Research Postings

AMSRG brings together top medical researchers and data scientists from across the world. These experts use the power of large datasets and sophisticated data analysis techniques to make research breakthroughs on the path to better understanding SIDS and SUID.

Published Manuscripts

Results from our ongoing studies are published in prestigious peer-reviewed medical journals. Whenever possible these articles have been made open access for parents and clinicians so that they can learn and reference the content.

Five complimentary approaches are at the center of our comprehensive research plan to unravel the causes of SIDS and SUID.

Research pillars:

  1. Epidemiology
  2. Genetics
  3. Physiology
  4. Pathology
  5. Parental education

Together they form a solid science-based foundation that guides our strategies to prevent further deaths.

A selection of our recent papers are listed below, and organized by these categories.

Epidemiology

Factors Associated with Age of Death in Sudden Unexpected Infant Death

Kelty Allen, Tatiana M Anderson, Urszula Chajewska, Jan-Marino Ramirez, Edwin A Mitchell. January 2021. Acta Paediatrica.

Here we found that younger chronologic age at death was associated with maternal smoking and factors associated with lower socio-economic status, and older age was associated with low birthweight, prematurity, and admission to the neonatal intensive care unit.

Circadian Variation in Sudden Unexpected Infant Death in the United States

Tatiana M Anderson, Kelty Allen, Jan-Marino Ramirez, Edwin A Mitchell

This study identified features that are associated with SUID by time of day.  Features that were associated with nighttime SUID were bed sharing, younger infants, non-white infants, placed supine to sleep and found supine, and caregiver was the parent.  Daytime SUID death was associated with older infants, day care, white infants, sleeping in an adult bed, and prone sleep position. Factors not associated with time of death were sex of infant, smoking, and breastfeeding.

Geographic Variation in Sudden Unexpected Infant Death in the United States

Edwin A Mitchell, Xiaohan Yan, Shirley You Ren, Tatiana M Anderson, Jan-Marino Ramirez, Juan M Lavista Ferres, Richard Johnston. May 2020. The Journal of Pediatrics.

Here we addressed the question whether geographic factors play a role in SUID risk across the United States.  We found that there was marked geographic variation in SUID rates across the country, but the variation decreased after adjusting for known risk factors. After adjustment, nine states were found to have significantly higher or lower SUID mortality compared to the national average.

Distinct Populations of Sudden Unexpected Infant Death Based on Age

Juan M Lavista Ferres, Tatiana M Anderson, Richard Johnston, Jan-Marino Ramirez, Edwin A Mitchell. January 2020. Pediatrics.

This study found that SUID deaths that occur in the first week of life (days 0-6) are statistically different from deaths that occur between days 7-364.  The groups differed in assigned cause of death code, live birth order, marital status, age of mother, birth weight, and gestational length.

Maternal Smoking Before and During Pregnancy and the Risk of Sudden Unexpected Infant Death

Tatiana M Anderson, Juan M Lavista Ferres, Shirley You Ren, Rachel Y Moon, Richard D Goldstein, Jan-Marino Ramirez, Edwin A Mitchell. April 2019. Pediatrics

Study found that SUID risk more than doubled with any maternal smoking during pregnancy and increased twofold between no smoking and smoking a single cigarette daily throughout pregnancy. Assuming causality, we estimate 22% of SUID cases in the US can be directly attributed to maternal smoking during pregnancy.

Genetics

All five research pillars combined indicate that a vulnerable child succumbs to SIDS/SUID during their first year of life when exposed to external stressors such as lack of oxygen, a condition that is for example encountered when children sleep on their stomach.

Developmental factors that contribute to a child’s vulnerability such as maternal smoking have been confirmed by our epidemiological studies. Such scientific research has led to campaigns to reduce smoking and prone sleeping which has saved thousands of lives.

One important, yet still little understood, factor that renders a child vulnerable is genetic disposition. Recent advances in whole-genome and RNA-sequencing opened up the opportunity to genetically screen every child that succumbs to SUID in order to determine whether an underlying genetic vulnerability contributed to their death.

In the future, this evolving research area will allow us to develop effective strategies to prevent further deaths, such as newborn screening which can identify genetic risk factors.

The majority of our resources are invested in building the world’s largest SIDS-focused whole-genome database. Like the CDC data base, which has been instrumental for our published epidemiological research, we expect that this genetic data base will lead to many scientific manuscripts that will inform parents, researchers and clinicians, and will safe future lives.

Physiology

Advances in Cellular and Integrative Control of Oxygen Homeostasis within the Central Nervous System

Jan-Marino Ramirez, Liza J Severs, Sanja C Ramirez, Ibis M Agosto-Marlin. June 2018. The Journal of Physiology.

Failure to adequately regulate levels of oxygen and carbon dioxide in the brain has been associated with many disorders including sudden infant death syndrome. This review explores questions surrounding how the brain senses and regulates oxygen, carbon dioxide, and changes in pH.

Sudden Infant Death Syndrome, Sleep, and the Physiology and Pathophysiology of the Respiratory Network.

Jan-Marino Ramirez, Sanja C. Ramirez, Tatiana M Anderson. SIDS Sudden Infant and Early Childhood Death: The Past, the Present and the Future. Adelaide (AU): University of Adelaide Press; 2018 May. Chapter 27.

This book chapter describes how different risk factors can contribute to the sudden death, the failure to arouse, the specific conditions associated with sleep, and the neuronal networks controlling cardiorespiratory functions and how they contribute to the events leading to sudden death.

Having a better understanding of brainstem mechanics and how systems react to other influences (i.e. risk factors) can help us understand the significance of known risk factors that contribute to SIDS.

Inner Ear Lesion and the Differential Roles of Hypoxia and Hypercarbia in Triggering Active Movements: Potential Implication for the Sudden Infant Death Syndrome

Sanja Ramirez, Travis Allen, Lindsay Villagracia, Yooree Chae, Jan-Marino Ramirez, Daniel D Rubens. November 2016. Neuroscience.

Infants that succumb to SIDS have been identified with inner ear dysfunction at birth and on autopsy.  This study sought to investigate the individual roles of hypercarbia (increased carbon dioxide) and hypoxia (decreased oxygen) in eliciting movement during natural sleep in mice with inner ear damage compared to control mice with no ear damage. Hypoxia is the trigger for the movement response while carbon dioxide suppresses it.  Carbon dioxide does not trigger active movements under natural sleep conditions.

The Integrative Role of the Sigh in Psychology, Physiology, Pathology, and Neurobiology

Jan-Marino Ramirez. 2014. Progress in Brain Research.

Hypoarousal and failure to sigh have been associated with sudden infant death syndrome.  This book chapter delves into the neuroscience behind the sigh and its relationship with psychology, physiology, and pathology. In a state of decreased oxygen (hypoxia) a sigh is generated which evokes an arousal.

The Physiological Determinants of Sudden Infant Death Syndrome

Alfredo J Garcia 3rd, Jenna E Koschnitzky, Jan-Marino Ramirez June 2013. Respiratory Physiology and Neurobiology.

This review aims to explore the physiological determinants (cardiac and respiratory) that actually cause the sudden death of an infant, to figure out how the determinants are affected by known risk factors, and to propose new ideas for SIDS prevention. Epidemiological, pathological, and experimental data are used together to examine current and emerging perspectives.

Pathology

Hippocampal abnormalities and seizures: a 16-year single center review of sudden unexpected death in childhood, sudden unexpected death in epilepsy and SIDS

Fu Chuen Kon, Rita Zapata Vazquez, Andrew Lang, Marta C Cohen. September 2020, Forensic Science, Medicine, and Pathology.

Hippocampal abnormalites have been previously described in SUDEP (sudden unexpected death in epilepsy). The aim of this study was to determine the prevalence of abnormalities in the hippocampus, history of seizures, and demographic features in SUDC (sudden unexpected death in childhood), SUDEP, and SIDS cases.

Dual recombinase fate mapping reveals a transient cholinergic phenotype in multiple populations of developing glutamatergic neurons

Nailyam Nasirova, Lely A Quina, Ibis M Agosto‐Marlin, Jan‐Marino Ramirez, Evelyn K Lambe, Eric E Turner. August 2019. The Journal of Comparative Neurology.

Maternal smoking is a known risk factor for SUID. It is generally assumed that nicotine contained in cigarettes acts specifically on cholinergic neurons in the brain.

This study made the unexpected discovery that some neurons in the brain, including those implicated in the arousal response are transiently cholinergic at a critical developmental time window. Thus, these important brain networks become vulnerable to exposure to nicotine in utero which may explain the association between maternal smoking during pregnancy and sudden infant death syndrome.

Parental Education

In October of 2020, Microsoft hosted ‘Project Dream Catcher’ that used crowd-sourcing to label safe and unsafe sleep positions and environments.  The goals in the short-term were to raise SIDS awareness and educate parents on safe sleep practices, and in the long term, to build machine learning algorithms to automatically detect and alert parents to unsafe sleep conditions.

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