Purpose: The purpose of this study is to determine what factors, in addition to a positive first trimester aneuploidy screen, correlate with a pregnant patient's decision to undergo invasive prenatal testing. Methods: We conducted a retrospective cohort study of singleton pregnancies referred to the Johns Hopkins Prenatal Diagnosis and Treatment Center between 2001 and 2009 with an indication of positive first trimester screen. We compared demographic factors and numerical first trimester screen results with invasive testing uptake. Risk difference calculations and linear modeling were used for analysis. Results: A total of 171 eligible patients were identified. Maternal age, race, residual risk, marital status, and year of first trimester screen correlated significantly with invasive testing uptake. Family history was predictive of invasive testing uptake for patients younger than 35 years only. Type of elevated risk (trisomy 21 vs. 18 and 13), assisted reproductive technology status, parity, and increase from age-related risk were not predictive. A general linear model for relative risk with Gaussian error showed significant interaction between the variables of age and family history, so the two traits were analyzed separately (P ϭ 0.009). Conclusions: Among patients with positive first trimester screen results, several demographic traits are predictive of invasive testing uptake. This information can help providers to identify patients at increased risk of declining invasive testing and can help providers anticipate educational needs. Further investigation should be conducted to elucidate the causes of these differences, which may relate to misinformation about the testing options and differences in values systems. Genet Med 2011:13(6):539 -544.Key Words: prenatal diagnosis, first trimester screen, aneuploidy, invasive testing, genetic counseling P roviding pregnant patients with an accurate, low-risk assessment of fetal chromosome abnormalities has long been a goal in prenatal diagnostics. Chorionic villus sampling (CVS), performed at 11-13 weeks, and amniocentesis, performed at 16 -22 weeks, use karyotyping to detect fetal aneuploidy with a sensitivity of Ͼ99%. 1 These invasive tests are considered diagnostic. The risk of miscarriage after each test is Ͻ1% but can be a source of anxiety for patients. 2 Several noninvasive screening tests are available to assess patients' probability of fetal aneuploidy before exposing them to the risks of diagnostic testing. The second trimester maternal serum screen, developed in the late 1980s, is useful for patients considering amniocentesis and has dramatically reduced the uptake of invasive testing (IT) over time. 3 The more recent introduction of the first trimester screen (FTS) in the early 2000s assesses patients' risk during the 11th-13th week of pregnancy and is, therefore, useful for patients considering CVS or amniocentesis. It provides a probability that a fetus has one of the three most common trisomies, 21, 18, or 13, with a sensitivity of Ͼ95%. 4 The purpose...