In recent years, with the significant increase in survival rates of premature infants and low birth weight infants, the population susceptible to neonatal gastrointestinal diseases such as necrotizing enterocolitis (NEC) has increased. NEC mainly affects premature infants and has the characteristics of rapid progression and high mortality rate. The gold standard for diagnosing NEC is pathological examination, but it is not feasible in practical work. Currently, Bell staging criteria are commonly used to diagnose and evaluate the severity of the disease. Among them, Bell I is a suspected case, mainly manifested as gastric retention, accompanied by mildAbdominal distension and other symptoms are similar to those of feeding intolerance (FI), and the imaging findings are non-specific, making it difficult to identify FI early.NEC has a hidden onset, rapid disease progression, and high mortality rate. Survivors often have serious long-term complications such as short bowel syndrome, growth impairment, and neurodevelopmental impairment. However, existing diagnostic methods cannot provide continuous and dynamic observation to evaluate changes in organ hemodynamics and early assessment of clinical manifestations after organ perfusion changes.
FI is the inability of premature infants to digest enteral nutrition, manifested by gastric residual capacity exceeding 50% of the previous feeding amount, bloating and/or vomiting, leading to interruption of enteral feeding plan. The etiology of FI is unclear, which may be related to immature intestinal development caused by premature birth, or it may be an early clinical manifestation of serious diseases such as NEC or sepsis. It often occurs in premature infants with gestational age less than 32 weeks or birth weight less than 1500g. Currently, there is no recognized diagnostic criterion to effectively distinguish the prodromal symptoms of FI and NEC in the early stage. Research has found the concepts of developmental feeding intolerance (DFI) and pathological feeding intolerance (PFI) related to NEC, and it is believed that there is a close relationship between neonatal hemodynamic changes and FI. Near infrared spectroscopy (NIRS) technology is used to monitor neonatal intestinal tissue oxygen saturation (rSO2) or evaluate the presence of FI.NIRS is a sustainable technology for monitoring rSO2 and reflecting the blood flow perfusion status of specific tissues or organs, with the advantages of non-invasive, real-time, continuous, and bedside operation. The principle is to use near-infrared light (with a spectral range of 700-900 nm) that has good penetration into human tissues to monitor local tissue oxygenation and hemodynamics, and to reflect the dynamic balance of local tissue oxygen supply and consumption through changes in hemoglobin. Hemoglobin in different oxidation states absorbs near-infrared light in different wavelength ranges. Oxygenated hemoglobin (HbO2) mainly absorbs infrared light, while deoxygenated hemoglobin (Hb) mainly absorbs red light. NIRS was used to measure the changes in HbO2 and Hb concentrations in tissue blood vessels, and the modified Beer Lambert law was used to describe the relationship between HbO2 and Hb absorption of near-infrared light and their concentration in tissues. Finally, rSO2 was obtained. In summary, NIRS can rapidly and continuously measure changes in vascular oxygenation status and hemodynamics, measure organ rSO2, and reflect the presence of hypoxia and ischemia in local tissues.
In recent years, a major research hotspot in the field of neonatal gastrointestinal diseases has been how to prevent, early identify, and standardize the treatment of NEC. Studies have shown that intestinal oxygen supply disorders are one of the main factors causing NEC. Using NIRS may timely detect intestinal tissue ischemia in newborns, which is expected to improve intestinal tissue blood flow perfusion in the early stage, help reduce intestinal damage, and assist in the early identification of FI and NEC prodromal symptoms in clinical practice, so as to effectively distinguish and establish enteral feeding in the early stage of the disease.
In most studies, the monitoring site of NIRS is mainly below the navel. The method of using NIRS to simultaneously monitor oxygen saturation in the liver and below the navel is safe and feasible, but the correlation and consistency between liver and below the navel oxygen saturation values are poor. Regarding the optimal location for NIRS monitoring, further exploration is needed to determine the baseline values for NIRS monitoring in the liver and umbilicus of newborns, in order to more effectively apply NIRS technology to predict the onset and course of NEC in premature infants. Some scholars used four monitoring probes to simultaneously monitor four different parts of the abdomen of NEC newborns, and found that the rSO2 value in the right abdominal tract fluctuated the most violently and was significantly lower than the other three locations.
Research on NIRS Technology in Healthy Newborns
NIRS continuously monitored rSO2 in the intestines of healthy premature infants for 72 hours, while continuously monitoring mesenteric blood flow before and after feeding with 3D ultrasound. It was found that rSO2 in the intestines was significantly correlated with the hemodynamic performance of the superior mesenteric artery monitored by ultrasound, suggesting that NIRS can be used to monitor intestinal blood flow perfusion. The average value of intestinal rSO2 in healthy full-term infants on the first day after birth was 69.9% ± 12.1%, and on the second day it was 75.3% ± 12.4%. The intestinal rSO2 increased over time. Coincidentally, McNeill et al. observed using NIRS that the intestinal rSO2 of healthy premature infants fluctuated between 32% and 66%. The intestinal rSO2 value of healthy premature infants showed a decreasing trend in the first week after birth, reaching its lowest value at 4.5 to 7 days, and then began to rise. The normal intestinal rSO2 values for premature infants with gestational age<30 weeks were observed to be between 36.7% and 46.0%. The intestinal rSO2 is influenced by both gestational age and postnatal age, so a single reference range is not sufficient for individualized evaluation of newborns of different gestational ages and postnatal ages. The intestinal rSO2 values of 220 premature infants with gestational age<32 weeks and/or birth weight<1200g at 1 week after birth were recorded using a NIRS monitor. A predictive model was established for the first time, and it was found that the average intestinal rSO2 values of the enrolled premature infants showed a decreasing trend in the first 4 days, an increasing trend in the 5th to 7th days, and basically recovered to birth levels on the 7th day. This is similar to the results of McNeill et al.'s study. The research results of Zhang Jinghua et al. also support the above conclusion. By observing the intestinal rSO2 of extremely low birth weight infants, it was found that the intestinal rSO2 value could fluctuate with age in the first 2 weeks after birth. Similarly, Cortez et al. found that the intestinal rSO2 values of infants with gestational age<30 weeks showed a decreasing trend in the first 9 days after birth and an increasing trend from the 10th to 14th day. Therefore, it can be considered that there is variation in the intestinal rSO2 values of healthy premature infants at various time points after birth.
The Application of NIRS Technology in FI
Almost one-third of premature infants will develop FI due to immature gastrointestinal tract, and the clinical manifestations of FI are very similar to stage I NEC, making it difficult to effectively distinguish in the early stages. When FI occurs, enteral nutrition is usually interrupted, leading to a delay in establishing enteral nutrition and increasing the risk of infection in premature infants. This requires clinicians to effectively identify the prodromal symptoms of FI and NEC early on. However, there is currently no clear diagnostic criterion to distinguish between FI and NEC. It was found that the baseline values of intestinal rSO2 in infants who eventually developed NEC were significantly lower than those in infants who did not develop NEC. During the monitoring period, there may be a lack of variability in NIRS baseline values and NIRS signal loss in infants with NEC. However, infants who developed FI but did not develop NEC had a consistently low baseline value of intestinal rSO2, but there was variability. It is proposed that monitoring the intestinal rSO2 of premature infants can early distinguish the prodromal symptoms of FI and NEC. Li Xufang et al. used NIRS to monitor the rSO2 in the intestines and the cerebral regional oxygen saturation (CrSO2) in very low birth weight infants from the first to the fourth day after birth. At the same time, they monitored the changes in rSO2 in the intestines of children with FI during this period, and compared them with those of feeding tolerant newborns. They found that the baseline value of rSO2 in the intestines of children with FI fluctuated significantly one day before clinical manifestations such as gastric retention, vomiting or abdominal distention. They believed that continuous bedside NIRS monitoring of rSO2 changes in the intestines of very low birth weight infants was of great significance for timely adjustment of feeding plans. At present, there is a lack of effective research on the application of NIRS in FI both domestically and internationally. A large number of studies on the correlation between intestinal rSO2 and FI are needed to explore the early identification and diagnosis of FI.
The Application of NIRS Technology in NEC
5.1 Early prediction of NEC using NIRS technologyResearch has found that intestinal rSO2<30% increases the risk of NEC in extremely premature infants; To further clarify the practicality of intestinal rSO2<30% in predicting NEC in extremely premature infants, the intestinal rSO2 of 86 extremely premature infants was monitored. It was found that the average intestinal rSO2 of extremely premature infants who eventually developed NEC was<30%, while the average intestinal rSO2 of extremely premature infants who did not develop NEC was ≥ 30%. The viewpoint that NIRS technology can help identify infants who will not develop NEC was proposed.The probability of developing NEC in infants with intestinal rSO2<70% within 48 hours after birth is significantly increased. It is believed that infants already exhibit intestinal tissue hypoxia before the clinical occurrence of NEC, and monitoring neonatal intestinal rSO2 can identify NEC early. NIRS monitored the intestinal rSO2 of 100 infants with gestational age<32 weeks and weight<1.5 kg, and proposed that intestinal rSO2 ≤ 56% is an independent risk factor for NEC. It is believed that monitoring intestinal rSO2 in premature infants may help in early screening for infants at risk of NEC. It can be considered that NIRS can monitor intestinal rSO2, reflect local intestinal perfusion, and is a technique that can be used to assess the risk of NEC occurrence.
Monitoring the ratio of CrSO2 to intestinal rSO2 (cerebral splenic oxygenation ratio, CSOR) is more meaningful than monitoring intestinal rSO2 alone, as cerebral perfusion has self-regulation ability. Under normal circumstances, the ratio of visceral to cerebral blood oxygen can be considered constant, but during ischemia and hypoxia, this ratioMay be lower than the normal value; And using NIRS to simultaneously monitor CrSO2 and intestinal rSO2, it was found that CSOR<0.75 suggests the possibility of intestinal ischemia, while CSOR>0.96 can basically rule out intestinal ischemia. Compared with using intestinal rSO2 alone, CSOR can better predict intestinal ischemia. Monitoring the CrSO2 and intestinal rSO2 of a pair of 32 week premature twins (one normal and one diagnosed with NEC) revealed that the abdominal CSOR of healthy infants was greater than 0.75, while the abdominal CSOR of NEC patients was less than 0.75. By monitoring the intestinal rSO2 and CrSO2 of 75 premature infants and calculating the CSOR value, it is believed that for every 0.1 increase in CSOR, the probability of diagnosing NEC increases by about 28%. The high variability of intestinal rSO2 helps to exclude the possibility of NEC clinically, that is, for every 0.1 increase in coefficient of variation, the possibility of excluding NEC increases by 2.6 times.5.2 NIRS combined with biomarkers may provide more accurate prediction of NECAbdominal X-ray and ultrasound examination are classic methods for diagnosing NEC, but children with NEC often lack specific clinical manifestations before onset. Common methods such as abdominal X-ray and ultrasound are difficult to diagnose and treat early, and once diagnosed, the condition is often very critical and in a worsening stage. In recent years, an increasing number of studies have reported that NEC related biomarkers such as fatty acid binding proteins, cytokines, gut microbiota, etc. have potential value in prediction, early diagnosis, severity assessment, and prognosis. Biomarkers have objective, quantifiable, accurate, and remeasured characteristics. Some scholars have found that using NIRS combined with biomarkers to evaluate the occurrence of NEC is expected to provide direction for precise clinical diagnosis and personalized treatment. Peng Wenling et al. proposed that the combined application of NIRS and serum intestinal fatty acid binding protein (I-FABP) may improve the sensitivity and specificity of NIRS in predicting intestinal tissue ischemia, which can help better predict the occurrence and outcome of NEC. On the contrary, Kuik et al. evaluated whether the combined use of intestinal rSO2 and urinary I-FABP could predict intestinal recovery after NEC, including 27 premature infants with Bell stage ≥ II. The results showed that the role of urinary I-FABP in predicting intestinal recovery in NEC patients still needs to be validated. Subsequently, by monitoring the intestinal rSO2 of 57 premature infants and detecting serum C-reactive protein (CRP) levels, it was observed that the intestinal rSO2 of NEC group premature infants was lower than that of non NEC group, and the serum CRP level was higher than that of non NEC group. The diagnostic value of NIRS technology for NEC in premature infants was higher than that of CRP, and its diagnostic value with intestinal rSO2 combined with CRP for NEC in premature infants was comparable. In addition to the above biomarkers, new NEC biomarkers such as intestinal alkaline phosphatase and interleukin-27 have been discovered in recent years to identify early NEC. Further combined analysis of NIRS and these biomarkers can help better predict the occurrence and outcome of NEC. In summary, it can be concluded that low NIRS values in early newborns can help detect the occurrence of NEC early. Combining NIRS and biomarkers can highly predict the occurrence of NEC, which can help identify newborns with NEC earlier before clinical manifestations of the disease appear.
By using NIRS technology to monitor the intestinal rSO2 and CSOR of newborns, especially premature infants, abnormal intestinal hemodynamic manifestations can be identified, thereby early differentiation of NEC prodromal symptoms and FI, and early intervention of the disease to avoid further development; Meanwhile, the combined analysis of NIRS and other biomarkers may be able to more accurately predict the occurrence of NEC related clinical events. In future research, it is necessary to further evaluate the baseline values of rSO2 and CSOR in different parts of the intestine and different neonatal populations, as well as the NIRS changes in related diseases, especially regarding rSO2 in the intestine. This has profound significance for predicting neonatal FI and reducing the occurrence of NEC.
The Bolian Zhongke MOC series brain tissue oxygen saturation monitor can provide continuous, real-time, and non-invasive monitoring values of tissue oxygen saturation (rSO2), which can reflect specific organs (such as the brain, mesentery, kidneys, etc.) and systemic perfusion status. Research has shown that rSO2 monitoring can detect perfusion damage in the early stages that cannot be detected by conventional hemodynamic detection methods. It can timely monitor the oxygen supply and demand balance of brain and regional tissues, dynamic changes in cerebral blood flow, evaluate brain and tissue ischemia and hypoxia early, guide perioperative management, reduce the incidence of perioperative complications, sensitively reflect the oxygenation status of tissues and intervene, optimize the entire clinical treatment management, shorten hospitalization time, and improve patient prognosis.
