Association of placental histology and neonatal hematologic ... - Nature.com

Abstract

Objective

The objective of the paper was to investigate how neonatal hematologic outcomes vary by major placental histopathology categories.

Study design

Placental pathology reports from 5263 subjects were coded into individual placental lesions. Infant hematologic data (complete blood count parameters (n = 1945), transfusions, and phototherapy) were compared by placental pathologic phenotype.

Results

Red blood cell transfusions were more likely with maternal vascular malperfusion (MVM; OR 9.4 [2.2, 40.8]) and chronic inflammation (1.7 [1.04, 2.7]). White blood cells were decreased with MVM (10.6 103/μL vs 16.4) and elevated with acute inflammation (AI; 18.6 vs 11.9). Thrombocytopenia was associated with MVM (OR 3.7 [2.2, 5.1]) and fetal vascular malperfusion (FVM; OR 2.6 [1.5, 4.6]). Platelet transfusions were more likely with MVM (OR 8.3 [4.6, 15.0]) and FVM (OR 2.9 [1.4, 6.1]). Phototherapy was associated with MVM (OR 3.3 [2.7, 4.0]) and AI (OR 0.8 [0.6, 0.9]).

Conclusions

Neonatal hematologic outcomes are associated with the in utero environment described by placental pathology.

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

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

Buy

All prices are NET prices.

Fig. 1: Hematologic profiles by placental pathology.

Data availability

The datasets generated during and/or analyzed during the current study are not publicly available due to potential compromise of individual privacy, but are available from the corresponding author on reasonable request.

References

  1. Lewin S, Bussel JB. Review of fetal and neonatal immune cytopenias. Clin Adv Hematol Oncol. 2015;13:35–43.

    Google Scholar 

  2. Eaves LA, Enggasser AE, Camerota M, Gogcu S, Gower WA, Hartwell H, et al. CpG methylation patterns in placenta and neonatal blood are differentially associated with neonatal inflammation. Pediatr Res. 2022.

  3. Kush ML, Gortner L, Harman CR, Baschat AA. Sustained hematological consequences in the first week of neonatal life secondary to placental dysfunction. Early Hum Dev. 2006;82:67–72.

    Article  Google Scholar 

  4. Ernst LM. Maternal vascular malperfusion of the placental bed. APMIS. 2018;126:551–60.

    Article  Google Scholar 

  5. Voller SB, Chock S, Ernst LM, Su E, Liu X, Farrow KN, et al. Cord blood biomarkers of vascular endothelial growth (VEGF and sFlt-1) and postnatal growth: a preterm birth cohort study. Early Hum Dev. 2014;90:195–200.

    Article  Google Scholar 

  6. Mestan KK, Check J, Minturn L, Yallapragada S, Farrow KN, Liu X, et al. Placental pathologic changes of maternal vascular underperfusion in bronchopulmonary dysplasia and pulmonary hypertension. Placenta. 2014;35:570–4.

    Article  Google Scholar 

  7. Parks WT. Manifestations of hypoxia in the second and third trimester placenta. Birth Defects Res. 2017;109:1345–57.

    Article  Google Scholar 

  8. Parks WT. Placental hypoxia: the lesions of maternal malperfusion. Semin Perinatol. 2015;39:9–19.

    Article  Google Scholar 

  9. Koenig JM, Christensen RD. The mechanism responsible for diminished neutrophil production in neonates delivered of women with pregnancy-induced hypertension. Am J Obstet Gynecol. 1991;165:467–73.

    Article  Google Scholar 

  10. Koenig JM, Christensen RD. Incidence, neutrophil kinetics, and natural history of neonatal neutropenia associated with maternal hypertension. N Engl J Med. 1989;321:557–62.

    Article  Google Scholar 

  11. Wang Y, Gu Y, Philibert L, Lucas MJ. Neutrophil activation induced by placental factors in normal and pre-eclamptic pregnancies in vitro. Placenta. 2001;22:560–5.

    Article  Google Scholar 

  12. Litt JS, Hecht JL. Placental pathology and neonatal thrombocytopenia: lesion type is associated with increased risk. J Perinatol. 2014;34:914–6.

    Article  Google Scholar 

  13. Bester J, Pretorius E. Effects of IL-1beta, IL-6 and IL-8 on erythrocytes, platelets and clot viscoelasticity. Sci Rep. 2016;6:32188.

    Article  Google Scholar 

  14. Hom J, Dulmovits BM, Mohandas N, Blanc L. The erythroblastic island as an emerging paradigm in the anemia of inflammation. Immunol Res. 2015;63:75–89.

    Article  Google Scholar 

  15. Melvan JN, Bagby GJ, Welsh DA, Nelson S, Zhang P. Neonatal sepsis and neutrophil insufficiencies. Int Rev Immunol. 2010;29:315–48.

    Article  Google Scholar 

  16. Kuzniewicz MW, Puopolo KM, Fischer A, Walsh EM, Li S, Newman TB, et al. A quantitative, risk-based approach to the management of neonatal early-onset sepsis. JAMA Pediatr. 2017;171:365–71.

    Article  Google Scholar 

  17. American Academy of Pediatrics Subcommittee on Hyperbilirubinemia. Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics. 2004;114:297–316.

    Article  Google Scholar 

  18. Khong TY, Mooney EE, Ariel I, Balmus NC, Boyd TK, Brundler MA, et al. Sampling and definitions of placental lesions: Amsterdam Placental Workshop Group Consensus Statement. Arch Pathol Lab Med. 2016;140:698–713.

    Article  Google Scholar 

  19. Suresh SC, Freedman AA, Hirsch E, Ernst LM. A comprehensive analysis of the association between placental pathology and recurrent preterm birth. Am J Obstet Gynecol. 2022;227:887.e1–887.e15.

  20. Freedman AA, Keenan-Devlin LS, Borders A, Miller GE, Ernst LM. Formulating a meaningful and comprehensive placental phenotypic classification. Pediatr Dev Pathol. 2021;24:337–50.

    Article  Google Scholar 

  21. Haak MC, Oosterhof H, Mouw RJ, Oepkes D, Vandenbussche FP. Pathophysiology and treatment of fetal anemia due to placental chorioangioma. Ultrasound Obstet Gynecol. 1999;14:68–70.

    Article  Google Scholar 

  22. Zook KJ, Mackley AB, Kern J, Paul DA. Hematologic effects of placental pathology on very low birthweight infants born to mothers with preeclampsia. J Perinatol. 2009;29:8–12.

    Article  Google Scholar 

  23. La Gamma EF, Alpan O, Kocherlakota P. Effect of granulocyte colony-stimulating factor on preeclampsia-associated neonatal neutropenia. J Pediatr. 1995;126:457–9.

    Article  Google Scholar 

  24. Joslyn P, Rosenbaum C, Chapple AG, Heard A, Velez M, Barkemeyer B. The effects of maternal hypertension on the early neonatal platelet count. J Perinatol. 2022;42:796–802.

    Article  Google Scholar 

  25. Dubruc E, Lebreton F, Giannoli C, Rabilloud M, Huissoud C, Devouassoux-Shisheboran M, et al. Placental histological lesions in fetal and neonatal alloimmune thrombocytopenia: a retrospective cohort study of 21 cases. Placenta. 2016;48:104–9.

    Article  Google Scholar 

  26. Giesbers S, Bos M, Bulten J, van der Meeren L, van Drongelen J. Subamniotic hemorrhage, a possible new presentation of fetal and neonatal alloimmune thrombocytopenia. Fetal Diagn Ther. 2022;49:60–4.

    Article  Google Scholar 

  27. Macias RI, Marin JJ, Serrano MA. Excretion of biliary compounds during intrauterine life. World J Gastroenterol. 2009;15:817–28.

    Article  Google Scholar 

  28. Jemnitz K, Heredi-Szabo K, Janossy J, Ioja E, Vereczkey L, Krajcsi P. ABCC2/Abcc2: a multispecific transporter with dominant excretory functions. Drug Metab Rev. 2010;42:402–36.

    Article  Google Scholar 

  29. Briz O, Serrano MA, MacIas RI, Gonzalez-Gallego J, Marin JJ. Role of organic anion-transporting polypeptides, OATP-A, OATP-C and OATP-8, in the human placenta-maternal liver tandem excretory pathway for foetal bilirubin. Biochem J. 2003;371:897–905.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pediatrics, Division of Neonatology, NorthShore University HealthSystem, Evanston, IL, USA

    Andrew D. Franklin

  2. Department of Obstetrics and Gynecology, NorthShore University HealthSystem, Evanston, IL, USA

    Alexa Freedman

  3. Department of Pathology and Laboratory Medicine, NorthShore University HealthSystem, Evanston, IL, USA

    Linda M. Ernst

  4. Department of Pathology, University of Chicago Pritzker School of Medicine, Chicago, IL, USA

    Linda M. Ernst

Authors
  1. Andrew D. Franklin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alexa Freedman
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Linda M. Ernst
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

ADF conceptualized and designed the study, assisted with data analysis and interpretation, drafted the initial manuscript, and reviewed and revised the manuscript. AF performed the statistical analysis, assisted with data collection, and reviewed and revised the manuscript. LME conceptualized and designed the study, interpreted data, and reviewed and revised the manuscript. All authors approve the final manuscript as submitted and agree to be accountable for all aspects of the work.

Corresponding author

Correspondence to Andrew D. Franklin.

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

Verify currency and authenticity via CrossMark

Cite this article

Franklin, A.D., Freedman, A. & Ernst, L.M. Association of placental histology and neonatal hematologic outcomes. J Perinatol (2022). https://doi.org/10.1038/s41372-022-01595-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1038/s41372-022-01595-z

Popular posts from this blog