en Reproductive Health Reproductive Health پژوهشي Original Research <strong>Background</strong>: The introduction of next generation sequencing (NGS) in recent decade to determine fetal aneuploidies through cell free fetal DNA (cffDNA) in maternal circulation has caused new challenges for conventional prenatal first and trimester screening. Limiting the conventional screening tests to the most powerful criteria would be an appropriate strategy in reducing the time around and cost of traditional tests before non-invasive NGS method.<br /> <strong>Methods</strong>: In this study, the most important factors affecting the risk of Down syndrome was found using statistical and data mining analysis of pregnant women undergoing conventional prenatal screening.<br /> <strong>Results</strong>: First trimester proteinuria, previous history of Down syndrome, consanguinity, nuchal translucency (NT) and inhibin-A were the most significant factors identified to be associated with the risk of Down syndrome.<br /> <strong>Conclusion</strong>: Incorporating those critical factors into new screening software could be valuable in advance of cffDNA testing as a perfect accurate non-invasive prenatal screening. Data Mining, Down syndrome, Prenatal screening, Risk factor 1 8 http://caspjrm.ir/browse.php?a_code=A-12-120-2&slc_lang=en&sid=1 Fatemeh Karami 10031947532846002015 10031947532846002015 No Departement of Medical Genetics, Applied biophotonics research center, Science and Research Branch, Islamic Azad University, Tehran, Iran Nafiseh Sedaghat 10031947532846002016 10031947532846002016 No Computing Science Department, Simon Fraser University, British Columbia, Canada Sedigheh Kolivand 10031947532846002017 10031947532846002017 No Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran Maryam Esmaeili 10031947532846002018 10031947532846002018 No Department of Clinical Laboratory Sciences, Nilou Medical Laboratory, Tehran, Iran Sarang Younesi 10031947532846002019 10031947532846002019 No Department of Clinical Laboratory Sciences, Nilou Medical Laboratory, Tehran, Iran Mohammad Hossein Modarressi modaresi@tums.ac.ir 10031947532846002020 10031947532846002020 Yes Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran