Project Details

The genetic basis of neonatal disease

Thomas Hays, MD, PhD

Summary

BACKGROUND: Preterm infants suffer a great burden of death and severe illness, the causes of which are not fully known. Genetic disorders likely contribute to this burden, but this has not been investigated in a prospective, systematic manner. GAP: The contribution of genetic disorders to death and severe illness in preterm infants is unknown. HYPOTHESIS: Preterm infants have a disproportionate burden of genetic disorders, and affected infants will have novel, unappreciated manifestations. Infants with genetic disorders will be more likely to die or experience severe illness. METHODS: Preterm infants born weighing less than 1500 g will be recruited for genome-wide sequencing, and the detection of genetic disorders. Logistic regression will be performed to detect associations between genetic disorders and death or severe illnesses, controlling for known risk factors such as birth weight, gestational age, major malformations, sex, and maternal and environmental factors. RESULTS: Pending IMPACT: The results of this study, whether positive or negative, will provide crucial insight into the prevalence of genetic disorders in preterm infants, and how these disorders lead to death and illness, and will thus immediately allow neonatologist to prioritize who should get costly genetic testing. The results will also provide crucial risk prognostication to families and care providers, and help teams anticipate and prevent severe illness in preterm infants. If you wish to learn more about this project, or about precision newborn medicine, please email Thomas Hays, MD, PhD at th2712@cumc.columbia.edu.

Publications:

Hays T, Thompson MV, Bateman DA, Sahni R, Tolia VN, Clark RH, Gharavi AG. The prevalence and clinical significance of congenital anomalies of the kidney and urinary tract in preterm infants. JAMA Network Open. 2022 e2231626; PubMed PMID: 36103177. (https://pubmed.ncbi.nlm.nih.gov/36103177).

Leow EH, et al. Congenital anomalies of the kidney and urinary tract (CAKUT) in critically ill infants: a multicenter cohort study. Pediatr Nephrol. 2023;38(1):161-72. Epub 20220425. doi: 10.1007/s00467- 022-05542-0. PubMed PMID: 35467155. (https://pubmed.ncbi.nlm.nih.gov/35467155/).

Hays T, Wapner RJ. Genetic testing for unexplained perinatal disorders. Curr Opin Pediatr. 2021 Apr 1;33(2):195-202. PubMed Central PMCID: PMC8221376; PubMed PMID: 33605625. (https://pubmed.ncbi.nlm.nih.gov/33605625/)

Hays T, Hernan R, Disco M, Griffin E, Goldshtrom N, Vargas D, Krishnamurthy G, Rehman AU, Wilson AT, Guha S, Phadke S, Okur V, Robinson D, Felice V, Abhyankar A, Jobanputra V, Chung WK. Implementation of Rapid Genome Sequencing for Infants with Congenital Heart Disease. medRxiv. 2022:2022.12.16.22283479. (https://www.medrxiv.org/content/10.1101/2022.12.16.22283479v1

Hays T, The genetic basis of congenital kidney anomalies. In Neonatology Questions and Controversies, Fourth Ed. Edited by Richard Polin. [Accepted and in press].

Ahram DF, et al. Rare single nucleotide and copy number variants and the etiology of congenital obstructive uropathy: implications for genetic diagnosis. JASN. 2023. [Accepted and in press].

Hays T, Groopman EE, Gharavi AG. Genetic testing for kidney disease of unknown etiology. Kidney Int. 2020 Sep;98(3):590-600. PubMed Central PMCID: PMC7784921; PubMed PMID: 32739203. (https://pubmed.ncbi.nlm.nih.gov/32739203/).

Zhao E, Bomback M, Khan A, et al. The expanded spectrum of human disease associated with GREB1L likely includes complex congenital heart disease. Prenat Diagn. Mar 2024;44(3):343-351. doi:10.1002/pd.6527 PMID 38285371

Bomback M, Everett S, Lyford A, et al. The Contribution of Commonly Diagnosed Genetic Disorders to Small for Gestational Age Birth and Subsequent Morbidity and Mortality in Preterm Infants. medRxiv. 2023:2023.07.14.23292682. doi:10.1101/2023.07.14.23292682 4. Hays T, Hernan R, Disco M, et al. Implementation of Rapid Genome

Selin SE, Miles B, Rakesh S, et al. Prevalence and Clinical Significance of Commonly Diagnosed Genetic Disorders in Preterm Infants. medRxiv. 2023:2023.07.14.23292662. doi:10.1101/2023.07.14.23292662