By Stan Deresinski, MD, FACP

Clinical Professor of Medicine, Stanford University

SYNOPSIS: The diagnosis of congenital syphilis was delayed until the post-neonatal period in 2.2% of infants born in the United States 2014-2018.

SOURCE: Kimball A, Bowen VB, Miele K, et al. Congenital syphilis diagnosed beyond the neonatal period in the United States: 2014-2018. Pediatrics 2021;148:e2020049080.

Kimball and colleagues evaluated the extent of the problem of failure of diagnosis of congenital syphilis (CS) during the neonatal period i.e., during the first 28 days of life. They examined the National Notifiable Diseases Surveillance System to identify cases of this reportable disease throughout the United States among infants born 2014-2018, a period of time when the annual number of all cases of CS increased by 183% from 462 to 1,306. Of the total of 3,834 cases reported during that time, 84 (2.2%) were first diagnosed after the neonatal period, and 67 (including one twin set) born in the United States were symptomatic, while two were asymptomatic, and inadequate information was available for the remainder.

The median age at the time of diagnosis was 67 days, with the diagnosis first made after 3 months of age in 21 (31%) and after 6 months of age in four (6%). The median titer of the serum non-treponemal antibody tests was 1:256 (range 1:1-1:2,048). Two-thirds had physical findings consistent with CS, with the most frequently identified being skin rash, snuffles, and hepatosplenomegaly.

Long bone abnormalities were present in 38 (69%) of those with X-ray examination. Fifty infants underwent cerebrospinal fluid (CSF) examination venereal disease research laboratory (VDRL) testing, and the test was reactive in 18 (36%), while the protein concentration and/or white blood cell count was elevated in 22 (50%) of those tested. A 10-day course of parenterally administered penicillin was given to 61 (91%).

Fifty-five (83%) of the 66 mothers had had at least one prenatal care visit. Sixteen (24%) had primary or secondary syphilis and 25% had early latent infection, while 31 (47%) had late infection or infection of unknown duration. Sixteen (24%) seroconverted during pregnancy, with four of these conversions first detected after delivery. The diagnosis of maternal syphilis was often late, having been made, e.g., more than three days after delivery in 28 (42%) — with 15 of these only being made after the diagnosis in the infant. Three mothers received treatment for syphilis < 30 days prior to delivery.

COMMENTARY

There has been a disturbing increase in the incidence of CS in the United States since 2012. The Centers for Disease Control and Prevention (CDC) indicates that major reasons include missed opportunities, including a failure to provide adequate treatment despite time diagnosis, inadequate prenatal care, and lack of recommended testing, as well as late seroconversion during pregnancy and failed therapy of the mother. As pointed out by Kimball et al, this represents a failure of public health and healthcare systems as well as clinicians. The cases of late diagnosis reviewed here (along with 245 stillbirths) are “ultimate failures.”

The CDC recommends routine serological screening at the first prenatal visit and repeat testing at 28 weeks gestation and at delivery for those deemed at risk. Relying on assessment of risk has been reported to be inadequate and, as a consequence, some states recommend repeat testing for all. The CDC states, “No mother or newborn infant should leave the hospital without maternal serologic status having been documented at least once during pregnancy.” All neonates born to mothers with a serological diagnosis of syphilis should have a VDRL or rapid plasma reagin (RPR) test performed on serum (not from cord blood, which may contain passively transferred antibody). Those with positive tests should undergo intense examination (including CSF examination) for manifestations of central nervous system syphilis. Confirmed cases should receive 10 days of parenterally administered penicillin.

The experience reviewed here demonstrates the need for pediatricians to be alert to the potential for CS in post-neonatal infants with consistent clinical manifestations.

REFERENCE

  1. Centers for Disease Control and Prevention. Sexually Transmitted Infections Treatment Guidelines, 2021. Congenital Syphilis. https://www.cdc.gov/std/treatment-guidelines/congenital-syphilis.htm