Notice of Special Interest (NOSI): Understanding Sudden Death in the Young Through Research
Notice Number:

Key Dates

Release Date:


First Available Due Date:
October 05, 2023
Expiration Date:
January 07, 2028

Related Announcements

PA-20-185 - NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)

Issued by

National Heart, Lung, and Blood Institute (NHLBI)

National Institute of Neurological Disorders and Stroke (NINDS)


This Notice of Special Interest (NOSI) highlights interest in receiving grant applications focused on mechanistic, genetic, and other studies to evaluate causes and consequences of, and risk factors for sudden death in the young (SDY). Studies are required to use phenotypic data and/or DNA samples and/or associated sequence data from the NIH/CDC Sudden Death in the Young (SDY) Case Registry as foundations for their research. Studies may use SDY Case Registry phenotypic data and/or samples and/or sequence data alone or in combination with other cohorts. Results of such studies are required to adhere to the NIH Data Sharing Policy so that the data is disseminated widely and provides an evidence base to advance discussions about screening and prevention of SDY.

The sudden, unexpected loss of a child is a tragic event with significant impact on families and communities. The Sudden Death in the Young (SDY) Case Registry is a unique collaboration between the National Institutes of Health (NHLBI and NINDS), the Centers for Disease Control and Prevention (CDC), and state and local public health offices, who are supported for case ascertainment and data collection. The Data Coordinating Center is at the Michigan Public Health Institute, and the biorepository is at the University of Michigan. The Registry was designed to address critical knowledge gaps in the epidemiology and causes of SDY and to develop a resource for research that will enhance the evidence base to inform prevention efforts.

Fundamental gaps in knowledge about incidence, mechanisms, and risk factors for SDY limit the identification of effective prevention efforts. In the majority of SDY cases, after autopsy and investigation, a cause cannot be identified. In deaths where a cause can be identified, sudden, unexpected, non-injury-related infant and child deaths are often due to cardiac causes (myocarditis, cardiomyopathy, coronary artery anomalies, and ion channelopathies), respiratory causes (asthma, pneumonia), sudden unexpected death in epilepsy (SUDEP), and various other infections, neurological, hematologic, and gastrointestinal catastrophes. Because of the high number of unexplained deaths and the lack of evidence regarding their cause(s), there is disagreement about the best approach to prevent SDY. The SDY Case Registry and the associated research efforts should help close these knowledge gaps and provide a foundation of data that can be used to inform targeted prevention efforts.

The SDY Case Registry was first funded in 2013 to address critical knowledge gaps on the epidemiology and etiologies of SDY. The CDC is leading population-based surveillance efforts to identify 100% of cases of SDY in funded states/jurisdictions of the SDY Case Registry. To do this, they provide technical assistance to states/jurisdictions to increase case ascertainment and ensure consistent categorization of cases. Support by NHLBI and NINDS is focused on developing a resource for research on SDY by ensuring collection of a comprehensive battery of phenotypic data elements and collection of DNA and tissue samples to enable genomic analysis. Detailed phenotyping is performed for cases of sudden cardiac death in the young (SCDY), unexplained infant and child death, and sudden unexpected death in epilepsy (SUDEP), with limited data gathered on other explained SDY cases.

The SDY Case Registry is one of the largest population-based cohorts of children who have died suddenly in the US, including over 5000 SDY cases to date. The SDY Case Registry’s 13 currently funded states/jurisdictions include approximately 20% of SDYs in the US. The population of infants and children in the states/jurisdictions funded for the SDY Case Registry is 23% black. Ethnicity data is not available for all jurisdictions; the funded states include approximately 14% Hispanic/Latino infants and children. Data can be used to explore the causes of SCDY as well as sudden unexpected death in epilepsy (SUDEP), sudden unexpected infant death (SUID), and other causes of pediatric sudden death.

Inclusion criteria are infants and children up to age 20 who die suddenly and unexpectedly. Homicide, suicide, intentional/illicit drug overdoses and obvious injury-related deaths are excluded. Data is gathered about symptoms, activity/exercise, previous diagnoses, medications, treatments, seizures, family history, and resuscitation. Cases are categorized by cause using a standard algorithm by state/local experts in cardiology, neurology, and pathology, and, after informed consent from surviving family members, blood/tissue are collected for DNA extraction and stored in the biorepository at the University of Michigan to enable research. This consent allows for use of the child’s biospecimen for research, access to the autopsy report (where allowable by states/jurisdictions), and re-contact for return of results or discussions of future research opportunities. In addition, families are given the option to consent to re-contact by investigators for the purposes of obtaining additional information or returning clinically actionable results. Consent has been obtained for research on approximately 400 cases to date, and whole genome sequencing has been performed on 372 cases. Sequence data is available to investigators through the NIH data repository (dbGaP). Controls are not included in the Registry and must be sought elsewhere.

State public health agencies (or their bona fide agents) participating in the SDY Case Registry have proprietary rights over the data they enter in the Registry; however, under a specific agreement, data from individual states is combined into a single de-identified dataset. The SDY Case Registry’s Data Coordinating Center at the Michigan Public Health Institute will facilitate the initiation of data use agreements between investigators and state public health agencies to access the dataset.

The SDY Case Registry’s Data Coordinating Center (DCC) is at the Michigan Public Health Institute. The DCC provides administrative support to the SDY Case Registry, creates case report forms for phenotypic data, develops consent forms for participation in the Registry, maintains the SDY database, and subcontracts to a biorepository at the University of Michigan for DNA/tissue extraction and storage of samples. The DCC works closely with research teams to establish data use agreements with the SDY Case Registry data collection sites (state public health agencies or their bona fide agents) for access to phenotypic data and DNA/tissue samples for study. The DCC does not provide statistical support or conduct data analysis for each funded research project. Rather, they facilitate access to the data and act as liaisons between investigators and the jurisdictions that collect the data.

Selected Research Examples for this NOSI

Research questions and topics of interest include, but are not limited to the following:

  • What is the role of ion channel mutations in SDY, SCDY, and/or SUDEP?
  • Investigate novel genetic mechanisms underlying SDY using sequencing and functional analyses.
  • What is the frequency with which pathogenic variants in genes associated with congenital arrhythmia susceptibility and cardiomyopathy are inherited from a parent rather than arising de novo?
  • What is the prevalence of cardiac disease in relatives of a SDY victim?
  • Identify and validate genetic variants that might be used for future newborn screening efforts for Long QT syndrome.
  • Is competitive athletics a risk factor for SCDY?
  • What is the role of sleep/sleep apnea in SDY and/or SUDEP?
  • How is ventilatory control affected in sudden unexpected infant deaths (SUID) relative to other causes of SDY?
  • What role do diurnal factors play in SCDY and/or SUDEP?
  • How do ion channel mutations differ between SUID cases and cases of SDY in older children?
  • Are there access to care and/or health equity issues that may have contributed to an increased risk of SDY?
  • Are there significant environmental or contextual differences between cases and controls, such as socioeconomic status, history of drug exposure, serum toxicology screens, family history, and other factors?
  • Is postmortem genetic testing in autopsy-negative cases of SDY useful? How many tests result in a genetic finding?
  • Can machine learning or complex genetic models be used to identify novel SDY risk genes?
  • Are infections contributing to SDY and/or SUDEP?

Applications that seek to determine the incidence of SDY are outside the scope of this NOSI and will not be considered under this NOSI.

Application and Submission Information

This notice applies to due dates on or after October 5, 2023, and subsequent receipt dates through January 6, 2028.

Submit applications for this initiative using the following funding opportunity announcements (FOAs) or any reissues of this announcement through the expiration date of this notice.

  • PA-20-185 NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)

All instructions in the SF424 (R&R) Application Guide and the funding opportunity announcement used for submission must be followed.

For funding consideration, applicants must include NOT-HL-22-040 (without quotation marks) in the Agency Routing Identifier field (box 4B) of the SF424 R&R form. Applications without this information in box 4B will not be considered for this initiative.

Investigators planning to submit an application in response to this NOSI are strongly encouraged to contact and discuss their proposed research/aims with Program staff/Scientific Contacts listed on this NOSI well in advance of the application receipt date to better determine appropriateness and interest of the relevant Institute.

NINDS, as part of NIH, strives for rigor and transparency in all research it funds. For this reason, NINDS explicitly emphasizes the NIH application instructions related to rigor and transparency ( and provides additional guidance to the scientific community ( For example, the biological rationale for the proposed experiments must be based on rigorous and robust supporting data, which means that data should be collected via methods that minimize the risk of bias and be reported in a transparent manner. If previously published or preliminary studies do not meet these standards, applicants should address how the current study design addresses the deficiencies in rigor and transparency. Proposed experiments should likewise be designed in a manner that minimizes the risk of bias and ensures validity of experimental results.

Applications nonresponsive to terms of this NOSI will not be considered for the NOSI initiative.


Please direct all inquiries to the contacts in Section VII of the listed funding opportunity announcements with the following additions/substitutions:

Scientific/Research Contact(s)

Kristin M. Burns, MD
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-594-6859

Vicky Whittemore, PhD
National ?Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 240-274-6696

Peer Review Contact(s)

Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).

Financial/Grants Management Contact(s)

Leslye Fulwider
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-480-9544

Chief Grants Management Officer
National Institute of Neurological Disorders and Stroke (NINDS)