Offer Early Genetic Screening, Prompt Disclosure


SCOTTSDALE, ARIZ. — Noninvasive genetic screening has a higher detection rate when done in the first trimester of pregnancy and should be offered with prompt disclosure of results, Joe Leigh Simpson, M.D., said at the annual meeting of the Central Association of Obstetricians and Gynecologists.

An offer of amniocentesis or chorionic villus sampling (CVS) to every pregnant woman regardless of age also should be considered, according to Dr. Simpson, chairman of obstetrics and gynecology at Baylor College of Medicine, Houston.

“I believe a good case could be made for universal invasive screening,” he said. “I believe amniocentesis and CVS are much safer than generally touted. The 1-in-200 [loss rate] figure we have told our patients is doing them a disservice, because it is not a valid figure in 2005.”

He predicted karyotyping will become obsolete as a diagnostic tool within the next 5–10 years. Chromosomal microarrays currently in development are more accurate than karyotypes, and should soon be able to detect many common Mendelian disorders, Dr. Simpson said after describing ongoing research at Baylor, where he also is a professor in the department of molecular and human genetics.

“I don't think there is any question the public will demand this approach and not karyotypes,” he said. “Karyotypes have a limited future in terms of the diagnostic field.”

The American College of Obstetricians and Gynecologists is reviewing the current guideline for invasive and noninvasive screening, adopted in 1996, according to Dr. Simpson. He predicted a revision with a “cafeteria of options” will be announced early next year.

Among the noninvasive options he listed are sequential first and second trimester screening with various serum analytes, nuchal translucency ultrasound, and nasal bone inspection.

“Noninvasive first-trimester screening shows clear improvement, 5%–10%, over second-trimester screening, and is more applicable to multiple gestations,” he said, citing recent results from a new analysis of data from the First and Second Trimester Evaluation of Risk for Aneuploidy (FASTER) trial. “Successful incorporation with nasal bone [screening] could yield over 90% detection.”

Dr. Simpson said nuchal translucency ultrasound in the first trimester is especially useful in women with multiple gestations, as it allows assessment of individual fetuses. With serum testing alone, he said, detection rates in this population can dip as low as 25% with second-trimester screening.

First-trimester screening for absence of nasal bone was not successful in a 2003 report from the FASTER trial, but other studies have reported Down syndrome detection rates as high as 73%, according to Dr. Simpson. He advocated using nasal bone inspection with other noninvasive tests rather than as the sole measure.

In two recent studies from the United Kingdom, he said 30,564 women and 15,822 women, respectively, were screened by four measures: pregnancy-associated plasma protein A (PAPP-A), human chorionic gonadotropin (hCG), nuchal translucency, and nasal bone inspection. The detection rates were 93% and 97%, respectively.

“Early is better for issues of privacy and access to management, but it is also [better] for sensitivity,” Dr. Simpson said.

Addressing the controversy over disclosure of first-trimester results before a woman returns for second-trimester screening, he warned of the potential for litigation if the patient fails to return or is somehow lost to follow-up without learning she is at high risk.

“What if you have someone who would have had a procedure if you told her the results in the first trimester, and she just did not get around to coming back to you, or there is a hurricane or whatever?” he said, adding that second-trimester detection rates have been shown not to decline as feared when high-risk women were advised of first-trimester results.

As for invasive procedures, Dr. Simpson said the fetal loss rates are “probably no more than 1 in 500.” He cited several large studies showing fetal loss rates as low as 1 in 667 amniocentesis procedures.

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