Twin Pregnancy Ticker
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Prenatal testing is testing for diseases or conditions in a fetus or embryo before it is born. The aim is to detect birth defects such as neural tube defects, Down syndrome, chromosome abnormalities, genetic diseases and other conditions, such as spina bifida, cleft palate, Tay Sachs disease, sickle cell anemia, thalassemia, cystic fibrosis, and fragile x syndrome. Screening can also determine the sex of the fetus. Common testing procedures include amniocentesis, sonograms, nuchal translucency ultrasound, serum marker testing, or genetic screening. In some cases, the tests are administered to determine if the fetus will be aborted, though physicians and patients also find it useful to diagnose high-risk pregnancies early so that delivery can be scheduled in a tertiary care hospital where the baby can receive appropriate care.
Diagnostic prenatal testing can be by invasive or non-invasive methods. An invasive method involves probes or needles being inserted into the placenta, e.g. amniocentesis, which can be done from about 14 weeks gestation, and usually up to about 20 weeks, and chorionic villus sampling, which can be done earlier (between 9.5 and 12.5 weeks gestation) but which is slightly more risky to the fetus. Non-invasive methods, called "screens", can only evaluate risk of a condition and cannot determine 100% if the fetus has a condition. Non-invasive techniques include examinations of the woman's womb through ultrasonography and maternal serum screens (i.e. Alpha-fetoprotein). Non-invasive genetic tests for Down Syndrome, Trisomy 18, and Trisomy 13 fetal DNA present in maternal blood are in development. If an elevated risk of chromosomal or genetic abnormality is indicated by a non-invasive screening test, a more invasive technique may be employed to gather more information. In the case of neural tube defects, a detailed ultrasound can non-invasively provide a definitive diagnosis.
Fetal screening has also been done to determine characteristics generally not considered birth defects. In some parts of the world, if a fetus is determined to be female, it is sometimes aborted. The rise of designer babies and parental selection for specific traits raises a host of bioethical and legal issues that will dominate reproductive rights debates in the 21st century.
Fetal versus maternal
Some screening tests performed on the woman are intended to detect traits or characteristics of the fetus. Others detect conditions in the woman that may have an adverse effect on the fetus, or that threaten the pregnancy. For example, abnormally low levels of the serum marker PAPP-A have been shown to correspond to an increased risk of pre-eclampsia, in which the mother's high blood pressure can threaten the pregnancy, though many physicians find regular blood-pressure monitoring to be more reliable.
Reasons for prenatal diagnosis
There are three purposes of prenatal diagnosis: (1) to enable timely medical or surgical treatment of a condition before or after birth, (2) to give the parents the chance to abort a fetus with the diagnosed condition, and (3) to give parents the chance to "prepare" psychologically, socially, financially, and medically for a baby with a health problem or disability, or for the likelihood of a stillbirth.
Having this information in advance of the birth means that healthcare staff can better prepare themselves and parents for the delivery of a child with a health problem. For example, Down Syndrome is associated with cardiac defects that may need intervention immediately upon birth
Many expectant parents would like to know the sex of their baby before birth. Methods include amniocentesis with karyotyping, and prenatal ultrasound. In some countries, health care providers are expected to withhold this information from parents, while in other countries they are expected to give this information.
Methods of prenatal screening and diagnosis
Types
There are multiple ways of classifying the methods available, including the invasiveness and the time performed.
Integrated, Sequential, and Contingent screening tests use serum samples from both first and second trimester, as well as the nuchal translucency measurement to calculate risks. With Integrated screening, a report is only produced after both samples have been analyzed. With Sequential screening, a first report is produced after the first trimester sample has been submitted, and a final report after the second sample. With Contingent screening, patients at very high or very low risks will get reports after the first trimester sample has been submitted. Only patients with moderate risk will be asked to submit a second trimester sample, after which they will receive a report combining information from both serum samples and the NT measurement.
Risk factors qualifying a pregnant woman for prenatal testing
Because of the miscarriage and fetal damage risks associated with amniocentesis and CVS procedures, many women prefer to first undergo screening so they can find out if the fetus' risk of birth defects is high enough to justify the risks of invasive testing. Since screening tests yield a risk score which represents the chance that the baby has the birth defect, the most common threshold for high-risk is 1:270. A risk score of 1:300 would therefore be considered low-risk by many physicians. However, the trade-off between risk of birth defect and risk of complications from invasive testing is relative and subjective; some parents may decide that even a 1:1000 risk of birth defects warrants an invasive test while others wouldn't opt for an invasive test even if they had a 1:10 risk score.
ACOG guidelines currently recommend that all pregnant women, regardless of age, be offered invasive testing to obtain a definitive diagnosis of certain birth defects. Therefore, most physicians offer diagnostic testing to all their patients, with or without prior screening and let the patient decide.
The following are some reasons why a patient might consider her risk of birth defects already to be high enough to warrant skipping screening and going straight for invasive testing.
- Women over the age of 35
- Women who have previously had premature babies or babies with a birth defect, especially heart or genetic problems
- Women who have high blood pressure, lupus, diabetes, asthma, or epilepsy
- Women who have family histories or ethnic backgrounds prone to genetic disorders, or whose partners have these
- Women who are pregnant with multiples (twins or more)
- Women who have previously had miscarriages
Typical screening sequence
California provides a useful guide to most of the currently available screening paradigms.
At early presentation of pregnancy at around 6 weeks, and early dating ultrasound scan may be offered to help confirm the gestational age of the embryo, and check whether a single or twin pregnancy, but such a scan is unable detect common abnormalities. Details of prenatal screening and testing options may be provided.
Around weeks 10-11, nuchal thickness scan (NT) may be offered which can be combined with blood tests for PAPP-A and beta-hCG, two serum markers that correlate with chromosomal abnormalities, in what is called the First Trimester Combined Test. The results of the blood test are them combined with the NT ultrasound measurements, maternal age, and gestational age of the fetus to yield a risk score for Down Syndrome, Trisomy 18, and Trisomy 13. First Trimester Combined Test has a sensitivity (i.e. detection rate for abnormalities) of 82-87% and a false-positive rate around 5%.
Altenatively a second trimester Quad blood test may be taken (the triple test is widely considered obsolete but in some states, such as Missouri, where Medicaid only covers the Triple test, that's what the patient typically gets). Performing this in addition to the First Trimester Combined Test is called the Fully Integrated test, which has a sensitivity of 95% with a 5% false-positive rate, though can also be analyzed in such a way as to offer a 90% sensitivity with a 2% false-positive rate. However patients may not wish to wait between these two sets of test.
If First Trimester Combined test suggests an unacceptably high risk of chromosomal abnormalities may be confirmed with invasive procedures of chorionic villus sampling (CVS) available from 9 weeks, or the second trimester amniocentesis, which is considered to have a lower risk of miscarriage than CVS. Whereas those who receive a low-risk score may consider further unnecessary. Care programs that offer 2nd trimester Quad tests to those with medium risks (lower than 1:50) are termed a Sequential test, and if only to those with an intermediate risk score (between 1:50 and 1:2000) from the 1st Trimester Combined test (with lower risk patients skipping the Quad test and higher risk patients going for invasive testing) are termed a Contingent Screen with an 88-94% sensitivity and 5% false-positive rate for Down Syndrome.
Finally for patients who do not receive an NT ultrasound in the 1st trimester may still receive a Serum Integrated test involving measuring PAPP-A serum levels in the 1st trimester and then doing a Quad test in the 2nd trimester. This offers an 85-88% sensitivity and 5% false-positive rate for Down Syndrome. Also, patient may skip 1st trimester screening entirely and receive only a 2nd trimester Quad test, with an 81% sensitivity for Down Syndrome and 5% false-positive rate.
Use of NT ultrasound will screen for Down Syndrome (Trisomy 21), Edwards S
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