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The incidence of neonatal herpes infection

      Objective

      The incidence of perinatal transmission of neonatal herpes infection has recently been reported at 1 in 3200 births. The main objective of this study was to determine a population-based incidence of neonatal herpes simplex virus infection.

      Study Design

      This was a retrospective chart review of newborn infants presenting with herpes infection established by cerebrospinal fluid polymerase chain reaction or lesion culture between 1999 and 2003. Only infants delivered at our institution were considered to establish a population-based incidence.

      Results

      Four cases of neonatal herpes infection were identified based on polymerase chain reaction and culture diagnosis. During the study period 78,115 infants were delivered at our institution yielding an incidence of 1 in 20,000 live births.

      Conclusion

      The incidence of neonatal herpes infection at our institution is lower than reported elsewhere. A national surveillance program of neonatal herpes is needed to measure the burden of disease across the United States.

      Key words

      The outcome of neonatal herpes (HSV) infection has improved dramatically over the past 20 years with the advent of progressive antiviral treatment, yet mortality and morbidity still remain a significant concern. We originally reported an incidence of neonatal herpes from 1988 through 1993 as 1 in 33,000 live births at our institution, a publicly supported county facility.
      • Roberts S.W.
      • Cox S.M.
      • Dax J.
      • et al.
      Genital herpes during pregnancy: no lesions, no cesarean.
      More recently, the incidence of neonatal herpes infection has been reported to be as high as 1 in 3200 live births
      • Brown Z.A.
      • Wald A.
      • Morrow R.A.
      • Selke S.
      • Zeh J.
      • Corey L.
      Effect of serologic status and cesarean delivery on transmission rates of herpes simplex virus from mother to infant.
      ; this would result in an estimated 1500 new cases annually in America. We sought to measure the contemporary incidence of neonatal herpes in our population.

      Materials and Methods

      Infants from birth to 28 days of age diagnosed with neonatal herpes infection were identified with the existing ICD-9 codes 771 (infections specific to the perinatal period) and 771.2 (other congenital infections) from medical records at Parkland Hospital. Records at the adjacent Children’s Medical Center Dallas hospital were also reviewed to capture all cases of neonatal herpes admitted after the delivery discharge. Only records of infants delivered at our institution between 1999 and 2003 were included for incidence determination. For inclusion in the study, a diagnosis of neonatal herpes required identification of HSV by culture or cerebrospinal fluid (CSF) polymerase chain reaction (PCR).

      Results

      In the 5-year study period from 1999-2003, 78,115 infants were delivered at our institution. Four cases of neonatal herpes infection were identified, yielding an incidence of 5.1 per 100,000 (95% CI 1.4/100,000-13.1/100,000) live births.
      Two cases were admitted to the neonatal intensive care unit at the county hospital and 2 to the specialized children’s hospital pediatric service with neonatal HSV infection. Admissions occurred at a median of 15 days from delivery with a range of 1-28 days. One infant, admitted to the neonatal intensive care unit at 31 weeks for respiratory distress, developed skin lesions after 7 days. Three subjects were diagnosed with skin, eye, and/or mouth (SEM) disease by HSV culture: 1 with HSV-1, and 2 with HSV-2 infection. One diagnosis of central nervous system disease was made by CSF PCR. All infants were treated with intravenous acyclovir. All were discharged alive. Long-term follow-up was not available.
      The median age of mothers of infected infants was 23 years with a range of 21-29 years. Three women were black and 1 was white. The mean age of all mothers delivered at our institution during the study period was 25 years, and the racial distribution was 81% Hispanic, 13% black, and 4% white. No mothers had visible herpes lesions at delivery, nor a history of genital herpes infection. All had spontaneous vaginal deliveries with rupture of membranes, and 1 woman had prolonged rupture of membranes, longer than 24 hours.

      Comment

      The incidence of neonatal herpes infection is lower at our institution than reported elsewhere in the United States. Recently, Brown et al
      • Brown Z.A.
      • Wald A.
      • Morrow R.A.
      • Selke S.
      • Zeh J.
      • Corey L.
      Effect of serologic status and cesarean delivery on transmission rates of herpes simplex virus from mother to infant.
      reported a 1 in 3200 (31.2 per 100,000) incidence of neonatal herpes infection in a Seattle community, a statistic that is widely used as the incidence of disease in the United States. An estimate of the incidence in California has remained steady at about 11 in 100,000 deliveries from 1985-1995.
      • Gutierrez K.M.
      • Falkovitz-Halpern M.S.
      • Maldonado Y.
      • et al.
      The epidemiology of neonatal herpes simplex virus infections in California from 1985 to 1995.
      In 1989 a national surveillance conducted by the Center for Disease Control found an incidence of 4 in 100,0000.
      • Stone K.M.
      • Brooks C.A.
      • Guinan M.E.
      • Alexander E.R.
      National surveillance for neonatal herpes simplex virus infections.
      Nahmias
      • Nahmias A.J.
      Neonatal HSV infection Part II: obstetric considerations—a tale of hospitals in two cities (Seattle and Atlanta, USA).
      recently reported on an Atlanta population with a rate of 15-20 cases of neonatal herpes per 100,000 deliveries from 1996-999. In comparison, most developed countries have low rates of neonatal herpes, less than 5 per 100,000.
      • Freedman E.
      • Mindel A.
      • Jones C.A.
      Epidemiological, clinical and laboratory aids for the diagnosis of neonatal herpes—an Australian perspective.
      • Gaytant M.A.
      • Steegers E.A.
      • van Cromvoirt P.L.
      • et al.
      Incidence of herpes neonatorum in Netherlands.
      • Fonnest G.
      • de la Fuente Fonnest I.
      • Weber T.
      Neonatal herpes in Denmark 1977-1991.
      • Kropp R.Y.
      • Wong T.
      • Cormier L.
      • et al.
      Neonatal herpes simplex virus infections in Canada: results of a 3-year national prospective study.
      • Fleming D.T.
      • McQuillan G.M.
      • Johnson R.E.
      • et al.
      Herpes simplex virus type 2 in the United States, 1976 to 1994.
      This wide discrepancy in reporting may be attributed to community based seroprevalence of HSV disease, method of detection, and ascertainment of neonatal herpes infection. We do not believe that the majority of important diagnoses of neonatal herpes were missed in our system, because the 2 hospitals provide the overwhelming amount of medical care to infants born at Parkland Hospital. It is possible that disease of lesser severity did not present to the hospital.
      This study has several limitations. We do not know the specific prevalence of HSV-1 and 2 seropositivity in our population. Estimates of HSV-2 seropositivity in Mexican-Americans (15% and 29%) are close to that of whites (15% and 22%) when considering 20-29 year old and 30-39 year old age groups respectively in the United States.
      • Fleming D.T.
      • McQuillan G.M.
      • Johnson R.E.
      • et al.
      Herpes simplex virus type 2 in the United States, 1976 to 1994.
      We note that in our population, comprised of 81% Hispanic mothers, there were no cases of neonatal herpes.
      Some degree of controversy exists about the actual incidence of neonatal herpes in the United States because it is not a disease that must be reported to the CDC, and because there are such wide variations in the published rates of infection in different geographic areas. Ascertainment bias inherent to systems locked into retrospective reporting of important diseases may underestimate the true incidence. The lack of an ICD-9 code specific for neonatal herpes is also a limitation to our study as it is to others.
      • Nahmias A.J.
      Neonatal HSV infection Part II: obstetric considerations—a tale of hospitals in two cities (Seattle and Atlanta, USA).
      • Donoval B.A.
      • Passaro D.J.
      • Klausner J.D.
      The public health imperative for a neonatal herpes simplex virus infection surveillance system.
      Further research is necessary to explore cost-effective methods to prevent and identify herpes infections in pregnant women and their neonates. We support the concept of a national surveillance program to determine an incidence of neonatal herpes. Accurate knowledge of the disease burden is critical to guide future public health planning and practice guidelines concerning the prevention of neonatal herpes.

      Acknowledgments

      We achnowledge Alvie M. Richardson, MD, Women and Infants Hospital of Rhode Island (Brown University) and Pablo Sanchez, MD, UT Southwestern Medical Center of Dallas.

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