Introduction

Sudden infant death syndrome (SIDS) is defined as the sudden death of an infant less than 1 year of age that remains unexplained after a complete autopsy and death scene investigation (1). Typically, SIDS is associated with a sleep period and with risk factors in the sleep environment — for example, prone/face-down sleep, bed sharing, soft bedding, and over-bundling (2-4). Despite national safe sleep campaigns, SIDS remains the leading cause of post-neonatal infant mortality in the United States, with an overall rate of 0.40 SIDS deaths per 1,000 live births (5).

SIDS is a complex heterogeneous disorder that presents in seemingly healthy infants as death — sudden and unexplained. For the family, it comes without warning, devastating all of those in and surrounding the family. For the medical examiner, it comes with the challenge of distinguishing the SIDS death from other sudden and unexpected deaths in infancy, those associated with accidental asphyxia (e.g. accidental suffocation while bed sharing), unidentified infection, or trauma. An ultimate goal in SIDS research is to identify specific biomarkers of SIDS risk which can be used to prevent a SIDS death from occurring (via successful intervention), thus alleviating the burden to the family; or, if the death does occur, to identify a readily accessible biomarker of SIDS death, thus alleviating the burden of the medical examiner adjudicating the death. In this chapter we will address the concept of biomarkers of SIDS, biomarkers of a SIDS death, and biomarkers of SIDS risk.

Biomarkers, defined as objective indicators of a pathologic process, medical condition, or medical state, can be presented in many different forms or types of measurements. They can be biochemical biomarkers with a distinct signature of a single metabolite or group of metabolites specific to a disease process, genomic biomarkers defined as a DNA or RNA characteristic associated with a pathogenic process, or biomarkers which utilize physiological tests (e.g. heart rate and blood pressure) to identify or predict a disease state or disease risk. There have been several studies reporting physiological biomarkers (apnea, cardiac rate abnormalities, and arousal deficits) in infants who subsequently died of SIDS (6-10). Likewise, there have been genetic studies reporting on the potential association of genetic alterations with SIDS death (11-25).