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.

  • Brief Communication
  • Published:

Feasibility of a non-invasive method to assess fetal hemolysis in utero during the third trimester

Journal of Perinatology volume 43, pages 1437–1439 (2023)Cite this article

Subjects

Hemolytic disease of the fetus and newborn (HDFN) occurs when the lifespan of fetal/neonatal red blood cells is significantly shortened, elevating bilirubin production and increasing the risk of anemia [1]. During a pregnancy where HDFN is known or suspected, fetal blood sampling by cordocentesis can be used to assess the presence of anemia and quantify its severity. However, such sampling carries procedure-related risks, thus non-invasive means of detecting fetal anemia have been evaluated. A useful method is middle cerebral artery (MCA) doppler peak systolic flow velocity [2]. Despite its utility, limitations are well known. These include false positive rates of 6 to 15%, particularly after 32–34 weeks gestation [2]. Additionally, cases of fetal hemolytic disease that are not severe enough to cause fetal anemia can, never-the-less, result in severe neonatal hyperbilirubinemia. On that basis, an MCA doppler reading is not always predictive of whether severe neonatal jaundice will be a problem [1, 2].

To our knowledge, detecting fetal hemolysis in utero by measuring maternal ETCOc has not previously been reported. Therefore, we initially assessed, in a small pilot study, whether measuring maternal ETCOc during the third trimester when a woman was carrying a fetus with a hemolytic condition would even be feasible. We also desired to assess whether ETCOc values would be elevated in these women, and if so whether it would fall to normal after delivery, and whether their neonate would have an elevated ETCOc to potentially explain a slightly elevated reading in the pregnant mother. To accomplish this, we approached women in our Intermountain Health high-risk pregnancy clinics who had a diagnosis of HDFN and were ≥ 32 weeks. With their consent, we attempted serial ETCOc measurements between 32 weeks and delivery, and again after delivery, and on their newborn infants.

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: Schematic representation.

Data availability

Deidentified data will be shared on request to the corresponding author.

References

  1. de Winter DP, Kaminski A, Tjoa ML, Oepkes D. Hemolytic disease of the fetus and newborn: systematic literature review of the antenatal landscape. BMC Pregnancy Childbirth. 2023;23:12.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Lyu CJ, Xu C, Yu J, Xia LP. Diagnostic performance of doppler ultrasonography for the detection of fetal anemia: a meta-analysis. Ultrasound Q. 2019;35:339–45.

    Article  PubMed  Google Scholar 

  3. Christensen RD, Lambert DK, Henry E, Yaish HM, Prchal JT. End-tidal carbon monoxide as an indicator of the hemolytic rate. Blood Cells Mol Dis. 2015;54:292–6.

    Article  CAS  PubMed  Google Scholar 

  4. Christensen RD, Malleske DT, Lambert DK, Baer VL, Prchal JT, Denson LE, et al. Measuring end-tidal carbon monoxide of jaundiced neonates in the birth hospital to identify those with hemolysis. Neonatology. 2016;109:1–5.

    Article  CAS  PubMed  Google Scholar 

  5. Pakdeeto S, Christensen TR, Bahr TM, Gerday E, Sheffield MJ, Christensen KS, et al. Reference intervals for end tidal carbon monoxide of preterm neonates. J Perinatol. 2022;96:448–50.

    Google Scholar 

  6. Friedman P, Guo XM, Stiller RJ, Laifer SA. Carbon monoxide exposure during pregnancy. Obstet Gynecol Surv. 2015;70:705–12.

    Article  PubMed  Google Scholar 

  7. Baum M, Schiff E, Kreiser D, Dennery PA, Stevenson DK, Rosenthal T, et al. End-tidal carbon monoxide measurements in women with pregnancy-induced hypertension and preeclampsia. Am J Obstet Gynecol. 2000;183:900–3.

    Article  CAS  PubMed  Google Scholar 

  8. Kreiser D, Baum M, Seidman DS, Fanaroff A, Shah D, Hendler I, et al. End tidal carbon monoxide levels are lower in women with gestational hypertension and pre-eclampsia. J Perinatol. 2004;24:213–7.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Sasikarn Pakdeeto MD, Neonatology, Mahidol University, Bangkok, Thailand for the original illustration and for reviewing the manuscript. We also thank Molly Adams, Intermountain Health Research, for assistance with the IRB review. We also thank Paul Vanasco MT(ASCP) and Terry Rees MT(ASCP)(SBB) of the Intermountain Health Transfusion Service for expert technical assistance. We also thank Robert L. Andres MD, Paul W. Whitecar MD, Douglas S. Richards MD, and Ibrahim A. Hammad, MD for referring patients for study.

Author information

Authors and Affiliations

  1. Obstetric and Neonatal Operations, Intermountain Health, Murray, UT, USA

    Timothy M. Bahr & Robert D. Christensen

  2. Division of Neonatology, Department of Pediatrics, University of Utah, Salt Lake City, UT, USA

    Timothy M. Bahr & Robert D. Christensen

  3. Student, University of Utah, Salt Lake City, UT, USA

    Thomas R. Christensen

  4. Student, University of Georgia, Athens, GA, USA

    Lillian S. Cheatham

  5. Division of Maternal-Fetal Medicine, Intermountain Health, Murray, Utah and Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Utah, Salt Lake City, UT, USA

    Jessica M. Page

Authors
  1. Timothy M. Bahr
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Thomas R. Christensen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lillian S. Cheatham
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jessica M. Page
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Robert D. Christensen
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

TMB, conception and design, assembly of data, data analysis, manuscript writing, final approval of the manuscript. TRC, collection of ETCOc samples from mothers and neonates, manuscript writing, and final approval of the manuscript. LSC, collection of ETCOc samples from mothers and neonates and final approval of the manuscript. JMP, manuscript writing, and final approval of the manuscript. RDC, conception and design, collection and assembly of data, data analysis and interpretation, original draft of the manuscript, writing, revising, and approving the last version of the manuscript.

Corresponding author

Correspondence to Timothy M. Bahr.

Ethics declarations

Competing interests

The authors declare no competing interests.

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

Bahr, T.M., Christensen, T.R., Cheatham, L.S. et al. Feasibility of a non-invasive method to assess fetal hemolysis in utero during the third trimester. J Perinatol 43, 1437–1439 (2023). https://doi.org/10.1038/s41372-023-01764-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41372-023-01764-8

Search

Advanced search

Quick links