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While elevated levels of proinflammatory cytokines are clearly associated with preterm birth, the relation between cytokines and fetal growth is unclear. The authors examined associations between umbilical cord serum cytokine concentrations and risk of small-for-gestational-age (SGA) and preterm birth. This cross-sectional analysis was nested within a National Institute of Child Health and Human Development-University of Alabama population-based cohort study of high-risk prenatal care patients in Jefferson County, Alabama. Patients were enrolled between 1985 and 1988. For 370 singletons, umbilical cord serum concentrations of interferon gamma (IFN-gamma), tumor necrosis factor alpha, and interleukins 12p70, 4, and 10 were determined. Associations between each cytokine and SGA and preterm delivery were evaluated using log binomial regression. Increasing log concentration of tumor necrosis factor alpha was associated with an increased risk of preterm birth (risk ratio (RR) = 2.00, 95% confidence interval (CI): 1.31, 3.06). IFN-gamma was associated with a decreased risk of SGA birth (RR = 0.78, 95% CI: 0.61, 1.01). After stratification for preterm birth status, the association between IFN-gamma concentration and SGA birth was pronounced among preterm babies (RR = 0.56, 95% CI: 0.31, 1.01). The observations regarding IFN-gamma, which is involved in the activation of adaptive immune responses and regulation of trophoblast function, suggest that IFN-gamma levels at birth may be related to fetal growth restriction.