This study shows that very early in the course of infection the microcirculation of term newborns is disturbed with a significant decrease in vessels with continuous flow. These changes are visible even before the increase in laboratory values. We also found that in the term newborn the ear conch is a readily accessible spot to observe such changes and better than the area under the axilla we used in our previous studies in preterm infants. The skin of term infants is thicker and the capillary architecture is more mature with capillary loops than in preterm infants. The focus point istherefore deeper and the quality of scan worsens, whereas at ear conch a dense subepidermal plexus with no loops is observed (). The ear conch is perfused by terminal branches of the external carotid artery and thus part of the more central circulation just as sublingual vessels which are used for imaging in adults. While this is still possible to obtain images in term infants at the axilla this location has distinct disadvantages. The skin is considerably thicker in term than in preterm infants as mentioned above. Measurements at the arm are also more prone to bias caused by pressure as the image quality from arm appears to improve with slight pressure as more vessels are seen. The ear conch is a very small area in newborns and easy to access. Due to its size all the imaging is done on virtually the same spot, which results in similar scans for the different measurement times. Pressure is immediately apparent as the blood flow suddenly appears to be slower or even disappears. The sucking reflex of infants may impede imaging of the sublingual vessels [16
], but other groups have successfully obtained buccal images in newborns [15
]. In opposite to measurements in the oral cavity the tip of the probe can be seen at the ear which helps to avoid pressure artefacts.
Examples OPS images of the capillary network seen on the ear conch (a) and upper arm (b). In the ear conch more capillary networks can be seen in the ear conch and in the video sequence the type of flow can be identified and easier classified.
The hypercoagulation state of newborns infants may explain the microcirculatory changes we observed in mild to moderate infection [2
]. Newborns might be more prone to these processes as they have a relative overproduction of cytokines compared to adults [21
]. Neonatal sepsis or infection cannot be defined by positive blood cultures as in adults since blood cultures might be falsely negative due to the low yield caused by insufficient sample volumes [24
] or intermittent or low-density bacteremia due to inhibition of bacterial growth by earlier (i.e., intrapartum) antibiotic administration [25
]. In our unit 1
mL of blood is usually sampled for blood culture. Fischer estimated that if 1
mL of blood is sent for culture, the sensitivity of this test is only between 30–40% whereas if 3
mL are sent for culture, the sensibility rises to 70–80% [26
]. With the low sensitivity of the test in neonates and the time required for final results, neonatologists cannot rely on positive blood cultures for the diagnosis of infection or sepsis. In the present study in just one infant (6%) spinal fluid culture was positive and no positive blood cultures were found. Determinations of C-reactive protein levels have been shown to be useful in the diagnostic evaluation of neonates with suspected infection [25
]. Therefore, we defined neonatal infection as a CRP serum level of more than 0.5
mg/dL. Only infants showing an elevated CRP were included into the infection group of the study. We are aware that this definition might have led to an over diagnosis of infection. In clinical practice therefore infants without infection frequently receive antibiotics. In fact, in four infants with presumed infection, microcirculation appeared normal with more than 85% of the vessels showing a continuous microcirculatory blood flow. These infants were clinically well without signs of infection and their CRP levels were between 0.62 and 2.0
mg/dL. Without positive blood cultures it is difficult to prove that an increase in disturbed microcirculatory blood flow >20% might be more sensitive as an early marker of infection in neonates than laboratory values.
In our study there was no difference in the blood flow between healthy males and females as reported in other studies [31
]. Boys and girls with infection could not be compared since the majority of the infants with infection were male (see ). Comparing healthy versus infection for both genders separately, the significant difference between both groups remained.
In contrast to our findings in preterm infants with late onset infection, FVD did not decrease in term infants with early onset infection. We did observe a trend to lower FVD in the ear conch in the infants with infection but this difference did not reach statistical significance. This could be due to the different method of FVD determination (grid versus Capiscope) but we did compare both methods and found an excellent correlation (data not shown).