Introduction. Forecasting and prevention of very early premature birth is undoubtedly an urgent problem of modern obstetrics. It is premature babies with extremely low body weight that largely determine the high level of perinatal morbidity and mortality. Objective. To assess clinical and immunological risk factors for very early preterm birth. Materials and methods. 120 pregnant women, 80 patients with threatening preterm birth at 22—27 weeks (TPB) and 40 with uncomplicated pregnancy (UB) were included into the study. In all cases the outcome of pregnancy and condition of newborn were assessed. The content of sRAGE and S100B protein, as well as the level of antibodies to the main infectious agents were determined by ELISA method. Results. Risk factors in the development of TPB in 22—27 are repeated pregnancy and the upcoming first birth (OR 1.38), early onset of sexual life (OR 1.45), two or more consecutive miscarriages in history (OR 1.62), menstrual disorders in women (OR 1.35), inflammatory diseases of the reproductive system (OR 1.42) and vaginitis (OR 1.16). Among the complications of this pregnancy, the risk factors for very early preterm should include the threat of abortion in the first trimester (OR 1.96) and acute respiratory disease in the second trimester of pregnancy (OR 1.4). Of the concomitant extragenital pathology, thyroid disorders (OR 1.47) and chronic urinary tract diseases (OR 1.44) are risk factors for TPB at 22—27 weeks. Conclusions. The most significant risk factors for preterm birth after a threatening premature birth at 22—27 weeks are habitual miscarriage (OR 4.08) and cervical insufficiency (OR 3.50), sRAGE less than or equal to 619.5 pg/ml ( OR 3.7), the S100B protein content is less than or equal to 43.66 mc/ml (OR 3.15). The diminished level of sRAGE in patients with the threatened miscarriage at 22—27 weeks of gestation is a prognostic criterion for the development of perinatal hypoxic lesions of the Central nervous system in newborns.