Improvement of point of care testing device for accurate whole blood glucose measurement in early neonates.

BACKGROUND: It is important that blood glucose concentrations be accurately and conveniently measured in infants. However, especially in the early neonatal period, point-of-care testing devices used for adults may not accurately measure blood glucose concentrations in neonates. METHODS: In Study 1, the accuracy of neonatal whole-blood glucose measurements was evaluated for the existing glucose analyser Glutest Mint® (hereinafter MINT1; Sanwa Kagaku Kenkyusho, Nagoya, Japan) by comparing the data with reference blood glucose concentrations. In Study 2, we used MINT2, which was modified based on the findings from Study 1, to measure whole-blood glucose concentrations in newborns, and the accuracy of the measurements was compared with that of MINT1. RESULTS: Blood glucose concentrations were measured in 100 infants each in Study 1 and 2. In Study 1, the whole-blood glucose concentrations measured using MINT1 were found to be significantly lower than the reference blood glucose concentrations in early neonates. The results of Study 1 suggested that characteristics of erythrocyte membranes in early neonates affected the measurements. Therefore, we conducted Study 2 using MINT2, which was modified to be less susceptible. MINT2 was found to accurately measure whole-blood glucose concentrations in the early neonatal period. CONCLUSION: The study showed that the point-of-care testing device could be improved to allow for accurate whole-blood glucose measurements in the early neonatal period.

Impact of hydrogen gas inhalation during therapeutic hypothermia on cerebral hemodynamics and oxygenation in the asphyxiated piglet.

We previously reported the neuroprotective potential of combined hydrogen (H2) gas ventilation therapy and therapeutic hypothermia (TH) by assessing the short-term neurological outcomes and histological findings of 5-day neonatal hypoxic-ischemic (HI) encephalopathy piglets. However, the effects of H2 gas on cerebral circulation and oxygen metabolism and on prognosis were unknown. Here, we used near-infrared time-resolved spectroscopy to compare combined H2 gas ventilation and TH with TH alone. Piglets were divided into three groups: HI insult with normothermia (NT, n = 10), HI insult with hypothermia (TH, 33.5 ± 0.5 °C, n = 8), and HI insult with hypothermia plus H2 ventilation (TH + H2, 2.1-2.7%, n = 8). H2 ventilation and TH were administered and the cerebral blood volume (CBV) and cerebral hemoglobin oxygen saturation (ScO2) were recorded for 24 h after the insult. CBV was significantly higher at 24 h after the insult in the TH + H2 group than in the other groups. ScO2 was significantly lower throughout the 24 h after the insult in the TH + H2 group than in the NT group. In conclusion, combined H2 gas ventilation and TH increased CBV and decreased ScO2, which may reflect elevated cerebral blood flow to meet greater oxygen demand for the surviving neurons, compared with TH alone.

Transcutaneous bilirubin-based screening reduces the need for blood exchange transfusion in Myanmar newborns: A single-center, retrospective study.

Background: Neonatal hyperbilirubinemia is a significant health problem in Myanmar. We introduced transcutaneous bilirubin (TcB) measurements in 2017 and developed an hour-specific TcB nomogram for early detection and treatment of hyperbilirubinemia in Myanmar neonates. This study aimed to evaluate whether our screening method for hyperbilirubinemia decreased the requirement of blood exchange therapy (ET). Methods: This retrospective cohort study was conducted at the Central Women's Hospital, Yangon. Two groups were included as follows: group 1 (control group; comprising infants born in 2016 and screened on the basis of Kramer's rule), and group 2 (intervention group; comprising infants born in 2019 and screened by TcB measurement using a nomogram). The number of ETs was analyzed based on causes of hyperbilirubinemia and number of days after birth. Results: Groups 1 and 2 comprised 12,968 and 10,090 infants, respectively. Forty-six and two infants in Groups 1 and 2, respectively, required an ET. The odds ratio for ET was 18.0 (Group 1 to Group 2; 95% confidence interval [CI]: 4.8-67.1; p = 0.000). Serum bilirubin values at the time ET was administered were significantly higher in Group 1 than those in Group 2 (median: 23.0 and 16.8, respectively). Conclusion: The management of hyperbilirubinemia using our screening method (TcB Nomogram) can effectively reduce the need for ET in neonates in Myanmar.

Cerebral hemodynamics during neonatal transition according to mode of delivery.

Cerebral haemodynamics during the immediate transition period in neonates may differ depending on whether delivery is vaginal or by caesarean section. However, these differences have never been confirmed by near-infrared time-resolved spectroscopy (TRS). Therefore, the purpose of this study was to compare cerebral blood volume (CBV) and cerebral haemoglobin oxygen saturation (ScO2) between healthy term neonates by mode of delivery. Subjects were 31 healthy term neonates who did not require resuscitation. Thirteen neonates were delivered vaginally (VD group) and 18 were delivered by elective caesarean section (CS group). Absolute oxyhaemoglobin, deoxyhaemoglobin, and total haemoglobin concentrations were measured continuously by TRS; oxyHb × 100/totalHb (ScO2) (%) and CBV (mL/100 g brain tissue) were also calculated. Measurements were started as soon as possible after birth, obtained from 1 to 2 min after birth, and continued until 15 min after birth. CBV was significantly higher in the VD group than in the CS group in the 4 min after birth but not thereafter. There were no significant between-group differences in ScO2 and SpO2. These findings indicate that there is a difference in cerebral haemodynamic patterns in the first 4 min after delivery between term neonates by mode of delivery when CBV is monitored by TRS.

Intravenous Edaravone plus Therapeutic Hypothermia Offers Limited Neuroprotection in the Hypoxic-Ischaemic Newborn Piglet.

BACKGROUND: Therapeutic hypothermia (TH) is a standard therapy for neonatal hypoxic-ischaemic encephalopathy. One potential additional therapy is the free radical scavenger edaravone (EV; 3-methyl-1-phenyl-2-pyrazolin-5-one). OBJECTIVES AND METHODS: This study aimed to compare the neuroprotective effects of edaravone plus therapeutic hypothermia (TH + EV) with those of TH alone after a hypoxic-ischaemic insult in the newborn piglet. Anaesthetized piglets were subjected to 40 min of hypoxia (3-5% inspired oxygen), and cerebral ischaemia was assessed using cerebral blood volume. Body temperature was maintained at 39.0 ± 0.5°C in the normothermia group (NT, n = 8) and at 33.5 ± 0.5°C (24 h after the insult) in the TH (n = 7) and TH + EV (3 mg/kg intravenous every 12 h for 3 days after the insult; n = 6) groups under mechanical ventilation. RESULTS: Five days after the insult, the mean (standard deviation) neurological scores were 10.9 (5.7) in the NT group, 17.0 (0.4) in the TH group (p = 0.025 vs. NT), and 15.0 (3.9) in the TH + EV group. The histopathological score of the TH + EV group showed no significant improvement compared with that of the other groups. CONCLUSION: TH + EV had no additive neuroprotective effects after hypoxia-ischaemia in neurological and histopathological assessments.

Hour-specific nomogram for transcutaneous Bilirubin in newborns in Myanmar.

BACKGROUND: Neonatal hyperbilirubinemia is a significant health problem in Myanmar, and the rate of kernicterus is also higher than in developed countries. Non-invasive methods for early detection and treatment of hyperbilirubinemia are urgently needed. In this study, we used transcutaneous bilirubin (TcB) measurements to develop an hour-specific TcB nomogram for the effective management of hyperbilirubinemia in Myanmar newborns. METHODS: The bilirubin levels of neonates born in Central Women Hospital in Yangon, Myanmar were measured three times a day within 72 h after birth using a transcutaneous bilirubinometer. An hour-specific TcB nomogram was created based on the data. RESULTS: Participants were 512 infants (287 boys, 225 girls) born in Central Women's Hospital in Yangon. The mean (±SD) gestational age was 38.4 ± 1.2 weeks; birthweight was 3078 ± 412 g. A total of 3,039 plots were obtained, and the TcB nomogram was created with smoothed percentile curves (97.5th, 50th, and 2.5th percentiles) for 0-72 h after birth. CONCLUSIONS: An hour-specific TcB nomogram was successfully created to manage hyperbilirubinemia in Myanmar newborns.

Hydrogen ventilation combined with mild hypothermia improves short-term neurological outcomes in a 5-day neonatal hypoxia-ischaemia piglet model.

Despite its poor outcomes, therapeutic hypothermia (TH) is the current standard treatment for neonatal hypoxic-ischaemic encephalopathy (HIE). In this study, due to its antioxidant, anti-inflammatory, and antiapoptotic properties, the effectiveness of molecular hydrogen (H2) combined with TH was evaluated by means of neurological and histological assessments. Piglets were divided into three groups: hypoxic-ischaemic insult with normothermia (NT), insult with hypothermia (TH, 33.5 ± 0.5 °C), and insult with hypothermia with H2 ventilation (TH-H2, 2.1-2.7%). H2 ventilation and TH were administered for 24 h. After ventilator weaning, neurological assessment was performed every 6 h for 5 days. On day 5, the brains of the piglets were harvested for histopathological analysis. Regarding the neurological score, the piglets in the TH-H2 group consistently had the highest score from day 2 to 5 and showed a significantly higher neurological score from day 3 compared with the NT group. Most piglets in the TH-H2 group could walk at day 3 of recovery, whereas walking ability was delayed in the two other groups. The histological results revealed that TH-H2 tended to improve the status of cortical gray matter and subcortical white matter, with a considerable reduction in cell death. In this study, the combination of TH and H2 improved short-term neurological outcomes in neonatal hypoxic-ischaemic piglets.

Bilirubin photoisomers in rhesus monkey serum.

As rhesus monkeys exhibit physiological jaundice during the neonatal period, we used rhesus monkey serum to examine changes in bilirubin photoisomers. Bilirubin-rhesus monkey serum solution was irradiated with blue light-emitting diode, and changes in the absorbance and bilirubin fraction were compared with those in bilirubin- human serum albumin (HSA) and bilirubin-rat albumin solutions. The λmax decreased with light irradiation. The mean production rate of cyclobilirubin IXα was 1.98, 199 and 0.76 × 10-2/min in rhesus monkey serum, HSA and rat albumin, respectively. There was no significant difference between rhesus monkey serum and HSA. The (ZE)-bilirubin IXα/(ZZ)-bilirubin IXα ratio was 0.33, 0.45, and 0.10, respectively, differing significantly among the groups. The (EZ)-bilirubin IXα/(ZZ)-bilirubin IXα ratio was 0.020, 0.010, and 0.062, respectively, with no significant difference between rhesus monkey serum and HSA. The production rate of (EZ)-cyclobilirubin XIIIα(= (ZE)-cyclobilirubin XIIIα) was 0.73, 1.60, and 0.51 × 10-2/min, respectively, with differing significantly among the groups. The (EZ)-bilirubin IIIα/(ZZ)-bilirubin IIIα ratio was significantly different among the groups at 0.20, 0.38, and 0.15, respectively. This is the first report demonstrating the photoisomerization of bilirubin in rhesus monkey serum and the animal with the same cyclobilirubin production rate as HSA.Rhesus monkeys may be used as an animal model for neonatal hyperbilirubinemia in humans to evaluate the efficacy of phototherapy.

Relationship between prolonged neural suppression and cerebral hemodynamic dysfunction during hypothermia in asphyxiated piglets.

OBJECTIVES: Hypothermia (HT) improves the outcome of neonatal hypoxic-ischemic encephalopathy. Here, we investigated changes during HT in cortical electrical activity using amplitude-integrated electroencephalography (aEEG) and in cerebral blood volume (CBV) and cerebral hemoglobin oxygen saturation using near-infrared time-resolved spectroscopy (TRS) and compared the results with those obtained during normothermia (NT) after a hypoxic-ischemic (HI) insult in a piglet model of asphyxia. We previously reported that a greater increase in CBV can indicate greater pressure-passive cerebral perfusion due to more severe brain injury and correlates with prolonged neural suppression during NT. We hypothesized that when energy metabolism is suppressed during HT, the cerebral hemodynamics of brains with severe injury would be suppressed to a greater extent, resulting in a greater decrease in CBV during HT that would correlate with prolonged neural suppression after insult. METHODS: Twenty-six piglets were divided into four groups: control with NT (C-NT, n = 3), control with HT (C-HT, n = 3), HI insult with NT (HI-NT, n = 10), and HI insult with HT (HI-HT, n = 10). TRS and aEEG were performed in all groups until 24 h after the insult. Piglets in the HI-HT group were maintained in a hypothermic state for 24 h after the insult. RESULTS: There was a positive linear correlation between changes in CBV at 1, 3, 6, and 12 h after the insult and low-amplitude aEEG (<5 µV) duration after insult in the HI-NT group, but a negative linear correlation between these two parameters at 6 and 12 h after the insult in the HI-HT group. The aEEG background score and low-amplitude EEG duration after the insult did not differ between these two groups. DISCUSSION AND CONCLUSION: A longer low-amplitude EEG duration after insult was associated with a greater CBV decrease during HT in the HI-HT group, suggesting that brains with more severe neural suppression could be more prone to HT-induced suppression of cerebral metabolism and circulation.

Effects of bilirubin photoisomers on the measurement of direct bilirubin by the bilirubin oxidase method.

Background We occasionally encounter increases in direct bilirubin value on reanalysis of the surplus serum collected in the past from a neonate with indirect hyperbilirubinemia. But the details of this phenomenon are unclear. We evaluated the change of direct bilirubin and the relation of bilirubin photoisomer of the serum exposed to room light. Methods Surplus serum samples from neonates with indirect hyperbilirubinemia were exposed to room light for 24 h. The bilirubin fraction assay of samples was performed by the bilirubin oxidase method (Nescauto and Aqua-auto Kainos reagent) and high-performance liquid chromatography. Results Direct bilirubin increased significantly from 0.61 to 2.36 mg/dL. The respective ratios of bilirubin photoisomers before and after exposure were as follows: cyclobilirubin (0.007 to 0.29) and (EZ)-bilirubin (0.018 to 0.041) increased significantly, (ZZ)-bilirubin decreased 0.84 to 0.55 significantly. The difference of the cyclobilirubin concentration was most closely associated with those of the direct bilirubin concentration. Conclusion Direct bilirubin value was increased after exposure to the room light, and increase in direct bilirubin was significantly correlated by cyclobilirubin increase in the serum samples from neonates with indirect hyperbilirubinemia.

Hypoxic-Ischemic Encephalopathy-Associated Liver Fatty Degeneration and the Effects of Therapeutic Hypothermia in Newborn Piglets.

BACKGROUND: Although liver can be injured under the hypoxic-ischemic encephalopathy (HIE) condition, there is currently no histopathological evidence. Therapeutic hypothermia is used to protect the brain; however, the therapeutic potential for concomitant liver injury is unknown. OBJECTIVES: This study aimed to histopathologically prove HIE-associated liver injury and to investigate the influence of therapeutic hypothermia in a newborn piglet HIE model. METHODS: Eighteen newborn piglets were divided into 3 groups: control (n = 4), HIE (n = 8), and therapeutic hypothermia (n = 6) groups. The hypoxic insult was induced by decreasing the fraction of inspiratory oxygen from 21 to 2-4% over 40 min while monitoring cerebral blood volume and cerebral hemoglobin oxygen saturation. For therapeutic hypothermia, whole-body cooling at 33-34°C was administered for 24 h after the hypoxic insult. We hematologically and histopathologically investigated the liver injury in all groups. RESULTS: Alanine transaminase and lactate dehydrogenase levels in the HIE group were significantly elevated compared with those in the control group. Micro-lipid droplet accumulation in the periportal zone, but not in the perivenous zone, was significantly greater in the HIE group than in the control group and significantly smaller in the therapeutic hypothermia group than in the HIE group. CONCLUSIONS: We demonstrated that micro-lipid droplet accumulation in the cytoplasm of hepatocytes in the periportal zone occurs under the HIE condition and that this accumulation is suppressed by therapeutic hypothermia.

Surgery for gastroesophageal reflux disease with Gaucher disease type 2.

Gaucher disease, the most common lysosomal storage disease, is sometimes complicated with gastroesophageal reflux disease (GERD). The present patient was a 136-day-old Japanese boy with Gaucher disease type 2. Enzyme replacement therapy and chemical chaperone therapy were successful for the skin disorders, joint contractures, hepatosplenomegaly and thrombocytopenia, but he also had GERD. Accordingly, a Nissen fundoplication with gastrostomy was performed. There was no vulnerability of organs, easy bleeding or difficulty of maintaining the visual field because of hepatosplenomegaly during operation. In the perioperative period, there was no prolonged wound healing or infection. GERD was improved. In the near future, the number of long-term survivors of Gaucher disease will increase due to improvements in medical therapy. Therefore, it is expected that the number of patients requiring fundoplication will also increase. In patients with successful medical therapy, surgical fundoplication can be safely and effectively performed.

Current incidence of clinical kernicterus in preterm infants in Japan.

Clinical kernicterus in preterm infants has recently been reported in Japan, diagnosed on the basis of clinical findings during the neonatal and infancy periods. We investigated the incidence of clinical kernicterus in preterm infants <30 weeks gestational age (GA) based on a nationwide survey conducted in 233 certified educational facilities for neonatologists. The numbers of infants admitted and infants who died within 14 days after birth during 2011, and the number of infants who subsequently developed clinical kernicterus, were recorded. A total of 2720 infants were analyzed, representing 59% (2720/4623) of all preterm live births <30 weeks GA in Japan in 2011. Of these, 159 (5.8%) died within 14 days after birth, similar to the national rate. Five infants developed clinical kernicterus in infancy (5/2720, 0.18%). The current incidence of clinical kernicterus in Japan is therefore estimated at 1.8 per 1000 live births <30 weeks GA.

Simultaneous measurement of cerebral hemoglobin oxygen saturation and blood volume in asphyxiated neonates by near-infrared time-resolved spectroscopy.

BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) usually results in a poor clinical outcome even when treated with hypothermic therapy (HT). Early postnatal changes in cerebral blood oxygenation and hemodynamics may be critical determinants of brain injury and the efficacy of HT. OBJECTIVES: We measured cerebral hemoglobin oxygen saturation (ScO2) and cerebral blood volume (CBV) by near-infrared time-resolved spectroscopy (TRS) in HT-treated and non-HT-treated neonatal HIE patients to assess the influence of these parameters on clinical outcome. METHODS: We retrospectively compared ScO2, CBV, and clinical outcomes of 11 neonates with HIE: 5 were treated by HT (HT-treated; 33.5°C±0.5°C for 72h starting approximately 6h after delivery) and 6 were not (non-HT-treated). Both CBV and ScO2 were measured by TRS at 6, 24, 48, and 72h after birth. Magnetic resonance imaging (MRI) was performed 1-2weeks after birth to assess brain injury. RESULTS: Five neonates had adverse outcomes (3 HT-treated, 2 non-HT-treated). Of these, 1 died within 3days of birth and 4 had abnormal MRI findings, including basal ganglia, white matter, and/or thalamic lesions. The other 6 neonates had normal MRI findings (favorable outcome). At 6h after birth, CBV was significantly higher in neonates with adverse outcomes compared with those with a favorable outcome. At 24h after birth, ScO2 was significantly higher in neonates with adverse outcomes. Furthermore, we found that combined CBV at 24h after birth plus ScO2 had the best predictive ability for neurological outcome: sensitivity, specificity, positive predictive value, and negative predictive value were all 100%. CONCLUSION: Early postnatal CBV and ScO2 elevations were predictive of a poor outcome in HIE. Therefore, measuring combined CBV plus ScO2 at 24h after birth can allow more precise prediction of neurological outcome. Control of postnatal CBV and ScO2 is critical for effective HIE treatment.

Cerebral blood volume measurement using near-infrared time-resolved spectroscopy and histopathological evaluation after hypoxic-ischemic insult in newborn piglets.

The aim of this study was to assess the relationship between the cerebral blood volume (CBV) measured by near-infrared time-resolved spectroscopy (TRS) and pathological change of the brain in a hypoxic-ischemic (HI) piglet model. Twenty-one anesthetized newborn piglets, including three sham controls, were studied. An HI event was induced by low inspired oxygen. CBV was measured using TRS (Hamamatsu TRS-10). Data were collected before, during, and 6h after the insult. CBV was calculated as the change from the end of the insult. The piglets were allowed to recover from anesthesia for 6h after the insult. At the age of 5 days, the brains of the piglets were perfusion-fixed, and histologic evaluations of brain tissue were performed. The extent of histopathological damage was graded in 0.5-unit intervals on a 9-step scale. CBV increments were well correlated with histopathological scores, especially at 1 and 3h after resuscitation. Spearman's rank-correlation coefficients at 1, 3, and 6h after resuscitation in the gray matter were 0.9016, 0.9127, and 0.6907, respectively. We conclude that an increased CBV after HI insult indicates more marked histological brain damage. CBV measurement immediately after resuscitation provides a more precise prediction of the histological outcome.

Evaluation of cerebral circulation and oxygen metabolism in infants using near-infrared light.

Bedside monitoring of cerebral circulation or oxygen metabolism in infants to appropriately manage circulation and establish the oxygen dose, aiming at improving the neurological prognosis, is needed in general clinical practice. Near-infrared spectroscopy is used for measurements of neonatal cerebral Hb oxygen saturation, cerebral blood volume, cerebral blood flow and cerebral metabolic rate of oxygen. Near-infrared time-resolved spectroscopy is particularly useful for bedside evaluation of cerebral circulation and oxygen metabolism because of its simple measurement procedure. Combined evaluation of cerebral blood volume and cerebral Hb oxygen saturation is expected to contribute to treatment centering on the brain in neonatal medical care.

Relationship between early changes in cerebral blood volume and electrocortical activity after hypoxic-ischemic insult in newborn piglets.

BACKGROUND: Early changes in cerebral hemodynamics and depressed electrocortical activity have been reported after a hypoxic-ischemic (HI) insult. However, the relationship between these two parameters is unclear. This study aimed to examine the relationship between changes in cerebral blood volume (CBV) and cerebral Hb oxygen saturation (ScO2) after a HI insult and the low amplitude-integrated electroencephalography (aEEG) duration concomitantly observed. METHODS: Sixteen newborn piglets obtained within 24h of birth were used (n=3 controls). Thirteen piglets were subjected to a HI insult of 20-min low-amplitude aEEG (<5 µV, LAEEG), after which a low mean arterial blood pressure (<70% of baseline) was maintained for 10 min. We measured changes in CBV and ScO2 using near-infrared time-resolved spectroscopy (TRS) and cerebral electrocortical activities using aEEG until 6h after the insult. RESULTS: A positive correlation was observed between the LAEEG duration and CBV increase, but not ScO2, after the insult. CONCLUSION: These results suggest that a larger increase in CBV reflected a more severe failure in cerebral circulation to maintain cell membrane action potentials, which induced a more extended recovery period of electrocortical activity after the insult. We conclude that an early increase in CBV and longer LAEEG indicate severe brain injury.

Hour-specific nomogram for transcutaneous bilirubin in Japanese neonates.

BACKGROUND: The measurement of transcutaneous bilirubin (TcB) is very important to screen for hyperbilirubinemia in newborns. Until now, however, there has been no hour-specific, percentile-based TcB nomogram during the early neonatal period in Japanese neonates. The aim of this study was to develop a TcB nomogram within 72 h of birth in Japanese neonates. METHODS: A total of 3152 TcB measurements for 181 healthy Japanese neonates (gestational age ≥36 weeks, birthweight ≥2300 g) were obtained within 72 h of birth. All measurements were performed with a Konica Minolta jaundice meter, the JM-103. A nomogram curve was plotted to show the trend of TcB level over time. RESULTS: The nomogram curves rose almost linearly for all percentiles until 72 h after birth. CONCLUSION: An hour-specific, percentile-based TcB nomogram during the first 72 h after birth in Japanese neonates was successfully developed. Because Japanese neonates have higher and later peak bilirubin, an original hour-specific 97.5th percentile-based TcB nomogram may be needed to identify early-onset jaundice and manage neonatal hyperbilirubinemia.

Extrauterine environment influences spontaneous low-frequency oscillations in the preterm brain.

Low-frequency oscillations in cerebral blood flow that are suggestive of resting-state brain activity have recently been reported, but no study on the development of resting-state brain activity in preterm infants has been performed. The objective of this study was to measure the cerebral blood flow oscillations, which are assumed to represent brain function in the resting state, in preterm and term infants of the same postconceptional age. The subjects were 9 preterm infants who had reached full term (gestational age (GA): 23-34 weeks, postconceptional age: 37-46 weeks) and 10 term infants (GA: 37-40 weeks, postconceptional age: 37-41 weeks). Their changes in concentration of oxyhemoglobin ([oxyHb]) and deoxyhemoglobin ([deoxyHb]) were measured in the parieto-temporal region during quiet sleep using multi-channel near-infrared spectroscopy, and the power spectral densities (PSD) of the oscillations in the concentrations of these molecules were analyzed and compared. The preterm infants displayed a higher proportion of 0.06-0.10 Hz low frequency oscillations of [oxyHb] and [deoxyHb] than the term infants, and the gestational age and the proportion of low frequency oscillations were inversely correlated. These findings suggest that resting-state cerebral blood flow oscillations differ between preterm and term infants, and that the development of circulatory regulation and nerve activity in preterm infants are influenced by the extrauterine environment.