Procedure-Related Miscarriages and Down Syndrome–Affected Births: Implications for Prenatal Testing Based on Women’s Preferences MIRIAM KUPPERMANN, PhD, MPH, ROBERT F. NEASE, Jr, PhD, LEE A. LEARMAN, MD, PhD, ELENA GATES, MD, BRUCE BLUMBERG, MD, AND A. EUGENE WASHINGTON, MD, MSc Objective: To determine how pregnant women of varying ages, races, ethnicities, and socioeconomic backgrounds value procedure-related miscarriage and Down–syndrome- affected birth. Methods: We studied cross-sectionally 534 sociodemo- graphically diverse pregnant women who sought care at obstetric clinics and practices throughout the San Francisco Bay area. Preferences for procedure-related miscarriage and the birth of an infant affected by Down syndrome were assessed using the time trade-off and standard gamble metrics. Because current guidelines assume that procedure- related miscarriage and Down syndrome–affected birth are valued equally, we calculated the difference in preference scores for those two outcomes. We also collected detailed information on demographics, attitudes, and beliefs. Results: On average, procedure-related miscarriage was preferable to Down syndrome–affected birth, as evidenced by positive differences in preference scores for them (time trade-off difference: mean  0.09, median  0.06; standard gamble difference: mean  0.11, median  0.02; P < .001 for both, one-sample sign test). There was substantial subject- to-subject variation in preferences that correlated strongly with attitudes about miscarriage, Down syndrome, and diagnostic testing. Conclusion: Pregnant women tend to find the prospect of a Down syndrome–affected birth more burdensome than a procedure-related miscarriage, calling into question the equal risk threshold for prenatal diagnosis. Individual pref- erences for those outcomes varied profoundly. Current guidelines do not appropriately consider individual prefer- ences in lower-risk women, and the process for developing prenatal testing guidelines should be reconsidered to better reflect individual values. (Obstet Gynecol 2000;96:511–16. © 2000 by The American College of Obstetricians and Gynecologists.) For several decades, prenatal diagnoses of chromo- somal disorders, including amniocentesis and later cho- rionic villus sampling (CVS), have been reserved for women aged 35 years or older at delivery. 1 With the emergence of expanded maternal serum and ultra- sonography screening programs, that age- and risk- based cutoff has become entrenched further. Insurance coverage for invasive testing has become more available to younger women, but only to the extent that they have been found via serum or ultrasonographic screening to be at least as high a risk as an unscreened 35 year old. Recommendations have emerged that, regardless of age, invasive prenatal diagnosis be offered only to women whose risk of giving birth to an infant with a chromosomal disorder is higher than that of an un- screened 35-year-old. 2 The 35-year-old risk threshold was selected for sev- eral reasons, including resource considerations and From the Department of Obstetrics, Gynecology and Reproductive Sciences, School of Medicine, the Medical Effectiveness Research Center for Diverse Populations, and the Department of Epidemiology and Biostatistics, School of Medicine, University of California, San Fran- cisco, San Francisco, California; the Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri; and Kaiser Permanente Medical Group, San Francisco, California. Support for this study was provided by grants from the Agency for Healthcare Research and Quality (formerly the Agency for Health Care Policy and Research), no. U01 HS07373) and the National Center for Human Genome Research (no. R01 HG01255). We thank Virginia Gildengorin, PhD, for statistical support. We also thank Bryna Harwood, MD, James Lewis, MD, Ruth Schaber MD, and David Walton, MD, at Kaiser Permanente, and the following physicians for their participation in this study: Albert L. Brooks, MD, Carol Eades, MD, Chris Grover, MD, Susan Sykes, MD (La Clinica de la Raza); Curtis E. Montgomery, MD, Alex Moy, MD, Lawrence Newman, MD, Laura Norell, MD, M. Ming Quan, MD, Kimberly Sorem, MD, and Jonathan Wong, MD (North East Medical Services). 511 VOL. 96, NO. 4, OCTOBER 2000 0029-7844/00/$20.00 PII S0029-7844(00)00969-8