Validity of non-invasive hemoglobin measured by pulse co-oximeter in neonates - An observational study

Background: Hemoglobin is a frequently ordered investigation in neonatal intensive care units. There is a need for hemoglobin estimation by point of care methods to reduce iatrogenic anemia and to alleviate pain associated with repeated venous sampling. Pulse co-oximeters have been developed to measure hemoglobin non-invasively based on spectrophotometric method. We compared hemoglobin measured by pulse co-oximeter with reference venous hemoglobin in neonates admitted to a tertiary care newborn unit. Design: This was an observational study. Duration: The study duration was from November 2016 to December 2016. Setting: Department of Neonatology, Institute of Child Health and Hospital for Children, Egmore. Methods: Neonates admitted in nursery who warranted hemoglobin estimation underwent both invasive venous hemoglobin estimation by automated hematology analyzer and non-invasive hemoglobin estimation by pulse co-oximeter (Masimo SET radical 7). Results: Of 158 newborns enrolled, the device failure rate was 12.5%. The bias between transcutaneous and venous hemoglobin was 1.66±2.26 g/dl (mean ± standard deviation). Transcutaneous and venous hemoglobin showed moderate agreement on Bland Altman plot with intraclass correlation coefficient of 0.56. At lower levels of hemoglobin, we noted higher bias. It was 2.69±1.87 g/dl at hemoglobin <13 g/dl and 3.29±1.86 at hemoglobin ≤10 g/dl. On regression analysis, only the level of hemoglobin influenced bias and device failure rate. Conclusion: Non-invasive hemoglobin measured by pulse co-oximeter shows only a moderate agreement with reference venous hemoglobin in neonates admitted to nursery. We report a high device failure rate of 12.6%. Level of hemoglobin is the single most determinant of device failure and degree of agreement. With high device failure rates and poor agreement at low hemoglobin levels, the clinical utility appears negligible

Transcriptomic profile of adverse neurodevelopmental outcomes after neonatal encephalopathy

A rapid and early diagnostic test to identify the encephalopathic babies at risk of adverse outcome may accelerate the development of neuroprotectants. We examined if a whole blood transcriptomic signature measured soon after birth, predicts adverse neurodevelopmental outcome eighteen months after neonatal encephalopathy. We performed next generation sequencing on whole blood ribonucleic acid obtained within six hours of birth from the first 47 encephalopathic babies recruited to the Hypothermia for Encephalopathy in Low and middle-income countries (HELIX) trial. Two infants with blood culture positive sepsis were excluded, and the data from remaining 45 were analysed. A total of 855 genes were significantly differentially expressed between the good and adverse outcome groups, of which RGS1 and SMC4 were the most significant. Biological pathway analysis adjusted for gender, trial randomisation allocation (cooling therapy versus usual care) and estimated blood leukocyte proportions revealed over-representation of genes from pathways related to melatonin and polo-like kinase in babies with adverse outcome. These preliminary data suggest that transcriptomic profiling may be a promising tool for rapid risk stratification in neonatal encephalopathy. It may provide insights into biological mechanisms and identify novel therapeutic targets for neuroprotection

Parental and professional perceptions of informed consent and participation in a time-critical neonatal trial: a mixed-methods study in India, Sri Lanka and Bangladesh

Introduction Time-critical neonatal trials in low-and-middle-income countries (LMICs) raise several ethical issues. Using a qualitative-dominant mixed-methods design, we explored informed consent process in Hypothermia for encephalopathy in low and middle-income countries (HELIX) trial conducted in India, Sri Lanka and Bangladesh.Methods Term infants with neonatal encephalopathy, aged less than 6 hours, were randomly allocated to cooling therapy or usual care, following informed parental consent. The consenting process was audio-video (A-V) recorded in all cases. We analysed A-V records of the consent process using a 5-point Likert scale on three parameters—empathy, information and autonomy. In addition, we used exploratory observation method to capture relevant aspects of consent process and discussions between parents and professionals. Finally, we conducted in-depth interviews with a subgroup of 20 parents and 15 healthcare professionals. A thematic analysis was performed on the observations of A-V records and on the interview transcripts.Results A total of 294 A-V records of the HELIX trial were analysed. Median (IQR) score for empathy, information and autonomy was 5 (0), 5 (1) and 5 (1), respectively. However, thematic analysis suggested that the consenting was a ceremonial process; and parental decision to participate was based on unreserved trust in the treating doctors, therapeutic misconception and access to an expensive treatment free of cost. Most parents did not understand the concept of a clinical trial nor the nature of the intervention. Professionals showed a strong bias towards cooling therapy and reported time constraints and explaining to multiple family members as key challenges.Conclusion Despite rigorous research governance and consent process, parental decisions were heavily influenced by situational incapacity and a trust in doctors to make the right decision on their behalf. Further research is required to identify culturally and context-appropriate strategies for informed trial participation