Health: Clinical Advances; Confident Obstetricians Discovering New Frontiers of Prenatal Diagnosis
By GINA KOLATA
Published: May 12, 1988
With growing confidence in their abilities to perform delicate procedures, obstetricians are pushing the limits of prenatal diagnosis, offering tests at times in pregnancy when the tests had been thought too dangerous.
Until recently, women at least 16 weeks pregnant were offered amniocentesis, in which doctors extract the amniotic fluid that bathes a fetus and analyze the fetal cells in it. Women 9 to 12 weeks pregnant were offered chorionic villus sampling, in which doctors extract and analyze fetal cells from tissue surrounding the fetus. Nothing was available from the 12th to the 16th week, and no one did tests before 9 weeks.
Now obstetricians at major medical centers have begun offering amniocentesis as early as 10 weeks of pregnancy. Others are offering chorionic villus sampling later than normal, sometimes into the second trimester when amniocentesis was the only choice. In such cases, the doctors take tissue from the placenta, which is made of fetal tissue and nourishes the fetus, rather than from chorionic villi, which are hairlike projections present early in pregnancy before the placenta is fully formed.
Doctors say they are learning, to their surprise, that their methods of prenatal diagnosis are far more widely applicable than expected. Dramatic Changes Cited
''The ways we've diagnosed fetuses have changed dramatically,'' said Dr. Ronald Wapner of Jefferson Medical College in Philadelphia. ''We used to be afraid to put a needle anywhere. Now we'll put it everywhere.'' Dr. Mark I. Evans of Wayne State University School of Medicine in Detroit said, ''We're doing things now that three years ago we wouldn't have believed possible.''
The experts stress, however, that early amniocentesis and late chorionic villus sampling are still experimental. The only data available comparing the safety of sampling to amniocentesis are from a recent study by the National Institute of Child Health and Human Development.
It compared amniocentesis at 16 to 18 weeks to sampling at 9 1/2 to 12 weeks of pregnancy and found that 1.3 percent of the women who had amniocentesis miscarried, while 2 percent of the women who had the other test miscarried. Because early amniocentesis and late chorionic sampling are so new, there are no studies on their safety.
It was as much by accident as by design that amniocentesis was offered only after 16 weeks of pregnancy and sampling only from 9 to 12 weeks, experts said. When amniocentesis was developed about 20 years ago, doctors had no way of seeing inside the uterus when they probed for amniotic fluid. For that reason, Dr. Wapner said, they waited until 16 weeks or later, when a woman's uterus was big enough and the amniotic fluid volume great enough that they would have a good chance of obtaining amniotic fluid with a needle. Ultrasonic Techniques
Gradually, ultrasound was introduced, enabling doctors to bounce high-frequency sound off of a fetus and the amniotic fluid to obtain an interior view of the uterus. Ultrasound has now become so good that Dr. Evans and others say they can guide a needle into a quarter-inch space.
In the last year, Dr. Evans and others began trying amniocentesis earlier in pregnancy. He said it began when women would come in just after the period when chorionic villus sampling normally is used. They would be 13 weeks pregnant, for example, and not want to wait three or four weeks for amniocentesis.
Dr. B. Rafael Elejalde of the University of Wisconsin Medical School is among the most experienced at early amniocentesis. He has done it on a handful of women who were just 9 weeks pregnant and six others who were 10 weeks pregnant.
Meanwhile, some doctors began offering chorionic villus sampling later in a pregnancy. They had originally decided that the sampling should be done only from about 9 to 12 weeks of pregnancy because there were reports of miscarriages when doctors performed it at other times. But, once again, they were driven by patients to try later testing, said Dr. Laird Jackson of Jefferson Medical College.
They would see a woman who was 20 weeks pregnant and had had a routine ultrasound examination revealing that ''something was not quite right'' with her fetus. The woman would want prenatal diagnosis and results as soon as possible, because the longer she waited, the more difficult an abortion would be. Need for Quick Results
But, at 20 weeks of pregnancy, it can still take a week or longer with amniocentesis before fetal cells can be grown in the laboratory in sufficient quantities for analysis. With chorionic villus sampling, the cells can be analyzed immediately.
''It occurred to many of us that maybe we ought to try to find out if we can stick a needle into the placenta and get results in a hurry,'' Dr. Jackson said.
Once they realized that late sampling worked, Dr. Jackson and others reasoned that perhaps they could also do the tests in the 12- to 16-week period when they had been telling women that no prenatal diagnosis method was available.
At this point, Dr. Jackson said, their findings ''switched a light on.'' He added: ''We could see no reason to artificially limit prenatal diagnoses to any procedure. We have an armamentarium of things to do.''
Dr. Joseph Schulman, director of the Genetics and IVF Institute in Fairfax, Va., said: ''The answer is that no one method is going to be right for all patients at any gestational age. In a way, this makes it a little bit foolish and naive to ask what's the best way to do prenatal diagnosis. It is impossible that any one way will be right for everybody.''
A woman with a huge placenta across the front of her uterus might not be a good candidate for amniocentesis, no matter when she came in, Dr. Schulman said. To do it, doctors would have to push a needle through the placenta, risking bleeding. She might do better with trans-abdominal chorionic villus sampling, in which a needle is put through her abdomen and a small amount of placental tissue withdrawn. Further Gains Expected
Dr. Schulman and Dr. Jackson think the next step is to do sampling at six weeks of pregnancy, just two weeks after a woman has missed a menstrual period and a time when the fetus is just a centimeter long.
To do this, doctors would use a newly available ultrasound probe in a woman's vagina. These more accurate vaginal probes, ''will facilitate very early prenatal diagnosis - they have to,'' Dr. Schulman said.
Dr. Mitchell Golbus of the University of San Francisco Medical Center said, however, that so many fetuses die naturally around six weeks of pregnancy that there will, necessarily, be a high miscarriage rate if the sampling is done very early. Even though most of the miscarriages would have occurred anyway, women and their doctors would always think that the procedure killed the fetus. For that reason, Dr. Golbus thinks it is best to wait until at least nine weeks before doing the tests. Simpler Test Being Sought
While obstetricians extend the use of more traditional prenatal tests for birth defects, investigators at several medical centers are trying to develop a radical alternative that would eliminate safety concerns altogether: a test requiring only a blood sample from a pregnant woman.
The idea is to fish out fetal cells from maternal blood and analyze them for genetic abnormalities, just as experts now analyze fetal cells they obtain from amniocentesis or chorionic villus sampling.
A blood test for prenatal diagnosis ''is a very attractive idea,'' said Dr. Laird Jackson of Jefferson Medical College in Philadelphia, because it would pose no risk to the fetus. Chorionic villus sampling and amniocentesis cause miscarriages in a small percentage of women.
It has been known for years that fetal cells sometimes appear in the blood of pregnant women, but the investigators are trying to determine whether they always appear and, if so, when they can be found.
Dr. Joe Leigh Simpson of the University of Tennessee in Memphis said one reason a prenatal blood test had not been developed was that fetal cells might be present in small numbers and might not divide, making it difficult to obtain enough genetic materials for analysis. But with new methods of molecular biology, he said, ''We can get around those limitations.''
Dr. Jackson said the only holdup now was demonstrating that the fetal cells were always there. ''No one's turned that key yet,'' he said. ''But if we do get an answer, the door is opened.''
Photo of an ultrasound image (Columbia Presbyterian Medical Center)