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Maternal Blood Test Might be A New, Safe Technique to Detect Birth Defects / Congenital Disorder

Birth defects are defined as abnormalities of structure, function, or body metabolism that are present at birth. These abnormalities lead to mental or physical disabilities or are fatal. There are more than 4,000 different known birth defects ranging from minor to serious, and although many of them can be treated or cured, they are the leading cause of death in the first year of life.

Birth defect is a widely-used term for a structural malformation of a body part, recognizable at birth, which is significant enough to be considered a problem.Congenital conditions can be referred to as diseases, defects, disorders, anomalies, or simply genetic differences. The usage overlaps, but also involves a value judgement as to the harmfulness of the condition.

Congenital disorders include minor physical anomalies (e.g., a birthmark), severe malformations of single systems (e.g., congenital heart disease or amelia of the legs), and combinations of abnormalities affecting several parts of the body. Defects of metabolism are also considered congenital disorders. A congenital disorder can have trivial or grave effects. The most severe, such as anencephaly, are incompatible with life. Birth defects are a leading cause of death in early infancy, accounting for the deaths of nearly 2 out every 1000 infants .

Most babies with birth defects are born to two parents with no obvious health problems or risk factors. A woman can do everything her doctor recommends to deliver a healthy child and still have a baby with a birth defect.The type of birth defect is also related to the time of exposure to a teratogen. For instance the heart is susceptible from three to eight weeks, but the ear is susceptible from a slightly later time to about twelve weeks.

Infection in the mother early in the third week may damage the heart. An infection in the eleventh week is less likely to damage the heart, but the baby may be born deaf.In fact, according to the March of Dimes, about 60% of birth defects have unknown causes. The rest are caused by environmental or genetic factors, or some combination of the two.

If you have detected a problem with your unborn child or you are at risk for developing a problem based on your personal medical history, The Center for Advanced Fetal Care can help. Those risks include:

Family history, such as single gene disorder
Congenital heart disease, mental retardation, or other syndromes
Advanced maternal age
Abnormal triple screen or abnormal ultrasound
Multiple gestation (twins or more!)
Congenital infection, such as Fifth disease
Intrauterine growth restriction
Abnormal amniotic fluid
Maternal medical problems affecting baby

A new, noninvasive method of prenatal testing may one day help to detect birth defects in unborn babies.But it'll be a while before the technique comes to market.

"We've shown the first abnormality, and this is proof of principle to show that this technology can be a noninvasive test from maternal blood," said study author Dr. Ravinder Dhallan, founder and chief executive officer of Ravgen Inc., in Columbia, Md. "Next, we will do a larger study and start building the infrastructure to go to market."

Dhallan wouldn't speculate on when such a test might become commercially available, saying only, "We don't intend to rush it. The health of a baby is the most important thing in anyone's life, but we are moving with deliberate speed."

Dr. Michael Katz, senior vice president for research and global programs at the March of Dimes, called the experimental test a "good system if it can be sustained by more extensive tests. It also dovetails with the current suggestion by the American College of Obstetricians and Gynecologists that prenatal diagnosis should be applied to all women."

Currently, tests to detect chromosomal abnormalities before a baby is born pose a number of problems.

Ultrasound is noninvasive but does require subsequent invasive testing before a final diagnosis can be made. And invasive diagnostic tests, such as amniocentesis and chorionic villus sampling, can pose risks to the pregnancy, including miscarriage.

"Even though the current invasive tests are quite safe, relatively speaking, they are invasive, and there are complications," Katz said. "Moreover, they have to be done somewhat later [in the pregnancy], and the sooner one makes this diagnosis, the better."

Scientists have known for several decades that fetal cells are present in the mother's blood as early as five weeks into the pregnancy. The problem is that the cells are extremely rare, representing only about one in a million of total cells.

The reason for their rarity? The mother's cells are very much like water balloons: From the moment blood is drawn, her cells burst and let loose maternal DNA into the blood stream. This serves to dilute the fetal DNA, Dhallan explained.

"Every time a mother's cell bursts, it dilutes the fetal DNA, particularly when you transport samples and when you centrifuge and process samples to get the DNA out of the plasma," he said.

In March 2004, Dhallan solved that problem in a study that showed that adding formaldehyde to the blood sample caused the mother's cells to harden ("like Ping-Pong balls"), reducing dilution and increasing fetal DNA to 25 percent.

The next challenge was how to distinguish maternal DNA from fetal DNA and how to identify abnormalities.

For the new study, the researchers examined blood samples from 60 pregnant women and the "stated biological fathers," and analyzed single nucleotide polymorphisms (SNPs or "snips"), the tiny variations in the DNA sequence that exist between individuals.

There are about 3 million variable sites where human DNA differs from person to person, out of a total of 3 billion base pairs. "The key is finding where they differ," Dhallan said.

Combining mathematics and genetics technology, the researchers determined the ratio (between mother and child) of SNPs on different chromosomes. That ratio should be the same for all chromosomes. "If it's not, you have a problem," Dhallan said.

The method correctly identified the number of chromosomes in 58 of 60 samples, including two cases of trisomy 21 (which causes Down syndrome), Dhallan said. One case of trisomy 21 went undetected, while one normal sample was incorrectly identified as trisomy 21.

Katz said: "They have one mistake one way and one the other way. That's a little too risky if you compare this with invasive techniques where you have virtually 100 percent accuracy. Also, one can never be absolutely certain that this is the biological father. In addition, there may be some times when the father is not available."

A second study, this one appearing in the Feb. 3 British Medical Journal, questions the rise of "boutique ultrasonography," where commercial companies offer "keepsake" scans to expectant parents without medical supervision.

Three- and four-dimensional, as well as moving images, can sell for up to $500, the study author stated.

While the companies claim the ultrasound poses no danger to mother or baby, several official organizations, including the American Institute of Ultrasound in Medicine and the U.S. Food and Drug Administration, have expressed concerns about the practice.

Although there are steps you can take to prevent birth defects, remember that a birth defect can happen even if you or your partner have no history of birth defects in your families or if you've had healthy children in the past.By testing and identifying fetal abnormalities as early as possible, you give your baby the best opportunity for treatment or for proper care after birth.