Insulin concentration correlates negatively with sex hormone-binding globulin (SHBG) in adults, although the age at which this relationship develops is unknown. The present study assesses this relationship in a cohort of European, Maori, South Asian, and Pacific Islands neonates from 125 normal and 35 pregnancies complicated by diabetes. Maternal glycemia was assessed with a 3-h 100-g oral glucose tolerance test with fasting glucose and fructosamine concentrations determined at 36-38 weeks. Umbilical cord blood was taken for insulin, C peptide, fructosamine, SHBG, sex hormone, and insulin-like growth factor I (IGF-I) measurements, and neonatal anthropometry was measured 24 h after delivery. Babies from pregnancies complicated by diabetes were heavier, fatter, hyperinsulinemic (90.4 vs. 130.6 pmol/L, respectively; P < 0.01), with similar SHBG (44.0 +/- 6.5 vs. 44.2 +/- 12.0) and sex hormone levels and higher IGF-I concentrations (57.1 +/- 24.2 vs. 70.1 +/- 37.1; P < 0.05). There were no ethnic differences in cord SHBG, sex hormones, or IGF-I. SHBG correlated negatively with cord insulin concentrations [males, -0.31 (P < 0.01); females, -0.35 (P < 0.001)], birth weight [males, -0.25 (P < 0.05); females, -0.36 (P < 0.001)] and other measures of neonatal size. In both normal pregnancies and those complicated by diabetes, cord IGF-I correlated with cord C peptide levels [0.32 (0.32 (P < 0.001) and 0.42 (P < 0.05), respectively] and neonatal size, but only in normal babies was there a correlation between IGF-I and insulin [0.43 (P < 0.001) and 0.10] or SHBG [-0.28 (P < 0.01) and -0.01]. These data confirm that relationships between insulin concentration and SHBG are present at birth and are likely to be physiological.