Evaluation of maternal health and labor and delivery conditions as risk factors for childhood leukemias in children with Down syndrome Susan E. Carozza a, *, Harold Bae a , Thomas Meath a, 1 , Adam Branscum a , Marit L. Bovbjerg a , Peter H. Langlois b a College of Public Health and Human Sciences, Oregon State University, Corvallis, OR 97331 b Birth Defects Epidemiology and Surveillance Branch, Texas Department of State Health Services, Austin, TX 78714 A R T I C L E I N F O Article history: Received 26 July 2016 Received in revised form 28 November 2016 Accepted 2 December 2016 Available online xxx Keywords: Down syndrome Childhood cancers Leukemia Epidemiology A B S T R A C T Children with Down syndrome (DS) have a remarkably high risk of developing leukemia during childhood; the mechanisms driving that risk are not well understood, and no clear prevention strategies exist. We conducted a nested case-control study in a Texas DS birth cohort to investigate possible links between maternal health, labor/delivery conditions, and leukemia risk. For most of the factors studied there was no evidence of an increased risk of total leukemias, or the subtypes acute lymphoid or acute myeloid leukemia. Ultrasound use showed an almost 2-fold increased odds of leukemia, but this result is likely an example of confounding by indication. There was a pattern of increased risk seen for presence of co-occurring heart anomalies, including tetralogy of Fallot, ventricular septal defects, atrial septal defects, and patent ductus arteriosus. Further investigation of the links between co-occurring heart defects in children with DS and development of leukemia may provide new understanding of cancer mechanisms, and ultimately lead to prevention opportunities for this high-risk population. © 2016 Elsevier Ltd. All rights reserved. 1. Introduction Children with trisomy 21, or Down syndrome (DS), face a variety of health challenges, including a remarkably high risk for developing leukemia in their childhood years. Previous research indicates that children with DS are more than 50 times as likely to develop leukemia before age 5 years than non-DS children; this risk decreases dramatically with age, pointing to a likely intrauterine origin [1]. Although epidemiological studies of leukemia risk among children with DS have investigated a variety of environmental exposures [2–4], maternal health conditions during pregnancy [5,6] and health conditions of children with DS in early childhood [7,8], no clear pattern of risk has been identified. As the birth prevalence of DS is increasing around the world [9], it is also likely mirrored by an increasing prevalence of leukemia in this high-risk population. A recent review noted that essentially only two research teams have produced all the epidemiological information available about potential risk factors for leukemia among children with DS [10]; clearly additional epidemiological studies in this population are needed. Mezei et al. [10] noted in their review that there is currently no evidence to suggest that potentially carcinogenic environmental exposures act differently in DS versus non-DS children, leading them to conclude that studying risk factors for leukemia among children with DS may also contribute to the understanding of childhood leukemia in the general population. To this end, we used a nested case-control study design to evaluate whether factors related to maternal health and the circumstances of labor and delivery, including the presence of co-occurring birth defects, influenced risk of subsequent development of leukemia in children born with DS in the state of Texas. 2. Materials and methods 2.1. Study subjects Birth certificate data files for the birth cohort consisting of children born to Texas residents between January 1, 1996 and December 31, 2009 were provided by the Vital Statistics Unit and the Center for Health Statistics of the Texas Department of State * Corresponding author. E-mail addresses: susan.carozza@oregonstate.edu (S.E. Carozza), Harold.bae@oregonstate.edu (H. Bae), meath@ohsu.edu (T. Meath), Adam.branscum@oregonstate.edu (A. Branscum), Marit.bovbjerg@oregonstate.edu (M.L. Bovbjerg), peter.langlois@dshs.state.tx.us (P.H. Langlois). 1 Present address: Center for Health Systems Effectiveness, Oregon Health & Science University, 3030 SW Moody Ave., Suite 200, Portland, OR 97239. http://dx.doi.org/10.1016/j.canep.2016.12.003 1877-7821/© 2016 Elsevier Ltd. All rights reserved. Cancer Epidemiology 46 (2017) 36–41 Contents lists available at ScienceDirect Cancer Epidemiology The International Journal of Cancer Epidemiology, Detection, and Prevention journal homepage: www.cancerepidemiology .net