Comparison of nSOFA and RSS for predicting bronchopulmonary dysplasia in preterm infants: a retrospective cohort study

Abstract

Background

This study aimed to compare the efficacy of the Neonatal Sequential Organ Failure Assessment (nSOFA) and the Respiratory Severity Score (RSS) in predicting Bronchopulmonary Dysplasia (BPD).

Methods

We conducted a retrospective study that included preterm infants who required invasive mechanical ventilation (IMV) within 24 hours of birth. The accuracy of each scoring system was assessed and compared using the area under the curve (AUC) derived from receiver operating characteristic (ROC) analysis. Additionally, Spearman’s correlation was used to evaluate the association between RSS and nSOFA, and logistic regression models were constructed to adjust for potential confounders.

Results

A total of 85 preterm infants were analysed, of whom 53 (62.4%) were diagnosed with BPD. Both nSOFA and RSS demonstrated strong predictive abilities for BPD, with AUCs of 0.82 and 0.81, respectively. Logistic regression analysis indicated that the relationship between the two scoring systems and BPD remained stable. However, nSOFA exhibited better predictive accuracy than RSS (0.75 vs 0.69). A significant positive correlation was observed between nSOFA and RSS (r=0.707, p<0.001).

Conclusions

In preterm infants requiring IMV, both nSOFA and RSS are effective predictors of BPD, with nSOFA showing superior accuracy.

WHAT IS ALREADY KNOWN ON THIS TOPIC.

WHAT THIS STUDY ADDS

• RSS and nSOFA demonstrate comparable predictive abilities for BPD in preterm infants, but nSOFA shows superior predictive accuracy than RSS.

• There was a significant positive correlation between RSS and nSOFA.

HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY

• nSOFA is a more practical and accurate tool for the early identification of BPD in mechanically ventilated preterm infants.

• Integrating nSOFA into electronic health records to enhance quality-improvement initiatives can improve long-term respiratory outcomes in preterm infants.

INTRODUCTION

Bronchopulmonary dysplasia (BPD) is a serious chronic lung condition that significantly contributes to morbidity and mortality in preterm infants.¹ Despite advances in neonatal care, including the use of gentle ventilation techniques, postnatal surfactant and antenatal and postnatal steroids, the incidence of BPD has continued to rise.^{2 3} BPD is associated with a range of long-term complications, including pulmonary hypertension, neurodevelopmental deficits and an increased risk of respiratory diseases later in life.4,6 The considerable burden imposed by BPD underscores the urgent need for early identification of high-risk infants to facilitate timely interventions and improve long-term outcomes.

Neonatal respiratory failure is a common and life-threatening condition worldwide,⁷ with a considerable proportion of preterm infants requiring invasive mechanical ventilation (IMV). A recent analysis of data from a US neonatal research network found that more than 75% of infants born at 27 weeks gestational age (GA) required IMV, with the percentage rising to nearly 100% for infants born at 22 to 23 weeks GA.⁸ Unfortunately, prolonged IMV can lead to ventilator-induced lung injury, which in turn contributes significantly to the development of BPD.⁹

The Respiratory Severity Score (RSS)¹⁰ and the Neonatal Sequential Organ Failure Assessment (nSOFA) score,¹¹ as non-invasive indices to assess pulmonary status have been used as predictive indicators to identify high-risk infants with BPD and to assess severity.12,14 However, limited studies have directly compared the predictive performance of these two scoring systems for BPD in preterm infants requiring IMV.

The objective of this study was to systematically compare the predictive power of the RSS and nSOFA for the risk of BPD in preterm infants receiving IMV.

METHODS

Study design and population

This retrospective, single-centre cohort included preterm infants with GA less than 32 weeks and birth weight (BW) lower than 1500 g who were admitted to the neonatal intensive care unit (NICU) in the First Affiliated Hospital of Anhui Medical University between 1 January 2021 and 31 December 2022. The exclusion criteria were as follows: (1) admission after 24 hours of life; (2) no IMV within the initial 24 hours of life; (3) death before 36 weeks of postmenstrual age; (4) auto-discharge with unknown outcomes and (5) incomplete clinical data. The study was approved by the Ethics Committee of the First Affiliated Hospital of Anhui Medical University (No. PJ 2023-14-71). The requirement for informed consent was waived due to the retrospective study design.

Data collection

Medical records were systematically reviewed to collect demographic and clinical data for all participants during their hospitalisation. To calculate the RSS and nSOFA score, the following clinical characteristics were extracted: mean airway pressure (MAP), fraction of inspired oxygen (FiO₂), peripheral oxygen saturation, any requirement for glucocorticoids, inotropic or vasoactive drugs and platelet count within the 72 hours after delivery. The maximum scores from each scoring system during this period were used for analysis.

Calculation of scores

The RSS is equal to the MAP multiplied by the FiO₂.¹⁰ MAP was calculated based on the following equation: MAP=PEEP+((PIP-PEEP)×(t_i/(t_i+t_e)), where PEEP represents the positive end-expiratory pressure, PIP represents the peak inspiratory pressure, t_i represents the inspiratory time and t_e represents the expiratory time.¹⁵

The nSOFA score (range from 0 to 15) is calculated based on respiratory, cardiovascular and hematologic parameters. Specifically, the respiratory function component (score range, 0–8) is based on the need for mechanical ventilation and oxygen supplementation, hemodynamic compromise component (score range, 0–4) is evaluated based on the administration of inotropic and vasoactive medications, including corticosteroids, and hematologic dysfunction component (score range, 0–3) is reflected by the platelet count¹⁶ (table 1).

Table 1. Neonatal Sequential Organ Failure Assessment (nSOFA) Components and Scoring^*.

Component	nSOFA scores
Respiratory score	0	2	4	6	8
Criteria	Not intubated or intubated, SpO2/FiO2≥300	Intubated, SpO2/FiO2<300	Intubated, SpO2/FiO2<200	Intubated, SpO2/FiO2<150	Intubated, SpO2/FiO2<100
Cardiovascular score	0	1	2	3	4
Criteria†	No inotropes and no systemic corticosteroid treatment	No inotropes and systemic corticosteroid treatment	1 inotrope and no systemic corticosteroid treatment	≥ 2 inotropes or 1 inotrope and systemic corticosteroid treatment	≥2 inotropes and systemic corticosteroid treatment
Haematologic score	0	1	2	3	NA
Criteria‡	Platelet count§ ≥ 150 × 103	Platelet count 100–149×103	Platelet count < 100 × 103	Platelet count < 50 × 103

^*Score range, 0 (best) to 15 (worst).

^†Medications considered as inotropic or vasoactive included dopamine, dobutamine, epinephrine, norepinephrine, vasopressin and phenylephrine.

^‡Most recent platelet count available to the clinician.

^§SI conversion factor: To convert platelet count to×109 /L, multiply by 1.

FiO₂, fraction of inspiratory oxygen; NA, not applicable; nSOFA, neonatal sequential organ failure assessment; SpO₂, peripheral oximetric saturation.

Outcomes

The primary outcome of our study was the development of BPD, defined by the 2001 National Institutes of Health consensus criteria based on the need for supplemental oxygen therapy for at least 28 days.¹⁷

Respiratory management strategies

According to local protocol, infants were started on IMV if they experienced apnea episodes (more than four times per day or more than twice per hour, requiring positive pressure ventilation) despite medical treatment or non-invasive ventilation support, or FiO₂>0.6 with PaO₂<50 mmHg or TcSO₂<85% (excluding cyanotic congenital heart disease) or PaCO₂>65 mmHg with persistent acidosis (pH<7.20). Ventilation modes and parameters should be set and adjusted according to the patient’s condition to maintain PaCO₂ at 50–60 mmHg, pH >7.20 and PaO₂ at 50–70 mmHg or SpO₂ at 90–95%. Infants were extubated based on the following criteria: adequate spontaneous breathing, clinical stability, MAP <6–8 cmH ₂O, FiO₂ <0.30, pH >7.25 and PaCO₂<60 mmHg.

Patient and public involvement

This research did not involve patients or the public in its design, conduct, reporting or dissemination activities.

Statistical analysis

Data were expressed as mean (SD), median (IQR) and count (%) for parametric, non-parametric and categorical variables, respectively. Group comparisons were performed using Student’s t-test, Mann-Whitney U-test or χ² test, as appropriate. Receiver operating characteristic (ROC) curves and area under the curve (AUC) were calculated to assess the predictive ability of the scoring systems for BPD. Cut-off points were determined using the Youden index to classify participants into high-score and low-score groups for nSOFA and RSS. Sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) were calculated for each scoring system. In addition, Spearman’s correlation was used to assess the relationship between RSS and nSOFA. Logistic regression models were constructed to adjust for potential confounders: model 1 unadjusted, model 2 adjusted for GA and BW and model 3, including pneumonia and a duration of IMV for more than 7 days. Statistical analyses were carried out by SPSS Version 25 (IBM Corp., Armonk, NY) or GraphPad Prism 9.0 (GraphPad Inc., San Diego, CA, USA) software. Results were considered significant at a P-value of less than 0.05.

RESULTS

Characteristics of the study participants

We identified 85 premature infants with GA less than 32 weeks and BW less than 1500 g, and they were included in the study. Of these, 53 infants (62.4%) were diagnosed with BPD, while 32 infants (37.6%) did not. The study flow diagram is shown in figure 1. The mean GA of the study participants was 28.73±1.66 weeks, with a median BW of 1100 g (IQR, 900–1250 g). The BPD group had significantly lower GA and BW compared with the no-BPD group (95% CI 1.13 to 2.40; p<0.001 and 95% CI 0.002 to 0.004; p=0.003, respectively). Additionally, the proportion of infants who required IMV for more than 7 days and with pneumonia was higher in the BPD group than in the no-BPD group (56.6% vs 12.5%; p<0.001 and 98.1% vs 78.1%; p=0.004, respectively). Both RSS (3.60 (IQR, 3.00–5.10) vs 2.58 (IQR, 2.18–3.15); p<0.001) and nSOFA (4 (IQR, 2–5) vs 2 (IQR, 0–2); p<0.001) were significantly higher in the BPD group. The baseline characteristics of the study participants are detailed in table 2.

Figure 1. Flow diagram of the patient selection process. BPD, Bronchopulmonary Dysplasia; BW, birth weight; GA, gestational age.

Table 2. Baseline characteristics of participants.

Characteristics	Total patients (n=85)	BPD (n=53)	Non-BPD (n=32)	P-value
GA (week), mean (SD)	28.73 (1.66)	28.07 (1.55)	29.83 (1.22)	< 0.001
BW (g), median (IQR)	1100.0 (900.0, 1250.0)	990.0 (850.0, 1170.0)	1235.0 (960.0, 1367.5)	0.003
Sex
Male, n (%)	52 (61.2)	32 (60.4)	20 (62.5)	1.000
Female, n (%)	33 (38.8)	21 (39.6)	12 (37.5)
Multiple pregnancy, n (%)	31 (36.5)	21 (39.6)	10 (31.3)	0.492
Caesarean delivery, n (%)	63 (74.1)	38 (71.7)	25 (78.1)	0.613
Assisted reproduction, n (%)	24 (28.2)	17 (32.1)	7 (21.9)	0.335
Maternal age, year, mean (SD)	31.44 (4.53)	31.23 (4.73)	31.78 (4.23)	0.587
HDP, n (%)	25 (29.4)	12 (22.6)	13 (40.6)	0.091
GDM, n (%)	30 (35.3)	17 (32.1)	13 (40.6)	0.486
PROM>18 hour, n (%)	22 (25.9)	15 (28.3)	7 (21.9)	0.613
Antenatal steroid use, n (%)	63 (74.1)	39 (73.6)	24 (75.0)	1.000
Apgar score at 5 min, median (IQR)	8 (6, 8)	8 (6, 8)	8 (7, 8)	0.328
Intubated in the delivery room, n (%)	73 (85.9)	46 (86.8)	27 (84.4)	0.758*
Surfactant use, n (%)	81 (95.3)	52 (98.1)	29 (90.6)	0.148*
Caffeine use, n (%)	81 (95.3)	51 (96.2)	30 (93.8)	0.630*
IMV time >7d, n (%)	34 (40.0)	30 (56.6)	4 (12.5)	< 0.001
Pneumonia	77 (90.6)	52 (98.1)	25 (78.1)	0.004*
PDA, n (%)	32 (37.6)	20 (37.7)	12 (37.5)	1.000
RSS, median (IQR)	3.15 (2.58, 4.40)	3.60 (3.00, 5.10)	2.58((2.18,3.15)	< 0.001
nSOFA, median (IQR)	2 (2,5)	4 (2, 5)	2 (0, 2)	< 0.001

^*Fisher’s exact test

BPD, bronchopulmonary dysplasia; BW, birth weight; GA, gestational age; GDM, gestational diabetes mellitus; HDP, hypertensive disorders of pregnancy; IMV, invasive mechanical ventilation; IQR, interquartile range; nSOFA, neonatal sequential organ failure assessment; PDA, patent ductus arteriosus; PROM, prolonged rupture of membranes; RSS, respiratory severity score; SD, standard deviation.

The predictive validity of scoring systems for BPD

For predicting BPD in preterm infants receiving IMV, RSS and nSOFA demonstrated similar predictive performance, with an AUC of 0.81 (95% CI 0.72 to 0.90) for RSS and 0.82 (95% CI 0.72 to 0.91) for nSOFA. The difference in AUC was not statistically significant (difference: −0.002, 95% CI −0.09 to 0.10, p=0.965). The ROC curves and corresponding AUC values, which assess the predictive accuracy of RSS and nSOFA for BPD, were presented in figure 2. Table 3 shows the cut-off scores together with sensitivity, specificity, accuracy, PPV, NPV and likelihood ratios (LR+and LR-). The results indicate that nSOFA had superior accuracy to RSS (0.75 vs 0.69) in predicting BPD. In addition, there was a significant positive correlation between RSS and nSOFA (r=0.707, p<0.001), as shown in figure 3.

Figure 2. ROC curve analysis of RSS and nSOFA in predicting BPD. BPD, Bronchopulmonary Dysplasia; nSOFA, Neonatal Sequential Organ Failure Assessment; RSS, Respiratory Severity Score.

Table 3. Comparison of nSOFA and RSS in predicting BPD based on best cut-off scores.

Variable	nSOFA	RSS
Cut-off point	2.5	3.225
AUC (95% CI)	0.82 (0.72 to 0.91)	0.81 (0.72 to 0.90)
Sensitivity	0.70	0.59
Specificity	0.84	0.88
PPV	0.88	0.89
NPV	0.63	0.56
Accuracy	0.75	0.69
Positive LR	4.46	4.68
Negative LR	0.36	0.47
P-value	<0.001	<0.001

AUC, area under the curve; BPD, bronchopulmonary dysplasia; CI, confidence interval; LR, likelihood ratio; NPV, negative predictive value; nSOFA, neonatal sequential organ failure assessment; PPV, positive predictive value; RSS, respiratory severity score.

Figure 3. The correlation between RSS and nSOFA. nSOFA, Neonatal Sequential Organ Failure Assessment; RSS, Respiratory Severity Score.

Association between scoring systems and BPD

A regression approach was used to adjust for probable risk factors associated with the development of BPD，as presented in table 4 . In the unadjusted model, both RSS and nSOFA were significantly associated with the risk of BPD, with ORs of 4.07 (95% CI 1.86 to 8.88) and 1.94 (95% CI 1.41 to 2.67), respectively. In the multivariate regression model, after adjusting for GA and BW, the adjusted odds ratio (aOR) was 3.15 (95% CI 1.42 to 6.97) for RSS and 1.69 (95% CI 1.21 to 2.37) for nSOFA. The associations remained statistically significant after adjusting for GA, BW, pneumonia and IMV duration over 7 days, with an aOR of 2.86 (95% CI 1.20 to 6.79) for RSS and 1.62 (95% CI 1.12 to 2.34) for nSOFA. The optimal cut-off values for predicting BPD were 3.225 for RSS and 2.5 for nSOFA, classifying participants into high-score and low-score groups. Regression analysis across these groups confirmed that the associations of RSS and nSOFA with BPD were consistent.

Table 4. Association of the nSOFA and RSS with BPD.

Variable	Event	Unadjusted		Model 1		Model 2
		Or (95% CI)	P-value	Or (95% CI)	P-value	Or (95% CI)	P-value
nSOFA	53/85	1.94 (1.41 to 2.67)	<0.001	1.69 (1.21 to 2.37)	0.002	1.62 (1.12 to 2.34)	0.010
nSOFA group
Low nSOFA	43/85	Reference		Reference		Reference
High nSOFA	42/85	12.49 (4.07 to 38.27)	<0.001	8.40 (2.42 to 29.07)	0.001	6.71 (1.76 to 25.66)	0.005
RSS	53/85	4.07 (1.86 to 8.88)	<0.001	3.15 (1.42 to 6.97)	0.005	2.86 (1.20 to 6.79)	0.018
RSS group
Low RSS	50/85	Reference		Reference		Reference
High RSS	35/85	9.86 (3.03 to 32.15)	<0.001	6.41 (1.77 to 23.16)	0.005	4.69 (1.16 to 18.95)	0.030

Model 1, adjusted for gestational age and birth weight.

Model 2, adjusted for gestational age, birth weight, pneumonia and duration of invasive mechanical ventilation time＞7d.

BPD, bronchopulmonary dysplasia; CI, confidence interval; nSOFA, neonatal sequential organ failure assessment; RSS, respiratory severity score.

DISCUSSION

In this retrospective cohort study, we compared the predictive abilities of RSS and nSOFA for BPD in preterm infants receiving IMV. Our findings indicate that both the RSS and nSOFA are reliable predictors of BPD, with nSOFA demonstrating superior accuracy.

RSS is a non-invasive biomarker widely used to assess the severity of respiratory illness.^{18 19} Previous research had established a significant association between the RSS and BPD in preterm infants.¹² Kielt et al¹³ found that elevated RSS strongly predicts adverse in-hospital outcomes for patients with severe BPD, with an AUC of 0.90 (95% CI 0.85 to 0.94) and an aOR of 1.5 (95% CI 1.3 to 1.7). Beer et al²⁰ recently reported that higher RSS values were associated with an increased risk of BPD-associated pulmonary hypertension (aOR 1.3, 95% CI: 1.2 to 1.4). Consistent with these findings, our study indicated that RSS is a predictor of BPD in preterm infants receiving IMV, with an AUC of 0.81 (95% CI 0.72 to 0.90) and an aOR of 2.86 (95% CI 1.20 to 6.79).

The nSOFA score was initially developed to forecast mortality in very low BW infants with late-onset sepsis.¹¹ Subsequently, the nSOFA score has been adapted for use in other neonatal conditions.^{21 22} Recent studies have also confirmed its association with BPD.^{14 23} Poggi et al¹⁴ reported that maximal nSOFA score during the first 24 hours after the onset of late-onset sepsis showed an AUC of 0.70 (95% CI 0.60 to 0.80) for BPD and an OR of 4.86 (95% CI 1.54 to 15.28) when maximal nSOFA was ≥4. Our previous study indicated that the maximal nSOFA score within the first 72 hours after delivery reliably predicted BPD in preterm infants, with an AUC of 0.79 (95% CI 0.73 to 0.85) and an aOR of 2.09 (95% CI 1.57 to 2.76).²³ In this study, restricting the cohort to preterm infants receiving IMV, the predictive performance of nSOFA remained stable, with an AUC of 0.82 (95% CI 0.72 to 0.91) and an aOR of 1.62 (95% CI 1.12 to 2.34).

The present study revealed that, although the AUC values of both scoring systems were similar, nSOFA exhibited higher predictive accuracy. A recent study by Hao et al²⁴ also indicated that nSOFA was more effective than SNAPPE-II and CRIB-II in predicting mortality in preterm infants. This may be attributed to the comprehensive assessment provided by nSOFA. Unlike RSS, which focuses only on respiratory function, nSOFA also assesses cardiovascular and hematologic systems.¹¹ Furthermore, we observed a significant positive correlation between RSS and nSOFA, suggesting that both scoring systems may reflect similar clinical features in assessing the respiratory status of preterm infants.

Early identification of preterm infants at high risk of BPD is critical for targeted interventions and improved clinical outcomes. Currently, several models have been developed, incorporating clinical indicators, biomarkers, imaging data and genomic parameters.25,28 The potential challenges and complexities in evaluating these variables in clinical practice, coupled with increased medical costs,²⁹ limit their generalisability. By contrast, nSOFA is non-invasive, easily obtainable, applicable early after birth and simple to calculate.³⁰ It can be integrated into electronic health records for dynamic monitoring and automated alerts, enabling early identification of intubated preterm infants at high risk of BPD. This facilitates timely interventions, including non-invasive respiratory support, restrictive fluid management and optimised nutrition, which may improve pulmonary outcomes, reduce healthcare utilisation and generate data for quality improvement and prospective research.¹⁶

Limitations

This study has some limitations inherent to a single-centre retrospective design. External validation could not be performed, which may limit the generalisability of our findings. Given the limited sample size, we restricted the number of covariates in the multivariable model to avoid overfitting. However, residual confounding from unmeasured factors cannot be excluded. Future studies with larger multicentre prospective cohorts and external validation are warranted to further verify these findings. Furthermore, BPD in this study was defined as oxygen supplementation ≥28 days and excluding preterm infants who died from respiratory causes before 36 weeks’ postmenstrual age. Future studies should consider including these early mortality cases and evaluate the predictive performance of nSOFA and RSS using updated definitions and severity classifications, such as the 2019 Jensen criteria.^{31 32}

CONCLUSIONS

Among preterm infants receiving IMV, both RSS and nSOFA are effective predictors of BPD. nSOFA, as a comprehensive scoring system, shows superior predictive accuracy compared with RSS. Nevertheless, multicentre studies are needed to further validate the predictive performance of both scoring systems in preterm infants.

Data availability statement

Data are available upon reasonable request.