Predictive Value of C-Reactive Protein-to-Albumin Ratio for Neonatal Sepsis

Figures & data

Table 1 Basic Characteristics of Study Subjects

Variables	Control (n = 452)	Sepsis (n = 624)	Sepsis
			Mild Sepsis (n = 263)	Severe Sepsis (n = 361)
Age (days)	7.0 (4.0, 12.0)	11.0 (6.0, 17.0)^a	11.0 (6.0, 19.0)^c	11.0 (6.0, 16.0)^d
Male, n (%)	264 (58.4)	388 (62.2)	170 (64.6)	218 (60.4)
Weight (kg)	3.3 ± 0.5	3.2 ± 0.6^a	3.3 ± 0.6	3.1 ± 0.7^bd
Temperature (°C)	37.0 ± 0.5	37.4 ± 0.8^a	37.4 ± 0.7^c	37.3 ± 0.8^d
Respiratory (rate/minute)	46.6 ± 7.7	49.8 ± 10.1^a	49.4 ± 9.6^c	50.1 ± 10.4^d
Heart rate (bpm)	142.8 ± 16.1	150.7 ± 18.1^a	149.7 ± 17.6^c	151.4 ± 18.4^d
SBP (mm Hg)	76.4 ± 7.1	76.3 ± 8.1	79.3 ± 5.6^c	74.1 ± 9.0^bd
DBP (mm Hg)	46.7 ± 7.4	46.3 ± 7.8	47.8 ± 7.5^c	45.1 ± 7.9^bd
PCT (ng/mL)	0.14 (0.09, 0.23)	0.30 (0.14, 1.52)^a	0.22 (0.11, 0.76)^c	0.37 (0.16, 2.19)^bd
CRP (mg/L)	0.7 (0.7, 0.7)	0.7 (0.7, 14.1)^a	0.7 (0.7, 9.2)^c	0.7 (0.7, 17.3)^bd
Biochemical parameters
AST (U/L)	37.6 (30.0, 50.0)	38.4 (27.9, 53.7)	36.1 (27.8, 48.0)	39.6 (27.9, 61.7)^b
ALT (U/L)	15.1 (20.0, 33.4)	28.5 (22.0, 38.0)^a	28.6 (22.3, 36.2)^c	28.5 (21.9, 39.6)^d
TP (g/L)	57.1 ± 6.1	53.7 ± 7.0^a	54.4 ± 6.1^c	53.3 ± 7.6^d
ALB (g/L)	33.7 ± 4.0	30.3± 4.6^a	31.2 ± 4.3^c	29.7 ± 4.7^bd
BUN (mM)	2.2 (1.4, 3.3)	3.1 (1.9, 4.3)^a	2.8 (1.9, 3.9)^c	3.2 (1.9, 4.8)^bd
CREA (μM)	50.1 (41.3, 57.6)	45.5 (36.0, 60.3)^a	43.4 (34.7, 53.1)^c	47.7 (37.2, 64.8)^b
UA (μM)	137.4 (103.0, 179.1)	144.2 (106.6, 198.5)^a	143.5 (106.9, 185.4)	145.5 (106.5, 208.4)^d
CAR (10^−3)	0.021 (0.019, 0.024)	0.026 (0.022, 0.438)^a	0.024 (0.021, 0.277)^c	0.029 (0.022, 0.606)^bd

Notes: All values are presented as the mean ± SD or n (%) or as the median (interquartile range). ^aP < 0.05 for sepsis vs control. ^bP < 0.05 for severe sepsis vs mild sepsis. ^cP < 0.05 for mild sepsis vs control. ^dP < 0.05 for severe sepsis vs control.

Abbreviations: SBP, systolic blood pressure; DBP, diastolic blood pressure; PCT, procalcitonin; hsCRP, high sensitivity C-reactive protein; AST, aspartate aminotransferase; ALT, alanine aminotransferase; TP, total protein; ALB, albumin; BUN, blood urea nitrogen; CREA, creatinine; UA, uric acid; CAR, C-reactive protein-to-albumin ratio.

Figure 1 Study participant analysis of suspected sepsis neonates.

Table 2 The Presence and Severity of Neonatal Sepsis According to CAR Tertiles

Variables	Tertile 1 (< 0.021*10^−3) (n = 361)	Tertile 2 (0.021*10^−3 – 0.028*10^−3) (n = 356)	Tertile 3 (> 0.028*10^−3) (n = 359)	P
Age (days)	9.0 (6.0, 14.0)	8.0 (5.0, 15.0)	10.0 (5.0, 16.0)	0.524
Male, n (%)	204 (56.5)	213 (59.8)	235 (65.5)	0.046
PCT (ng/mL)	0.13 (0.09, 0.21)	0.17 (0.11, 0.35)	0.52 (0.19, 3.15)	<0.001
Clinical data
Control, n (%)	238 (65.9)	143 (40.2)	71 (19.8)	<0.001
Overall sepsis	123 (34.1)	213 (59.8)	288 (80.2)	<0.001
Mild sepsis, n (%)	66 (18.3)	94 (26.4)	103 (28.7)	<0.001
Severe sepsis, n (%)	57 (15.8)	119 (33.4)	185 (51.5)	<0.001

Abbreviations: SBP, systolic blood pressure; DBP, diastolic blood pressure; PCT, procalcitonin; hsCRP, high sensitivity C-reactive protein; AST, aspartate aminotransferase; ALT, alanine aminotransferase; TP, total protein; ALB, albumin; BUN, blood urea nitrogen; CREA, creatinine; UA, uric acid; CAR, C-reactive protein-to-albumin ratio.

Table 3 Correlations Between CAR and Clinical Parameters

Variables	Overall Population		Neonates with Sepsis
	r	P	r	P
Age (day)	0.011	0.717	−0.038	0.343
Weight (kg)	−0.057	0.060	−0.027	0.504
Temperature (°C)	0.117	<0.001	0.015	0.717
Respiratory (rate/minute)	0.130	<0.001	0.089	0.026
Heart rate (bpm)	0.127	<0.001	0.076	0.061
SBP (mm Hg)	−0.057	0.062	−0.057	0.153
DBP (mm Hg)	−0.077	0.011	−0.033	0.416
PCT (ng/mL)	0.473	<0.001	0.448	<0.001
AST (U/L)	−0.044	0.148	−0.028	0.486
ALT (U/L)	0.067	0.027	0.025	0.538
TP (g/L)	−0.553	<0.001	−0.431	<0.001
CREA (μM)	−0.006	0.844	0.006	0.872
UA (μM)	0.038	0.208	0.014	0.727
BUN	0.118	<0.001	0.087	0.029

Abbreviations: SBP, systolic blood pressure; DBP, diastolic blood pressure; PCT, procalcitonin; hsCRP, high sensitivity C-reactive protein; AST, aspartate aminotransferase; ALT, alanine aminotransferase; TP, total protein; ALB, albumin; BUN, blood urea nitrogen; CREA, creatinine; UA, uric acid; CAR, C-reactive protein-to-albumin ratio.

Table 4 Regression Analysis to Assess the Presence of Neonatal Sepsis and Severe Sepsis According to CAR Tertiles

Variables	Univariate		Multivariate*
	OR (95% CI)	p	OR (95% CI)	p
Presence of sepsis
CAR	20.596 (8.304–51.085)	<0.001	10.144 (4.151–24.790)	<0.001
CAR tertiles
Tertile 1	1		1
Tertile 2	2.882 (2.127–3.905)	<0.001	2.599 (1.767–3.824)	<0.001
Tertile 3	7.849 (5.593–11.014)	<0.001	5.166 (3.406–7.837)	<0.001
Presence of severe sepsis
CAR	1.876 (1.562–2.253)	<0.001	1.391 (1.141–1.696)	0.001
CAR tertiles
Tertile 1	1		1
Tertile 2	2.678 (1.871–3.833)	<0.001	2.416 (1.587–3.677)	<0.001
Tertile 3	5.670 (3.994–8.051)	<0.001	3.767 (2.476–5.732)	<0.001

Notes: *Adjusted for age, temperature, heart rate, respiratory rate, weight, PCT, AST, ALT, TP, UREA and UA.

Abbreviations: SBP, systolic blood pressure; DBP, diastolic blood pressure; PCT, procalcitonin; hsCRP, high sensitivity C-reactive protein; AST, aspartate aminotransferase; ALT, alanine aminotransferase; TP, total protein; ALB, albumin; BUN, blood urea nitrogen; CREA, creatinine; UA, uric acid; CAR, C-reactive protein-to-albumin ratio.

Figure 2 ROC curve of CAR, CRP, and ALB in predicting sepsis and severe sepsis in neonates. (A) The ROC curve for CAR, CRP, and ALB in predicting sepsis. (B) The ROC curve for CAR, CRP, and ALB in predicting severe sepsis.

Figure 3 Distribution of neonates in high or low CAR groups. (A) The distribution of neonates with sepsis in high (≥0.023) or low (<0.023) CAR groups. (B) The distribution of neonates with severe sepsis in high (≥0.024) or low (<0.024) CAR groups.