Vascular functions in infants, children and their mothers

Abstract

The function of the microvascular system was studied during early postnatal circulatory adaptation and in early-onset neonatal sepsis. We also studied large and small artery functions in infants and schoolchildren of low birthweight, a risk factor related to later development of cardiovascular disease and hypertension.

In healthy newborn infants, we studied longitudinally skin microcirculation and vascular reactivity during the first day of life. Skin perfusion and postocclusive reactive hyperemia, measured with a laser Doppler instrument, did not change significantly between 2 and 24 h of postnatal age. The overall degree of reactive hyperemia was 69 (0 - 458) % in excess of basal perfusion and time to postocclusive peak perfusion was 4.6 (2.0 - 18) s. A correlation was found between skin perfusion and local skin temperature, with increasingly high perfusion values at skin temperatures above 31 - 32 oC (r = 0.55, p<0.001).

In newborn infants with suspected early-onset neonatal sepsis, the diagnostic value of cutaneous reactive hyperemia was compared to that of circulating levels of the proinflammatory cytokines IL-6, IL-8 and TNF-alpha. On admission to the neonatal ward, both the postocclusive reactive hyperemia and the cytokine levels were significantly higher in the group with sepsis than in the one without. The relative perfusion change during reactive hyperemia increased to a median of 170 % in the sepsis versus 37 % in the no sepsis group (p<0.001). In the sepsis group, a correlation was found between the degree of reactive hyperemia and log IL-6 and IL-8 values (r = 0.80 and 0.71, respectively, p<0.001). Reactive hyperemia showed a sensitivity and specificity equal to or even higher than those found for IL-6, IL-8 and TNF-alpha suggesting that reactive hyperemia may be useful as an additional diagnostic marker in neonatal sepsis.

In the second part of this thesis, endothelial function in skin was studied in newborn infants of low birthweight and in their mothers; and the prevalence of two early markers of increased vascular risk - i.e., endothelial dysfunction and inelastic arteries - were studied in healthy schoolchildren of low birthweight.

Newborn infants of low birthweight for gestational age (SGA) showed an impaired endothelium-dependent (ACh-induced) vasodilation, compared to normal birthweight controls. The peak skin perfusion increase in response to local application of ACh was 240 ± 125 % in SGA infants, but 650 ± 250 % in controls (p<0.001). By contrast, the degree of ACh-induced vasodilation was higher in mothers of SGA infants than in those of control infants (p<0.05). Subdividing the SGA group, SGA infants with leanness at birth had a lower ACh-induced vasodilation than those born Proportionately small (p<0.01). Healthy schoolchildren of low birthweight for gestational age (LBW) had a lower endothelium-dependent (ACh-induced) vasodilation than schoolchildren of normal birthweight (p<0.001). In the LBW group, children lean at birth had a lower endotheliumdependent vasodilation than proportionately small LBW children (p<0.01). Endotheliumindependent vasodilation, induced by local application of nitroglycerin, was similar in both groups. The elastic properties of the abdominal aorta and common carotid artery were measured with an ultrasonic vessel-wall tracking system, but no differences were found between the two groups. However, when the LBW group was subdivided, increased carotid stiffness was found in lean LBW children, compared to those born proportionately small (p<0.05). The aortic stiffness was about the same in lean and proportionately small LBW children.

Endothelial dysfunction and increased arterial stiffness may be important links between low birthweight and increased susceptibility to adult cardiovascular disease.