C reactive protein and procalcitonin: Reference intervals for preterm and term newborns during the early neonatal period
Introduction
The utility of C reactive protein (CRP) for the diagnosis of early-onset neonatal infection has been the subject of controversy because of its unsatisfactory sensitivity. The CRP concentration increases physiologically in newborns within the first days after birth. This dynamic behavior may in part account for the low diagnostic accuracy of CRP measurements in neonatal infection, particularly when measured shortly after birth. Similarly, other markers of inflammation including procalcitonin (PCT) demonstrate a natural increase within a few days after birth, necessitating careful adjustments to the normal ranges. Thus, in estimating the sensitivities and specificities of these neonatal markers for the diagnosis of sepsis throughout the first days of life, it is important to consider their normal kinetics and their pattern(s) of response in the healthy neonate.
Data pertaining to reference intervals for CRP during the neonatal period are limited. In the majority of published reports, CRP upper limits have been obtained from symptomatic uninfected patients [1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11]. There are few studies of upper limits for CRP in the healthy newborn [12], [13], [14], [15]. Furthermore, most of these were based on relatively small sample sizes with wide-ranging postnatal ages [12], [13], [14]. More important, although advances in neonatal intensive care have led to increasing preterm birth rates, to our knowledge, there is still no study evaluating the influence of gestational age (GA) per se in the development of CRP reference intervals during the neonatal period. Finally, though high-sensitivity assay for CRP has become available over the last decade in standard clinical laboratories, there is no study assessing the CRP postnatal changes in the healthy preterm and term neonates using this analytic method.
Data pertaining to reference intervals for PCT are also limited. In a previous cross-sectional study, we showed that in the healthy term neonates circulating concentrations of PCT increase gradually from birth to reach peak values at about 24 h of age and then decrease gradually by 48 h of life [16]. No similar normogram exists for the healthy preterm infants even though they may have different pharmacokinetics.
For these reasons, we sought to describe the reference ranges for both CRP and PCT in a large sample of healthy preterm and term newborns during the first days of life by using more sensitive CRP and PCT assays than those previously reported [1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18].
Section snippets
Subjects
Our population consisted of healthy preterm and term infants who, from birth, were prospectively recruited over an 18-month period to the Neonatal Unit of Policlinico Umberto I° Hospital, Sapienza University of Rome. The study protocol was approved by the clinical research ethics committee of the Hospital. Eligible for enrollment were neonates who were delivered from singleton pregnancies with birth weights (BWs) appropriate for GA and with normal results on physical examination at birth that
Subject characteristics
Table 1 presents maternal and neonatal characteristics of the study population, of whom 221 were born at term (range 37.0–39.0 weeks) while 200 were preterm (range 30.0–36.0 weeks), with 27 out of the 200 preterm infants (13.5%) below 33 weeks of gestational age. Most babies (94.8%) were born to Caucasian mothers.
C reactive protein
Using multiple log-linear regression analysis, it was found that GA had a significant, positive effect on CRP independently of gender and sampling time. Babies' mean CRP increased by 6.0%
Discussion
The main purpose of this study was to determine age-related reference intervals for CRP and PCT in the preterm and term baby during the early neonatal period. Our data show that clinical use of CRP over the first days of life requires the use of cutoff values specific not only to postnatal age, but also to GA. In fact, we found that healthy preterm babies have a lower and shorter CRP response compared with that in healthy term babies, demonstrating the effects of development per se on CRP
Acknowledgments
We are indebted to Silvano Castrechini for his excellent technical assistance.
References (31)
- et al.
Serum C-reactive protein and problems of newborn infants
J Pediatr
(1982) - et al.
Serum C-reactive protein in normal and infected neonates
Clin Chim Acta
(1985) - et al.
C-reactive protein as biochemical indicator of bacterial infection in neonates
Clin Biochem
(1986) - et al.
Influence of perinatal conditions on C-reactive protein production
J Pediatr
(1992) - et al.
Umbilical artery doppler screening for detection of the small fetus in need of antepartum surveillance
Am J Obstet Gynecol
(2000) - et al.
Histologic chorioamnionitis, antenatal steroids, and perinatal outcomes
Obstet Gynecol
(2000) - et al.
Do antenatal corticosteroids help in the setting of preterm rupture of membranes?
Am J Obstet Gynecol
(2001) - et al.
Isolation and characterization of serum procalcitonin from patients with sepsis
Peptides
(2001) - et al.
C-reactive protein (CRP) in early diagnosis of neonatal septicemia
Acta Paediatr Scand
(1979) - et al.
Sequential determination of CRP, alpha 1-antitrypsin and haptoglobin in neonatal septicaemia
Acta Paediatr Scand
(1983)
Coagulase-negative staphylococci as true pathogens in newborn infants: a cohort study
Pediatr Infect Dis J
Diagnostic audit of C-reactive protein in neonatal infection
Eur J Pediatr
The value of the C-reactive protein assay for the early diagnosis of neonatal infection at the maternity ward and pediatric service of a general hospital center
Ann Pédiatr
C-reactive protein and bacterial infection in preterm infants
Eur J Pediatr
Acute phase reactants in neonatal bacterial infection
J Perinatol
Cited by (172)
Neonatal bacterial infections: Diagnosis, bacterial epidemiology and antibiotic treatment
2024, Journal de Pediatrie et de PuericultureNeonatal bacterial infections: Diagnosis, bacterial epidemiology and antibiotic treatment
2023, Infectious Diseases NowGlobal health systems' data science approach for precision diagnosis of sepsis in early life
2022, The Lancet Infectious DiseasesCitation Excerpt :Serial measurements of C-reactive protein concentrations are required as one-off tests lack sensitivity, and therefore the measurement of C-reactive protein has limited usefulness for rapid assessment. C-reactive protein values for neonates are also affected by events around birth, such as premature rupture of membrane, maternal fever, meconium aspiration, fetal distress, and gestational age.39–45 Tests require skilled technicians and, when available, they are often too costly for most families in LMICs, who mostly self-fund their health care.
Salivary C-reactive protein and mean platelet volume as possible diagnostic markers for late-onset neonatal pneumonia
2024, World Journal of Clinical PediatricsPerinatal asphyxia does not influence presepsin levels in neonates: A prospective study
2024, Acta Paediatrica, International Journal of Paediatrics