Angiopoietin‐2 in the perinatal period and the role of intrauterine growth restriction

BACKGROUND: Angiopoietin-2, an angiogenic factor, causing destabilization and postnatal remodeling of blood vessels, is upregulated by hypoxia. We hypothesized that circulating Angiopoietin-2 levels might differ in intrauterine growth restricted and appropriate for gestational age fetuses and neonates, as the former have restricted growth and development and suffer from in utero hypoxia. METHODS: This is a prospective, controlled study, including forty asymmetric, mainly due to hypertension or pre-eclampsia intrauterine growth restricted (0-9 customized centiles, corrected for gestational age, sex, maternal weight, height, ethnic group, and parity), and 20 appropriate for gestational age (42-82 customized centiles) full-term infants, as well as their mothers. Blood samples were drawn from mothers, from the doubly clamped umbilical cord (mixed arteriovenous blood, representing fetal state), and from neonates on days 1 (N1) and 4 (N4) of life (representing transition and stabilization to extrauterine life, respectively). Circulating angiopoietin-2 levels were measured by enzyme immunoassay and the statistical analysis involved t-test and Pearson correlation. RESULTS: Angiopoietin-2 levels were significantly higher in intrauterine growth restricted cases only in N4 (p = 0.04). No dependence on the mode of delivery and gender was documented. CONCLUSIONS: These findings may suggest that intrauterine hypoxia possibly does not upregulate circulating angiopoietin-2 levels in intrauterine growth restricted fetuses and day 1 neonates; however, increased angiopoietin-2 on N4, after stabilization to extrauterine life, might signify initiation of catch-up growth-related angiogenesis and stimulation of angiogenic factors, granted that angiopoietin-2 is critically involved in postnatal vascular remodeling.