From the Journals

Earlier diagnosis, treatment needed to curb dramatic rise in neonatal HSV

View on the News

Diagnostic conundrum persists despite new data

The rise in herpes simplex virus cases among neonates reported by Mahant et al. is significant, but there are other possible explanations that warrant additional research, James Gaensbauer, MD, and Joseph A. Grubenhoff, MD, wrote in an accompanying editorial.

Among those explanations, Dr. Gaensbauer and Dr. Grubenhoff cite recommendations made nationally in 2013 to screen asymptomatic infants who had been exposed to HSV at the time of delivery as one possible factor elevating the number of cases being reported. More widespread use of polymerase chain reaction (PCR)–based diagnostic testing, which is reported to be more sensitive, also could play a role in increasing the number of cases being identified.

As part of a larger diagnostic “conundrum” challenging clinicians, the editorialists noted that, at present, there is no uniform consensus for performing HSV testing and providing empirical treatment. “Current recommendations from the American Academy of Pediatrics identify and emphasize the importance of recognition of the factors associated with increased likelihood of HSV infection but do not specify a more comprehensive (e.g., all febrile infants) strategy.” Stakeholders should build flexibility into their recommended treatment approaches for the benefit of practitioners operating on the front lines, they advised.

Ultimately, if the increase in incidence of neonatal HSV cases proves largely attributable to the changing behaviors of young women, who have been engaging more frequently in oral sex, as Dr. Mahant and his colleagues suggest, further research will be warranted, cautioned Dr. Gaensbauer and Dr. Grubenhoff.

“With their work, the authors contribute further nuance to a complicated and ongoing question: How do we correctly identify all infants with neonatal HSV in a timely manner while avoiding subjecting large numbers of children to unnecessary tests and empirical treatments?” This debate “is likely to be transformed by increasing availability of rapid PCR testing for HSV,” they said.

The “pathway to better clarity will depend on researchers and clinicians such as Mahant et al., who continue to provide important data and ask critical questions,” Dr. Gaensbauer and Dr. Grubenhoff concluded.

Dr. Gaensbauer and Dr. Grubenhoff are affiliated with the Denver Health Medical Center; the Children’s Hospital Colorado, Aurora; and the department of pediatrics at University of Colorado at Denver, Aurora. This is a summarization of their editorial, which accompanied the article by Mahant et al. (Pediatrics. 2019 Mar. doi: 10.1542/peds.2019-0159). They received no external funding and had no relevant financial disclosures.



A 56% increase in neonatal herpes simplex virus (HSV) infection over 7 years was determined as part of a retrospective, multistate, longitudinal cohort study using information collected from the MarketScan Medicaid Database, reported Sanjay Mahant, MD, of the University of Toronto, and his associates.

Comprehensive coordinated care – as well as public health strategies targeting disease prevention, early diagnosis, and treatment – are needed to manage the growing number of neonates diagnosed with HSV, Dr. Mahant and his colleagues said.

A total of 900 newborn Medicaid enrollees aged 0-28 days were chosen from 2,107,124 births for inclusion in the study. All patients, who were diagnosed with HSV infection during hospital admission, were born during Jan. 1, 2009–Dec. 31, 2015.

Susceptibility to primary HSV-1 infection among younger women has been attributed to an increase in oral sex practices over the past 2 decades, which is putting adolescents and young adults at greater risk of genital HSV-1 infection (J Infect Dis. 2007;196[12]:1852-9). As a result, more “primary or nonprimary genital HSV-1 infections among childbearing women” are believed to be the likely cause for the increasing numbers of neonatal HSV cases, the authors speculated, citing a recent study (J Infect Dis. 2014 Feb 1;209[3]:315-7).

HSV, a rare infection typically contracted immediately before or after birth, has both high morbidity and mortality rates; transmission rates “after exposure and during delivery increase from 2% in recurrent infection to 25% and 60% in nonprimary and primary infections, respectively,” Dr. Mahant and his colleagues noted.

Over the study period, disease incidence grew from 3.4/10,000 births in 2009 (1/2,941 births) to 5.3/10,000 births in 2015 (1/1,886 births).

Dr. Mahant and his associates noted several limitations in the study that might explain the increase in incidence.

ICD diagnosis codes, which they characterized as imperfect in their ability to correctly identify neonatal HSV infections, may have led researchers to include infants who were not actually infected or (less likely) to have excluded infants who were infected. States participating in the MarketScan Medicaid Database also may have changed over the study period. Incomplete follow-up after hospitalization made it impossible to track infants who had changed insurers, moved to other states, or died during the study. They also cautioned that outcomes may not be transferable to the general population because outcomes were specific to Medicaid enrollees.

The total cost for initial hospitalization and treatments provided during 6 months of follow-up was $60,620,431 ($87,602 median cost per patient) for the cohort of 900 infants. This is significant given that the authors reported a median length of stay of 18 days for initial hospitalization. Of the 846 patients discharged (54, or 6%, died during initial hospitalization), follow-up data was available for 692 (81%). A total of 316 (46%) infants required at least one subsequent visit to the emergency room, and another 112 (16%) experienced at least one hospital readmission.

That Dr. Mahant and his colleagues “observed high health care use and associated payments over the first 6 months, including and after hospitalization for neonatal HSV” suggests that there is a need for comprehensive, coordinated care once neonatal patients receive a diagnosis of HSV.

“Public health strategies that are targeted on disease prevention and early diagnosis and treatment are needed,” they advised.

The authors had no relevant financial disclosures. The study was funded by the National Institutes of Health.

SOURCE: Mahant S et al. Pediatrics. 2019 Mar. doi: 10.1542/peds.2018-3233.

Next Article: