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Placental epigenetic age and adolescent blood pressure: the Extremely Low Gestational Age Newborn cohort
Anisha Gerber1, Kyle R Roell2, Katelyn K Huff3
1Division of Pediatric Nephrology, Department of Pediatrics, University of Virginia, Charlottesville, VA, USA. anisha.gerber@uvahealth.org.
Insights
Placental epigenetic age acceleration is linked to higher systolic blood pressure in adolescent males born extremely preterm. This finding suggests placental epigenetic age may serve as a biomarker for cardiovascular risk in this population.
Area of Science:
- Perinatal epigenetics
- Developmental origins of health and disease
- Pediatric cardiovascular health
Background:
- Extremely preterm birth (<28 weeks' gestation) poses long-term health risks.
- Placental epigenetic gestational age (eGA) may reflect developmental trajectories.
- The association between placental eGA acceleration and adolescent cardiovascular health is underexplored.
Purpose of the Study:
- To investigate the relationship between placental eGA acceleration and adolescent systolic blood pressure (SBP).
- To explore potential sex differences in this association among individuals born extremely preterm.
Main Methods:
- Analysis of a subset from the Extremely Low Gestational Age Newborn cohort.
- Calculation of placental eGA acceleration using the Robust Placental Clock.
- Mixed effects models to assess the association between eGA acceleration and adolescent SBP, including sex interaction.
Main Results:
- No significant association was found between placental eGA acceleration and adolescent SBP in the overall cohort (N=193).
- A significant association was observed in males: each 1-week eGA acceleration correlated with a 3.6 mmHg increase in SBP (p=0.01).
- No such association was found in females.
Conclusions:
- Placental eGA acceleration is associated with increased SBP in adolescent males born extremely preterm, but not females.
- These sex-specific findings support placental eGA as a potential biomarker for childhood cardiovascular outcomes.
- Further evaluation in diverse cohorts is warranted to validate placental eGA for risk stratification of elevated blood pressure.
Background:
We examined the association between placental epigenetic gestational age (eGA) acceleration and adolescent systolic blood pressure (SBP) in a cohort born extremely preterm.
Methods:
Study participants were a subset of the Extremely Low Gestational Age Newborn cohort (born <28 weeks' gestation) who had placental DNA methylation quantified and had SBP measured during adolescent follow-up. eGA acceleration was calculated as the residual from the regression of predicted placental eGA (using the Robust Placental Clock) onto chronological gestational age. Unadjusted and adjusted mixed effects models were used to test the association between eGA acceleration and adolescent SBP. We also tested the interaction of eGA acceleration and sex on SBP.
Results:
In the overall sample (N = 193), we found no association between placental eGA acceleration and adolescent SBP. When interaction between eGA acceleration and sex was tested, males had a 3.6 mmHg increase in SBP (95% CI 0.9, 6.4; p = 0.01) for every 1-week acceleration in eGA after adjusting for confounders.
Conclusion:
Placental eGA acceleration is associated with SBP increase in adolescent males but not females born extremely preterm, supporting the hypothesis that placental eGA could be evaluated as a risk biomarker for childhood cardiovascular outcomes.
Impact:
This study examines the association between placental epigenetic gestational age (eGA) and adolescent blood pressure. For every 1-week acceleration in placental eGA, adolescent males born extremely preterm had a 3.6 mmHg increase in systolic blood pressure (95% CI 0.9, 6.4; p = 0.01) after adjusting for confounders. The same association was not seen in females or the overall cohort. Our sex-specific finding supports the hypothesis that differences in placental eGA are associated with childhood health. Placental eGA estimation as a tool for identifying children who are at risk for developing elevated blood pressure should be further evaluated in other cohorts.
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01:46Epigenetic Regulation
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Physiological Factors: