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

Pediatric Research (2024)Cite this article

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.

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Fig. 1: Study cohorts and assessed outcomes.
Fig. 2: Plasma cytokine levels of infants at 6 months follow up.
Fig. 3: Spearman Correlation demonstrating association between different cytokines.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors thank the Multiplex Analysis Core at the Indiana University Melvin and Bren Simon Comprehensive Cancer Center for providing support in analyzing samples and interpretation of data.

Funding

This study is supported by R01HL122215 (R.S.T, L.S.H), K08HD109636 (K.L.K), March of Dimes Basil O’Connor Award (K.L.K).

Author information

Author notes

  1. These authors contributed equally: Kok Lim Kua, Eli Rhoads.

Authors and Affiliations

  1. Department of Pediatrics, Division of Neonatal‐Perinatal Medicine, Indiana University School of Medicine, Indianapolis, IN, USA

    Kok Lim Kua, Shanique Edwards & Laura S. Haneline

  2. Department of Pediatrics, Division of Pediatric Pulmonology, University of Nebraska Medical Center, Omaha, NE, USA

    Eli Rhoads

  3. Department of Biostatistics and Health Data Sciences, Indiana University School of Medicine, Indianapolis, IN, USA

    James E. Slaven

  4. Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, IN, USA

    David M. Haas

  5. Division of Pulmonary and Sleep Medicine, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Clement L. Ren

  6. Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Clement L. Ren

  7. Department of Pediatrics, Division of Pulmonary, Allergy, and Sleep Medicine, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA

    Christina Tiller, Jeffrey Bjerregaard & Robert S. Tepper

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Contributions

K.L.K was responsible for the data analysis and interpretation and wrote the initial and final drafts. E.R. was responsible for data collection, data analysis and interpretation, and wrote the initial and final drafts. J.E.S was responsible for the data analysis and interpretation and revised the manuscript. S.E was responsible for data collection and revised the manuscript. D.M.H was responsible for study design and revising the manuscript C.L.R was responsible for data interpretation and revising manuscript. C.T and J.B were responsible for data collection and revising manuscript. D.M.H, L.S.H, and R.S.T were responsible for study design, data analysis and interpretation, and revising manuscript. All authors approved the final version of manuscript.

Corresponding author

Correspondence to Robert S. Tepper.

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Kua, K.L., Rhoads, E., Slaven, J.E. et al. Decreased vascular reactivity associated with increased IL-8 in 6-month-old infants of mothers with pre-eclampsia. Pediatr Res (2024). https://doi.org/10.1038/s41390-024-03132-4

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  • DOI: https://doi.org/10.1038/s41390-024-03132-4

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