LOS ANGELES (August 23, 1999) -- A researcher well known for her contributions in the field of first-trimester prenatal screening for chromosomal abnormalities has become a research scholar in the Department of Obstetrics and Gynecology at Cedars-Sinai Medical Center.
While at King's College Hospital in London, England, Rosalinde Snijders, Ph.D., set up and coordinated a pilot study of a first-trimester ultrasound screening program. The results of that study confirmed the hypothesis that the ultrasound measurement of the thickness of the skin on the back of an unborn baby's neck could improve detection of chromosome defects, such as Down syndrome, at an early stage in pregnancy.
When these findings were published in 1992, demand for first-trimester screening increased dramatically and Dr. Snijders and her colleagues at King's College Hospital developed a training program to teach the technique to other health professionals. Since that time, she has helped launch training programs and additional studies throughout the world. In the United States, she served as a consultant to the National Institutes of Health in the development of the study referred to as "The First Trimester Maternal Serum Biochemistry and Fetal Ultrasound Nuchal Translucency Screening Study," or BUN study.
Cedars-Sinai's Department of Obstetrics and Gynecology has served as the Los Angeles area's training and quality assurance center since the BUN study was started last year. Lawrence D. Platt, M.D., a specialist in maternal-fetal medicine and prenatal diagnosis, and chairman of the Department of Obstetrics and Gynecology, is the trial's principal investigator at Cedars-Sinai.
"Having one of the pioneers of these studies on board adds even more depth to a staff that is nationally recognized for its size and leadership in research in first-trimester screening. For our patients, the arrival of Dr. Snijders means greater experience and opportunity," said Dr. Platt, who also serves as president of the American Institute of Ultrasound in Medicine and is one of the world's most respected authorities on ultrasound and the development of three-dimensional ultrasound imaging.
The BUN study screens women for several factors that together appear to indicate whether a fetus is at high risk for a chromosomal abnormality, particularly Down syndrome. The result of the genetic defect that creates an extra copy of chromosome 21, Down syndrome is the most common chromosome anomaly, comprising about 50 percent of all chromosomally abnormal babies. The level of risk is determined by looking at two proteins in the mother's blood, the thickness of the skin on the baby's neck, and the mother's age.
Specifically, the two blood proteins that have been found to be indicators of risk are called "free beta human chorionic gonadotropin" (hCG) and "pregnancy associated plasma protein A" (PAPP-A). If hCG is present in the mother's blood in high concentrations, and PAPP-A is low, the baby is considered to be at high risk.
It also has been found that fetuses with Down syndrome and other abnormalities tend to have an excess of skin at the back of the neck, which can now be visualized by ultrasonography in the first trimester. Risk also increases with advanced maternal age. While first-trimester screening can be performed on pregnant women of all ages, women who will be 35 or older at the time of delivery are especially encouraged to participate in the BUN study.
According to estimates, screening by maternal age and nuchal translucency now identifies more than 80 percent of fetuses with Down syndrome. When the maternal blood protein markers are taken into account, the detection rate may be as high as 90 percent.
When these non-invasive early screenings provide good news about the health of the baby, women in high-risk categories can feel more at ease in the remaining months of their pregnancies. When the early screenings indicate there might be a problem, physicians are able to recommend more invasive tests. By having screenings and diagnostic tests available earlier in the pregnancy, women are better prepared to make informed decisions and to plan well in advance for a baby who may need special medical intervention at the time of birth.
In addition to taking a leadership role in the NIH-funded BUN study, Cedars-Sinai's obstetrics and gynecology program is conducting a concurrent NIH-funded study comparing the diagnostic capabilities of two invasive tests - transabdominal chorionic villus sampling (CVS) and early amniocentesis, which is defined as amniocentesis taking place before 15 complete weeks of gestation.
Amniocentesis has traditionally been performed at 15 to 18 weeks gestation. During this procedure, the physician inserts a thin needle through the abdomen, into the uterus and into the amniotic sac. A small amount of fluid - which contains discarded cells from the developing fetus - is withdrawn. The cells are later cultured and examined microscopically.
CVS can be done as early as 10 to 12 weeks gestation. Instead of removing amniotic fluid, the doctor takes a small sample from the mat of chorionic villi, or fingerlike projections on the fetal side of the chorion frondosum, which is the placenta before it is technically called the placenta. Chorionic villi may be removed transabdominally, in much the same way amniocentesis is done. It also can be performed transcervically.
Kate Bird is a Cedars-Sinai Medical Center employee who has seen the value of early prenatal diagnostics from several angles. As a cytogenetics technologist, she performs chromosome analysis on amniotic fluid cells and CVS cells. And as a mom in the over-35 age category who is now pregnant with her second child, she and her husband, Aidan, have experienced the benefits of prenatal diagnostics first-hand.
In early 1997, when Kate underwent nuchal translucency screening before the November birth of their son, Eagan, the results were in the borderline high/normal range.
"At that time, there wasn't any known correlation for high/normal. It didn't look like that had any special significance," said Kate. "It was not desirable maybe but nobody knew what it meant, so we weren't alarmed based on that."
But about a month before Eagan's birth, researchers announced that high/normal results were often being associated with heart defects. Eagan did, in fact, have a heart condition, called transposition of the great vessels, which was detected with a subsequent ultrasound.
"With a condition like this, babies have to have neonatal surgery," Kate said. "It makes a huge difference to know before delivery. Everybody was lined up. The surgeon knew he could schedule the surgery, barring any special problems that Eagan might have. Newborn intensive care was ready for him. Everybody knew what was going to happen, so we weren't taken by surprise." Now approaching his second birthday, Eagan is doing fine.
The BUN study did not exist at the time of Kate's pregnancy with Eagan. This time, though, she underwent first-trimester nuchal translucency and maternal blood screening. Based on those results, no additional early testing was needed. A routine amniocentesis performed later "looks fine," and Kate and Aidan are expecting a girl in January.
According to Dr. Platt, the department is now studying the practicality of using 3D ultrasound in nuchal translucency measurement. "We're looking to see if we might be able to use it to get a more accurate measurement," he said.
"We'll be looking at three-dimensional ultrasound in several ways," said Dr. Snijders. "We want to see whether 3D improves the accuracy and reproducibility of the neck measurement. In addition, if we find an increased fluid collection or something that appears suspicious in two-dimensional ultrasound, we want to see whether three-dimensional ultrasound can give us clues as to whether or not there is actually a problem.
"Especially for increased nuchal thickness, we can offer invasive testing to diagnose or exclude a chromosome defect, but unfortunately, these tests do not exclude other problems such as genetic syndromes or heart defects," said Dr. Snijders. "We hope that the use of three-dimensional ultrasound will help us to diagnose these problems if they exist and that in most cases it will allow us to reassure women that the baby looks healthy."
Born in Denekamp, the Netherlands, Dr. Snijders received her bachelor's degree in biology and a master's degree in human behavior/medical biology from the University of Groningen. She earned her doctorate in medicine from the University of Utrecht. She has made more than 200 presentations, provided more than 40 seminars on first-trimester screening, and developed and designed software to support clinical activities and to facilitate audit and research.
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