Cord blood netrin-1 and -4 concentrations in term pregnancies with normal, restricted and increased fetal growth

OBJECTIVE: To determine levels of the possible angioregulatory molecules netrin-1 and -4, in intrauterine-growth-restricted (IUGR), large for gestational age (LGA) (both groups characterized by altered angiogenic mechanisms) and appropriate-for-gestational-age (AGA) pregnancies. METHODS: Cord blood (UC) netrin-1 and -4 concentrations were measured in 30 IUGR, 30 LGA and 20 AGA infants and their mothers (MS). RESULTS: Netrin-1 and -4 concentrations did not differ in all groups. UC netrin-4 increased with gestational age (b = 0.075, 95% CI 0.029-0.121, p = 0.002). In the IUGR group, MS netrin-4 decreased as birth-weight centiles increased [b = -0.058, 95% CI -0.112 to -0.004, p = 0.036]. In the LGA group, MS netrin-1 decreased with advanced gestational age [b = -0.063, 95% CI -0.105 to -0.022, p = 0.004]. In all cases, MS netrin-1 positively correlated with MS netrin-4 (r = 0.299, p = 0.007), while UC netrin-1 negatively correlated with UC netrin-4 (r = -0.239, p = 0.033). CONCLUSIONS: Increased UC netrin-4 levels with advancing gestational age may reflect its effect on fetal development. Decreased maternal netrin-1 levels in the LGA group possibly represent a negative feedback mechanism against increased angiogenesis. Increased maternal netrin-4 levels in IUGR neonates may reflect in utero hypoxia, while the negative correlations between fetal netrin-1 and -4 levels may exert the dynamic balance between their angio- and anti-angiogenic properties.