Brainstem abnormalities found in “SIDS” infants, in all kinds of sleep environments

SIDS researchers report that many infants dying suddenly and unexpectedly, in all kinds of sleep environments, have underlying brainstem abnormalities and are not all normal prior to death.

This research was performed by a team of investigators lead by Dr. Hannah Kinney at Boston Children’s Hospital in conjunction with the medical examiner’s office in San Diego in the United States. An Australian SIDS researcher, Dr. Jhodie Duncan, now at the Florey Institute of Neuroscience and Mental Health, Melbourne, participated in this work during research years at Boston Children’s Hospital with Dr. Kinney’s team and continues to collaborate with the team on an international initiative exploring the causes of sudden death in infants and children.

The researchers also point to the need to detect and treat this underlying vulnerability early. They report their findings in the December issue of Pediatrics.

Research by Dr. Kinney’s team at Boston Children’s Hospital has shown over the last 20 years that infants who die suddenly, unexpectedly and without explanation—whose deaths are generally attributed to sudden infant death syndrome (SIDS)—have differences in brainstem chemistry that set them apart from infants dying of other causes.

These abnormalities impair brainstem circuits that help control breathing, heart rate, blood pressure and temperature control during sleep, and, the researchers believe, prevent sleeping babies from rousing when they rebreathe too much carbon dioxide (due to inadequate ventilation), breathe too little oxygen or become overheated (from overbundling).

At the same time, epidemiologic studies have shown that infants dying suddenly and unexpectedly are often found sleeping face down with their face in the pillow, or sleeping next to an adult in the bed—environments that have the potential to lead to smothering and death by asphyxia.

In the new study researchers asked if all these infants are truly normal. They re-examined their data, reviewing the cases of 71 infants who died suddenly and unexpectedly, were autopsied at the San Diego County Medical Examiner’s office from 1997 to 2008, and had brainstem samples available for analysis. The researchers grouped the infants according to sleep circumstances—those that were considered likely to generate asphyxia and those that were not—based upon death-scene investigation reports.

In the end, they compared 15 infants with SIDS whose deaths were deemed not to involve asphyxia (group A), 35 SIDS infants whose deaths were possibly asphyxia-related (group B) and 9 infants who clearly died from other causes (controls). They excluded the other infants, who either had insufficient data or had evidence of other clear risk factors for death, such as exposure to drugs or extremes of temperature.

Brainstem neurochemical abnormalities—involving serotonin, serotonin receptors, GABA receptors and 14-3-3 (a protein that regulates serotonin)—were found in both group A and group B. Infants in these two groups—with and without environmental risk factors for asphyxia—had the same brainstem abnormalities, and both groups differed significantly from the controls.

Even the infants dying in a potentially asphyxia-generating situation had an underlying brainstem abnormality that probably made them vulnerable to sudden death if there was any degree of asphyxia. The abnormality prevents the brainstem from responding to the asphyxial challenge and waking.

The investigators believe these findings confirm that sudden unexplained death in infants is associated with underlying vulnerabilities, and that not all infants who die in compromised sleep environments are normal.

Dr. Duncan currently acts as the Australian Scientific coordinator for the continued international efforts to understand why infants and children may die sudden and unexpectedly.  She works closely with families in Australia who are raising money for research into both SIDS and SUDC through River’s Gift and the Cooper Trewin SUDC Research Fund.

Bairnsdale-based parents, Robert and Kylie Trewin who lost their son Cooper suddenly and unexpectedly in 2010 when he was 16 months of age have raised more than $260,000 to study sudden unexplained death in childhood (a term used for children over 12 months of age who would otherwise be described as dying from sudden infant death syndrome). “Our ability to explore the underlying causes of death in these infants is greatly enhanced through international efforts with researchers at Children’s and overseas that is made possible by the support of families that have experience such tragedy” says Dr. Duncan. “While safe sleep practices remain extremely important and to date have undoubtedly saved thousands of lives, together we are focused on being able to identify why some infants appear more vulnerable irrespective of how they are placed to sleep. The ultimate goal is to be able to identify these infants or children and prevent SIDS or SUDC from affecting any other family”.

SIDS and Kids Australia has committed to matching the funds provided by the Trewin Foundation to support the Australian arm of the research and has provided $30,000 dollars in 2013.

Other funders of the study included the National Institutes of Health, the National Institute of Child Health and Development (# R01-HD20991), First Candle, the CJ Foundation for SIDS, the Jacob Neil Boger Foundation for SIDS, the Marley Jaye Cerella Foundation for SIDS, River’s Gift and the Intellectual and Developmental Disabilities Research Center at Boston Children’s Hospital (# P30-HD18655).

The Florey is an internationally renowned research institute focused on neuroscience. It is the fourth most-cited neuroscience institute in the world. Its laboratories are based at the University of Melbourne adjacent to the Royal Melbourne Hospital and at Austin Health in Heidelberg. Some 600 staff work in eight distinct divisions in both basic and translational research. Areas studied include neurodegenerative diseases – multiple sclerosis, Alzheimer’s, Parkinson’s, Huntington’s, motor neurone disease and stroke – as well as traumatic brain and spinal cord injury, addiction, epilepsy, brain development in premature babies, autism, heart failure and a range of mental illnesses.

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