Potential Biomarker for Sudden Infant Death Syndrome (SIDS)
Sudden Infant Death Syndrome is defined as a sudden and unexplained cause of death in a seemingly healthy baby that is less than a year old. This type of death usually occurs during sleep and the cause has alluded researchers for decades. As of 2019, there were approximately 1,250 deaths from SIDS, according to the CDC. It has no obvious cause and is only diagnosed after a thorough scene investigation, interview of the caregivers, and a forensic autopsy. In the United States, 4,500 infants die with no obvious cause each year and about half of those are due to SIDS. Peak incidence is between the ages of 2 and 4 months of age. Since 1990, the overall rate of SIDS has declined by more than 50%. The diagnosis is made on an exclusion basis only. However, multiple factors could have contributed to the death such as sleeping on the stomach, sharing a bed with another person, and maternal smoking.
Typically, a child is put to bed after taking a bottle, then found dead in the same position in which he or she had been placed in the bed. There have been reports of babies not being themselves, diarrhea, vomiting, and listlessness in the weeks prior to death. Observations made have been cyanosis (blue coloring) in 50-60% of cases, breathing difficulties in 50% of cases, and abnormal limb movements in 35% of cases. When taking a history of these cases, it is very difficult to get parents to calm down and give an accurate timeline, which of course is understandable. Multiple questions should be asked about the time period prior to the incident which includes medical history, course of pregnancy, position of the child, activity of the child, observations in chronological order, breathing patterns of the infant, skin color of the infant, muscle tone of the infant, how long the incident lasted, was CPR performed, etc.
Circumstances surrounding SIDS deaths are usually that the baby was healthy, the death was silent, EMS resuscitation was unsuccessful, age usually under 7 months, multiple births, cigarette use during pregnancy, defects in feeding, diminished infant weight, prior hospital admissions, and medical issues such as thrush, pneumonia, spitting, fast breathing, fast heart rate, and blue skin due to lack of oxygen.
During autopsy, there has been the discovery of morphological differences noted in these infant’s brainstems. Thus, it has been concluded that SIDS may represent an immature development of the parts of the brain that are responsible for arousal, heart functions, and breathing functions. Therefore, when the heart and the lungs become compromised due to unfavorable environmental conditions while the infant is sleeping, the infants that have immature arousal centers may not become aroused and be able to defend themselves against the conditions, resulting in SIDS.
Multiple hypotheses have been studied and proposed as causes for SIDS, but nothing has been proven conclusively. Three main factors have been isolated which are intrinsic abnormalities in cardiorespiratory control, critical period in the development of homeostatic control mechanisms, and other triggering factors. Another hypothesis is the QT interval hypothesis which is a heart rhythm abnormality of either a prolonged QT interval or a shortened QT interval. Another variant of the QT hypothesis is the congenital anomaly called long QT syndrome or LQTS. This is a genetic disorder that comes in both autosomal dominant and autosomal recessive forms. In other words, two different genetic syndromes.
Another hypothesis is that these infants have apnea which is when breathing stops, or hypoxia that can be acute or chronic. Autopsy findings that are significant when this occurs is pleural petechiae.
The critical diaphragm failure theory suggests that when an infant sleeps on their stomach their diaphragm has to work harder for them to breathe. Infants younger than 6 months have underdeveloped diaphragms. If infants have had a systemic infection, the significant reduction in the ATP generating capacity of the diaphragm’s muscle tissue can decrease the strength of the diaphragm. There also could be a phenomenon during REM sleep when the bilateral muscle of the diaphragm is paralyzed resulting in respiratory failure.
Other theories proposed have to do with behavioral disability, primary autonomic nervous system instability, defective nerve cell development, vertebral artery compression, immune system conversion from maternal to infant, infection, defects of fatty acid beta-oxidation, unstable temperature control, vulnerable periods in brainstem maturation, exaggerated vagal response, sleep disorders, and autonomic dysfunction. Thus, it is believed that many factors may contributed to SIDS.
A new study published in eBioMedicine, June 2022, has recently been greatly publicized. This study was performed in New South Wales, Australia, on children who died from categorized SIDS at less than 24 months of age between July 2018 and July 2020. Since autonomic dysfunction had been implicated in earlier studies as a possible cause of SIDS, and butyrylcholinesterase (BChE) is an enzyme of the cholinergic branch of this system, the researchers felt that BChE might be a good measure of this autonomic dysfunction. Dried blood spots are taken at birth as part of the newborn screening process in Australia and these were collected over a five-year period from 2016-2020. They measured the activity of BChE and total protein in these blood spots. They analyzed 722 dried blood spots which included 67 dried blood spots from 26 SIDS and 41 non-SIDS cases, and 655 date of birth and gender matched controls. SIDS infants exhibited significantly lower BChE levels compared to infants who died from other causes and compared to the control sample. This is the first study to identify a biochemical marker in SIDS infants prior to death. Therefore, since this is a very promising finding, much more research is urgently needed to confirm this study. Despite having 600 control samples, the researchers felt that they still did not know how common this abnormality was in a wider population. There were also limitations to the study.
References
(Harrington, Hafid, & Waters, 2022)
(CDC, 2020)
(Burnett, Updated 2022)
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