Metabolomic Profiles During and After a Hypertensive Disorder of Pregnancy: The EPOCH Study
Abstract
1. Introduction
2. Results
2.1. Study Participants
2.2. Antepartum Comparisons
2.3. Postpartum Comparisons
2.4. Mid-Life Comparisons
2.5. Temporal Analyses
2.6. Covariates
3. Discussion
3.1. Prior Studies
3.2. Limitations
3.3. Conclusions
4. Materials and Methods
4.1. Study Design
4.2. Sample Collection
4.3. Metabolomic Assays
4.4. Case–Control Comparisons
4.5. Multivariate Modeling
4.6. Temporal Analyses
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Antepartum Visit | Postpartum Visit | Mid-Life Visit | |||||||
---|---|---|---|---|---|---|---|---|---|
Cases (n = 32) | Controls (n = 42) | p- Value | Cases (n = 44) | Controls (n = 36) | p-Value | Cases (n = 71) | Controls (n = 74) | p-Value | |
Clinical characteristics | |||||||||
Race * | |||||||||
White | 12 (38%) | 25 (60%) | 0.10 | 22 (50%) | 23 (64%) | 0.31 | 38 (54%) | 45 (61%) | 0.47 |
Asian/Pacific Islander | 7 (22%) | 12 (29%) | 0.70 | 10 (23%) | 10 (28%) | 0.80 | 17 (24%) | 25 (34%) | 0.26 |
Black/African American | 1 (3%) | 2 (5%) | 1.00 | 1 (2%) | 2 (6%) | 0.59 | 3 (4%) | 3 (4%) | 1.00 |
Native American/Alaskan | 0 (0%) | 0 (0%) | 1.00 | 1 (2%) | 0 (0%) | 1.00 | 1 (1%) | 2 (3%) | 1.00 |
Not reported | 12 (38%) | 5 (12%) | 0.005 | 11 (25%) | 2 (6%) | 0.03 | 16 (23%) | 8 (11%) | 0.09 |
Hispanic ethnicity | 9 (28%) | 6 (14%) | 0.14 | 14 (32%) | 4 (11%) | 0.03 | 19 (27%) | 14 (19%) | 0.26 |
Gestational diabetes | 8 (25%) | 0 (0%) | 0.0004 | 9 (20%) | 0 (0%) | 0.003 | 6 (8%) | 0 (0%) | 0.01 |
Preterm HDP onset (<37 weeks) | 31 (97%) | 0 (0%) | NA | 25 (57%) | 0 (0%) | NA | 31 (44%) | 0 (0%) | NA |
Gestational age at delivery (weeks) | 34.6 (2.6) | 39.2 (1.3) | <0.0001 | 36.5 (3.2) | 39.1 (1.6) | 0.0001 | 37.0 (3.2) | 38.4 (2.8) | 0.006 |
Characteristics at study visit | |||||||||
Study visit timing † | 33.3 (3.2) | 33.0 (3.8) | 0.68 | 16.9 (12.3) | 9.7 (5.6) | 0.002 | 6.0 (3.5) | 5.9 (3.8) | 0.88 |
Age (years) | 33.4 (5.5) | 32.9 (4.4) | 0.65 | 34.3 (4.4) | 33.5 (3.7) | 0.41 | 40.6 (6.3) | 41.0 (5.3) | 0.54 |
Parity | 0.8 (1.1) | 0.4 (0.5) | 0.05 | 1.6 (1.0) | 1.4 (0.5) | 0.21 | 2 (1.2) | 2 (0.8) | 0.63 |
Nulliparous/primiparous ‡ | 19 (59%) | 25 (60%) | 0.99 | 28 (64%) | 23 (64%) | 0.98 | 26 (37%) | 22 (30%) | 0.35 |
Gravidity | 2.6 (1.6) | 1.8 (0.8) | 0.005 | 2.3 (1.3) | 1.8 (0.8) | 0.04 | 3 (1.9) | 3 (1.6) | 0.52 |
Body mass index (kg/m2) | 33.2 (6.8) | 26.2 (3.6) | <0.0001 | 28.5 (6.6) | 24.2 (3.6) | 0.002 | 27 (4.9) | 24 (4.9) | 0.005 |
Blood pressure § | |||||||||
Systolic | 132 (14.6) | 105 (7.0) | <0.0001 | 115 (9.1) | 106 (7.9) | 0.0006 | 119 (10.7) | 112 (11.5) | 0.0003 |
Diastolic | 82 (5.9) | 64 (6.7) | <0.0001 | 73 (7.3) | 68 (5.9) | 0.005 | 75 (8.5) | 70 (9.3) | 0.001 |
Antihypertensive treatment || | 9 (28%) | 0 (0%) | 0.0002 | 2 (5%) | 0 (0%) | 0.21 | 7(10%) | 2 (3%) | 0.006 |
Metabolite Name | Class | Pathway | Log2 (Fold-Change) | Adjusted p-Value |
---|---|---|---|---|
10,20-Dihydroxyeicosanoic acid * | Eicosanoid and resolvin | Eicosanoid and resolvin metabolism | −2.05 | 0.00001 |
Pregnenolone sulfate | Gonadal steroid | Gonadal steroid metabolism/xenobiotic metabolism | −1.13 | 0.00003 |
Cortisol | Steroids and derivatives | Cholesterol, cortisol, non-gonadal steroid metabolism | −1.98 | 0.00003 |
11β-Hydroxyprogesterone | Steroids and derivatives | Gonadal steroid metabolism | −2.01 | 0.00021 |
Butyrylcarnitine | Acyl carnitines | Fatty Acid Oxidation and Synthesis | 0.84 | 0.00026 |
L-Tyrosine | Amino acids and derivatives | Tyrosine and phenylalanine metabolism | 0.42 | 0.00026 |
Estrone 3-sulfate | Steroids and derivatives | Gonadal steroid metabolism/xenobiotic metabolism | −1.81 | 0.00027 |
Hydroxyoctadienoic acid | Lipid and lipid-like | Fatty acid oxidation and synthesis | 0.72 | 0.00030 |
C7H15N3O2 | NA | NA | 0.87 | 0.00030 |
Pregnanolone sulfate | Steroids and derivatives | Gonadal steroid metabolism/xenobiotic metabolism | −0.67 | 0.00032 |
C17H27NO4 | NA | NA | 0.87 | 0.00033 |
Estriol-3-glucuronide | Steroids and derivatives | Gonadal steroid metabolism/xenobiotic metabolism | −1.74 | 0.00033 |
Dihydrocortisol ** | Steroids and derivatives | Cholesterol, cortisol, non-gonadal steroid Metabolism | −2.38 | 0.00034 |
Hydroxyestrone sulfate | Steroids and derivatives | Gonadal steroid metabolism/xenobiotic metabolism | −1.70 | 0.00034 |
9-Nor-1-,25-dihydroxyvitamin D2 | Vitamins and derivatives | Vitamin metabolism | −0.68 | 0.00037 |
L-Phenylalanine | Amino acids and derivatives | Tyrosine and phenylalanine metabolism | 0.30 | 0.00047 |
Gamma-glutamyl-L-isoleucine | Dipeptide | Protein digestion or protein catabolism | 0.46 | 0.00047 |
Glutamylphenylalanine | Dipeptide | Protein digestion or protein catabolism | 0.46 | 0.00092 |
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Hlatky, M.A.; Shu, C.-H.; Bararpour, N.; Murphy, B.M.; Sorondo, S.M.; Leeper, N.J.; Wong, F.; Stevenson, D.K.; Shaw, G.M.; Stefanick, M.L.; et al. Metabolomic Profiles During and After a Hypertensive Disorder of Pregnancy: The EPOCH Study. Int. J. Mol. Sci. 2025, 26, 6150. https://doi.org/10.3390/ijms26136150
Hlatky MA, Shu C-H, Bararpour N, Murphy BM, Sorondo SM, Leeper NJ, Wong F, Stevenson DK, Shaw GM, Stefanick ML, et al. Metabolomic Profiles During and After a Hypertensive Disorder of Pregnancy: The EPOCH Study. International Journal of Molecular Sciences. 2025; 26(13):6150. https://doi.org/10.3390/ijms26136150
Chicago/Turabian StyleHlatky, Mark A., Chi-Hung Shu, Nasim Bararpour, Brenna M. Murphy, Sabina M. Sorondo, Nicholas J. Leeper, Frank Wong, David K. Stevenson, Gary M. Shaw, Marcia L. Stefanick, and et al. 2025. "Metabolomic Profiles During and After a Hypertensive Disorder of Pregnancy: The EPOCH Study" International Journal of Molecular Sciences 26, no. 13: 6150. https://doi.org/10.3390/ijms26136150
APA StyleHlatky, M. A., Shu, C.-H., Bararpour, N., Murphy, B. M., Sorondo, S. M., Leeper, N. J., Wong, F., Stevenson, D. K., Shaw, G. M., Stefanick, M. L., Boyd, H. A., Melbye, M., Sedan, O., Wong, R. J., Snyder, M. P., Aghaeepour, N., & Winn, V. D. (2025). Metabolomic Profiles During and After a Hypertensive Disorder of Pregnancy: The EPOCH Study. International Journal of Molecular Sciences, 26(13), 6150. https://doi.org/10.3390/ijms26136150