Calprotectin in pregnancy and pregnancy-associated diseases: a systematic review and prospective cohort study
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Calprotectin, a marker of acute and chronic inflammation, may play a role in pregnancy-associated disorders. We aimed to summarize available clinical data on calprotectin in pregnancy and to establish normal values of calprotectin during the course of pregnancy.
We performed a systematic review of the databases PubMed and Cochrane Central Register of Controlled Trials to identify experimental and clinical evidence assessing the role of calprotectin in pregnancy. In addition, we performed a prospective cohort study assessing serum and urine calprotectin throughout pregnancy.
We identified 17 studies investigating 1638 pregnant women, 151 newborns, and 99 non-pregnant controls, measuring calprotectin in different compartments. Calprotectin was present in meconium and elevated in fecal samples of pregnant women with active inflammatory bowel disease. In women with pregnancy-induced hypertension, mild and severe preeclampsia (PE), calprotectin was significantly elevated in maternal plasma and serum, but not in fetal serum, amniotic fluid, and umbilical cord blood. For the cohort study, we recruited 196 pregnant women. PE and concomitant renal disease were present in 6/196 (3%) and 11/196 (5.6%) of women, respectively. Throughout pregnancy, median serum and urine levels of calprotectin largely exceed reported concentrations of the healthy non-pregnant population, but showed no significant variations between trimesters 1–3 and post-partum. Calprotectin in serum was correlated with systolic blood pressure and in urine with leukocytes and total protein. No significant differences were found in subgroup analyses of smokers vs. non-smokers, PE vs. none, and renal disease (kidney stones, reflux) vs. none.
Calprotectin concentrations in amnion fluid and stools serve as potential indicators of inflammatory states during pregnancy. Urinary calprotectin concentrations are continuously high during pregnancy and show no significant variations between trimesters 1–3 and post-partum.
KeywordsCalprotectin Pregnancy Renal disease Preeclampsia
Enzyme-linked immunosorbent assay
Inflammatory bowel disease
Intrauterine growth restriction
Pregnancy-associated hypertensive disorder
Prospective case–control study
Prospective cohort study
Prospective case series
Premature rupture of membranes
Randomized controlled trial
Systemic inflammatory disease
The study was funded by the German Research Foundation (Research Unit FOR1368).
TW designed the study, CF collected the material, GR, ZH, and CT analyzed the data and wrote the manuscript. All authors read and approved the final manuscript.
Compliance with ethical standards
Conflict of interest
All authors declare that they have no conflict of interest.
This study was approved by the Ruhr-Universität Bochum Ethics Committee. Written informed consent was obtained from all patients described in the prospective cohort study.
The data sets used and analyzed during the current study are available from the corresponding author on reasonable request.
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