Diagnostic and prognostic utility of D-dimer and heparin-binding protein in neonatal sepsis: A prospective case-control study

Table 1 Demographic, basal characteristics and risk factors for sepsis of the studied groups, n (%)/mean ± SD

Parameter	Sepsis group (n = 45)		P value1	Controls (n = 45)	P value2
	Proven sepsis (n = 28)	Suspected sepsis (n = 17)
Sex (Males)	15 (53.6)	10 (58.8)	0.73	22 (48.9)	0.77
Age (days)	11.88 ± 11.74	11.74 ± 10.29	0.81	11.74 ± 10.29	0.11
Gestational age
Term	14 (50.0)	10 (58.8)	0.56	27 (60.0)	0.69
Preterm	14 (50.0%)	7 (41.2)		18 (40.0)
Birth weight (kg)
Normal birth weight	18 (64.3)	14 (82.4)	0.33	36 (80.0)	0.18
Low birth weight	8 (28.6)	3 (17.6)		9 (20.0)
Very low birth weight	2 (7.1)	0 (0.0)		0.0
Apgar score	8.07 ± 2.16	8.71 ± 2.14	0.29	9.96 ± 0.21	< 0.0001
Resuscitation	13 (46.4)	5 (29.4)	0.25	0.0	< 0.0001
Delayed first cry	13 (46.4)	5 (29.4)	0.25	0.0	< 0.0001
Infant of diabetic mother	0.0	0.0	N/A	5 (11.1)	0.56
Sepsis onset
Early onset	14 (50.0)	7 (41.2)	0.56	0.0	N/A
Late onset	14 (50.0)	10 (58.8)		0.0
Outcome
Survivors	23 (82.1)	17 (100)	0.14	45 (100)	0.004
Nonsurvivors	5 (17.9)	0.0		0.0
Days of admission	17.68 ± 5.09	10.65 ± 1.93	0.03	4.78 ± 2.36	< 0.0001
Maternal risk factors
PROM	16 (57.1)	8 (47.1)	0.51	5 (11.1)	< 0.0001
Preeclampsia	6 (21.4)	1 (5.9)	0.23	0.0	0.02
Antepartum hemorrhage	3 (10.7)	2 (11.8)	1.0	0.0	0.03
Urinary tract infection	3 (10.7)	0.0	0.03	0.0	0.02
Chorioamnionitis	1 (3.6)	0.0	0.01	0.0	0.01
Mode of delivery
Vaginal	2 (7.1)	1 (5.9)	1.0	5 (11.1)	0.89
Caesarian	26 (92.9)	16 (94.1)		40 (88.9)

¹Proven sepsis vs suspected sepsis.

²Sepsis group vs controls.

N/A: Not applicable; PROM: Premature rupture of membrane.

Table 2 Initial diagnosis, involved organisms, and antimicrobial type and duration, n (%)/mean ± SD

Initial diagnosis	Sepsis group (n = 45)		P value1	Controls (n = 45)	P value2
	Proven (n = 28)	Suspected (n = 17)
Respiratory disease
Respiratory distress syndrome	8 (28.5)	3 (17.6)	0.405	0.0	N/A
Pneumonia	8 (28.5)	8 (47.1)		0.0
Meconium aspiration	2 (7.1)	0.0		0.0
TTN	0.0	0.0		4 (8.9)
Gastrointestinal disease
Gastroenteritis	1 (3.6)	3 (17.6)	0.4	0.0	N/A
Necrotizing enterocolitis	2 (7.1)	0.0		0.0
Central nervous system
Infection	2 (7.1)	0.0	1.0	0.0	N/A
Ruptured meningocele	1 (3.6)	1 (5.9)		0.0
Others
Septic arthritis	2 (7.1)	0.0	0.467	0.0	N/A
Neonatal jaundice	5 (17.9)	4 (23.5)		37 (82.2)	< 0.0001
Antimicrobials
No treatment	0.0	0.0	0.002	42 (93.3)	< 0.0001
B-Lactam and aminoglycoside	4 (14.3)	7 (41.2)		3 (6.7)
B-Lactam and cephalosporins3	4 (14.3)	10 (58.8)		0.0
Aminoglycoside and carbapenem	3 (10.7)	0.0		0.0
Glycopeptide and carbapenem	17 (60.7)	0.0		0.0
Duration of antimicrobials (days)	15.8 ± 4.9	10.1 ± 2.2	0.04	1.5 ± 0.21	< 0.0001

¹Proven sepsis vs suspected sepsis.

²Sepsis group vs controls.

³Third generation.

N/A: Not applicable; TTN: Transient tachypnea of newborn.

Table 3 Sepsis serological markers according to the causative organism, sepsis onset, gestational age and sepsis outcome, mean ± SD

Sepsis group (n = 45)	CRP (mg/L)	D-dimer (ng/mL)	HBP (ng/mL)
Causative organism
No growth (n = 17)	21.35 ± 16.16	1915.9 ± 1093.1	261.79 ± 147.93
Pneumococci (n = 5)	45.60 ± 31.06	2481.68 ± 682.1	439.56 ± 226.10
Staphylococcus (n = 7)	42.29 ± 34.40	3317.7 ± 2350.7	462.05 ± 290.22
Klebsiella (n = 5)	40.40 ± 37.80	2389.1 ± 1936.5	247.35 ± 210.26
Group beta Streptococci (n = 6)	42.83 ± 41.82	2028.4 ± 1443	405.01 ± 344.63
Enterobacter (n = 5)	41.60 ± 34.48	2623.1 ± 3104.9	341.47 ± 299.08
P value	0.39	0.80	0.41
Sepsis onset
Early onset (n = 21)	30.29 ± 33.23	2283 ± 1666.07	345.2 ± 249.2
Late onset (n = 24)	38.25 ± 26.68	2395.3 ± 1785.1	333.8 ± 235.2
P value	0.158	0.829	0.666
Gestational age
Term (n = 24)	63.08 ± 3.52	2647.3 ± 1674.9	387.75 ± 251.19
Preterm (n = 21)	50.76 ± 2.88	1995.2 ± 1727.3	283.37 ± 216.95
P value	0.13	0.07	0.15
Birth weight
Normal birth weight (n = 32)	39.37 ± 32.73	2535.1 ± 1879.8	362.13 ± 262.7
LBW (n = 11)	21.27 ± 17.8	1528.4 ± 755.4	300.16 ± 170.1
VLBW (n = 2)	30.0 ± 8.48	3749.2 ± 1126.6	182.85 ± 52.11
P value	0.252	0.91	0.754
Sepsis outcome
Survivors (n = 40)	33.05 ± 29.53	1933.2 ± 1181.6	317.1 ± 221.6
Nonsurvivors (n = 5)	46.40 ± 33.06	5621.3 ± 1873.7	514.8 ± 326.2
P value	0.33	< 0.0001	0.23
Effect size (Cohen's d)	0.43	2.35	0.7

LBW: Low birth weight; VLBW: Very low birth weight; CRP: C-reactive protein; HBP: Heparin binding protein.

Table 4 Univariate and multivariate logistic regression analysis for the independent parameters associated with sepsis

Parameter	Univariate		Multivariate
	OR (95%CI)	P value	OR (95%CI)	P value
Sepsis vs controls
CRP (mg/L)	1.25 (1.09-1.43)	0.001	1.20 (0.96-1.51)	0.11
HBP (ng/mL)	1.04 (1.02-1.06)	0.001	1.03 (1.00-1.05)	0.04
D-dimer (ng/mL)	1.09 (1.01-1.18)	0.03	1.15 (0.93-1.42)	0.05
WBCs (× 103/mm3)	1.38 (1.23-1.56)	< 0.0001	1.28 (0.99-1.65)	0.054
Neutrophils (%)	1.16 (1.11-1.24)	< 0.0001	1.00 (0.89-1.12)	0.99
Platelets (× 103/mm3)	0.43 (0.0-8.48 × 1052)	0.99	NI
Proven vs suspected sepsis
CRP (mg/L)	1.03 (1.00-1.06)	0.03	1.01 (0.97-1.06)	0.48
HBP (ng/mL)	1.00 (1.00-1.01)	0.007	1.007 (1.00-1.01)	0.04
D-dimer (ng/mL)	1.00 (1.00-1.00)	0.01	1.00 (1.00-1.00)	0.21
WBCs (× 103/mm3)	1.03 (0.94-1.13)	0.45	NI
Neutrophils (%)	1.02 (0.98-1.07)	0.26	NI
Platelets (× 103/mm3)	0.99 (0.95-1.03)	0.57	NI

CRP: C-reactive protein; HBP: Heparin binding protein; WBCs: White blood cells; NI: Not included.

Table 5 Correlation between sepsis parameters among the studied patients

Variable	D-dimer (ng/mL)		Heparin binding protein (ng/mL)
	r	P value	r	P value
White blood cells (× 10³/mm³)	0.52	< 0.0001	0.5	< 0.0001
Neutrophils (%)	0.50	< 0.0001	0.5	< 0.0001
Platelets (× 10³/mm³)	-0.53	< 0.0001	-0.4	< 0.0001
C-reactive protein (mg/L)	0.64	< 0.0001	0.76	0.01
Heparin binding protein (ng/mL)	0.7	0.01

Table 6 Univariate and multivariate logistic regression analysis for the independent parameters associated with mortality

Parameter	Univariate			Multivariate
	OR (95%CI)		P value	OR (95%CI)	P value
Survivors vs nonsurvisors
Platelets (× 103/mm3)	0.987 (0.943-1.032)	0.569		0.987 (0.922-1.057)	0.716
D-dimer (ng/mL)	1.002 (1.0-1.004)	0.021		1.002 (1.0-1.003)	0.023

OR: Odds ratio.