Pregnancy-specific reference intervals for C-reactive protein improve diagnostic accuracy for infection: A longitudinal study

Dockree, Samuel; Brook, Jennifer; James, Tim; Shine, Brian; Impey, Lawrence; Vatish, Manu

doi:10.1016/j.cca.2021.02.015

Cited by 19 publications

(18 citation statements)

References 25 publications

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“…The hepatic synthesis of CRP may be influenced by the amount of adipose tissue, through increased IL-6 secretion in situ ( 34 , 35 ). In addition, CRP has been proposed to increase with BMI during pregnancy ( 25 , 36 ), aligning our data reporting correlations, though weak, between CRP levels and BMI during the first and second trimesters. Altogether, both BMI and the gestational age should be considered as potential influencers.…”

Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

“…CRP has been reported elevated in pregnant compared to non-pregnant women ( 25 , 31 – 33 ). In our study, CRP levels were similar in the first two trimesters and increased during the third trimester, which is in line with an older Swedish study by Larsson et al ( 24 ), but in contrast to the recent observation by Dockree et al ( 25 ). However, our cohort only consisted of women with a BMI within the range of 18–25 kg/m 2 at the time-point of conception which was not the case in the study by Dockree et al CRP has been shown to be further elevated in overweight and obese women and BMI-specific reference intervals has been proposed ( 25 ).…”

Section: Discussionmentioning

confidence: 99%

“…Infections during pregnancies are common and CRP is frequently measured as a surrogate marker of infection. Studies investigating CRP and PTX3 levels longitudinal during pregnancy are scarce (24)(25)(26)(27)(28). Establishing population specific reference intervals is necessary for evaluating laboratory analytes.…”

Section: Introductionmentioning

confidence: 99%

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Plasma C-Reactive Protein and Pentraxin-3 Reference Intervals During Normal Pregnancy

et al. 2021

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Although several biomarkers are available to monitor the acute phase response, the short pentraxin C-reactive protein (CRP) is dominating in clinical practice. The long pentraxin 3 (PTX3) is structurally and functionally related to CRP, but not liver-derived. In addition, increased levels of PTX3 have been linked to preeclampsia. Reference intervals are usually based on healthy blood donors. Several physiological and immunological alterations occur during normal pregnancy with subsequent potential effects on blood analytes. Hence, this study aims to determine pregnancy-specific reference intervals for CRP and PTX3. Longitudinal clinical data and blood plasma samples from the 1st, 2nd and 3rd trimester of 100 healthy, non-medicating, females aged 18–40 at the time-point of conception were available to us. High‐sensitivity CRP measurements were performed by turbidimetry and enzyme-linked immunosorbent assay (ELISA) was used to quantify PTX3. CRP and PTX3 levels followed each other during the first two trimesters and both increased during the third trimester. CRP showed a median of 4.12 mg/L in the third trimester, and were significantly higher compared to the first (median 2.39 mg/L, p<0.0001) and the second (median 2.44 mg/L, p=0.0006) trimesters. In the third trimester PTX3 levels reached a median of 7.70 µg/L, and were significantly higher compared to the first (median 3.33 µg/L, p<0.0001) and the second (median 3.70 µg/L, p<0.0001) trimesters. Plasma albumin was inversely correlated with CRP (rho=-0.27, p<0.0001), but not with PTX3. In conclusion, it is important to consider pregnancy-specific reference values as elevations of CRP and PTX3 during the later phase may occur in absence of infection.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Plasma C-Reactive Protein and Pentraxin-3 Reference Intervals During Normal Pregnancy

et al. 2021

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“…** For reference, conventional non-parametric reference intervals are presented with 90% confidence intervals, in accordance with CLSI/IFCC guidance, 12 showing strong concordance between the two methods. pregnancy, which is persistently raised from the first trimester, and which is most accurately interpreted using a single pregnancy-specific RI at any stage of pregnancy [8].…”

Section: Total Wbc and Neutrophilsmentioning

confidence: 99%

White blood cells in pregnancy: reference intervals for before and after delivery

Dockree¹,

Shine²,

Pavord³

et al. 2021

eBioMedicine

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Background White blood cells (WBC) are commonly measured to investigate suspected infection and inflammation in pregnant women, but the pregnancy-specific reference interval is variably reported, increasing diagnostic uncertainty in this high-risk population. It is essential that clinicians can interpret WBC results in the context of normal pregnant physiology, given the huge global burden of infection on maternal mortality. Methods We performed a longitudinal, repeated measures population study of 24,318 pregnant women in Oxford, UK, to map the trajectory of WBC between 8-40 weeks of gestation. We defined 95% reference intervals (RI) for total WBC, neutrophils, lymphocytes, eosinophils, basophils, and monocytes for the antenatal and postnatal periods. Findings WBC were measured 80,637 times over five years. The upper reference limit for total WBC was elevated by 36% in pregnancy (RI 5.7-15.0×10 9 /L), driven by a 55% increase in neutrophils (3.7-11.6×10 9 /L) and 38% increase in monocytes (0.3-1.1×10 9 /L), which remained stable between 8-40 weeks. Lymphocytes were reduced by 36% (1.0-2.9×10 9 /L), while eosinophils and basophils were unchanged. Total WBC was elevated significantly further from the first day after birth (similar regardless of the mode of delivery), which resolved to pre-delivery levels by an average of seven days, and to pre-pregnancy levels by day 21. Interpretation There are marked changes in WBC in pregnancy, with substantial differences between cell subtypes. WBC are measured frequently in pregnant women in obstetric and non-obstetric settings, and results should be interpreted using a pregnancy-specific RI until delivery, and between days 7-21 after childbirth. Funding None.

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Adverse perinatal outcomes are strongly associated with degree of abnormality in uterine artery Doppler pulsatility index

Dockree,

Aye,

Ioannou

et al. 2024

Ultrasound in Obstet & Gyne

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ObjectivesTo investigate the association between varying degrees of abnormality in the uterine artery Doppler pulsatility index (UtA‐PI) and adverse perinatal outcomes.MethodsProspective study of 33,364 women who gave birth to singleton, non‐anomalous babies in Oxford, following universal measurement of UtA‐PI in mid‐pregnancy. Relative risk ratios for the primary outcomes of extended perinatal mortality and live birth with severe small‐for‐gestational‐age (SGA) were calculated by multinomial logistic regression, for early preterm birth (<34+0) and late preterm/term birth (≥34+0). The risks were also investigated for iatrogenic preterm birth or a composite adverse outcome before 34+0 weeks.ResultsCompared with women with normal UtA‐PI, the risk of extended perinatal mortality before 34+0 weeks was higher in women with UtA‐PI >90th centile (RRR 4.7, 95% CI 2.7‐8.0, p<0.001), but this was not demonstrated in later births. The risk of severe SGA birth was strongly associated with abnormal UtA‐PI for both early births (RRR 26.0, 95% CI 11.6‐58.2, p<0.001), and later births (RRR 2.3, 95% CI 1.8‐2.9, p<0.001). Women with a raised UtA‐PI were more likely to undergo early iatrogenic birth (RRR 7.8, 95% CI 5.5‐11.2, p<0.001). For each of the outcomes and the composite outcome, the risk increased significantly in association with the degree of abnormality, through the 90th, 90‐94th, 95‐99th and >99th centiles (ptrend<0.001).ConclusionsAn elevated UtA‐PI is a key predictor of iatrogenic preterm birth, severe SGA and perinatal loss up to 34+0 weeks. It is the 90th centile that should be used, and management should be further tailored to the degree of abnormality, as pregnancies with very raised UtA‐PI measurements constitute a group at extreme risk.This article is protected by copyright. All rights reserved.

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Pregnancy-specific reference intervals for C-reactive protein improve diagnostic accuracy for infection: A longitudinal study

Cited by 19 publications

References 25 publications

Plasma C-Reactive Protein and Pentraxin-3 Reference Intervals During Normal Pregnancy

Plasma C-Reactive Protein and Pentraxin-3 Reference Intervals During Normal Pregnancy

White blood cells in pregnancy: reference intervals for before and after delivery

Adverse perinatal outcomes are strongly associated with degree of abnormality in uterine artery Doppler pulsatility index

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