C-reactive protein, interleukin-6 and pre-eclampsia: large-scale evidence from the GenPE case-control study

Abstract

Multiple small studies have suggested that women with pre-eclampsia present elevated levels of C-reactive protein (CRP) and interleukin-6 (IL-6). However, little is known regarding the source of this CRP and IL-6 increase. Therefore, the aim of this study was to evaluate the relationship between CRP and IL-6 levels with pre-eclampsia considering different confounding factors. Using data from a large Colombian case-control study (3,590 cases of pre-eclampsia and 4,564 normotensive controls), CRP and IL-6 levels were measured in 914 cases and 1297 controls. The association between maternal serum levels of CRP and IL-6 with pre-eclampsia risk was evaluated using adjusted logistic regression models. Pre-eclampsia was defined as presence of blood pressure ≥140/90 mmHg and proteinuria ≥300mg/24 h (or ≥1 + dipstick). There was no evidence of association between high levels of CRP and IL-6 with pre-eclampsia after adjusting for the following factors: maternal and gestational age, ethnicity, place and year of recruitment, multiple-pregnancy, socio-economic position, smoking, and presence of infections during pregnancy. The adjusted OR for 1SD increase in log-CRP and log-IL-6 was 0.96 (95%CI 0.85, 1.08) and 1.09 (95%CI 0.97, 1.22), respectively. Although previous reports have suggested an association between high CRP and IL-6 levels with pre-eclampsia, sample size may lack the sufficient power to draw robust conclusions, and this association is likely to be explained by unaccounted biases. Our results, the largest case-control study reported up to date, demonstrate that there is not a causal association between elevated levels of CRP and IL-6 and the presence of pre-eclampsia.

Keywords:

• Pre-eclampsia
• inflammation
• interleukin-6
• C-reactive protein
• Colombia
• case-control studies

Acknowledgements

We thank to Dr. Eleonara Staines-Urias for analysis and interpretation of data and the staff at the hospitals that conducted the recruitment of the participants in the GenPE study. Also, we thank to the medical students Cesar Barragan from Universidad CES, and Sara E. from UNAB for their invaluable contributions to the project.

Contribution to authorship

All authors significantly contributed to the intellectual content of this manuscript during the conception and design of the study, acquisition of data, analysis and interpretation of data, drafting or revising the content, and final approval of the paper. NCS and JPC designed the study, and MB, CCM, PKBN, SES, RO, SMB, AM, JM, CMM, MLL, and WS, enrolled patients, collected data, and systematically reviewed the relevant literature. CCM, MCP, and EG were involved in data transfer and cleaning. DCQL analyzed the data, with support from CCM, JPC, and NCS. NCS and JPC were involved in data interpretation and wrote the first draft of the manuscript, which was then reviewed and revised by all co-authors.

Disclosure statement

The authors declare that there is no conflict of interests regarding the publication of this paper.

Additional information

Funding

This project has been funded by project grants from Colciencias - Colombia [code: 14134319235] and from the Universidad Autónoma de Bucaramanga UNAB [code: EGEN22].