The research mission of Robert's Program is to determine the causes and pathogenesis of sudden unexpected death in pediatrics (SUDP) utilizing interdisciplinary and state-of-the-art approaches. We do not consider every death as due to the same cause, nor do we think that detailing risk factors is the same as explaining a cause. Our work seeks to uncover the medical, genetic, and environmental factors that may contribute to these tragic losses in infants and young children with medically verified evidence for the cause. By combining clinical investigation, advanced technology, and collaboration across medical disciplines, we aim to find answers where few currently exist. Our focus is especially upon the first three years of life when the risk of sudden unexpected death is the greatest, although children who have died under the age of 18 are also eligible to enroll. Our research not only brings the most advanced methods to exploring what happened but also supports grieving families in their search for understanding while contributing to broader efforts to prevent future deaths.
Kinney HC, Thach BT. The sudden infant death syndrome. N Engl J Med. 2009 Aug 20;361(8):795-805. PubMed PMID:
This is the best example of the understanding of sudden infant death syndrome (SIDS) as we began Robert’s Program, with clear descriptions of important discoveries about what happens in SIDS and why, written by two giants in the field. This exceptional review was written before research in genetics and neuropathological markers introduced many of the core hypotheses that underly our current efforts.
Goldstein RD, Nields HM, Kinney HC. A New Approach to the Investigation of Sudden Unexpected Death in Pediatrics, Pediatrics, 2017; Jul 5. pii: e20170024. doi: 10.1542/peds.2017-0024.
This manuscript announces Robert’s Program to the field of pediatrics. We present the medical model of our assessment program and the process of reaching conclusions, highlighting the initial cases. SUDP is presented as the potential consequence of a number of extreme phenotypes of undiagnosed or potentially undiscovered diseases. Pilot data was used to show plausible hypotheses for contributing vulnerabilities as well as overt pathologic findings in metabolic, cardiac, infectious, and neurological diseases. Pathogenic variants in genes of interest are reported using American College of Medical Genetics guidelines.
Kinney HC, Cryan JB, Haynes RL, Paterson DS, Haas EA, Mena OJ, Minter M, Journey KW, Trachtenberg FL, Goldstein RD, Armstrong DD. Dentate gyrus abnormalities in sudden unexplained death in infants: morphological marker of underlying brain vulnerability. Acta neuropathologica. 2015 Jan 1; 129(1): 65-80. PubMed PMID: 25421424; PubMed Central PMCID: PMC4282685.
This study brought SIDS into the current era by showing that specific types of brain abnormalities in the hippocampus might be linked to sudden unexplained deaths in infants, including cases of SIDS. While most research had focused on the brainstem — the part of the brain that controls breathing and other vital functions — this research examined the hippocampus, another brain region that helps regulate breathing and heart rate through its connections to the brainstem. This research found that a particular abnormality in the hippocampus, known as focal granule cell bilamination, appeared in about 41% of unexplained cases but only 8% of explained cases and often occurred alongside other signs of disrupted brain development. Since these findings have also been described in epilepsy patients, it opened up new thinking about the relationship of seizures to sudden infant deaths.
Hefti, M.M., Cryan, J.B., Haas, E.A. et al. Hippocampal malformation associated with sudden death in early childhood: a neuropathologic study. Forensic Sci Med Pathol 12, 14–25 (2016). doi: 10.1007/s12024-015-9731-3.
This study highlights the role of the hippocampus in sudden unexplained death in children (SUDC) aged 1-6. Previous research had linked febrile seizures to sudden death, but the specific brain changes involved were not well understood. Through close examination of the hippocampal pathology of 42 cases, the researchers identified a pattern of hippocampal maldevelopment, now called “hippocampal maldevelopment associated with sudden death” (HMASD), which appears to increase vulnerability to sudden death in some children. In addition to characterizing HMASD, researchers sought to identify potential new entities responsible for sudden, unexplained death in young children without HMASD/febrile seizure phenotypes. These findings provide important insights into the neuropathology of unexplained childhood deaths and may help guide future research and risk evaluation.
Kinney HC, Poduri A, Cryan JB, Haynes RL, Teot L, Sleeper LA, Holm IA, Berry GT, Prabhu S, Warfield SK, Brownstein C, Abram HS, Kruger M, Kemp WL, Hargutai B, Garstang J, Mena OJ, Haas EA, Dastjerdi R, Armstrong DD, Goldstein RD. Hippocampal Formation Maldevelopment and Sudden Unexpected Death Across the Pediatric Age Spectrum. J Neuropathol Exp Neurol, 2016; 75 (10): 981-997. Doi: 10.1093/jnen/nlw075.
While sudden infant death syndrome (SIDS) and sudden unexplained death in childhood (SUDC) are distinguished from each other by age criteria, our separate studies of SIDS and SUDC provided evidence of shared hippocampal abnormalities, specifically focal dentate bilamination, a lesion classically associated with temporal lobe epilepsy. This research found anomalies in the dentate gyrus across the age spectrum, arguing for a common pathological vulnerability that defies the one-year age cutoff between SIDS and SUDC.
Koh, H. Y., Haghighi, A., Keywan, C., Alexandrescu, S., Plews-Ogan, E., Haas, E. A., ... & Goldstein, R. D. (2022). Genetic determinants of sudden unexpected death in pediatrics. Genetics in Medicine, 24(4), 839-850.
This study explored how genetic factors may contribute to sudden unexpected death in children. About one in nine children dying from SIDS and SUDC carried genetic changes that likely played a role in their death. Some of these changes were in well-known genes linked to heart or brain conditions, while others were in genes not previously connected to sudden death. Overall, the study provides strong evidence that genetics can play a significant role in sudden unexpected deaths in children and points to both known and newly identified genes as important areas for future research.
Goldstein RD, Lederman RI, Lichtenthal WG, Morris SE, Human M, Elliott AJ, Tobacco D, Angal J, Odendaal H, Kinney HC, Prigerson HG. The Grief of Mothers After the Sudden Unexpected Death of Their Infants. Pediatrics. 2018 May 1; 141(5). PubMed PMID: 29712764; PubMed Central PMCID: PMC6173829.
This research describes the characteristics and severity of grief in mothers after SIDS. This study involved more than 400 mothers in the two to 48 months following the death of their infant. The prevalence of prolonged grief disorder in the mothers was six times greater than reference populations and remained very persistent. Role confusion and anger were shown to be prevalent features of their grief. The severity of symptoms was the same whether the mothers were rich or poor, and wherever they lived.
Wojcik M, Poduri A, Holm I, MacRae CA, Goldstein RD. The fundamental need for unifying phenotypes in sudden unexpected pediatric deaths. Frontiers in Medicine. Lausanne (Switzerland). 2023 Jun 2; 10. doi: 10.3389/fmed.2023.1166188.
This paper examines why many sudden and unexpected deaths in infants and children remain unexplained despite decades of research. It highlights that age-based distinctions may obscure shared biological features between infant and childhood deaths, leaving potential commonalities largely understudied. The research introduces a unified “phenotyping” strategy for sudden unexpected pediatric deaths, integrating brain, heart, and metabolic findings with genetic, environmental, and family data to better understand each case. This framework treats these deaths as potentially undiagnosed medical conditions, opening new opportunities for discovery and providing answers and support to families affected by the heartbreaking tragedy of SUDP.
Kristensen P, Dyregrov A, Rognum TO, Goldstein RD. Bereaved parents’ perceptions of the doll reenactment after sudden unexpected infant deaths. Pediatrics. 2025 Jan; 155(1): e2024066731. doi: 10.1542/peds.2024-066731.
McCarthy SR, Goldstein RD. If the Unthinkable Happens: Families After SUID. In: Moon, Rachel Y., editor(s). Infant Safe Sleep, 2nd edition. Cham (Switzerland): Springer Nature Switzerland AG. 2025. Available from: https://link.springer.com/book/10.1007/978-3-031-84294-8
Plews-Ogan E, Keywan C, Morris SE, Goldstein RD. The parental role before and after SIDS. Death studies. 2022 Jan 1; 46(10): 2316-2326. PMID: 34101544. doi: 10.1080/07481187.2021.1936296.
Goldstein RD, Petty CR, Morris SE, Human M, Odendaal H, Elliott AJ, Tobacco D, Angal J, Brink L, Prigerson HG. Transitional objects of grief. Comprehensive psychiatry. 2020 Jan 11; 98: 152161. PMID: 31978784. doi: 10.1016/j.comppsych.2020.152161.
Morris S, Fletcher K, Goldstein RD. The Grief of Parents After the Death of a Young Child. Journal of clinical psychology in medical settings. 2018 Nov 28. PubMed PMID: 30488260. doi: 10.1007/s10880-018-9590-7.
Goldstein RD, Petty CR, Morris SE, Human M, Odendaal H, Elliott A, Tobacco D, Angal J, Brink L, Kinney HC, Prigerson HG. Pre-loss personal factors and prolonged grief disorder in bereaved mothers. Psychological medicine. 2018 Nov 9: 1-9. PubMed PMID: 30409237. doi: 10.1017/S0033291718003264.
Goldstein RD, Lederman RI, Lichtenthal WG, Morris SE, Human M, Elliott AJ, Tobacco D, Angal J, Odendaal H, Kinney HC, Prigerson HG. The Grief of Mothers After the Sudden Unexpected Death of Their Infants. Pediatrics. 2018 May 1; 141(5). PubMed PMID: 29712764; PubMed Central PMCID: PMC6173829. doi: 10.1542/peds.2017-3651.
Goldstein RD. What Conversations Do Bereaved Parents Remember? J Palliat Care Med. 2015 Jan; 5(1): 4. doi: 10.4172/2165-7386.1000I202
Quinones-Perez B, Collura CD, Sandholm A, Gray K, Goldstein RD. Sudden unexpected infant death rates, risk factors, and generational effects in Hispanic infants. JAMA Network Open. 2025 Jun. PMID: 40522659; PMCID: PMC12171938. doi: 10.1001/jamanetworkopen.2025.15986.
Martin B, Vargas SO, Hindman HB, Rothstein A, Folberg R, Goldstein RD. Sudden Death in a Child With Ocular Lesions. JAMA Ophthalmology. 2024 Apr 1; 142(4): 388-389. PMID: 38451535. doi: 10.1001/jamaophthalmol.2024.0089.
Ramachandran PS, Okaty BW, Riehs M, Wapniarski A, Hershey D, Harb H, Zia M, Haas EA, Alexandrescu S, Sleeper LA, Vargas SO, Gorman MP, Campman S, Mena OJ, Levert K, Hyland K, Goldstein RD, Wilson MR, Haynes RL. Multiomic Analysis of Neuroinflammation and Occult Infection in Sudden Infant Death Syndrome. JAMA neurology. 2024 Mar 1; 81(3): 240-247. PMID: 38285456; PMCID: PMC10825787. doi: 10.1001/jamaneurol.2023.5387.
Goldstein RD, Poduri A. Seizures and Sudden Death Beyond SUDEP. Neurology. 2024 Feb 13; 102(3): e208119. PMID: 38175993. doi: 10.1212/WNL.0000000000208119.
Wojcik M, Poduri A, Holm I, MacRae CA, Goldstein RD. The fundamental need for unifying phenotypes in sudden unexpected pediatric deaths. Frontiers in Medicine. Lausanne (Switzerland). 2023 Jun 2; 10. doi: 10.3389/fmed.2023.1166188.
Wojcik M, Henry KF, Goldstein RD. Sudden Unexplained Death in Childhood: Current Understanding. Pediatric Emergency Care. 2023 Dec 1;39(12):979-983. PMID: 38019718. doi: 10.1097/PEC.0000000000003074.
Goldstein RD, Kinney HC, Guttmacher A. Only Halfway There with Sudden Infant Death Syndrome. New England Journal of Medicine. 2022 May 14; 386(20): 1873-1875. PMID: 35551514. doi: 10.1056/NEJMp2119221.
Keywan C, Poduri A, Goldstein RD, Holm I. Genetic factors underlying sudden infant death syndrome. Application of Clinical Genetics. 2021 Feb 14. PMCID: PMC7894824 PMID: 33623412. doi: 10.2147/TACG.S239478.
Goldstein RD. Sudden Unexplained Infant Deaths and Day of Life 0. Pediatrics. 2020;145(1):e20193212. PMCID: 31818864. doi: 10.1542/peds.2019-3212
Anderson TM, Lavista Ferres JM, Ren SY, Moon RY, Goldstein RD, Ramirez JM, Mitchell EA. Maternal Smoking Before and During Pregnancy and the Risk of Sudden Unexpected Infant Death. Pediatrics. 2019 Apr 1; 143(4). PubMed PMID: 30858347; PMCID: PMC6564075. doi: 10.1542/peds.2018-3325.
Rochtus AM, Trowbridge S, Goldstein RD, Sheidley BR, Prabhu SP, Haynes R, Kinney HC, Poduri A. Mutations in NRXN1 and NRXN2 in a patient with early-onset epileptic encephalopathy and respiratory depression. Cold Spring Harbor Molecular Case Studies. Forthcoming 2019; 5(1). PubMed PMID: 30709877; PMCID: PMC6371743. doi: 10.1101/mcs.a003442.
Brownstein C, Poduri A, Goldstein RD, Holm I. The Genetics of Sudden Infant Death Syndrome. In: JR Duncan and RW Byard (editors). SIDS, Sudden Infant and Early Childhood Death: The Past, the Present and the Future. University of Adelaide Press. 2018. Available from: https://www.ncbi.nlm.nih.gov/books/NBK513378/.
Brownstein C, Goldstein RD, Thompson CH, Haynes RL, Giles E, Sheidley B, Bainbridge M, Haas EA, Mena OJ, Lucas J, Schaber B, Holm I, George AL, Kinney HC, Poduri A. SCN1A variants associated with sudden infant death syndrome. Epilepsia. 2018 Apr 1; 59(4): e56-e62. PubMed PMID: 29601086. doi: 10.1111/epi.14055.
Goldstein RD, Kinney HC. Race, Ethnicity, and SIDS. Pediatrics. 2017 Jun 1; 139(6). PubMed PMID: 28562296. doi: 10.1542/peds.2017-0898.
Kinney HC, Poduri AH, Cryan JB, Haynes RL, Teot L, et al. Hippocampal Formation Maldevelopment and Sudden Unexpected Death across the Pediatric Age Spectrum. J Neuropathol Exp Neurol. 2016 Oct;75(10):981-997. PubMed PMID: 27612489. doi: 10.1093/jnen/nlw075.
Hefti MM, Kinney HC, Cryan JB, Haas EA, Chadwick AE, et al. Sudden unexpected death in early childhood: general observations in a series of 151 cases. Forensic Sci Med Pathol. 2016 Mar;12(1):4-13. PubMed PMID: 26782961; PMCID: PMC4752958. doi: 10.1007/s12024-015-9724-2.
Goldstein RD, Kinney HC, Willinger M. Sudden Unexpected Death in Fetal Life Through Early Childhood. Pediatrics. 2016 Jun 1; 137(6). PubMed PMID: 27230764; PMCID: PMC4894250. doi: 10.1542/peds.2015-4661.
Goldstein RD, Trachtenberg FL, Sens MA, Harty BJ, Kinney HC. Overall Postneonatal Mortality and Rates of SIDS. Pediatrics. 2016 Jan;137(1). PubMed PMID: 26634772. doi: 10.1542/peds.2015-2298.
Kinney HC, McDonald AG, Minter ME, Berry G, Poduri A, Goldstein RD. Witnessed sleep-related seizure and sudden unexpected death in infancy: a case report. Forensic science, medicine, and pathology. 2013 Sep 1; 9(3): 418-21. PubMed PMID: 23852931; PMCID: PMC3897270. doi: 10.1007/s12024-013-9448-0.
Holm IA, Poduri A, Crandall L, Haas E, Grafe MR, et al. Inheritance of febrile seizures in sudden unexplained death in toddlers. Pediatr Neurol. 2012 Apr;46(4):235-9. PubMed PMID: 22490769; NIHMSID: NIHMS567758; PMCID: PMC4009678. doi:10.1016/j.pediatrneurol.2012.02.007.
Duncan JR, Paterson DS, Hoffman JM, Mokler DJ, Borenstein NS, et al. Brainstem serotonergic deficiency in sudden infant death syndrome. JAMA. 2010 Feb 3;303(5):430-7. PubMed PMID: 20124538. doi: 10.1001/jama.2010.45.
Filiano JJ, Kinney HC. A perspective on neuropathologic findings in victims of the sudden infant death syndrome: the triple-risk model. Biol Neonate. 1994;65(3-4):194-7. PubMed PMID: 8038282. doi: 10.1159/000244052.
