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SIDS in the Future

Chapter Five
SIDS in the Future

Experiments with Tadpoles
“SIDS Is Not a Mystery”
Could SIDS be Caused by Bacteria?
“The Most Disastrous Thing that Can Happen”
The Genetic Link
A Federal Mandate
Looking Toward Tomorrow

Sudden infant death syndrome has often been called one of the most tragic medical mysteries. The idea that thousands of babies die for no apparent reason is unthinkable, yet it continues to happen year after year. By educating parents about known risk factors, researchers and health-care professionals are trying to reduce the prevalence of SIDS. Yet they are the first to admit that avoiding these risk factors is no guarantee against SIDS. Even infants who are exposed to no risk factors whatsoever still die of SIDS, while many others who are at higher risk do not. That is one reason why SIDS is so baffling, and it is also why scientists are fiercely committed to studying it. Their goal is to find the cause, or causes, of SIDS in an effort to put an end to this terrible killer of babies.

Experiments with Tadpoles

To support SIDS research, the National Institutes of Health (NIH) allocates nearly $80 million per year for research funding. Millions more are allocated for research by private SIDS foundations. One project that received a $1 million grant from the NIH is being conducted at the University of Alaska at Fairbanks (UAF). The research involves rather unusual laboratory creatures: tadpoles. Assistant professor Barbara Taylor ex- plains why: “The tadpoles are a model we can use in experiments that would be difficult in rats or mice and impossible in humans. The brain stem, which sets the rhythm of breathing, is remarkably similar in tadpoles and humans. What we learn from our experiments on tadpoles may help us explain and prevent SIDS.”69 One reason why the UAF researchers are aggressively pursuing SIDS studies is that the prevalence of SIDS in Alaska is twice the national average. Among Alaskan Natives it is nearly four times higher than the national average. The focus of Taylor's research is to examine the effects smoking and alcohol have on babies who are still in the womb.

Using a microscope, researchers surgically remove a tadpole's tiny brain stem, which they are able to keep alive and “breathing” for up to three days. They add either alcohol or nicotine to the aquarium water to simulate prenatal exposure to these substances in order to determine how such exposure influences the brain stem's control of breathing. Taylor says they have found that exposure to alcohol and nicotine impairs the tadpoles' breathing responses to high carbon dioxide (hypercapnic response) and low oxygen (hypoxia response). “Such impaired responses, when they occur in human infants, are a factor in SIDS deaths,” she says. Taylor continues:

Babies born to mothers who smoke or drink during pregnancy have a higher risk of SIDS. The impairment of hypercapnic and hypoxic responses varies with the timing (when in development) and duration (how long it lasts) of exposure. Tadpoles can recover from the nicotine-induced impairment of their hypercapnic response if they are allowed a period of development when they are nicotine-free. We are currently determining if this recovery results from the regenerative capacity of amphibians or if mammals would be capable of such recovery. We have learned, however, that tadpoles cannot recover, with respect to breathing responses, from developmental exposure to alcohol.70

“SIDS Is Not a Mystery”

As with Taylor's research, laboratory animals are used in a number of SIDS studies, while others utilize the organs of humans who have died. The results of an infant brain study were announced in 2006 by researchers at the Children's Hospital in Boston and Harvard Medical School. The team examined the brains of thirty-one infants who had died of SIDS and compared them with the brains of ten infants who had died of other causes. Their focus was on an area of the brain known as the medulla oblongata, which is the lowest part of the brain stem. The medulla contains nerve cells that make and use serotonin, a chemical that transmits messages between nerve cells. Sero-

tonin is known to help regulate sleep, appetite, and moods, as well as inhibit pain. It is also believed to help control breathing, blood pressure, sensitivity to carbon dioxide, and body temperature. The brains of the SIDS babies showed abnormalities in their serotonin systems. According to SIDS researcher Hannah Kinney, who coauthored the study, the team's findings indicate that SIDS is not as mysterious as researchers have long believed. Instead, they say that it is a biological problem. She explains: “SIDS is not a mystery. It's not something that parents did. SIDS is a disease. It's a scientific problem, and it can be tackled with scientific methods.”71 Kinney's team found that such brain defects occurred more often in male infants than in female infants. This could possibly unlock the secret of why baby boys die of SIDS much more often than baby girls.

The researchers also discovered that 65 percent of the SIDS victims had been sleeping on their stomachs. Kinney says that the brain defects that they observed could potentially reveal why stomach-sleeping babies die more often from SIDS than babies who sleep on their backs. She explains: “We feel that this kind of biological data gives an explanation to the ‘Back to Sleep' messages, which might seem a little crazy at first blush. Why would putting a baby on its back save a life?” The reason, according to Kinney and the research team, is that SIDS babies may lack the reflex action that causes them to wake up and shift positions in order to get better air. “A normal baby would sense the low oxygen and turn its head and wake up,”72 she says. If babies lack the ability to turn their heads to get better air, they continue to breathe in toxic carbon dioxide. Kinney adds that these sorts of abnormalities likely develop long before birth, while the infant is still in the mother's womb and the brain stem is developing. If that proves to be true, the research discoveries could eventually lead to the development of a diagnostic test that identifies babies who are at risk of developing SIDS.

Could SIDS be Caused by Bacteria?

Scientists in the United Kingdom are also aggressively pursuing SIDS research. One study was published in the May 2008 issue of the British medical journal Lancet. It was based on the old theory that bacterial infection could play a role in some cases of unexplained infant deaths. In 1934, for instance, pathologist Sidney Farber published a report in the New England Journal of Medicine, in which he suggested that streptococcus infections in infants could be the cause of sudden infant death. For the new research, scientists at Great Ormond Street Hospital for Children in London analyzed the autopsies of nearly 500 infants who had died suddenly and unexpectedly between 1996 and 2005. The team organized the cases into three groups: autopsies that revealed no obvious cause of death; those that revealed a likely cause of bacterial infection; and those that revealed evidence of another cause that was not related to bacteria. High levels of Staphylococcus aureus (staph) and E. coli bacteria were found in 181 of the babies whose death could not be explained. These bacteria are commonly carried by

humans, generally in the nose and on the skin, and do not usually cause any harm. But in this study most of the bacteria were detected in the infants' lungs and spleens. This indicates that they played some sort of role in infection, which could have contributed to SIDS. The researchers say that this discovery could potentially help explain why SIDS deaths happen so quickly, with the transition from seemingly good health to death often occurring within as little as an hour. SIDS researcher James A. Morris explains: “The only way to imagine that this could occur is by the release of bacterial toxins into the bloodstream.”73 The research project expanded on Morris's 1999 study that showed heavier growths of bacteria in nasal samples taken from babies who slept on their stomachs compared with those who slept on their backs. The new findings reinforce the researchers' belief that bacterial infection might play a role in the development of SIDS in some babies. Morris explains: “If bacterial toxins are responsible for SIDS, this would explain why [back sleeping] improves survival… . The next step is not just to look for the bacteria in these babies, but to look for the toxins that the bacteria are producing. That is where this new science comes in.”74

According to Cheryl Cipriani, a pediatric specialist from Texas, Morris's research does not necessarily prove that SIDS and dangerous bacteria are connected. She adds, however, that it could be an important component in the search for what causes SIDS. “This is another building block in our knowledge about these kinds of deaths,” she says, “but association doesn't mean cause. But it's a large enough group of babies where you think the findings need to be paid attention to.”75

“The Most Disastrous Thing that Can Happen”

Daniel Rubens is also searching for what causes SIDS. He is not a researcher nor even a SIDS specialist, but this is a priority for him, and he has developed an interesting theory. Rubens is an anesthesiologist at Seattle Children's Hospital and Regional Medical Center. His work involves putting babies to sleep and then monitoring their breathing while they undergo surgery. Over the years he has watched the babies of friends and acquaintances die from SIDS, and it frustrates him to see that a scientific understanding of SIDS is still lacking. “I'm a parent myself, I work with babies,” he says. “SIDS is the most disastrous thing that can happen. [W]hen it comes to understanding why SIDS happens, I don't think we've moved very much at all.”76

Several years ago Rubens began to wonder whether SIDS might be connected to the workings of the inner ear. He followed his intuition and decided to pursue the theory, as he explains: “I had the idea that we've missed something in medicine about the way the body controls breathing and that the missing piece might be in the specialized nerve tissue found in the inner ear.”77 Rubens decided to embark on his own study, and he turned to Susan Norton, an audiologist who has done extensive research on newborn hearing. Between 1993 and 2000 Norton led a national study to compare the effectiveness of various newborn hearing tests. Rubens and his colleagues analyzed an archive of the hearing tests. By comparing the test results of babies who had died of SIDS with other babies who survived, Rubens found that all of the SIDS babies had hearing deficiencies in the right ear. He believes that babies who die from SIDS suffer some sort of injury during birth. For instance, high levels of pressure and the mother's extended labor can disrupt blood flow, causing blood to course through the baby. This, says Rubens, can damage tiny, delicate hairs in the inner ear that are important for transmitting information to the brain about breathing and carbon dioxide levels in the blood. If these hairs are damaged, they are prevented from warning the brain about carbon dioxide levels so breathing can be adjusted. An infant who has this sort of dysfunction is at greater risk during sleep because breathing is slower and shallower than normal. Rubens says that SIDS babies suffocate because they are not getting enough oxygen.

Rubens's research findings have proved to be highly controversial. He has been challenged, and even scorned, by some other health-care professionals and researchers. Even some of his own colleagues questioned the validity of his study, as he

explains: “My impression was that they thought I was nuts.”78 Others, however, are curious about it and say that Rubens's discovery should be pursued in larger studies. If his theory is correct, a simple, standard hearing test could possibly detect SIDS in newborns.

The Genetic Link

While Rubens continues to examine the possible connection between inner ear injury and SIDS deaths, others are focusing on the role of genetics. Researchers at the Mayo Clinic have been studying the link between genes and SIDS for many years. In 2001 a team led by cardiologist Michael J. Ackerman announced that a cardiac gene known as SCN5A was clearly linked to SIDS. In 2005 researchers discovered that genes associated with a potentially fatal heart disorder known as long QT syndrome were present in 5 to 10 percent of SIDS cases. Long QT syndrome, which is a subtle electrical disturbance in the heart, is a medical condition that causes sudden, extremely rapid heart rates and can lead to potentially fatal heart rhythms known as arrhythmias. In May 2006 the Mayo Clinic researchers added two more cardiac genes to its list of potential links to SIDS. They say that the presence of these defective heart genes may cause as many as 15 percent of SIDS cases.

Researchers from Vanderbilt University are also pursuing genetic studies, and in January 2007 they published their most recent findings. The team found that nearly 10 percent of SIDS victims had mutations or variations in several different genes that are associated with arrhythmias. According to genomics researcher Alfred L. George Jr., senior author of one of the studies, the findings also suggest that testing infants could help identify whether they carry these defective genes. He explains: “We are not recommending that a population-wide genetic screening be done, but there may be simpler, cost-effective measures that should be investigated further, perhaps performing ECG (electrocardiogram) screening of infants, although this idea is controversial.”79 George adds that inherited arrhythmias are manageable conditions that can be treated with medications or implantable devices. Thus, if such defects were to be found in infants, they could receive treatment and possibly avoid being victims of SIDS.

George and the other researchers continue to analyze other genes that are linked to arrhythmias. They are also planning studies that will determine if the parents of SIDS victims carry the same mutations. “This is critical because knowing how often mutations are transmitted from parents rather than occur spontaneously, will help establish the risk to siblings of SIDS victims,” he says. His hope is that eventually scientists will be able to identify all the causes of SIDS, including genetic factors as well as environmental and developmental factors. He explains: “Many years from now, ‘SIDS' may not be a term we use anymore because we will understand all causes of sudden infant death. But right now, SIDS is a bona fide disease category, and we should strive to understand it fully.”80

A Federal Mandate

Because SIDS is still so poorly understood, scientific research is essential in order to find what causes it and how it can be prevented. Another important step is for SIDS diagnoses to be more accurate than they are today. The Scripps Howard studies have revealed how inconsistent coroners and other healthcare professionals are in diagnosing SIDS. Theresa Covington,

SIDS Decline or Sloppy Reporting?

A Scripps Howard study published in October 2007 reported that there was “enormous variation in how the deaths of infants are investigated and classified. The SIDS rate, according to the data, is 12 times higher in Mississippi than in New York. Most experts agree that the big differences are caused by how the deaths are classified, not by how the babies died.” One finding of the study was that in 2003, the Mississippi legislature passed a law ordering state coroners to conduct death scene investigations for all sudden infant deaths. In 2002, before the new law was passed, the number of reported cases of SIDS was fifty-four; afterward, it jumped to ninety-four cases.

Thomas Hargrove and Lee Bowman, “Saving Babies: Exposing Sudden Infant Death in America,” Scripps Howard News Service, October 8, 2007.

director of the University of Michigan's National Center for Child Death Review Policy and Practice, explains: “There's no rhyme or reason to what medical examiners are diagnosing as SIDS, suffocation, strangulation or undetermined. The variability is across the country and within the states.”81 The problem, as pointed out by the studies, is that the quality of infant death investigations, the level of training for coroners, and the amount of oversight and review vary widely across the country. The result is that many babies who are diagnosed as having died of SIDS actually died from other causes—and if those causes had been known, their deaths may have been prevented. James Kemp, who is a leading SIDS researcher at St. Louis University, says that the lack of a countrywide standard approach to investigating and classifying infant deaths hinders SIDS research and puts babies at risk.

In June 2008 then–U.S. senator Barack Obama proposed legislation that would improve the way America investigates and accounts for sudden infant deaths. If passed, the bill would provide funding for federal public health agencies, including the CDC, to set up national registries of sudden, unexpected infant deaths. Having access to such a vast database would help researchers better understand the causes and trends related to the deaths. Specifically, Obama's bill calls for the development of a surveillance and monitoring system that is based on thorough and complete death scene investigation data, clinical history, and autopsy findings. It also calls for a system of collecting standardized information about the environmental, medical, social, and genetic circumstances surrounding infant deaths. Another component is the establishment of a standardized classification system for defining subcategories of SIDS and SUID for surveillance and prevention research activities.

A number of SIDS groups have endorsed the proposed legislation, including the AAP's Task Force on SIDS, the American SIDS Alliance, and First Candle, among others. Marian Sokol, president of First Candle, explains her group's reaction: “First Candle applauds Sen. Obama for introducing this ground-breaking bill. Without consistency in defining, investigating and reporting these tragic deaths, families are left searching

for answers and there is no hope for a future where these deaths can be prevented.”82

Looking Toward Tomorrow

No one doubts that sudden infant death syndrome is a tragic, mystifying baby killer. Scientists have identified many risk factors and have educated the public about them, but still, all babies are at risk for SIDS. Even with all the research that has been done, the cause of SIDS remains unknown, and it cannot be prevented. However, progress is being made. Brain studies, genetic studies, and other sophisticated research, along with improved diagnostic techniques, are bringing scientists closer to a better understanding of SIDS. Hopefully, in the same way that numerous childhood diseases and disorders have been conquered, SIDS will someday be conquered as well. Jessica Tamblin shares her thoughts:

I'm always ecstatic when I hear on the news about all the SIDS research that's being done, and how scientists are looking so hard to find a cause and how it can be prevented. I will admit that was somewhat bittersweet for me, though. I am so very hopeful that they'll succeed so not one more parent has to lose a precious child. But no matter what they do, or when they do it, it's already too late for my baby. And that's the really, really hard part.83

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