Clinica Chimica Acta 412 (2011) 1888
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Clinica Chimica Acta
j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / c l i n c h i m
Letter to the Editor
CRP in term and preterm newborns
Dear Editor,
With great interest we read the article on the influence of
gestational age on the C-reactive protein (CRP) and procalcitonin
(PCT) reference values during the first days of life by Chiesa et al. [1]
As stated in the study CRP is known to be of limited sensitivity in the
diagnosis of early onset infections, especially when the blood sample
is taken shortly after birth. The correct interpretation of CRP values
during the first days of life is further complicated by the non infection-
related rise shortly after birth.
In agreement with the findings of Chiesa et al. we have recently
reported on lower CRP values in preterm compared to term newborns
during the first 72 h of life. [2] In our cohort of 532 newborns (179
term and 353 preterm newborns hospitalized at the neonatal
intensive care unit) CRP values significantly correlated with gesta-
tional age (p b .001). In 499 early onset sepsis negative newborns
preterm infants had lower CRP values compared to term infants
(median 0.5 mg/L (95% confidence interval 0–9 mg/L) vs. 2 mg/L (0–
26.2 mg/L), p b 0.001). CRP increased by 0.405 mg/L for every one
week increase in gestational age (unpublished data). CRP values
differed in sepsis positive newborns as well with median values of
9 mg/L (0–40.4 mg/L) in preterm and 18.5 mg/L (4.9-98.6 mg/L) in
term newborns (p b .001). The performance of CRP in the diagnosis of
sepsis was lower in preterm compared to term newborns (area under
the receiver operating characteristics curve 799 vs. .890, sensitivity
53% vs. 86% at the cut-off 8 mg/L).
Some previous studies have addressed the influence of gestational
age on infectious and non infectious CRP responses. Turner et al. [3]
have demonstrated a correlation of gestational age with the
magnitude of clinically relevant CRP responses during the first
seven days after birth. In case of a clinically relevant CRP raise
N10 mg/L the proportion of a pronounced response N60 mg/L
increased with gestational age from 8% in newborns from 24 to
27 weeks to 25% in newborns from 40 to 41 weeks. Similarly, Doellner
et al. [4] described a significantly lower CRP increase induced by
infection in preterm compared to term infants. In their cohort of 42
newborns with either culture proven or probable sepsis infants with a
gestational age less than 35 weeks had lower CRP values (0 mg/L,
range 0–26 mg/L) and lower CRP peak values (18 mg/L, range 0–
109 mg/L) compared to infants with a gestational age greater than
35 weeks (15 mg/L, range 0–105 mg/L; CRP peak values 52 mg/L,
range 0–105 mg/L). Seibert et al. [5] found no difference in the
performance of CRP in diagnosis of bacterial infections between
extremely low gestational age newborns from 23 to 28 weeks when
compared to premature infants from 29 to 31 weeks.
When applying Chiesa's reference values to our cohort of 499
sepsis negative newborns 8.8% had values above the 95th percentile.
The reference values worked well in preterm newborns with only
6.3% having values above the 95th percentile (day 1: 11.1%, day 2:
0009-8981/$ – see front matter © 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.cca.2011.06.005
5.4%, day 3: 8.3%). In term newborns 15.8% had values above the 95th
percentile (day 1: 14.2%, day 2: 23.0%, day 3: 17.1%). Chiesa et al.
created the reference values from data of healthy term and preterm
newborns including only infants with the assumption of an
uncomplicated hospital stay and normal results on physical exami-
nation at birth with no need for empiric management. Actually, these
conditions exclude basically all term infants hospitalized at the
neonatal intensive care unit. The variety of underlying pathologies in
our cohort of term newborns including cases of meconium aspiration
syndrome, severe asphyxia and complicated antenatal histories may
explain the divergence of the CRP values.
In contrast, our data from preterm infants correlate well with
Chiesa's reference values. Though a part of the premature infants was
hospitalized with severe diagnoses as well, many had a rather
uncomplicated hospital course according to Chiesa's cohort.
Chiesa et al. provide further evidence for the influence of
gestational age on CRP kinetics during the first days of life. Separate
reference values for preterm and term newborns also signify separate
cut-off values in the diagnosis of sepsis. This attempt is supported by
the current literature reporting on lower CRP responses in the
premature infant. We will look forward to further studies on the
validity of gestational age dependent reference values.
Conflict of interest: None
Financial disclosure: None
References
[1] Chiesa C, Natale F, Pascone R, et al. C reactive protein and procalcitonin: reference
intervals for preterm and term newborns during the early neonatal period. Clin
Chim Acta 2011;412:1053–9.
[2] Hofer N, Müller W, Resch B. Non-infectious conditions and gestational age influence
C-reactive protein values in newborns during the first 3 days of life. Clin Chem Lab
Med 2011;49:297–302.
[3] Turner MA, Power S, Emmerson AJB. Gestational age and the C reactive protein
response. Arch Dis Child Fetal Neonatal Ed 2004;89:F272–3.
[4] Doellner H, Arntzen KJ, Haereid PE, Aag S, Austgulen R. Interleukin-6 concentrations
in neonates evaluated for sepsis. J Pediatr 1998;132:295–9.
[5] Seibert K, Yu VY, Doery JC, Embury D. The value of C-reactive protein measurement
in the diagnosis of neonatal infection. J Paediatr Child Health 1990;26:267–70.
Nora Hofer⁎
Bernhard Resch
Research Unit for Neonatal Infectious Diseases and Epidemiology,
Division of Neonatology, Department of Pediatrics and Adolescent
Medicine, Medical University of Graz, Auenbruggerplatz 30,
8036 Graz, Austria
⁎Corresponding author at: Division of Neonatology,
Pediatric Department, Medical University of Graz,
Auenbruggerplatz 30, A-8036 Graz, Austria.
Tel.: + 43 316 385 81134; fax: + 43 316 385 2678.
E-mail address: nora.hofer@medunigraz.at. (N. Hofer).
1 June 2011