The study of 8,216 women at a dozen U.S. medical centers confirms findings in England and elsewhere, where the combination is already widely used.
"It's earlier by about a month, so we've moved the standard testing to the first trimester and improved its accuracy," said lead researcher Dr. Ronald Wapner, chairman of obstetrics and gynecology at Drexel University College of Medicine in Philadelphia. "The absolute biggest advantage is this allows women to make private decisions" before they are visibly pregnant.
The usual blood screenings done in this country identify up to 75 percent of Down syndrome babies, but do not yield results until about 20 weeks into pregnancy, when abortion is more dangerous for women and often difficult to obtain.
The new combination - two blood tests, ultrasound and the mother's age - correctly identified 85 percent of fetuses with Down syndrome and yielded results at about 12 weeks.
Nine percent of the time, it incorrectly indicated a fetus probably had Down syndrome.
About one in 800 babies has Down syndrome, the most common chromosomal birth defect. Children with the syndrome suffer mental retardation and deformities such as a broad, flat face, short hands and a small head and ears.
When the four indicators together show a high probability of Down syndrome, women can choose a definitive - and invasive - test. In chorionic villus sampling, cells are withdrawn from the placenta with a needle, usually at 10 to 12 weeks of pregnancy. In amniocentesis, which is more commonly done in this country, fluid is drawn from the amniotic sac with a needle; it is done at 14 weeks or later. Both techniques carry about a 1 percent risk of miscarriage.
The study was reported in Thursday's New England Journal of Medicine.
Dr. Mark I. Evans, director of the Institute for Genetics and Fetal Medicine at St. Luke's's/Roosevelt Hospital Center in New York, said the study will cause a gradual shift from second-trimester screening to this method.
"There have been literally hundreds of thousands of patients evaluated worldwide who confirm these data," said Evans, president of the Fetal Medicine Foundation of America. "It's being routinely used all over the United Kingdom, Israel, Brazil and many other countries."
But in an accompanying editorial, Drs. Michael T. Mennuti and Deborah A. Driscoll of the University of Pennsylvania School of Medicine wrote that second-trimester screening should continue to be the standard until detailed guidelines can be developed for using the ultrasound and other tests.
Because mothers 35 or older have a higher risk of having a Down syndrome baby - one chance in 270 - most get one of the invasive tests.
In addition to looking at the mother's age, the screening combination tested by Wapner and colleagues looks for low levels of a protein called pregnancy-associated plasma protein A, and for high levels of a type of the hormone human chorionic gonadotropin.
The ultrasound test looks for telltale high levels of fluid in the fetus' neck.
Evans, who has researched the ultrasound test and been using it for a decade, said it is the single best marker of Down syndrome. But he also warned that correctly reading the ultrasound requires specialized training and experience. It is available at some U.S. academic medical centers.
Wapner said doctors might cut in half the number of invasive tests by using the combined screening to correctly identify normal as well as Down syndrome fetuses.
Currently, the screening generally used in this country tests the mother's blood for unusual levels of a different type of gonadotropin hormone, a protein called alpha-fetoprotein and the hormone estriol, which together are 65 percent accurate. Adding a new test for the hormone inhibin A increases reliability to up to 75 percent.
The new combination of blood tests and ultrasound also proved highly effective at detecting the second-most common of the severe chromosome abnormalities that do not usually kill the fetus, a condition known as trisomy 18.
In trisomy 18, the fetus has three copies of chromosome 18, instead of the normal two, or one each from the mother and father. In Down syndrome, the fetus has three copies of chromosome 21.
By Linda A. Johnson