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

Abstract

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. © 2006 Taylor & Francis.