Prenatal diagnosis is the process of detecting and diagnosing fetal abnormalities before birth. The techniques currently in use or under investigation for prenatal diagnosis include (1) fetal tissue sampling through amniocentesis, chorionic villi sampling (CVS), percutaneous umbilical blood sampling, percutaneous skin biopsy, and other organ biopsies, including muscle and liver biopsy; (2) fetal visualization through ultrasound, fetal echocardiography, embryoscopy, fetoscopy, magnetic resonance imaging, and radiography; (3) screening for neural tube defects by measuring maternal serum
alpha-fetoprotein (MSAFP); (4) screening for fetal Down syndrome by measuring MSAFP, unconjugated estriol, and human chorionic gonadotropin; (5) separation of fetal cells from the mother's blood; and (6) preimplantation biopsy of blastocysts obtained by in vitro fertilization. The more common techniques are amniocentesis, performed at the 14th to 20th week of gestation, and CVS, performed between the 9th and 13th week of gestation. If the fetus is found to be affected with a disorder, the couple can plan for the birth of an affected child or opt for elective abortion.
Prenatal diagnosis comprises all diagnostic measures by which diseases or undesirable developments of the unborn child can be identified and possibly excluded. In its broadest meaning, it sets in with the first routine examination a pregnant woman undergoes with her gynecologist and that every woman is entitled to. Its exclusive purpose is to give individual counselling and care to the expectant mother and the child during pregnancy and in preparation of birth. The aim of any prenatal diagnosis is to detect developmental disorders by means of suitable examination methods, to ensure optimum care for the pregnant woman and the unborn child by establishing an early diagnosis, to put fears and concerns of the expectant mother into perspective or to ease them.
With any pregnancy there is a basic risk that the child may develop diseases or undesirable developments. The degree of frequency for such disturbances, which are partially or completely influenced by genetic factors, is usually assessed at 3 - 5 %. Merely a part of these disorders is recognized in the routine check-ups. Not even the best care feasible could completely abolish this risk.
The general routine examination for expectant mothers during which ultrasound scans and clinical data and measurements are used is referred to as untargeted prenatal diagnosis. In contrast to this, a targeted prenatal diagnosis focuses on a suspected disease or developmental disorder. The ultrasound scan makes the uterus, the amniotic sac and the child's development visible on a screen and allows an assessment on the basis of comparable medical data. In a regular, inconspicuous pregnancy, examinations of the mother's blood and urine as well as blood pressure monitoring complete the routine check-up.
A targeted prenatal diagnosis is done when there is a concrete suspicion that there might be a particular disorder. It may be applied only if the necessary methods for clearing up this suspicion are available and if the result promises a sufficient degree of security. A medical reason why a specific prenatal diagnosis might be offered is usually given when an explicitly higher risk for developing a detectable disorder is known. In such a situation a pregnant woman has the right to claim complete information and to receive competent counselling, before she might eventually opt for finding clarification and agrees to a prenatal diagnosis.
This is a non-invasive procedure that is harmless to both the fetus and the mother. High frequency sound waves are utilized to produce visible images from the pattern of the echos made by different tissues and organs, including the baby in the amniotic cavity. The developing embryo can first be visualized at about 6 weeks gestation. Recognition of the major internal organs and extremities to determine if any are abnormal can best be accomplished between 16 to 20 weeks gestation. Although an ultrasound examination can be quite useful to determine the size and position of the fetus, the size and position of the placenta, the amount of amniotic fluid, and the appearance of fetal anatomy, there are limitations to this procedure. Subtle abnormalities may not be detected until later in pregnancy, or may not be detected at all. A good example of this is Down syndrome (trisomy 21) where the morphologic abnormalities are often not marked, but only subtle, such as nuchal thickening.
Amniocentesis is a relatively safe and accurate test used to diagnose certain birth defects in the second or third trimester of pregnancy. Amniocentesis is generally performed between 14 and 17 weeks of pregnancy. Amniocentesis involves inserting a needle, under ultrasound guidance, through the mother's abdomen and into the uterus. A small amount of amniotic fluid is then withdrawn. Fetal cells from the skin, bladder, and gastrointestinal tract are in the fluid and can be grown for chromosome analysis. Results of the testing are usually available within two weeks. For prenatal diagnosis, most amniocenteses are performed between 14 and 20 weeks gestation. However, an ultrasound examination always proceeds amniocentesis in order to determine gestational age, the position of the fetus and placenta, and determine if enough amniotic fluid is present. Within the amniotic fluid are fetal cells (mostly derived from fetal skin) which can be grown in culture for chromosome analysis, biochemical analysis, and molecular biologic analysis.
In the third trimester of pregnancy, the amniotic fluid can be analyzed for determination of fetal lung maturity. This is important when the fetus is below 35 to 36 weeks gestation, because the lungs may not be mature enough to sustain life. This is because the lungs are not producing enough surfactant. After birth, the infant will develop respiratory distress syndrome from hyaline membrane disease. The amniotic fluid can be analyzed by fluorescence polarization (fpol), for lecithin:sphingomyelin (LS) ration, and/or for phosphatidyl glycerol (PG).
Risks with amniocentesis are uncommon, but include fetal loss and maternal Rh sensitization. The increased risk for fetal mortality following amniocentesis is about 0.5% above what would normally be expected. Rh negative mothers can be treated with RhoGam. Contamination of fluid from amniocentesis by maternal cells is highly unlikely. If oligohydramnios is present, then amniotic fluid cannot be obtained. It is sometimes possible to instill saline into the amniotic cavity and then remove fluid for analysis.
Chorionic Villus Sampling (CVS)
Chorionic villus sampling (CVS) is a relatively new procedure used to diagnose certain birth defects in the first trimester of pregnancy. The test has been performed regularly since 1982, and many thousand have been performed around the world. The CVS procedure involves inserting a small catheter (tube) through the cervix and into the developing placenta. Prior to the procedure, an ultrasound examination is performed to confirm fetal viability, location of the placenta, and length of gestation. Then, the women will lie on her back and place her feet in stirrups while the vagina and cervix are prepared. The catheter is then put through the cervix and a bit of placental tissue is gently suctioned into a syringe. The procedure is performed under ultrasound guidance and most women experience very little discomfort during the testing. Once the procedure is completed, the patient may resume normal activity. Both the placental and fetal tissues originate from the same cell line and are genetically identical. Thus, by obtaining a tiny sample of the chorionic villi from the placenta, one can determine certain genetic characteristics of the fetus.
CVS is performed between ten and twelve weeks from the first day of the last menstrual period. CVS can detect chromosome abnormalities such as Down syndrome and may detect certain genetic conditions when there is a family history of the disease. Couples who may wish to consider CVS include: Women 35 years of age and older; Parents who have had a child with Down syndrome or other chromosome abnormality; Couples who are known carriers of a chromosome rearrangement; Couples who have a family history of a genetic condition for which testing is available.
CVS has the disadvantage of being an invasive procedure, and it has a small but significant rate of morbidity for the fetus; this loss rate is about 0.5 to 1% higher than for women undergoing amniocentesis. Rarely, CVS can be associated with limb defects in the fetus. The possibility of maternal Rh sensitization is present. There is also the possibility that maternal blood cells in the developing placenta will be sampled instead of fetal cells and confound chromosome analysis. If a couple decides to pursue CVS, an ultrasound examination should be performed at 18 to 20 weeks of pregnancy to evaluate fetal growth and anatomy. Also, the option of maternal serum alpha fetoprotein (MSAFP) screening between the 15th and 18th week of pregnancy should be offered. MSAFP is a blood test which screens for neural tube defects such as open spina bifida and anencephaly. Amniotic fluid AFP levels are evaluated when an amniocentesis is performed, and MSAFP screening is not necessary following an amniocentesis.
Maternal blood sampling for fetal blood cells
This is a new technique that makes use of the phenomenon of fetal blood cells gaining access to maternal circulation through the placental villi. Ordinarily, only a very small number of fetal cells enter the maternal circulation in this fashion (not enough to produce a positive Kleihauer-Betke test for fetal-maternal hemorrhage). The fetal cells can be sorted out and analyzed by a variety of techniques to look for particular DNA sequences, but without the risks that these latter two invasive procedures inherently have. Fluorescence in-situ hybridization (FISH) is one technique that can be applied to identify particular chromosomes of the fetal cells recovered from maternal blood and diagnose aneuploid conditions such as the trisomies and monosomy X. The problem with this technique is that it is difficult to get many fetal blood cells. There may not be enough to reliably determine anomalies of the fetal karyotype or assay for other abnormalities.
Maternal serum alpha-fetoprotein (MSAFP)
The developing fetus has two major blood proteins--albumin and alpha-fetoprotein (AFP). Since adults typically have only albumin in their blood, the MSAFP test can be utilized to determine the levels of AFP from the fetus. Ordinarily, only a small amount of AFP gains access to the amniotic fluid and crosses the placenta to mother's blood. However, when there is a neural tube defect in the fetus, from failure of part of the embryologic neural tube to close, then there is a means for escape of more AFP into the amniotic fluid. Neural tube defects include anencephaly (failure of closure at the cranial end of the neural tube) and spina bifida (failure of closure at the caudal end of the neural tube). The incidence of such defects is abbout 1 to 2 births per 1000 in the United States. Also, if there is an omphalocele or gastroschisis (both are defects in the fetal abdominal wall), the AFP from the fetus will end up in maternal blood in higher amounts.
In order for the MSAFP test to have the greates utility, the gestational age must be known with certainty. This is because the amount of MSAFP increasses with gestational age (as the fetus and the amount of AFP produced increase in size). Also, the race of the mother and presence of gestational diabetes are important to know, because the MSAFP can be affected by these factors. The MSAFP is typically reported as multiples of the mean (MoM). The greater the MoM, the more likely a defect is present. The MSAFP has the greatest sensitivity between 16 and 18 weeks gestation, but can still be useful between 15 and 22 weeks gestation.
However, the MSAFP can be elevated for a variety of reasons which are not related to fetal neural tube or abdominal wall defects, so this test is not 100% specific. The most common cause for an elevated MSAFP is a wrong estimation of the gestational age of the fetus.Using a combination of MSAFP screening and ultrasonography, almost all cases of anencephaly can be found and most cases of spina bifida. Neural tube defects can be distinguished from other fetal defects (such as abdominal wall defects) by use of the acetylcholinesterase test performed on amniotic fluid obtained by amniocentesis--if the acetylcholinesterase is elevated along with MSAFP then a neural tube defect is likely. If the acetylcholinesterase is not detectable, then some other fetal defect is suggested.
Maternal serum beta-HCG
This test is most commonly used as a test for pregnancy. Beginning at about a week following conception and implantation of the developing embryo into the uterus, the trophoblast will produce enough detectable beta-HCG (the beta subunit of human chorionic gonadotropin) to diagnose pregnancy. Thus, by the time the first menstrual period is missed, the beta-HCG will virtually always be elevated enough to provide a positive pregnancy test. The beta-HCG can also be quantified in serum from maternal blood, and this can be useful early in pregnancy when threatened abortion or ectopic pregnancy is suspected, because the amount of beta-HCG will be lower than expected.
Later in pregnancy, in the middle to late second trimester, the beta-HCG can be used in conjunction with the MSAFP to screen for chromosomal abnormalities, and Down syndrome in particular. An elevated beta-HCG coupled with a decreased MSAFP suggests Down syndrome.
Very high levels of HCG suggest trophoblastic disease (molar pregnancy). The absence of a fetus on ultrasonography along with an elevated HCG suggests a hydatidiform mole. The HCG level can be used to follow up treatment for molar pregnancy to make sure that no trophoblastic disease, such as a choriocarcinoma, persists.
Maternal serum estriol
The amount of estriol in maternal serum is dependent upon a viable fetus, a properly functioning placenta, and maternal well-being. The substrate for estriol begins as dehydroepiandrosterone (DHEA) made by the fetal adrenal glands. This is further metabolized in the placenta to estriol. The estriol crosses to the maternal circulation and is excreted by the maternal kidney in urine or by the maternal liver in the bile. The measurement of serial estriol levels in the third trimester will give an indication of general well-being of the fetus. If the estriol level drops, then the fetus is threatened and delivery may be necessary emergently. Estriol tends to be lower when Down syndrome is present and when there is adrenal hypoplasia with anencephaly.
More information on pregnancy
Pregnancy - Pregnancy is period of time between fertilization of the ovum (conception) and birth, during which mammals carry their developing young in the uterus (see embryo).
Pregnancy signs and symptoms - During pregnancy a woman's body undergoes a number of changes to allow the fetus to develop inside the womb. The symptoms of pregnancy vary from woman to woman.
Pregnancy tests - A pregnancy test is a test of blood or urine used to determine whether a woman is pregnant. There are two types of pregnancy tests - blood and urine tests.
Home pregnancy test - A home pregnancy test measures the presence of the hormone human chorionic gonadotropin (hCG) in your urine. All home pregnancy test kits test your pregnancy on the basis of your urine sample.
Pregnancy stages - There are three stages of pregnancy called trimesters. Each trimester is three months. The word "trimester" comes from a Latin word meaning "three months long."
First trimester of pregnancy - First trimester pregnancy is the early stage of pregnancy from conception to 12 weeks gestation, or about 14 weeks from the first day of the last normal menstrual period (LNMP).
Second trimester of pregnancy - In the second trimester the embryo, now known as a fetus, is recognisable as human in form, but is not developed enough to be viable if born. The second trimester is often called the planning trimester.
Third trimester of pregnancy - The third trimester of pregnancy lasts from 28 weeks after your last menstrual period (LMP) until the birth, which usually occurs between the 38th and 42nd weeks of pregnancy.
Calculating pregnancy due date - The due date is usually computed from the first day of the last regular period. In the calendar, this can be figured by taking that date, subtracting three months, and adding seven days.
Prenatal diagnosis - Prenatal diagnosis is the process of detecting and diagnosing fetal abnormalities before birth. A targeted prenatal diagnosis is done when there is a concrete suspicion that there might be a particular disorder.
Healthy pregnancy diet - A balanced diet is key to having a healthy pregnancy. Pregnancy places substantial demands on the availability of iron in the body.
Nutrition during pregnancy - Nutrition is an essential component of prenatal care. During pregnancy, your body needs more nutrients in order to provide a baby with what it needs. Eat enough food to gain weight at the rate recommended by your health care provider.
Exercise during pregnancy - Exercise plays an important role in promoting health and well-being for pregnant women. Excessive levels of physical activity in pregnancy can reduce fetal growth and increase the risk of preterm delivery.
Spotting during pregnancy - Spotting is light bleeding similar to your period and it can happen at any time during pregnancy, but it is most common during the first trimester.
Bleeding during pregnancy - Bleeding from the vagina in early pregnancy is very common. First trimester bleeding is any vaginal bleeding during the first 3 months of pregnancy.
Smoking during pregnancy - Cigarette smoking during pregnancy can cause serious health problems to an unborn child. Many complications of pregnancy are more likely to occur in smokers.
Sex during pregnancy - Sex and sexual intercourse are not harmful during pregnancy. For most women and their partners, sex during pregnancy is fine as long as both partners consent and are comfortable.
Prenatal care - Prenatal care is the health care that a woman receives before her baby is born. Prenatal care is provided for women during the period between conception and birth of the baby.
Teenage pregnancy - Teenage pregnancy is a pregnancy that occurs in an adolescent. Babies born to teenagers are at risk for neglect and abuse.
Twins and multiple birth - Multiple pregnancies are on the rise in recent years with more and more twins and other types of multiples being born. A multiple birth is when more than one human baby results from a single pregnancy.
Childbirth - Childbirth (also called labour, birth, or parturition) is the culmination of pregnancy, the emergence of a child from its mother's uterus.
Obstetrics - Obstetrics is the surgical specialty dealing with the care of a woman and her offspring during pregnancy, childbirth and the puerperium (the period shortly after birth).
Pregnancy ultrasound - Pregnancy ultrasound is a method of imaging the fetus and the female pelvic organs during pregnancy.
Chinese lunar pregnancy calendar - The Chinese pregnancy calendar was allegedly discovered about 700 years ago. The accuracy of the chart has been proved by thousands of people and is believed to be 99 percent accurate.
Fertility charting - Fertility charting allows you to predict ovulation, pinpoint your most fertile time in your cycle, and increase your chances of becoming pregnant.
Ovulation: calendar, prediction, test - Ovulation is the process of discharging a mature ovum (egg) from an ovary after a Graafian follicle - representing the final stage of follicular development before ovulation - has been formed.
Getting pregnant - The best or most fertile time to get pregnant is the period of ovulation in your menstrual cycle. Most women ovulate (release an egg from the ovary) about two weeks before their period.
Gender selection - There are three main techniques of sex selection: pre-natal testing and termination of pregnancy, pre-implantation genetic testing of embryos, and sperm sorting.
Prenatal tests - Prenatal tests are one of the many ways your practitioner can check on the well-being of your growing baby and find out whether you're at risk for complications.
Genetic screening - Genetic screening is a process used to find out what diseases or birth defects a child might inherit from his or her parents.
Genetic counseling - Genetic counseling is the process of determining the risk you have of passing on an inheritable disease to your baby.
Birth control (contraception, pregnancy prevention) - Birth control is the practice of preventing or reducing the probability of pregnancy without abstaining from sexual intercourse; the term is also sometimes used to include abortion.
Male condoms - Condoms are thin barriers made of latex, plastic, or natural membranes. The male condom fits over a man's penis. The female condom fits inside a woman's vagina.
Female condoms - The female condom is a polyurethane sheath or pouch about 17 cm (6.5 inches) in length. It is worn by a woman during sex.
Diaphragm - A diaphragm is a rubber disc a woman places into her vagina. The diaphragm blocks a man's semen from entering the cervix (the opening to the womb).
Cervical cap - The cervical cap is a small latex cup that a woman inserts into her vagina before sexual intercourse. The cervical cap fits snugly over the woman's cervix.
Birth control pills - The birth control pill is a small, usually white, tablet that is taken orally (by mouth). The pill usually comes in a packet that has days marked off for a cycle lasting about a month.
Norplant - Contraceptive implants (Norplant?) are six match stick size implants inserted into the upper arm. Norplant is a form of progestin that is placed under the skin.
Depo Provera - Depo Provera is a hormone, much like the progesterone a woman produces during the last two weeks of each monthly cycle. Depo-Provera or progesterone stops the woman's ovaries from releasing an egg.
Spermicides - Spermicides are chemicals that make the sperm unable to function. Spermicide can be used alone or with other birth control methods to reduce the risk of pregnancy.
Emergency contraceptive pill - Emergency contraception is the use of certain methods after unprotected intercourse to prevent pregnancy.
Natural family planning - Natural family planning is defined as the understanding and use of the natural phases of fertility and infertility by a couple in order to either achieve or avoid pregnancy.
Intrauterine device (IUD) - An intrauterine device (intra meaning within, and uterine meaning of the uterus), is a birth control device also known as an IUD or a coil.
Birth control patch - The birth control patch is a thin plastic patch (1 3/4 inch square) placed directly on the skin of the woman. It is a hormonal method of contraception obtained by prescription.
Sterilization (vasectomy) - Sterilization is a surgical technique leaving a male or female unable to procreate. It is a method of birth control.
Fertility awareness method (FAM) - Fertility awareness is a means of understanding a woman's reproductive cycle by observing and writing down fertility signs.
Abstinence - Periodic abstinence is a way that sexually active women prevent pregnancy by becoming familiar with their fertility patterns and abstaining from vaginal intercourse on the days they think they could become pregnant.
Pre-eclampsia, eclampsia - Pre-eclampsia is a condition which only occurs during pregnancy. It causes high blood pressure, protein leaks from the kidneys, and other symptoms may develop.
HELLP Syndrome - The HELLP syndrome is a complication of pregnancy featuring a combination of abnormal conditions including emolysis, elevated liver enzymes, and low platelet count.
Intrauterine growth restriction - Intrauterine growth restriction (IUGR) refers to the condition in which a foetus is unable to grow to its genetically determined potential size to a degree that may affect the health of the foetus.
Premature birth - Premature birth is defined medically as a birth occurring earlier than 37 weeks. Infants born prematurely have an increased risk of death in the first year of life.
Stillbirth - Stillbirth refers to the death of a baby after 24 weeks of pregnancy but before birth. A pregnancy that ends before the twentieth week is called a miscarriage rather than a stillbirth.
Caesarean section - A Caesarean section (Cesarean section AE), is a surgical procedure to deliver one or more babies through an incision in the mother's abdomen and uterus.
Preterm labor - Preterm labor, or premature labor, is when the uterus (womb) contracts and the cervix opens earlier than normal.
Rh incompatibility - Rh incompatibility is a condition that occurs when the mother of a fetus or newborn has Rh-negative blood type and the fetus or newborn has Rh-positive blood.
Ectopic pregnancy - An ectopic pregnancy is one in which the fertilized ovum is implanted in any tissue other than the uterine wall.
Pregnancy diabetes (gestational diabetes) - Gestational diabetes is a condition in which the glucose level is elevated and other diabetic symptoms appear during pregnancy in a woman who has not previously been diagnosed with diabetes.
Group B strep - Group B streptococcus (group B strep) is a type of bacteria that causes infection among newborns, pregnant women or women after childbirth.
Morning sickness (NVP) - Morning sickness, also called nausea and vomiting of pregnancy (NVP), affects between 50 and 85 percent of all pregnant women.
Hyperemesis gravidarum - Hyperemesis gravidarum means excessive vomiting during pregnancy. The severe vomiting associated with hyperemesis gravidarum requires medical attention.
Miscarriage (spontaneous abortion) - Miscarriage is the term used for a pregnancy that ends on it's own, within the first 20 weeks of gestation.
Postpartum hemorrhage - Postpartum bleeding (severe postpartum bleeding) is the loss of more than a pint of blood within the first 24 hours after delivering a baby.
Pregnancy-induced hypertension - Pregnancy-induced hypertension (also referred to as toxemia, preeclampsia and eclampsia) is a condition that may develop during the second half of a woman's pregnancy.
Pica - Pica is a pattern of eating non-nutritive substances (such as dirt or paper), lasting for at least one month.