Cerebral rSO₂ is usually lower than splanchnic or renal rSO₂ because the metabolic activity of and demand for oxygen of the brain are higher than those of other living organs [12]. Standard cerebral rSO₂ is different according to different studies. It was reported to be 57% to 77% by McCormick et al. [12], 62% to 78% by Lemmers et al. [13], 56% to 76% by Petrova and Mehta [14], and 66% to 83% by McNeill et al. [15]. Generally, the standard neonatal value of cerebral rSO₂ is 60% to 80%. Cerebral rSO₂ baseline values are affected by altered blood flow due to arteriovenous malformations, superior sagittal sinus, or epidural hemorrhage, by extracranial structures, and by the placement of sensor on the forehead [16,17]. Thus, evaluating the baseline value of cerebral rSO₂ is important. After evaluating the baseline cerebral rSO₂ value, we need to focus on its trend. Cerebral rSO₂ is normally low for several minutes immediately after birth. It then increases [18,19] and becomes stable 7 minutes after birth [20]. Pichler et al. [21] suggested reference ranges for the cerebral rSO₂ and FTOE in neonates immediately after birth to prevent cerebral hyper- and hypooxygenation. They reported that the cerebral rSO₂ is low at birth. It then increases for several minutes and becomes stable. On the contrary, the cerebral FTOE is high at birth. It then decreases for several minutes and becomes stable (Figure 2) [21]. The cerebral rSO₂ was decreased during immediate postnatal 15 minutes in preterm infants who needed FiO₂ >0.3 compared to that in preterm infants who needed FiO₂ ≤0.3 [11]. This suggests that in some preterm infants, oxygen has to be supplied liberally, not restrictively, to decrease early postnatal hypoxia. On the contrary, Sorensen and Greisen [22] reported that healthy preterm infants have lower FTOE and higher cerebral rSO₂ with elevated blood pCO₂, meaning higher cerebral oxygenation, compared to term infants. They concluded that prematurity itself is not more prone to cerebral hypoxia than term.

Neonates with hypoxic ischemic encephalopathy have increased cerebral rSO₂ and decreased cerebral FTOE [23]. This means that cerebral perfusion is increased with improper cerebral autoregulation, while cerebral oxygen consumption is decreased with secondary energy failure during hypoxic ischemic encephalopathy [24]. Among infants with hypoxic ischemic encephalopathy, those with poor neurodevelopmental outcomes have higher initial cerebral rSO₂ than those with better neurodevelopmental outcomes [23]. Infants with hypoxic ischemic brain injury identified using brain magnetic resonance imaging have higher initial cerebral rSO₂ than those without hypoxic ischemic brain injury [25].

Preterm infants have different cerebral rSO₂ baselines at immediate postnatal stage according to gestational age. Preterm infants have increased cerebral rSO₂ and decreased cerebral FTOE compared to term infants at birth. The younger the gestational age, the higher the cerebral rSO₂ and the lower the cerebral FTOE [26,27]. Cerebral rSO₂ decreases while cerebral FTOE increases according to gestational age at birth, reaching the nadir of rSO₂ and the peak of the FTOE at a gestational age between 38 and 39 weeks [28]. Cerebral rSO₂ also decreases as preterm infants mature, reaching the nadir between 6 and 8 postnatal weeks [28].

Variations in the cerebral blood flow according to the cerebral perfusion pressure is limited by cerebral autoregulation. Preterm infants are at a high risk of impaired cerebral autoregulation mainly due to immaturity of the cerebral vessels. It has been reported that impaired cerebral autoregulation in preterm infants is highly associated with neonatal death [29]. Caregivers can assess cerebral blood flow and perfusion pressure by measuring cerebral rSO₂ using the NIRS in order to quickly identify impaired cerebral autoregulation. Cerebral rSO₂ monitoring may help in the early diagnosis of impaired cerebral autoregulation and prevent irreversible brain injury or death [30].

Decreased cerebral oxygenation due to HSDA adversely influences brain growth and neurodevelopmental outcome [31]. Ductus arteriosus requiring surgical ligation was associated with lowest cerebral rSO₂ before closure (rScO₂ <40%) and brain damage in preterm infants [31]. Preterm infants with HSDA generally have lower cerebral rSO₂ but higher cerebral FTOE compared to preterm infants without HSDA [32]. Furthermore, these values are normalized after closure of the HSDA [32]. However, the interpretation of cerebral rSO₂ values in relation to ductus arteriosus remains controversial. Schwarz et al. [33] found higher cerebral FTOE (0.43± 0.05 vs. 0.38±0.05, P=0.038) but no difference in cerebral rSO₂ (54%±5% vs. 58%±5%, P=0.102) when they compared preterm infants with HSDA to those without HSDA.

There are still controversies about the effect of the closure of ductus arteriosus on cerebral blood flow and cerebral oxygen delivery. Indomethacin decreases cerebral blood flow and cerebral oxygen delivery whereas ibuprofen does not alter cerebral blood flow or cerebral oxygen delivery [34]. Underwood et al. [35] also reported that cerebral rSO₂ is decreased whereas somatic rSO₂ is increased after the administration of indomethacin. Huning et al. [36] reported that cerebral oxygenation does not change, although cerebral blood flow immediately after ligation of the ductus arteriosus shows a brief increase. On the contrary, Lemmers et al. [37] reported that cerebral rSO₂ is decreased immediately after ligation of the ductus arteriosus. Vanderhaegen et al. [38] showed that cerebral rSO₂ is increased while cerebral FTOE is decreased during ligation of the ductus arteriosus but returns to baseline following ligation. This suggests that ligation of the ductus arteriosus does not adversely influence cerebral oxygenation.

NIRS has been used most frequently for the perioperative monitoring of cerebral oxygenation during neonatal cardiac surgery to prevent hypoxic damage or shock. The decrease in cerebral rSO₂ detected using NIRS during operation to treat congenital heart disease is frequent because cardiopulmonary bypass can cause an abrupt change in cerebral blood flow and oxygenation. Therefore, cerebral rSO₂ monitoring is required during cardiac surgery to monitor cerebral oxygenation and to prevent hypoxic damage [39]. Hansen et al. [40] reported that decreased cerebral rSO₂ after cardiac surgery might be related to redistribution of blood flow from cerebral circulation to somatic circulation. It has been suggested that increased cerebral vascular resistance and pharmacological afterload reduction can cause redistribution of blood flow from cerebral circulation to somatic circulation, eventually resulting in decreased oxygen delivery to the brain. Low cerebral rSO₂ (<56%) detected using NIRS, during the first 48 postoperative hours, is associated with subsequent poor outcome such as death, need for extracorporeal membrane oxygenation, or longer hospitalization in the intensive care unit [41]. Hence, monitoring of cerebral oxygenation is highly recommended to promptly identify patients at risk of poor outcome since poor outcome can be prevented by improving cerebral oxygenation.

Splanchnic rSO₂ is usually higher than cerebral rSO₂ due to higher metabolic activity in the brain. McNeill et al. [15] reported that splanchnic rSO₂ is 5% to 15% higher than cerebral rSO₂ while Patel et al. [42] reported that the splanchnic rSO₂ in preterm infants without necrotizing enterocolitis is 63% to 91%.

Necrotizing enterocolitis is one of the most common gastrointestinal morbidities in preterm infants. The pathogenesis of necrotizing enterocolitis is multifactorial. However, intestinal ischemia is known to precede necrotizing enterocolitis. Preterm infants without necrotizing enterocolitis have higher splanchnic rSO₂ during the first week of life compared to preterm infants who develop necrotizing enterocolitis later (77.3% vs. 70.7%, P =0.002) [42]. Preterm infants with splanchnic rSO₂ ≤56% are at 11 times increased risk of developing necrotizing enterocolitis compared to preterm infants with splanchnic rSO₂ >56% [42]. Low splanchnic rSO₂ and high splanchnic FTOE in preterm infants are associated with complicated necrotizing enterocolitis, impending bowel perforation, or death compared to preterm infants with uncomplicated necrotizing enterocolitis [43]. Thus, NIRS monitoring is required to differentiate preterm infants who would subsequently develop complicated necrotizing enterocolitis from those who would not. Splanchnic rSO₂ monitoring may contribute to the early diagnosis of necrotizing enterocolitis and prevent bowel perforation or death.