Introduction Despite adverse effects on children, poly-substance use during pregnancy continues to be a major public health issue [1]. Psycho- active drugs are toxic to the developing brain, especially during the second and third trimester of pregnancy [2]. Given that insults to the central nervous system have their greatest impact upon cells, circuits and processes that are in accelerated development during the fetal period [3], maternal substance use is strongly associated with short- and long-term negative neurological consequences on Purpose: Substance use during pregnancy is a public health problem. Prenatal drug exposure (PDE) is linked to abnormal physical growth, altered brain organization, and cognitive, emotional, and behavioral problems later in life. Working memory (WM) plays an important role in the cog- nitive processes required for academic achievement, particularly for problem-solving, planning, and decision-making. The purpose of this study was to conduct a systematic review of studies measuring the effect of PDE on children’s WM. Methods: Using the Joanna Briggs Institute Reviewers’ Manual, we systematically reviewed eight studies (published 2008 to 2019) that measured the effects of PDE on WM among children ages 5 to 12. Results: Studies measuring prenatal exposure to methamphetamine, tobacco, or cocaine did not find differences in WM between PDE groups and controls. Nonetheless, three of the studies found that alcohol had negative effects on children’s WM, pinpointing the potential of alcohol to disrupt neurocognitive development. Conclusion: We were not able to generate conclusions regarding the consequences of PDE on children’s WM, but we discuss methodological issues and implications for future research on this phenomenon. Keywords: Child; Prenatal exposure delayed effects; Systematic review; Memory, short-term pISSN 2635-909X • eISSN 2635-9103 Ann Child Neurol 2020;28(3):107-117 https://doi.org/10.26815/acn.2020.00094 Received: May 8, 2020 Revised: June 22, 2020 Accepted: June 24, 2020 Corresponding author: Nelson D. Cruz-Bermúdez, PhD Department of Psychology, University of Puerto Rico, Río Piedras Campus, 9 Ave Universidad, Suite 901, San Juan 00925, Puerto Rico Tel: +1-787-764-0000 (87570) Fax: +1-787-763-4599 E-mail: nelson.cruz6@upr.edu Effects of Prenatal Drug Exposure on Children’s Working Memory: A Systematic Review Samariz Laboy-Hernández, PhD 1 , Nelson D. Cruz-Bermúdez, PhD 1 , Guillermo Bernal, PhD 2 1 Department of Psychology, University of Puerto Rico, Río Piedras Campus, San Juan, Puerto Rico 2 Department of Psychology and Institute for Psychological Research, University of Puerto Rico, Río Piedras Campus, San Juan, Puerto Rico Original article the offspring. Short-term effects include abnormal brain growth and organization [4], along with long-term effects that comprise serious cognitive, emotional, behavioral and social problems [5]. Prenatal drug exposure (PDE) is considered a risk factor affecting children’s development and thus, it has received considerable atten- tion by researchers in recent years [6-9]. According to averaged data (2012 to 2013) from the National Survey on Drug Use and Health of the United States (NSDUH), about 15.4% of pregnant women ages 15 to 44 had smoked ciga- rettes, 9.4% used alcohol, and 5.4% used illicit drugs [10]. Like- 107 www.annchildneurol.org Copyright © 2020 Korean Child Neurology Society This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.