Background
Anemia affects up to one-third of pregnant women and has been associated with adverse maternal and neonatal outcomes (1, 2). However, little is known about the impact of maternal red cell (RBC) transfusions. The objective of this study was to evaluate the association of maternal transfusions in the 7 days prior to or at delivery with neonatal outcomes, taking maternal anemia into consideration.
Methods
This study retrospectively evaluated linked maternal and neonatal data from the Recipient Epidemiology and Donor Study IV Pediatric (REDS-IV-P) database, for which the Westat single Internal Review Board waived informed consent. The analytical cohort included deliveries ≥24 weeks gestation from 2019 to 2024 at 7 community and university hospitals in the United States. Bivariate comparisons were made for neonatal outcomes by maternal transfusions. Multivariable logistic regression analyses, adjusting for relevant maternal diagnoses available via ICD-10 codes, delivery mode, and infant’s gestational age at birth, were completed. Maternal hemoglobin level near delivery was captured.
Results
There were 137,760 neonates born to 135,216 mothers, with the most common maternal age range being 30-<35 years (34%) and the most common race being White (45%). Relevant maternal diagnoses collected included hypertension during pregnancy (18%), pre-eclampsia (8%), placenta previa (4.4%), sickle cell disease (0.2%), and bleeding disorders (0.9%), among others (Supplemental Table 1). Blood components were transfused to 2,386 (1.8%) of mothers, with 98% of transfusions given the day of delivery. Among transfused women, the majority (2,262, 95%) received RBCs, with 540 of them also receiving another blood product and with another 124 solely receiving plasma, platelets, or cryoprecipitate. 1.9% of RBC transfused mothers had stillborn deliveries, compared to 0.5% of non-transfused mothers. Compared to non-transfused mothers, infants of RBC transfused mothers were more likely to be born preterm (<37 weeks; 25.7% vs. 9%) and with low birth weight (<2,500g; 19.3% vs. 7.9%). 79% of infants born to RBC transfused mothers also had a prolonged hospital stay (longer than median for gestational age), compared with 49% of infants born to non-transfused mothers. Supplemental Table 2 shows a bivariate analysis of neonatal outcomes by maternal RBC transfusion status.
Logistic regression analysis was performed to examine the relationship between maternal RBC transfusion or hemoglobin prior to delivery and neonatal outcomes, adjusting for gestational age and maternal demographic and clinical factors (Supplemental Table 3). Maternal RBC transfusion near delivery was associated with a significantly increased odds of stillbirth and of live infants having prolonged hospitalization. Infants born to RBC transfused mothers also had a >3-fold increase in the odds of hypoxic ischemic encephalopathy (HIE) and therapeutic hypothermia, and higher odds of meconium aspiration and respiratory distress (Figure 1). Lower maternal hemoglobin prior to delivery was associated with an increased odds of preterm delivery (<37 wks) and respiratory distress. Neither maternal bleeding disorder nor sickle cell disease were associated with any studied outcome. Among infants <1,500g, maternal RBC transfusion was not associated with intraventricular hemorrhage, necrotizing enterocolitis, bronchopulmonary dysplasia, or retinopathy of prematurity.
Figure 1.
Odds ratios and confidence intervals of adverse neonatal outcomes for maternal RBC transfusion status and nadir hemoglobin in the 7 days prior to or at delivery, adjusted for multiple maternal morbidities, delivery type, and neonatal gestational age. Each row represents a single logistic regression model.
Discussion
In this 5-year study involving 7 hospitals across the U.S., neonates born to mothers transfused with RBCs near delivery were more likely to be stillborn or have adverse outcomes than neonates born to non-transfused mothers. Most significantly, neonates born to transfused mothers had higher odds of HIE, even after adjusting for maternal diagnoses associated with acute fetal distress. Maternal RBC transfusions were also associated with higher odds of meconium aspiration and respiratory distress. These neonatal complications likely account for at least part of the strong association observed between maternal RBC transfusion and prolonged neonatal hospital stay.
Prior studies have evaluated the association between maternal anemia and/or iron deficiency and neonatal outcomes (1–3). Although select studies have evaluated the risks of maternal RBC transfusions in women with anemia (4, 5), few have analyzed the impact of maternal hemoglobin and transfusion on neonatal outcomes. We found neonatal morbidities to be more strongly associated with RBC transfusion compared to maternal anemia.
A strength of our analysis is the large population studied across different hospital types. However, it is difficult to separate the role of maternal events leading to transfusion from the sequelae of the transfusion; it is also possible some included maternal transfusions were given after the actual delivery. Further, ICD-10 codes may not be accurate and unmeasured variables remain unaccounted for.
In conclusion, neonates born to mothers transfused with RBCs just prior to or at delivery (compared to non-transfused mothers) were more likely to have adverse outcomes. Optimizing treatment of maternal conditions that increase transfusion risk may decrease these neonatal complications.
Supplementary Material
Acknowledgements
The authors gratefully acknowledge the manuscript writing team and keen insights and support of this study from the REDS-IV-P Executive Committee. The NHLBI Recipient Epidemiology Donor Evaluation Study – IV – Pediatric (REDS-IV-P) domestic program is the responsibility of the following:
Hubs
A.E. Mast and L. Baumann Kreuziger, Versiti Wisconsin, Milwaukee, WI
B.S. Custer, Vitalant Research Institute, San Francisco, CA and E.P. Vichinsky, Benioff Children’s Hospital Oakland, Oakland, CA
J.E. Hendrickson, Yale University School of Medicine, New Haven, CT and B.R. Spencer, American Red Cross, Dedham, MA
E.A. Hod, Columbia University Medical Center, New York, NY and B.S. Sachais, New York Blood Center, New York, NY
Data Coordinating Center
K. Chapman, Westat, Rockville, MD
E. Rowley, Westat, Rockville, MD
N.L. Luban, Children’s National Medical Center, Washington, D.C.
Central Laboratory
P.J. Norris and M. Stone, Vitalant Research Institute, San Francisco, CA
Publications Committee Chairman
P.M. Ness, Johns Hopkins University, Baltimore, MD
Steering Committee Chairpersons
C.D. Josephson, Johns Hopkins All Children’s Hospital, St. Petersburg, FL, and Johns Hopkins University School of Medicine, Baltimore, MD
S.H. Kleinman, University of British Columbia, Victoria, BC, Canada
National Institute of Child Health and Human Development (NICHD)
R. Tamburro
National Heart, Lung, and Blood Institute, National Institutes of Health
D. Frank, B. Hailu, and K. Malkin
Funding source:
The authors were supported by research contracts from the National Heart, Lung, and Blood Institute (NHLBI Contracts HHSN 75N92019D00032, HHSN 75N92019D00034, HHSN 75N92019D00035, HHSN 75N92019D00036, and HHSN 75N92019D00037). Additional funding was provided by the National Institute of Child Health and Human Development (NICHD)
Conflict of interest statement:
Other than research funding, the authors have no conflicts of interest to disclose.
Availability of data and materials:
REDS-IV-P vein-to-vein data are planned to be available as a public use dataset.
References:
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
REDS-IV-P vein-to-vein data are planned to be available as a public use dataset.