Published online December 1, 2006
PEDIATRICS
Vol. 118
No. 6
December 2006, pp.
2543-2544
(doi:10.1542/peds.2006-2066)
Neonatal Herpes in Premature Infants: A Special Problem
Lawrence R. Stanberry, MD, PhD
Department of Pediatrics and the Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, Texas
Abbreviations: HSV, herpes simplex virus • PCR, polymerase chain reaction
The study by O'Riordan et al1 in this issue of Pediatrics focuses our attention on the special problem of herpes simplex virus (HSV) infections in premature infants. We recognize the deadly and complex nature of neonatal herpes, thanks to an exceptional body of work by Whitley, Arvin, Prober, Kimberlin, Nahmias, Corey, Brown, and other luminaries. Their research has established the role of mother-to-infant transmission in most cases.2 This body of work has clarified that most mothers of infected infants have no known history of genital herpes but may have a history of other sexually transmitted diseases and demonstrated that maternal immunity to HSV infection affords some type-specific immunity to the infant.3,4 They have shown the importance of cesarean delivery in reducing but not eliminating the risk of mother-to-infant transmission.5,6 These investigators developed the classification system that distinguishes between disease apparently limited to the portals of entry (the skin, eyes, and mouth) and more severe forms of encephalitis and disseminated infection.7 They have documented the aggressive nature of HSV infection of the newborn and demonstrated the importance of early prompt antiviral treatment in reducing morbidity and mortality.7–10 They have increased our awareness of neonatal HSV infection and guided our thinking about when to consider the diagnosis and how to approach the management of the infant with proven or suspected neonatal herpes. Although earlier studies of neonatal herpes included premature infants, the retrospective review by O'Riordan et al looks exclusively at this unique population. Relative to healthy term newborns who generally develop clinical signs of neonatal herpes after discharge from the nursery, premature infants, especially those of <32 weeks' gestation, frequently have complex medical conditions that may mask subtle signs of HSV infection. The study by O'Riordan et al finds that, as with older infants, premature infants with neonatal HSV infection were most often born to women without history of genital herpes and without evidence of genital herpes-like lesions at delivery. Similarly, the vesicular skin lesions that are characteristic of HSV infections were present in less than half of preterm or term infants with proven neonatal herpes. Other less pathognomonic findings of neonatal herpes such as lethargy, hypotension, temperature instability, and elevated aspartate aminotransferase levels were inconsistently observed in the HSV-infected preterm infants. However, 2 findings, respiratory distress and thrombocytopenia, were present in 100% and 73% of infected premature infants, respectively. Because respiratory distress resulting from noninfectious causes is common among ill preterm infants, it is unlikely that respiratory distress alone will arouse much suspicion of neonatal herpes, especially when one considers that only 12 cases of proven neonatal HSV infection occurred among 4440 preterm infants at Johns Hopkins Hospital over a 15-year period. Suspicion of HSV infection may be aroused by a maternal history of genital herpes or other sexually transmitted infections and a constellation of findings. These findings could include respiratory distress, particularly deteriorating respiratory status, in combination with 1 or more of the following findings: thrombocytopenia, elevated aspartate aminotransferase levels, vesicular skin lesions, or seizures. The clinical diagnosis of HSV infection is notoriously unreliable, and laboratory tests are critical in establishing the diagnosis. The highest yield in the O'Riordan study was by culture of endotracheal and oropharyngeal or nasopharyngeal secretions; however, samples from other sites were positive in some patients. This observation and similar findings from other studies suggest that when considering the diagnosis of neonatal herpes, tests from multiple sites should be the rule. Targeting sites for culture or polymerase chain reaction (PCR) should generally be directed by clinical findings. When lesions are present, they should be cultured; infants with respiratory distress should have endotracheal and/or pharyngeal secretions cultured; those with evidence of disseminated infection should have blood cultured or tested by PCR; and regardless of specific clinical findings, in most cases the cerebrospinal fluid should be examined by PCR. Such evaluation can occur even after initiation of intravenous acyclovir, because it is possible to detect HSV by culture or PCR for several days after therapy has begun. As with the infants described in the O'Riordan et al report, when neonatal herpes is suspected, therapy should never be delayed while awaiting culture or PCR results. Given the poor outcomes of the premature infants described in the O'Riordan et al report, this is particularly critical even when faced with the complex decision-making of the myriad reasons that premature infants could have some of these symptoms.
The report by O'Riordan et al is particularly dramatic in illustrating the devastating nature of neonatal HSV infection, with 9 of the 12 infants dying and 2 of the 3 survivors known to have neurologic sequelae. Premature infants, especially those of <25 weeks' gestation, may be more vulnerable because of greater immaturity of their immune system and less opportunity to acquire protective maternal HSV antibodies. The poor outcome reported by O'Riordan et al occurred despite the superb care available at Johns Hopkins Hospital and points to the need for more rapid diagnostic tests, more effective antiviral therapy, and, most of all, the development of effective vaccines to prevent HSV infections.11,12
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FOOTNOTES
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Accepted Jul 26, 2006.
Address correspondence to Lawrence R. Stanberry, MD, PhD, Department of Pediatrics and the Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, 301 University Blvd, Galveston, TX 77555-0351. E-mail: l.stanberry{at}utmb.edu
The author has indicated he has no financial relationships relevant to this article to disclose.
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PEDIATRICS (ISSN 1098-4275). ©2006 by the American Academy of Pediatrics
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