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SIDS RESEARCH, PART II : CURRENT AND FUTURE DIRECTIONS

-reprinted with permission from the Information Exchange the newsletter of the National SIDS Resource Center

The best hope for eliminating SIDS lies in discovering its cause. For this reason, research is crucial. Part I summarizes the various components of the overall research effort, explains prevailing theories, and explores the issue of risk factors. Part 2 of the article describes specific new avenues of inquiry, focusing on the research of the National Institute on Child Health and Human Development (NICHD). Part 3 completes the series with highlights of the SIDS-related projects funded as Special Projects of Regional and National Significance (SPRANS) by the Maternal and Child Health Bureau (MCHB).

Part I of this article discussed the importance of research in eliminating SIDS, the forms that research takes, and the recent findings that are shaping its current direction. Part II describes the specific types of investigations that are in progress and planned, focusing on the research role of the Federal Government. Part III of the series will cover Federal SIDS initiatives such as Special Projects of Regional and National Significance (SPRANS) research grants and other area of research.

GENERAL DIRECTIONS

As mentioned in Part I, most researchers now believe that babies who die of SIDS are born with one or more conditions that make them especially vulnerable to stresses that occur in the normal life of a baby, including both internal and external influences. This hypothesis is considered by many to be the primary contribution of SIDS research in the past decade and is the basis for much of the ongoing research that is being conducted and recommended. Research into the final events that cause death (perhaps cardiac or respiratory failure) continues, but is now focused on the interrelationship between such events and the underlying characteristics that make the infant susceptible.

THE NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

Within the Federal Government, primary responsibility for research on SIDS rests with the National Institute of Child Health and Human Development (NICHD), which is one of the National Institutes of Health. The NICHD's research program investigates possible causes of SIDS in the fields of biology, epidemiology, and behavior. Its current areas of emphasis are developmental neurophysiology; disturbances of the autonomic nervous system (the division of the nervous system that regulates involuntary action, such as that of the heart and glands); sleep state; respiratory, larynx, and heart functions and responses to stimuli; immunology and infection; genetic factors; environmental circumstances; and anatomic pathology. In 1989, at the request of the U.S. Senate, the NICHD created a 5-year research plan that builds on the recent research findings discussed in Part I of this article, particularly those of the NICHD SIDS Cooperative Epidemiological Study, published in 1988, which was the largest SIDS study ever conducted.

The NICHD SIDS Cooperative Epidemiological Study

The cooperative SIDS study involved 6 study sites across the country. This was a retrospective study, i.e., a study and analysis of past events and other relevant information. A total of 757 infants who died of SIDS composed the study group. Two living control subjects for each case were also studied. "Control" infants are normal babies who are matched with the SIDS babies for characteristics the researcher wants to control (keep the same), such as ethnicity or birthweight, in the hope of identifying other characteristics as markers. Each control group was matched to the study group using predetermined criteria. Past events and information from each control group were compared to the study group. Researchers also studied the common characteristics of the SIDS study group. One goal of the NICHD study was to uncover risk factors specific to SIDS beyond those associated with race and low birthweight.

Therefore, one of the control groups was matched with the SIDS group for race and low birthweight while the other control was matched only for age. The study identified certain SIDS-specific risk factors. Statistically, certain factors were found to be more common to SIDS cases than the general population. Risk factors help researchers narrow their study to certain groups in order to conduct further research and to make a clearer determination of cause. Some risk factors are more significant than others, but none of the risk factors uncovered in the study is strong enough to enable prevention of SIDS in vulnerable infants. The NICHD study found statistically significant risk factors for pregnant women and infants. For pregnant women these include maternal cigarette smoking during pregnancy, being a single mother, and being a mother younger than 20 years old at first pregnancy. These and other maternal risk factors such as poor prenatal care, low weight gain, anemia, illicit drug use, sexually transmitted disease, and urinary tract infection suggest that SIDS is associated with harmful in-utero environments. The in-utero dangers are often subtle and undetectable.

For new infants, statistically significant SIDS risk factors include cyanosis (skin discoloration due to inadequate oxygenation of the blood), tachycardia (accelerated heartbeat), fever, respiratory distress (difficulty with breathing), irritability, hypothermia (abnormally low body temperature), poor feeding, and tachypnea (accelerated breathing). A review of outpatient medical records found that SIDS infants were ill more frequently than the control group. Diarrhea and vomiting (during the last two weeks of life or, in the case of living infants, the two weeks prior to maternal interview) were more common in SIDS infants to a statistically significant degree. As reported by parents of the SIDS infants and the control infants the number of colds and fever in both groups of infants was almost equal, indicating that these are not statistically significant risk factors for SIDS. Data from medical records and parental interview also strongly suggest that there is no association between the diphtheria-tetanus-pertussis (DPT) vaccination and SIDS. Fewer of the SIDS infants had the DPT vaccination and 75 percent of both the SIDS and control infants had the vaccination over 2 weeks prior to death or the interview (in cases of the control infants).

In addition, the study provided evidence that newborn apnea is not a risk factor for SIDS (although the significance of postneonatal apnea is still debatable). Documented cases of apnea in medical records were very uncommon, but parental interviews generated additional information on babies who, according to parents, turned blue or stopped breathing. More SIDS cases did experience these episodes, but they were only 9 percent of the total cases. Only 0.2 percent of the SIDS cases had medically documented recurrent apnea.

The 5-Year Research Plan

In February 1989, the National Institute of Child Health and Human Development submitted a report to Congress outlining its 5-year research plans for SIDS. In June 1989, NICHD launched the plan by convening a workshop to review twenty years of scientific evidence regarding SIDS; and to determine whether progress was sufficient to revise current criteria for SIDS diagnosis, particularly for those cases which serve as a base for research on SIDS. The expert panel was charged with determining whether subsets of SIDS cases for research purposes could be defined based on common characteristics. The group drafted a new definition of SIDS and a consensus statement emphasizing that cases of sudden infant death without a complete postmortem investigation should not be diagnosed as SIDS. The research approach at the NICHD has been to study the occurrence of SIDS in the population as well as the biological, medical and physical aspects of SIDS.

The studies are initiated and supervised by the Pregnancy and Perinatology Branch of the Institute 's Center for Research for Mothers and Children and by the Biometry Branch of the Prevention Research Program. The research plan calls for experts from a variety of specialties. These experts will contribute information to the common theme that a developmental abnormality makes some infants vulnerable to internal or external stresses, which may trigger death. A thorough understanding of normal fetal and infant development is required to evaluate the differences in research results from SIDS victims. During Fiscal Year 1991, NICHD is funding research on animal models to explore some aspects of SIDS to identify and understand what leads to sudden death in infancy.

Based on the results of the cooperative study and research findings of pathology and physiology of SIDS victims, the following research areas have been incorporated into the NICHD 5-year plan.

Epidemiology. Epidemiological research studies the relationships of various factors which in turn determine the frequency and distribution of SIDS in various populations. The 5-year plan recommends studying babies who are premature, small for gestational age, or both to learn more about these babies, to identify babies at high risk, and to develop strategies for prevention. NICHD plans to set up a repository to collect, store, and distribute brain and tissue specimens obtained from autopsies performed on SIDS victims and infants dead from other causes. Qualified researchers will be able to use the repository to research developmental disorders of the nervous system.

Neonatology. The NICHD plan calls for research into the normal development of the brain, cardiac, respiratory, and immune systems and newborns' responses to stress factors such as changes in temperature or sleep patterns, exposure to toxins, and infections. Appropriate animal models will be identified to clarify the relationship between intrauterine growth retardation and SIDS. Clinical sites around the country and a data coordination and analysis center will receive funds to conduct a standard common protocol for high risk infants. The objectives of the protocol are to determine whether home apnea monitors that record respiratory, cardiac, and oxygenation events are effective in identifying clinically relevant episodes and to determine the conditions that optimize the use of monitors for these infants.

Cardiorespiratory and Sleep Factors. Infants' responses to environmental and internal changes that affect breathing and heart function will be explored to ascertain how these response mechanisms change during the first year of life, particularly in the highest risk period between 2 and 4 months of age. Data from normal infants and infants at higher risk of SIDS will be compared. The influence of cardiorespiratory function on sleep control will be examined, as will the development of the central nervous system.

Neuroscience. The 5-year plan advocates integrative analysis of the neurosystems involved in controlling cardiorespiratory function and sleep to learn how normal systems respond to common environmental stress factors. Anatomical studies that employ new methods of measurement and analysis are encouraged, as is research into the functional development of neural membranes and transmitters. Noninvasive methods should be used in neurological examinations of normal and high-risk babies; including recording brain activity from the scalp, assessing behavior, and using imaging techniques.

Behavior. Research on normal patterns of behavioral and physiological development may identify the states at which developmental delays may make some infants more vulnerable to SIDS. Improved reporting of victims' behavior shortly before death will help in this regard.

Pathology. A group of noted pathologists and researchers met at NICHD and updated the definition of SIDS, which will help further distinguish SIDS from other types of infant deaths. However, efforts will continue to be made to use common SIDS characteristics identified by pathologists to evaluate the definition of SIDS. The NICHD recommends investigation of mechanisms that trigger SIDS deaths. The establishment of a tissue and specimen bank containing samples from autopsies of SIDS and selected control infants will make such materials more available to researchers across the Nation. A set of guidelines developed by the Division of Maternal and Child Health should be applied more widely to ensure greater uniformity of data collection. These guidelines were included in an article entitled "The Examination of the Sudden Infant Death Syndrome Infant: Investigative and Autopsy Protocols."

Infectious Diseases and Immunology. The NICHD plan includes research to examine the development of the immune system during the period when antibodies passively acquired from the mother are lost. The presence and effects of viral infections in SIDS infants should be examined, and studies will be conducted on the relationship, if any, between SIDS and substances that the body releases to fight infections.

Metabolism. SIDS victims should be examined for metabolic disorders, and screening should be introduced to detect inherited metabolic disorders in certain high risk populations. Some metabolic disorders in newborns can be corrected by use of drugs or dietary changes.

Conclusion. The NICHD 5-year research plan proceeds on the hypothesis, upon which most experts agree, that infants who die of SIDS are more vulnerable than average infants to internal or external stress factors, due to some developmental abnormalities that occur in fetal development. The challenge at this stage in the search for a means of prevention is to learn how and why some infants are physiologically vulnerable, identify the markers of vulnerability, and determine how the vulnerability and particular stresses interact to result in death.

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