Evaluating emergency-release blood transfusion of newborn infants at the Intermountain Healthcare hospitals.

BACKGROUND: An emergency-release blood transfusion (ERBT) protocol (uncrossmatched type O-negative red blood cells, AB plasma, AB platelets) is critical for neonatology practice. However, few reports of emergency transfusions are available. We conducted an ERBT quality improvement project as a basis for progress. STUDY DESIGN AND METHODS: For each ERBT in the past 8 years, we logged indications, products, locations and timing of the transfusions, and outcomes. RESULTS: One hundred forty-nine ERBTs were administered; 42% involved a single blood product, and 58% involved two or more. The incidence was 6.25 ERBT per 10,000 live births, with a higher rate (9.52 ERBT/10,000) in hospitals with a Level 3 neonatal intensive care unit (NICU) (p < 0.001). Seventy percent of ERBTs were administered in a NICU and 30% in a delivery room, operating room, or emergency department. Indications were abruption/previa (32.2%), congenital anemia (i.e., fetomaternal hemorrhage; 15.4%), umbilical cord accident (i.e., velamentous insertion; 15.0%), and bleeding/coagulopathy (12.8%). Fifty-eight percent of those with hemorrhage before birth did not have a hemoglobin value reported on the umbilical cord gas; thus, anemia was not recognized initially. None of the 149 ERBTs were administered using a blood warmer. The mortality rate of recipients was 35%. CONCLUSION: Based on our findings, we recommend including a hemoglobin value with every cord blood gas after emergency delivery to rapidly identify fetal anemia. We also discuss two potential improvements for future testing: 1) the use of a warming device for massive transfusion of neonates and 2) the use of low-titer group O cold-stored whole blood for massive hemorrhage in neonates.

First report of using low-titer cold-stored type O whole blood in massive postpartum hemorrhage.

BACKGROUND: In cases of massive hemorrhage in the US military, improved outcomes have been reported with the use of warm, fresh whole blood transfusions. Cold-stored low-titer type O whole blood (LTOWB) has become the preferred product for resuscitation of severe bleeding in deployed surgical units. Reports of LTOWB use in civilian trauma are becoming more frequent. CASE REPORT: We report our experience with emergency transfusion of LTOWB for a woman with massive postpartum hemorrhage. The patient had two previous cesarean section deliveries at term without complications. With her third elective cesarean section at term, blood loss during surgery was not excessive, but 3 to 4 hours later she had an estimated blood loss of 3600 mL. Despite measures to control the hemorrhage, she rapidly became hypotensive and tachycardic, and our massive transfusion protocol (MTP) was activated. The transfusion service had very recently incorporated LTOWB into Trauma Pack 1 of the MTP. She received two LTOWB units, after which her hemorrhaging ceased, blood pressure normalized, and she became alert. One hour later she received one unit of fresh frozen plasma and one unit of red blood cells (RBCs). The following morning she received one unit of crossmatched RBCs, for a hematocrit of 20.7%. She was discharged home on Day 4, and she remains healthy. CONCLUSIONS: This is the first report of which we are aware of massive postpartum hemorrhage treated using LTOWB. Our positive experience leads us to speculate that this approach could have a role in massive obstetric hemorrhage.

Validation of Test Weighing Protocol to Estimate Enteral Feeding Volumes in Preterm Infants.

OBJECTIVE: To evaluate the accuracy of pre- and postfeeding weights to estimate enteral feeding volumes in preterm infants. STUDY DESIGN: Single-center prospective cohort study of infants 28-36 weeks' corrected age receiving gavage feedings. For each test weight, 3 pre- and 3 postgavage feeding weights were obtained by study personnel, blinded to feeding volume, via a specific protocol. The correlation between test weight difference and actual volume ingested was assessed by the use of summary statistics, Spearman rho, and graphical analyses. The relationship between categorical predictive variables and a predefined acceptable difference (±5 mL) was assessed with the χ2 or Fisher exact test. RESULTS: A total of 101 test weights were performed in 68 infants. Estimated and actual feeding volumes were highly correlated (r = 0.94, P < .001), with a mean absolute difference of 2.95 mL (SD: 2.70; range: 0, 12.3 mL; 5th, 95th percentile: 0, 9.3); 85% of test weights were within ±5 mL of actual feeding volume and did not vary significantly by corrected age, feeding tube or respiratory support type, feeding duration or volume, formula vs breast milk, or caloric density. With adherence to study protocol, 89% of test weights (66/74) were within ±5 mL of actual volume, compared with 71% (19/27, P = .04) when concerns about protocol adherence were noted (eg, difficulty securing oxygen tubing). CONCLUSIONS: Via the use of a standard protocol, feeding volumes can be estimated accurately by pre- and postfeeding weights. Test weighing could be a valuable tool to support direct breastfeeding in the neonatal intensive care unit.

Method of home tube feeding and 2-3-year neurodevelopmental outcome.

OBJECTIVE: To describe the Bayley Scales of Infant Development 3rd Edition (Bayley-III) of infants discharged home receiving tube feeds. STUDY DESIGN: Retrospective review of infants discharged with nasogastric or gastrostomy tube feeds and completed a Bayley-III assessment at 2-3-years of age through a neonatal follow-up program. Results were reported using descriptive statistics. RESULTS: Of infants discharged with nasogastric feeds, median Bayley-III scores were in the low-average to average range, and full oral feeds were achieved in 75%. Of infants discharged with gastrostomy tube feeds, median Bayley-III scores were in the extremely low range, and full oral feeds were achieved in 36%. Our data set did not demonstrate a distinct patient demographic that correlated to the type of feeding tube at discharge. CONCLUSION: Neurodevelopmental outcome at 2-3 years does not appear to be negatively impacted by the decision to discharge an infant from the NICU with home NG feedings.

Short-term outcomes of newborns with perinatal acidemia who are not eligible for systemic hypothermia therapy.

OBJECTIVE: To determine short-term outcomes of infants who had perinatal acidemia and were evaluated for hypothermia therapy but did not qualify based on a standardized neurologic examination. STUDY DESIGN: Retrospective, single-site cohort study of inborn infants of ≥ 36 weeks gestation who had perinatal acidemia from October 2005-September 2008 and had a standardized neurologic examination performed by a certified neonatologist to assess eligibility for hypothermia therapy. An abnormal short-term nursery outcome was defined as death, seizures, brain magnetic resonance imaging consistent with hypoxic-ischemic encephalopathy, abnormal neurologic examination at discharge, gastrostomy tube feeding, or inability to nipple all feeds beyond the first week of age. RESULTS: One hundred forty-four (0.3%) of 46 887 newborns with perinatal acidemia had a neurologic examination performed that was either normal (n = 29) or consistent with mild encephalopathy (1 or 2 abnormal categories; n = 60). Of the latter infants classified as having mild encephalopathy, 12 (20%) experienced an abnormal short-term outcome (feeding difficulties, n = 8; abnormal neurologic examination at discharge, n = 7; abnormal brain magnetic resonance imaging, n = 6; seizures, n = 5; gastrostomy, n = 1; or death, n = 1). CONCLUSIONS: Twenty percent of newborns with perinatal acidemia and a neurologic examination that revealed only mild encephalopathy had abnormal short-term outcomes that could be attributed to the encephalopathy. Adjunctive tools or biomarkers for optimal assessment of infants with fetal acidemia for hypothermia therapy are needed.

Perinatal asphyxia with hyperoxemia within the first hour of life is associated with moderate to severe hypoxic-ischemic encephalopathy.

OBJECTIVE: To determine whether early hyperoxemia in neonates with severe perinatal acidemia is associated with the development of hypoxic-ischemic encephalopathy (HIE). STUDY DESIGN: We identified 120 infants at ≥ 36 weeks gestational age with perinatal acidosis born at Parkland Hospital who qualified for a screening neurologic exam for cooling therapy. Based on a PaO2 measurement during the first hour of life, the cohort was divided into infants with hyperoxemia (PaO2 >100 mmHg) and those without hyperoxemia (PaO2 ≤ 100 mmHg). The rate of moderate-severe encephalopathy was compared between the groups using χ(2) analysis, as well as multiple logistic regression, taking into account baseline characteristics and confounding variables. RESULTS: Thirty-six infants (30%) had an initial PaO2 >100 mmHg. Infants with and without hyperoxemia had similar baseline maternal and infant characteristics. Infants with hyperoxemia had a higher incidence of HIE than those without hyperoxemia (58% vs 27%; P = .003). Admission hyperoxemia was associated with a higher risk of HIE (OR, 4; 95% CI, 1.4-10.5; adjusted P = .01). Among the neonates with moderate-severe HIE during the first 6 hours of life, those with hyperoxemia had a higher incidence of abnormal brain magnetic resonance imaging results, consistent with hypoxic ischemic injury, compared with those without hyperoxemia (79% vs 33%; P = .015). CONCLUSION: In neonates with perinatal acidemia, admission hyperoxemia is associated with a higher incidence of HIE. Among neonates with HIE, admission hyperoxemia is associated with abnormal brain magnetic resonance imaging findings. The judicious use of oxygen during and after resuscitation is warranted.

A quality improvement initiative for neonatal hypoglycemia screening and management in a level III neonatal intensive care unit.

OBJECTIVE: To bring screening and management of neonatal hypoglycemia in alignment with the 2011 AAP hypoglycemia clinical report METHODS: A multidisciplinary team developed a quality improvement initiative for neonatal hypoglycemia in neonates ≥35 weeks gestational age in a Level III neonatal intensive care unit between July 2020 and December 2021. A key driver diagram identified interventions for plan-do-study-act testing with corresponding measures to implement a hypoglycemia management protocol and improve adherence to AAP guidelines. RESULTS: Time to first blood glucose measurement increased from 49.8 to 122.7 min of life and time to first enteral feed decreased from 14.2 to 3.6 h of life. Neonates receiving intravenous dextrose decreased from 97.1 to 24.7% and discharge rates as a mother-neonate dyad increased from 35 to 62.4%. CONCLUSIONS: Adherence to the AAP guidelines improved during testing and implementation of a hypoglycemia protocol and was associated with an increased mother-neonate dyad discharge rate.

Blanket temperature during therapeutic hypothermia and outcomes in hypoxic ischemic encephalopathy.

OBJECTIVE: Determine whether blanket temperatures during therapeutic hypothermia (TH) are associated with 18-22 month outcomes for infants with hypoxic ischemic encephalopathy (HIE). STUDY DESIGN: Retrospective cohort study of 181 infants with HIE who received TH in two randomized trials within the Neonatal Research Network. We defined summative blanket temperature constructs and evaluated for association with a primary composite outcome of death or moderate/ severe disability at 18-22 months. RESULTS: Each 0.5 °C above 33.5 °C in the mean of the highest quartile blanket temperature was associated with a 52% increase in the adjusted odds of death/ disability (aOR 1.52, 95% CI 1.09-2.11). Having >8 consecutive blanket temperatures above 33.5 °C rendered an aOR of death/disability of 5.04 in the first 24 h (95% CI 1.54-16.6) and 6.92 in the first 48 h (95% CI 2.20-21.8) of TH. CONCLUSIONS: Higher blanket temperature during TH may be an early, clinically useful biomarker of HIE outcome.

Darbepoetin as a neuroprotective agent in mild neonatal encephalopathy: a randomized, placebo-controlled, feasibility trial.

OBJECTIVE: To assess the feasibility and safety of one dose of Darbepoetin alpha (Darbe) administered to neonates ≥34 weeks with mild neonatal encephalopathy (NE). METHODS: Randomized, masked, placebo-controlled study including neonates ≥34 weeks gestation with mild NE. Neonates were randomized to receive one dose of Darbe (10 µg/kg IV) or placebo. Clinical and laboratory maternal and newborn data were collected. The Bayley Scales of Infant and Toddler Development, third edition (Bayley-III) and a standardized neurological examination at 8-12 months of corrected age were assessed. RESULTS: There were no differences in baseline characteristics of the 21 infants randomized (9 Darbe, 12 placebo). Adverse events were not reported at any time. Bayley-III scores were average in both Darbe and placebo groups. CONCLUSION: This study demonstrates that a randomized, masked, placebo-controlled trial is safe and feasible. A large, randomized trial is warranted to assess the effect of Darbe in this population.

Dexmedetomidine Use in Infants Undergoing Cooling Due to Neonatal Encephalopathy (DICE Trial): A Randomized Controlled Trial: Background, Aims and Study Protocol.

Background: Neonatal hypoxia-ischemia encephalopathy (HIE) is the leading cause of neonatal death and poor neurodevelopmental outcomes worldwide. Therapeutic hypothermia (TH), while beneficial, still leaves many HIE treated infants with lifelong disabilities. Furthermore, infants undergoing TH often require treatment for pain and agitation which may lead to further brain injury. For instance, morphine use in animal models has been shown to induce neuronal apoptosis. Dexmedetomidine is a potent α2-adrenergic receptor agonist that may be a better alternative to morphine for newborns with HIE treated with TH. Dexmedetomidine provides sedation, analgesia, and prevents shivering but does not suppress ventilation. Importantly, there is increasing evidence that dexmedetomidine has neuroprotective properties. Even though there are limited data on pharmacokinetics (PK), safety and efficacy of dexmedetomidine in infants with HIE, it has been increasingly administered in many centers. Objectives: To review the current approach to treatment of pain, sedation and shivering in infants with HIE undergoing TH, and to describe a new phase II safety and pharmacokinetics randomized controlled trial that proposes the use of dexmedetomidine vs. morphine in this population. Methods: This article presents an overview of the current management of pain and sedation in critically ill infants diagnosed with HIE and undergoing TH for 72 h. The article describes the design and methodology of a randomized, controlled, unmasked multicenter trial of dexmedetomidine vs. morphine administration enrolling 50 (25 per arm) neonates ≥36 weeks of gestation with moderate or severe HIE undergoing TH and that require pain/sedation treatment. Results and Conclusions: Dexmedetomidine may be a better alternative to morphine for the treatment of pain and sedation in newborns with HIE treated with TH. There is increasing evidence that dexmedetomidine has neuroprotective properties in several preclinical studies of injury models including ischemia-reperfusion, inflammation, and traumatic brain injury as well as adult clinical trials of brain trauma. The Dexmedetomidine Use in Infants undergoing Cooling due to Neonatal Encephalopathy (DICE) trial will evaluate whether administration of dexmedetomidine vs. morphine is safe, establish dexmedetomidine optimal dosing by collecting opportunistic PK data, and obtain preliminary neurodevelopmental data to inform a large Phase III efficacy trial with long term neurodevelopment impairment as the primary outcome.

The impact of the Baby Friendly Hospital Initiative on neonatal hypoglycemia.

OBJECTIVE: To assess Neonatal Intensive Care Unit (NICU) admissions for hypoglycemia after the introduction of the Baby Friendly Hospital Initiative (BFHI), followed by implementation of American Academy of Pediatrics recommended hypoglycemia guidelines. STUDY DESIGN: Retrospective review of NICU admissions for hypoglycemia. Eligible subjects were healthy infants >35 weeks gestation transferred to a NICU for hypoglycemia. Infants admitted with other pathologies were excluded. NICU admissions from 3 different 18-month epochs (1 = pre-BFHI; 2 = post-BFHI; 3 = post-BFHI+hypoglycemia guidelines) were compared. RESULTS: After implementation of BFHI there was a statistically significant increase in admissions for hypoglycemia (Epoch 2 = 1.23% vs Epoch 1 = 0.55%, p < 0.001). Followed by a decrease in admissions after the implementation of hypoglycemia guidelines (Epoch 2 = 1.23% vs Epoch 3 = 0.76%, p = 0.03). CONCLUSION: NICU admissions for hypoglycemia increased with the BFHI. Hypoglycemia guidelines decreased NICU admissions, but not to the pre-BFHI baseline.