Can Red Blood Cell and Platelet Transfusions Have a Pathogenic Role in Bronchopulmonary Dysplasia?

OBJECTIVE: To evaluate whether transfusions in infants born preterm contribute to the pathogenesis of bronchopulmonary dysplasia (BPD). STUDY DESIGN: We conducted a multihospital, retrospective study seeking associations between red blood cell or platelet transfusions and BPD. We tabulated all transfusions administered from January 2018 through December 2022 to infants born ≤29 weeks or <1000 g until 36 weeks postmenstrual age and compared those with BPD grade. We performed a sensitivity analysis to assess the possibility of a causal relationship. We then determined whether each transfusion was compliant with restrictive guidelines, and we estimated effects fewer transfusions might have on future BPD incidence. RESULTS: Eighty-four infants did not develop BPD and 595 did; 352 developed grade 1 (mild), 193 grade 2 (moderate), and 50 grade 3 (severe). Transfusions were given at <36 weeks to 7% of those who did not develop BPD, 46% who did, and 98% who developed severe BPD. For every transfusion the odds of developing BPD increased by a factor of 2.27 (95% CI, 1.59-3.68; P < .001). Sensitivity analyses suggested that transfusions might contribute to BPD. Fifty-seven percent of red blood cell transfusions and 68% of platelet transfusions were noncompliant with new restrictive guidelines. Modeling predicted that complying with restrictive guidelines could reduce the transfusion rate by 20%-30% and the moderate to severe BPD rate by ∼4%-6%. CONCLUSIONS: Transfusions were associated with BPD incidence and severity. Lowering transfusion rates to comply with current restrictive guidelines might result in a small but meaningful reduction in BPD rates.

Platelet Transfusions in a Multi-Neonatal Intensive Care Unit Health Care Organization Before and After Publication of the PlaNeT-2 Clinical Trial.

OBJECTIVES: To evaluate whether implementing more restrictive neonatal intensive care unit (NICU) platelet transfusion guidelines following the Platelets for Neonatal Transfusion - Study 2 randomized controlled trial (transfusion threshold changed from 50 000/µL to 25 000/µL for most neonates) was associated with fewer NICU patients receiving a platelet transfusion, without adversely affecting outcomes. STUDY DESIGN: Multi-NICU retrospective analysis of platelet transfusions, patient characteristics, and outcomes during 3 years before vs 3 years after revising system-wide guidelines. RESULTS: During the first period, 130 neonates received 1 or more platelet transfusions; this fell to 106 during the second. The transfusion rate was 15.9/1000 NICU admissions in the first period vs 12.9 in the second (P = .106). During the second period, a smaller proportion of transfusions was administered when the platelet count was in the 50 000-100 000/µL range (P = .017), and a larger proportion when it was <25 000/µL (P = .083). We also saw a fall in the platelet counts that preceded the order for transfusion from 43 100/µL to 38 000/µL (P = .044). The incidence of adverse outcomes did not change. CONCLUSIONS: Changing platelet transfusion guidelines in a multi-NICU network to a more restrictive practice was not associated with a significant reduction in number of neonates receiving a platelet transfusion. The guideline implementation was associated with a reduction in the mean platelet count triggering a transfusion. We speculate that further reductions in platelet transfusions can safely occur with additional education and accountability tracking.

Associations between blood donor sex and age, and outcomes of transfused newborn infants.

BACKGROUND: It is controversial whether the sex or age of red blood cell (RBC) donors affects mortality or morbidities of transfused newborn infants. We assessed these issues using a multi-year, multi-hospital database linking specific outcomes of neonatal transfusion recipients with RBC donor sex and age. STUDY DESIGN AND METHODS: We performed retrospective analyses of all neonates receiving ≥ one RBC transfusion during a 12-year period in all Intermountain Healthcare hospitals, matching mortality and specific morbidities of each transfusion recipient with the sex and age of each donor. RESULTS: There were 6396 RBC transfusions administered to 2086 infants in 15 hospitals. A total of 825 infants were transfused exclusively with RBC from female donors, 935 infants were transfused exclusively with RBC from male donors, and 326 infants were transfused with RBC from both female and male donors. No differences in baseline characteristics were identified among the three groups. Infants who received blood from both male and female donors had more RBC transfusions (5.3 ± 2.9 transfusions if received both male and female donor blood vs. 2.6 ± 2.2 if received blood from only one sex, mean ± SD, p < .001). We identified no significant differences in mortality or morbidities associated with the sex or the age of blood donors. Similarly, an analysis of matched vs. mismatched donor/recipient sex revealed no associations with death or neonatal morbidities. CONCLUSION: These data support the practice of transfusing newborn infants with RBC obtained from donors of either sex and regardless of donor age.

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.

Neonatal Reference Intervals for the Complete Blood Count Parameters MicroR and HYPO-He: Sensitivity Beyond the Red Cell Indices for Identifying Microcytic and Hypochromic Disorders.

OBJECTIVE: To create neonatal reference intervals for the MicroR and HYPO-He complete blood count (CBC) parameters and to test whether these parameters are sensitive early markers of disease at early stages of microcytic/hypochromic disorders while the CBC indices are still normal. STUDY DESIGN: We retrospectively collected the CBC parameters MicroR and HYPO-He, along with the standard CBC parameters, from infants aged 0-90 days at Intermountain Healthcare hospitals using Sysmex hematology analyzers. We created reference intervals for these parameters by excluding values from neonates with proven microcytic disorders (ie, iron deficiency or alpha thalassemia) from the dataset. RESULT: From >11 000 CBCs analyzed, we created reference intervals for MicroR and HYPO-He in neonates aged 0-90 days. The upper intervals are considerably higher in neonates than in adults, validating increased anisocytosis and polychromasia among neonates. Overall, 52% of neonates with iron deficiency (defined by reticulocyte hemoglobin equivalent <25 pg) had a MicroR >90% upper interval (relative risk, 4.14; 95% CI, 3.80-4.53; P < .001), and 68% had an HYPO-He >90% upper interval (relative risk, 6.64; 95% CI, 6.03-7.32; P < .001). These 2 new parameters were more sensitive than the red blood cell (RBC) indices (P < .001) in identifying 24 neonates with iron deficiency at birth. CONCLUSIONS: We created neonatal reference intervals for MicroR and HYPO-He. Although Sysmex currently designates these as research use only in the US, they can be measured as part of a neonate's CBC with no additional phlebotomy volume or run time and can identify microcytic and hypochromic disorders even when the RBC indices are normal.

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.

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.

Banked term umbilical cord blood to meet the packed red blood cell transfusion needs of extremely-low-gestational-age neonates: a feasibility analysis.

OBJECTIVES: To assess the feasibility of drawing, processing, safety-testing, and banking term umbilical cord blood to meet the packed red blood cell transfusion (RBC Tx) needs of extremely-low-gestational-age neonates (ELGANs). DESIGN: (1) Retrospectively analyze all ELGANs RBC Tx over the past three years, (2) Estimate local cord blood availability, (3) Assess interest in this project, and implementation barriers, through stakeholder surveys. RESULTS: In three years we cared for 266 ELGANs; 165 (62%) received ≥1 RBC Tx. Annual RBC Tx averaged 197 (95% CI, 152-243). If 10% of our 10,353 annual term births had cord blood drawn and processed, and half of those tested were acceptable for Tx, collections would exceed the 95th % upper estimate for need by >four-fold. Interest exceeded 97%. Identified barriers included FDA approval, training to collect cord blood, and cost. CONCLUSION: RBC Tx needs of ELGANS could be met by local cord blood collection.

Reference intervals for end-tidal carbon monoxide of preterm neonates.

OBJECTIVES: We constructed reference intervals for end-tidal carbon monoxide (ETCOc) levels of neonates 28 0/7 to 34 6/7 weeks gestation in order to assess hemolytic rate. STUDY DESIGN: This is a prospective four-NICU study in Bangkok, Thailand, and Utah, USA. RESULTS: Of 226 attempted measurements, 92% were successful. Values from day 1 through 28 were charted and upper (>95th percentile) reference interval limits calculated. During the entire 28 days, the ETCOc upper reference intervals from babies in Bangkok were higher than those in Utah (p < 0.01). No differences were found due to sex, or earliest vs. latest gestation at birth (both p > 0.1). Similar to term neonates, preterm neonates in Bangkok and Utah had higher ETCOc values during the first 48 h after birth than thereafter (p < 0.01). CONCLUSIONS: Using this methodology, and the reference interval chart, the hemolytic rate of preterm infants ≥28 weeks can be assessed.

Reconciling markedly discordant values of serum ferritin versus reticulocyte hemoglobin content.

OBJECTIVE: To determine why serum ferritin and reticulocyte hemoglobin (RET-He), drawn to assess neonatal iron sufficiency, sometimes have markedly discordant results. STUDY DESIGN: Retrospective records review of five NICUs over 28 months, identifying all patients with a ferritin and RET-He within 48 h. We examined records of all who had marked discordance (one value >95th % reference interval, the other <5th %). RESULTS: Of 190 paired ferritin and RET-He measurements, 16 (8%) were markedly discordant. Fifteen of the 16 discordant samples involved a high ferritin and a low RET-He. In these, low MCV and high %Micro-R, and low MCH and high %HYPO-He were present. In total, 8 of the 15 had laboratory or clinical evidence of an inflammatory process and five had suspicion of infection documented. CONCLUSIONS: When ferritin and RET-He were discordant, erythrocyte microcytosis and hypochromasia suggested that the RET-He gave the more accurate interpretation; that iron deficiency was likely present.

Exchange transfusion for hemolytic hyperbilirubinemia: could some be averted by emergent administration of an inhibitor of bilirubin production?

OBJECTIVES: The objective of this study is to explore the hypothetical number of neonates where an exchange transfusion (ET) could be prevented by emergency administration of an inhibitor of bilirubin production. STUDY DESIGN: We identified all neonates who received an ET in our NICUs during the past 12 years. We reviewed the indications for ET and recorded the time between ordering and beginning the exchange. RESULTS: Forty-six neonates underwent ET, 37 (80.4%) for hemolytic hyperbilirubinemia (36.9 ± 2.9 weeks gestation and 2.5 ± 2.1 days old at ET). The mean delay period was 7.5 ± 3.5 h. Nine (19.6%) had ET not involving bilirubin. CONCLUSIONS: A trial testing compounds that can inhibit bilirubin production would have about three eligible neonates/years in our system. Since our births are 1% of national, up to 300 neonates/years might qualify for such a study.

Rapid prototyping of polymer microsystems via excimer laser ablation of polymeric moulds.

This study presents a novel method for rapid prototyping of polymer microsystems. The method is based on excimer laser ablation of a thermally and mechanically stable polymer, such as PEEK (poly-ether-ether-ketone). A negative of the desired microsystem is laser machined in PEEK, which can then be used directly for hot embossing or injection moulding of a series of prototypes. This approach is very rapid and considerably cheaper than more traditional approaches to toolmaking, while still performing well in terms of reproduction of tool dimensions. The reduction in time and cost for a master tool using this method opens up new possibilities for testing small series in the R&D phase of a microsystem. Finally, two particular applications of the technique are presented.