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.

Neonatal Thrombocytopenia: Factors Associated With the Platelet Count Increment Following Platelet Transfusion.

OBJECTIVE: To understand better those factors relevant to the increment of rise in platelet count following a platelet transfusion among thrombocytopenic neonates. STUDY DESIGN: We reviewed all platelet transfusions over 6 years in our multi-neonatal intensive care unit system. For every platelet transfusion in 8 neonatal centers we recorded: (1) platelet count before and after transfusion; (2) time between completing the transfusion and follow-up count; (3) transfusion volume (mL/kg); (4) platelet storage time; (5) sex and age of platelet donor; (6) gestational age at birth and postnatal age at transfusion; and magnitude of rise as related to (7) pre-transfusion platelet count, (8) method of enhancing transfusion safety (irradiation vs pathogen reduction), (9) cause of thrombocytopenia, and (10) donor/recipient ABO group. RESULTS: We evaluated 1797 platelet transfusions administered to 605 neonates (median one/recipient, mean 3, and range 1-52). The increment was not associated with gestational age at birth, postnatal age at transfusion, or donor sex or age. The rise was marginally lower: (1) with consumptive vs hypoproductive thrombocytopenia (P < .001); (2) after pathogen reduction (P < .01); (3) after transfusing platelets with a longer storage time (P < .001); and (4) among group O neonates receiving platelets from non-group O donors (P < .001). Eighty-seven neonates had severe thrombocytopenia (<20 000/µL). Among these infants, poor increments and death were associated with the cause of the thrombocytopenia. CONCLUSION: The magnitude of post-transfusion rise was unaffected by most variables we studied. However, the increment was lower in neonates with consumptive thrombocytopenia, after pathogen reduction, with longer platelet storage times, and when not ABO matched.

Sex Differences in the Association of Pretransfusion Hemoglobin Levels with Brain Structure and Function in the Preterm Infant.

OBJECTIVE: To assess sex-specific differences in early brain structure and function of preterm infants after red blood cell (RBC) transfusions. STUDY DESIGN: A single-center subset of infants with a birth weight <1000 g and gestational age 22-29 weeks were enrolled from the National Institute of Child Health and Human Development's Neonatal Research Network Transfusion of Prematures Trial. Hemoglobin (Hb) concentration obtained directly before each transfusion (pretransfusion Hb [ptHb]) was obtained longitudinally throughout each infant's neonatal intensive care unit stay and used as a marker of degree of anemia (n = 97). Measures of regional brain volumes using magnetic resonance imaging were obtained at ∼40 weeks postmenstrual age or at hospital discharge, if earlier (n = 29). Measures of brain function were obtained at 12 months corrected age using the Bayley Scales of Infant & Toddler Development, 3rd Edition (n = 34). RESULTS: PtHb was positively correlated with neonatal cerebral white matter volume in males (B = +0.283; P = .006), but not females (B = -0.099; P = .713), resulting in a significant sex interaction (P = .010). Bayley-III gross motor scores and a pooled mean score were significantly lower in association with higher ptHb in females (gross motor score: B = -3.758; P = .013; pooled mean score: B = -1.225; P = .030), but not males (gross motor score: B = +1.758; P = .167; pooled mean score: B = +0.621; P = .359). Higher ptHb was associated with descriptively lower performance on multiple Bayley-III subscales in females, but not in males. CONCLUSIONS: This study demonstrates sex-specific associations between an early marker of anemia and RBC transfusion status (ie, ptHb) with both neonatal white matter volume and early cognitive function at age 12 months in preterm infants.

Variation in Neonatal Transfusion Practice.

OBJECTIVE: To estimate the incidence of blood product transfusion, including red blood cells, platelets, and plasma, and characterize pretransfusion hematologic values for infants during their initial hospitalization after birth. STUDY DESIGN: Retrospective cohort study using data from 7 geographically diverse US academic and community hospitals that participated in the National Heart Lung and Blood Institute Recipient Epidemiology and Donor Evaluation Study-III (REDS-III) from 2013 to 2016. Pretransfusion hematologic values were evaluated closest to each transfusion and no more than 24 hours beforehand. RESULTS: Data from 60 243 infants were evaluated. The incidence of any transfusion differed by gestational age (P < .0001), with 80% (95% CI 76%-84%) transfused at <27 weeks of gestation (n = 329) and 0.5% (95% CI 0.5%-0.6%) transfused at ≥37 weeks of gestation (n = 53 919). The median pretransfusion hemoglobin was 11.2 g/dL (10th-90th percentile 8.8-14.1) for the entire cohort, ranging from 10.5 g/dL (8.8-12.3) for infants born extremely preterm at <27 weeks of gestation to 13.0 g/dL (10.5-15.5) for infants born at term. The median pretransfusion platelet count (×109/L) was 71 (10th-90th percentile 26-135) for the entire cohort, and was >45 for all gestational age groups examined. The median pretransfusion international normalized ratio for the entire cohort was 1.7 (10th-90th percentile 1.2-2.8). CONCLUSIONS: There is wide variability in pretransfusion hemoglobin, platelet count, and international normalized ratio values for neonatal transfusions. Our findings suggest that a large proportion of neonatal transfusions in the US are administered at thresholds greater than supported by the best-available evidence and highlight an opportunity for improved patient blood management.

Primary hemostasis in neonates with thrombocytopenia.

OBJECTIVE: To evaluate the relationship between platelet counts and the platelet function analyzer-100 closure times (CTs) in neonates with thrombocytopenia, and to determine what other factors significantly affect CTs. STUDY DESIGN: In a single institution prospective cross-sectional study, blood samples from neonates with platelet counts <150 × 10(9)/L were tested on the platelet function analyzer-100 with CT-collagen/epinephrine (CT-Epi) and CT-collagen/adenosine diphosphate (CT-ADP) cartridges. RESULTS: The mean platelet count was 95 ± 28 × 10(9)/L for 48 infants with a mean gestational age 30.9 ± 5.3 weeks and median postnatal age of 5 (3-18) days. No association was evident between CT-Epi and platelet count. However, the CT-ADP was prolonged in many (but not all) infants with platelet counts <90 × 10(9)/L. Among infants <32 weeks gestational age, we found a moderate negative correlation between CT-ADP and platelet count (r = -0.54, P = .0045). The negative correlation was strongest in infants <32 weeks and <10 days old (r = -0.8, P = .0017). Other variables examined (hematocrit, infection, Score of Neonatal Acute Physiology II) did not have a significant effect on CT-ADP in a linear regression model. CONCLUSIONS: Platelet counts <90 × 10(9)/L are associated with prolonged CT-ADP times in some but not all infants. Gestational and postnatal age-related differences in platelet function account for some of this variability. The predictive value of CT-ADP on neonatal bleeding risk remains to be studied.

Do red cell transfusions increase the risk of necrotizing enterocolitis in premature infants?

OBJECTIVE: To test the hypothesis that red blood cell (RBC) transfusions increase the risk of necrotizing enterocolitis (NEC) in premature infants, we investigated whether the risk of "transfusion-associated" NEC is higher in infants with lower hematocrits and advanced postnatal age. STUDY DESIGN: Retrospective comparison of NEC patients and control patients born at < 34 weeks gestation. RESULTS: The frequency of RBC transfusions was similar in NEC patients (47/93, 51%) and control patients (52/91, 58%). Late-onset NEC (> 4 weeks of age) was more frequently associated with a history of transfusion(s) than early-onset NEC (adjusted OR, 6.7; 95% CI, 1.5 to 31.2; P = .02). Compared with nontransfused patients, RBC-transfused patients were born at earlier gestational ages, had greater intensive care needs (including at the time of onset of NEC), and longer hospital stay. A history of RBC transfusions within 48-hours before NEC onset was noted in 38% of patients, most of whom were extremely low birth weight infants. CONCLUSIONS: In most patients, RBC transfusions were temporally unrelated to NEC and may be merely a marker of overall severity of illness. However, the relationship between RBC transfusions and NEC requires further evaluation in extremely low birth weight infants using a prospective cohort design.