title: Systematic Review and Meta-analysis: Gene Association Studies in Neonatal Sepsis.
abstract: BackgroundAssociation studies of various gene variants in neonatal sepsis show conflicting results.ObjectiveWe performed a systematic review of candidate gene association studies in neonatal sepsis to provide pooled estimates of risk for selected gene variants.MethodsWe performed a search using MeSH terms "infection," "sepsis," "infant," "genetic variation," "polymorphism," and "genetic association studies." We included studies evaluating associations between neonatal sepsis and genetic variants (2000-2015). We excluded case reports/series, commentaries, narrative reviews, and nonhuman research. We assessed quality of studies using STREGA guidelines. Following estimation of odds ratios (ORs), data were pooled using random effects models.ResultsTwenty eight of 1,404 identified studies were included. Meta-analyses were performed for interleukin (IL)-6, tumor necrosis factor-α (TNF-α), and IL-10 as these gene variants were tested in multiple studies. TNF-α 308GG genotype demonstrated trends toward increased sepsis risk in the primary analysis of culture-proven sepsis (OR 1.18, 95% confidence interval [CI] 0.97-1.44). IL-10 1082GG genotype was associated with lower sepsis odds in very low-birth-weight (VLBW) infants (OR 0.51, 95% CI 0.29-0.91).ConclusionWe uncovered an association between IL-10 1082 gene variation and sepsis in VLBW infants but did not identify associations between neonatal sepsis and TNF-α 308 or IL-6 gene variation. Larger cohort replication studies are required to validate these findings.
authors.affiliation: Division of Neonatology, Department of Pediatrics, The Children's Hospital of Philadelphia and Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Srinivasan
authors.affiliation: Division of Neonatology, Department of Pediatrics, The Children's Hospital of Philadelphia and Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Swarr
authors.affiliation: Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Megha
authors.initials: M
authors.lastname: Sharma
authors.affiliation: Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina.
authors.forename: C Michael
authors.initials: CM
authors.lastname: Cotten
authors.affiliation: Division of Neonatology, Department of Pediatrics, The Children's Hospital of Philadelphia and Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Haresh
authors.initials: H
authors.lastname: Kirpalani
mesh_terms: D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007231:Infant, Newborn; D019102:Infant, Very Low Birth Weight; D016753:Interleukin-10 / Q000235:genetics*; D015850:Interleukin-6 / Q000235:genetics*; D000071074:Neonatal Sepsis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: C508609:IL10 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10