Serum cytokine patterns in first half of pregnancy

Abstract

Introduction: Human pregnancy is a state of elevated maternal systemic inflammation, and pregnancy complications are often associated with a dysfunctional immune response. The network of cytokines reflects this complex immune activity, and broad serum cytokine profiling provides a new tool to understand the changes in immune status during pregnancy. Objective: This study aimed to determine how maternal serum cytokine patterns change during the first half of pregnancy. Methods: Maternal peripheral serum samples collected at a mean gestation of 10, 13, 18 and 24 weeks were included from a prospective clinical study of healthy women (n=110) in first half of normal pregnancy. The serum samples were analysed for 27 different cytokines using multiplex magnetic bead-based immunoassays, and high sensitivity C-reactive protein (CRP) was analysed by ELISA. Serum cytokine and CRP patterns were explored with linear mixed effects models (LMM) and multilevel partial least squares discriminant analysis (PLS-DA). Results: Serum cytokine profiling provided partial overview of the maternal immune status and corresponding reference values for serum cytokine levels during the first half of pregnancy. Several cytokines decreased in concentration from first to second trimester.Cytokine pattern analysis revealed that chemokines provided the most sensitive measurement of variation with gestational age in normal pregnancies. The nine inflammatory cytokines showed the highest intra-group correlation during pregnancy, while CRP levels did not correlate with changes in the inflammatory cytokines. Conclusion:Chemokines showed the greatest gestational variation and inflammatory cytokines showed a strong intra-group correlation during the first half of pregnancy.

Blood cytokine, chemokine and growth factor profiling in a cohort of pregnant women from tropical countries

“…Pregnant women were recruited at the first antenatal visit, regardless of gestational age. We could not perform a full longitudinal analysis of pregnancy (excluding delivery) but we were able to study the correlation of biomarker concentrations and gestational age, finding limited evidences of association, in contrast to a recent study showing in general higher biomarker levels in the second compared to the first trimester of pregnancy (8). Nevertheless, we observed that biomarker concentrations postpartum were higher than during pregnancy, and at delivery higher than at enrolment.…”

“…However, controlled pro-inflammatory cytokine responses during gestation are necessary during embryo implantation, placentation, labor and defense against infections (5). As the status of the immune system evolves during pregnancy, some studies have investigated longitudinal changes in cytokines over different trimesters or compared to postpartum (6)(7)(8), showing in general a decrease in levels over pregnancy with some exceptions and conflicting results. Other studies focused on the distinct patterns present in the peripheral, placental and cord compartments at delivery (9,10).…”

“…With few exceptions (6,8), prior works have only analyzed limited sets of biomarkers, while a wider breath of responses needs to be simultaneously studied to unravel the complex relationships between cytokine networks.…”

Cytokine Patterns in Maternal Serum From First Trimester to Term and Beyond

“…Earlier attempts have shown strong impact of pregnancy on serum cytokine levels but resulted in conflicting conclusions, as reviewed by Spence et al (14). While analysis of few or single cytokines has dominated the literature (14), broad cytokine profiling in pregnancy is feasible (4,13,(15)(16)(17)(18)(19)(20)(21) but these studies have typically employed small study samples or examined only parts of pregnancy.…”

Cord blood DNA methylation reflects cord blood C-reactive protein levels but not maternal levels: a longitudinal study and meta-analysis

“…We modeled linear associations with the understanding that higher inflammation is indicative of cellular damage, but in the context of pregnancy, it is possible that some non-linear relationships exist for the lowest and the highest CRP levels. Second, CRP levels have been shown not to correlate with other cytokines measured early in pregnancy [31].…”