentesis technique differs in twin pregnancies and requires additional operator training. The two different approaches are the single-needle technique and two-needle insertion technique.

If used for prenatal genetic diagnosis, fetal cells may be separated by centrifugation from the extracted sample and grown in a culture medium in order to perform genetic tests. 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. Some sources recommend house rest for the initial 24 hours after the procedure, though data supporting this recommendation is limited. Follow-up one week after the procedure is recommended to undergo ultrasound evaluation for fetal viability and assess healing of the puncture site. Post-procedural pain and discomfort should be minimal and temporary and may be managed with acetaminophen. Patients will be instructed to report to an emergency room if they experience vaginal bleeding or leakage of fluid, intense uterine pain, or a fever greater than 38 °C.

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.

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.

title: Amniocentesis


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Bengt Jönsson (Oxenstierna)

Bengt Jönsson (Oxenstierna), (1390s–1450s) Swedish statesman and noble. Under the Kalmar Union, he served as co-regent of Sweden, from January to June 1448, together with his brother Nils Jönsson (Oxenstierna). Member of the Privy Council of Sweden from 1435, and magistrate of Uppland in 1439. Dubbed as knight by King Christopher of Bavaria following his coronation in 1441, and Master of the Royal Court from the same year.

His farm was Salsta manor (Salsta slott) at Lena parish in Norunda, Uppland. He made large donations to Tensta Church (Tensta kyrka) and was featured in a fresco made in 1437 by the artist Johannes Rosenrod.

He married in 1416 with Kristina Kristiernsdotter (Vasa), widow of Karl Stensson Blad, with whom he had four sons including Jöns Bengtsson Oxenstierna, Archbishop of Uppsala (1448–1467).

license: Creative Commons - Attribution Share-Alike - https://creativecommons.org/licenses/by-sa/4.0/

title: Bengt Jönsson (Oxenstierna)


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Amniotic sac

The amniotic sac, also called the bag of waters or the membranes, is the sac in which the embryo and later fetus develops in amniotes. It is a thin but tough transparent pair of membranes that hold a developing embryo (and later fetus) until shortly before birth. The inner of these membranes, the amnion, encloses the amniotic cavity, containing the amniotic fluid and the embryo. The outer membrane, the chorion, contains the amnion and is part of the placenta. On the outer side, the amniotic sac is connected to the yolk sac, the allantois, and via the umbilical cord, the placenta.

The yolk sac, amnion, chorion, and allantois are the four extraembryonic membranes that lie outside of the embryo and are involved in providing nutrients and protection to the developing embryo. They form from the inner cell mass; the first to form is the yolk sac followed by the amnion which grows over the developing embryo. The amnion remains an important extraembryonic membrane throughout prenatal development. The third membrane is the allantois, and the fourth is the chorion which surrounds the embryo after about a month and eventually fuses with the amnion.

Amniocentesis is a medical procedure where fluid from the sac is sampled during fetal development, between 15 and 20 weeks of pregnancy, to be used in prenatal diagnosis of chromosomal abnormalities and fetal infections.

Structure
The amniotic cavity is the closed sac between the embryo and the amnion, containing the amniotic fluid. The amniotic cavity is formed by the fusion of the parts of the amniotic fold, which first makes its appearance at the cephalic extremity and subsequently at the caudal end and sides of the embryo. As the amniotic fold rises and fuses over the dorsal aspect of the embryo, the amniotic cavity is formed.

Development
At the beginning of the second week, a cavity appears within the inner cell mass, and when it enlarges, it becomes the amniotic cavity. The floor of the amniotic cavity is formed by the epiblast. Epiblast migrates between the epiblastic disc and trophoblast. In this way the epiblastic cells migrate between the embryoblast and trophoblast. The floor is formed by the epiblast which later on transforms to ectoderm while the remaining cells which are present between the embryoblast and trophoblast are called amnioblasts (flattened cells). These cells are also derived from epiblast which is transformed into ectoderm.

The amniotic cavity is surrounded by an extraembryonic membrane, called the amnion. As the implantation of the blastocyst progresses, a small space appears in the embryoblast, which is the primordium of the amniotic cavity. Soon, amniogenic (amnion-forming cells) called amnioblasts separate from the epiblast and line the amnion, which encloses the amniotic cavity.

The epiblast forms the floor of the amniotic cavity and is continuous peripherally with the amnion. The hypoblast forms the roof of the exocoelomic cavity and is continuous with the thin exocoelomic membrane. This membrane along with hypoblast forms the primary yolk sac. The embryonic disc now lies between the amniotic cavity and the primary yolk sac. Cells from the yolk sac endoderm form a layer of connective tissue, the extraembryonic mesoderm, which surrounds the amnion and yolk sac.

Birth
If, after birth, the complete amniotic sac or big parts of the membrane remain coating the newborn, this is called a caul.

When seen in the light, the amniotic sac is shiny and very smooth, but tough.

Once the baby is pushed out of the mother's uterus, the umbilical cord, placenta, and amniotic sac are pushed out in the afterbirth.

Function
The amniotic sac and its filling provide a liquid that surrounds and cushions the fetus. It is a site of exchange of essential substances, such as oxygen, between the umbilical cord and the fetus. It allows the fetus to move freely within the walls of the uterus. Buoyancy is also provided.

Clinical significance
Chorioamnionitis is inflammation of the amniotic sac (chorio- + amnion + -itis), usually because of infection. It is a risk factor for neonatal sepsis.

During labor, the amniotic sac must break so that the child can be born. This is known as rupture of membranes (ROM). Normally, it occurs spontaneously at full term either during or at the beginning of labor. A premature rupture of membranes (PROM) is a rupture of the amnion that occurs prior to the onset of labor. An artificial rupture of membranes (AROM), also known as an amniotomy, may be clinically performed using an amnihook or amnicot in order to induce or to accelerate labour.

The amniotic sac has to be punctured to perform amniocentesis. This is fairly routine procedure, but can lead to infection of the amniotic sac in a very small number of cases. Infection more commonly arises vaginally.

title: Amniotic sac


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Amnion

The amnion (: amnions or amnia) is a membrane that closely covers human and various other embryos when they first form. It fills with amniotic fluid, which causes the amnion to expand and become the amniotic sac that provides a protective environment for the developing embryo. The amnion, along with the chorion, the yolk sac and the allantois protect the embryo. In birds, reptiles and monotremes, the protective sac is enclosed in a shell. In marsupials and placental mammals, it is enclosed in a uterus.

The amnion is a feature of the vertebrate clade Amniota, which includes reptiles, birds, and mammals. Amphibians and fish lack the amnion and thus are anamniotes (non-amniotes). The amnion stems from the extra-embryonic somatic mesoderm on the outer side and the extra-embryonic ectoderm or trophoblast on the inner side.

Etymology
Traditionally, the term amnion has been assumed to derive from Ancient Greek ἀμνίον : amníon, 'little lamb', diminutive of ἀμνός : amnós, 'lamb'. It is cognate with the English verb 'yean', bring forth young (usually lambs). However, this etymology is perhaps incorrect as the term may actually refer to an ancient Greek goddess of childbirth worshipped in Amnisos on the island of Crete

In humans
In the human embryo, the earliest stages of the formation of the amnion have not been observed; in the youngest embryo that has been studied the amnion was already present as a closed sac, and appears in the inner cell-mass as a cavity. This cavity is roofed in by a single stratum of flattened, ectodermal cells, the amniotic ectoderm, and its floor consists of the prismatic ectoderm of the embryonic disk. Outside the amniotic ectoderm is a thin layer of mesoderm, which is continuous with that of the somatopleure and is connected by the body-stalk with the mesodermal lining of the chorion.

When first formed, the amnion is in contact with the body of the embryo, but about the fourth or fifth week amniotic fluid (also called liquor amnii) begins to accumulate within it. This fluid increases in quantity and causes the amnion to expand and ultimately to adhere to the chorion's inner surface, so that the extra-embryonic part of the coelom is obliterated. The amniotic fluid increases in quantity up to the sixth or seventh month of pregnancy, after which it diminishes somewhat; at the end of pregnancy it amounts to about one liter.

The amniotic fluid allows the free movements of the fetus during the later stages of pregnancy, and also protects it by diminishing the risk of injury from without. It contains less than two percent solids, consisting of urea and other extractives, inorganic salts, a small amount of protein, and frequently a trace of sugar. That some of the liquor amnii is swallowed by the fetus is proved by the fact that epidermal debris and hairs have been found among the contents of the fetal alimentary canal.

Clinical significance
Extra-amniotic pregnancy is a rare condition that results from a rupture of the amnion, leading to development of the fetus within the extraembryonic coelom.

Other animals
In reptiles, birds, and many mammals the amnion develops in the following manner:

At the point of constriction where the primitive digestive tube of the embryo joins the yolk sac a reflection or folding upward of the somatopleure takes place.

This, the amniotic fold, first makes its appearance at the cephalic extremity, and subsequently at the caudal end and sides of the embryo, and gradually rising, its different parts meet and fuse over the dorsal aspect of the embryo, and enclose a cavity, the amniotic cavity. This kind of amnion is known as pleuroamnion (formed by folding), as opposed to schyzoamnion (formed by delamination).

After the fusion of the edges of the amniotic fold, the two layers of the fold become completely separated, the inner forming the amnion, the outer the false amnion or serosa.

The space between the amnion and the serosa constitutes the extra-embryonic celom, and for a time communicates with the embryonic celom.

Cats and dogs are born inside of the amnion; the mother cuts it open and eats it.

In elephants, "The amnion is continued from the base of the umbilical cord upon the allantois, which is of considerable size, and is so interposed between the chorion and amnios, as to prevent any part of the amnios attaining the inner surface of the placenta. The amnios consists of two layers:one is the granular layer, continued upon the inner or foetal surface of the allantois, and thence upon the umbilical cord; the other is the smooth outer layer, continued upon the outer or chorional surface of the allantois, and thence upon the inner surface of the chorion."

Application
The amniotic membrane is used as a biological dressing to heal incurable wounds. For this purpose, the placenta in cesarean delivery is collected and under aseptic conditions, the amniotic membrane is separated and packaged and sold commercially. In valid commercial products to prevent transmission of viral infections such as HIV and hepatitis, the donor's blood (mother) is tested. Products usually pass the sterility and endotoxin test in accordance with the rules of the Food and Drug Administration of the country of manufacture.

title: Amnion


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User:Koyaanis Qatsi

I'm around wikipedia only sporadically; if you need to contact me your best bet is to email me.

Wiki vitae: pix: wisteria, Hippeastrum, honeysuckle, push printing, angle of view x4, perspective distortion x4, pansy violet, pistachio, almond, Spanish moss, Wandering Jew, shrimp plant, depth of field x5, color temperature, canna lily, kiwifruit, and spiderwort. Also the emphatically mediocre photos at Uxmal and Palenque, taken with a point-and-click camera in Summer 1997 and not the slightest idea of how to take a photo beyond "point, and click," as well as the bad aerial pix of a Los Angeles, California interstate at freeway interchange--which were taken with a camera whose focus ring was slipping, at a non-perpendicular angle through a dual-paned dirty window of a descending plane, and then went through the rather strong X-rays at LAX not once but twice before being developed. All in all, not a good day for the Nikon. I've released all the pix above (good, bad, & mediocre) into the public domain because I think copyright is commonly abused to stifle creativity and/or free expression, both of which I value more than money. Google images likes some of those pictures too.

articles I've contributed to considerably: Blood Simple (which could use a bit more external information for me to be happy with it: on funding, lenses used, time to get it all in the can etc.) McCabe & Mrs. Miller (cannibalizing the DVD commentary), The Man Who Wasn't There, Sid Davis, Six O'Clock News, Time Indefinite, Henriette Roosenburg, Mark Jonathan Harris, Dziga Vertov, Ingmar Bergman, Joel and Ethan Coen, The Thin Blue Line.

All of my contributions are of course completely open for revision, refactoring, removal, replacement, etc., and if you can improve them then please do so. Chat with me here or use the "email this user" link at left (that works only if you're logged in also and have provided your own email address). :-)

funny links

 * http://www.spinnwebe.com/a1/?3 (caption your own photos. love the Medusa one)
 * http://www.redvsblue.com/archive/ (making short films from video games)

cool links

 * http://www.infinitewheel.com/infinite_wheel.html (dub generator. good mindless fun)
 * http://news.bbc.co.uk/1/hi/uk/3046791.stm (a sculpture which makes water appear to flow uphill perpetually, a la M. C. Escher)
 * http://www.kittyspit.net/erik/mp3/linkpage.html (mp3 pages galore)

fr:Utilisateur:Koyaanis Qatsi

title: User:Koyaanis Qatsi


text:
Talk:Great White

Add references section
Someone needs to add a Footnotes section and take the direct external page links and change them into reference links. If I get the time, I'll do it later--Bamadude 23:05, 14 September 2007 (UTC)

unsigned blather from anons
nice ironic lyrical coment.

I honestly don't think that lyric is needed, and it seems out of context and pointless, other than for irony. If nobody objects, I'll remove it.

~I removed the lyric, mainly because "once bitten" was a cover, Great White didn't write the lyrics thus they shouldn't be attributede to them, even if they do mention fire.

I have a picture of the band to add under the information box. I'm not sure how to insert it. Here's the link to it. If someone wants to add it theirself, or/and show me how? Thanks. http://i95.photobucket.com/albums/l144/DaysOfThunder/GreatWhite.jpg

Allright, I got it up now. :-)

Michael Lardie & Audie Desbrow
Is there a reason why Michael Lardie & Audie Desbrow don't have their own biographies? When you click on their names it just redirects back to the Great White page.

 * This is usually the case throughout Wikipedia when a member of a band has virtually nothing significant outside their involvement in the band; e.g., no popular solo albums, no personal problems, no newsworthy info, etc. I don't know if that's the case with these two, but that's why that sort of thing happens.  They may also have already had an article which was folded into and redirected back to the main article.--Bamadude 23:03, 14 September 2007 (UTC)

Fair use rationale for Image:Once Bitten Twice Shy sample from Twice Shy.ogg
Image:Once Bitten Twice Shy sample from Twice Shy.ogg is being used on this article. I notice the image page specifies that the image is being used under fair use but there is no explanation or rationale as to why its use in this Wikipedia article constitutes fair use. In addition to the boilerplate fair use template, you must also write out on the image description page a specific explanation or rationale for why using this image in each article is consistent with fair use.

Please go to the image description page and edit it to include a fair use rationale. Using one of the templates at Fair use rationale guideline is an easy way to insure that your image is in compliance with Wikipedia policy, but remember that you must complete the template. Do not simply insert a blank template on an image page.

If there is other fair use media, consider checking that you have specified the fair use rationale on the other images used on this page. Note that any fair use images lacking such an explanation can be deleted one week after being tagged, as described on criteria for speedy deletion. If you have any questions please ask them at the Media copyright questions page. Thank you.

BetacommandBot (talk) 14:27, 2 January 2008 (UTC)

Lineup
I think the lineup should be reformatted to match the one in AC/DC here (from Template:AC/DC timeline). — RevRagnarok  Talk Contrib 02:02, 4 April 2012 (UTC)
 * Sure, go ahead and do it. Might be a bit tricky with the two bands co-existing now, but maybe there is a way to do it. --Muhandes (talk) 09:55, 4 April 2012 (UTC)

List of Great White band members
 Support split - Members section takes up close to half of the page, and should be split to a new article entitled List of Great White band members. --Jax 0677 (talk) 20:38, 5 December 2015 (UTC)

Assessment comment
Substituted at 16:41, 29 April 2016 (UTC)

title: Talk:Great White


text:
Karl Knutsson

Karl Knutsson Bonde (c. 1408–1470), also known as Charles VIII and called Charles I in Norwegian contexts, was King of Sweden (1448–1457, 1464–1465 and 1467–1470) and King of Norway (1449–1450).

Early life
Karl Knutsson Bonde was born in October 1408 or 1409, at Ekholmen Castle, the son of Knut Tordsson (Bonde), knight and member of the privy council (riksråd), and Margareta Karlsdotter (Sparre av Tofta), the only daughter and heiress of Karl Ulfsson, Lord of Tofta. His father Knut was first cousin of Erik Johansson Vasa's father. His first marriage, in 1428, to Birgitta Turesdotter (Bielke) (died 1436) gave him his daughter Christina. His second marriage, in 1438, to Catherine (Gumsehuvud, died in 1450) produced his second daughter Magdalena, who married Ivar Axelsson (Tott). He also had two children by his third wife (and former mistress) Christina Abrahamsdotter, Anna and Karl. His father was said by contemporary legends to descend from a younger brother of King Eric IX (Saint Eric). His mother, an important heiress, descended from Jarl Karl the Deaf and consequently from some ancient Folkunge earls of Sweden, as well as from Ingegerd Knutsdotter, a daughter of Canute IV of Denmark and Adela of Flanders.

Growing influence
In 1434, Karl became a member of the Privy Council of Sweden and in October of the same year he assumed one of its most senior offices, Lord High Constable of Sweden, or Riksmarsk. Because of the growing dissatisfaction with King Eric of Pomerania among the Swedish nobility, Karl was in 1436 made Rikshövitsman, an office equating to Military Governor of the Realm, and finally replaced the king as an elected regent from 1438 to 1440, as the result of the rebellion by Engelbrekt Engelbrektsson. During Karl's brief regentship, the so-called Rebellion of David (a peasant rebellion) took place in Finland. Eric of Pomerania was forced to step down from the throne and in 1440 Christopher of Bavaria, was elected king of Sweden, Norway and Denmark. At the coronation of Christopher in September 1441, Karl was dubbed a knight and appointed Lord High Justiciar of Sweden, or Riksdrots. In October he resigned as Lord High Justiciar and resumed his office as Lord High Constable. From 1442, he was the military governor, hövitsman, at Viborg in Finland (Fief of Viborg).

Karl acquired extensive fiefs, for example in Western Finland. His first seat was in Turku. Soon, Christopher's government began to take back fiefs and positions and he was forced to give up the castle of Turku. Karl's next seat was the castle of Viborg, on Finland's eastern border, where he kept an independent court, taking no heed of Christopher and exercising his own foreign policy in relation to such powers in the region as the Hanseatic League, the Russian city of Novgorod and the Teutonic Knights in what are today Estonia and Latvia.

King of Sweden and Norway
At the death of Christopher in 1448, without a direct heir, Karl was elected king of Sweden on 20 June, and on 28 June, he was hailed as the new monarch at the Stones of Mora, not far from Uppsala, mostly due to his own military troops being present at the place, against the wishes of regents Bengt and Nils Jönsson (Oxenstierna). The Danish had in September 1448 elected Christian I as their new monarch. A rivalry ensued between Karl and Christian for the throne of Norway, which had also been ruled by Christopher, with both kings gaining support from various factions in the Norwegian Council of the realm. In 1449, a portion of the Norwegian council elected Karl as king of Norway, and he was crowned in Nidaros Cathedral in Trondheim on 20 November. However, Christian also continued pursuing his claim to Norway. The Swedish aristocracy was reluctant to back Karl in a war against Denmark over Norway, and already in June 1450, he was forced to relinquish the throne of Norway in favour of Christian.

From 1451, Sweden and Denmark were in state of war against each other. Because of devastating warring, a growing opposition against Karl emerged among the nobility in Sweden. The strongest opponent was the Swedish church which opposed his efforts to concentrate royal and secular power. Other opponents were the family group of Oxenstierna and the House of Vasa, which had been on the opposing side in the election of king and lost.

Later reigns
During the next 20 years, Karl was deposed twice, only to regain the throne and reign three times (1448–1457, 1464–65, 1467–1470).

In 1457, a rebellion took place, led by Archbishop Jöns Bengtsson (Oxenstierna) and a nobleman, Erik Axelsson Tott. Karl went into exile to Danzig (Gdańsk). The two leaders of the revolt took the regentship, and organized the election of Christian I of Denmark as king (firstly in Turku, then in Stockholm).

In 1463, King Christian quarrelled with the Archbishop because of his taxation policies. The Archbishop was imprisoned, which resulted in a rebellion by his relatives, and led to Christian being driven out of Sweden. Karl was recalled by the rebels and returned at the head of a force of German and Polish mercenaries. Upon arrival in Sweden, he found himself at war with the Archbishop, and after two bloody battles in the winter of 1464–1465, he was again exiled. In 1467, the regent Erik Axelsson Tott, now having reverted to support Karl Knutsson, once more had him crowned. He then reigned for three years, sharing power with the Riksråd, until his death in Stockholm in May 1470.

Family
With his wife Birgitta Turesdotter (Bielke), Karl had:
 * Ture Karlsson (Bonde) (died young before 1447)
 * Christina Karlsdotter (Bonde) (c. 1432 – before 1500), married 1446 to the noble, councillor, and courtier Erik Eriksson (Gyllenstierna)

With his wife Catherine, he had:
 * Margaret Karlsdotter (Bonde) (1442–1462)
 * Magdalena of Sweden (1445–1495), married to noble Ivar Axelsson (Tott) in 1466
 * Richeza Karlsdotter (Bonde) (born c. 1445), nun at Vadstena Abbey
 * Bridget Karlsdotter (Bonde) (1446–1469), nun at Vadstena Abbey
 * four sons died early

With his mistress Christina Abrahamsdotter, he had:
 * Anna Karlsdotter (Bonde), married to the noble Håkan Svensson (Bölja), governor of Västerås castle.
 * Karl Karlsson (Bonde) (1465–1488)

Karl was survived by only one son, born of Christina Abrahamsdotter, whom he married on his deathbed. Though she was recognized as queen, the Swedish government did not allow the suddenly legitimized boy to succeed him, but appointed one of their number, Sten Sture the Elder (who was Karl's nephew), as regent.

Regnal name
Karl Knutsson was the second Swedish king by the name of Karl (sometimes anglicized as Charles). Charles VIII is a posthumous invention, counting backwards from Charles IX (r. 1604–1611) who adopted his numeral according to a fictitious history of Sweden. Six others before Charles VII are unknown to any sources before Johannes Magnus's 16th century book Historia de omnibus gothorum sueonumque regibus, and are considered his invention. Karl Knutsson was the first Swedish monarch of the name to actually use a regnal number as Karl II (later retrospectively renumbered VIII), on his wife's tombstone (1451) at Vadstena.

Legacy
Karl represented a growing nationalist tendency among the Swedish aristocracy which tried first to subjugate the other Scandinavian countries under Sweden but soon focused on dissolving the Kalmar Union. In the next century, when the union was finally dissolved, he received some respect as an early champion of Swedish independence.

Karl's fight for power and kingship was more successful than his experience thereof. He allegedly recognized this himself and described his life in a brief poem:

When I was Lord of Fågelvik, (pronounced: foegle-veek)

Then I had wealth and might unique.

But once I was King of the Swedish land,

I was a poor and unhappy man.

Karl's great-granddaughter Christina Nilsdotter Gyllenstierna was married to Sten Sture the Younger whose regentship represented similar values: nationalism and Swedish independence.

Though the Bonde family, not descendants of Karl Knutsson himself but just his collateral relatives, remained prominent among the Swedish nobility and in politics into the 20th Century, Karl's own descendants did not ascend nor inherit any thrones until Prince Christian zu Schleswig-Holstein-Sonderburg-Glucksburg became Christian IX of Denmark in 1863. Karl's descendants have since ascended the thrones of Norway, Greece and Great Britain, Brunswick, Luxembourg, Belgium, Spain, Romania and Russia Empire together with Grand Duchy of Finland. Nicholas II was the first direct descendant on the Finnish throne.

His distant direct descendant, Sibylla of Saxe-Coburg-Gotha, married the Hereditary Prince of Sweden in the 20th century, and with the accession of Sibylla's son, Carl XVI Gustav, Karl Knutsson's blood returned to the Swedish throne.

title: Karl Knutsson