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Are elevated peripheral leukocytes markers of septic etiology in asphyxiated infants with neurological disability?

Journal of Perinatology volume 28, page 85 (2008)Cite this article

I read with interest the recent publication by Morkos AA et al.1 demonstrating the association between elevated leukocyte and neutrophil counts and poor neurological outcome following neonatal asphyxia. Neutrophils are known to mediate injury in acute ischemic stroke, especially during reperfusion. Hashimoto M et al.2 demonstrated reduced neutrophil expression of the adhesion molecule L-selectin (shed prior to neutrophil infiltration) in neonates with severe asphyxia. Recently the assessment of L-selectin cleavage on neutrophils has also been shown to be useful for the detection of Toll-like receptor pathway anomalies resulting in abnornal sepsis responses.3 Endotoxin dramatically sensitizes the immature brain to injury and induces cerebral infarction in response to short periods of hypoxia–ischemia that by themselves caused no or little injury. Both CD14 and Toll-like receptor-4 mRNA in the brain were altered in association with this sensitization of injury.4 In addition, clinical chorioamnionitis is independently associated with a four fold increased risk of cerebral palsy in term infants and a history of birth asphyxia was also strongly predictive of cerebral palsy.5 Did the authors find increased evidence of infection in infants with poor neurological outcomes, such as elevated C-reactive protein, positive bacterial cultures (blood or cerebrospinal fluid), maternal pyrexia or histological chorioamnionitis? I wondered if any records of cranial imaging, such as cranial ultrasounds, during the documented neutrophilia and leukocytosis were available to the authors.

Note: Incidentally Figures 1 and 2 raised some confusing points as both appeared to show elevated white blood cells and absolute neutrophil count (ANC) in the infants with good neurological outcomes. I assume that this is a case of mislabelling of the legends of these Figures.

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References

  1. Morkos AA, Hopper AO, Deming DD, Yellon SM, Wycliffe N, Ashwal S et al. Elevated total peripheral leukocyte count may identify risk for neurological disability in asphyxiated term neonates. J Perinatol 2007; 27: 365–370.

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  2. Hashimoto M, Nishida A, Minakami H, Takashima Y, Kato M, Okada Y et al. Decreased expression of L-selectin on peripheral blood polymorphonuclear leukocytes in neonates with severe asphyxia. Biol Neonate 2002; 81: 95–98.

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  4. Eklind S, Mallard C, Leverin AL, Gilland E, Blomgren K, Mattsby-Baltzer I et al. Bacterial endotoxin sensitizes the immature brain to hypoxic—ischaemic injury. Eur J Neurosci 2001; 13: 1101–1106.

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  5. Wu YW, Escobar GJ, Grether JK, Croen LA, Greene JD, Newman TB . Chorioamnionitis and cerebral palsy in term and near-term infants. JAMA 2003; 290: 2677–2684.

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  1. National Maternity Hospital, Holles Street, Dublin, Dublin, Ireland. E-mail: elesean@hotmail.com,

    E Molloy

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Molloy, E. Are elevated peripheral leukocytes markers of septic etiology in asphyxiated infants with neurological disability?. J Perinatol 28, 85 (2008). https://doi.org/10.1038/sj.jp.7211855

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