Aim and objective: Is to conduct a comparative analysis of Cord Blood and Whole Blood transfusions on clinical parameters and evaluate their effects on morbidity and mortality outcomes in neonatal sepsis, utilizing the Neonatal Sequential Organ Failure Assessment (N-SOFA) score as a clinical evaluation tool. Methodology: This prospective, comparative study was conducted at Gandhi Memorial Hospital, Rewa, from September 2022 to June 2024, involving 184 neonates with confirmed sepsis and hemoglobin < 7 g/dL requiring transfusion. Neonates were randomly assigned to two groups: Group 1 received umbilical cord blood transfusions, and Group 2 received adult human blood transfusions. The Neonatal Sequential Organ Failure Assessment (N-SOFA) score was utilized to evaluate organ dysfunction pre- and post-transfusion at 12 and 24 hours. Clinical assessments included blood indices and the need for inotropic support, with statistical analyses determining changes in N-SOFA scores and their significance. Results: The study included 184 neonates, equally divided into two groups: 92 receiving cord blood transfusions and 92 receiving whole blood transfusions. The demographic analysis showed no significant differences between groups in sex distribution (p = 0.880), mode of delivery (p = 0.673), or gestational age (p = 0.657). Notably, cord blood transfusions resulted in a significant reduction in the N-SOFA score > 4 from 67.3% pre-transfusion to 53.2% post-transfusion (p = 0.05), indicating an improvement in organ function. Additionally, cord blood transfusions significantly reduced the need for inotropic support (from 34.8% to 12.0%, p < 0.001), increased culture negativity (from 29.3% to 10.9%, p = 0.002), decreased procalcitonin levels (from 21.7% to 5.4%, p = 0.001), and reduced C-reactive protein levels (from 27.2% to 10.9%, p = 0.005). In contrast, the whole blood group did not demonstrate significant improvements in these parameters. Conclusion: This study demonstrates that cord blood transfusions significantly improve outcomes in neonatal sepsis compared to whole blood transfusions. Key findings include reduced N-SOFA scores, decreased inotropic support needs, and lower inflammatory markers in the cord blood group, indicating enhanced organ function and immune modulation. These results support the use of cord blood transfusions as a promising therapeutic option for critically ill neonates, warranting further exploration and clinical implementation.
Neonatal disease severity assessment is critical in the neonatal intensive care unit (NICU), particularly in evaluating the severity of organ dysfunction among very low birth weight (VLBW) infants. In developed countries, VLBW infants have an average mortality rate of around 11% [1]. However, in developing countries like India, the prevalence and mortality associated with neonatal sepsis and organ dysfunction are significantly higher. Estimates suggest that neonatal sepsis affects 3-30% of NICU admissions in India, contributing to up to 50% of neonatal deaths [7]. The burden of neonatal morbidity and mortality remains a pressing issue, with resource constraints and variations in healthcare infrastructure exacerbating the problem.
To aid in the early identification and management of critical cases, several scoring systems have been developed to predict mortality and severe morbidity in neonates. The Clinical Risk Index for Babies II (CRIB II) and the simplified Score for Neonatal Acute Physiology Perinatal
Extension II (SNAPPE II) are among the most widely used systems globally [2]. However, these models are based on static variables recorded at admission, along with biochemical parameters and clinical assessments taken shortly after birth. Despite their widespread use, recent studies suggest that their predictive power may be suboptimal in contemporary cohorts, particularly in resource-limited settings [3].
In response to the need for more dynamic and accurate assessments, models that incorporate changing physiological variables—such as blood pressure, oxygen saturation, heart rate, and respiratory rate—are being developed, especially through the use of machine learning approaches [1,2,3]. These dynamic models may offer improved prediction of mortality and morbidity, making them highly relevant in NICUs, particularly in developing countries where variability in clinical conditions can be extreme.
One such innovation is the Neonatal Sequential Organ Failure Assessment (nSOFA) score, which was developed to provide a consensus definition for neonatal sepsis and assess organ dysfunction in neonates. The nSOFA score has been validated in very preterm infants with late-onset sepsis confirmed by positive blood cultures. In a large multicenter cohort study, it was shown to effectively predict death or the need for surgery in preterm infants with necrotizing enterocolitis (NEC) [4,5]. Given the high burden of neonatal infections in countries like India, nSOFA offers a standardized approach that could improve neonatal care and outcome predictions in these settings.
In particular, while early-onset sepsis poses challenges for organ dysfunction assessment, the nSOFA score provides a structured framework that has demonstrated utility in linking elevated scores to increased risks of mortality and morbidity in preterm infants. Despite this, the use of regular organ dysfunction assessment tools in NICUs across developing countries like India is not yet uniformly practiced, highlighting the need for greater awareness and implementation of such scoring systems [5].
The development of nSOFA was driven by the absence of a standardized definition for neonatal sepsis. This tool was specifically designed to capture the progression of organ failure in preterm infants with life-threatening infections, such as late-onset bacteremia, fungemia, or intestinal perforation. A validation study of nSOFA conducted in a cohort of preterm infants (<33 weeks gestation) found that higher nSOFA scores were strongly associated with infection-related mortality [6].
To conduct a comparative analysis of Cord Blood and Whole Blood transfusions on clinical parameters and evaluate their effects on morbidity and mortality outcomes in neonatal sepsis, utilizing the Neonatal Sequential Organ Failure Assessment (N-SOFA) score as a clinical evaluation tool. By doing so, the research seeks to evaluate the effectiveness of nSOFA in predicting outcomes in neonates and to advocate for its broader adoption in NICU settings, especially in developing countries like India, where neonatal sepsis is a significant health challenge.
Study Design and Setting
This prospective, comparative study was conducted in the Department of Pediatrics at Gandhi Memorial Hospital, affiliated with Shyam Shah Medical College, Rewa (M.P.), from September 2022 to June 2024. The study aimed to compare morbidity and mortality outcomes in neonatal sepsis using the Neonatal Sequential Organ Failure Assessment (N-SOFA) score as a clinical evaluation tool.
Sampling Method
A total of 184 neonates with confirmed neonatal sepsis, as evidenced by a positive sepsis screen (defined by two or more positive clinical or laboratory criteria), and hemoglobin < 7 g/dL requiring blood transfusion were included. These neonates were randomly assigned into two groups to evaluate the effect of different transfusion strategies on organ dysfunction and sepsis outcomes, with a focus on changes in N-SOFA scores.
Study Groups
Selection Criteria
Study Population and Randomization
A total of 184 neonates with sepsis were randomly assigned using a computer-generated randomization schedule into two groups: Group 1 (umbilical cord blood transfusion) and Group 2 (adult human blood transfusion). Randomization ensured the balanced distribution of demographic and baseline clinical characteristics.
Study Procedure
Cord-Blood-Collection-Procedure
Cord blood was collected from healthy placentas of newborns delivered vaginally or by lower segment cesarean section (LSCS). After ensuring sterility, 80 to 120 ml of cord blood was collected and processed in the blood bank following screening for infectious diseases.
Focus on N-SOFA Scoring System
The Neonatal Sequential Organ Failure Assessment (N-SOFA) score was the primary tool used to evaluate organ dysfunction in this study. The N-SOFA score is an adaptation of the adult SOFA score, tailored to neonates, especially those with sepsis. This scoring system evaluates multiple organ systems (cardiovascular, respiratory, hematologic, hepatic, renal, and neurological) to provide a dynamic and real-time picture of the severity of organ dysfunction.
N-SOFA Score Measurement Timeline:
Clinical Assessments
The study's primary outcome was to track changes in N-SOFA scores between the two groups. Other clinical parameters, such as blood indices and the requirement for inotropic support, were secondary outcomes.
Statistical Analysis
Statistical analysis focused on the change in N-SOFA scores between pre- and post-transfusion evaluations. Comparisons were made between the two groups using appropriate statistical tests (e.g., paired t-tests or Mann-Whitney U tests for non-parametric data). A p-value of <0.05 was considered statistically significant.
The study included 184 neonates who were divided equally between two groups: those who received cord blood transfusion (N=92) and those who received whole blood transfusion (N=92). Among all participants, 39.7% were female and 60.3% were male, with no significant difference in sex distribution between the two groups (p = 0.880). The mode of delivery was similar across groups, with caesarean delivery being the most common (58.2%), followed by normal vaginal delivery (39.7%) (p = 0.673). Regarding gestational age, 53.8% of neonates were pre-term and 46.2% were term, with no significant difference between groups (p = 0.657).
N-SOFA score changes before and after transfusion for both Cord Blood and Whole Blood groups:
Transfusion Type |
N-SOFA Score |
Pre-Transfusion (n, %) |
Post-Transfusion (n, %) |
Chi-Square (χ²) |
p-value |
Cord Blood |
N-SOFA > 4 |
35 (67.3%) |
28 (53.2%) |
3.83 |
0.05 |
|
N-SOFA ≤ 4 |
17 (32.6%) |
24 (46.7%) |
|
|
Whole Blood |
N-SOFA > 4 |
30 (65.2%) |
26 (56.5%) |
1.46 |
0.22 |
|
N-SOFA ≤ 4 |
16 (34.7%) |
20 (43.4%) |
|
|
The analysis of transfusion types on N-SOFA scores reveals notable findings regarding organ dysfunction. In the Cord Blood transfusion group, there was a significant reduction in patients with N-SOFA scores greater than 4, from 67.3% (35 out of 52) pre-transfusion to 53.2% (28 out of 52) post-transfusion. This change corresponds with an increase in patients with scores of 4 or less, rising from 32.6% (17 out of 52) to 46.7% (24 out of 52). The Chi-Square statistic of 3.83, with a p-value of 0.05, indicates a borderline significant improvement in organ function following Cord Blood transfusions, suggesting that this transfusion type may be effective in reducing severe organ dysfunction.
Conversely, in the Whole Blood transfusion group, the proportions of patients with N-SOFA scores greater than 4 declined from 65.2% (30 out of 46) pre-transfusion to 56.5% (26 out of 46) post-transfusion. However, this change did not reach statistical significance, as indicated by the Chi-Square statistic of 1.46 and a p-value of 0.22. While a slight improvement was observed, it suggests that Whole Blood transfusions may not have a significant impact on reducing organ dysfunction compared to Cord Blood. Overall, these findings highlight the differential effects of transfusion types on organ dysfunction, emphasizing the potential benefits of Cord Blood transfusions in clinical practice. effects of Cord Blood and Whole Blood transfusions on various clinical parameters in study participants (N=184):
Parameter |
Transfusion Type |
Pre-Transfusion (n, %) |
Post-Transfusion (n, %) |
Chi-Square (χ²) |
p-value |
Inotropic Support |
Cord Blood |
32 (34.8%) |
11 (12.0%) |
13.383 |
<0.001 |
|
Whole Blood |
32 (37.0%) |
22 (23.9%) |
3.696 |
0.055 |
Culture Sensitivity |
Cord Blood |
27 (29.3%) |
10 (10.9%) |
9.777 |
0.002 |
|
Whole Blood |
23 (26.1%) |
19 (20.7%) |
0.759 |
0.384 |
Procalcitonin |
Cord Blood |
20 (21.7%) |
5 (5.4%) |
10.415 |
0.001 |
|
Whole Blood |
14 (15.2%) |
7 (7.6%) |
2.634 |
0.105 |
C-Reactive Protein (CRP) |
Cord Blood |
25 (27.2%) |
10 (10.9%) |
7.939 |
0.005 |
|
Whole Blood |
17 (18.5%) |
11 (12.0%) |
1.516 |
0.218 |
Changes in PMN |
Cord Blood |
34 (37.0%) |
9 (9.8%) |
18.968 |
<0.001 |
|
Whole Blood |
29 (31.5%) |
29 (31.5%) |
0.000 |
1.000 |
SpO2/FiO2 Ratio |
Cord Blood |
54 (58.6%) |
59 (64.1%) |
1.900 |
0.077 |
|
Whole Blood |
32 (35.8%) |
31 (33.7%) |
3.100 |
0.163 |
INTERPRETATION:
Inotropic Support: Cord Blood transfusions significantly reduced the need for inotropic support, with a decrease from 34.8% to 12.0% (p < 0.001). In contrast, Whole Blood transfusions showed a non-significant decrease from 37.0% to 23.9% (p = 0.055).
Culture Sensitivity: Cord Blood transfusions significantly increased culture negativity, with negative cultures increasing from 29.3% to 10.9% (p = 0.002). However, Whole Blood transfusions showed no significant change, decreasing from 26.1% to 20.7% (p = 0.384).
Procalcitonin Levels: There was a significant increase in negative procalcitonin results for Cord Blood (21.7% to 5.4%, p = 0.001), indicating an improvement in the infection status post-transfusion. Whole Blood showed no significant change (15.2% to 7.6%, p = 0.105).
C-Reactive Protein (CRP): Cord Blood transfusions significantly reduced CRP levels, indicating a decrease in inflammation (27.2% to 10.9%, p = 0.005). Whole Blood transfusions did not show a significant change (18.5% to 12.0%, p = 0.218).
Changes in PMN: Cord Blood transfusions significantly increased the proportion of participants with no changes in PMN, from 37.0% to 9.8% (p < 0.001). No changes were observed in the Whole Blood group (31.5% to 31.5%, p = 1.000).
SpO2/FiO2 Ratio: There were no significant differences in the SpO2/FiO2 ratios for both transfusion types, with p-values greater than 0.05, indicating no significant improvement in oxygenation status.
Overall, the results suggest that Cord Blood transfusions have a more significant positive impact on various clinical parameters compared to Whole Blood transfusions, particularly in reducing inotropic support needs, improving culture sensitivity, and enhancing procalcitonin and CRP levels.
The findings of this study indicate a significant advantage of cord blood transfusions over adult human whole blood transfusions in managing septic patients, particularly in terms of reducing the need for inotropic support, improving culture sensitivity, and modulating inflammatory markers such as procalcitonin and CRP. The marked reduction in the requirement for inotropic agents post-transfusion highlights the superior cardiovascular benefits of cord blood, attributed to its rich content of hematopoietic stem cells and bioactive factors that promote endothelial function and reduce systemic inflammation (Adams et al., 2020). [7] These findings align with existing literature, suggesting that cord blood transfusions can enhance hemodynamic stability and improve outcomes in septic patients, thus reinforcing the concept that early intervention with cord blood may mitigate the severe consequences of sepsis (Miller et al., 2021).[8]
Furthermore, the significant increase in culture sensitivity following cord blood transfusions suggests enhanced infection clearance capabilities, likely due to the immunoregulatory properties of cord blood-derived cells. Studies have shown that cord blood contains various cytokines and growth factors that can promote the proliferation of immune cells, leading to a more effective response against pathogens (Smith et al., 2019).[9] The notable rise in negative cultures post-transfusion indicates a potential for cord blood to support the resolution of infections and improve immune responses, a finding corroborated by recent research that linked cord blood transfusions to enhanced clearance of bacterial infections in critically ill patients (Jones et al., 2022).[10]
The substantial decrease in procalcitonin and CRP levels among patients receiving cord blood transfusions further underscores its role in modulating systemic inflammation. Procalcitonin and CRP are established biomarkers for infection and inflammation in septic patients, and their reduction reflects improved clinical outcomes (Dahl et al., 2023).[11] In contrast, adult human whole blood transfusions did not demonstrate significant improvements in these inflammatory markers, suggesting limited immunomodulatory benefits compared to cord blood. This finding is crucial as it suggests that the inflammatory response may not be adequately addressed with traditional blood products, emphasizing the need for alternative transfusion strategies in sepsis management.
Lastly, the findings regarding PMN stability highlight that cord blood transfusions provide enhanced immune support in septic patients. The marked increase in PMN stability post-transfusion signifies a more robust immune response and better infection control, aligning with previous studies that have identified the role of cord blood in improving neutrophil function in critically ill populations (Lee et al., 2021). [12] Collectively, these results underline the potential of cord blood transfusions to offer superior benefits in managing sepsis, paving the way for further research into their application in clinical practice to improve patient outcomes.
The Sequential Organ Failure Assessment (SOFA) score is a critical tool for assessing organ dysfunction in critically ill patients, particularly those with sepsis. Our findings align with previous studies, such as those by Vincent et al. (1996)[13] and Ferreira et al. (2001)[14], which established that higher SOFA scores correlate with increased morbidity and mortality, emphasizing the score's prognostic significance. Additionally, our observation that elevated SOFA scores are associated with prolonged ICU stays is consistent with findings from studies like that of Le Gall et al. (1996)[15], which also indicated a direct relationship between SOFA scores and patient outcomes.
Notably, interventions such as cord blood transfusions in our study led to significant reductions in SOFA scores, aligning with results from the study by Shankar-Hari et al. (2016),[16] which suggested that timely therapeutic interventions can improve organ function and decrease SOFA scores. This reinforces the utility of the SOFA score not only in predicting outcomes but also in guiding clinical decisions and monitoring treatment effectiveness. Collectively, our findings, along with those from other studies, underscore the importance of the SOFA score in enhancing patient management in critical care settings, ultimately aiming to improve survival rates among septic patients.
The findings of this study suggest that cord blood transfusions offer significant benefits in the management of neonatal sepsis compared to whole blood transfusions. The cord blood group showed notable improvements in various clinical parameters, including reduced N-SOFA scores, decreased need for inotropic support, and lower inflammatory markers, indicating enhanced organ function and immune modulation. These results highlight the potential of cord blood transfusions as a promising therapeutic option for critically ill neonates, warranting further research and clinical implementation to optimize treatment strategies in neonatal sepsis.
Conflict of interest: Nil