Leukocytes of pregnant women with small-for-gestational age neonates have a different phenotypic and metabolic activity from those of women with preeclampsia

Abstract

Objective. Preeclampsia and pregnancies complicated by small-for-gestational age (SGA) neonates share several underlying mechanisms of disease. However, while an exaggerated systemic maternal inflammatory response is regarded as one of the hallmarks of the pathogenesis of preeclampsia, the presence of a similar systemic intra-vascular inflammation in mothers of SGA neonates without hypertension is controversial. The aim of this study was to determine phenotypic and metabolic changes in granulocytes and monocytes of women who develop preeclampsia and those who deliver an SGA neonate, compared to normal pregnant women.

Methods. This cross-sectional study included patients with a normal pregnancy (n = 33), preeclampsia (n = 33), and an SGA without preeclampsia (n = 33), matched for gestational age at blood sample collection. Granulocyte and monocyte phenotypes were determined by flow cytometry, using monoclonal antibodies against selective cluster of differentiation (CD) antigens. The panel of antibodies included the following: CD11b, CD14, CD16, CD18, CD49d, CD62L, CD64, CD66b, and HLA-DR. Intracellular reactive oxygen species (iROS) were assessed at the basal state and after stimulation (oxidative burst). Results were reported as mean channel brightness (MCB) or intensity of detected fluorescence. Analysis was conducted with non-parametric statistics. A p-value < 0.01 was considered statistically significant.

Results. (1) Women who delivered an SGA neonate had a higher MCB of CD11b in granulocytes and monocytes than those with a normal pregnancy (p < 0.001 for both); (2) patients with preeclampsia had a lower median MCB of CD62L in granulocytes (p = 0.006) and a higher median basal iROS and oxidative burst in monocytes than women with an SGA neonate (p = 0.003 and p = 0.002, respectively).

Conclusion. Pregnancies complicated by the delivery of an SGA neonate are characterized by a higher activation of maternal peripheral leukocytes than in normal pregnancies, but lower than in pregnancies complicated by preeclampsia.

Keywords:

• SGA
• hypertension
• pregnancy
• maternal systemic inflammation
• leukocyte phenotype
• oxidative burst
• flow cytometry
• mean channel brightness
• CD62L
• CD11b

Acknowledgments

This research was supported by the Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS.