OBJECTIVE: The purpose of this study was to investigate whether birth of a small-for-gestational-age (SGA) baby (birthweight, 10th percentile) is preceded by altered maternal serum cytokine profiles at early pregnancy, compared with control babies (birthweight, 30-80th percentile). STUDY DESIGN: A retrospective case-control study of maternal serum collected prospectively across 7-10 weeks of gestation from women attending their first prenatal visit (SGA, 57 cases; control subjects, 71 cases selected retrospectively). Serum concentrations of 27 cytokines were measured in each sample and analyzed by 2-way analysis of variance and nonparametric tests. Logistic regression was used for predictive modeling. RESULTS: Of 21 detectable cytokines/chemokines, 14 analytes varied significantly (P ≤ .030) among those women who were destined to deliver an SGA baby, when compared with control subjects. Of the cytokines that varied in association with SGA, interferon-γ concentrations increased, and major proinflammatory (interleukin [IL]-2, -7, -12) and antiinflammatory (IL-1 receptor antagonist, -4, -10, -13) cytokine concentrations decreased. Eotaxin and macrophage inflammatory protein-1α were higher; monocyte chemoattractant protein-1 and IL-8 were lower. CONCLUSION: SGA births may be preceded by altered immune cytokine profiles at 7-10 weeks of gestation.