Abstract 2526: Fetal Programming of Hypertension: Decreased Compliance and IGF-I Plasma Levels in Umbilical Arteries of Infants with Intrauterine Growth Restriction

Abstract

Background : Epidemiological studies link intrauterine growth restriction (IUGR) to arterial hypertension in adulthood. Intrauterine stress may induce decreased arterial compliance that persists after birth, thus predisposing the individual for arterial hypertension in adult life. Methods and Results : We compared umbilical arteries from IUGR (n=13, <5 th weight percentile) vs. appropriate for gestational age (AGA) infants (n=13) using structural and functional analyses. Vessel wall thickness and stiffness were determined in umbilical artery-derived vessel rings. Vessel wall elastin, the main determinant of arterial elasticity, was quantified by elastin extraction. Cord blood was assayed for growth factors known to modulate vessel wall matrix. IUGR infants had decreased umbilical artery compliance in vivo in terms of an increased resistance-index (P<0.05). In parallel, the vessel wall area of umbilical arteries in the IUGR group was significantly smaller than in the AGA group (2.8 vs. 3.8 mm 2 , P<0.05). Myographic measurements showed that maximal tension [mN/mm] as well as maximal force [mN] were both significantly increased in IUGR arteries compared with AGA arteries (P<0.05). Serum levels of IGF-I, a regulator of elastin synthesis, were significantly lower in IUGR cord blood (P<0.01) than in AGA cord blood. These IGF-I serum levels correlated significantly with maximum tension in umbilical arteries (P<0.01). In parallel, we found a trend to reduced elastin content in the vessel wall of IUGR vessels. Conclusions : IUGR infants possess thinner and stiffer umbilical arteries than AGA infants. Low intrauterine IGF-I serum levels may account for reduced arterial elastin at birth, thereby providing a potential link to arterial hypertension in adulthood.