Transforming growth factor-alpha (TGF-alpha) and TGF-beta 1 are major anti-inflammatory cytokines and substantially contribute to normal pregnancy outcome. TGF-a stimulates placental mitosis, whereas TGF-beta 1 is a critical regulator of trophoblast invasion and fetal growth. We aimed to study cord blood TGF-a and TGF-beta 1 concentrations in intrauterine-growth-restricted (IUGR, usually associated with abnormal trophoblast invasion, uteroplacental vascular insufficiency and enhanced inflammation) and appropriatefor-gestational-age-(AGA) pregnancies, and investigate possible correlations of the above concentrations with several demographic parameters of infants at birth. Plasma TGF-a and TGF-beta 1 concentrations were determined by ELISA in 154 mixed arterio-venous cord blood samples from IUGR (n = 50) and AGA (n = 104) singleton full-term infants. After controlling for possible confounding factors (gender, birth-weight, gestational age, maternal age and parity), cord blood TGF-a and TGF-beta 1 concentrations were significantly higher in IUGR than AGA group (b = 0.402, SE = 0.179, p = 0.027 and b = 0.152, SE = 0.061, p = 0.014, respectively). Delivery mode had an effect on cord blood TGF-a and TGF-beta 1 concentrations, both being elevated in cases of vaginal delivery (b = -0.282, SE = 0.117, p = 0.018 and b = -0.123, SE = 0.059, p = 0.038, respectively). In conclusion, higher cord blood TGF-alpha and TGF-beta 1 concentrations may represent a compensatory response to the inflammatory process characterizing the IUGR state. Additionally, higher cord blood TGF-beta 1 concentrations in IUGRs could be attributed to increased shear stress, resulting from abnormal blood flow in IUGR fetal blood vessels. Finally, vaginal delivery-associated cytokine release may account for elevated TGF-alpha and TGF-beta 1 concentrations. (C) 2012 Elsevier Ltd. All rights reserved.