I. INTRODUCTION. Syphilis is a sexually transmitted infection caused by the spirochete Treponema pallidum. Pregnant women with syphilis can transmit it through the placenta to the fetus or at birth to the neonate. Congenital infection can have severe consequences to the fetus and newborn including perinatal death, premature delivery, low birth weight, congenital anomalies, active congenital syphilis, and/or long-term sequela such as deafness and neurologic impairment. Prevention of congenital syphilis depends on the identification and adequate treatment of pregnant women with syphilis.

A. Congenital syphilis results from transplacental passage of T. pallidum or contact with infectious lesions during birth. The risk of transmission to the fetus correlates largely with the duration of maternal infection—the more recent the maternal infection, the more likely transmission to the fetus. During the primary and secondary stages of syphilis, the likelihood of transmission from an untreated woman to her fetus is extremely high, approaching 100%. After the secondary stage, the likelihood of transmission to the fetus declines steadily until it reaches approximately 10% to 30% in late latency. Transplacental transmission of T. pallidum can occur throughout pregnancy.

1. Clinical presentation. Congenital infection may result in stillbirth, hydrops fetalis, prematurity, or a wide spectrum of symptoms and signs. Most affected infants will be asymptomatic at birth, but clinical signs
usually develop within the first 3 months of life. The most common signs of early congenital syphilis (<2 years old) include hepatosplenomegaly, rash, condylomata lata, watery nasal discharge (snuffles), jaundice, anemia or edema, and skeletal abnormalities (osteochondritis, periostitis, pseudoparalysis). Late congenital syphilis in an untreated older child (>2 years old) may have stigmata with bony changes (frontal bossing, short maxilla, high palatal arch, Hutchinson teeth, saddle nose), interstitial keratitis, and sensorineural deafness, among others.

2. Case definition. The Centers for Disease Control and Prevention (CDC) 2015 case definition for congenital syphilis includes the following:

Laboratory criteria for diagnosis

Demonstration of T. pallidum by darkfield microscopy, polymerase chain reaction (PCR), or immunohistochemical (IHC) test, or special stains of specimens from lesions, placenta, umbilical cord, or autopsy material.

Infant whose mother had untreated or inadequately treated syphilis at delivery, regardless of signs in the infant, or an

a. Infant or child who has a reactive nontreponemal test for syphilis (venereal disease research laboratory [VDRL], rapid plasma reagin [RPR] or equivalent) and any one of the following:

b. Any evidence of congenital syphilis on physical examination

c. Any evidence of congenital syphilis on radiographs of long bones

d. A reactive cerebrospinal fluid (CSF) VDRL test

e. An elevated CSF cell count or protein (without other cause)

Case that is laboratory confirmed

Symptoms and signs of congenital syphilis in neonates are similar to those of other neonatal infections, including toxoplasmosis, herpes simplex, cytomegalovirus, rubella, and neonatal sepsis. Clinical data from mother, physical findings, and laboratory tests can help to make the diagnosis.

B. Maternal infection can be divided into three stages.

1. First stage or primary syphilis is manifested by one or more chancres (painless indurated ulcers) at the site of inoculation, typically the genitalia, anus, or mouth. It is often accompanied by regional lymphadenopathy. Lesions appear around 3 weeks after exposure and heal spontaneously in a few weeks.

2. Second stage or secondary syphilis is a disseminated process that occurs in around 25% of untreated patients, 3 to 6 weeks after the appearance of the chancre. The secondary stage is characterized by a polymorphic rash, most commonly maculopapular, generalized, and involving the palms and soles, sparing the face. Sore throat, fever, headache, diffuse lymphadenopathy, myalgias, arthralgias, alopecia, condylomata lata, and mucous membrane plaques may also be present. The symptoms resolve without treatment in 3 to 12 weeks, leaving the person completely asymptomatic. A latent period follows. Most women present at this stage.

a. Latent syphilis is defined as “the period after infection” when patients are seroreactive but demonstrate no clinical manifestations of disease.

b. Early latent syphilis refers to infection <1 year.

c. Late latent syphilis if initial infection is >1 year or indeterminate.

3. Tertiary stage or tertiary syphilis usually occurs 4 to 12 years after the secondary stage in about one-third of untreated patients and is characterized by gummata, cardiovascular syphilis, especially inflammation of the great vessels, or neurosyphilis. These lesions are thought to be due to a pronounced immunologic reaction.

Neurosyphilis may occur at any stage of the disease especially in HIV patients and in neonates with congenital syphilis. Early manifestations include syphilitic meningitis, uveitis, and neurovascular disease. Late manifestations include dementia, posterior column disease (tabes dorsalis), and seizures, among others.

III. EPIDEMIOLOGY. Trends in congenital syphilis usually follow trends in primary and secondary syphilis among women, with a lag of 1 to 2 years.

CDC reported that the rate of primary and secondary syphilis among women declined 95.4% (from 17.3 to 0.8 cases per 100,000 females) during 1990 to 2004. And the rate of congenital syphilis declined by 92.4% (from a peak of 107.6 cases to 8.2 cases per 100,000 live births) during 1991 to 2005. Rates of both female primary and secondary and congenital syphilis increased during 2005 to 2008. During 2008 to 2012, rates of both female primary and secondary and congenital syphilis declined (from 1.5 to 0.9 cases per 100,000 population and from 10.5 to 8.4 cases per 100,000 live births, respectively). Rates of primary and secondary syphilis in women remained unchanged (0.9 cases), but rates of congenital syphilis increased (to 8.7 cases) during 2013.

The most important risk factors for congenital syphilis are lack of prenatal health care and maternal illicit drug use, particularly cocaine. Clinical scenarios that contribute to the occurrence of congenital syphilis include lack of prenatal care; no serologic test for syphilis (STS) performed during pregnancy; a negative STS in the first trimester, without repeat test later in pregnancy; a negative maternal STS around the time of delivery in a woman who was recently infected with syphilis but had not converted her STS yet; laboratory error in reporting STS results; delay in treatment of a pregnant woman identified as having syphilis; and failure of treatment in an infected pregnant woman.

IV. DIAGNOSIS OF SYPHILIS. Effective prevention and detection of congenital syphilis depends on the identification of syphilis in pregnant women and, therefore, on the routine serologic screening of pregnant women during the first prenatal visit. CDC recommends additional testing at 28 weeks’ gestation and again at delivery for women who are at increased risk or live in communities with increased prevalence for syphilis infection. Routine screening of newborn sera or umbilical cord blood is not recommended because it does not prevent symptomatic congenital syphilis. No mother or newborn infant should leave the hospital without maternal serologic status having been documented at least once during pregnancy, and preferably again at delivery.

1. Nontreponemal tests include the RPR card test, the VDRL slide test, the unheated serum reagin (USR), and the toluidine red unheated serum
test (TRUST). These tests measure antibody directed against a lipoidal antigen from T. pallidum and/or its interaction with host tissues. These antibodies give quantitative results, allowing establishment of a baseline titer, which allows evaluation of recent infection and response to treatment. Titers usually rise with each new infection and fall after effective treatment. A sustained fourfold decrease in titer of the nontreponemal test with treatment demonstrates adequate therapy; a similar increase after treatment suggests reinfection.

Nontreponemal tests will be positive in approximately 80% of cases of primary syphilis, nearly 100% of cases of secondary syphilis, and 75% of cases of latent and tertiary syphilis. In secondary syphilis, the RPR or VDRL test result is usually positive in a titer >1:16. In the first attack of primary syphilis, the RPR or VDRL test will usually become nonreactive 1 year after treatment, whereas in secondary syphilis, the test will usually become nonreactive approximately 2 years after treatment. In latent or tertiary syphilis, the RPR or VDRL test may become nonreactive 4 or 5 years after treatment or may never turn completely nonreactive. A cause of false-negative nontreponemal tests is the prozone phenomenon, a negative or weakly positive reaction that occurs with very high antibody concentrations. In this case, dilution of the serum will result in a positive test.