Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Comment
  • Published:

Understanding health disparities

Journal of Perinatology volume 39, pages 354–358 (2019)Cite this article

Subjects

Abstract

Based upon our recent insights into the determinants of preterm birth, which is the leading cause of death in children under five years of age worldwide, we describe potential analytic frameworks that provides both a common understanding and, ultimately the basis for effective, ameliorative action. Our research on preterm birth serves as an example that the framing of any human health condition is a result of complex interactions between the genome and the exposome. New discoveries of the basic biology of pregnancy, such as the complex immunological and signaling processes that dictate the health and length of gestation, have revealed a complexity in the interactions (current and ancestral) between genetic and environmental forces. Understanding of these relationships may help reduce disparities in preterm birth and guide productive research endeavors and ultimately, effective clinical and public health interventions.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Li J, Hong X, Mesiano S, Muglia LJ, Wang X, Snyder M, et al. Natural selection has differentiated the progesterone receptor among human populations. Am J Hum Genet. 2018;103:45–57.

    Article  CAS  Google Scholar 

  2. Liu L, Oza S, Hogan D, Chu Y, Perin J, Zhu J, et al. Global, regional, and national causes of under-5 mortality in 2000-15: an updated systematic analysis with implications for the Sustainable Development Goals. Lancet. 2016;388:3027–35.

    Article  Google Scholar 

  3. Timpson NJ, Greenwood CMT, Soranzo N, Lawson DJ, Richards JB. Genetic architecture: the shape of the genetic contribution to human traits and disease. Nat Rev Genet. 2018;19:110–24.

    Article  CAS  Google Scholar 

  4. Wise PH, Shaw GM, Druzin ML, Darmstadt GL, Quaintance C, Makinen E, et al. Risky business: meeting the structural needs of transdisciplinary science. J Pediatr. 2017;191:255–8.

    Article  Google Scholar 

  5. Stevenson DK, Shaw GM, Wise PH, Norton ME, Druzin ML, Valantine HA, et al. Transdisciplinary translational science and the case of preterm birth. J Perinatol. 2013;33:251–8.

    Article  CAS  Google Scholar 

  6. Muglia LJ, Katz M. The enigma of spontaneous preterm birth. N Engl J Med. 2010;362:529–35.

    Article  CAS  Google Scholar 

  7. Ghaemi MS, DiGiulio DB, Contrepois K, Callahan BJ, Ngo TTM, Lee-McMullen B, et al. Multiomics modeling of the immunome, transcriptome, microbiome, proteome, and metabolome adaptations during human pregnancy. Bioinformatics. 2018; https://doi.org/10.1093/bioinformatics/bty537.

  8. Sirota M, Thomas CG, Liu R, Zuhl M, Banerjee P, Wong RJ, et al. Enabling precision medicine in neonatology, an integrated repository for preterm birth research. Sci Data. 2018;5:180219.

    Article  Google Scholar 

  9. Fan HC, Blumenfeld YJ, Chitkara U, Hudgins L, Quake SR. Noninvasive diagnosis of fetal aneuploidy by shotgun sequencing DNA from maternal blood. Proc Natl Acad Sci USA. 2008;105:16266–71.

    Article  CAS  Google Scholar 

  10. Pan W, Ngo TTM, Camunas-Soler J, Song CX, Kowarsky M, Blumenfeld YJ, et al. Simultaneously monitoring immune response and microbial infections during pregnancy through plasma cfRNA sequencing. Clin Chem. 2017;63:1695–704.

    Article  CAS  Google Scholar 

  11. Ngo TTM, Moufarrej MN, Rasmussen MH, Camunas-Soler J, Pan W, Okamoto J, et al. Noninvasive blood tests for fetal development predict gestational age and preterm delivery. Science. 2018;360:1133–6.

    Article  CAS  Google Scholar 

  12. Bandura DR, Baranov VI, Ornatsky OI, Antonov A, Kinach R, Lou X, et al. Mass cytometry: technique for real time single cell multitarget immunoassay based on inductively coupled plasma time-of-flight mass spectrometry. Anal Chem. 2009;81:681322.

    Article  Google Scholar 

  13. Bendall SC, Simonds EF, Qiu P, Amir el AD, Krutzik PO, Finck R, et al. Single-cell mass cytometry of differential immune and drug responses across a human hematopoietic continuum. Science. 2011;332:687–96.

    Article  CAS  Google Scholar 

  14. Fragiadakis GK, Baca QJ, Gherardini PF, Ganio EA, Gaudilliere DK, Tingle M, et al. Mapping the fetomaternal peripheral immune system at term pregnancy. J Immunol. 2016;197:4482–92.

    Article  CAS  Google Scholar 

  15. Gaudilliere B, Ganio EA, Tingle M, Lancero HL, Fragiadakis GK, Baca QJ, et al. Implementing mass cytometry at the bedside to study the immunological basis of human diseases: distinctive immune features in patients with a history of term or preterm birth. Cytometry A. 2015;87:817–29.

    Article  CAS  Google Scholar 

  16. Bengsch B, Ohtani T, Khan O, Setty M, Manne S, O’Brien S, et al. Epigenomic-guided mass cytometry profiling reveals disease-specific features of exhausted CD8 T cells. Immunity. 2018;48:1029-45–e1025.

    Article  Google Scholar 

  17. Frei AP, Bava FA, Zunder ER, Hsieh EW, Chen SY, Nolan GP, et al. Highly multiplexed simultaneous detection of RNAs and proteins in single cells. Nat Methods. 2016;13:269–75.

    Article  CAS  Google Scholar 

  18. Aghaeepour N, Ganio EA, McIlwain D, Tsai AS, Tingle M, Van Gassen S, et al. An immune clock of human pregnancy. Sci Immunol. 2017;2:eaan2946.

    Article  Google Scholar 

  19. Owen CM, Goldstein EH, Clayton JA, Segars JH. Racial and ethnic health disparities in reproductive medicine: an evidence-based overview. Semin Reprod Med. 2013;31:317–24.

    Article  Google Scholar 

  20. Ehn NL, Cooper ME, Orr K, Shi M, Johnson MK, Caprau D, et al. Evaluation of fetal and maternal genetic variation in the progesterone receptor gene for contributions to preterm birth. Pediatr Res. 2007;62:630–5.

    Article  CAS  Google Scholar 

  21. Langmia IM, Apalasamy YD, Omar SZ, Mohamed Z. Progesterone Receptor (PGR) gene polymorphism is associated with susceptibility to preterm birth. BMC Med Genet. 2015;16:63.

    Article  Google Scholar 

  22. Manuck TA, Lai Y, Meis PJ, Dombrowski MP, Sibai B, Spong CY, et al. Progesterone receptor polymorphisms and clinical response to 17-alpha-hydroxyprogesterone caproate. Am J Obstet Gynecol. 2011;205:135 e131–9.

    Article  Google Scholar 

  23. Zachariades E, Mparmpakas D, Pang Y, Rand-Weaver M, Thomas P, Karteris E. Changes in placental progesterone receptors in term and preterm labour. Placenta. 2012;33:367–72.

    Article  CAS  Google Scholar 

  24. Yudell M, Roberts D, DeSalle R, Tishkoff S. Science and society. Taking race out of human genetics. Science. 2016;351:564–5.

    Article  CAS  Google Scholar 

  25. DiGiulio DB, Callahan BJ, McMurdie PJ, Costello EK, Lyell DJ, Robaczewska A, et al. Temporal and spatial variation of the human microbiota during pregnancy. Proc Natl Acad Sci USA. 2015;112:11060–5.

    Article  CAS  Google Scholar 

  26. Callahan BJ, DiGiulio DB, Goltsman DSA, Sun CL, Costello EK, Jeganathan P, et al. Replication and refinement of a vaginal microbial signature of preterm birth in two racially distinct cohorts of US women. Proc Natl Acad Sci USA. 2017;114:9966–71.

    Article  CAS  Google Scholar 

  27. Shachar BZ, Mayo JA, Lyell DJ, Baer RJ, Jeliffe-Pawlowski LL, Stevenson DK, et al. Interpregnancy interval after live birth or pregnancy termination and estimated risk of preterm birth: a retrospective cohort study. BJOG. 2016;123:2009–17.

    Article  CAS  Google Scholar 

Download references

Funding

This work was supported in part by the Bill and Melinda Gates Foundation, the March of Dimes Prematurity Research Center at Stanford University, and the Charles and Marie Robertson Foundation.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, 94305, USA

    David K. Stevenson, Ronald J. Wong, Gary L. Darmstadt, Jeffrey B. Gould, Michael Katz, Jingjing Li, Cecele C. Quaintance, Gary M. Shaw & Paul H. Wise

  2. Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA

    Nima Aghaeepour, Martin S. Angst & Brice Gaudilliere

  3. Department of Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA

    Daniel B. DiGiulio & David A. Relman

  4. Infectious Diseases Section, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, 94306, USA

    Daniel B. DiGiulio & David A. Relman

  5. Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, CA, 94305, USA

    Maurice L. Druzin & Ronald S. Gibbs

  6. Department of Genetics, Stanford Center for Genomics and Personalized Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA

    Jingjing Li & Michael P. Snyder

  7. Departments of Bioengineering and Applied Physics, Stanford University and Chan Zuckerberg Biohub, Stanford, CA, 94305, USA

    Mira N. Moufarrej & Stephen R. Quake

  8. Center on the Early Life Origins of Disease, Department of Population, Family and Reproductive Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, 21205, USA

    Xiaobin Wang

  9. Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA

    Xiaobin Wang

Authors
  1. David K. Stevenson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ronald J. Wong
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nima Aghaeepour
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Martin S. Angst
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Gary L. Darmstadt
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Daniel B. DiGiulio
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Maurice L. Druzin
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Brice Gaudilliere
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ronald S. Gibbs
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Jeffrey B. Gould
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Michael Katz
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Jingjing Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Mira N. Moufarrej
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Cecele C. Quaintance
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Stephen R. Quake
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. David A. Relman
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Gary M. Shaw
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Michael P. Snyder
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Xiaobin Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Paul H. Wise
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to David K. Stevenson.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Stevenson, D.K., Wong, R.J., Aghaeepour, N. et al. Understanding health disparities. J Perinatol 39, 354–358 (2019). https://doi.org/10.1038/s41372-018-0298-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41372-018-0298-1

This article is cited by

Search

Advanced search

Quick links