19 Mar 24. Katie McKinnon - prize winner

Neonatal Registrar and Research Fellow, Dr Katie McKinnon wins prize at the Neonatal Society Spring 2024 meeting

Dr Katie McKinnon, based within the Neonatal unit at the Simpson Centre for Reproductive Health, Royal Infirmary Edinburgh, was awarded the "Best Trainee Presentation" at The Neonatal Society Spring meeting in London. Her presentation title, "Epigenetic scores indicate differences in the proteome of preterm infants"  tested the hypotheses that preterm birth and socioeconomic status (SES) are associated with alterations in a set of Epigenetic scores (EpiScores) enriched for inflammation-associated proteins.

Further details concerning Dr McKinnon's research, presentation and paper are below. Well done Katie!:

Abstract: 

Introduction: EpiScores, reflecting DNA methylation (DNAm)-based surrogates for complex traits, have been developed for multiple circulating proteins. EpiScores for pro-inflammatory proteins, such as C-reactive protein (DNAm CRP), are associated with brain health and cognition across the lifespan, and with inflammatory comorbidities of preterm birth in neonates. Social disadvantage can become embedded in child development through inflammation, and deprivation is over-represented in preterm infants. 

Methods: 104 protein EpiScores were derived from saliva samples of 332 neonates born at gestational age (GA) 22+1 to 42+1 weeks. Participants were born at the Royal Infirmary Edinburgh and recruited to a longitudinal cohort study (2012-2021). Saliva sampling was between 36+4 and 47+1 weeks. We built linear regression models for each EpiScore, examining the relationship with birth GA, SES (as either the Scottish Index of Multiple Deprivation, maternal education, or maternal occupation), and a birth GA*SES interaction, adjusting for sampling GA, sex, and methylation processing batch. In a preterm sub-group (n=217, median [range] GA 22+2 weeks [22+1 to 33+0 weeks]), we additionally adjusted for inflammatory exposures (sepsis, bronchopulmonary dysplasia, necrotising enterocolitis, and histological chorioamnionitis). We used principal component analysis for data-driven correction for multiple comparisons.

Ethical approval: NRES, South-East Scotland REC (11/55/0061, 13/SS/0143, 16/SS/0154), and NHS Lothian Research and Development (2016/0255).

Funding: Theirworld, UKRI Medical Research Council Programme Grant MR/X003434/1

Results: Forty-three (41%) EpiScores were associated with low GA at birth (standardised estimates |0.14-0.88|, Bonferroni-adjusted p-value <8.3x10^-3, Figure 1). These included EpiScores for chemokines, growth factors, proteins involved in neurogenesis and vascular development, cell membrane proteins and receptors, and other immune proteins. Three EpiScores were associated with SES, or the interaction between birth GA and SES: afamin, intercellular adhesion molecule 5 and hepatocyte growth factor-like protein (standardised estimates |0.06-0.13|, Bonferroni-adjusted p-value <8.3x10^-3). In the preterm sub-group, SES-EpiScore associations did not remain statistically significant after adjustment for inflammatory exposures.

Conclusions: Low birth GA is substantially associated with a set of EpiScores. The set was enriched for inflammatory proteins, providing new insights into immune dysregulation in preterm infants. SES had fewer associations with EpiScores; these tended to have small effect sizes and were not statistically significant after adjusting for inflammatory comorbidities. This suggests that inflammation is unlikely to be the primary axis through which SES becomes embedded in the development of preterm infants in the neonatal period.

Summary: EpiScores are DNA methylation-based surrogates for circulating proteins. We found that low birth gestation is associated with 43 EpiScores in a set enriched for inflammatory proteins, providing new insights into immune dysregulation in preterm infants. 

Preprint link: https://www.medrxiv.org/content/10.1101/2023.12.19.23300227v1 (currently under peer review)

Keywords:

• C-reactive protein
• DNA
• Epigenetic