Infrared Thermography with High Accuracy in a Neonatal Incubator.

As the accuracy of body temperature measurement is especially critical in premature infants on admission to the neonatal intensive care unit (NICU), noninvasive measurement using infrared thermography (IRT) has not been widely adopted in the NICU due to a lack of evidence regarding its accuracy. We have established a new calibration method for IRT in an incubator, and evaluated its accuracy and reliability at different incubator settings using a variable-temperature blackbody furnace. This method improved the accuracy and reliability of IRT with an increase in percentage of data with mean absolute error (MAE) < 0.3 °C to 93.1% compared to 4.2% using the standard method. Two of three IRTs had MAE < 0.1 °C under all conditions examined. This method provided high accuracy not only for measurements at specific times but also for continuous monitoring. It will also contribute to avoiding the risk of neonates' skin trouble caused by attaching a thermistor. This study will facilitate the development of novel means of administering neonatal body temperature.

Incubator humidity and temperature control in infants born at 22-23 weeks' gestation.

BACKGROUND: Preterm infants, especially those born at ≤23 gestational weeks (GW), present with extremes in insensible water loss (IWL) and changes in water balance. AIMS: To prevent water loss from the skin and achieve skin maturation without infection, we investigated transepidermal water loss (TEWL), IWL from the skin (IWL-s), and electrolyte balance with differences in high incubator humidity and temperature control from birth to postnatal 1 month in 22-23 GW and 24-25 GW infants. STUDY DESIGN: Prospective cohort study. SUBJECTS: Extremely preterm infants born at 22-23 GW (n = 11) and 24-25 GW (n = 11), admitted to the neonatal intensive care unit between September 2018 and October 2019. OUTCOME MEASURES: Total fluid intake (TFI), fluid output volume, TEWL, IWL-s, and electrolyte balance were compared between the two groups with controlled incubator humidity and temperature, gradually decreasing the humidity and ambient temperature from 95% to 50% and from 37.0 to 34.0 °C, respectively, while maintaining the central body temperature at 36.5-37.5 °C. RESULTS: TEWL and IWL-s between the 22-23 and 24-25 GW was not significantly different for infants at postnatal age. No significant difference in electrolyte imbalance was noted between the two groups, within the first 7 days. Differences in TEWL and IWL-s were eliminated with corresponding humidity and temperature adjustments. CONCLUSIONS: Incubator humidity and temperature control should aid management of 22-23 GW infants to reduce IWL, facilitate skin maturation, and prevent infection.

A method for improving semantic segmentation using thermographic images in infants.

BACKGROUND: Regulation of temperature is clinically important in the care of neonates because it has a significant impact on prognosis. Although probes that make contact with the skin are widely used to monitor temperature and provide spot central and peripheral temperature information, they do not provide details of the temperature distribution around the body. Although it is possible to obtain detailed temperature distributions using multiple probes, this is not clinically practical. Thermographic techniques have been reported for measurement of temperature distribution in infants. However, as these methods require manual selection of the regions of interest (ROIs), they are not suitable for introduction into clinical settings in hospitals. Here, we describe a method for segmentation of thermal images that enables continuous quantitative contactless monitoring of the temperature distribution over the whole body of neonates. METHODS: The semantic segmentation method, U-Net, was applied to thermal images of infants. The optimal combination of Weight Normalization, Group Normalization, and Flexible Rectified Linear Unit (FReLU) was evaluated. U-Net Generative Adversarial Network (U-Net GAN) was applied to thermal images, and a Self-Attention (SA) module was finally applied to U-Net GAN (U-Net GAN + SA) to improve precision. The semantic segmentation performance of these methods was evaluated. RESULTS: The optimal semantic segmentation performance was obtained with application of FReLU and Group Normalization to U-Net, showing accuracy of 92.9% and Mean Intersection over Union (mIoU) of 64.5%. U-Net GAN improved the performance, yielding accuracy of 93.3% and mIoU of 66.9%, and U-Net GAN + SA showed further improvement with accuracy of 93.5% and mIoU of 70.4%. CONCLUSIONS: FReLU and Group Normalization are appropriate semantic segmentation methods for application to neonatal thermal images. U-Net GAN and U-Net GAN + SA significantly improved the mIoU of segmentation.

Accuracy of a battery-powered portable capnometer in premature infants.

Carbon dioxide measurement is useful for confirmation of successful tracheal intubation and ensuring adequate ventilation. There are two types of CO2 detectors, i.e., single-use-only colorimetric devices and capnometers. Although portable capnometers are widely used for resuscitation, there have been no reports regarding their clinical utility in neonates. The correspondence between end-tidal CO2 (PetCO2) level determined using a battery-powered portable capnometer and arterial CO2 (PaCO2) was investigated using paired data obtained simultaneously from 26 neonates weighing 1262 ± 589 g at examination on mechanical ventilation. PetCO2 level and PaCO2 showed a strong correlation (r = 0.839, P < 0.001), and the correlation equation was: PetCO2 = 0.8 × PaCO2 + 1.1. Therefore, PetCO2 readings obtained with a battery-powered portable capnometer were likely to be underestimated. This became more pronounced with decreasing infant body weight at examination as the net difference in measurements of PaCO2 and PetCO2 was significantly positively correlated with infant body weight at examination (r = 0.451, P < 0.001). The observations presented here may be helpful in the use of battery-powered portable capnometers in neonates requiring controlled ventilation with tracheal intubation.

Risk Factors for Mortality and Neurodevelopmental Impairment among Neonates Born at 22-23 Weeks' Gestation.

INTRODUCTION: We aimed to evaluate the risk factors for mortality and neurodevelopmental impairment (NDI) among infants of 22-23 weeks' gestational age, which currently remain unclear. METHODS: This retrospective case-control study included 104 infants delivered at 22-23 weeks' gestation at Kagoshima City Hospital from 2006 to 2015. We compared 65 and 34 cases of survival to discharge and postnatal in-hospital death (5 excluded), respectively, and 26 and 35 cases with and without NDI, respectively, using maternal, prenatal, and postnatal records. A high rate of survivors' follow-up (61/65) was achieved in this study. RESULTS: The survival rate was 75.0% (21/28) and 62.0% (44/71) among infants born at 22 and 23 weeks' gestation, respectively. Infants who died weighed less (525.5 vs. 578 g, p = 0.04) and their intrauterine growth retardation (IUGR) rate (<5th percentile) was higher (14.7 vs. 1.5%, p = 0.02). Mortality was associated with an increased incidence of bradycardia on fetal heart rate monitoring (11.8 vs. 1.5%, p = 0.046), periventricular hemorrhagic infarction (PVHI; 32.4 vs. 6.2%, p = 0.001), necrotizing enterocolitis (NEC, surgery or drain tube; 14.7 vs. 0.0%, p = 0.004), and tension pneumothorax (29.4 vs. 6.2%, p = 0.004). There were significant differences in the proportion of PVHI (15.4 vs. 0%, p = 0.03) between infants with and without NDI. CONCLUSIONS: IUGR, bradycardia, PVHI, NEC, and tension pneumothorax were associated with neonatal mortality among infants born at 22-23 weeks' gestation. NDI at 36-42 months' chronological age was associated with PVHI.

Safety, speed, and effectiveness of air transportation for neonates.

BACKGROUND: In Japan, 44.3% of neonates are delivered in private clinics without an attending pediatrician. Obstetricians in the clinics must resuscitate asphyxiated neonates in unstable condition, such as respiratory failure, and they are frequently transferred to tertiary perinatal medical centers. There has been no study comparing the physiological status and prognosis of neonates transported by ambulance with those transported by helicopter. METHODS: Medical and transport records were used to compare the physiological status of neonates transported to Kagoshima City Hospital by land and those transported by air between January 1, 2013, and December 31, 2017. RESULTS: Data from 425 neonates transferred by land and 143 by air were analyzed. There were no significant differences between the two groups in mean gestational age, mean birthweight, fetal blood pH, Apgar score, or the Score for Neonatal Acute Physiology with Perinatal Extension-II (SNAPPE-II) on arrival to the tertiary center (16.3 ± 15.4 [95% confidence interval (CI): 13.2-17.7] vs 16.4 ± 15.4 [95% CI: 13.9-19.0], respectively; P = 0.999); both groups had SNAPPE-II score 10-19, indicating no difference in mortality risk. The times to starting first aid and to admission to the intensive care unit were significantly reduced in neonates transported by air than by land. In subgroup analysis of patients of a gestational age ≤28 weeks, all cases of severe intraventricular hemorrhage (IVH) were observed in the land transportation group. CONCLUSIONS: Neonatal transportation by air is as safe as land transportation, and time to first aid and intensive care are significantly reduced by transportation by air than by land. Air transport could also contribute to the prevention of IVH in neonatal transportation.

Assessment of risk factors for cystic periventricular leukomalacia.

AIM: Periventricular leukomalacia (PVL) is an important cause of cerebral palsy in premature infants, and cystic PVL is the most serious form of the disease. The risk factors for cystic PVL in singleton fetuses at a gestational age of <35 weeks are unclear. METHODS: This study included 2013 singleton birth infants delivered at a gestational age of <35 weeks in Kagoshima City Hospital between 2006 and 2017. The findings for 30 infants with cystic PVL were compared with those for 63 matched control infants by gestational age and birth weight. RESULTS: The cystic PVL was associated with increased incidence of recurrent late deceleration (L/D) (43.4% vs. 15.9%, P = 0.004) and loss of variability (LOV) (10.0% vs. 0.0%, P = 0.03) in fetal heart rate monitoring and late-onset circulatory dysfunction (LCD) (33.3% vs. 11.1%, P = 0.02). Logistic regression analysis revealed that recurrent L/D (odds ratio [OR] = 3.57, 95% confidence interval [CI]: 1.29-10.15, P = 0.01) and LCD (OR = 3.41, 95% CI: 1.09-11.04, P = 0.03) were risk factors associated with cystic PVL. LOV was not included in the multivariate analysis as there were too few cases in both the cystic PVL and control groups. CONCLUSION: Recurrent L/D, LOV and LCD are strongly associated with cystic PVL. In cases of fetal acidosis related to recurrent L/D or loss of variability, cystic PVL may occur.

Extracorporeal membrane oxygenation in 61 neonates: Single-center experience.

BACKGROUND: There have been few reports on the outcome of extracorporeal membrane oxygenation (ECMO) in newborn Japanese infants. METHODS: A review was carried out of 61 neonates with ECMO between January 1995 and December 2015 at a single center. ECMO was used in neonates with oxygenation index >20 after conventional treatment. Background factors, such as etiology, vascular access mode (veno-venous [VV] or veno-arterial [VA]), number of days with ECMO, and early ECMO (within 24 h after birth), were analyzed in relation to outcome with respect to survival to hospital discharge (SHD). RESULTS: Survival to hospital discharge was achieved in 35 infants (57%), while the remaining 26 died during hospital stay. Gestational age at birth was significantly higher and number of days with ECMO was significantly lower in SHD infants compared with those with adverse outcome (median, 4.0 vs 5.5 days, respectively; P = 0.008). The SHD rate was significantly higher for those with VV than VA vascular access mode (78%, 18/23 vs 45%, 17/38, respectively; P = 0.016), and for those with than without early ECMO (72%, 28/39 vs 32%, 7/22, respectively; P = 0.003). The SHD rate was relatively high in neonates with meconium aspiration syndrome (86%, 12/14), persistent pulmonary hypertension associated with hypoxic ischemic encephalopathy (75%, 6/8), and emphysema (80%, 4/5). On stepwise logistic regression analysis two independent factors of SHD were identified: early ECMO (OR, 9.63; 95%CI: 2.47-37.6) and ECMO length <8 days (OR, 8.05; 95%CI: 1.94-33.5). CONCLUSIONS: Neonates with early ECMO and those with ECMO duration <8 days may benefit from ECMO with respect to SHD.

Polymyxin B-immobilized fiber column direct hemoperfusion and continuous hemodiafiltration in premature neonates with systemic inflammatory response syndrome.

BACKGROUND: There have been no previous studies regarding whether combined use of Polymyxin B-immobilized fiber column direct hemoperfusion (PMX-DHP) and continuous hemodiafiltration (CHDF) is helpful in the treatment of preterm infants with systemic inflammatory response syndrome (SIRS) and hypercytokinemia. METHODS: A retrospective review was carried out of 18 SIRS infants born at gestational week 24-28. Eight with blood interleukin (IL)-6 ≥ 1000 pg/mL were treated actively with 2 h PMX-DHP followed by 2 h PMX-DHP and CHDF. Ten with IL-6 < 500 pg/mL were treated conventionally (with neither PMX-DHP nor CHDF) and served as controls. RESULTS: Demographic characteristics were similar except for IL-6, arterial-to-alveolar oxygen tension ratio (a/APO2 ), and number of immature neutrophils between the two groups. Baseline a/APO2 was significantly lower in infants with than without active treatment (0.44 vs 0.67, respectively, P = 0.002). After 4 h treatment, the IL-6 decreased to < 500 pg/mL in all eight infants, and a/APO2 improved significantly to 0.62 (P = 0.006). Bronchopulmonary dysplasia occurred in a similar proportion (63%, 5/8 vs 80%, 8/10, respectively), but the number of days on inhaled oxygen (30 vs 47 days, respectively, P = 0.033) and tracheal intubation (36 vs 51 days, respectively, P = 0.040) was significantly lower in infants with than without active treatment. Prevalence of adverse events was similar (13%, 1/8 vs 50%, 5/10 for active vs conventional treatment, respectively). CONCLUSION: Active treatment with PMX-DHP and CHDF was helpful in the reduction of days on inhaled oxygen and tracheal intubation in preterm SIRS infants with hypercytokinemia. Further prospective randomized studies are warranted.

Calcium concentration in hypoxic-ischemic encephalopathy during hypothermia.

BACKGROUND: The aim of this study was to investigate the relationship between prognosis and the changes in serum-ionized calcium concentration in neonates with hypoxic-ischemic encephalopathy (HIE) before and during brain hypothermia (BHT). METHODS: Serum samples were obtained from 16 HIE neonates who underwent BHT. All patients underwent developmental testing at 18 months of age. RESULTS: Mean serum-ionized calcium concentration in the poor outcome group (developmental quotient [DQ], <80; nine infants) was significantly lower than in the good outcome group (DQ >80; seven infants), both immediately before and after 6 h of BHT. Mean serum-ionized calcium concentration significantly decreased in both groups for 6 h, and the lowest adjusted serum-ionized calcium during 6 h of BHT was <1.05 mmol/L, known as the cut-off value for poor outcome, in 57.1% of the good outcome group. CONCLUSION: The influx of calcium into cells continues regardless of neurological prognosis during the early phase of BHT, but BHT might protect some high-risk patients against neurological damage at low adjusted serum-ionized calcium concentration.

Predicting onset of chronic lung disease using cord blood cytokines.

BACKGROUND: Applicability of cord blood interleukin-6 (IL-6) and interleukin-8 (IL-8) as markers for early prediction of the onset of chronic lung disease (CLD) due to intrauterine infection was investigated in the present study. METHODS: Eighty very low-birthweight infants with chorioamnionitis were divided into two groups: the CLD group (42 patients) and the non-CLD group (38 patients), according to the presence or absence of CLD, and the clinical background and cord blood IL-6 and IL-8 levels in each group were compared and investigated. RESULTS: The CLD group had significantly longer duration of mechanical ventilation and hospitalization (P < 0.05) and significantly higher IL-6 and IL-8 (P < 0.01) than the non-CLD group. Using the receiver operating characteristic curves of CLD onset for both IL-6 and IL-8, the cut-off value of IL-6 for predicting onset of CLD was 48.0 pg/mL, and its sensitivity and specificity were 76% and 96%, respectively. The cut-off value for IL-8 was 66.0 pg/mL, and its sensitivity and specificity were 71% and 82%, respectively. CONCLUSION: The cord blood levels of both IL-6 and IL-8 were significantly higher in the CLD group, indicating that both IL-6 and IL-8 are useful predictors of onset of CLD.

Septic neonate rescued by polymyxin B hemoperfusion.

Sepsis caused by group B streptococcus has been well controlled with aminobenzylpenicillin, but the incidence of Escherichia coli sepsis has increased in proportion. E. coli is a Gram-negative bacillus associated with poor prognosis due to the release of endotoxins. Conventional treatment with antibiotics alone may not be sufficient because the inflammatory response exacerbates the unstable hemodynamic status. Polymyxin B hemoperfusion has been established as a treatment option for septic shock in adults. Polymyxin B hemoperfusion adsorbs endotoxins and cannabinoids such as anandamide and 2-arachidonoylglycerol. Reported herein is a case of severe septic shock induced by E. coli. The concomitant use of polymyxin B hemoperfusion rapidly reduced the requirement for catecholamines and the patient was discharged without short-term neurological or respiratory sequelae. It is suggested that polymyxin B hemoperfusion might be an innovative therapy for severe sepsis, and could improve outcome.

New diagnostic technique in multi-slice computed tomography for in-stent restenosis: pixel count method.

OBJECTIVES: A diagnostic technique to objectively determine coronary in-stent stenosis was developed with multi(16)-slice computed tomography (MSCT), and it was compared with coronary angiography (CAG) in clinical cases. BACKGROUND: MSCT is expected to replace coronary angiography as a new non-invasive examination. Evaluation of highly calcified or in-stent lesions with CT is generally thought to be difficult. METHODS: Twenty lesions among 16 consecutive patients that were implanted with coronary stents were examined with both MSCT and CAG at follow-up. The minor axis cross sections of the stents were reconstructed at intervals of 1.5 mm with multiplanar reformation (MPR). The pixel with a higher CT value than the lowest CT value in the standard cross section at the proximal site out of stent was counted to determine the presence/absence of a stenotic lesion. RESULTS: Among 20 lesions, one case was not able to be evaluated with MSCT. MSCT correctly detected 3 of 4 cases with in-stent stenosis (sensitivity 75%), and 14 of 16 cases with no in-stent stenosis (specificity 88%, negative predictive value 93%, positive predictive value 75%). If analysis was made per-artery, sensitivity and specificity were 100% (3 of 3) and 87% (13 of 15), respectively, for detection of in-stent stenosis. CONCLUSIONS: This study was performed to examine a unique diagnostic technique: pixel count method, for coronary in-stent stenosis with MSCT. It showed that the coronary in-stent stenosis could be determined when stent struts were clearly imaged. Further examination is required with various stents, especially those with a diameter of 3.0 mm or smaller.

Amelioration of hyperglycemia in streptozotocin-induced diabetic mice with fetal pancreatic allografts: prevention of rejection by donor specific transfusion in conjunction with CTLA4Ig.

INTRODUCTION: Fetal pancreas has been considered as an alternative donor source for islet transplantation since it has potent capacity for beta cell differentiation and proliferation. However, prevention of fetal pancreatic allograft rejection can be hardly achieved compared with adult islet allografts. AIMS: The aim of the study is to determine whether donor specific transfusion (DST) in conjunction with CTLA4Ig has any favorable effect on prevention of fetal pancreatic allograft rejection in mice. METHODS: BALB/c splenocytes (SPC, 1 x 10) were injected iv into C57BL/6 mice in conjunction with CTLA4Ig (ip, 50 microgram, day 0, 2, and 4). Fourteen days later, the mice were made diabetic with streptozotocin (STZ, iv) and donor specific or third party pancreatic allografts were transplanted beneath the kidney capsule. RESULTS: Morphologically, it was found that rejection of fetal pancreatic allografts can be prevented at 30 days after transplantation only when donor specific allografts were grafted into the mice treated with DST in conjunction with CTLA4Ig. Functionally, 3 out of 9 diabetic mice became normoglycemic by 120 days after transplantation of fetal pancreatic allografts. CONCLUSION: DST in conjunction with CTLA4Ig can have a favorable effect on prevention of fetal pancreatic allograft rejection resulting in amelioration of STZ-induced diabetes in mice.

Acceptance of islet allografts in the liver of mice by blockade of an inducible costimulator.

BACKGROUND: An inducible costimulator (ICOS) has been found to be a novel costimulator for T-cell activation, although its precise role in transplant immunobiology remains unclear. This study determined whether ICOS plays an essential role in rejection of intrahepatic islet allografts in streptozotocin-induced diabetic mice. METHODS: Mononuclear cells in the liver of mice were isolated and examined by flow cytometry with respect to expression of ICOS in association with rejection, and the effects of in vivo treatment with an anti-ICOS antibody on survival of intrahepatic islet allografts were determined. RESULTSFlow cytometric analysis of mononuclear cells in the liver of normal untreated mice revealed that ICOS is expressed on CD4+CD3int natural killer T cells. The expression of ICOS was up-regulated on CD4+CD3bright T cells and expanded CD8 T cells in the liver in association with rejection. Posttransplant short-term administration of anti-ICOS antibody alone produced a significant prolongation of islet allograft survival. Administration of the antibody in conjunction with a subtherapeutic regimen of FK506 prevented rejection, leading to the acceptance of islet allografts. CONCLUSION: ICOS has an essential role in rejection of intrahepatic islet allografts and the blockade of ICOS interaction might be a novel approach for preventing islet allograft rejection.