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Journal Article Ppublish 6 citations

PubMed: 39087326 DOI: 10.1161/HYPERTENSIONAHA.124.22695

Epigenetic Clock at Birth and Childhood Blood Pressure Trajectory: A Prospective Birth Cohort Study.

Hypertension 81(10):e113-e124

Authors: Jie Hu, Anat Yaskolka Meir, Xiumei Hong, Guoying Wang, Frank B Hu, Xiaobin Wang, Liming Liang

Affiliations

  • Department of Epidemiology (J.H. A.Y.M. F.B.H. L.L.), Harvard T.H. Chan School of Public Health, Boston, MA. Center for Genomic Medicine and Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston (J.H.).
  • Department of Epidemiology (J.H. A.Y.M. F.B.H. L.L.), Harvard T.H. Chan School of Public Health, Boston, MA.
  • Center on the Early Life Origins of Disease, Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD (X.H. G.W. X.W.).
  • Department of Nutrition (F.B.H.), Harvard T.H. Chan School of Public Health, Boston, MA.
  • Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (F.B.H.).
  • Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD (X.W.).
  • Department of Biostatistics (L.L.), Harvard T.H. Chan School of Public Health, Boston, MA.

Abstract

BACKGROUND

The impact of methylation gestational age (GAmAge; a biomarker of fetal maturity) at birth on childhood blood pressure (BP) trajectories is unknown.

METHODS

This cohort study included 500 boys and 440 girls with data on cord blood DNA methylation and BP at 3 to 15 years of age. Systolic BP (SBP) and diastolic BP percentiles were calculated based on clinical guidelines. Time-series K-means clustering identified 4 distinct SBP and diastolic BP percentile trajectories: high-steady, high-decrease, normal-increase, and normal-steady. GAmAge was estimated using an existing pediatric epigenetic clock. Extrinsic age acceleration was calculated as residuals of associations between GAmAge and chronological gestational age. Intrinsic age acceleration was calculated using the same method adjusting for cord blood cell compositions.

RESULTS

Extrinsic age acceleration and intrinsic age acceleration were inversely associated with repeated measures of BP percentiles. Significant inverse associations were observed between extrinsic age acceleration and SBP percentiles in boys (β=-2.02; =0.02) but not in girls (β=-0.49; =0.58). Both extrinsic age acceleration and intrinsic age acceleration were inversely associated with SBP percentiles in girls born preterm (<37 weeks; β=-2.95; β=-3.00; <0.05). Compared with the normal-steady SBP trajectory, significant inverse associations were observed between intrinsic age acceleration and high-steady, high-decrease, and normal-increase SBP trajectories in boys (odds ratio, 0.73-0.81; <0.03), and significant positive associations were observed for high-decrease and normal-increase SBP trajectories in girls (odds ratio, 1.26-1.38; <0.01). Significant sex differences were observed (<2×10).

CONCLUSIONS

GAmAge acceleration at birth was inversely associated with child BP, and such association was more pronounced in boys than in girls. Our findings may shed new light on the developmental origins of high BP and sex differences in cardiovascular risk.

MeSH

Blood, Parturition, Blood Pressure, Fetal Blood, Cohort Studies, Gestational Age, Biomarkers, Odds Ratio, Sex Characteristics, Sex, Hemodynamics, Child, Sex Differences

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