Faculty Bibliography

AIM:Socio-economic status (SES) and ethnicity have been associated with worse maternal and fetal outcomes. Counties Manukau is a region of New Zealand which has a high portion of the population living in areas of low SES and has a higher population of ethnic minorities (Pacific Islander, Asian and Maaori). To determine whether SES and ethnicity are associated with worse mortality and morbidity in preterm infants in Counties Manukau Hospital, New Zealand. METHODS:This retrospective cohort study compared the infants of mothers who live in the most deprived neighbourhoods to the infants of mothers who live in the least deprived neighbourhoods. Infants born between 2000 and 2019 were included if <30 weeks gestation or <1500 g and born in hospital. Primary outcome was combined mortality/morbidity. RESULTS:Univariate analysis showed demographic differences between the SES and ethnic groups, for example maternal age and maternal smoking. Using logistic regression, SES was not associated with worse neonatal outcomes for the most deprived SES (n = 624) compared to least deprived SES (n = 164). Ethnicity (n = 1326) was not associated with worse neonatal outcomes. Gestational age and maternal smoking were associated with neonatal mortality/morbidity; gestational age and antenatal steroids were associated with neonatal mortality. It was notable that the proportion of the study population in the less deprived groups used for the comparisons was relatively low. CONCLUSIONS:For preterm, in-hospital births in Counties Manukau over a 20-year period, neonatal outcomes were the same regardless of SES or ethnicity.

OBJECTIVE:Due to logistical constraints, physicians traditionally delay diagnostic imaging for neonatal hypoxic-ischemic encephalopathy (HIE) until the neonate has completed all 72 hours of therapeutic hypothermia and rewarming. In some cases, neonates may require neuroimaging before 72 hours has passed. STUDY DESIGN:We present a case in which an MRI was acquired during active hypothermia. RESULTS:Upon return to the NICU, Baby X's temperature probe read 33.6 degrees, indicating that hypothermia was likely maintained at the target temperature. CONCLUSION:Active hypothermia is possible during MRI.

BACKGROUND:Withholding enteral feedings during hypothermia lacks supporting evidence. OBJECTIVES:We aimed to determine if minimal enteral nutrition (MEN) during hypothermia in patients with hypoxic-ischemic encephalopathy was associated with a reduced duration of parenteral nutrition, time to full oral feeds, and length of stay, but would not be associated with increased systemic inflammation or feeding complications. METHODS:We performed a pilot, retrospective, matched case-control study within the Florida Neonatal Neurologic Network from December 2012 to May 2016 of patients who received MEN during hypothermia (n = 17) versus those who were not fed (n = 17). Length of stay, feeding-related outcomes, and brain injury identified by MRI were compared. Serum inflammatory mediators were measured at 0-6, 24, and 96 h of life by multiplex assay. MRI were scored using the Barkovich system. RESULTS:MEN subjects had a reduced length of hospital stay (mean 15 ± 11 vs. 24 ± 19 days, p < 0.05), days receiving parenteral nutrition (7 ± 2 vs. 11 ± 6, p < 0.05), and time to full oral feeds (8 ± 5 vs. 18 ± 18, p < 0.05). MEN was associated with a significantly reduced serum IL-12p70 at 24 and 96 h (p < 0.05). Brain MRI scores were not significantly different between groups. CONCLUSION:MEN during hypothermia was associated with a reduced length of stay and time to full feeds, but did not increase feeding complications or systemic inflammation.

Temporal developmental progression is highly coordinated in Caenorhabditis elegans. However, loss of nicotinamidase PNC-1 activity slows reproductive development, uncoupling it from its typical progression relative to the soma. Using LC/MS we demonstrate that pnc-1 mutants do not salvage the nicotinamide released by NAD(+) consumers to resynthesize NAD(+), resulting in a reduction in global NAD(+) bioavailability. We manipulate NAD(+) levels to demonstrate that a minor deficit in NAD(+) availability is incompatible with a normal pace of gonad development. The NAD(+) deficit compromises NAD(+) consumer activity, but we surprisingly found no functional link between consumer activity and reproductive development. As a result we turned to a comparative metabolomics approach to identify the cause of the developmental phenotype. We reveal widespread metabolic perturbations, and using complementary pharmacological and genetic approaches, we demonstrate that a glycolytic block accounts for the slow pace of reproductive development. Interestingly, mitochondria are protected from both the deficiency in NAD(+) biosynthesis and the effects of reduced glycolytic output. We suggest that compensatory metabolic processes that maintain mitochondrial activity in the absence of efficient glycolysis are incompatible with the requirements for reproductive development, which requires high levels of cell division. In addition to demonstrating metabolic requirements for reproductive development, this work also has implications for understanding the mechanisms behind therapeutic interventions that target NAD(+) salvage biosynthesis for the purposes of inhibiting tumor growth.

Cervical spinal cord injuries may occur with catastrophic sequelae (e.g. quadriplegia) in collision sport activities. The discovery was made that the head-down tackling technique in football straightens the spine into a position vulnerable for compression and, thus, is responsible for these incidents. This led to rule changes requiring head-up tackling, which in turn resulted in the reduction of the incidence of these injuries. However, the dramatic initial reduction in the occurrence - from 32 and 34 catastrophic injuries in 1975 and 1976, respectively, down to 12 in 1977 - has levelled off with ten and eight reported cases in 2006 and 2007, respectively. The football community has increased their efforts to prevent head-down tackling with additional rule changes. Brachial plexus injury prevention must rely on properly fitted shoulder pads and use of equipment such as 'cowboy' collars. Furthermore, physicians must take into consideration cervical cord neurapraxia, congenital stenosis and other risk factors in patients who wish to return to contact sports.