http://informahealthcare.com/jmf ISSN: 1476-7058 (print), 1476-4954 (electronic) J Matern Fetal Neonatal Med, 2017; 30(10): 1249–1253 ! 2016 Informa UK Limited, trading as Taylor & Francis Group. DOI: 10.1080/14767058.2016.1210123 ORIGINAL ARTICLE The introduction of the absolute risk for the detection of fetal aneuploidies in the first-trimester screening Francesco Padula 1 , Antonio Simone Lagana ` 2 , Salvatore Giovanni Vitale 2 , Laura D’Emidio 1 , Claudio Coco 1 , Diana Giannarelli 3 , Maria Cariola 4 , Alessandro Favilli 5 , and Claudio Giorlandino 1 1 Department of Prenatal Diagnosis, Altamedica Fetal-Maternal Medical Centre, Rome, Italy, 2 Department of Human Pathology in Adulthood and Childhood ‘‘G. Barresi’’, Unit of Gynecology and Obstetrics, University of Messina, Messina, Italy, 3 Scientific Direction, Biostatistical Unit, Regina Elena Cancer Institute, Rome, Italy, 4 Department of General Surgery and Medical Surgical Specialties, University of Catania, Catania, Italy, and 5 Department of Obstetrics and Gynecology, University of Perugia, Perugia, Italy Abstract Purpose: Maternal age is a crucial factor in fetal aneuploidy screening, resulting in an increased rate of false-positive cases in older women and false-negative cases in younger women. The absolute risk (AR) is the simplest way to eliminate the background maternal age risk, as it represents the amount of improvement of the combined risk from the maternal background risk. The aim of this work is to assess the performance of the AR in the combined first-trimester screening for aneuploidies. Materials and methods: A retrospective validation of the AR in the combined first-trimester screening for fetal aneuploidies, in an unselected population at Altamedica Fetal-Maternal Medical Center in Rome, between March 2007 and December 2008. Results: Of 3845 women included in the study, we had a complete follow-up on 2984. We evaluated that an AR 53 would individuate 22 of 23 cases of aneuploidy with a detection rate of 95.7% (95%CI 87.3–100), a false-positive rate of 8.7% (95%CI 7.7–9.7) and a false-negative rate of 4.3% (95%CI 0–12.7). Conclusions: In our study, the AR ameliorates the detection rate for aneuploidy. Further research and a prospective study on a larger population would help us to improve the AR in detecting most cases of aneuploidy. Keywords Absolute risk, aneuploidy, Down syndrome, first trimester screening, nuchal translucency History Received 11 April 2016 Revised 24 June 2016 Accepted 4 July 2016 Published online 20 July 2016 Introduction First-trimester screening for trisomy 21, using a combination of maternal age, fetal nuchal translucency (NT) thickness, maternal free beta-human chorionic gonadotropin (b-hCG) and pregnancy-associated plasma protein-A (PAPP-A) at 11 +0 –13 +6 weeks of gestation, is established as an effective screening program, with a reported detection rate of approxi- mately 90% for a 5% false positive rate (FPR) [1]. The risk of aneuploidy increases with maternal age [2], but only altered values of NT, free b-hCG and PAPP-A are directly related to chromosomal aberrations. In contrast, the background risk is a statistical assertion over all pregnant women of the same age, but does not relate directly to the individual case which is examined [3]. Thus, the effect of maternal age on the risk assessment is substantial, and only a few studies have been concentrated on it. It has been suggested that elimination of the background maternal age risk from the algorithm might improve screening performance [2–4]. The absolute risk (AR) represents the simplest way to eliminate the background maternal age risk, as it is calculated by dividing the combined risk by the maternal age risk. Because of the higher maternal age risk in older women, most of them have a false positive result [5], and the lower maternal age risk in younger women results in an increase in the number of false negative results [6–9]. Considering this evidence, the aim of this study is to evaluate the AR method as a screening approach for fetal aneuploidies, in patients undergoing first-trimester combined screening in an unselected population related to a specialized center for prenatal medicine. We recently used the same population to analyze the performance of the first-trimester combined screening [10]. Materials and methods Study design and participants We designed a retrospective cohort study that included 3,610 single fetuses of all consecutive non-selected Caucasian pregnant women who attended spontaneously the Address for correspondence: Antonio Simone Lagana `, M.D., Department of Human Pathology in Adulthood and Childhood ‘‘G. Barresi’’, Unit of Gynecology and Obstetrics, University of Messina, Via C. Valeria 1, 98125 – Messina, Italy. Tel: (+39) 0902212183. Fax: (+39) 0902937083. E-mail: antlagana@unime.it