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First Candle Funded Projects

In 2002-2003, First Candle provided $187,500 in research support, and in 2003-2004, $134,000 was provided. In 2004-2005, $95,000 was spent on our grants program. In 2005-2006 a total of $150,000 will have been paid out to support First Candle’s research programs. View or download a printer friendly version our Medical Research Program (PDF 200 kb). 

Research Projects

Spontaneous Arousal in Preterm Infants:  Effect of Gestational Age, Post Menstrual Age & Risk for SIDS 

In a previous pilot study supported by First Candle, Dr. Ariagno was able to show reduced duration and frequency of spontaneous arousal during sleep in 14 preterm infants in prone versus supine position. These findings, in addition to those reported in the literature on reduced elicited arousal during prone sleep, suggest arousal deficiency as an underlying mechanism for Sudden Infant Death Syndrome (SIDS).

The present study will expand on these findings by recording the duration and frequency of spontaneous arousal in a large number (262) of preterm infants with gestational age of 23-36 weeks, already recorded for sleep apnea studies at 35-65 weeks PMA. The study hypothesizes that both frequency and duration of arousal will be reduced as a function of reduced gestational age. This may explain the three to eight times higher risk of SIDS in very low birth weight and extremely low birth weight preterm infants.

The study’s second hypothesis is that this reduction will be greater at 48-52 week PMA, a period of maximum vulnerability for SIDS in preterm infants. Furthermore, by comparing arousal in symptomatic and asymptomatic preterm infants, the study will examine the role of apnea of prematurity as an additional risk factor for SIDS.

SIDS in the United States: Development of Socioeconomic Surveillance Methods

Sudden Infant Death Syndrome (SIDS) remains the leading cause of postneonatal mortality in the United States.  Major risk factors for SIDS include maternal age (<18 years), maternal education (< 12 years) and high parity (> 3 previous pregnancies).  These characteristics represent the best substitutes for socioeconomic status available from public use data.  The fact that these “substitutes” for socioeconomic status are so consistently associated with an increased risk for SIDS, suggests that a more direct assessment of socioeconomic status and its association with SIDS could help in understanding why this association exists. 

One of the objectives of this research proposal will be to correlate census data that contains specific socioeconomic information with SIDS deaths occurring at the county level within the United States.  Changes in socioeconomic conditions within counties over time may provide helpful information in understanding changes in SIDS incidence within those counties over time.  As part of this exercise, geo-coding or observing the trends in SIDS over time at the county level may also offer insights into whether or not SIDS rates change as much on the local level as they do on a national level or if certain localities contribute more to changes in SIDS rates than others.  In highlighting those changes that may have occurred in certain localities, reviews of socioeconomic or other demographic changes could help in understanding what might have caused those changes, thus providing models for implementing change in counties where little change in SIDS deaths has occurred. 

A final goal of this research is to examine changes in the SIDS death rate at the county level over time in the context of changes in other causes of sudden unexplained infant deaths (SUIDs).  Because of the increasing incidence in SUIDs exclusive of SIDS over the last few years, a better understanding is needed of where this is occurring.  By identifying areas at the county level where the postneonatal rate is remaining the same in spite of a declining SIDS rate, but with an increasing SUIDs rate, further attention can be paid to those areas to determine if this reflects a change in death certifiers’ preferences for SUIDs over SIDS or if more rigid criteria are being applied in order to accept a death as a SIDS death.

SIDS Center of Excellence for Brainstem Research
The Contribution of Maternal Smoking to SIDS and Unexplained Stillbirth: The Interrelations Between Nicotine and Serotonergic Neurons
 

In 1992, the SIDS Alliance established the first Center of Excellence for SIDS Research at the Pediatric Neuroscience Center at Boston Children's Hospital and Harvard University under the coordination of Dr. Kinney. Utilizing experts from the Departments of Neurology, Neurosurgery and Pathology, Dr. Kinney has been able to conduct a series of integrated studies of the brain and brainstem of infants. These multidisciplinary studies have also received funding from the National Institute of Child Health and Human Development (NICHD).

Even though the risk of SIDS has been significantly reduced in recent years. SIDS is still the leading cause of postneonatal infant mortality with an overall incidence of 0.6/1000 live births in the United States. While the underlying etiology is likely to be multi-factorial in nature, the causes of SIDS and potentially unexplained Stillbirth are still largely unknown; however epidemiological evidence suggests that maternal smoking during pregnancy increases the risk of SIDS 5 fold. We hypothesize that prenatal nicotine exposure, via maternal smoking, affects the medullary serotonergic system in developing the brainstem. As the serotonergic system is responsible for life sustaining functions, abnormalities that arise due to nicotine neurotoxicity may result in failure of the neuroprotective responses to external stressors, such as hypoxia, particularly if they occur during sleep thus resulting in SIDS. The aims of this project are to determine the neuroanatomic inter relationship between nicotinic receptors and serotonergic neurons in the human medulla during prenatal development and into infancy. This study will also investigate the potential role of nicotine neurotoxicity in dysfunction of the medullary ser0tonergic system during development and in SIDS cases and cases of unexplained Stillbirth. The knowledge to be gained from this study will increase our understanding of human brainstem development and the mechanisms involved in serotonergic dysfunction. Ultimately this project will aid in deciphering the pathogenesis of SIDS and or unexplained Stillbirth and could lead to the implementation of strategies to try to prevent the adverse effects of nicotine exposure via maternal smoking during pregnancy.

The Rostral Ventral Medulla, Sleep, and Breathing

The purpose of this investigation is to evaluate sleep and arousal patterns in an animal model in order to study the role of a specific region of the brain, the rostral ventral medulla (RVM). The RVM is composed of several subcomponents that are believed to be involved in the control of heart rate, blood pressure, breathing, thermoregulation, and numerous other autonomic functions.

It has been suggested that abnormalities in this region in human infants may lead to sudden death by disrupting the normal protective response to potentially life-threatening situations commonly encounter during sleep, such as hypoxia (low blood oxygen levels), hypercapnia (high blood levels of CO2), and reflex apnea.

The investigators will try to determine the effects of inhibiting neurons in the RVM on the sleep and breathing patterns of piglets in a natural environment. In contrast to the format of most animal studies using piglets, they will use telemetry to study the piglets in an unanaesthetized and freely mobile state, housed with their mother and siblings in a “natural” farm environment. This will enable investigators to make a preliminary assessment of the role of the RVM in sleep and cardiorespiratory control, which will serve as a basis for future investigations.

Characteristics of Very Low Birth Weight SIDS

and Trends in SIDS and Postneonatal Proportionate Mortality Ratios

This project seeks to determine what factors may put very low birth weight (VLBW) infants (weighing < 1500 grams at birth) at higher risk of SIDS than other infants. Members of the research team will make comparisons between VLBW infants that die of SIDS and those that die of other causes, and will also compare their characteristics to those infants that survive.

They will also look at trends in how infant deaths are classified in populations, comparing SIDS diagnoses with other types of infant death over time. In addition, they will evaluate the proportionate mortality ratios (this refers to the proportion of infant deaths due to various causes that occur in a given population over a specific period of time) for SIDS and related causes of death, such as asphyxiation and suffocation.

To accomplish the above goals, they will sample from a large dataset containing vital statistics data on infant deaths over an eight-year time period (1991-1998). By identifying the demographic and birth characteristics of VLBW infants and reviewing trends in infant deaths over the specified time period, these researchers may be able to compose a risk profile that enables health workers to design appropriate interventions to help reduce SIDS and other infant deaths.

Standardization of Diagnosis of SUDS and SIDS

This epidemiological study is a collaborative effort between Michigan State University, the Michigan SIDS Alliance, the state board of medical examiners and the state department of health. The investigators will attempt to address a long-standing problem in the SIDS field: the wide variation in diagnostic practices for diagnosing SIDS deaths. Specifically, they will collect and analyze data on SIDS diagnoses and will develop a standardized formula for investigating and diagnosing infant deaths.                      

The project involves three phases:

Pilot Study of Cross-Cultural Bed Sharing Practices in Virginia

This project will involve quantitative and qualitative methods to study bed sharing practices among a sample of parents of infants under two years of age. Using a brief quantitative survey, families who bed share would be identified. The mother would then be invited to participate in one-on-one interviews to probe the experience of bed sharing from each family’s perspective.

Participants will be recruited from six family practice and pediatric offices affiliated with the University of Virginia, located in Charlottesville, Virginia. The results from this pilot study would be used to seek funding for a larger scale study.

Investigation of Post-Infancy Sudden Unexplained Death

There is very little medical literature about sudden unexplained death of children beyond 12 months of age (SUDC). The purpose of this study is to increase our understanding of the characteristics, circumstances surrounding death, medical histories and pathology of children from ages 1year through 11 years who died suddenly and unexpectedly. In this two-year project, both retrospective and prospective cases of SUDC will be reviewed for subsequent analysis. Inclusion/exclusion criteria for the study are:

1. Cases will be included if the child’s cause of death is either “Postinfancy SIDS,” “Sudden Death of Childhood,” “Undetermined,” “Late SIDS,” or a vague description of symptoms of “undetermined etiology,” or a diagnosis acknowledged to be speculative by the prospecting pathologist;
2. The manner of death must have been ruled “Natural” or “Undetermined” or “Accidental,” the latter with cause of death unknown; and,
3. Only parents and legal guardians proficient in the English language will be included in this study.

San Diego SIDS Collaborative Research Initiative

The purpose of this effort is to collect consistent postmortem specimens along with clinical, epidemiological and pathological data on infants dying suddenly and unexpectedly. The project began in 1991; more than 500 cases have already been entered with approximately 250 pieces of information collected per case.

A variety of SIDS research investigations are being conducted at different centers around the world using the San Diego data and materials. These include: brainstem research at Harvard Medical School in Boston, Massachusetts (Hannah Kinney, MD); pulmonary arteriolar and bronchiolar structure studies at Texas Children’s Hospital and Baylor College of Medicine in Dallas, Texas (Claire Langston, MD); vascular endothelial growth factor levels research at the University of Louisville School of Medicine in Louisville, Kentucky (David Gozal, MD); studies on fetal hemoglobin levels at Florida Atlantic University (Gary Perry, MD and Enid Gilbert-Barness, MD); sex steroid hormone level studies at University of Miami School of Medicine in Miami, Florida (Michael Emery, MD); and research on laryngeal basement membrane thickness at Hebrew University in Tel Aviv, Israel (Anat Shatz, MD).

In addition to serving as a major source of specimens for each of the research efforts, the San Diego Collaborative SIDS Research Projects provides an opportunity to correlate the results of each study so that a variety of functions and abnormalities can be compared within the same infant dying of SIDS.