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.

The complement system constitutes a crucial part of the innate immunity, mediating opsonization, lysis, inflammation, and elimination of potential pathogens. In general, there is an increased activity of the complement system during pregnancy, which is essential for maintaining the host’s defense and fetal survival. Unbalanced or excessive activation of the complement system in the placenta is associated with pregnancy complications, such as miscarriage, preeclampsia, and premature birth. Nonetheless, the actual clinical value of monitoring the activation of the complement system during pregnancy remains to be investigated. Unfortunately, normal reference values specifically for pregnant women are missing, and for umbilical cord blood (UCB), data on complement protein levels are scarce. Herein, complement protein analyses (C1q, C3, C4, C3d levels, and C3d/C3 ratio) were performed in plasma samples from 100 healthy, non-medicated and non-smoking pregnant women, collected during different trimesters and at the time of delivery. In addition, UCB was collected at all deliveries. Maternal plasma C1q and C3d/C3 ratio showed the highest mean values during the first trimester, whereas C3, C4, and C3d had rising values until delivery. We observed low levels of C1q and C4 as well as increased C3d and C3d/C3 ratio, particularly during the first trimester, as a sign of complement activation in some women. However, the reference limits of complement analyses applied for the general population appeared appropriate for the majority of the samples. As expected, the mean complement concentrations in UCB were much lower than in maternal plasma, due to the immature complement system in neonates.