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Prematurity predisposes to cardiovascular disease; however the underlying mechanisms remain elusive. Disturbance of the endothelial glycocalyx (EG), an important regulator of vessel function, is thought to contribute to vascular pathology. Here, we studied the EG with respect to gestational and postnatal age in preterm and term neonates. The Perfused Boundary Region (PBR), an inverse measure of glycocalyx thickness, was measured postnatally in 85 term and 39 preterm neonates. Preterm neonates were further analyzed in two subgroups i.e., neonates born < 30 weeks gestational age (group A) and neonates born ≥ 30 weeks (group B). In preterm neonates, weekly follow-up measurements were performed if possible. PBR differed significantly between preterm and term neonates with lowest values representing largest EG dimension in extremely premature infants possibly reflecting its importance in fetal vascular development. Linear regression revealed a dependence of PBR on both, gestational age and postnatal age. Furthermore, hematocrit predicted longitudinal PBR changes. PBR measured in group A at a corrected age of > 30 weeks was significantly higher than in group B at birth, pointing towards an alteration of intrinsic maturational effects by extrinsic factors. These changes might contribute to the increased cardiovascular risk associated with extreme prematurity.

Background: Hypotension remains a common complication in preterm infants and is associated with high neonatal morbidity and mortality. The underlying mechanisms are still not fully understood. We studied the microcirculation in extremely low birth weight infants to understand the relationship between blood pressure and skin perfusion., Methods: In 21 patients (gestational age <30 wk, birth weight <1,225 g), functional vessel density (FVD) and diameter distribution were obtained prospectively by side stream dark-field imaging at the right arm in the first 48 h after birth. Infants with blood pressure below gestational age and receiving catecholamines were defined as hypotensive as compared with the remaining normotensive control group., Results: In the first 6 h after birth, FVD was significantly higher in the hypotensive group than in the control group. After 12 h, there were no significant differences in either blood pressure or FVD between the two groups. FVD did not change significantly during the observation period in either group., Conclusion: Hypotensive infants have a higher FVD, possibly due to loss of microvascular tone leading to vasodilation and flow redistribution. However, the link between blood pressure and perfusion remains unclear, and no definitive correlation could be found.

Changes in microcirculation have been recognized as central to many disease processes. The aim of this study was to evaluate factors, which influence the microcirculation of the skin during the first month of life in premature infants. Red blood cell (RBC) velocity, vessel diameter, and functional small vessel density (FSVD) were measured daily for the first 30 d on the upper arm in preterm infants with gestational age <30 wk. Orthogonal polarization spectral (OPS) images were analyzed off-line with the Capi- Scope-Image program. In 25 infants, FSVD decreased significantly from week 1 (mean +/- SD 236 +/- 33 cm/cm2) to week 4 (207 +/- 30 cm/cm2) and correlated directly with Hb levels and incubator temperature. Vessel diameters and RBC velocity did not change significantly, nor did clinical parameters such as blood pressure, heart rate or body temperature. Microvascular parameters were not dependent on gestational or postnatal age. The microcirculation of the skin might be an easily accessible window to obtain better understanding of circulatory changes in the postnatal period. Our data are essential as basis for further studies in this field. Hb levels and possible incubator temperatures have a substantial influence on functional small vessel density and therefore need to be taken in account.

The optimal thermal environment for sick preterm infants is unknown. Incubator temperature can be regulated to an abdominal wall temperature of 36.5 degrees C [neutral temperature (NT)] or to a minimal temperature difference (<2 degrees C) between abdominal wall and extremities [comfort temperature (CT)]. This could affect the microcirculation, particularly in infants with impaired perfusion. We assessed the microvascular perfusion with near-infrared photoplethysmography (NIRP) at these two target temperatures between d 1 and 4 of life in preterm infants with normal (NL group) or impaired (RED group) microcirculation as determined by a clinical score. Signal strength variables such as area under the curve (AUC) and the first derivate of the amplitude (FLUX) were calculated. Starting temperature was randomized to NT or to CT and then followed by the other temperature. A significant increase of FLUX and AUC in the RED group was found with NT as starting temperature (FLUX: 282 +/- 76 at NT versus 627 +/- 211 at CT; p = 0.025; AUC: 73 +/- 47 at NT versus 234 +/- 112 at CT; p = 0.009), but not with CT. In NL infants, both parameters did not change significantly. Increasing the incubator temperature to CT changes thermoregulatory flow to the extremities in preterm infants with impaired microvascular perfusion and might improve tissue flow.

Direct visualization of the microcirculation at the level of the skin capillaries may provide information on the quality of tissue perfusion. Orthogonal polarization spectral imaging (OPS) enables noninvasively direct observation of those blood vessels. OPS was applied to the upper arm of 13 preterm anemic infants [median (95% confidence interval) gestational age: 26 wk (25-26 wk); birth weight: 730 g (652-789 g)] before and 2 and 24 h after transfusion (Tx). OPS images of skin perfusion were continuously recorded on video. Off-line quantitative data of microvascular perfusion were obtained by measuring functional capillary density, vessel diameter, red blood cell velocity, and flow. We found a significant increase in functional capillary density 2 h after transfusion with an additional significant rise after 24 h [before: 142 (134-155); 2 h after Tx: 185 (166-196); 24 h after Tx: 206 (185-219) cm/cm2; p < 0.001), thus indicating improved microvascular perfusion. Vessel diameter, red blood cell velocity, and flow did not change significantly. There were no significant changes in clinical variables, such as blood pressure, heart rate, or body temperature. Whereas conventional monitoring methods did not show any changes after transfusion, quantitative analyses of OPS images indicated improved perfusion; hence, it seems a useful monitor for assessing the response to therapies aimed to improve tissue perfusion.

Objective: To assess the bioavailability of vitamins A and E administered parenterally with either water-soluble or lipid-soluble preparations., Study Design: A water soluble preparation (MVI Pediatric) administered with a glucose-amino acid solution and a lipid soluble preparation (Vitalipid N Infant) infused with a lipid emulsion were subjected to phototherapy light, different flow rates, light protection, different tubing materials and tubing sizes, and concentrations in the effluents were determined., Results: Recovery of retinol in glucose-amino acid solution was poor under all conditions (16-30% without; 21-42% with light protection tubing) and increased to 61% with polyethylene and to 44% with polyurethane tubings. Polyurethane tubings with reduced volume improved retinol delivery to 56%. Retinylpalmitate (Vitalipid) losses were low, with recovery of 86 and 77% with and without light protection, respectively. Recoveries of alpha-tocopherylacetate in GLUC-AA were 103-107% without and 94-102% with light protection and of alpha-tocopherol in LIPID 89% without and 85% with light protection., Conclusions: Parenteral vitamin A delivery is improved by the infusion of retinylpalmitate with lipids. Light protecting tubings provide only a marginal benefit with artificial light and none with phototherapy light. Polyethylene and polyvinylchloride tubings adsorb less retinol than polyurethane tubings. Small tubing diameters resulting in higher flow rates enhance retinol delivery.

Little is known about the microvascular perfusion of the skin postnatally. Skin microvascular parameters can be assessed noninvasively with orthogonal polarization spectral imaging (OPS), a technique where, through the use of special optics, a virtual light source is created at a depth of 1 mm within the tissue. The light is absorbed by the Hb, yielding an image of the illuminated Hb-carrying structures in negative contrast. In nine term (weight 2100-4470 g) and 28 preterm infants (weight 550-2070 g; gestational age 24-33 wk) red blood cell velocity and vessel diameter and density were determined off-line with the Cap-Image program in vessels video-recorded by OPS near the axilla on d 1 and 5 of life. Blood pressure, heart rate, hematocrit, and body and incubator temperature were noted. Vessel diameter ranged from 6 to 24 microm, vessel density from 219 to 340 cm/cm(2) with no change between d 1 or 5 and no difference between term and preterm infants. Red blood cell velocity increased in preterm infants from d 1 [median 528 microm/s, 95% confidence interval (CI) 486-564 microm/s] to d 5 (median 570 microm/s; 95% CI 548-662 microm/s; p = 0.001) and correlated with the decrease in median hematocrit from 44% (CI 40%-60%) to 39% (CI 37%-43%) with r(2) = -0.37 with a 95% CI -0.59 to -0.11, p = 0.006. Hematocrit correlates with red blood cell velocity in the microvessels of the skin. The new technology can be used to assess quantitative changes in the microvessels and thus allows noninvasive assessment of tissue perfusion in term and preterm infants.

Changes in high-density lipoprotein (HDL) subclass distribution were evaluated in a group of premature infants during the early postnatal period to ascertain whether enteral feeding brought about a rapid shift from neonatal to adult-like distributions. All infants were fed a combination of breast milk and formula. Cord blood of premature infants had a predominance of large, less dense (HDL2b)gge and a paucity of intermediate-sized (HDL3a)gge particles. Lack of a peak in the (HDL3a)gge is a characteristic feature for cord blood, whereas a prominent (HDL3a)gge peak is characteristic of adult plasma. After the start of enteral feeding, blood was obtained at two time-points: 6-14 days (sample A) and 17-32 days (sample B) postdelivery. With the onset of feeding, triglyceride increased significantly from an average of 34 mg/dl in cord blood to 120 mg/dl in sample B, and cholesterol increased from 86 to 112 mg/dl in the same period. Increases in plasma lipid concentrations were paralleled by a redistribution of subclasses such that three components of almost equal intensity were evident in sample B; these consisted of (HDL2b)gge, (HDL2a2)gge, and (HDL3b)gge. A paucity of (HDL3a)gge particles persisted even after onset of enteral feeding; thus, increases in plasma triglyceride and cholesterol per se are not sufficient to induce the adult-like distribution. It is suggested that development of the normal adult HDL subclass pattern is complex and is probably related to the development and interaction of several factors, including plasma enzymes involved in lipid hydrolysis and esterification, lipid exchange proteins, and hormonal status.