Iron deposition in infants undergoing ECMO: A retrospective analysis of Postmortem tissue samples.

BACKGROUND: Infants undergoing ECMO may have elevated serum ferritin and iron levels, raising concerns about iron overload. Recent studies question the utility of these markers for acute vs. chronic iron overload during ECMO. This study evaluates iron content and localization in autopsy tissues from deceased infants who received or were considered for ECMO. METHODS: This retrospective single-center case-control study analyzed paraffin-embedded tissues from the basal ganglia, liver, spleen, pancreas, and kidney. Tissue sections were stained to quantify iron deposition and an independent pathologist reviewed samples for iron accumulation. RESULTS: Eighteen deceased infants' tissues were analyzed: nine underwent ECMO, and nine were considered for it. Both groups showed multi-organ iron accumulation with no significant difference between ECMO and non-ECMO cohorts. Red blood cell transfusions were linked to increased iron content in adrenal (p = 0.004), hepatic (p = 0.042), and splenic (p = 0.013) tissues. CONCLUSIONS: ECMO exposure alone does not independently increase iron content in infants' organs. Multi-organ iron accumulation in both groups suggests iron deposition in critically ill pediatric patients irrespective of ECMO exposure. Further research is needed to understand the mechanisms and implications.

Low-Titer Type O Whole Blood for Transfusing Perinatal Patients after Acute Hemorrhage: A Case Series.

Objective Acute and massive blood loss is fortunately a rare occurrence in perinatal/neonatal practice. When it occurs, typical transfusion paradigms utilize sequential administration of blood components. However, an alternative approach, transfusing type O whole blood with low anti-A and anti-B titers, (LTOWB) has recently been approved and utilized in trauma surgery. Study Design Retrospective analysis of all perinatal patients who have received LTOWB after acute massive hemorrhage at the Intermountain Medical Center. Results LTOWB was the initial transfusion product we used to resuscitate/treat 25 women with acute and massive postpartum hemorrhage and five infants with acute hemorrhage in the first hours/days after birth. We encountered no problems obtaining or transfusing this product and we recognized no adverse effects of this treatment. Conclusion Transfusing LTOWB to perinatal patients after acute blood loss is feasible and appears at least as safe a serial component transfusion. Its use has subsequently been expanded to multiple hospitals in our region as first-line transfusion treatment for acute perinatal hemorrhage. Key Points Low-titer type O whole blood (LTOWB) was our initial transfusion product for 30 perinatal patients with acute hemorrhage. Twenty-five of these were obstetrical patients and five were neonatal patients. We encountered no problems with, or adverse effects from LTOWB in any of these patients. LTOWB transfusions to women were ten days since donor draw (interquartile range, 8-13) and to neonates was six days (5-8).

A pilot study to evaluate clinical factors associated with iron and ferritin elevations during pediatric extracorporeal membrane oxygenation.

Introduction: Elevations in serum ferritin and serum iron occur during pediatric extracorporeal membrane oxygenation (ECMO). Previous reports attribute the elevation to frequent red blood cell transfusions and/or hemolysis. Chronic transfusion can cause iron deposition in tissues leading to multisystem organ dysfunction. This study aims identify clinical factors associated with elevated ferritin and iron in pediatric ECMO patients, along with post-decannulation magnetic resonance imaging (MRI) assessment of iron deposition in liver and brain.Methods: Prospective, pilot study, using descriptive statistics to investigate potential associations between patient characteristics, serum ferritin and iron levels, and post-decannulation hepatic and basal ganglia iron deposition.Results: In this study, nine patients (100%) had elevated serum ferritin levels during ECMO. High ferritin levels were more common with veno-arterial than with veno-venous cannulation (p = 0.026) and were also associated with high plasma free hemoglobin levels (p < 0.001). Five patients presented with elevated serum iron levels. High serum iron levels were associated with higher daily (p = 0.016) and cumulative transfusion volumes (p = 0.013) as well ECMO duration beyond 7 days. MRI scans were performed on three patients with no evidence of abnormal iron deposition detected in the liver or brain.Conclusions: This pilot study shows that during pediatric ECMO, elevations in serum ferritin and serum iron occur and those elevations may be related to the cannulation modality, ECMO duration, amount of hemolysis, and volume of red blood cell transfusions. Further investigation is warranted to fully understand the implications of elevated serum iron and ferritin in pediatric ECMO.

Transforming neonatal care with artificial intelligence: challenges, ethical consideration, and opportunities.

Artificial intelligence (AI) offers tremendous potential to transform neonatology through improved diagnostics, personalized treatments, and earlier prevention of complications. However, there are many challenges to address before AI is ready for clinical practice. This review defines key AI concepts and discusses ethical considerations and implicit biases associated with AI. Next we will review literature examples of AI already being explored in neonatology research and we will suggest future potentials for AI work. Examples discussed in this article include predicting outcomes such as sepsis, optimizing oxygen therapy, and image analysis to detect brain injury and retinopathy of prematurity. Realizing AI's potential necessitates collaboration between diverse stakeholders across the entire process of incorporating AI tools in the NICU to address testability, usability, bias, and transparency. With multi-center and multi-disciplinary collaboration, AI holds tremendous potential to transform the future of neonatology.

Neonatal subgaleal hemorrhage: twenty years of trends in incidence, associations, and outcomes.

BACKGROUND: In 2011, we reported 38 neonates with subgaleal hemorrhage (SH), relating an increasing incidence. It is unclear whether the incidence in our hospitals continued to rise and which risk factors and outcomes are associated with this condition. DESIGN: We retrospectively analyzed every recognized case of SH in our hospitals from the end of our previous report (2010) to the present (2022). We redescribed the incidence, scored severity, tabulated blood products transfused, and recorded outcomes. RESULTS: Across 141 months, 191 neonates were diagnosed with SH; 30 after vacuum or forceps. The incidence (one/1815 births) was higher than in our 2011 report (one/7124 births). Also, severe SH (requiring transfusion) was more common (one/10,033 births vs. one/20,950 births previously). Four died (all with severe SH) and 12 had neurodevelopmental impairment. CONCLUSION: Recognized cases of SH are increasing in our system without a clear explanation. Adverse outcomes are rare but continue to occur.

Current Practices for Genetic Testing in Neonatal Extracorporeal Membrane Oxygenation: Findings from a National survey.

Introduction: Comprehensive genetic testing with whole-exome (WES) or whole-genome (WGS) sequencing facilitates diagnosis, can optimize treatment, and may improve outcomes in critically ill neonates, including those requiring extracorporeal membrane oxygenation (ECMO) for respiratory failure. Our objective was to describe practice variation and barriers to the utilization of comprehensive genetic testing for neonates on ECMO.Methods: We performed a cross-sectional survey of Level IV neonatal intensive care units in the United States across the Children's Hospitals Neonatal Consortium (CHNC).Results: Common indications for WES and WGS included concerning phenotype, severity of disease, unexpected postnatal clinical course, and inability to wean from ECMO support. Unexpected severity of disease on ECMO was the most common indication for rapid genetic testing. Cost of utilization was the primary barrier to testing. If rapid WES or WGS were readily available, 63% of centers would consider incorporating universal screening for neonates upon ECMO cannulation.Conclusion: Despite variation in the use of WES and WGS, universal testing may offer earlier diagnosis and influence the treatment course among neonates on ECMO. Cost is the primary barrier to utilization and most centers would consider incorporating universal screening on ECMO if readily available.

First report of transfusing low-titer cold-stored type O whole blood to an extremely-low-birth-weight neonate after acute blood loss.

BACKGROUND: Multiple reports suggest that cold-stored low-titer type O whole blood (LTOWB) is becoming a preferred transfusion product for resuscitating massive hemorrhage across trauma, obstetrical, and pediatric services. However, we know of no reports of using this product for emergency transfusion of newborn infants after acute severe hemorrhage. CASE REPORT: We report our experience with emergency transfusion of re-warmed LTOWB using a fluid warmer for the resuscitation of a hypotensive 25-week gestation neonate following acute and severe placental abruption. The transfusion was tolerated well, without evidence of hemolysis or other complications. CONCLUSIONS: This is the first report of which we are aware of transfusing warmed LTOWB to a preterm neonate. Our positive experience leads us to speculate that this product could have a role for neonates following acute severe blood loss.

Fetomaternal hemorrhage: Evidence from a multihospital healthcare system that up to 40% of severe cases are missed.

BACKGROUND: We previously reported fetomaternal hemorrhage (FMH) in 1/9160 births, and only one neonatal death from FMH among 219,853 births. Recent reports indicate FMH is not uncommon among stillbirths. Consequently, we speculated we were missing cases among early neonatal deaths. We began a new FMH initiative to determine the current incidence. METHODS: We analyzed births from 2011 to 2020 where FMH was diagnosed. We also evaluated potential cases among neonates receiving an emergent transfusion just after birth, whose mothers were not tested for FMH. RESULTS: Among 297,403 births, 1375 mothers were tested for FMH (1/216 births). Fourteen percent tested positive (1/1599 births). Of those, we found 25 with clinical and laboratory evidence of FMH adversely affecting the neonate. Twenty-one received one or more emergency transfusions on the day of birth; all but two lived. We found 17 others who received an emergency transfusion on the day of birth where FMH was not tested for, but was likely; eight of those died. The 42 severe (proven + probable) cases equate to 1/7081 births. We judged that 10 of the 42 had an acute FMH, and in the others it likely had more than a day before birth. CONCLUSIONS: We estimate that we fail to diagnose >40% of our severe FMH cases. Needed improvements include (1) education to request maternal FMH testing when neonates are born anemic, (2) education on false-negative FMH tests, and (3) improved FMH communications between neonatology, obstetrics, and blood bank.

Factors Associated with Outpatient Therapy Utilization in Extremely Preterm Infants.

OBJECTIVE: Factors influencing utilization of outpatient interventional therapies for extremely low gestational age newborns (ELGANs) after discharge remain poorly characterized, despite a significant risk of neurodevelopmental impairment. We sought to assess the effects of maternal, infant, and environmental characteristics on outpatient therapy utilization in the first 2 years after discharge using data from the Preterm Erythropoietin Neuroprotection (PENUT) Trial. STUDY DESIGN: This is a secondary analysis of 818, 24 to 27 weeks gestation infants enrolled in the PENUT trial who survived through discharge and completed at least one follow-up call or in-person visit between 4 and 24 months of age. Utilization of a state early intervention (EI) program, physical therapy (PT), occupational therapy (OT), and speech therapy (ST) was recorded. Odds ratios and cumulative frequency curves for resource utilization were calculated for patient characteristics adjusting for gestational age, treatment group, and birth weight. RESULTS: EI was not accessed by 37% of infants, and 18% did not use any service (PT/OT/ST/EI). Infants diagnosed with severe morbidities (intraventricular hemorrhage, retinopathy of prematurity, bronchopulmonary dysplasia, necrotizing enterocolitis), discharged with home oxygen, or with gastrostomy placement experienced increased utilization of PT, OT, and ST compared with peers. However, substantial variation in service utilization occurred by the state of enrollment and selected maternal characteristics. CONCLUSIONS: ELGANs with severe medical comorbidities are more likely to utilize services after discharge. Therapy utilization may be impacted by maternal characteristics and state of enrollment. Outpatient therapy services remain significantly underutilized in this high-risk cohort. Further research is required to characterize and optimize the utilization of therapy services following NICU discharge of ELGANs. KEY POINTS: · Outpatient therapy is underutilized in ELGANs.. · Medical comorbidities may impact therapy use.. · Maternal characteristics may impact therapy use.. · State of enrollment may impact therapy use..

Early iron supplementation and iron sufficiency at one month of age in NICU patients at-risk for iron deficiency.

In order to reduce iron deficiency in neonates at-risk for iron deficiency, we implemented a guideline to increase the consistency of early iron supplementation in infants of diabetic mothers, small for gestational age neonates and very low birthweight premature neonates. Three years following implementation we performed a retrospective analysis in order to assess adherence to the guideline and to compare timing of early iron supplementation and reticulocyte-hemoglobin (RET-He) values at one month of life in at-risk infants. Adherence with early iron supplementation guidelines was 73.4% (399/543) with 51% (275/543) having RET-He values obtained at one month. Despite good adherence, 16% (44/275) had RET-He <25 pg (5th percentile for gestational age). No infants receiving red blood cell transfusion (0/20) had RET-He <25 pg vs. 26.1% (40/153) of those treated with darbepoetin (p < 0.001). There was no evidence of increased feeding intolerance (episodes of emesis/day) with early iron supplementation.

Supplementation-based hypoglycemia guidelines including donor breast milk reduce NICU admission.

OBJECTIVE: To study the effects of a supplementation-based hypoglycemia guideline including donor (DM) on NICU admission, exclusive breastfeeding, and blood glucose concentrations in infants at-risk for neonatal hypoglycemia (NH). PROJECT DESIGN: We integrated DM, feeding supplementation, and reduced frequency of blood glucose testing into an NH bundle for term and late-preterm newborns. We then examined NICU admission rates and rates of exclusive breastfeeding at discharge. RESULTS: NICU admission rates were reduced to 6% (-10%). Exclusive breastfeeding rates increased to 55% (+22%). Median cost of DM utilization was $13.73 per patient with an average volume of 50.8 ml/infant. DM supplementation resulted in similar times to last hypoglycemic episode and greater increases in blood glucose compared to expressed breast milk or breastfeeding alone (+9.6 mg/dL, p < 0.05). CONCLUSIONS: A supplementation-based hypoglycemia guideline including donor milk may be an effective way to reduce NICU admissions for asymptomatic hypoglycemia and support mothers in achieving breastfeeding goals.

Extracorporeal Life Support in Pediatric Patients with Bronchopulmonary Dysplasia and Associated Pulmonary Hypertension.

This retrospective study reviews outcomes of 281 pediatric patients with bronchopulmonary dysplasia (BPD) managed with extracorporeal life support (ECLS). Data from 1982 to 2018 from the Extracorporeal Life Support Organization (ELSO) registry were queried for children aged 60 days to 18 years with a prior diagnosis of BPD, and all patients with secondary pulmonary hypertension (PH) were identified. Overall survival of patients with and without PH was 86.7% and 68.0%, respectively (p = 0.23). There was no report of patients with PH before 2004. Patients with BPD + PH were more likely to have associated intraventricular hemorrhage (p = 0.002) and retinopathy of prematurity (p = 0.05), as well as a greater reported use of sildenafil (p = 0.0001) and milrinone (p = 0.008) before ECLS. The most common primary diagnosis in patients with BPD was viral respiratory infection (45.3%) and in patients with BPD + PH was respiratory failure without mention of infection (40.0%). Inotrope use was the most common complication reported (36.7%) with survival of 54.4%. We conclude that data from the ELSO registry demonstrate reasonable survival in both, patients with BPD and BPD + PH. Thus, patients with BPD and associated PH should be considered candidates for ECLS.

Maternal diabetes and obesity influence the fetal epigenome in a largely Hispanic population.

BACKGROUND: Obesity and diabetes mellitus are directly implicated in many adverse health consequences in adults as well as in the offspring of obese and diabetic mothers. Hispanic Americans are particularly at risk for obesity, diabetes, and end-stage renal disease. Maternal obesity and/or diabetes through prenatal programming may alter the fetal epigenome increasing the risk of metabolic disease in their offspring. The aims of this study were to determine if maternal obesity or diabetes mellitus during pregnancy results in a change in infant methylation of CpG islands adjacent to targeted genes specific for obesity or diabetes disease pathways in a largely Hispanic population. METHODS: Methylation levels in the cord blood of 69 newborns were determined using the Illumina Infinium MethylationEPIC BeadChip. Over 850,000 different probe sites were analyzed to determine whether maternal obesity and/or diabetes mellitus directly attributed to differential methylation; epigenome-wide and regional analyses were performed for significant CpG sites. RESULTS: Following quality control, agranular leukocyte samples from 69 newborns (23 normal term (NT), 14 diabetes (DM), 23 obese (OB), 9 DM/OB) were analyzed for over 850,000 different probe sites. Contrasts between the NT, DM, OB, and DM/OB were considered. After correction for multiple testing, 15 CpGs showed differential methylation from the NT, associated with 10 differentially methylated genes between the diabetic and non-diabetic subgroups, CCDC110, KALRN, PAG1, GNRH1, SLC2A9, CSRP2BP, HIVEP1, RALGDS, DHX37, and SCNN1D. The effects of diabetes were partly mediated by the altered methylation of HOOK2, LCE3C, and TMEM63B. The effects of obesity were partly mediated by the differential methylation of LTF and DUSP22. CONCLUSIONS: The presented data highlights the associated altered methylation patterns potentially mediated by maternal diabetes and/or obesity. Larger studies are warranted to investigate the role of both the identified differentially methylated loci and the effects on newborn body composition and future health risk factors for metabolic disease. Additional future consideration should be targeted to the role of Hispanic inheritance. Potential future targeting of transgenerational propagation and developmental programming may reduce population obesity and diabetes risk.

Evaluating the effects of a neonatal hypoglycemia bundle on NICU admission and exclusive breastfeeding.

OBJECTIVE: Early feeding, skin-to-skin contact, and dextrose gel have been independently shown to promote breastfeeding and decrease NICU admission for neonatal hypoglycemia. We combined these interventions to decrease NICU admissions for asymptomatic hypoglycemia and increase exclusive breastfeeding rates. PROJECT DESIGN: The IHI Model for Improvement was used to design a bundle including feeding within 1 h of birth, 1 h of uninterrupted skin-to-skin within 2 h of birth, and administration of buccal 40% dextrose gel for hypoglycemic infants. RESULTS: Utilization of dextrose gel was 94% following implementation. There were no trends in exclusive breastfeeding at discharge or NICU admissions for asymptomatic hypoglycemia. Post hoc multivariate analysis identified cesarean delivery as an independent risk factor for compliance failure and failure of exclusive breastfeeding but not for NICU admission. CONCLUSIONS: Despite high compliance with dextrose gel utilization, there was no change in exclusive breastfeeding at discharge or NICU admission rates for asymptomatic hypoglycemia.

Extended Maternity Leave and Breastfeeding in Active Duty Mothers.

BACKGROUND AND OBJECTIVES: In 2016, the Department of Defense extended maternity leave from 6 to 12 weeks for active duty mothers to support breastfeeding initiation and duration. Limited data exist regarding the impact of prolonged maternity leave. Our objective was to evaluate the prolongation of maternity leave on the initiation and duration of breastfeeding in active duty mothers. METHODS: In this single-center retrospective cohort study, we used data collected from Department of Defense electronic health care records of infants born to active duty mothers who were delivered during calendar years 2014 and 2016. The primary outcomes were initiation and duration of breastfeeding and breastfeeding exclusivity evaluated throughout the first year of life. Secondary outcomes were differences in breastfeeding rates between military-branch affiliation and military rank. RESULTS: No changes in breastfeeding initiation occurred between the 2 cohorts (n = 423 and 434). However, an increase in breastfeeding establishment was identified at the 2- (81.5% vs 72.4%; P = .002), 4- (70.5% vs 56.7%; P < .001), 6- (60.3% vs 46.5%; P < .001), and 9-month (45.4% vs 34.9%; P = .003) visits in the 12-week leave cohort. Exclusive breastfeeding increased at 2 (56.4% vs 47.2%; P = .007), 4 (47.5% vs 36.4%; P = .001), and 6 (37.3% vs 29.3%; P = .016) months. CONCLUSIONS: Increases in maternity leave correlated with increased breastfeeding duration and exclusivity through 9 months for active duty mothers. These data support the benefit of extended maternity leave in the military and the need for future studies to validate findings at other military treatment facilities.

Dysnatremia in extremely low birth weight infants is associated with multiple adverse outcomes.

OBJECTIVE: The objective of this study is to discern patterns of serum sodium in a broad cohort of extremely low birth weight (ELBW) infants and associate those patterns with hospital outcomes. STUDY DESIGN: Retrospective cohort study of ELBW infants from 323 neonatal intensive care units (NICUs) discharged from 2004 to 2014. We included patients who survived at least 7 days and had daily sodium levels available, and categorized infants by their minimum and maximum sodium levels. RESULTS: We identified 26,871 infants of whom 12,428 met inclusion criteria. Only 1964 (15.8%) maintained eunatremia for the first week. We found most dysnatremias to be associated with increased overall mortality compared with eunatremic patients including moderate hyponatremia (12.9% vs. 8.6%, p < 0.05) and severe hypernatremia (34.8% vs. 8.6%, p < 0.001). Most of these associations were maintained after regression modeling for mortality. CONCLUSION: Sodium fluctuations occurring within the first week of life are associated with increased mortality.