Earlier is Better in Prenatal Diagnosis

May 10, 2005

There is no such thing as too early when it comes to prenatal screening and diagnosis of chromosomal abnormalities. For women under 35, the American College of Obstetricians and Gynecologists (ACOG) has long recommended noninvasive screening in the second trimester. For older women, chorionic villus sampling (CVS) or amniocentesis were typically recommended, although these invasive procedures are now offered to women of any age during the second trimester.

There is no such thing as too early when it comes to prenatal screening and diagnosis of chromosomal abnormalities. For women under 35, the American College of Obstetricians and Gynecologists (ACOG) has long recommended noninvasive screening in the second trimester. For older women, chorionic villus sampling (CVS) or amniocentesis were typically recommended, although these invasive procedures are now offered to women of any age during the second trimester.

Those typical recommendations are about to change, warned Joe Leigh Simpson, MD, (pictured at right) Professor and Chair of Obstetrics and Gynecology at Baylor College of Medicine in Houston. Dr. Simpson is also a member of Contemporary Ob/Gyn's Editorial Board.

Recent data indicate that noninvasive screening during the first trimester produces equal or better detection rates than second-trimester screens, Dr. Simpson announced during the 3rd Scientific Session, the March of Dimes Lecture, yesterday afternoon. He predicted that invasive procedures will soon be replaced by maternal serum cultures, electro-mechanical systems, chromosomal microarray analysis, and other emerging technologies.

"First-trimester screening is preferred to second trimester screening," he said. "If you add second-trimester screening on top of early screening, you can add about 5% to the detection rate."

Noninvasive screening such as nuchal translucency (NT) during the first trimester produces a detection rate of about 75%, Dr. Simpson explained. That compares very favorably with maternal serum analysis, which produces detection rates of 65% with three analytes and 75% with four analytes. Starting with NT and adding a second screen such as PAPP-A boosts detection rates to 88%.

Technology is adding new noninvasive screening procedures. The absence of a nasal bone on ultrasound is being studied as an indicator for Down syndrome and other chromosomal problems. Detection of fetal cells in maternal blood is emerging as a new frontier in noninvasive screening. Trisomic fetal cells can be identified using fluorescent markers. A five-color fluorescent assay has achieved a 74% detection rate for aneuploidy, but the process is time-consuming and meticulous. An easier-to-use, more specific, and more reliable assay is needed.

The next generation of assays is already in bench top form.

A company called Biocept has created a micro electro mechanical system (MEMS for short), which can detect trophoblasts in the endocervical mucus. Mucus is collected with a standard cervical swab, Dr. Simpson said, and MEMS does the rest of the work. Once collected, trophoblasts can be analyzed or cultured with other systems. Dr. Simpson said he had no financial interest in the company.

Baylor is developing a fourth-generation microarray with 362 clones that correspond to specific disorders or target sequences.

"We have a lot of options on the table," Dr. Simpson concluded. "Microarrays will become the standard in 5 to 10 years and cervical swabs will replace invasive procedures."