A “Wear and Tear” Hypothesis to Explain Sudden Infant Death Syndrome

Abstract

Sudden infant death syndrome (SIDS) is the leading cause of death among USA infants under 1 year of age accounting for ~2,700 deaths per year. Although formally SIDS dates back at least 2,000 years and was even mentioned in the Hebrew Bible (Kings 3:19), its etiology remains unexplained prompting the CDC to initiate a sudden unexpected infant death case registry in 2010. Due to their total dependence, the ability of the infant to allostatically regulate stressors and stress responses shaped by genetic and environmental factors is severely constrained. We propose that SIDS is the result of cumulative painful, stressful, or traumatic exposures that begin in utero and tax neonatal regulatory systems incompatible with allostasis. We also identify several putative biochemical mechanisms involved in SIDS. We argue that the important characteristics of SIDS, namely male predominance (60:40), the significantly different SIDS rate among USA Hispanics (80% lower) compared to whites, 50% of cases occurring between 7.6 and 17.6 weeks after birth with only 10% after 24.7 weeks, and seasonal variation with most cases occurring during winter, are all associated with common environmental stressors, such as neonatal circumcision and seasonal illnesses. We predict that neonatal circumcision is associated with hypersensitivity to pain and decreased heart rate variability, which increase the risk for SIDS. We also predict that neonatal male circumcision will account for the SIDS gender bias and that groups that practice high male circumcision rates, such as USA whites, will have higher SIDS rates compared to groups with lower circumcision rates. SIDS rates will also be higher in USA states where Medicaid covers circumcision and lower among people that do not practice neonatal circumcision and/or cannot afford to pay for circumcision. We last predict that winter-born premature infants who are circumcised will be at higher risk of SIDS compared to infants who experienced fewer nociceptive exposures. All these predictions are testable experimentally using animal models or cohort studies in humans. Our hypothesis provides new insights into novel risk factors for SIDS that can reduce its risk by modifying current infant care practices to reduce nociceptive exposures.

Adversarial childhood events are associated with Sudden Infant Death Syndrome (SIDS): an ecological study

“…Cohort studies are also problematic due to the difficulty of finding suitable controls and accounting for external stressors, which vary widely among countries, cultures, and socio-economic status and can render association studies ambiguous. These methodological difficulties have resulted in over 100 explanations for SIDS that appeared in Medical Hypotheses [5] and much confusion between cause and effect. For instance, it has been reported that breastfeeding for a duration of at least two months is associated with a reduced risk of SIDS [51], however, it does not mean that breastfeeding confers protection against SIDS, as an infant's refusal to feed may be a symptom of other SIDS risk factors, like MNC [52,53].…”

“…The allostatic load hypothesis, initially proposed to explain how stress influences the pathogenesis of diseases [56] and later applied to specific disorders [e.g., 57], proposes that prolonged and repetitive stressful, painful, and traumatic experiences during the periand pre-natal developmental periods lead to the accumulation of allostatic load that may be lethal [5]. Thereby, both hypotheses consider external stressors but disagree on the definition of at-risk infants.…”

“…The triple risk hypothesis is more deterministic and implies that, in some cases, SIDS is unavoidable. The allostatic load hypothesis considers any infant to be at risk in a direct proportion to their genetic vulnerabilities and the cumulative stressors they have experienced (a wear and tear process) [5].…”

“…The allostatic load hypothesis for SIDS [5] purports that prolonged and repetitive exposure to stressors (e.g., poor postnatal weight gain [6], hyperthermia [7], and maternal smoking [8]) is maladaptive and has a cumulative effect that increases the risk of SIDS. It differs from the triple risk hypothesis [5], which posits that SIDS is caused by an exposure to intrinsic and external factors during a critical developmental stage. That hypothesis cannot explain the four main characteristics of SIDS, namely male predominance (60:40) in the US, the 39% lower SIDS rate among US Hispanics compared to non-Hispanics [9], the seasonal variation with most cases occurring in winter [10], and that 50% of cases occur between 7.6 and 17.6 weeks after birth with only 10% past 24.7 weeks.…”

“…To test the predictions of the allostatic load hypothesis for SIDS, we identified two common stressors [5], male neonatal circumcision (MNC) and premature birth, for which latitudinal data were available and tested their association with SIDS. Both stressor are male-biased [11] and may explain the male predominance of SIDS, whereas the first stressor may also explain the lower SIDS rates in Hispanics.…”