Decreased vascular reactivity associated with increased IL-8 in 6-month-old infants of mothers with pre-eclampsia

Abstract

Background: Offspring born to mothers with pre-eclampsia (Pre-E) suffer higher risks of adult cardiovascular diseases, suggesting that exposure to an antiangiogenic environment in-utero has a lasting impact on the development of endothelial function. The goal of this study is to test the hypothesis that in-utero exposure to Pre-E results in alterations of angiogenic factors/cytokines that negatively impact vascular development during infancy.

Methods: Infants born from mothers with and without Pre-E were recruited and followed up at 6 months. Plasma cytokines, blood pressure, microvessel density, and vascular reactivity were assessed.

Results: 6-month-old infants born to mothers with Pre-E had unchanged blood pressure (p = 0.86) and microvessel density (p = 0.57). Vascular reactivity was decreased in infants born to mothers with Pre-E compared to infants born to healthy mothers (p = 0.0345). Interleukin 8 (IL-8) (p = 0.03) and Angiopoeitin-2 (Ang-2) (p = 0.04) were increased in infants born to mothers with Pre-E. We observed that higher IL-8 was associated with lower vascular reactivity (rho = -0.14, p < 0.0001).

Conclusion: At 6 months of age, infants born to mothers with Pre-E had impaired vascular reactivity and higher IL-8 and Ang-2, but similar blood pressure and microvessel density compared to infants born to non-Pre-E mothers.

Impact statement: Changes in cord blood antiangiogenic factors are documented in infants of mothers with pre-eclampsia and may contribute to offspring risks of adult cardiovascular disease. How these factors evolve during early infancy and their correlation with offspring vascular development have not been studied. This study found that 6-month-old infants born to mothers with pre-eclampsia had decreased vascular reactivity, which was correlated with higher IL-8. These findings underscore the lasting impact of maternal pre-eclampsia on offspring vascular development and highlight the need for long-term follow-up in children born to mothers with pre-eclampsia.

Fig. 1. Study cohorts and assessed outcomes.

a Numbers of patients enrolled in the study and infants who had outcomes measured. b Representative graph of cutaneous perfusion measured using Periflux System 5000. Perfusion unit was assessed using laser doppler probe at time 0 (baseline), and then followed by Acetylcholine chloride solution delivered via iontophoresis at the rate of 1.8 mg over 10 s. Every 10 sec therefore represents an increment of 1.8 mg in Acetylcholine dose.

Fig. 2. Plasma cytokine levels of infants at 6 months follow up.

Bar graph showing mean ± SEM of a IL-8 and b Angiopoeitin-2 of infants born to control (Con) mothers and mothers with Pre-eclampsia (Pre-E). Each dot represents cytokine level of a patient, *p < 0.05 by regular t-test.

Fig. 3. Spearman Correlation demonstrating association between different cytokines.

a Correlation between IL-8 with VEGFR-1 (rho = 0.1096, p = 0.1880). b Correlation between VEGFR-1 with Ang-2 (rho = 0.0800, p = 0.3369). c Correlation between IL-8 with Ang-2 (rho = 0.2601, p = 0.0015). black circles represent data from Con infants, open circles represent data from Pre-E infants.