Headlines
As reported by The New York Times, July 27, 2004.
Prenatal Tests: More Information, Less Risk
By Jane E. Brody
At age 35, Angelica decided to start a family. Knowing that her age was associated with an increased risk of bearing a child with a chromosomal defect, at 18 weeks of pregnancy she underwent amniocentesis, an analysis of fetal cells from amniotic fluid extracted by a large needle inserted into the womb through the abdomen.
The test revealed a fetus with the extra chromosome that causes Down syndrome, and a distraught Angelica chose to end the pregnancy.
A year and a half later she was pregnant again. This time she did not want to wait until the fourth month to find out if the fetus had a chromosomal problem, so at 10 weeks she underwent chorionic villus sampling, or C.V.S., an analysis of fetal cells extracted from the placenta. No chromosomal abnormality was found, and six and a half months later she gave birth to a healthy boy.
Now 39, Angelica is pregnant once more. Based on her age, her risk of bearing a child with Down syndrome is 1 in 80. But this time there is to be no amniocentesis or C.V.S., for both tests are costly and invasive, with a small but not insignificant risk of miscarriage or fetal damage.
Instead, she underwent a series of simple blood tests plus a detailed sonogram at 12 weeks. These tests revealed that there was only a 1 in 981 chance that her child would have a chromosomal abnormality or neural tube defect, about the same risk as that faced by a woman of 29.
Measuring the Hazards
More women are having babies later in their reproductive lives, at ages when the chance of conceiving a child with a major chromosomal defect rises precipitously. The American College of Obstetricians and Gynecologists and the American College of Medical Genetics recommend that prenatal diagnosis by amniocentesis or C.V.S. be offered to all pregnant women 35 and older, as well as to younger women with positive results on screening blood tests.
But using age as the sole criterion has resulted in rising numbers of the invasive and expensive tests, as well as an increase in miscarriages of what are often hard-won pregnancies among older women. And so experts in obstetrics and fetal medicine have devised a series of simple blood tests that, when factored together with a woman's age and often with the results of a sonogram, are greatly reducing the numbers of women undergoing the more involved tests without compromising the chances of detecting serious fetal abnormalities.
A new study, reported by the June issue of Obstetrics & Gynecology, illustrates this trend. According to the study, the number of women in Connecticut who had amniocentesis or C.V.S. declined 50 percent from 1991 to 2002, while the share of Down syndrome births did not increase even though more women were becoming pregnant at "an advanced maternal age."
Dr. Peter A. Benn, a geneticist at the University of Connecticut Health Center in Farmington, where the study was done, said fewer women had the procedures because more of them had blood tests and sonograms to screen for abnormalities.
Before September 1991, Dr. Benn said, women at his center were identified as facing a high risk of a chromosomally abnormal fetus based on their age or family history, or based on their having a low level of alpha-fetoprotein, a substance in blood. That month, though, the center began screening for Down syndrome in the second trimester of pregnancy using maternal blood levels of three substances - alpha-fetoprotein plus human chorionic gonadotropin and estriol - and combining those levels with the woman's age to obtain a risk estimate.
In 1996, structural abnormalities visible on a sonogram were used to modify the blood-test risk estimate. In 1999, the center added a fourth substance in blood, inhibin-A, to the risk calculation.
In 1991, there were 48,566 live births there, with 6,082, or 12 percent, to women 35 or older at delivery. In 2002, the number of live births declined to 41,690, but the number born to women 35 and older rose to 9,040, 21.7 percent of the total.
Despite the 58 percent increase in the share of women 35 and older at delivery, referrals to the center for an invasive test based on age alone declined 68 percent as those receiving the prenatal blood and ultrasound tests grew.
"Using age as the sole criterion for an invasive test is not an efficient use of resources," Dr. Benn said in an interview. He added that reducing the number of invasive tests did not result in a failure to detect affected pregnancies.
"We're getting at least as many, if not more," he said, at a much lower cost and with minimal trauma to the woman and her unborn child. An amniocentesis or C.V.S. costs $2,000 or more, while the blood tests and sonogram cost about $300.
In some areas of the country, blood tests plus the sonogram, which among other things measures a translucent area at the back of the fetal neck, are being performed in the first trimester, as was done in Angelica's case. This approach relieves overall maternal anxiety, because the overwhelming majority of tested pregnancies give a low-risk result. It also permits abortion of an affected pregnancy before other people know the woman is pregnant.
First-trimester screening has been used in Europe for several years but is only now becoming part of American obstetrical practice, Dr. Benn said.
Understanding the Data
Doctors, midwives and nurses can estimate the risk of having a baby with chromosomal abnormalities, but each woman must decide herself what to do with that information. In a report in the May/June issue of The Journal of Midwifery & Women's Health, Dr. Elena A. Gates, an obstetrician-gynecologist at the University of California, San Francisco, explored the factors influencing a woman's perception of risk.
"We toss numbers around but don't appreciate the difficulties people have in understanding the figures," Dr. Gates said in an interview.
She added that among the factors influencing a woman's perception of risk are her ideas "when she walks in the door - what she's read or heard from her friends, and how familiar she is with the condition, whether a friend, neighbor or family member had an affected child or she had a prior affected pregnancy."
Also important, she said, is how the information is presented. "Do you say you have a 5 percent chance of Down syndrome," she asked, "or a 95 percent chance that the baby is not affected?"
In reviewing studies of how women perceive risk, Dr. Gates said, she discovered that it was much harder for most women to understand greater or lesser risk when proportions were used - say, 1 in 384 versus 1 in 112 - than when the same risks were expressed as a rate, like 2.6 per 1,000 versus 8.9 per 1,000.
It takes time to explain risk estimates to pregnant women and their partners, and to be sure they grasp the full meaning of the numbers within the context of personal experience and knowledge.
"Providers should bear in mind that a woman's individual values are much more important to optimizing decision-making than are her risks of any particular outcome," Dr. Gates concluded.
But she added a cautionary note: because of economics, lack of access to doctors and clinics, or simply a delay in receiving care, only about half of all pregnant women in this country receive prenatal diagnostic tests early enough to abort an affected pregnancy or prepare for the birth of an affected child.