Genetic disorders and congenital malformations, which may be genetic, are the leading cause of infant mortality in the United States. However, we still do not fully understand which genetic disorders are responsible for infant deaths and the full scope of their impact. This NIH K23 research proposal represents a multidisciplinary effort to gain further understanding into the genetic contributions to infant mortality, leveraging the expertise that Dr. Wojcik has already gained through her dual training in clinical genetics and in neonatal-perinatal medicine and providing further training in genomic analysis, epidemiology and biostatistics, and clinical research study design. Building off of Dr. Wojcik's prior research on the implications of genetic diagnoses in the infant and neonatal period and her experience in exome analysis for novel disease gene discovery, the objective of this study is to determine the prevalence of Mendelian genetic disorders within a cohort of deceased infants (Aim 1) and to evaluate the public health impact of these diagnoses using parental survey data (Aim 2) and data obtained from the National Center for Health Statistics (Aim 3). Under the mentorship of internationally-recognized experts in neonatology and genomic medicine (Pankaj Agrawal, MD, MSSc), human genetics and rare disease gene discovery (Heidi Rehm, PhD), the ethical/legal/social implications of clinical genetics (Ingrid Holm, MD, MPH) and in collaboration with experts in parental grief after the loss of an infant (Richard Goldstein, MD), clinical genetics (Wen-Han Tann, MBBS), perinatal mortality/epidemiology (Dominique Heinke, ScD), with additional research and career mentoring from successful researchers in human genomics (Alan Beggs, PhD and Robert Green, MD, MPH), Dr. Wojcik will strive to provide answers to bereaved families. Concurrently, she will gain the training necessary to build her own career as an independent clinician- researcher with a focus on the intersection of clinical genetics and neonatology towards a better understanding of infant mortality and ultimately its prevention.
Although genetic disorders and birth defects (which may also be genetic) are the leading cause of infant mortality in the United States, many infants die without a confirmed genetic diagnosis, and this limits our ability to fully understand the genomic landscape of infant mortality in order to provide optimal care and to develop approaches to prevent these deaths. This project presents a plan to identify genetic disorders in infants who die to learn more about which genetic conditions are responsible for infant mortality and to evaluate the importance of this information for the infant's family. What we learn from this research will inform the clinical evaluation and management of these tragic losses and will suggest strategies for their prevention.