{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Varner MW"],"funding":["National Institute of Neurological Disorders and Stroke","Eunice Kennedy Shriver National Institute of Child Health and Human Development","NICHD NIH HHS","NCRR NIH HHS","Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)"],"pagination":["e2710-e2716"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10948377"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["41(S 01)"],"pubmed_abstract":["<h4>Objective</h4>This study aimed to evaluate whether there are genetic variants associated with adverse neurodevelopmental outcomes in extremely low birth weight (ELBW) infants.<h4>Study design</h4>We conducted a candidate gene association study in two well-defined cohorts of ELBW infants (<1,000 g). One cohort was for discovery and the other for replication. The discovery case-control analysis utilized anonymized DNA samples and evaluated 1,614 single-nucleotide polymorphisms (SNPs) in 145 genes concentrated in inflammation, angiogenesis, brain development, and oxidation pathways. Cases were children who died by age one or who were diagnosed with cerebral palsy (CP) or neurodevelopmental delay (Bayley II mental developmental index [MDI] or psychomotor developmental index [PDI] < 70) by 18 to 22 months. Controls were survivors with normal neurodevelopment. We assessed significant epidemiological variables and SNPs associated with the combined outcome of CP or death, CP, mental delay (MDI < 70) and motor delay (PDI < 70). Multivariable analyses adjusted for gestational age at birth, small for gestational age, sex, antenatal corticosteroids, multiple gestation, racial admixture, and multiple comparisons. SNPs associated with adverse neurodevelopmental outcomes with <i>p</i> < 0.01 were selected for validation in the replication cohort. Successful replication was defined as <i>p</i> < 0.05 in the replication cohort.<h4>Results</h4>Of 1,013 infants analyzed (452 cases, 561 controls) in the discovery cohort, 917 were successfully genotyped for >90% of SNPs and passed quality metrics. After adjusting for covariates, 26 SNPs with <i>p</i> < 0.01 for one or more outcomes were selected for replication cohort validation, which included 362 infants (170 cases and 192 controls). A variant in SERPINE1, which encodes plasminogen activator inhibitor (PAI1), was associated with the combined outcome of CP or death in the discovery analysis (<i>p</i> = 4.1 × 10<sup>-4</sup>) and was significantly associated with CP or death in the replication cohort (adjusted odd ratio: 0.4; 95% confidence interval: 0.2-1.0; <i>p</i> = 0.039).<h4>Conclusion</h4>A genetic variant in SERPINE1, involved in inflammation and coagulation, is associated with CP or death among ELBW infants.<h4>Key points</h4>· Early preterm and ELBW infants have dramatically increased risks of CP and developmental delay.. · A genetic variant in SERPINE1 is associated with CP or death among ELBW infants.. · The SERPINE1 gene encodes the serine protease inhibitor plasminogen activator inhibitor.."],"journal":["American journal of perinatology"],"pubmed_title":["Genetic Predisposition to Adverse Neurodevelopmental Outcome of Extremely Low Birth Weight Infants."],"pmcid":["PMC10948377"],"funding_grant_id":["U10 HD040485","UG1 HD087192","U10 HD027904","U10 HD027905","U10 HD040560","U24 HD036801","U10 HD034122","U10 HD034208","U10 HD027860","M01 RR016587","UG1 HD034216","UG1 HD027851","U10 HD027869","UG1 HD027853","U10 HD021364","U10 HD040689","U10 HD027915","UG1 HD027856","U10 HD027917","U01 HD036790","U10 HD034116","U10 HD027871","UG1 HD040544","UG1 HD040500","UG1 HD040545","U10 HD021373","UG1 HD021364","U10 HD021410","U10 HD040512","UG1 HD027904","U10 HD040461","UG1 HD027869","U01 HD036801","U10 HD036801","UG1 HD034116","U10 HD027880","U10 HD021385","UG1 HD040512","U10 HD040544","U10 HD040500","M01 RR007122","U10 HD040545","UG1 HD027915","UG1 HD040492","U10 HD036790","U10 HD040498","U10 HD040492","M01 RR000080","U01 HD019897","U10 HD034136","U10 HD034216","U10 grants","U10 HD027851","UG1 HD034208","M01 RR008084","UG1 HD040689","U10 HD027856","U10 HD021397","UG1 HD021385","UG1 HD040485","U10 HD027853","UG1 HD027880","M01 RR006022","UG1 HD040560"],"pubmed_authors":["Ramin SM","Dudley DJ","Rouse DJ","Thorp JM","Saade GR","Cotten CM","Sorokin Y","Page GP","Carpenter MW","O'Sullivan MJ","Mercer BM","Peaceman AM","Varner MW","Costantine MM","Thom EA","Caritis SN","Hintz SR","Eunice Kennedy Shriver National Institute of Child Health Human Development Maternal-Fetal Medicine Units Network Neonatal Research Network"],"additional_accession":[]},"is_claimable":false,"name":"Genetic Predisposition to Adverse Neurodevelopmental Outcome of Extremely Low Birth Weight Infants.","description":"<h4>Objective</h4>This study aimed to evaluate whether there are genetic variants associated with adverse neurodevelopmental outcomes in extremely low birth weight (ELBW) infants.<h4>Study design</h4>We conducted a candidate gene association study in two well-defined cohorts of ELBW infants (<1,000 g). One cohort was for discovery and the other for replication. The discovery case-control analysis utilized anonymized DNA samples and evaluated 1,614 single-nucleotide polymorphisms (SNPs) in 145 genes concentrated in inflammation, angiogenesis, brain development, and oxidation pathways. Cases were children who died by age one or who were diagnosed with cerebral palsy (CP) or neurodevelopmental delay (Bayley II mental developmental index [MDI] or psychomotor developmental index [PDI] < 70) by 18 to 22 months. Controls were survivors with normal neurodevelopment. We assessed significant epidemiological variables and SNPs associated with the combined outcome of CP or death, CP, mental delay (MDI < 70) and motor delay (PDI < 70). Multivariable analyses adjusted for gestational age at birth, small for gestational age, sex, antenatal corticosteroids, multiple gestation, racial admixture, and multiple comparisons. SNPs associated with adverse neurodevelopmental outcomes with <i>p</i> < 0.01 were selected for validation in the replication cohort. Successful replication was defined as <i>p</i> < 0.05 in the replication cohort.<h4>Results</h4>Of 1,013 infants analyzed (452 cases, 561 controls) in the discovery cohort, 917 were successfully genotyped for >90% of SNPs and passed quality metrics. After adjusting for covariates, 26 SNPs with <i>p</i> < 0.01 for one or more outcomes were selected for replication cohort validation, which included 362 infants (170 cases and 192 controls). A variant in SERPINE1, which encodes plasminogen activator inhibitor (PAI1), was associated with the combined outcome of CP or death in the discovery analysis (<i>p</i> = 4.1 × 10<sup>-4</sup>) and was significantly associated with CP or death in the replication cohort (adjusted odd ratio: 0.4; 95% confidence interval: 0.2-1.0; <i>p</i> = 0.039).<h4>Conclusion</h4>A genetic variant in SERPINE1, involved in inflammation and coagulation, is associated with CP or death among ELBW infants.<h4>Key points</h4>· Early preterm and ELBW infants have dramatically increased risks of CP and developmental delay.. · A genetic variant in SERPINE1 is associated with CP or death among ELBW infants.. · The SERPINE1 gene encodes the serine protease inhibitor plasminogen activator inhibitor..","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 May","modification":"2026-06-01T10:59:05.946Z","creation":"2026-04-08T11:40:29.818Z"},"accession":"S-EPMC10948377","cross_references":{"pubmed":["37726016"],"doi":["10.1055/s-0043-1774312"]}}