Predictive values and correlation of CRIB Score II and perfusion index in assessment of severity of illness in sick preterm neonates: An observational study

Abstract

BACKGROUND:

Perfusion index (PI) and CRIB (Clinical risk index of babies) Score II both are minimally invasive tools for prediction of mortality and morbidity in sick neonates. This study aims to know the predictive values of both PI and CRIB Score II in assessment of severity of illness in preterm neonates of 28 to 32 weeks and their correlation.

METHODS:

PI and CRIB II Score of 125 sick preterm neonates admitted in NICU were assessed within 12 hours of admission. Severity noted in form of outcome. Correlation between PI and CRIB Score II were observed.

RESULTS:

Receiver operating characteristic (ROC) curve were plotted for PI and CIRB Score II with outcome (discharged vs expired). Area under curve for perfusion index was 0.776 at 95% confidence interval. Optimum cutoff point based on ROC curve was 1.65 with sensitivity of 84%., specificity of 37.2% with positive predictive value of 70% and negative predictive value of 57%. Area under curve for CRIB Score II was 0.622 (p value < 0.028), optimum cut off point based on ROC curve for CRIB II score was 3.5 with sensitivity 79.10% of specificity of 40% positive predictive value is 43.03% and negative predictive value of 76.9%. Spearman’s correlation coefficient between PI and CRIB II score was –0.272 and p value is 0.002.

CONCLUSION:

This study concluded that perfusion index (p < 0.001) is better for predicting the severity compared to CRIB II score (p < 0.028). A weak negative correlation exists between PI and CRIB II score (r = –0.272).

Keywords

Area under curve confidence interval perfusion index preterm-neonates receiver operating characteristic

1 Introduction

According to the World Health Organization (WHO), about 8 million infants annually die within first 12 hours of life [1] Prematurity, low birth weight and congenital malformations are the most important cause of neonatal mortality [2]. Preterm newborns, mainly those admitted to Neonatal Intensive Care Units (NICUs), are known to be at risk of developing several adverse outcomes, especially during the first week of life. The immaturity of the cardiovascular and autonomous nervous system may lead to hypo perfusion states that, when prolonged, can result in acute organ failure [3 –6]. Under normal conditions the skin perfusion is higher but during the period of stress body has to maintain the blood supply to vital organs like heart, brain and adrenals hence the skin perfusion is reduced which can be measured by Perfusion index (PI). It is the ratio of the pulsatile blood flow to the non-pulsatile or static blood in peripheral tissue. When peripheral hypoperfusion exists, the pulsatile component decreases, and the ratio drops because the non-pulsatile component does not change [7]. Thus, PI, is a noninvasive numerical measure of real time changes in peripheral perfusion measured continuously and noninvasively, easily obtained from the newer pulse-oximeters. Earlier identification and management of poor perfusion / shock in newborns can reduce the mortality and morbidities. In clinical practice, tissue perfusion and oxygenation are usually assessed by noninvasive techniques such as heart rate, blood pressure (BP), oxygen saturation (SpO2), capillary refill time and temperature [8, 9]. However, it is suggested that these methods are poor representatives of microcirculation. While indirect measures such as urine output, capillary refill time and serum lactate levels, are poor indicators of acute blood flow changes in the immediate neonatal period especially in first few days of life. The clinical parameters are liable to subjective variation. So, there is a need for objective identification /assessment of poor perfusion in the newborn which will be useful in early identification and management of the sick babies. To counter the above discussed problems, we wanted to study if perfusion index could be a useful objective parameter in prediction of severity of illness.

Sickness severity scores are widely used for neonates admitted to neonatal intensive care units to predict severity of illness and risk of mortality and long-term outcome [10]. CRIB II score is a simple, reliable, validated, easily applicable and an accurate test widely used risk-adjustment instrument for predicting mortality among preterm low birth weight babies [11]. Both perfusion index and CRIB II score are novel minimally invasive technique (ABG in CRIB II) to assess severity of illness in sick preterm neonates. Thus, we conducted this study on sick preterm babies born between 28–32 weeks of gestational age to find out the efficacy of CRIB II score and perfusion index individually as an objective tool for assessment of severity of illness and their correlation. The novelty of our study lies in focusing exclusively on preterm infants, where we assessed both the correlation and predictive values of CRIB II score and perfusion index. Moreover, there is a scarcity of similar studies conducted in resource-constrained countries.

2 Methodology

This cross-sectional study was carried out on sick preterm of 28–32 weeks of gestational age assessed by new Ballard score [12] admitted in Neonatal intensive care unit & Sick new born care unit of UPUMS, Saifai during January 2020 to July 2021. A sample size of 125 neonates was determined based on a previous study conducted in a tertiary center, where a correlation of 0.30 between perfusion index and CRIB II score was observed in sick neonates [13]. Ethical Clearance from institutional ethics review committee was obtained (Ethical clearance no.106/2019-20). Written and informed consent from parents of new-borns was taken. After proper history and examination, newborns with one or more of the following conditions were included in the study i.e requiring ventilation (Invasive or Non-Invasive), hypothermia recorded by digital thermometer, clinical signs suggestive of shock like cold extremities with capillary refill time longer than 3 seconds & weak and fast pulse, with decreased urine output or required fluid boluses and/or Inotropes, neonates with seizure, Respiratory Distress (based on Downes Score) and Hypoglycemia (<40 mg/dl), Pre-term neonates with unstable vitals. Term Neonate, Neonates requiring surgical intervention, Preterm who’s perfusion index &/or CRIB II score could not be recorded in predefined time (within 12 hour of admission) were excluded from study. Severity of sickness was assessed by perfusion index and CRIB II Score. Perfusion index was recorded within 12 h of admission using portable pulse oximeter on right upper limb of the newborn after a gentle application of the pulse oximeter probe, when the limb is at rest and without agitation by sister in-charge of NICU/ SNCU, who was unaware of the newborn illness severity score in order to reduce bias, after the pulse wave was verified to be artifact-free and regular, readings were taken every 30 seconds for 10 minutes and the average of 20 readings was calculated. Perfusion index reading was obtained from the display of pulse oximeter with signal extraction technology. This method for recording the readings was similar to previous study on PI [13]. In some previous studies Perfusion index value less than 1.24 were considered as indicator of severe illness in newborn [14, 15].

CRIB II score of eligible neonates were recorded within 12 hours of admission by the principal investigator. Parameter recorded for CRIB II score includedbirth weight (using electric scale with sensitivity of 10 gm), gestational age (using New Ballard score), body temperature (using electronic thermometer), base excess (obtained from arterial blood gas analysis) and sex of newborn (Fig. 1). The scores were further classified into four levels as follows, Level 1(0 to 5), Level 2(6 to10), Level 3 (11–15), and Level 4 > 15 [11].

Fig. 1

CRIB Score II.

To minimize observer and instrumental bias, the perfusion index and CRIB Score II were calculated by a single individual using the same pulse oximeter and other instruments. Vital monitoring of a newborns was done at regular interval. Complete blood count, Random blood sugar, Arterial blood gas analysis and Serum calcium were obtained in every newborn while other investigations were sent based on nature of disease if required. Data was collected and analyzed to find out if any correlation existed between CRIB II Score and perfusion index^. Outcome of newborn were noted in form of successfully discharge (when newborn was feeding from breast or katori spoon, gained weight for 3 consecutive days, were able to maintain normal body temperature, when roomed-in with mother and Mother was confident of taking care of the baby), expired, left against medical advice (LAMA), absconded and referral. Data was complied, analyzed and interpreted statistically through relevant statistical methods using Statistical Package for Social Sciences (SPSS) version 22.0.

3 Result

Table 1 Showing demographic profile of study population. Out of 125 newborns, 76 (60.8%) were male and 49 (39.2%) were female.

Table 1
Demographic Profile of study population

Variable N(125) Percent

Gender Male 76 60.8%

Female 49 39.2%

Weight <1000 gm 4 3.2%

1000–1500 gm 47 37.6%

>1500 gm 74 59.2%

Mode of delivery Normal 95 76%

Caesarean section 30 24%

Gesational age by new ballard score 28–30 wk 47 37.6%

30–32 wk 78 62.4%

Place of delivery Inborn 52 41.6%

Outborn 73 58. 4%

Respiratory distress score value <4 71 56. 8%

4–7 45 36%

>7 9 7.2%

Urine output >1 ml/kg/hr 117 93.6%

<1 ml/kg/hr 8 6.4%

Requirement of bolus/inotropes Not needed 51 40.8%

Bolus 68 54.4%

inotropes 6 4.8%

Mode of ventilation Not needed 9 7.2%

CPAP 57 45.6%

NIPPV 40 32%

SIMV 19 15.2%

RBS value >40 121 96.8%

<40 4 3.2%

C Reactive protien Negative 114 91.2%

Positive 11 8.8%

Arterial blood gas analysis Normal 73 58.4%

Metabolic acidosis 37 29.6%

Metabolic alkalosis 7 5.6%

Respiratory acidosis 2 1.6%

Respiratory alkalosis 6 4.8%

Variable		N(125)	Percent
Gender	Male	76	60.8%
	Female	49	39.2%
Weight	<1000 gm	4	3.2%
	1000–1500 gm	47	37.6%
	>1500 gm	74	59.2%
Mode of delivery	Normal	95	76%
	Caesarean section	30	24%
Gesational age by new ballard score	28–30 wk	47	37.6%
	30–32 wk	78	62.4%
Place of delivery	Inborn	52	41.6%
	Outborn	73	58. 4%
Respiratory distress score value	<4	71	56. 8%
	4–7	45	36%
	>7	9	7.2%
Urine output	>1 ml/kg/hr	117	93.6%
	<1 ml/kg/hr	8	6.4%
Requirement of bolus/inotropes	Not needed	51	40.8%
	Bolus	68	54.4%
	inotropes	6	4.8%
Mode of ventilation	Not needed	9	7.2%
	CPAP	57	45.6%
	NIPPV	40	32%
	SIMV	19	15.2%
RBS value	>40	121	96.8%
	<40	4	3.2%
C Reactive protien	Negative	114	91.2%
	Positive	11	8.8%
Arterial blood gas analysis	Normal	73	58.4%
	Metabolic acidosis	37	29.6%
	Metabolic alkalosis	7	5.6%
	Respiratory acidosis	2	1.6%
	Respiratory alkalosis	6	4.8%

Table 2 showing distribution of study population at different CRIB II levels and their mean perfusion index. Level 1 had maximum no of patients, while level 4 had no patient. Mean Perfusion index of study population was found to be 2.37 + /–1.06.

Table 2

Distribution of study Population and their perfusion index at different CRIB Score II levels

CRIB Score levels	N (%)	Perfusion index at different CRIB score (Mean±SD)
Level 1 (0–5)	70 (56.0%)	2.62±1.17
Level 2 (6–10)	52 (41.6%)	2.04±0.81
Level 3 (11–15)	03 (02.40%)	2.30±0.78
Level 4 (> 15)	0(0%)	–
Total	125 (100%)	2.37 ± 1.06 (P Value = 0.009)

Applied one way ANOVA Mean CRIB II in patients who were discharged from NICU was 4.52±3.15 (n = 75) and who expired were 5.81±2.88, While mean Perfusion index of patients who were discharged was 2.77±1.14 and in expired patients it was 1.74±0.51. Tables 4 and 5 showing outcome according to CRIB II and Perfusion index. (Table 3)

Table 3

CRIB II score and Perfusion Index at different outcome

Outcome	N (%)	CRIB II score (Mean±SD)	Perfusion index (Mean±SD)
Discharge	81(64.8%)	4.52±3.15	2.77±1.14
Expired	36 (28.8%)	5.81±2.88	1.74±0.51
Left Against Medical advice	07 (05.6%)	4.17±2.14	1.94±0.52
Referred	01 (0.08%)	6.00	1.90
(Total)	125(100%)	4.96±3.05 (P Value = 0.141)	2.37±1.06 (P Value < 0.001)

Table 4

Sensitivity and specificity of Perfusion index and CRIB score II in prediction of mortality

	Area under	95% Confidence
	curve	interval
		Lower bound	Upper bound	Cut off	Sensitivity	Specificity
Perfusion Index	0.776	0.694	0.857	1.65	84.0	37.2
CRIB Score II	0.622	0.520	0.723	3.5	79.10	40

Receiver operating characteristic (ROC) of perfusion index and CRIB II among discharged and expired patients were determined. Area under curve for Perfusion index vs outcome was 0.776 at 95% confidence interval which is statistically significant. Optimum cutoff point based on ROC curve was 1.65 withsensitivity of 84%, specificity of 37.2% with positive predictive value of 70% and negative predictive value of 57%. Area under curve for CRIB Score II was 0.622 (p value < 0.028), optimum cut off point based on ROC curve for CRIB II score was 3.5 with sensitivity 79.10% of specificity of 40% positive predictive value is 43.03% and negative predictive value of 76.9% (Table 4, Figs. 2 and 3).

Fig. 2

ROC of perfusion index.

Fig. 3

ROC of CRIB Score II.

Correlation between perfusion index and CRIB II was calculated. Spearman’s correlation coefficient between perfusion index and CRIB II score was –.272 and p value was 0.002 (Fig. 4).

Fig. 4

Correlation between Perfusion index and CRIB Score.

4 Discussion

To assess the severity of illness in preterm infants born between 28 to 32 weeks of gestational age, we investigated the correlation and efficacy of Perfusion Index and CRIB Score II individually as objective assessment tools. We collected data on Perfusion Index and CRIB Score II from 125 premature neonates admitted with severe illness. We focused on premature babies due to their high mortality rate globally and their increased susceptibility to illness compared to term newborns. Perfusion Index measures peripheral circulation, with higher values indicating better circulation, which aligns with our finding that higher Perfusion Index values correlated with better survival rates. Conversely, lower values indicate cardiovascular instability, which increases the risk of mortality in sick preterm infants. This conclusion is supported by studies by Pisasek et al. and Mathew et al. [16, 13]. While Kroese et al. suggested limitations to the predictive value of Perfusion Index due to large variations, our study did not encounter significant variability. We found that a single Perfusion Index reading within the first 12 hours after delivery could predict outcomes effectively. Our analysis revealed a lower mean trend of Perfusion Index in infants who expired compared to those who were discharged [15]. Similarly, De Felice et al. discovered that the mean PI stood at 1.54±0.8, with a PI value below 1.24 proving to be a reliable indicator of high illness severity [14]. In contrast, Monteiro et al., in their research, concluded that newborns with a PI value below 0.72 were significantly prone to morbidity and mortality [17]. While previous studies by De Felice et al. and others have primarily focused on mean PI values derived from post-ductal (lower limb) measurements and recorded perfusion index within the first 24 hours of life, our study opted for pre-ductal (upper limb) reference ranges as established by Jardim et al. [18]. Additionally, we restricted our readings to within the initial 12 hours of life, potentially contributing to discrepancies in perfusion index cutoffs. Variations in PI cutoff values across similar studies can also be attributed to differences in sample sizes and gestational ages.The CRIB II score incorporates gestation, birthweight, gender, temperature at admission, and base excess. Numerous studies have highlighted CRIB II as a superior predictive tool. For instance, Reid et al. observed that the predictive accuracy of CRIB II was comparable to that of SNAPPE II, yet CRIB II boasted a simpler calculation process [19]. Sarquis et al. recommended employing the CRIB score over relying solely on birth weight and gestational age because of its greater utility and simplicity of application [20]. On the other hand, Manktelow et al. indicated that while CRIB II served as a good predictive score overall, it fell short in the temperature subgroup. So, they proposed the utilization of a recalibrated CRIB II score (CRIB II –temperature) [21].

De Felice et al. concluded that the CRIB score, CRIB II score, gestational age, and birth weight exhibited no significant differences in predicting mortality. However, our findings indicated that the CRIB II score served as a reliable predictive measure. Discharged newborns had a lower mean CRIB II score (4.52±3.15) compared to expired newborns, who presented a higher mean CRIB II score (5.81±2.88). This discrepancy yielded a p-value of 0.028, with a confidence interval of 0.520 to 0.723 [22].

In contrast to Mathew et al.’s findings, our study revealed a weak negative correlation (–0.2) between CRIB II score and perfusion index. This variance may be attributed to our relatively small sample size, which comprised solely very preterm neonates. Moreover, both CRIB II and perfusion index parameters were recorded within 12 hours of life in our study, whereas Mathew et al. observed correlations in both term and preterm neonates with a larger sample size (n = 200), and perfusion index was recorded within 12 hours of life while CRIB II score parameters were noted up to 24 hours of life. However, Kinoshita m et al. concluded that no correlation existed between CRIB II score and median PI value [23].

Our study has several limitations Despite our efforts to mitigate confounding variables by selecting only preterm sick babies with unstable vitals, we were unable to eliminate all confounders due to variations in their diseases and corresponding treatments, as well as differences in gestational age and maternal factors among them.

The gestational age of newborns was evaluated using the new Ballard score instead of relying on first-trimester scans, as many patients did not have complete antenatal records. The perfusion index (PI) values were not consistently taken after the same duration of admission, which could result in overlooking physiological changes over time. Additionally, there were no newborns in CRIB II score level 4, which is associated with the highest mortality, potentially limiting the generalizability of our findings. Furthermore, we did not record the mean duration of stay in the study population, which could have an impact on final outcomes. Follow-up to assess long-term consequences of prematurity was also not included in our study.

Lack of interpersonal variability, use of preductal perfusion index, inclusion of large number of parameter affecting the outcome such as birth weight, antenatal factor, place of delivery, requirement of bolus/inotropes, ventilatory support etc. and comparable sample size were strength of our study.

5 Conclusion

This study concluded that perfusion index (p < 0.001) is better at predicting mortality compared to CRIB II score (p < 0.028). A weak negative correlation exists between Perfusion Index (PI) and CRIB II score (r = –0.272) with higher PI value and lower CRIB II score have a better survival rate. Our result suggest that PI is an easily applicable, non-invasive method for monitoring early postnatal changes in peripheral perfusion in preterm and should be routinely used as a monitoring tool along with CRIB II score.

Funding

None.

Conflict of interest

None.

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