Lack of progress in lowering rates of preterm delivery (PTD) in the U.S. has stimulated investigations into potential explanatory factors that are outside the current realm of prenatal care. These include factors at the micro' level, such as genes, and factors that are 'upstream' such as acute/chronic stress and social class gradient which has consistently been shown to be related to PTD. There are a growing number of studies focusing on immune system-related genes and PTD because of strong evidence that some pathways to PTD have an infection and/or inflammation component. However, most of these studies have lacked information on other relevant biomarkers (e.g.cytokines, bacterial vaginosis), underlying pathologic processes (e.g. chorioamnionitis, placental infarcts, incomplete conversion of spiral arteries), and upstream factors(e.g. maternal stress), making it difficult to contextualize gene polymorphism-PTD findings. The proposed study builds on the NIH funded, multi-ethnic, community-based Pregnancy Outcomes and Community Health (POUCH) Study of women enrolled in mid-pregnancy from 52 clinics in 5 Michigan communities. The POUCH study has data on prenatal maternal social conditions, health behaviors, psychological well-being, medical complications, histopathologic abnormalities of placenta/fetal membranes, vascular-related DNA polymorphisms, and mid-pregnancy biomarkers (e.g. maternal cortisol, plasma CRH, serum and vaginal fluid cytokines). In this CDC-funded """"""""add on"""""""" to the POUCH study we have expanded our research team to include preeminent researchers in the area of PTD-related gene polymorphisms. We have selected nine immune system-related gene polymorphisms (TLR-4, CD14, MBL. IL-lra, TNFR2, MMP-9, Fas, TNFa and IL-1/3) that will be evaluated in 1,363 POUCH case-cohort mothers (311 preterm; 1,052 term), and 818 case-cohort offspring. Gene polymorphisms, as main effects and as modifiers of other relevant risk factors (e.g. bacterial vaginosis, stress), will be assessed in relation to PTD overall and PTD-subtypes (e.g., < 35 weeks' gestation, spontaneous labor intact membranes, PROM, histopathologic evidence of chorioamnionitis). This study of gene polymorphisms, situated within the rich database of the POUCH study, offers : 1) a chance to learn more about underlying processes leading to PTD that may involve maternal and/or fetal gene polymorphisms and gene-environment interactions: and 2) a chance to determine if maternal gene polymorphisms are useful, along with other biomarkers, as predictive factors that could guide selective enrollment into clinical trials with interventions targeted at specific underlying processes.

Agency
National Institute of Health (NIH)
Institute
National Center for Chronic Disease Prev and Health Promo (NCCDPHP)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01DP000143-03
Application #
7228228
Study Section
Special Emphasis Panel (ZDP1-AJS (02))
Program Officer
Patterson, Beth
Project Start
2005-06-01
Project End
2010-05-31
Budget Start
2007-06-01
Budget End
2008-05-31
Support Year
3
Fiscal Year
2007
Total Cost
$501,075
Indirect Cost
Name
Michigan State University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
193247145
City
East Lansing
State
MI
Country
United States
Zip Code
48824
Culverhouse, R C; Saccone, N L; Horton, A C et al. (2018) Collaborative meta-analysis finds no evidence of a strong interaction between stress and 5-HTTLPR genotype contributing to the development of depression. Mol Psychiatry 23:133-142
Li, Yu; Margerison-Zilko, Claire; Strutz, Kelly L et al. (2018) Life Course Adversity and Prior Miscarriage in a Pregnancy Cohort. Womens Health Issues 28:232-238
Dunietz, G L; Strutz, K L; Holzman, C et al. (2017) Moderately elevated blood pressure during pregnancy and odds of hypertension later in life: the POUCHmoms longitudinal study. BJOG 124:1606-1613
Margerison-Zilko, Claire E; Strutz, Kelly L; Li, Yu et al. (2017) Stressors Across the Life-Course and Preterm Delivery: Evidence From a Pregnancy Cohort. Matern Child Health J 21:648-658
Tian, Yan; Holzman, Claudia; Siega-Riz, Anna M et al. (2016) Maternal Serum 25-Hydroxyvitamin D Concentrations during Pregnancy and Infant Birthweight for Gestational Age: a Three-Cohort Study. Paediatr Perinat Epidemiol 30:124-33
Talge, Nicole M; Allswede, Dana M; Holzman, Claudia (2016) Gestational Age at Term, Delivery Circumstance, and Their Association with Childhood Attention Deficit Hyperactivity Disorder Symptoms. Paediatr Perinat Epidemiol 30:171-80
Slaughter-Acey, Jaime C; Holzman, Claudia; Calloway, Danuelle et al. (2016) Movin' on Up: Socioeconomic Mobility and the Risk of Delivering a Small-for-Gestational Age Infant. Matern Child Health J 20:613-22
Mudd, Lanay M; Holzman, Claudia B; Evans, Rhobert W (2015) Maternal mid-pregnancy lipids and birthweight. Acta Obstet Gynecol Scand 94:852-60
Thombre, Madhavi K; Talge, Nicole M; Holzman, Claudia (2015) Association between pre-pregnancy depression/anxiety symptoms and hypertensive disorders of pregnancy. J Womens Health (Larchmt) 24:228-36
Mudd, Lanay M; Pivarnik, Jim M; Pfeiffer, Karin A et al. (2015) Maternal Physical Activity During Pregnancy, Child Leisure-Time Activity, and Child Weight Status at 3 to 9 Years. J Phys Act Health 12:506-14

Showing the most recent 10 out of 33 publications