Association between Multi-Organ Involvement and Brain Injury in Cooled Newborns: A Statistical Approach.

INTRODUCTION: In the event of fetal hypoxia-ischemia, circulation to the brain and central organs is thought to be preserved. The objective of the study was to explore the relationship between the presence of brain injury on MRI and multi-organ involvement, as reflected in routinely collected laboratory (lab) values in babies who have undergone therapeutic hypothermia (TH) after hypoxic-ischemic encephalopathy (HIE). METHODS: Peak and trough values, and age at peak/trough, were obtained for 10 lab markers collected for clinical care, representing hematopoiesis, coagulation, inflammation, hepatic, and renal function, from 71 consecutively recruited newborns from four tertiary neonatal centers undergoing TH. Cerebral MR images obtained as part of clinical care were assessed by two raters with expertise, in a blinded fashion. RESULTS: There was no significant association between the presence of cerebral injury on MRI and systems involvement in newborns who have undergone TH. However, the peak/trough platelet ratio was significantly associated with cerebral injury. Also, the peak platelet, lymphocyte, and urea counts occurred significantly later in babies with substantial brain injury compared to those without. CONCLUSION: Using a statistical approach, we demonstrate that there is no clear relationship between multi-organ involvement and cerebral injury in babies with HIE who have undergone TH. We infer that babies may have cerebral injury in the absence of involvement of other organ systems. The platelet count ratio as an independent biomarker of cerebral injury in this group requires further investigation. Reference ranges of lab values for term newborns undergoing TH are provided.

Alterations in the Stool Microbiome in Newborns Undergoing Mild Therapeutic Hypothermia after Hypoxic-Ischemic Encephalopathy.

BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) is associated with brain injury in newborns and may lead to disability or death. Mild therapeutic hypothermia (TH) is an effective neuroprotective intervention and an established standard of care in western countries. The gut microbiome, the genomic and physicochemical contribution of the gut microbiota, serves important functions and is increasingly recognized as a major influencer on development. The impact of HIE and TH on the evolving gut microbiota of the newborn remains to be elucidated. OBJECTIVE: The objective of this study was to carry out an exploratory study on the effects of HIE and TH on the gut microbiome in term neonates. METHODS AND RESULTS: Stool samples were obtained from 28 newborns with HIE (median age 68 h) undergoing TH on the neonatal unit (HIE TH group), with a follow-on stool sample available for 20 of these babies (median age 151 h). For comparison, a single stool specimen was obtained from 19 healthy newborns on the postnatal ward (median age 34 h). The microbiota composition was determined using established microbial DNA extraction and 16S rRNA gene sequencing methodology. There was no difference in the mode of delivery or the method of feeding the newborns, once established, between the 2 groups. All the infants in the HIE TH group had received antibiotics compared to only one of the controls. A lower α-diversity, quantified by the Shannon diversity index, was noted in the microbiota of the HIE TH group in comparison to the control group. The HIE TH group had a higher mean relative abundance (MRA) of facultative anaerobes and aerobes such as Staphylococcus species and a lower MRA of strict anaerobes, such as members of the Bacteroides genus, compared to the control. Also, there was a significant reduction in the MRA of the genus Bifidobacterium in the HIE TH group. Although the mode of delivery exerts a profound influence on the gut microbiota of the newborn, distance-based redundancy analysis showed that TH may exert an independent influence. This study could not determine the independent contribution of the use of antibiotics or the neonatal intensive care unit environment. CONCLUSION: In this study, we demonstrate an alteration in the microbiota composition in newborns undergoing TH for HIE.