Heel-Prick Blood Biomarker May Identify Risk for SIDS

Sudden infant death syndrome is many parents’ worst nightmare. You put an apparently completely healthy baby to sleep in the evening, and the next morning, it is lying dead in its cot. Scientists in Australia are now causing a stir. In The Lancet’s open-access journal eBioMedicine, they write that they have found a way to identify babies at increased risk of sudden infant death syndrome shortly after their birth.

The primary author of the case-control study is the Australian biochemist Carmel Therese Harrington, PhD, a sleep medicine expert and honorary research fellow at the Children’s Hospital at Westmead, Australia. Harrington herself lost a child to sudden infant death syndrome. The entire study was financed through a crowdfunding campaign dedicated to her late son.

Effective Information Campaigns

“There are no up-to-date surveys on the number of sudden infant deaths in Germany. Still, it is known that sudden infant death syndrome is responsible for half of all deaths [in the first year of life] beyond the first month of life,” Ursula Felderhoff-Müser, MD, vice-president of the German Society of Pediatrics and Adolescent Medicine (DGKJ), told Medscape Medical News.

Figures from the start of the 2000s show that the incidence rate for sudden infant death syndrome was 0.45 per 1000 children in the first year of life. “Information campaigns managed to reduce this figure by half since then,” said Felderhoff-Müser, who also is director of the first clinic for pediatric medicine at the University Hospital of Essen, Germany.

Cause Remains Unclear

It is not fully understood how sudden infant death occurs. It is assumed that the following three risk factors must occur simultaneously: a (previously unknown) vulnerability in the child, a still incompletely matured autonomic nervous system, and an exogenic stressor.

“The autonomic nervous system is responsible for regulating the sleep-wake cycle and also for the breath drive. It is assumed that for children who die from sudden infant death syndrome, there is a problem with the maturation of the autonomic nervous system,” said Felderhoff-Müser.

“External stressors may be a blanket, a pillow, or a cuddly toy that lands on the baby’s nose,” she added. “For vulnerable children, this can already be enough to prevent a normal physiological breath drive and sleep rhythm.” Nicotine in the home, a sleeping environment that is too warm, and sleeping in the parents’ bed have all been proven to be risk factors for sudden infant death.

The enzymes acetylcholinesterase and butyrylcholinesterase play an important role in the autonomic nervous system. Harrington and her team want to use their study to examine whether these enzymes may work as biomarkers for dysfunction in the autonomic nervous system and, therefore, for increased risk of sudden infant death syndrome.

Failed Acetylcholinesterase Investigation

The authors had planned to investigate the activity of both enzymes in blood samples from infants participating in newborn screening in New South Wales, Australia. This screening involves collecting a small quantity of blood from the heel. The blood is then dropped onto prepared filter paper cards to test for congenital metabolic diseases and endocrinopathy.

However, they encountered technical difficulties during the analysis. “In exploratory studies such as ours, it would have been ideal to investigate both acetylcholinesterase and butyrylcholinesterase,” write the authors. “However, this was not possible with the blood samples collected from the dry blood cards.”

Butyrylcholinesterase Analysis

Therefore, Harrington and her colleagues from the Sudden Infant Death Syndrome and Sleep Apnea Research Group at the pediatric hospital in Westmead decided to investigate only the activity of butyrylcholinesterase.

In the case-control study, they included 67 children who had died suddenly and unexpectedly between the ages of 1 and 104 weeks. For 26 of them, the cause of death was sudden infant death syndrome; for the other 41 children, there was another reason, or the ages of the children were not in the typical age range of 1 month to 2 years. The control group was composed of 655 surviving children, who were matched according to age and sex.

“Our aim was to find out whether children who die of sudden infant death syndrome have a different level of butyrylcholinesterase activity at birth, which could serve as a biomarker for the vulnerability of children for sudden infant death syndrome,” write the researchers.

Significantly Lower Activity

For the dry blood eluate from the 26 children who died of sudden infant death syndrome, the measurements revealed a butyrylcholinesterase activity of 5.6 U/mg. This activity was significantly higher in the control group, at 7.7 U/mg. For each U/mg decrease in butyrylcholinesterase activity, the risk of sudden infant death syndrome increased by 27% (odds ratio, 0.73; P = .0014).

There was no association with butyrylcholinesterase activity for the children whose cause of death was other than sudden infant death syndrome, the researchers report.

Early Identification

“Our study identified biomarkers that can distinguish children who died from sudden infant death syndrome from healthy control subjects and children who died from other causes, before the sudden infant death occurs,” write Harrington and colleagues. She postulated that this reduced butyrylcholinesterase activity indicates autonomic cholinergic dysfunction and thus a congenital vulnerability in the children who died of sudden infant death syndrome.

“This opens up the possibility of identifying infants at increased risk of sudden infant death early on and paves the way for future research projects on specific interventions,” write the researchers.

Too Early?

For Felderhoff-Müser, the study demonstrates a “clear trend that is worth pursuing further.” She pointed out, however, that the study included only 26 typical cases of sudden infant death syndrome.

“Before we can even consider including the activity of butyrylcholinesterase in newborn screenings, further research is necessary into, for example, what the normal values actually are, how reliable the measurements from the dry blood cards are, and — as originally planned by Harrington and her team — what role the activity of acetylcholinesterase plays,” she said.

Should it be confirmed that the activity of butyrylcholinesterase is a reliable biomarker for sudden infant death syndrome, the finding could have an enormous influence on medical practice. “We have seen how effectively information campaigns were able to reduce the frequency of sudden infant death syndrome,” said Felderhoff-Müser. “Perhaps informing parents using such a measurement would be even more effective than anything else to date.”

This article was translated from the Medscape German edition.

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