Journal of Clinical Immunology

, Volume 39, Issue 2, pp 200–206 | Cite as

Severe Transitory Neonatal Neutropenia Associated with Maternal Autoimmune or Idiopathic Neutropenia

  • Julie SeguierEmail author
  • Vincent Barlogis
  • Laure Croisille
  • Marie Audrain
  • Mikael Ebbo
  • Blandine Beaupain
  • Benoit Meunier
  • Blandine Vallentin
  • Rodolphe Jean
  • Jean-Robert Harle
  • Jean Donadieu
  • Nicolas Schleinitz
Original Article



Neonatal immune neutropenia is observed in rare cases in newborns from mothers with idiopathic or autoimmune neutropenia, secondary to passive transfer of maternal granulocyte auto-antibodies.


We performed a literature review and report four supplementary cases from the French registry of neutropenia.


Only 14 cases (11 mothers, 14 newborns) have been reported. Granulocyte aggregation (GAT) and granulocyte indirect immunofluorescence test (GIFT) are the recommended laboratory procedures for antibody detection. Monoclonal antibody-specific immobilization of granulocyte antigens (MAIGA)-confirmed antibody specificity.

Antibody detection in newborns is not generally possible owing to extreme neutropenia. In half of the cases autoantibodies against neutrophils (AAN) were positive in maternal sera (7 out of 11). In some newborns tested, IgG+ AAN were also positive, with disappearance in parallel of spontaneous neutrophil count improvement. No correlation between maternal type of AAN and titer and neonatal neutropenia can be established. Neutropenia resolved spontaneously between 2 weeks and 4 months. Infections in newborns were observed in 43% of cases, with no deaths reported. Granulocyte colony-stimulating factor (G-CSF) was administered to some newborns (5 out of 14) in the case of infections. Low-dose G-CSF administered to childbearing women during pregnancy could be proposed to prevent neutropenia in newborns.


From the few cases reported so far it is impossible to draw any conclusions regarding frequency, risk factors, and outcome, but the overall prognosis for newborns seems good. Because it can be associated with potentially severe neonatal infections, autoimmune neutropenia in childbearing mothers should be closely monitored in collaboration with gynecologists and pediatricians.


Neonatal neutropenia Autoimmune neutropenia Transitory neutropenia Anti-neutrophil antibody 


Compliance with Ethical Standards

Conflicts of Interest

The authors declared that they have no conflicts of interest.


  1. 1.
    Lalezari P, Khorshidi M, Petrosova M. Autoimmune neutropenia of infancy. J Pediatr. 1986;109(5):764–9.CrossRefGoogle Scholar
  2. 2.
    Farruggia P. Immune neutropenias of infancy and childhood. World J Pediatr. 2016;12(2):142–8.CrossRefGoogle Scholar
  3. 3.
    Bux J, Behrens G, Jaeger G, Welte K. Diagnosis and clinical course of autoimmune neutropenia in infancy: analysis of 240 cases. Blood. 1998;91(1):181–6.Google Scholar
  4. 4.
    Sicre de Fontbrune F, Moignet A, Beaupain B, Suarez F, Galicier L, Socié G, et al. Severe chronic primary neutropenia in adults: report on a series of 108 patients. Blood. 2015;126(14):1643–50.CrossRefGoogle Scholar
  5. 5.
    Fung YL, Pitcher LA, Taylor K, Minchinton RM. Managing passively acquired autoimmune neonatal neutropenia: a case study. Transfus Med. 2005;15(2):151–5.CrossRefGoogle Scholar
  6. 6.
    Davoren A, Saving K, McFarland JG, Aster RH, Curtis BR. Neonatal neutropenia and bacterial sepsis associated with placental transfer of maternal neutrophil-specific autoantibodies. Transfusion. 2004;44(7):1041–6.CrossRefGoogle Scholar
  7. 7.
    Kameoka J, Funato T, Miura T, Harigae H, Saito J, Yokoyama H, et al. Autoimmune neutropenia in pregnant women causing neonatal neutropenia. Br J Haematol. 2001;114(1):198–200.CrossRefGoogle Scholar
  8. 8.
    Van Leeuwen EF, Roord JJ, de Gast GC, Vander Plas-Van Dalen C. Neonatal neutropenia due to maternal autoantibodies against neutrophils. Br Med J (Clin Res Ed). 1983;287(6385):94.CrossRefGoogle Scholar
  9. 9.
    Stefanini M, Mele RH, Skinner D. Transitory congenital neutropenia: a new syndrome. Am J Med. 1958;25(5):749–58.CrossRefGoogle Scholar
  10. 10.
    Donadieu J, Beaupain B, Mahlaoui N, Bellanné-Chantelot C. Epidemiology of congenital neutropenia. Hematol Oncol Clin North Am. 2013;27(1):1–17.CrossRefGoogle Scholar
  11. 11.
    Donadieu J, Beaupain B, Fenneteau O, Bellanné-Chantelot C. Congenital neutropenia in the era of genomics: classification, diagnosis, and natural history. Br J Haematol. 2017;179(4):557–74.CrossRefGoogle Scholar
  12. 12.
    Capsoni F, Sarzi-Puttini P, Zanella A. Primary and secondary autoimmune neutropenia. Arthritis Res Ther. 2005;7(5):208–14.CrossRefGoogle Scholar
  13. 13.
    Bux J, Jung KD, Kauth T, Mueller-Eckhardt C. Serological and clinical aspects of granulocyte antibodies leading to alloimmune neonatal neutropenia. Transfus Med. 1992;2(2):143–9.CrossRefGoogle Scholar
  14. 14.
    Verheugt FW, von dem Borne AE, van Noord-Bokhorst JC, Engelfriet CP. Autoimmune granulocytopenia: the detection of granulocyte autoantibodies with the immunofluorescence test. Br J Haematol. 1978;39(3):339–50.CrossRefGoogle Scholar
  15. 15.
    Heinzl MW, Schönbacher M, Dauber E-M, Panzer S, Mayr WR, Körmöczi GF. Detection of granulocyte-reactive antibodies: a comparison of different methods. Vox Sang. 2015;108(3):287–93.CrossRefGoogle Scholar
  16. 16.
    Heinz WJ, Buchheidt D, Christopeit M, von Lilienfeld-Toal M, Cornely OA, Einsele H, et al. Diagnosis and empirical treatment of fever of unknown origin (FUO) in adult neutropenic patients: guidelines of the infectious diseases working party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO). Ann Hematol. 2017;96(11):1775–92.CrossRefGoogle Scholar
  17. 17.
    Simonsen KA, Anderson-Berry AL, Delair SF, Davies HD. Early-onset neonatal sepsis. Clin Microbiol Rev. 2014;27(1):21–47.CrossRefGoogle Scholar
  18. 18.
    Carr R, Modi N, Doré C. G-CSF and GM-CSF for treating or preventing neonatal infections. Cochrane Database Syst Rev. 2003;(3):CD003066.Google Scholar
  19. 19.
    Dale DC, Bolyard AA. An update on the diagnosis and treatment of chronic idiopathic neutropenia. Curr Opin Hematol. 2017;24(1):46–53.CrossRefGoogle Scholar
  20. 20.
    Boxer LA, Bolyard AA, Kelley ML, Marrero TM, Phan L, Bond JM, et al. Use of granulocyte colony-stimulating factor during pregnancy in women with chronic neutropenia. Obstet Gynecol. 2015;125(1):197–203.CrossRefGoogle Scholar
  21. 21.
    Zeidler C, Grote UAH, Nickel A, Brand B, Carlsson G, Cortesão E, et al. Outcome and management of pregnancies in severe chronic neutropenia patients by the European branch of the severe chronic neutropenia international registry. Haematologica. 2014;99(8):1395–402.CrossRefGoogle Scholar
  22. 22.
    Maheshwari A. Neutropenia in the newborn. Curr Opin Hematol. 2014;21(1):43–9.CrossRefGoogle Scholar
  23. 23.
    Lee JA, Sauer B, Tuminski W, Cheong J, Fitz-Henley J, Mayers M, et al. Effectiveness of granulocyte colony-stimulating factor in hospitalized infants with neutropenia. Am J Perinatol. 2017;34(5):458–64.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Julie Seguier
    • 1
    Email author
  • Vincent Barlogis
    • 2
  • Laure Croisille
    • 3
  • Marie Audrain
    • 4
  • Mikael Ebbo
    • 1
  • Blandine Beaupain
    • 5
  • Benoit Meunier
    • 1
  • Blandine Vallentin
    • 2
  • Rodolphe Jean
    • 6
  • Jean-Robert Harle
    • 1
  • Jean Donadieu
    • 5
  • Nicolas Schleinitz
    • 1
  1. 1.Aix-Marseille University, APHM, Médecine Interne Hôpital de la TimoneMarseilleFrance
  2. 2.Aix-Marseille University, APHM, Pédiatrie et hématologie pédiatrique Hôpital de la TimoneMarseilleFrance
  3. 3.Laboratoire HLA, EFS Ile de FranceCréteilFrance
  4. 4.Laboratoire d’immunologie, Institut de biologie, CHU de NantesNantesFrance
  5. 5.Service d’hématologie pédiatrique, Hôpital Trousseau, APHPParisFrance
  6. 6.Aix-Marseille University, APHM, Médecine Interne Hôpital de la ConceptionMarseilleFrance

Personalised recommendations