Chorioamnionitis, Cytokines, and Brain Injury
John M. Freeman, MDJohns Hopkins University
Pediatric Epilepsy Center
Baltimore, MD 21287-7247
To the Editor.—
The important study by Shalak et al1 unfortunately left me confused and perplexed. Their stated purpose was to determine if any of the cytokines "were correlated with short-term neonatal neurologic outcomes including depression at birth ... and hypoxic-ischemic encephalopathy." They have indeed found such a correlation but have, I believe, misdiagnosed "hypoxic-ischemic encephalopathy" (HIE).
The authors state that HIE and/or seizures were defined in accordance with recommendations of the American Academy of Pediatrics and the American College of Obstetricians and Gynecologists. These criteria are unfortunately stated out of context. The presence of the findings of low Apgar scores at 5 minutes and a low cord pH, etc, were not meant to make a positive diagnosis of hypoxic-ischemic injury, but to exclude a hypoxic cause for subsequent neurologic deficit.2 Thus, in the absence of signs of encephalopathy, one could not claim that the cerebral palsy, mental retardation, or other neurologic deficit was the result of hypoxic injury. However, in the presence of these signs, one could ask if this encephalopathy was attributable to hypoxic/ischemic injury. The article by Shalak et al1 adds additional documentation to the growing body of evidence that the constellation of symptoms that were often termed signs of "birth asphyxia" or "HIE" may be attributable to multiple etiologies—including chorioamnionitis. As was recently stated by Nelson, "The diagnoses of HIE is not warranted unless there is positive evidence of interruption to oxygen supply as a precipitating pathologic event."3 Perhaps we should all use the descriptive term neonatal encephalopathy, as did Willoughby in his accompanying commentary,4 and avoid ascribing a cause when the cause is unsubstantiated. When, in the future, we can accurately identify a cause, there may be specific, major therapeutic implications.
REFERENCES
- Shalak LF, Laptook AR, Jafri HS, Ramilo O, Perlman JM. Clinical chorioamnionitis, elevated cytokines, and brain injury in term infants.
Pediatrics.2002; 110
:673
–680
[Abstract/Free Full Text] - Freeman JM, Nelson KB. Intrapartum asphyxia and cerebral palsy.
Pediatrics.1988; 82
:240
–249
[Abstract/Free Full Text] - Nelson KB. The epidemiology of cerebral palsy in term infants. Ment Retard Dev Dis Res Rev.2002; 8 :146 –150
- Willoughby RE. Maternal infections are depressing.
Pediatrics.2002; 110
:832
–833
[Free Full Text]
Lina F. Shalak, MD
Abbot R. Laptook, MD
Jeffrey M. Perlman, MB
UT Southwestern Medical Center
Department of Pediatrics
Dallas, TX 75390-9063
We appreciate the interest and comments of Dr Freeman regarding our article.1 His comments, as always, are provocative and thoughtful. However, we have to disagree with him regarding the diagnosis of HIE. We agree that the constellation of findings of a low Apgar score and low cord pH in the absence of encephalopathy, cannot be equated with hypoxic-ischemic cerebral injury. Indeed, we and others have shown the resilience of the fetal brain to severe stress, ie, pathologic fetal acidemia (umbilical cord pH: <7.00). Thus, the overwhelming majority of infants delivered under these conditions are triaged to a regular newborn nursery, and have an uncomplicated clinical course.2 The infants in our report had to have evidence of an acute intrapartum insult (sentinel event) followed by signs of perinatal depression (low Apgar score, low cord pH) and then followed by signs of encephalopathy (at least stage 2 or 3 Sarnat3) to fulfill the criteria for the diagnosis of HIE. Moreover, 3 of the 5 infants had evidence of bilateral diffuse infarction on magnetic resonance imaging. The constellation of findings strongly support the diagnosis of acute hypoxic-ischemic cerebral injury that manifested as an encephalopathy. We concur with Dr Freeman that acute hypoxic-ischemic cerebral injury resulting in encephalopathy may be a consequence of multiple etiologies including chorioamnionitis. Indeed, we discuss this point in the concluding paragraph of the article.
REFERENCES
- Shalak LF, Laptook AR, Jafri HS, Ramilo O, Perlman JM. Clinical chorioamnionitis, elevated cytokines, and brain injury in term infants. Pediatrics.2002; 110 :673 –680
- King TA, Jacksin JL, Josey AS, et al. The effect of profound umbilical artery acidemia in term neonates admitted to a newborn nursery. J Pediatr.1998; 132 :624 –629[CrossRef][Web of Science][Medline]
- Sarnat HB, Sarnat MS. Neonatal encephalopathy following fetal distress: clinical and electrographic presentation. Arch Neurol.1976; 33 :669 –773
PEDIATRICS (ISSN 1098-4275). ©2003 by the American Academy of Pediatrics
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