Premature birth, or the delivery of an infant before 37 weeks gestation, is the result of preterm labor and it affects approximately 10% of pregnancies world-wide with growing numbers now at 12% in the United States. In spite of advances in technology, prematurity results in substantial morbidity and mortality as high as 80% in infants born earlier than 33 weeks gestation in developing countries. Surviving infants have high rates of cognitive delay, cerebral palsy, chronic lung disease, blindness and deafness. The enormity of this problem, which disproportionately affects the poor and minority groups, is devastating in its impact on individuals, families, and society and compels investigations into etiologies that may lead to improvements in treatment and prevention. While some specific causes of prematurity are recognized, such as twin pregnancies and cervical incompetence, the majority are """"""""spontaneous"""""""". Potential initiators include infection, poor nutrition, and inherited factors. Twin and family studies suggest that genetic factors underlie 40% of this risk and the single best predictor for preterm delivery is a previous preterm birth. While there are many approaches to identifying causal mechanisms in complex traits such as prematurity, genetic investigations afford the opportunity to not only validate previously suspected etiologies but to identify unanticipated factors. ? ? A major challenge in studying genetic factors in prematurity is that the risk case is not explicitly defined as it might be either the mother and her uterus, the infant/placental unit, or the two together. We have assembled a team of investigators including obstetricians, pediatricians, quantitative geneticists, and molecular biologists to undertake a comprehensive approach to identify genetic causes of prematurity. We will use a family collection scheme in which either the infant or the mother can be studied as a potential case and a powerful three generation collection approach coupled to genome-wide searches to identify some of the multiple genes likely contributing to prematurity and its secondary outcomes. Our group has worked together for many years and will use our extensive experience in clinical ascertainment, molecular genetics and statistical approaches for gene identification.
Specific aims i nclude: I. Case identification and characterization. II. Candidate gene evaluation. III. Genome-wide scans using both linkage and linkage disequilibrium. IV. Fine-mapping for gene identification. The outcome will be confirmation (or rejection) of previously suspected factors, identification of new genetic contributions, and the establishment of a platform that will enable us to move quickly into studies of environmental covariates, biological mechanisms and clinical trials for prevention and treatment. ? ? ?

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD052953-02
Application #
7277299
Study Section
Genetics of Health and Disease Study Section (GHD)
Program Officer
Ilekis, John V
Project Start
2006-08-15
Project End
2011-05-31
Budget Start
2007-06-01
Budget End
2008-05-31
Support Year
2
Fiscal Year
2007
Total Cost
$572,474
Indirect Cost
Name
University of Iowa
Department
Pediatrics
Type
Schools of Medicine
DUNS #
062761671
City
Iowa City
State
IA
Country
United States
Zip Code
52242
Bandoli, Gretchen; Jelliffe-Pawlowski, Laura L; Feuer, Sky K et al. (2018) Second trimester serum cortisol and preterm birth: an analysis by timing and subtype. J Perinatol 38:973-981
Jelliffe-Pawlowski, Laura L; Rand, Larry; Bedell, Bruce et al. (2018) Prediction of preterm birth with and without preeclampsia using mid-pregnancy immune and growth-related molecular factors and maternal characteristics. J Perinatol 38:963-972
Smith, Caitlin J; Ryckman, Kelli K; Bahr, Timothy M et al. (2017) Polymorphisms in CYP2C9 are associated with response to indomethacin among neonates with patent ductus arteriosus. Pediatr Res 82:776-780
Gimenez, Lucas G; Momany, Allison M; Poletta, Fernando A et al. (2017) Association of candidate gene polymorphisms with clinical subtypes of preterm birth in a Latin American population. Pediatr Res 82:554-559
Patel, Priti M; Momany, Allison M; Schaa, Kendra L et al. (2016) Genetic Modifiers of Patent Ductus Arteriosus in Term Infants. J Pediatr 176:57-61.e1
Wallenstein, Matthew B; Jelliffe-Pawlowski, Laura L; Yang, Wei et al. (2016) Inflammatory biomarkers and spontaneous preterm birth among obese women. J Matern Fetal Neonatal Med 29:3317-22
Gimenez, Lucas G; Krupitzki, Hugo B; Momany, Allison M et al. (2016) Maternal and neonatal epidemiological features in clinical subtypes of preterm birth. J Matern Fetal Neonatal Med 29:3153-61
Sampath, Venkatesh; Helbling, Daniel; Menden, Heather et al. (2016) Necrotizing Enterocolitis Is Not Associated With Sequence Variants in Antioxidant Response Genes in Premature Infants. J Pediatr Gastroenterol Nutr 62:420-3
Fuller, Tyson D; Spracklen, Cassandra N; Ryckman, Kelli K et al. (2015) Genetic variation in CYB5R3 is associated with methemoglobin levels in preterm infants receiving nitric oxide therapy. Pediatr Res 77:472-6
Pitlick, M M; Orr, K; Momany, A M et al. (2015) Determining the prevalence of cytomegalovirus infection in a cohort of preterm infants. J Neonatal Perinatal Med 8:427

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