Identification of preventable causes of preterm delivery, a primary determinant of infant morbidity and mortality, is an important but elusive goal. In order to address promising hypotheses concerning the role of iron, zinc and folate, we will conduct a cohort and nested case-control study of preterm delivery, building upon the ongoing study of Pregnancy, Infection and Nutrition (PIN Study). A food frequency questionnaire and biological markers of nutrient status are being collected between 24 and 29 weeks gestation. In the current funding period, we expect to enroll a cohort of 2,300 women (approximately half Black, half White), with 300 preterm delivery cases and 450 randomly selected controls, which will be expanded to 3,050 in the proposed study for a total of 410 preterm cases and 615 controls. Diet questionnaire data will be used to construct indices of iron, zinc, and folate intake for the three months preceding the survey. Blood samples will be used to construct indices of iron, zinc, and folate intake for the three months preceding the survey. Blood samples will be assayed for transferrin receptor concentrations and serum ferritin concentration as indicators of iron status, and plasma and red cell folate levels, with information on hemoglobin levels and hemocrit obtained from medical records. We plan to conduct an intensive diet validation study of 130 women, evenly divided between Black and White women. These women will be asked to provide three 24-hour recall on randomly selected days in each trimester, and will complete food frequency questionnaires addressing each trimester and one addressing the entire pregnancy period. Other risk factors which may act as confounders for the micronutrients of interest, include genital tract infections, vitamin C, tobacco use, cocaine use, and psychosocial stress. We will analyze the relationship between dietary intake of iron, zinc, and folate, as well as biological markers of iron and folate, in relation to the risk of preterm delivery using logistic regression. We will address subsets of preterm delivery due to preterm labor, preterm PROM, and medical indications, and examine patterns of association among Black and White women. Given the size of the study, the combination of questionnaire data and biological markers of nutrient status, and the careful assessment of potential confounding factors, this study promises to markedly advance our knowledge of the potential role of iron, zinc, and folate in the etiology of preterm delivery.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
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Special Emphasis Panel (ZRG4-HPD (13))
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Spong, Catherine
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University of North Carolina Chapel Hill
Schools of Medicine
Chapel Hill
United States
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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
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