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.

  • Clinical Research Article
  • Published:

Impact of race on heart rate characteristics monitoring in very low birth weight infants

Pediatric Research volume 94, pages 575–580 (2023)Cite this article

Abstract

Background

A multicenter RCT showed that displaying a heart rate characteristics index (HRCi) predicting late-onset sepsis reduced mortality for VLBW infants. We aimed to assess whether HRCi display had a differential impact for Black versus White infants.

Methods

We performed secondary data analysis of Black and White infants enrolled in the HeRO RCT. We evaluated the predictive performance of the HRCi for infants with Black or White maternal race. Using models adjusted for birth weight, we assessed outcomes and interventions for a race × randomization interaction.

Results

Among 2607 infants, Black infants had lower birth weight, gestational age, length of stay, and ventilator days, while sepsis and mortality were similar. The HRCi performed equally for sepsis prediction in Black and White infants. We found no differential effect of randomization by race on sepsis, mortality, antibiotic days, length of stay, or ventilator days. However, there was a differential randomization effect by race for blood cultures per patient: White RR 1.11 (95% CrI 1.04–1.18), Black RR 1.00 (0.93–1.07).

Conclusions

The HRCi performed similarly for sepsis prediction in Black and White infants. Randomization to HRCi display increased blood cultures in White but not in Black infants, while the impact on other outcomes or interventions was similar.

Impact

  • Predictive analytics, such as heart rate characteristics (HRC) monitoring for late-onset neonatal sepsis, should have equal impact among patients of different race. Infants with Black or White maternal race randomized to HRC display had similar outcomes, but randomization to the study arm increased a related clinical intervention, blood cultures, in White but not in Black infants.

  • This study provides evidence of a differential effect of predictive models on clinical care by race.

  • The work will promote consideration and analysis of equity in the implementation of predictive analytics.

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

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

Fig. 1: Box and whisker plots of HRC index by race and study arm.
Fig. 2: Calibration curves for HRC predicted versus observed sepsis by race.
Fig. 3: Predicted number of antibiotics days (left) and the number of blood cultures (right) by infant race and study arm, adjusted for birth weight and site.

Similar content being viewed by others

Data availability

Data are available upon reasonable request.

References

  1. Beck, A. F. et al. The color of health: how racism, segregation, and inequality affect the health and well-being of preterm infants and their families. Pediatr. Res. 87, 227–234 (2020).

    Article  PubMed  Google Scholar 

  2. Hamilton, B., Martin, J. & Osterman, M. Births: Provisional Data for 2020 (Centers for Disease Control and Prevention, 2021)

  3. DeSisto, C. L., Hirai, A. H., Collins, J. W. & Rankin, K. M. Deconstructing a disparity: explaining excess preterm birth among U.S.-born black women. Ann. Epidemiol. 28, 225–230 (2018).

    Article  PubMed  Google Scholar 

  4. Travers, C. P. et al. Prematurity and race account for much of the interstate variation in infant mortality rates in the United States. J. Perinatol. 40, 767–773 (2020).

    Article  PubMed  Google Scholar 

  5. Anderson, J. G. et al. Racial and ethnic disparities in preterm infant mortality and severe morbidity: a population-based study. Neonatology 113, 44–54 (2018).

    Article  PubMed  Google Scholar 

  6. Travers, C. P. et al. Racial/ethnic disparities among extremely preterm infants in the united states from 2002 to 2016. JAMA Netw. Open 3, e206757 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  7. Profit, J. et al. Racial/ethnic disparity in NICU quality of care delivery. Pediatrics 140, e20170918 (2017).

  8. Stoll, B. J. et al. Late-onset sepsis in very low birth weight neonates: a report from the National Institute of Child Health and Human Development Neonatal Research Network. J. Pediatr. 129, 63–71 (1996).

    Article  CAS  PubMed  Google Scholar 

  9. Stoll, B. J. et al. Late-onset sepsis in very low birth weight neonates: the experience of the NICHD Neonatal Research Network. Pediatrics 110, 285–291 (2002).

    Article  PubMed  Google Scholar 

  10. Hornik, C. P. et al. Early and late onset sepsis in very-low-birth-weight infants from a large group of neonatal intensive care units. Early Hum. Dev. 88(Suppl. 2), S69–S74 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  11. Sullivan, B. A. et al. Clinical and vital sign changes associated with late-onset sepsis in very low birth weight infants at 3 NICUs. J. Neonatal Perinat. Med. 14, 553–561 (2021).

    Article  CAS  Google Scholar 

  12. Wallace, M. E. et al. Racial/ethnic differences in preterm perinatal outcomes. Am. J. Obstet. Gynecol. 216, 306.e1–306.e12 (2017).

    Article  PubMed  Google Scholar 

  13. Greenberg, R. G. et al. Late-onset sepsis in extremely premature infants: 2000-2011. Pediatr. Infect. Dis. J. 36, 774–779 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  14. Griffin, M. P. & Moorman, J. R. Toward the early diagnosis of neonatal sepsis and sepsis-like illness using novel heart rate analysis. Pediatrics 107, 97–104 (2001).

    Article  CAS  PubMed  Google Scholar 

  15. Griffin, M. P. et al. Abnormal heart rate characteristics preceding neonatal sepsis and sepsis-like illness. Pediatr. Res. 53, 920–926 (2003).

    Article  PubMed  Google Scholar 

  16. Moorman, J. R. et al. Mortality reduction by heart rate characteristic monitoring in very low birth weight neonates: a randomized trial. J. Pediatr. 159, 900.e1–906.e1 (2011).

    Article  Google Scholar 

  17. Fairchild, K. D. et al. Septicemia mortality reduction in neonates in a heart rate characteristics monitoring trial. Pediatr. Res. 74, 570–575 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  18. Sullivan, B. A. & Fairchild, K. D. Vital signs as physiomarkers of neonatal sepsis. Pediatr. Res. https://doi.org/10.1038/s41390-021-01709-x (2021)

  19. Sullivan, B. A., Grice, S. M., Lake, D. E., Moorman, J. R. & Fairchild, K. D. Infection and other clinical correlates of abnormal heart rate characteristics in preterm infants. J. Pediatr. 164, 775–780 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  20. Johnson, G. M. Algorithmic bias: on the implicit biases of social technology. Synthese https://doi.org/10.1007/s11229-020-02696-y (2020)

  21. Gianfrancesco, M. A., Tamang, S., Yazdany, J. & Schmajuk, G. Potential biases in machine learning algorithms using electronic health record data. JAMA Intern. Med. 178, 1544–1547 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  22. Vehtari, A., Gelman, A. & Gabry, J. Practical Bayesian model evaluation using leave-one-out cross-validation and WAIC. Stat. Comput. 27, 1413–1432 (2017).

    Article  Google Scholar 

  23. Bürkner, P.-C. brms: an R package for bayesian multilevel models using stan. J. Stat. Softw. 80, 1–28 (2017).

  24. Ryan, R. M. et al. Black race is associated with a lower risk of bronchopulmonary dysplasia. J. Pediatr. 207, 130.e2–135.e2 (2019).

    Article  Google Scholar 

  25. Burris, H. H., Hwang, S. S., Collins, J. W., Kirpalani, H. & Wright, C. J. Re-conceptualizing associations between race and morbidities of extreme prematurity. J. Pediatr. 207, 10.e1–14.e1 (2019).

    Article  Google Scholar 

  26. Howell, E. A. et al. Differences in morbidity and mortality rates in black, white, and hispanic very preterm infants among new york city hospitals. JAMA Pediatr. 172, 269–277 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  27. Fairchild, K. D. et al. Endotoxin depresses heart rate variability in mice: cytokine and steroid effects. Am. J. Physiol. Regul. Integr. Comp. Physiol. 297, R1019–R1027 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Fairchild, K. D., Srinivasan, V., Moorman, J. R., Gaykema, R. P. A. & Goehler, L. E. Pathogen-induced heart rate changes associated with cholinergic nervous system activation. Am. J. Physiol. Regul. Integr. Comp. Physiol. 300, R330–R339 (2011).

    Article  CAS  PubMed  Google Scholar 

  29. Hill, L. K., Watkins, L. L., Hinderliter, A. L., Blumenthal, J. A. & Sherwood, A. Racial differences in the association between heart rate variability and left ventricular mass. Exp. Physiol. 102, 764–772 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  30. Lombardi, F. & Stein, P. K. Origin of heart rate variability and turbulence: an appraisal of autonomic modulation of cardiovascular function. Front. Physiol. 2, 95 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  31. Fonkoue, I. T., Schwartz, C. E., Wang, M. & Carter, J. R. Sympathetic neural reactivity to mental stress differs in black and non-Hispanic white adults. J. Appl. Physiol. 124, 201–207 (2018).

    Article  PubMed  Google Scholar 

  32. Carnethon, M. R. et al. Cardiovascular health in african americans: a Scientific Statement from the American Heart Association. Circulation 136, e393–e423 (2017).

    Article  PubMed  Google Scholar 

  33. Whitehill, L. et al. Socio-demographic factors related to parent engagement in the NICU and the impact of the SENSE program. Early Hum. Dev. 163, 105486 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  34. Ioannidis, J. P. A., Powe, N. R. & Yancy, C. Recalibrating the use of race in medical research. JAMA 325, 623–624 (2021).

    Article  PubMed  Google Scholar 

  35. Kaplan, J. B. & Bennett, T. Use of race and ethnicity in biomedical publication. JAMA 289, 2709–2716 (2003).

    Article  PubMed  Google Scholar 

Download references

Funding

This study was supported by the National Institutes of Health (K23 HD 097254 [PI B.A.S.] and R01 HD 092071 [PI K.D.F.].

Author information

Authors and Affiliations

  1. Division of Neonatology, Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, VA, USA

    Brynne A. Sullivan & Karen D. Fairchild

  2. Colorado School of Public Health, Aurora, CO, USA

    Camille J. Hochheimer

  3. Department of Public Health Sciences, University of Virginia School of Medicine, Charlottesville, VA, USA

    Pavel Chernyavskiy

  4. Medical Predictive Sciences Corporation, Charlottesville, VA, USA

    William E. King

Authors
  1. Brynne A. Sullivan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Camille J. Hochheimer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pavel Chernyavskiy
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. William E. King
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Karen D. Fairchild
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; B.A.S. wrote the first draft of the manuscript and all other authors revised it critically for important intellectual content; and all authors gave final approval of the version to be published.

Corresponding author

Correspondence to Brynne A. Sullivan.

Ethics declarations

Competing interests

W.E.K. is Chief Executive Officer of Medical Predictive Science Corporation. The other authors declare no competing interests.

Ethics approval and consent to participate

This study analyzed data from a randomized clinical trial that required informed consent from a parent of every patient prior to enrollment.

Additional information

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

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sullivan, B.A., Hochheimer, C.J., Chernyavskiy, P. et al. Impact of race on heart rate characteristics monitoring in very low birth weight infants. Pediatr Res 94, 575–580 (2023). https://doi.org/10.1038/s41390-023-02470-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41390-023-02470-z

Search

Advanced search

Quick links