The aim of this study was to investigate possible alterations in circulating concentrations of surfactant protein D (SP-D)-an important component of the innate immune system that is upregulated in pulmonary diseases-in appropriate for gestational age (AGA) and intrauterine growth-restricted (IUGR) pregnancies, because the latter are characterized by structural lung immaturity, impaired immunocompetence, and increased risk of respiratory infections and chronic obstructive lung disease in later life. Serum SP-D concentrations were determined in 40 mothers and their 20 IUGR and 20 AGA full-term fetuses-neonates on postnatal day 1 (N1) and 4 (N4). Fetal SP-D concentrations were higher in the IUGR group (b = 18.16, 95% CI: 6.86-29.47, P = .002) and negatively correlated with infants' customized centiles and gestational age (r = -.326, P = .04, and r = -.446, P = .004, respectively). In both groups, fetal SP-D concentrations were lower than N1 and N4 ones (P <or= .015 in all cases). In the IUGR group, N1 SP-D concentrations were higher in vaginal deliveries (P = .032). Higher SP-D concentrations in IUGR fetuses may reflect structural lung immaturity, leading to increased alveolar-vascular permeability and protein leakage into the circulation. Alternatively, SP-D production may be increased due to intrauterine glucocorticoid exposure, leading to accelerated lung maturation. Surfactant protein D concentrations postnatally increase and are higher in neonates born vaginally, probably as a consequence of lung liquid reabsorption, concomitant with initiation of breathing and delivery stress. A progressive decrease in placental function may result in downregulated SP-D production, accounting for the negative correlation between fetal SP-D concentrations and gestational age.