Published online November 1, 2005
PEDIATRICS Vol. 116 No. 5 November 2005, pp. 1260-1261 (doi:10.1542/10.1542/peds.2005-1677)

This Article Extract Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services E-mail this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to My File Cabinet Download to citation manager Request Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Zanardo, V. Articles by Chiarelli, S. Search for Related Content PubMed PubMed Citation Articles by Zanardo, V. Articles by Chiarelli, S. Related Collections Blood Social Bookmarking                         What's this?

Leukemoid Reaction and Bronchopulmonary Dysplasia: A Primary Inflammatory Mechanism?

Vincenzo Zanardo, MD
Stefania Vedovato, MD
Daniele Trevisanuto, MD
Department of Pediatrics

Silvia Chiarelli, MD
Department of Oncological and Surgical Sciences
Padua University
35100 Padua, Italy

To the Editor.—

We read with great interest "Outcome of Extremely Low Birth Weight Infants With Leukemoid Reaction" by Hsiao and Omar.¹ Their objective was to examine the effect of leukemoid reaction (LR) in morbidity, mortality, and long-term developmental outcome in extremely low birth weight (ELBW) infants. The study showed that LR in ELBW infants is associated with a higher incidence of bronchopulmonary dysplasia (BPD), compared with no-LR infants.

Although hypothesized in their discussion, the study by Hsiao and Omar did not investigate if LR in ELBW infants is associated with conditions known to present an excess of proinflammatory cytokines. It is worth clarifying this aspect, because neonatal LR seemed to be the kinetic result of a transient acceleration in neutrophil production by granulocyte colony-stimulating factor (G-CSF).² G-CSF is one of the key cytokines that orchestrate the granulopoiesis,³ mediate inflammation-induced preterm labor,⁴ accelerate fetal lung maturity, inducing surfactant synthesis,⁵ and produce neonatal LR postnatally in sufficiently high doses.⁶ Nevertheless, in a recent case-control study of preterm infants with a gestational age of <32 weeks, BPD was associated with a higher incidence of LR (5 of 50 vs 0 of 50; P = .001), and it was postulated that the similarities of a primary inflammatory mechanism underlie the development of an LR and BPD.⁷

To evaluate the possible relationship between histologic chorioamnionitis (HCA) and LR, we currently are performing a prospective study of premature infants with a gestational age of <32 weeks, 6 days who were admitted to a perinatal center. We hypothesized that exposure to prenatal inflammation, indicated as histologically diagnosed chorioamnionitis, would be associated with an increased incidence of LR and that patients with LR would exhibit a prenatal systemic inflammatory response.

Of 61 preterm neonates with HCA, 8 (13%) developed LR, whereas 4 of 162 (2%) preterm infants without HCA developed LR (odds ratio: 5.2; 95% confidence interval: 1.5–18.1). Neonates with both LR and HCA differ from neonates with LR and without HCA in terms of delivery modalities (62% vs 100% cesarean delivery; P < .01), gestational age (26 ± 1.6 vs 29.7 ± 1.7 weeks; P < .01), and percentage of BPD (63% vs 25%; P < .01).

By studying the relationship between LR and HCA, we identified 2 populations of low birth weight infants with LR who differ for maternal history, neonatal characteristics, and respiratory sequelae. We therefore believe that different pathogenetic mechanisms other than HCA are involved in LR occurrence, and new studies are necessary to better understand this life-threatening phenomenon of NICU-admitted low birth weight infants.

REFERENCES

1. Hsiao R, Omar SA. Outcome of extremely low birth weight infants with leukemoid reaction. Pediatrics. 2005;116 (1). Available at: www.pediatrics.org/cgi/content/full/116/1/e43
2. Calhoun DA, Kirk JF, Cristensen RD. Incidence, significance, and kinetic mechanism responsible for leukemoid reaction inpatients in the neonatal intensive care unit: a prospective evaluation. J Pediatr. 1996;129 :403 –409[CrossRef][Web of Science][Medline]
3. Cairo MS. Therapeutic implications of dysregulated colony-stimulating factor expression in neonates. Blood. 1993;82 :2269 –2272[Free Full Text]
4. Goldemberg RL, Andrews WW, Mercer BM, et al. The preterm prediction study: granulocyte colony-stimulating factor and spontaneous preterm birth. Am J Gynecol. 2000;182 :625 –630
5. Hallman M. Cytokines, pulmonary surfactant and consequences of intrauterine infection. Biol Neonate. 1999;76 :2 –9
6. Gillan ER, Christiansen RD, Suen Y, Ellis R, van de Ven C, Cairo MS. A randomized, placebo-controlled trial of recombinant human granulocyte colony-stimulating factor administration in newborn infants with presumed sepsis: significant induction of peripheral and bone marrow neutrophilia. Blood. 1994;84 :1427 –1433[Abstract/Free Full Text]
7. Zanardo V, Savio V, Giacomin C, Rinaldi A, Marzari F, Chiarelli S. Relationship between neonatal leukemoid reaction and bronchopulmonary dysplasia in low-birth-weight infants: a cross-sectional study. Am J Perinatol. 2002;19 :379 –386[CrossRef][Web of Science][Medline]

---

PEDIATRICS (ISSN 1098-4275). ©2005 by the American Academy of Pediatrics

CiteULike    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This Article Extract Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services E-mail this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to My File Cabinet Download to citation manager Request Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Zanardo, V. Articles by Chiarelli, S. Search for Related Content PubMed PubMed Citation Articles by Zanardo, V. Articles by Chiarelli, S. Related Collections Blood Social Bookmarking                         What's this?