Combining maternal serum alpha-fetoprotein measurements and age to screen for Down syndrome in pregnant women under age 35. New England Regional Genetics Group Prenatal Collaborative Study of Down Syndrome Screening.

Eight prenatal diagnostic centers in New England enrolled 77,273 second-trimester pregnant women between January 1986 and March 1987 to study prospectively the sensitivity and detection efficiency of maternal serum alpha-fetoprotein measurement as a screening test for Down syndrome. The study was limited to women under the age of 35 because it is accepted practice to offer amniocentesis to all women above that age. Based on risk estimates derived from a combination of maternal age and maternal serum alpha-fetoprotein measurement, 4.7% of the study population was initially classified as being at high risk for having a Down syndrome fetus (second-trimester odds for Down syndrome greater than or equal to 1:270). Forty percent of the high-risk population were subsequently placed in the low-risk category, usually because ultrasound findings corrected the gestational dates and caused the maternal serum alpha-fetoprotein interpretation to be changed. Seventy-six percent of the 2.7% of women remaining at high risk had amniocentesis; 18 fetuses with Down syndrome and 4 fetuses with trisomy 18 were identified in that group. Overall, one fetus with Down syndrome was detected per 89 amniocenteses, and an estimated 25% of all fetuses with Down syndrome were identified. These data establish the feasibility of maternal serum alpha-fetoprotein measurements as a method to screen for Down syndrome and suggest the possibility that such screening might be applicable in women over age 35 as well.