
C-reactive protein (CRP) is a widely used laboratory test for neonatal sepsis. It is part of the acute-phase reaction to infection and plays a central role in the humoral response to bacterial invasion. However, there is no established standard of practice for the use of CRP in infants. While some authors advocate for the use of serial CRP levels as an early diagnostic tool for confirming the presence of sepsis, others view it as a screening tool to rule out sepsis.
Initial criteria for normal and abnormal CRP levels were developed in adult populations, with generally, CRP levels <10 mg/L considered normal in adults and children. In healthy full-term and preterm infants, CRP levels may range from 2 to 5 mg/L during the first few days of life, and an established upper normal CRP level of 10 mg/L has been identified during the neonatal period. However, conflicting values and a lack of dynamic reference values that reflect the physiologic kinetics of CRP after birth add to the confusion and uncertainty in using CRP in clinical practice.
While CRP is a valuable tool, it has limitations, including low sensitivity during the early stages of infection and potential elevations due to non-infectious conditions such as maternal fever, stressful delivery, and meconium aspiration syndrome. Furthermore, the influence of prematurity on CRP kinetics is not well understood, and there may be differences in baseline CRP values and responses to infection between term and preterm infants.
Overall, while CRP is a useful test for neonatal sepsis, its accuracy can be improved by combining it with early sensitive markers such as procalcitonin, interleukin-6, and interleukin-8.
Characteristics | Values |
---|---|
CRP level in healthy full-term and preterm infants during the first few days of life | 2-5 mg/L |
Established upper normal CRP level in newborns | 10 mg/L |
CRP level in 94% of non-infected infants up to 3 days old | ≤15 mg/L |
CRP level in 82% of non-infected infants up to 3 days old | <10 mg/L |
CRP level in 96% of non-infected infants after 3 days old | <10 mg/L |
What You'll Learn
CRP levels in healthy full-term and pre-term infants
C-Reactive Protein (CRP) Levels in Healthy Full-Term and Pre-Term Infants
C-reactive protein (CRP) is a protein produced by the liver in response to inflammation, which can be caused by a variety of conditions, including infection. CRP levels can be measured through a blood test and are often used to help diagnose neonatal sepsis, a serious and potentially life-threatening condition.
CRP Levels in Healthy Full-Term Infants
CRP levels in healthy full-term infants may range from 2 to 5 mg/L during the first few days of life. However, it's important to note that these values can vary and some sources consider CRP levels below 10 mg/L as normal in full-term infants.
CRP Levels in Healthy Pre-Term Infants
CRP levels in healthy pre-term infants may also fall within the range of 2 to 5 mg/L in the first few days of life. Similar to full-term infants, there is some variation in the values, and levels up to 10 mg/L are often considered normal.
It is worth noting that CRP levels can be influenced by various factors and may not always be accurate indicators of infection, especially in pre-term infants. Other conditions such as asphyxia, shock, intraventricular hemorrhage, surgery, and meconium aspiration can also lead to elevated CRP levels. Therefore, CRP levels should be interpreted in conjunction with other clinical findings and diagnostic tests.
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CRP as a diagnostic tool for neonatal sepsis
C-reactive protein (CRP) is one of the most studied and most used laboratory tests for neonatal sepsis. CRP is part of the acute-phase reaction to infection and plays a central role in the humoral response to bacterial invasion.
CRP is a valuable tool for monitoring the response to treatment and guiding antibiotic therapy. However, it is not a perfect diagnostic tool and cannot replace clinical impression and the gold standard of culture results.
The sensitivity of CRP is known to be the lowest during the early stages of infection. Serial determinations 24–48 hours after the onset of symptoms are recommended as they improve diagnostic accuracy. A repeat CRP 24–48 hours after the initiation of antibiotic therapy has been reported to carry a 99% negative predictive value in accurately identifying uninfected neonates.
CRP has been investigated in combination with a variety of other infection markers, including cytokines, surface markers, and other acute-phase reactants, with promising results. The combination with an early sensitive marker such as procalcitonin, interleukin-6, or interleukin-8 increases the sensitivity of CRP to values between 90 and 100% in most studies.
Non-infectious Elevations of CRP
Interpretation of CRP in the diagnosis of early-onset sepsis may be hindered by several non-infectious conditions influencing values during the days after birth. These include meconium aspiration syndrome, perinatal maternal risk conditions, and non-infectious confounders such as surgery, rheumatic disorders, malignancies, and vasculitis.
Effects of Development and Maturation on CRP Performance
Gestational age and birth weight have been found to influence CRP kinetics in infected and uninfected infants. A growing body of evidence suggests a link between gestational age and CRP kinetics, with lower baseline CRP values and a lower CRP response to infection in preterm compared to term newborns.
CRP Reference Values
Reliable reference values are crucial for obtaining adequate diagnostic accuracy. Upper limits for CRP during the first days of life have mainly been established from uninfected but symptomatic neonates. The current most used upper limit for CRP during the first days of life is 10 mg/L. However, this static cutoff value does not reflect the physiologic kinetics of CRP after birth, and there is a need to reconsider this value and evaluate the advantages of introducing dynamic reference values.
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CRP levels and non-infectious conditions
CRP levels are used to diagnose neonatal sepsis, a serious and potentially life-threatening condition with a mortality rate of 5-50%. However, CRP levels are not always a reliable indicator of sepsis, as they can be influenced by non-infectious conditions such as meconium aspiration pneumonitis, fetal distress, and maternal fever. CRP levels are also influenced by gestational age and birth weight, with lower levels observed in preterm and low-birth-weight infants. The diagnostic accuracy of CRP can be improved by performing serial determinations 24-48 hours after the onset of symptoms and by combining it with other infection markers such as interleukins or procalcitonin. CRP is particularly useful for monitoring the response to treatment and guiding antibiotic therapy, but it should not be the sole criterion for discontinuing antibiotics.
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CRP levels and antibiotic treatment
C-reactive protein (CRP) is a widely used laboratory test for neonatal sepsis. It is a crucial part of the acute-phase response to bacterial invasion and plays a central role in the humoral response. CRP levels tend to be low during the early stages of infection, and diagnostic accuracy improves with serial determinations.
CRP is particularly useful for monitoring the response to treatment and guiding antibiotic therapy. Serial CRP measurements can help determine the duration of antibiotic treatment and identify possible complications. A repeat CRP test 24–48 hours after the initiation of antibiotic therapy has been reported to have a 99% negative predictive value in identifying uninfected newborns.
CRP levels can also help decide when antibiotic treatment can be safely discontinued. In a study by Ehl et al., CRP levels of less than 10 mg/L, determined later than 24 hours after beginning antibiotic treatment, correctly identified 120 out of 121 infants as not needing further antibiotics. This corresponds to a negative predictive value of 99%.
In another study, Chaudhuri et al. found that out of 150 suspected neonatal sepsis cases, antibiotics were paused in 42 neonates (28%) within 72 hours based on CRP levels. In the "Infection Likely" group, where CRP remained above 1 mg/dl even after 72 hours of antibiotic therapy, antibiotics were stopped whenever CRP levels fell below 1 mg/dl.
CRP has a high specificity and negative predictive value, making it a valuable tool for determining the duration of antibiotic therapy and hospitalization in newborns with suspected sepsis.
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CRP levels in pre-term vs term infants
C-reactive protein (CRP) is an acute-phase protein produced by the liver in response to inflammation. CRP levels are often elevated in newborns due to the stress of delivery and typically range from 2 to 5 mg/L during the first few days of life. While there is no established standard of practice for the use of CRP in infants, it is one of the most studied and most used laboratory tests for neonatal sepsis.
CRP levels in healthy full-term and preterm infants may range from 2 to 5 mg/L during the first few days of life. During the neonatal period, an established upper normal CRP level of 10 mg/L has been identified in many studies. Other research teams have used upper normal reference levels ranging from 6 to 20 mg/L as cutoff levels to indicate the presence of sepsis or infection.
Benitz et al. evaluated CRP levels in 1,186 term and preterm infants and found that serial CRP levels drawn 12 to 24 hours after the onset of signs and symptoms of infection are superior to a single level. They also found that a CRP level of 10 mg/L is the appropriate threshold level, or the level at which the test has the maximum ability to identify infants with proven or probable sepsis.
In a study by Doellner et al., preterm infants were found to have a lower sensitivity of CRP in the diagnosis of neonatal sepsis compared to term newborns (61.5% vs. 75%). Similarly, Hofer et al. reported that CRP levels in healthy preterm babies are lower and shorter compared to healthy term babies, demonstrating the independent effects of prematurity on CRP values.
In summary, while CRP levels in newborns can vary depending on gestational age and other factors, an established upper normal CRP level of 10 mg/L has been identified in many studies as a threshold for suspected sepsis or infection. Serial CRP measurements are often recommended for a more accurate diagnosis and to monitor the response to treatment.
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Frequently asked questions
CRP levels in healthy full-term and preterm infants may range from 2 to 5 mg/L during the first few days of life. During the neonatal period, an established upper normal CRP level of 10 mg/L has been identified in many studies.
CRP stands for C-reactive protein.
C-reactive protein is a protein that is produced in the liver in response to inflammation or tissue injury. It is a marker of inflammation and can be used to help diagnose infections, including sepsis in newborns.
The CRP level can be measured through a blood test.
A high CRP level in newborns can vary depending on the study and the cut-off value used. Some studies have used cut-off values ranging from 1.5 to 20 mg/L to define a high CRP level. However, the most commonly used cut-off value is 10 mg/L.