Maternal cytokine and cellular adhesion molecules profile in pregnant women with and without congenital heart disease.

Abstract

Introduction

Despite corrective surgery, patients with congenital heart disease (CHD) have residual regions of disturbed oscillatory blood flow which can induce upregulation of proinflammatory cytokines and adhesion molecules. Data on cytokine and cellular adhesion molecule (CAM) profiles in low risk pregnancy and pregnancy complicated by CHD are limited. The objective of this work was to study the profile of IL-6, IL-10, TNFα, ghrelin, GROα, and ICAM/VCAM in pregnancy in women with and without CHD and test the hypothesis that the circulating levels of these are correlated with obstetric outcomes.

Methods

Prospective study of women ≥18 years carrying a singleton low risk pregnancy low-risk (LR-group) and pregnant women with CHD (CHD-group). Study visits were conducted between 10 and 14, 18–22 and 30–34 weeks' gestation with blood sampling for immune profiling using the Bio-Plex® Multiplex Immunoassay. The immune profile was investigated in both groups and correlated with obstetric outcomes. This study was approved by the Health Research Authority and the London South East Research Ethics Committee (REC reference: 17/LO/0970).

Results

Forty-five samples in 30 participants with CHD and 45 gestational age-matched samples from 34 low-risk pregnant women were analysed. Women in the CHD-group delivered earlier (38 + 6 weeks vs 39 + 4 weeks, p = 0.005) and had smaller babies (2940 g, 30.0 centile vs 3415 g, 63.5 centile, p < 0.001). There were no significant differences in the levels of IL-6, IL-10 or TNFαin both groups across trimesters. Levels of GROα increased in both groups but less so in the CHD group. Levels of ghrelin decreased in both groups but less so in the CHD group. Levels of ICAM decreased as pregnancy progressed in the CHD group. Levels of VCAM increased in both groups but more significantly in the CHD-group (second trimester, p < 0.001; third trimester, p = 0.045). Women in the CHD-group had higher levels if IL-6 (p = 0.005) and ICAM (p < 0.001) lower levels of IL-10 in the third trimester (p = 0.018). There was a significant positive association between levels of IL-6 in the first trimester and birthweight centiles (r_s = 1.00, p < 0.001) in the CHD group.

Conclusion

There was minimal fluctuation in the levels of the studies cytokines during pregnancy with exception of GROα and ghrelin, both implicated in fetal growth. Women with CHD had higher levels of proinflammatory cytokines and ICAM in the first trimester, and lower levels of IL-10 in the third trimester, suggesting a more proinflammatory state. High levels of VCAM in the CHD group could be secondary to endothelial activation.