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Objectives Therapeutic hypothermia is an effective neuroprotective intervention for infants with moderate or severe hypoxic-ischemic encephalopathy (HIE). With the introduction of new medical therapy comes a learning curve with regards to its proper implementation and understanding of eligibility guidelines. We hypothesized that variation in patient selection and lack of adherence to established protocols contributed to the utilization drift away from the original eligibility guidelines. Methods A retrospective cohort study was conducted including infants who received therapeutic hypothermia in the neonatal intensive care unit (NICU) for HIE to determine utilization drift. We then used QI methodology to address gaps in medical documentation that may lead to the conclusion that therapeutic hypothermia was inappropriately applied. Results We identified 54% of infants who received therapeutic hypothermia who did not meet the clinical, physiologic, and neurologic examination criteria for this intervention based on provider admission and discharge documentation within the electronic medical record (EMR). Review of the charts identified incomplete documentation in 71% of cases and led to the following interventions: 1) implementation of EMR smartphrases; 2) engagement of key stakeholders and education of faculty, residents, and neonatal nurse practitioners; and 3) performance measurement and sharing of data. We were able to improve both adherence to the therapeutic hypothermia guidelines and achieve 100% documentation of the modified Sarnat score. Conclusions Incomplete documentation can lead to the assumption that therapeutic hypothermia was inappropriately applied when reviewing a patient’s EMR. However, in actual clinical practice physicians follow the clinical guidelines but are not documenting their medical decision making completely. QI methodology addresses this gap in documentation, which will help determine the true utilization drift of therapeutic hypothermia in future studies.

ObjectivesRecombinant human erythropoietin (rhEPO) has been shown to effectively and safely prevent the anemia of prematurity and to reduce the transfusion need in very low birth weight (VLBW) infants and has been licensed for this indication in Europe in 1997. The objective of the study was to obtain information on the use or non-use of rhEPO in neonatal units in Germany and other European countries.MethodsAnonymized 14-questions web-based questionnaire.ResultsSeventy-nine questionnaires from Germany and 63 questionnaires from other 15 European countries were completed. Of the responders, 39% indicated to use rhEPO routinely or occasionally in VLBW infants, whereas 61% responded to never use rhEPO in this population. The major reasons given for non-use were lack of recommendation in national guidelines (69%) and/or doubt about efficacy of rhEPO to reduce transfusion need (53%). Twenty-seven percent of the responders indicated to use rhEPO for neonates with birth weights above 1,500 g. Neuroprotection in VLBW infants (26%) and hypoxic ischemic encephalopathy in term neonates (27%) were given as indications for off label use of rhEPO.ConclusionsThis survey indicates that rhEPO is used for the anemia of prematurity as licensed in less than half of neonatal units in Germany and other European countries. On the other hand it seems to be used off label in neonates for neuroprotection in a considerable number of units although there is no final evidence on its neuroprotective effects.

Objective To describe the clinical characteristics and risk factors in infants with subcutaneous fat necrosis (SFN) following therapeutic hypothermia for hypoxic-ischemic encephalopathy (HIE). Methods A case-control study was performed by a retrospective chart review of infants with moderate or severe HIE admitted to a level IV regional perinatal center and who underwent whole-body cooling. Results A total of 14 (8.1%) of 171 infants with moderate or severe HIE who underwent whole-body cooling developed SFN during hospitalization. There were more females [71% (10/14)] and large-for-gestational age (LGA) infants [28% (4/14)] in the SFN group vs. 36% females (57/157) and 8% LGA infants (13/157) in the group without SFN (P-values of 0.009 and 0.015, respectively). The mean lowest platelet count was lower 108 ± 55 109/L vs. 146 ± 62 109/L and the mean highest calcium level was higher 11.3 ± 2.5 vs. 10.6 ± 0.8 mg/dL in infants with SFN vs. infants without SFN, respectively (P-values of 0.0078 and 0.006, respectively). Distribution of skin lesions followed distinctive patterns representing the areas with direct contact with the cooling blanket. One infant developed severe, life-threatening hypercalcemia that required aggressive management, including diuretics, corticosteroids and bisphosphonates. Conclusion Although SFN is a rare complication of therapeutic hypothermia, it can be a life-threatening condition if complicated by severe hypercalcemia. Infants who undergo therapeutic hypothermia for HIE need regular skin examinations to evaluate for SFN. If SFN is identified, monitoring of serum calcium levels to prevent life-threatening hypercalcemia is recommended.

Background Erythropoietin (EPO) appears to confer neuroprotection to the injured brain. Randomized clinical trials (RCTs) have demonstrated its safety in neonates with hypoxic-ischemic encephalopathy (HIE); however, the evidence is unclear. The objective of this study was to examine the role of EPO in perinatal HIE by a systematic review and meta-analysis. Methods Database search included Embase, MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Cochrane Central Register of Controlled Trials (CENTRAL). RCTs reporting a death, neurodevelopmental outcomes or brain injury were included. Two authors extracted the data independently from included studies and assessed the level of evidence (LOE). Results Six RCTs (EPO=5 and darbepoetin α=1) involving 454 neonates were included. A trend toward a lower risk of death was identified in infants treated with EPO [EPO with or without hypothermia: five RCTs, 368 participants, relative risk (RR) 0.74, 95% confidence interval (CI) 0.47–1.19, LOE−low; EPO without hypothermia: four RCTs, 318 participants, RR 0.89, 95% CI 0.49–1.32, LOE−low]. EPO treatment without hypothermia compared to placebo resulted in a reduced risk of cerebral palsy (two RCTs, 230 participants, RR 0.47, 95% CI 0.27–0.80, LOE−moderate) and moderate to severe cognitive impairment (two RCTs, 226 participants, RR 0.49, 95% CI 0.28–0.85, LOE−moderate). A reduced risk of brain injury was identified in EPO treated infants (EPO with or without hypothermia, two RCTs, 148 participants, RR 0.70, 95% CI 0.53–0.92, LOE−moderate). Conclusion EPO administration in neonates with perinatal HIE reduces the risk of brain injury, cerebral palsy and cognitive impairment. The evidence is limited to suggest its role as an adjuvant to hypothermia. Larger powered trials are underway to overcome this limitation.

BackgroundEvaluation of newborns for hypoxic ischemic encephalopathy (HIE) includes laboratory and clinical parameters, as well as amplitude integrated electroencephalogram (aEEG). Based on qualifying criteria, selective head cooling (SHC) is initiated for infants with evidence of moderate to severe HIE. However, some newborns may not qualify for hypothermia therapy based on normal aEEG.ObjectiveTo compare levels of serum glial fibrillary acidic protein (GFAP), ubiquitin c-terminal hydrolase-1 (UCHL-1) protein and phosphorylated axonal neurofilament heavy chain (pNF-H), in newborns who met initial screening criteria for HIE but did not qualify for head cooling, to the levels in healthy newborns.Study designNewborns ≥36 weeks of gestational age at risk for HIE, who were evaluated but did not qualify for SHC from July 2013 through June 2014 at NYU Langone Medical Center and Bellevue Hospital center were enrolled. A control group included healthy newborns from the newborn nursery (NBN). Serum samples were collected between 24 and 48 h of life from both groups.ResultsThere was no significant difference in the serum levels of GFAP, UCHL-1 protein and pNF-H between the two groups of infants.ConclusionNewborns at risk for HIE who met the initial criteria for head cooling but who were excluded based on normal aEEG did not show significant elevation of biomarkers of brain injury compared to healthy newborns. These findings may help to validate using aEEG as an additional evaluation criteria in cooling.

Objective:To evaluate the association between planned home birth and neonatal hypoxic ischemic encephalopathy (HIE).Methods:This is a case-control study in which a database of neonates who underwent head cooling for HIE at our institution from 2007 to 2011 was linked to New York City (NYC) vital records. Four normal controls per case were then randomly selected from the birth certificate data after matching for year of birth, geographic location, and gestational age. Demographic and obstetric information was obtained from the vital records for both the cases and controls. Location of birth was analyzed as hospital or out of hospital birth. Details from the out of hospital deliveries were reviewed to determine if the delivery was a planned home birth. Maternal and pregnancy characteristics were examined as covariates and potential confounders. Logistic regression was used to determine the odds of HIE by intended location of delivery.Results:Sixty-nine neonates who underwent head cooling for HIE had available vital record data on their births. The 69 cases were matched to 276 normal controls. After adjusting for pregnancy characteristics and mode of delivery, neonates with HIE had a 44.0-fold [95% confidence interval (CI) 1.7–256.4] odds of having delivered out of hospital, whether unplanned or planned. Infants with HIE had a 21.0-fold (95% CI 1.7–256.4) increase in adjusted odds of having had a planned home birth compared to infants without HIE.Conclusion:Out of hospital birth, whether planned home birth or unplanned out of hospital birth, is associated with an increase in the odds of neonatal HIE.

Aims: The association between the planned delivery mode and adverse perinatal outcomes of monochorionic diamniotic (MCDA) twin pregnancies at ≥36 weeks’ gestation was evaluated. Methods: This retrospective cohort study included uncomplicated MCDA twin pregnancies delivered after 36 weeks’ gestation during a 10-year period. Cases were classified into the trial of labor (TOL) or cesarean section (CS) group according to the planned delivery mode. The primary outcome was a composite of adverse outcomes for at least one twin, including intrauterine fetal death (IUFD) after 36 weeks, neonatal death, umbilical artery pH Results: We included the 310 pregnancies delivered after 36 weeks’ gestation. After excluding 15 patients, the final analysis included 295 MCDA pregnancies: 63% had delivered through TOL and 37% through CS. The incidences of composite adverse outcomes in the TOL and CS groups were 4.3% and 1.9%, respectively. No IUFD, neonatal death, MAS, RDS, or AFFH was observed; two infants in each group developed HIE. Adverse outcomes were not significantly associated with any risk factor, including delivery through TOL. Conclusion: TOL may not influence the perinatal outcomes of MCDA twin pregnancies delivered at ≥36 weeks’ gestation.

Objectives: There are few population-based studies of hypoxic ischemic encephalopathy (HIE) in sub-Saharan Africa, and the published criteria that are used to define and grade HIE are too variable for meaningful comparisons between studies and populations. Our objectives were (1) to investigate how the incidence of HIE in our region varies with different criteria for intrapartum hypoxia and (2) to determine how encephalopathy severity varies with different grading systems. Method: We reviewed the records of infants with a diagnosis of HIE born between September 2008 and March 2009 in public facilities in the Southern Cape Peninsula, South Africa. The incidence of HIE was calculated according to four definitions of intrapartum hypoxia and graded according to three methods. Results: Depending on which defining criteria were applied, the incidence of HIE varied from 2.3 to 4.3 per 1000 live births, of mild HIE ranged from 0.4 to 1.3 per 1000 live births, and of moderate-severe HIE ranged from 1.5 to 3.7 per 1000 live births. Ninety-seven of the 110 (88%) infants reviewed had at least one intrapartum-related abnormality. Only 62 (56%) infants had a blood gas performed in the first hour of life. Conclusion: The incidence and grade of HIE can vary more than 2-fold in the same population, depending on which defining criteria are used. Consensus definitions are needed for benchmarking.

Background: Recent newborn resuscitation guidelines recommend therapeutic hypothermia (TH) as a treatment to reduce long-term neurological deficit in hypoxic ischemic encephalopathy (HIE) survivors. In South Africa, varied resource constraints may present difficulties in the implementation of TH. Objective: To determine the opinions and practice of South African pediatricians, regarding TH and the management of HIE. Methods: We invited 288 South African pediatricians and neonatologists to participate in a web-based survey by e-mail. Practitioners were identified using the Medpages™ database. Results: Responses were received from 37.8% of the e-mails. Seventy-six percent of respondents stated that hypothermia was either effective or very effective while 4% stated TH was ineffective in the management of HIE. Only 42% of respondents offered TH and a further 9% transferred patients to other units for cooling. Twenty-four percent had not implemented TH nor planned to introduce it into practice in the near future. Ninety-eight percent of respondents stated TH should be the standard of care in tertiary neonatal units. Conclusion: Most pediatricians in South Africa who responded to the survey stated that TH is effective to reduce the neurological deficit in HIE, however, less than half offered it as a treatment.

AIM To analyze short-term neonatal outcome and the sampling to delivery interval in cases with severe intrapartum acidemia diagnosed with fetal scalp blood sampling (FBS). METHODS This is a secondary analysis of data from a trial of 2992 women, who were, when indicated, randomized to either lactate or pH analyses by FBS. Median and 95(th) centile values for lactate analyses were 2.9 mmol/L and 6.6 mmol/L, respectively. Corresponding pH values were 7.30 and 7.17. We defined severe intrapartum acidemia as lactate >6.6 mmol/L or pH

Objective: To establish a simple and quick method that could be used to predict the occurrence of hypoxic ischemic encephalopathy (HIE) as early as possible by investigating the variations of nucleated red blood cells per 100 white blood cell (NRBC/100 WBC) counts and lactate levels in cord blood. Methods: In 46 cases of acute fetal distress (AFD) and 54 cases of chronic fetal distress (CFD) neonates we measured the percentage (NRBCs/100 WBC) and lactate in the umbilical blood. Results: Both lactate levels and NRBC/100WBC counts were higher in CFD and AFD groups than in controls (both P

The possibility of a therapeutic role for cerebral hypothermia during or after resuscitation from perinatal asphyxia has been a long-standing focus of research. However, early studies had limited and contradictory results. It is now known that severe hypoxia-ischemia may not cause immediate cell death, but may precipitate a complex biochemical cascade leading to the delayed development of neuronal loss. These phases include a latent phase after reperfusion, with initial recovery of cerebral energy metabolism but EEG suppression, followed by a secondary phase characterized by accumulation of cytotoxins, seizures, cytotoxic edema, and failure of cerebral oxidative metabolism from 6 to 15 h post insult. Although many of the secondary processes can be injurious, they appear to be primarily epiphenomena of the 'execution' phase of cell death. This conceptual framework allows a better understanding of the experimental parameters that determine effective hypothermic neuroprotection, including the timing of initiation of cooling, its duration and the depth of cooling attained. Moderate cerebral hypothermia initiated in the latent phase, between one and as late as 6 h after reperfusion, and continued for a sufficient duration in relation to the severity of the cerebral injury, has been consistently associated with potent, long-lasting neuroprotection in both adult and perinatal species. The results of the first large multicentre randomized trial of head cooling for neonatal encephalopathy and previous phase I and II studies now strongly suggest that prolonged cerebral hypothermia is both generally safe - at least in an intensive care setting - and can improve intact survival up to 18 months of age. Both long-term followup studies and further large studies of whole body cooling are in progress.

An asphyxiated infant with severe hypoxic-ischemic encephalopathy was treated by brain hypothermia using extracorporeal membrane oxygenation (ECMO). The brain hypothermia using ECMO maintained cardiopulmonary functions and stabilized brain temperatures by stably supply of the cooled blood to the brain. Moreover,we measured the levels of glucose, lactate, ionized calcium and glutamate in plasma. The comparison between these levels in the artery and in the cephalic vein, suggests that glucose, lactate, ionized calcium and glutamate might be used as markers of the effects of hypothermia therapy.

BACKGROUND Phenobarbital is one of the oldest, cheapest and easily available cerebroprotective drugs for the hypoxic brain. However, its potential and various actions have not been fully explored. AIM To evaluate the effects of Phenobarbital on levels of oxidants and anti-oxidants in term and near term neonates with hypoxic ischemic encephalopathy. METHODS Design--randomized controlled trial. Setting--tertiary care referral perinatal centre. Procedure--asphyxiated neonates (gestation > or = 34 weeks) with HIE were randomized to receive Phenobarbital 20 mg/kg i.v. within first six hours of life or to control group. CSF levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx) and blood levels of vitamins A and E were estimated at 10-12 hours of age. RESULTS CSF levels of MDA, SOD, GPx and blood levels of vitamins A and E were significantly lower in the Phenobarbital group (p

OBJECTIVE To determine which intrapartum fetal heart rate parameters in the presence of severe neonatal acidosis (pH < 7.0) appropriately predicts the development of neonatal seizures in the context of hypoxic ischemic encephalopathy (HIE). METHODS The intrapartum fetal heart rate tracings of 25 neonates who developed neonatal seizures secondary to HIE were compared with 25 matched neonates with similar pH and gestational age who did not develop seizures. All patients had at least 2 hours of intrapartum fetal heart rate patterns available for review. We compared the fetal heart rate parameters of prolonged deceleration, variable and late decelerations, variability, accelerations, fetal heart rate baseline and duration of the fetal heart rate abnormality. Comparison between the groups was done using chi-square for nominal data and student t-tests for continuous data. RESULTS Neonates with seizures 2 degrees HIE had a significantly longer duration of abnormal fetal heart rate patterns (72 +/- 12 minutes vs 48 +/- 12 minutes, p < 0.001). DISCUSSION This study demonstrated that in the setting of neonatal acidosis the development of seizures is related to the period of stress (duration of the abnormal fetal heart rate pattern).

Two groups of 30 term newborns (normal and anoxic) were analyzed to study the influence of anoxia in the heart rate. The experiment consisted in a polygraphic EEG register before, during and after an acoustic stimulus. In basal conditions of active sleep, the heart rate in the asphyctic newborn was higher than in the normal group. The acoustic stimulation caused a transitional tachycardia. The variability of the heart rate was smaller in the asphyctic group. The basal heart rate varied in relation to the grade of Hypoxic-Ischemic Encephalopathy (HIE) and there was also a difference in the capacity of response to acoustic stimulation between the moderate HIE group and the normal group.