Sudden Infant Death Syndrome May Have a Biological Cause

New research has identified a potential cause of sudden infant death syndrome – an abnormality in serotonin receptors in the brainstem. The study is published in the Journal of Neuropathology and Experimental Neurology.

A leading cause of post-neonatal death

Sudden infant death syndrome (SIDS) describes a condition where an apparently healthy infant under the age of one passes away, usually while asleep, and extensive investigations cannot find a cause.

SIDS affects 38.4 of every 100,000 live births in the US, according to the Centers for Disease Control and Prevention, making it the leading cause of post-neonatal death (deaths between the ages of one month and one year). National public health campaigns in the 1990s promoted safer sleeping environments and better sleeping positions for infants, which initially reduced cases of SIDS, but incidence rates have remained constant since the early 2000s.

The authors of the new study had previously identified evidence of altered serotonin signaling in cases of SIDS, so in the new study, they analyzed serotonin signaling in the brainstems of 58 infants who died from SIDS between 2004 and 2011. When compared to brainstem analysis of 12 control cases of infant death the researchers identified an alteration in the serotonin 2A/C receptor in SIDS cases.

The 2A/C receptor

Previous research has shown that the 2A/C receptor plays a key role in autoresuscitation and arousal, which are associated with maintaining oxygen levels in the brain during sleep.

The researchers from the new study propose that as infants are in a critical period of cardiorespiratory development in their first year of life, the mutation to the 2A/C receptor – in combination with a stressor such as poor sleeping position – makes children with the mutation more vulnerable to SIDS. The team hypothesized that a brainstem network related to serotonin signaling that “fails to facilitate arousal and/or autoresuscitation in SIDS cases” could be the cause of death in the condition.

The paper’s lead author, Dr. Robin Haynes, said: “Although we have identified abnormalities in the serotonin 2A/C receptor in SIDS, the relationship between the abnormalities and cause of death remains unknown. Much work remains in determining the consequence of abnormalities in this receptor in the context of a larger network [...] that protects vital functions in cardiac and respiratory control.”

Haynes emphasized that there is currently no test to identify infants with mutations to the 2A/C receptor, making it crucial for parents to follow safe-sleep practices.

Reference: Haynes RL, Trachtenberg F, Darnall R, et al. Altered 5-HT2A/C receptor binding in the medulla oblongata in the sudden infant death syndrome (SIDS): Part I. Tissue-based evidence for serotonin receptor signaling abnormalities in cardiorespiratory- and arousal-related circuits. J Neuropathol Exp Neurol. 2023;82(6):467-482. doi: 10.1093/jnen/nlad030

This article is a rework of a press release. Material has been edited for length and content.