OBJECTIVE: Many studies have demonstrated that low levels of insulin-like growth factor-I (IGF-I) may be associated with the hypoxic-ischemic brain damage (HIBD) and that IGF-I has a neuroprotective effect. The role of IGF-II, a structurally and functurally homologous polypepties with IGF-I, is unclear in HIBD. This study was designed to observe the changes of serum and cerebrospinal fluid (CSF) IGF-II levels in neonates with hypoxic-ischemic encephalopathy (HIE) and to investigate its effects on HIE. METHODS: Serum and CSF IGF-II levels in 41 neonates with HIE were measured by radioimmunoassay in the acute phase (postnatal age 12-24 hrs) and the convalescence phase (postnatal age 10-12 days). The 41 HIE neonates included 10 cases of mild, 12 moderate, and 19 severe HIE. Serum samples of 10 normal neonates were used as controls. RESULTS: In the acute phase, serum IGF-II levels in the Mild HIE group (203.28±40.09 ng/mL) and the Moderate HIE group (192.33±39.66 ng/mL) were not significantly reduced, but were obviously reduced in the Severe HIE group (116.72±39.50 ng/mL) compared with normal controls (229.38±43.39 ng/mL) (P<0.01). During the convalescence phase, serum IGF-II levels in the Mild HIE group (285.53± 49.44 ng/mL ) and in the Moderate HIE group (278.69±51.34 ng/mL) increased significantly (P<0.01); CSF IGF-II levels increased in the Mild HIE group from 27.23±7.82 ng/mL (acute phase) to 81.58±9.77 ng/mL (convalescence phase) (P<0.01) and also increased in the Moderate HIE group from 23.43±7.79 ng/mL (acute phase) to 78.48±10.44 ng/mL (convalescence phase) (P<0.01). The patients from the severe HIE group whose neurological symptoms or signs were improved in the convalescence showed higher serum and CSF IGF-II levels than in the acute phase (254.08±48.50 ng/mL vs 122.21±46.26 ng/mL; 69.42±10.20 ng/mL vs 15.05±7.03 ng/mL; P<0.01 ). A positive correlation was found between the serum and CSF IGF-II levels in the HIE group (r=0.69, P<0.01 ). CONCLUSIONS: IGF-II levels in serum and CSF are associated with the pathogenesis and the prognosis of neonatal HIE.