Science / Medicine : SUDDEN INFANT DEATH SYNDROME : Researchers Have Not Yet Identified the Mysterious Killer, but They Have Begun to Narrow the List of Suspects
For more than three decades, the leading cause of mortality in children less than a year old has been attributed to the same culprit--but researchers don’t know what that culprit is.
For lack of a better name it is called sudden infant death syndrome (SIDS), and it mysteriously claims the lives of roughly one in 500 previously healthy infants in that age range.
Theories on the cause of SIDS, which is also called crib death, range from vitamin deficiencies to hyperactive thyroid glands, but 30 years of research has failed to find a principal cause. Researchers have, however, narrowed the possibilities.
“We’ve disproven an awful lot of hypotheses,” said University of Colorado pathologist and SIDS expert Bruce Beckwith. And with each theory they eliminate, researchers have been able to focus more intensely on the remaining areas that do show promise.
Three areas that have survived this elimination process and are being scrutinized by researchers are infant respiration, heart function and sleep. And it is increasingly thought that either singly or in conjunction with each other, these three may hold an answer to the condition, which strikes primarily in the second and third months of life, and rarely after the sixth month.
Since research into the syndrome began, the respiratory process has received considerable attention from doctors and scientists studying SIDS. Up until the late 1970s, a popular theory was that apnea, a condition in which sleeping individuals periodically stop breathing, might explain the infant deaths. But subsequent experiments using respiratory monitors that sounded an alarm when an infant stopped breathing did not lead to a drop in SIDS cases.
Evidence was found, however, linking SIDS with low oxygen levels in afflicted infants, indicating that some respiratory problem was probably occurring. In post-mortem analysis of eye fluid from SIDS babies, for example, unusually high levels of a chemical called hypoxantin have been found. The body’s hypoxantin level rises sharply if the oxygen available to it is reduced; one study found levels of the chemical six times higher in SIDS babies than in infants who had died of other causes.
Related research has shown that SIDS babies may have trouble clearing their lungs of foreign particles, a condition that could cause difficulty in breathing and perhaps lead to asphyxiation and death.
Dr. Abida Haque, a pathologist at the University of Texas Medical Branch, has studied the lungs of SIDS babies from rural and industrialized areas in Texas and has found microscopic asbestos bodies measuring a few millionths of an inch across in nearly half of the SIDS victims examined. An indication of exposure to asbestos, these bodies are an iron protein secreted by cells to coat inhaled asbestos fibers. Similar bodies were found in just 10% of infants who died of causes other than SIDS.
“It could be two things,” Haque explained, “One, that children dying of SIDS are being exposed to higher levels of asbestos than other children, or two, that there’s probably something wrong with the clearing mechanism” in the lungs of SIDS victims.
A potential source of this trouble could be defective cilia, the tiny hairs that line the lungs and help keep them clear, Haque said. Haque plans to use an electron microscope to examine cilia from SIDS babies and infants who died from other causes to determine if they are structurally or functionally different.
Haque has also found physiological irregularities in the lungs of many SIDS babies, which may complicate already difficult breathing.
“What I’m finding is that children who died of SIDS have more inflammation of the respiratory tree and bronchi . . . almost like (those found in) smokers,” she said. Similar to the asbestos bodies, this inflammation could indicate that SIDS babies are either exposed to more pollutants than other children or that something about their respiratory system is incapable of dealing with the pollution, she said. Haque believes the second explanation is more likely.
Additional research is examining whether oxygen deficiency in the fetus during late pregnancy, from factors such as maternal smoking or physical obstruction, may damage parts of the brain responsible for controlling breathing. Such damage could potentially cause infants to abruptly stop breathing or, over a period of time, reduce their intake of oxygen to the point of death.
An area that is often studied in conjunction with infant respiration is that of cardiac function and what role if any the heart may play in SIDS. Heart attack has long been considered a likely cause of death in many SIDS babies, but what could bring on a heart attack in an infant without leaving any clues behind has stumped scientists.
Dr. Daniel Shannon, a pediatric pulmonary specialist at Massachusetts General Hospital, has studied this problem.
“The general theory behind all this was that for an apparently healthy infant to die suddenly and unexpectedly there had to be something going on in one of the (life-sustaining organs)” such as the heart, brain or lungs, Shannon said. “You don’t die suddenly and unexpectedly from kidney, liver or skin disease.”
Based on that assumption, Shannon began evaluating electrocardiograms of thousands of infants from across the country, searching for a common feature that might help identify SIDS babies.
Shannon and Dror Sadeh, an astrophysicist at Tel Aviv University in Israel, adapted computer software normally used to study the electrical fields of stars, and within a few months sifted through 7,000 electrocardiograms of approximately 5,000 heartbeats each.
They compared the “repolarization” phases of the heartbeats, during which the heart relaxes and prepares for another contraction, and discovered an abnormality in the hearts of half the babies who subsequently died of SIDS.
In five of the 10 SIDS babies, the repolarization phase was “inappropriate in a way that said the heart muscle didn’t restore itself fast enough” to accept another beat properly, Shannon said. This irregularity was intensified if the heart rate was in any way increased, he said, which could lead to serious, potentially fatal complications.
“That (irregularity) makes the whole system vulnerable to two events: Either subsequent beats get blocked or the electrical activity is thrust into a chaotic phase with random electrical activity roaming through the heart, but never actually coordinating to a heartbeat,” Shannon said.
Whether electrocardiograms can be used to identify infants at a high SIDS risk, and what treatment might be given if such identification is possible, remains unknown, but research in the area will continue, Shannon said.
Because most SIDS deaths occur between midnight and 9 a.m., a time when infants are presumably sleeping, scientists have begun in recent years to examine what connection, if any, may exist between sleep patterns and SIDS rates.
Dr. Robert Vertes, a neuroscientist at Mercer University School of Medicine in Macon, Ga., is interested in the neural mechanisms controlling states of sleep, and believes there may be a correlation between SIDS and a lack of rapid eye movement sleep in infants.
REM sleep normally occurs throughout the night in 80- to 90-minute cycles. Unlike the restful, quiet sleep that makes up most of an evening’s slumber, REM is characterized by brain activity similar to that during wakefulness and is when most dreams occur.
Vertes believes that by stimulating the brain, REM sleep keeps the brain from falling into permanent unconsciousness, which could lead to a coma or death.
“It may be detrimental for the brain to remain off, or quiescent, for long periods of time as it is in slow-wave sleep,” Vertes explained. “REM is a mechanism that periodically reawakens the brain during sleep without arousing the organism or disturbing the continuity of sleep.”
“It is conceivable that the often unexplained symptomology underlying cases of sudden infant death syndrome may, in some instances, involve basic sleep or REM sleep-related deficiencies,” he concluded.
This possibility is supported by the fact that the highest incidence of SIDS occurs in infants about 3 months old--the same age at which the amount of REM sleep drops from approximately eight hours per day to four hours. “Failures of REM sleep would appear to be particularly destructive during the period of early infancy when REM occupies such a large percentage of total sleep time,” Vertes said.
Vertes also sees a possible connection between SIDS and a rare but symptomatically similar condition called Oriental nightmare death syndrome. Occurring almost exclusively in male Asian immigrants, ONDS is characterized by men dying in their sleep with no apparent cause. The deaths occur most often in the early hours of sleep, when REM is most sparse. As with SIDS, a REM sleep deficiency may underlie these deaths as well, Vertes believes.
Although an exact cause for SIDS has yet to be found, most in the field are encouraged by an increased public awareness of the condition and the expanded knowledge of SIDS brought by research. At the urging of South Carolina Sen. Ernest F. Hollings, who lost a grandchild to SIDS, the U.S. government last fall convened a panel of 25 leading SIDS researchers to develop a five-year plan for directing the nation’s SIDS research. In addition, federal funding for SIDS research was recently boosted from $1.8 million to $35 million annually, according to the National Institutes of Health Budget Office.
But despite this increased attention, the possibility remains that there may be no answer or cure for SIDS and that it is simply a phenomenon that will always claim a percentage of infants. Colorado’s Beckwith sees this as a strong possibility, and one that science must be prepared to face. “At about 2 or 3 months there may be some shift in brain functioning, possibly in the part that controls sleep patterns,” which some infants are able to handle and others are not, Beckwith said.
