Congenital syphilis: Clinical features and diagnosis

Author
Simon R Dobson, MD, FRCP(C)
Section Editors
Sheldon L Kaplan, MD
Leonard E Weisman, MD
Deputy Editor
Carrie Armsby, MD, MPH
Contributor disclosures
All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Jul 2016. | This topic last updated: Mar 08, 2016.
INTRODUCTION Congenital syphilis occurs when the spirochete Treponema pallidum is
transmitted from a pregnant woman to her fetus. Infection can result in stillbirth, prematurity, or a
wide spectrum of clinical manifestations; only severe cases are clinically apparent at birth [1].
The clinical features and diagnosis of congenital syphilis will be discussed here. The evaluation,
management, and prevention of congenital syphilis are discussed separately. (See "Congenital
syphilis: Evaluation, management, and prevention".)
Syphilis in pregnancy and acquired syphilis also are discussed separately:
(See "Syphilis in pregnancy".)
(See "Syphilis: Epidemiology, pathophysiology, and clinical manifestations in HIVuninfected patients".)
(See "Syphilis: Epidemiology, pathophysiology, and clinical manifestations in HIVuninfected patients", section on 'Clinical manifestations'.)
(See "Syphilis: Treatment and monitoring".)
(See "Neurosyphilis".)
(See "Syphilis: Screening and diagnostic testing".)
CASE DEFINITION The Centers for Disease Control and Prevention (CDC) case definition for
congenital syphilis is provided in the table (table 1) [1]. Other case definitions may differ slightly
from the CDC definition [2]. In general, case definitions for congenital syphilis require only one of
two criteria:
The child has physical, laboratory, or radiographic signs of congenital
syphilis (confirmed/highly probable congenital syphilis), or
The child was born to a mother with untreated, inadequately, or suboptimally treated
syphilis (presumed congenital syphilis) (table 2)
Some experts would also presume infants to have congenital syphilis if their mothers had contact
with a person with primary or secondary syphilis within 90 days before delivery and were not
treated or were inadequately treated [3,4].
EPIDEMIOLOGY Congenital syphilis is a significant public health problem, complicating an
estimated one million pregnancies per year throughout the world [5]. The incidence of congenital
syphilis reflects the rate of syphilis in women of childbearing age [6]. (See "Syphilis:
Epidemiology, pathophysiology, and clinical manifestations in HIV-uninfected patients", section
on 'Epidemiology'.)

Most cases develop because the mother received no prenatal care or insufficient treatment for
syphilis before or during pregnancy (table 2) [7-10]. Among women with untreated early syphilis,
40 percent of pregnancies result in spontaneous abortion [11]. (See "Syphilis in pregnancy",
section on 'Incidence and epidemiology'.)
In the United States, the rate of congenital syphilis among infants <1 year of age peaked at
approximately 100 cases per 100,000 live births in 1991 (in part because of a change in the case
definition to include infants born to women with untreated or inadequately treated syphilis in
1988), declined steadily until 2005, and fluctuated between 8 and 12 cases per 100,000 live births
between 2005 and 2014 (figure 1) [6,8,12]. Among the 458 cases of congenital syphilis reported
in 2014, nearly one-quarter were born to mothers who did not receive prenatal care [12]. Among
the 314 cases in which the mother received prenatal care, 135 (43 percent) received no treatment
for syphilis during the pregnancy and 94 (30 percent) received inadequate treatment.
The rate of congenital syphilis is increased among infants born to mothers with HIV infection.
However, the contribution of maternal coinfection with syphilis and HIV to vertical transmission of
either syphilis or HIV is not completely understood. (See "Epidemiology, clinical presentation, and
diagnosis of syphilis in the HIV-infected patient", section on 'Effect of syphilis on HIV'.)
The rate of congenital syphilis is generally low among children adopted internationally; however it
is relatively increased among those adopted from Africa (table 3). Given the difficulty in
confirming adequate treatment/treatment response of the birth mother and the risk of long-term
sequelae in untreated children, we recommend screening international adoptees for congenital
syphilis (regardless of the country of origin). (See "International adoption: Infectious disease
aspects", section on 'Syphilis'.)
TRANSMISSION Humans are the only natural host of T. pallidum [13]. Congenital syphilis
generally is acquired through transplacental transmission of spirochetes in the maternal
bloodstream or, occasionally, through direct contact with an infectious lesion during birth [14-16].
(See"Syphilis in pregnancy", section on 'Perinatal transmission'.)
Transplacental transmission of T. pallidum can occur at any time during gestation but occurs with
increasing frequency as gestation advances. Women with untreated primary or secondary
syphilis are more likely to transmit syphilis to their fetuses than women with latent disease (60 to
90 versus 40 percent in early latent and <10 percent in late latent syphilis) [17,18]. The risk of
transmission decreases with increasing time since primary or secondary infection and is only 2
percent after four years.
T. pallidum is not transferred in breast milk, but transmission may occur if the mother has an
infectious lesion (eg, chancre) on her breast [19].
PATHOGENESIS At the onset of congenital syphilis, T. pallidum is liberated directly into the
circulation of the fetus, resulting in spirochetemia with widespread dissemination to almost all
organs. The clinical manifestations result from the inflammatory response. The bones, liver,
pancreas, intestine, kidney, and spleen are the most frequently and severely involved. The
severity of the manifestations is variable and can range from isolated laboratory or radiographic
abnormalities to fulminant involvement of multiple organ systems. Overt infection can manifest in
the fetus, the newborn, or later in childhood (if the infant is not treated) [20].

The pathophysiology of and immune response to acquired syphilis infection are discussed
separately. (See "Syphilis: Epidemiology, pathophysiology, and clinical manifestations in HIVuninfected patients".)
EARLY CONGENITAL SYPHILIS
Clinical findings Early congenital syphilis is arbitrarily defined by clinical manifestations with
onset before two years of age [4]. Clinical manifestations in untreated infants usually appear by
three months of age, most often by five weeks [4,21].
Approximately 60 to 90 percent of live-born neonates with congenital syphilis are asymptomatic at
birth [12,22]. The presence of signs at birth depends upon the timing of intrauterine infection and
treatment [13]. Among symptomatic infants, the most common findings include [12,23]:
Hepatomegaly
Jaundice
Nasal discharge ("snuffles")
Rash
Generalized lymphadenopathy
Skeletal abnormalities
Manifestations of early clinical syphilis are varied and unpredictable (table 4) [1,4,13,19,24,25].
Common clinical findings are reviewed here:
Placenta and umbilical cord The placenta of neonates with congenital syphilis is often
large, thick, and pale (see "Syphilis in pregnancy", section on 'Placental findings'). The
umbilical cord is edematous and may resemble a "barber's pole" with spiral stripes of red
and light blue discoloration alternating with streaks of chalky white. It may be significantly
inflamed with an abscess-like foci of necrosis within Wharton's jelly, centered around the
umbilical vessels (necrotizing funisitis) [26,27]. (See "Care of the umbilicus and
management of umbilical disorders", section on 'Funisitis'.)
Hepatomegaly Hepatomegaly occurs in almost all infants with congenital syphilis
[10,19]. Hepatomegaly may or may not be associated with splenomegaly, but isolated
splenomegaly does not occur. When noted on fetal ultrasonography, hepatomegaly may
indicate failure of maternal treatment to prevent fetal infection [28]. Hepatomegaly is
associated with jaundice and cholestasis. Laboratory findings may include elevated
aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and direct
bilirubin; delayed prothrombin time; and visible spirochetes on liver biopsy (if one is
performed) (see 'Laboratory abnormalities' below). Abnormalities of liver function may be
exacerbated by penicillin therapy before improving [29]. Liver dysfunction generally resolves
slowly, even after adequate therapy.
Rhinitis Syphilitic rhinitis ("snuffles") (picture 1) may herald the onset of congenital
syphilis. It usually develops during the first week of life and seldom after the third month.
The nasal discharge is white and may be bloody (secondary to mucosal erosion) or purulent
if there is secondary bacterial infection. It is more severe and persistent than the nasal
discharge of the common cold (see "The common cold in children: Clinical features and
diagnosis", section on 'Clinical features'). The nasal discharge contains spirochetes and can

transmit infection by direct contact. It should be examined by darkfield microscopy to

confirm the diagnosis. (See 'Younger than one month' below.)
Rash The rash of congenital syphilis usually appears one to two weeks after the rhinitis.
It is maculopapular and consists of small, initially red or pink spots. The lesions may occur
anywhere, but are more prominent on the back, buttocks, posterior thighs, and soles
(picture 2). The rash generally progresses over one to three weeks, followed by
desquamation and crusting. As it fades, the lesions become dusky red or copper-colored,
and the pigmentation may persist. If present at birth, the rash may be widely disseminated
and bullous (pemphigus syphiliticus). Ulcerative lesions and bullous fluid contain
spirochetes and can transmit infection by direct contact; samples of such lesions should be
examined by darkfield microscopy to confirm the diagnosis. (See 'Younger than one
month' below.)
Other characteristic, but uncommon, cutaneous lesions of congenital syphilis include
fissures, mucous patches, and condylomata lata. The fissures occur around the lips, nares,
and anus. They bleed easily and heal with scarring. The mucous patches may occur on any
mucous membrane, particularly those in the mouth and genitalia. Condylomata lata are flat,
wart-like, moist lesions around the mouth, nares, anus, and other areas of the skin where
there is moisture or friction. They contain spirochetes and can transmit infection.
Generalized lymphadenopathy Generalized, nontender lymphadenopathy is a common
manifestation. Palpable epitrochlear lymphadenopathy in an infant is highly suggestive of
congenital syphilis [19].
Other manifestations Other manifestations of congenital syphilis may include
[1,4,10,13,19,24,25]:
Nonimmune fetal hydrops
Fever (may be more prominent in infants born to mothers who are affected late in
pregnancy and whose serology is negative at delivery)
Myocarditis
Pneumonia
Failure to move an extremity secondary to pain ("pseudoparalysis of Parrot")
Sepsis due to other bacteria (eg, Escherichia coli, group B
streptococci, Yersinia species)
Ophthalmologic manifestations Loss of eyebrows, chorioretinitis, uveitis, cataract,
glaucoma, and chancre of the eyelid
Gastrointestinal manifestations Rectal bleeding (from ileitis), necrotizing
enterocolitis, malabsorption
Nephrotic syndrome (immune complex mediated; responsive to penicillin) [30-33]
(see "Congenital and infantile nephrotic syndrome", section on 'Infectious causes')
CNS syphilis Central nervous system (CNS) syphilis in children with congenital infection may
be asymptomatic or symptomatic. Asymptomatic CNS syphilis is indicated by abnormalities in the
cerebrospinal fluid (see 'CSF abnormalities' below). Asymptomatic CNS syphilis occurs in
approximately 40 percent of infants who have clinical, laboratory, or radiographic abnormalities of
congenital syphilis, but is infrequent in infants without such manifestations [13,34-38].

Symptomatic CNS involvement is rare among infants with congenital syphilis in the era of
penicillin therapy but may develop from ongoing dissemination in infants who are not treated in
the neonatal period [13]. Symptomatic CNS syphilis in infants has two overlapping presentations:
acute syphilitic leptomeningitis and chronic meningovascular syphilis.
Acute syphilitic leptomeningitis typically manifests during the first year of life, usually
between three and six months. The clinical findings are suggestive of bacterial meningitis
(eg, vomiting, bulging fontanelle, increased head circumference, splitting of the cranial
sutures), but the CSF findings are more suggestive of aseptic meningitis (predominance of
mononuclear cells, modest increase in protein, normal glucose) [13,19]. Acute syphilitic
leptomeningitis generally responds to penicillin therapy.
Chronic meningovascular syphilis typically manifests toward the end of the first year [13].
The clinical findings include signs of progressive hydrocephalus, cranial nerve palsies,
papilledema, optic atrophy, neurodevelopmental regression, and seizures. Syphilitic
endarteritis may cause cerebral infarction in the second year of life.
In addition, pituitary gland involvement may manifest with persistent hypoglycemia or diabetes
insipidus [39,40].
Radiographic abnormalities
Long-bone radiographs Abnormal long-bone radiographs are a common manifestation of
early congenital syphilis (occurring in 60 to 80 percent) and may be the sole manifestation in
infants born to mothers with untreated syphilis [41,42]. The changes usually are present at birth
but may appear in the first few weeks of life. Long-bone abnormalities may be associated with
pathologic fractures or pain, which may limit movement of the involved extremity, giving the
appearance of paralysis ("pseudoparalysis of Parrot") [43].
The radiographic abnormalities characteristically are bilateral, symmetric, and polyostotic; the
femur, humerus, and tibia are most frequently involved. Findings may include [43-45]:
Metaphyseal lucent bands (this finding may occur in response to other systemic illnesses)
(image 1)
Symmetric localized demineralization and osseous destruction of the medial portion of the
proximal tibial metaphysis (Wimberger sign), which also may occur in neonatal
hyperparathyroidism and osteomyelitis
Metaphyseal serration ("sawtooth metaphysis," or Wegener sign)
Diaphyseal periostitis with new bone formation (may occur in other conditions) (image 2)
Irregular areas of increased density and rarefaction ("moth-eaten" appearance) (image
3 and image 4)
Long-bone abnormalities may be helpful in the diagnosis of congenital syphilis and may be
warranted in [46-48]:
Neonates who have Venereal Disease Research Laboratory (VDRL) or rapid plasma
reagin (RPR) titers <fourfold the maternal titer, normal physical examination, and whose
mothers were not treated or were inadequately treated (table 2); were treated 4 weeks
before delivery; or have evidence of relapse or reinfection (fourfold or greater increase in

titers). (See "Congenital syphilis: Evaluation, management, and prevention", section on

'Possible congenital syphilis'.)
Infants and children with reactive VDRL or RPR and with abnormal skeletal findings on
physical examination (eg, extremity pain, lack of movement of one or more extremities).
(See "Congenital syphilis: Evaluation, management, and prevention", section on 'Proven or
highly probable disease' and "Congenital syphilis: Evaluation, management, and
prevention", section on 'Evaluation and management of children >1 month of age'.)
Chest radiographs Complete opacification of both lung fields ("pneumonia alba") is the
classic radiographic appearance of pneumonia in infants with congenital syphilis. However, a
fluffy, diffuse infiltrate involving all lung areas is more common in the era of penicillin therapy.
Laboratory abnormalities
Hematologic studies Hematologic abnormalities of early congenital syphilis may include
[10,49,50]:
Anemia Direct Coomb's test (also known as direct antiglobulin test) negative hemolytic
anemia in the neonatal period; nonhemolytic anemia after the neonatal period
Thrombocytopenia
Leukopenia or leukocytosis
Hemolysis is often accompanied by cryoglobulinemia, immune complex formation, and
macroglobulinemia. It does not respond to therapy and may last for weeks.
CSF abnormalities Laboratory evidence of central nervous system (CNS) involvement may
include [10,47,48]:
Reactive cerebrospinal fluid (CSF) VDRL
CSF pleocytosis (defined by consensus as >25 white blood cells [WBC]/microL for infants
<1 month, although some experts use a threshold of >5 WBC/microL)
Elevated CSF protein (defined by consensus as >150 mg/dL in term infants <1 month of
age and >170 mg/dL in preterm infants <1 month of age, although some experts use a
threshold of >40 mg)
However, none of these findings is highly sensitive or specific [36,38]. In an observational study
that used the rabbit infectivity test as the reference standard for identification of spirochetes in the
CSF, the sensitivity and specificity of reactive CSF VDRL, elevated CSF WBC, and elevated CSF
protein were as follows [36]:
Reactive CSF VDRL: sensitivity 54 percent; specificity 90 percent
Elevated CSF WBC count: sensitivity 38 percent; specificity 88 percent
Elevated CSF protein: sensitivity 56 percent; specificity 78 percent
The significance of a reactive CSF VDRL in a neonate is not clear, since there may be false
positives (related to maternal nontreponemal IgG antibodies that cross the placenta and diffuse
into the fetal CSF or contamination of the CSF with blood from a traumatic lumbar puncture) and
false negatives (neonates with initial nonreactive CSF VDRL may subsequently develop signs of
neurosyphilis). (See 'Congenital neurosyphilis' below.)

Examination of the CSF for T. pallidum DNA by polymerase chain reaction (PCR) may prove
more useful for definitive diagnosis of congenital neurosyphilis [14,36,37], but this test is not
widely available. (See 'Diagnostic tests' below.)
LATE CONGENITAL SYPHILIS Late congenital syphilis is arbitrarily defined by clinical
manifestations with onset after two years of age [4]. Manifestations of late congenital syphilis are
related to scarring or persistent inflammation from early infection and are characterized by
gumma formation in various tissues [51]. Late congenital syphilis develops in approximately 40
percent of infants born to women with untreated syphilis during pregnancy. Some manifestations
of late congenital syphilis can be prevented by treatment of the mother during pregnancy or
treatment of the infant within the first three months of life [52,53]. However, other manifestations
(eg, keratitis, saber shins) may occur or progress despite appropriate therapy [54].
Manifestations of late congenital syphilis include (table 5) [1,19,53,55,56]:
Facial features Frontal bossing (picture 3); saddle nose; short maxilla; protuberant
mandible
Eyes Interstitial keratitis (picture 4) (bilateral, usually occurs around puberty, but can
occur anytime between 4 and 30 years); secondary glaucoma; corneal scarring; optic
atrophy.
Ears Sensorineural hearing loss associated with late congenital syphilis typically
develops suddenly at 8 to 10 years of age and often accompanies interstitial keratitis. The
higher frequencies are affected first; normal conversational tones are affected later.
Syphilis-associated hearing loss may respond to long-term glucocorticoid therapy [57].
Oropharynx Hutchinson teeth (hypoplastic, notched, widely spaced permanent teeth
[upper central incisors most commonly affected] (picture 5); before eruption, Hutchinson
teeth are visible on dental radiographs); mulberry molars (maldevelopment of the cusps of
the first molars) (picture 6); and perforation of the hard palate (picture 7) (virtually
pathognomonic for congenital syphilis)
Cutaneous Rhagades (perioral fissures or a cluster of scars radiating around the mouth
(picture 8)); gummas (granulomatous inflammatory response to spirochetes) in the skin or
mucous membranes
Neurologic Intellectual disability; arrested hydrocephalus; cranial nerve palsies
Skeletal Anterior bowing of the shins ("saber shins") (picture 9); enlargement of the
sternoclavicular portion of the clavicle (Higoumenakis sign); painless arthritis of the knees
("Clutton joints" (picture 10)) and, rarely, other joints
Hematologic Paroxysmal cold hemoglobinuria (see "Paroxysmal cold hemoglobinuria")
Among these manifestations, Hutchinson triad (Hutchinson teeth, interstitial keratitis, and
sensorineural hearing loss), mulberry molars, and Clutton joints are relatively specific for
congenital syphilis [19,55].
DIFFERENTIAL DIAGNOSIS The manifestations of congenital syphilis in neonates may be
similar to those of other neonatal infections or newborn conditions, including:
Toxoplasmosis infection (see "Toxoplasmosis and pregnancy", section on 'Fetal
infection' and "Congenital toxoplasmosis: Clinical features and diagnosis", section on
'Clinical features')

Rubella virus infection (see "Congenital rubella syndrome: Clinical features and diagnosis",
section on 'Evaluation and diagnosis')
Cytomegalovirus infection (see "Congenital cytomegalovirus infection: Clinical features
and diagnosis", section on 'Clinical manifestations')
Herpes simplex virus infection (see "Neonatal herpes simplex virus infection: Clinical
features and diagnosis", section on 'Evaluation and diagnosis')
Neonatal sepsis (see "Clinical features, evaluation, and diagnosis of sepsis in term and
late preterm infants", section on 'Evaluation and initial management')
Neonatal hepatitis (see "Causes of neonatal cholestasis")
Hydrops fetalis (see "Nonimmune hydrops fetalis", section on 'Disorders associated with
hydrops and antepartum management' and "Postnatal diagnosis and management of
hemolytic disease of the fetus and newborn", section on 'Diagnosis')
Long-bone abnormalities (eg, osteomyelitis, rickets, physical abuse) or failure to move an
extremity (see "Differential diagnosis of the orthopedic manifestations of child
abuse" and "Brachial plexus syndromes", section on 'Neonatal brachial plexus palsy')
Vesicular lesions (see "Vesiculobullous and pustular lesions in the newborn")
Historical features, additional findings, and/or laboratory testing usually differentiate these
conditions from congenital syphilis.
DIAGNOSTIC TESTS The diagnosis of syphilis is complicated by the absence of a method to
culture T. pallidum on laboratory media. In clinical settings, the diagnosis of syphilis may be
established by:
Direct visualization of T. pallidum by darkfield microscopy (picture 11) or fluorescent
antibody staining of infected body fluids or lesions, placenta, or umbilical cord
Demonstration of the T. pallidum by special stains (picture 12) or histopathologic
examination [58,59]
Demonstration of serologic reactions typical of syphilis
Tests that may be used to establish the diagnosis of congenital syphilis in research settings
include:
Animal inoculation (ie, rabbit infectivity test)
Detection of T. pallidum DNA in a clinical specimen (eg, polymerase chain reaction (PCR))
[14,36,37,60]
These testing methods are discussed in detail separately. (See "Syphilis: Screening and
diagnostic testing", section on 'Diagnostic tests'.)
Darkfield microscopy can be performed on body fluids (eg, nasal discharge) or moist skin lesions
[61]. Darkfield microscopy enables demonstration of thin, delicate, corkscrew-shaped organisms
with rigid, tightly wound spirals (picture 11). A positive darkfield slide illustrates the characteristic
motility associated with T. pallidum: a forward and backward motion with rotation about the
longitudinal axis [61]. Soft side-to-side bending and twisting may also be seen. Failure to identify
spirochetes with darkfield microscopy does not exclude the diagnosis of syphilis. Darkfield
microscopy depends upon the direct visualization of live, active spirochetes, characteristics that
are rapidly destroyed by the previous use of antibiotics.

Serologic testing can establish a diagnosis of proven/highly probable, at-risk, or unlikely

congenital syphilis infection (see 'Interpretation' below). Serologic tests include nontreponemal
tests (eg, Venereal Disease Research Laboratory [VDRL] or rapid plasma reagin [RPR]) and
treponemal tests (eg, fluorescent treponemal antibody absorption [FTA-ABS], T. pallidum particle
agglutination [TP-PA], enzyme immunoassay [EIA], chemiluminescence immunoassay [CIA],
microhemagglutination test for T. pallidum [MHA-TP]) [1].
Nontreponemal tests are inexpensive and rapidly performed. They are sensitive, but not specific.
Nontreponemal tests generally are used in the evaluation of neonates with possible congenital
syphilis because they provide quantitative results, which can be compared with simultaneously
obtained maternal results to categorize neonatal infection [48]. The neonate's nontreponemal titer
usually is one to two dilutions less than that of the mother [62]. When the mother's titer is low, the
neonate may have nonreactive serology but remains at risk for congenital syphilis.
(See 'Congenital syphilis less likely' below.)
Serologic tests for IgG antibodies are problematic because it is not possible to differentiate
between passively acquired maternal antibody and endogenous antibody produced by
the fetus/neonate. The ability to detect IgM antibodies, which do not cross the placenta, would
confirm fetal infection. Unfortunately, a sufficiently sensitive and specific IgM assay is not
currently available for routine use in the assessment of congenital syphilis [47]. The fluorescent
anti-treponemal IgM antibody test IgM FTA-ABS was used in the past, but because of lack of
sensitivity [63,64], the Centers for Disease Control and Prevention suspended its use for
diagnostic testing of infants.
The rabbit infectivity test (RIT), which involves the inoculation of CSF or other body fluids into
rabbits to determine the presence of viable T. pallidum, is the reference standard test for
congenital syphilis [19,21,51]. However, routine use of RIT is not practical because it involves
animal testing and is not widely available.
PCR has been used on neonatal blood and cerebrospinal fluid for diagnosis of congenital
syphilis, but these tests are not widely available [14,36,37,65]. Compared with isolation of the
spirochetes by rabbit infectivity testing, the sensitivity and specificity of PCR on cerebrospinal
fluid was 65 to 71 percent and 97 to 100 percent, respectively [36,37]. Among 17 infants who had
spirochetes detected in cerebrospinal fluid by rabbit inoculation, blood PCR was the best
predictor of central nervous system infection with T. pallidum [36].
APPROACH TO DIAGNOSIS The vagaries of the maternal history and signs or lack of signs
in the newborn in combination with the potential consequences of delayed or missed diagnosis of
congenital syphilis demand a "safety first" approach to both diagnosis and treatment [4]. The
Centers for Disease Control and Prevention (CDC) and the American Academy of Pediatrics
Committee on Infectious Diseases (AAP) provide guidelines for the evaluation and management
of congenital syphilis (algorithm 1 and table 6) [47,48]. Maternal nontreponemal test results are
required for entry into the algorithm.
The CDC and AAP guidelines recommend that maternal samples be screened according to the
traditional algorithm (ie, a nontreponemal test followed by a treponemal test if the nontreponemal
test is positive). However, some laboratories have begun to screen samples in reverse (ie, a
treponemal test before the nontreponemal test). Interpretation of results with reverse sequence

screening is discussed separately. (See "Syphilis: Screening and diagnostic testing", section on
'Serologic testing algorithms'.)
Clinical suspicion The diagnosis of congenital syphilis should be suspected in all infants born
to women who have reactive nontreponemal and treponemal tests for syphilis; the treponemal
test is necessary to exclude a false-positive nontreponemal test (see "Syphilis in pregnancy").
The diagnosis of congenital syphilis also should be suspected in infants born to women who are
identified clinically or through contact tracing as having early syphilis during the three months
after delivery [4].
In addition, the possibility of congenital syphilis should be considered in infants and children with
the following nonspecific clinical findings, particularly in infants born to women with a history of
syphilis or risk factors for syphilis (see "Syphilis in pregnancy", section on 'Incidence and
epidemiology'):
Unexplained prematurity (<37 weeks' gestation)
Unexplained hydrops fetalis
Enlarged placenta
Failure to move an extremity ("pseudoparalysis")
Persistent rhinitis (picture 1)
Persistent maculopapular or papulosquamous rash (picture 2), particularly in the diaper
area
Jaundice, hepatomegaly
Neonatal pneumonia
Generalized lymphadenopathy
Anemia (Coomb's [direct antiglobulin] test negative)
Thrombocytopenia
Sensorineural hearing loss
Interstitial keratitis
Finally, the possibility of congenital syphilis should be suspected in children who are adopted
internationally. (See "International adoption: Infectious disease aspects", section on 'Syphilis'.)
Initial evaluation
Younger than one month The initial evaluation of infants younger than one month of age who
were born to women with reactive nontreponemal and treponemal test results should include
(algorithm 1 and table 6) [47,48]:
A quantitative nontreponemal test (rapid plasma reagin [RPR] or Venereal Disease
Research Laboratory [VDRL]) on infant serum; testing umbilical cord blood could yield a
false positive result if the cord blood is contaminated with maternal blood. The
nontreponemal test that is performed on the infant should be the same that was done on the
mother so that the infant's titers can be compared with those of the mother.
Physical examination for evidence of congenital syphilis and darkfield microscopic
examination or direct fluorescent antibody (DFA) staining of suspicious lesions or body

fluids (eg, nasal discharge). (See 'Early congenital syphilis' above and 'Diagnostic
tests' above.)
Pathologic examination of the placenta or umbilical cord with specific fluorescent
antitreponemal antibody staining (if possible) [16,27,66]. Characteristic histopathologic
features are described separately. (See "Care of the umbilicus and management of
umbilical disorders", section on 'Funisitis'.)
Additional evaluation depends upon the findings from the initial evaluation and is discussed
separately. (See "Congenital syphilis: Evaluation, management, and prevention", section on
'Subsequent evaluation and management'.)
Older than one month The initial evaluation of infants and children older than one month of
age with clinical, radiographic, or laboratory manifestations compatible with congenital syphilis
should include a quantitative VDRL or RPR, physical examination, and darkfield microscopic
examination (if it is available) or DFA staining of suspicious body fluids [47,48].
Infants and children who are found to have reactive serologic tests for syphilis when they are
older than one month of age should have maternal serology and records reviewed to assess
whether the child has congenital or acquired syphilis, although this distinction may be difficult
[1,20]. Additional evaluation of such children may include [47,48]:
Cerebrospinal fluid (CSF) analysis for VDRL, cell count, and protein
Complete blood count (CBC) with differential and platelet count
Evaluation and testing for HIV infection
Other tests as clinically indicated (eg, chest radiograph, long-bone radiographs, liver
function tests, abdominal ultrasonography, ophthalmologic examination, and auditory brain
stem response, and neuroimaging studies)
CSF and CBC abnormalities may occur in both congenital and acquired syphilis, but radiographic
abnormalities are more suggestive of congenital than acquired syphilis. (See 'Radiographic
abnormalities' above.)
Interpretation To maximize treatment of children potentially infected with T. pallidum, the
CDC provides categories of congenital syphilis infection that encompass infants with proven or
highly probable disease, as well as those who are at risk of congenital syphilis without any clinical
evidence of infection. The inclusion of infants at risk for congenital syphilis helps to ensure that
possible cases are treated, although not all treated infants will be infected [47].
Proven or highly probable congenital syphilis Congenital syphilis is proven or highly
probable if the neonate (<1 month of age) has any of the following [47]:
An abnormal physical examination that is consistent with congenital syphilis
A serum quantitative nontreponemal serologic titer that is fourfold the corresponding
maternal titer (which is equivalent to two dilutions [eg, neonate's titer 1:32 and maternal titer
1:8])
A positive darkfield (picture 11) or fluorescent antibody test of lesions, body fluid(s),
placenta, or umbilical cord (these procedures may not be available in all centers)

Neonates with proven or highly probable congenital syphilis should undergo further evaluation
and treatment. (See "Congenital syphilis: Evaluation, management, and prevention", section on
'Subsequent evaluation and management'.)
Possible congenital syphilis Neonates with normal physical examination and serum VDRL
or RPR titers <fourfold the maternal titer, but whose mothers were not treated or
received inadequate/suboptimal therapy (table 2) are considered to have possible congenital
syphilis [47,48].
Some experts would also consider infants to have possible congenital syphilis if their mothers had
contact with a person with primary or secondary syphilis within 90 days before delivery and were
not treated or were inadequately treated, even if the mother had nonreactive serology [3,4].
Additional evaluation and management of infants with possible congenital syphilis are discussed
separately. (See "Congenital syphilis: Evaluation, management, and prevention", section on
'Possible congenital syphilis'.)
Congenital syphilis less likely Infection is less likely if a neonate has a normal physical
examination, serum VDRL or RPR titers are <fourfold the maternal titer, mother received
appropriate treatment >4 weeks before delivery, and mother has no evidence of reinfection or
relapse. However, these neonates are at risk and should receive treatment with a single dose of
intramuscular (IM) penicillin G benzathine [47,48,67]. No additional evaluation is needed [47].
Management of infants in whom congenital syphilis is less likely is discussed separately.
(See "Congenital syphilis: Evaluation, management, and prevention", section on 'Congenital
syphilis less likely'.)
Congenital syphilis unlikely A diagnosis of congenital syphilis is unlikely if the neonate has a
normal physical examination, serum VDRL or RPR titers are <fourfold the maternal titer, mother
was adequately treated before pregnancy, and mother's titers remained low (VDRL <1:2; RPR
<1:4) and stable before and during pregnancy and at delivery [47]. These infants generally do not
require any additional evaluation or treatment. (See "Congenital syphilis: Evaluation,
management, and prevention", section on 'Congenital syphilis unlikely'.)
Congenital neurosyphilis A lumbar puncture to evaluate central nervous system (CNS)
syphilis should be performed in infants <1 month with proven or highly probable congenital
syphilis; infants <1 month of age whose mothers were not adequately treated (possible congenital
syphilis); and in infants and children who were identified as having reactive serologic tests for
syphilis at older than one month of age (algorithm 1and table 6) [47,48]. (See "Congenital
syphilis: Evaluation, management, and prevention", section on 'Subsequent evaluation and
management'.)
The diagnosis of congenital neurosyphilis can be difficult to establish. Given the lack of a widely
available laboratory test with high sensitivity and specificity for CNS syphilis and the potential
consequences of untreated CNS syphilis, the diagnosis of CNS syphilis usually is presumed in
children with clinical, radiographic, and laboratory abnormalities compatible with congenital
syphilis. Children with presumed congenital neurosyphilis should be treated with 10 days of
parenteral penicillin [36]. (See 'CNS syphilis' above and "Congenital syphilis: Evaluation,
management, and prevention", section on 'Penicillin therapy'.)

Congenital versus acquired syphilis In children who are found to have reactive serologic
tests for syphilis when they are older than one month of age, the distinction between congenital
and acquired syphilis can be difficult [1]. The ultimate diagnosis may rest upon maternal history
and clinical judgment [1]. Radiographic abnormalities of the long bones are more suggestive of
congenital than acquired syphilis. (See 'Radiographic abnormalities' above.)
The possibility of sexual abuse must be considered in children who are determined to have
acquired syphilis. (See "Evaluation of sexual abuse in children and adolescents", section on
'Sexually transmitted infections'.)
REPORTING REQUIREMENTS In the United States, congenital syphilis is a national notifiable
disease [68]. However, reporting requirements vary by state. Reporting to the Centers for
Disease Control and Prevention by the states is voluntary. For reporting purposes, congenital
syphilis includes stillbirths due to syphilis, cases of congenital syphilis detected in newborns, and
cases of congenitally acquired syphilis in infants and children [1].

EVALUATION AND MANAGEMENT OF INFANTS <1 MONTH OF AGE The vagaries of the
maternal history of syphilis and signs or lack of signs in the newborn in combination with the
potential consequences of delayed or missed diagnosis of congenital syphilis demand a "safety
first" approach to both diagnosis and treatment [2]. The US Centers for Disease Control and
Prevention (CDC) and the American Academy of Pediatrics Committee on Infectious Diseases
(AAP) provide guidelines for the evaluation and management of congenital syphilis (algorithm
1 and table 1) [3,4].
Initial evaluation The diagnosis of congenital syphilis should be suspected in all infants
whose mothers have reactive nontreponemal and treponemal tests for syphilis; the treponemal
test is necessary to exclude a false-positive nontreponemal result. (See "Syphilis in pregnancy".)
The initial evaluation of infants born to mothers who have reactive nontreponemal and
treponemal test results should include [3,4]:
A quantitative nontreponemal test (Venereal Disease Research Laboratory test [VDRL] or
rapid plasma reagin [RPR]) on infant serum; testing umbilical cord blood could yield a false
positive result if the cord blood is contaminated with maternal blood. The nontreponemal
test that is performed on the infant should be the same as that which was done on the
mother so that the infant's titers can be compared with the mother's titers.
Physical examination for evidence of congenital syphilis (table 2) and darkfield microscopic
examination (picture 1) or direct fluorescent antibody (DFA) staining of suspicious lesions or
body fluids (eg, nasal discharge). (See "Congenital syphilis: Clinical features and diagnosis",
section on 'Early congenital syphilis' and "Congenital syphilis: Clinical features and
diagnosis", section on 'Diagnostic tests'.)
Pathologic examination of the placenta or umbilical cord with specific fluorescent
antitreponemal antibody staining
Additional evaluation depends upon the findings from the initial evaluation.

Subsequent evaluation and management The subsequent evaluation depends upon clinical,
serologic, and epidemiologic factors, including (algorithm 1 and table 1) [3,4]:
The neonate's syphilis serology (nonreactive or reactive; and if reactive, whether the
infant's titer is at least fourfold [two dilutions] higher than the corresponding maternal titer)
The mother's risk factors for syphilis (see "Syphilis in pregnancy", section on 'Incidence
and epidemiology')
The mother's syphilis serology (in relation to previous tests and/or treatment and in relation
to the neonate's titers)
If the mother has been treated for syphilis:
The timing of the treatment (before or during pregnancy; more or less than four weeks
before delivery)
The adequacy of therapy (table 3)
The likelihood of failure of maternal therapy to prevent congenital disease (higher
maternal titers and unknown duration of maternal syphilis are associated with failure of
maternal therapy to prevent congenital disease) [5]
Proven or highly probable disease Congenital syphilis is proven or highly probable if the
infant has at least one of the following [3,4]:
An abnormal physical examination that is consistent with congenital syphilis (table 2)
A serum VDRL or RPR titer that is fourfold the corresponding maternal titer (eg,
neonate's titer 1:32 and maternal titer 1:8)
A positive darkfield (picture 1) or fluorescent antibody test of body fluid(s), placenta, or
umbilical cord
Infants with proven or highly probable congenital syphilis should undergo the following evaluation
(algorithm 1 and table 1):
Cerebrospinal fluid (CSF) examination for cell count, protein, and VDRL
Complete blood count (CBC) with differential and platelet count
Additional tests as clinically indicated: long-bone radiographs (for lack of movement of
extremity), chest radiograph (for signs of lower respiratory tract disease), liver function tests
(for hepatomegaly, jaundice), cranial ultrasound (for neurologic manifestations),
ophthalmologic examination, and auditory brainstem response (for concerns about hearing)
We recommend that infants with proven or highly probable congenital syphilis be treated with 10
days of parenteral penicillin G [3,4]. (See 'Ten-day regimens' below.)
To prevent long-term morbidity, central nervous system syphilis is presumed in neonates with
clinical, radiographic, or laboratory abnormalities compatible with syphilis. Although CSF results
do not alter the treatment, examination of the CSF is necessary to determine the need for
subsequent monitoring and to provide a baseline for monitoring the response to therapy.
(See 'CSF evaluation' below.)
Possible congenital syphilis For neonates who have a normal physical examination and
reactive VDRL or RPR <fourfold the maternal titer, and whose mothers were not treated, were

inadequately treated (table 3), or had evidence of reinfection or relapse, the CDC and AAP
recommend the following evaluation (algorithm 1 and table 1) [3,4]:
CSF VDRL, cell count, and protein
CBC with differential and platelet count
Other tests as clinically indicated (eg, chest radiographs, long-bone radiographs, eye
examination, liver function tests, neuroimaging, and auditory brainstem response)
We recommend a full 10-day course of parenteral penicillin if any part of the evaluation is
abnormal or not performed, or if the CSF examination cannot be interpreted because it is
contaminated with blood [3,4]. (See 'Ten-day regimens' below.)
The neonate may be treated with a single dose of intramuscular (IM) penicillin G benzathine if all
three tests are performed, the results are normal, and follow-up of the infant is assured [3,4]
(see 'Single-dose regimen' below). Nonetheless, many experts prefer to treat such infants with a
full 10-day course, particularly if the mother has secondary syphilis at delivery or seroconverted
during the pregnancy [3,4] (see 'Ten-day regimens' below). Our preference is for the 10-day
course. For infants who will be treated with a 10-day course of penicillin, complete evaluation is
not necessary but may help to establish the diagnosis and need for long-term CSF follow-up
[3,6,7]. (See 'CSF evaluation' below.)
Congenital syphilis less likely No additional evaluation is necessary for the asymptomatic
neonate with reactive serology whose mother was treated during pregnancy, provided that all of
the following criteria are met (algorithm 1 and table 1):
The infant has a normal physical examination.
The infant's VDRL or RPR titer is reactive but less than fourfold the maternal titer.
Mother received adequate therapy during pregnancy that was suitable for the stage of her
infection and had an appropriate response (ie, VDRL or RPR titers decreased fourfold after
therapy for early syphilis; VDRL or RPR remained stable and low [VDRL 1:2; RPR 1:4] for
late syphilis).
Mother was treated more than four weeks before delivery.
Mother has no evidence of relapse or reinfection; relapse or reinfection are indicated by a
fourfold increase in titer.
In accord with the AAP and CDC, we suggest that neonates who meet the above criteria be
treated with a single dose of IM penicillin G benzathine(algorithm 1) [3,4] (see 'Single-dose
regimen' below). Infection of the fetus may occur despite appropriate maternal therapy during
pregnancy. The reported failure rates of maternal treatment to prevent congenital infection range
from 2 to 14 percent [5,8-10]; higher rates are more frequent in mothers with secondary syphilis.
Treating the infant at birth may prevent the development of clinical disease if maternal therapy
during pregnancy did not prevent fetal infection [11,12].
As an alternative, some specialists opt not to treat such infants, but to provide close (ie, monthly)
serologic follow-up, and provide treatment if the infant's titers do not decline as expected for
transplacentally acquired antibody. (See 'Nontreponemal tests' below.)

Congenital syphilis unlikely No additional evaluation is necessary for the asymptomatic

neonate whose mother was treated beforepregnancy, provided that all of the following criteria
are met [3]:
The infant has a normal physical examination
The infant's VDRL or RPR titer is <fourfold the maternal titer
Mother was appropriately and adequately treated before pregnancy
Mother's VDRL or RPR titer remained low and stable before and during pregnancy and at
delivery (ie, VDRL <1:2; RPR <1:4)
In accord with the AAP and CDC, we suggest that infants in this category do not require
treatment with penicillin (algorithm 1 and table 1) [3,4]. However, some experts would provide a
single dose of IM penicillin G benzathine if follow-up is uncertain (to protect the infant in the
unlikely event that the mother was reinfected). (See 'Single-dose regimen' below.)
Infant VDRL or RPR nonreactive The neonate who has a normal physical examination and
nonreactive VDRL or RPR does not require additional evaluation (algorithm 1 and table 1).
Such infants require treatment if the mother was not treated,
was inadequately/suboptimally treated (table 3), or has evidence of reinfection or relapse
(indicated by fourfold increase in titers after treatment) [4]. Some experts would also opt to treat
such infants even if their mothers were adequately treated [2,3,13]. Our preference is to treat
such infants whose mothers were adequately treated because a single dose of penicillin is
relatively benign compared with the risk of missed disease. (See 'Single-dose regimen' below.)
Treatment for neonates with nonreactive VDRL or RPR and normal physical examination
generally consists of a single dose of IM penicillin G benzathine. (See 'Single-dose
regimen' below.)
EVALUATION AND MANAGEMENT OF CHILDREN >1 MONTH OF AGE Children who are
identified as having reactive serologic tests for syphilis after one month of age should have
maternal serology and records reviewed to assess whether the child has congenital or acquired
syphilis, although this distinction may be difficult [1,14].
The evaluation of such children may include [3,4]:
Cerebrospinal fluid (CSF) analysis for Venereal Disease Research Laboratory test (VDRL),
white blood cell count, and protein
Complete blood count (CBC) with differential and platelet count
Evaluation and testing for HIV infection
Other tests as clinically indicated (eg, long-bone radiographs, chest radiograph, liver
function tests, abdominal ultrasonography, ophthalmologic examination, auditory brain stem
response, and neuroimaging studies)
The distinction between congenital and acquired syphilis can be difficult and ultimately may rest
upon maternal history and clinical judgment [1]. CSF and CBC abnormalities may occur in both
congenital and acquired syphilis, but radiographic changes in the metaphysis and epiphysis are
more suggestive of congenital syphilis. (See "Congenital syphilis: Clinical features and
diagnosis", section on 'Long-bone radiographs'.)

In a young child, the possibility of sexual abuse should be considered as a cause of acquired
syphilis. (See "Evaluation of sexual abuse in children and adolescents", section on 'Sexually
transmitted infections'.)
Children who are diagnosed with congenital syphilis after one month of age (including those with
previously untreated late congenital syphilis) require parenteral penicillin therapy [3,4]. (See '>1
month of age' below.)
EVALUATION OF SIBLINGS Evaluation of the siblings of an index case of congenital syphilis
may be warranted if such an evaluation did not occur previously [15].
PENICILLIN THERAPY Parenteral penicillin is the drug of choice for the treatment of
congenital syphilis [3,4]. Penicillin is the only drug with documented efficacy, and it has minimal
toxicity. T. pallidum is extremely sensitive to penicillin, as demonstrated by experimental animal
work [2]. The minimal inhibitory concentration (MIC) for penicillin is approximately 0.004 units (or
0.0025 mcg/mL). There is no evidence of increasing spirochete resistance to penicillin, but such
evidence would come only from the recognition of therapeutic failures.
Effective treatment of syphilis requires maintenance of a minimal inhibitory concentration (MIC) of
0.03 units/mL of penicillin in serum (or cerebrospinal fluid) for 7 to 10 days. Current regimens are
designed to achieve and maintain several times the necessary MIC and to avoid penicillin-free
intervals during therapy.
<1 month of age
Single-dose regimen The single-dose regimen for treatment of congenital syphilis is as
follows:
Penicillin G benzathine (50,000 units/kg, intramuscularly [IM] as a single dose)
Two randomized trials have evaluated the efficacy of single-dose penicillin therapy
in preventing/treating congenital syphilis in asymptomatic infants born to mothers with no
treatment or inadequate/suboptimal treatment for syphilis during pregnancy (table 3) [11,12]. One
compared single-dosepenicillin G benzathine with no therapy in asymptomatic infants at high risk
of congenital syphilis (untreated mothers with VDRL 1:32) [11]. None of 11 infants in the
treatment group developed congenital syphilis (defined by IgM Western blots and VDRL titers),
compared with four of eight infants who were not treated [11]. In the second trial, treatment of
asymptomatic infants (normal physical examination, normal CSF evaluation, normal long-bone
radiographs, and no visceral abnormalities) with either single-dose penicillin G benzathine or 10
days of parenteral procaine penicillin G was effective in preventing clinical evidence of congenital
syphilis and decreasing RPR by at least fourfold [12].
Single-dose therapy is contraindicated for asymptomatic infants born to women
with inadequate/suboptimal treatment (table 3) unless the infant has undergone appropriate
evaluation (CSF quantitative VDRL, cell count, and protein; CBC with differential and platelet
count; and long-bone radiographs) and has completely normal results [3,4]. The evaluation is
necessary to exclude CNS syphilis, which requires a full 10-day course of therapy. Treatment
failures with single-dose therapy have been reported among infants who developed clinical
findings of syphilis after incomplete evaluation [16,17]. The frequency of such treatment failures
appears to be low but is unknown. (See 'Possible congenital syphilis' above.)

Ten-day regimens There are two alternative 10-day penicillin regimens for the treatment of
congenital syphilis [3,4]:
Aqueous penicillin G 50,000 units/kg intravenously (IV) every 12 hours (for infants 7 days
of age) and every 8 hours (for infants >7 days of age) for a total of 10 days, or
Procaine penicillin G 50,000 units/kg intramuscularly (IM) as a single daily dose for 10
days
The levels of penicillin that are achieved in the CSF after IM procaine penicillin are lower than
those with IV aqueous penicillin [18]. However, the clinical significance of this observation is
unclear, since there have been no treatment failures reported after treatment with procaine
penicillin [4].
A full 10-day course of penicillin should be administered, even if the infant initially
received ampicillin for possible sepsis [3,4]. If more than one day of penicillin therapy is missed,
the entire course should be restarted.
>1 month of age Children who are diagnosed with congenital syphilis after one month of age
(including those with late congenital syphilis) and children with acquired syphilis should be treated
with aqueous penicillin G (50,000 units/kg intravenously every four to six hours for 10 days) [3,4].
In addition, for children with congenital syphilis or findings compatible with central nervous system
involvement, some experts suggest that the 10-day course of aqueous penicillin be followed with
a single dose of penicillin G benzathine (50,000 units/kg intramuscularly).
As an alternative for the child with positive syphilis serology, but no clinical manifestations of
disease, and normal CSF studies, some experts would treat with three weekly doses of penicillin
G benzathine (50,000 units/kg intramuscularly) [3,4].
Adverse effects
Jarisch-Herxheimer reaction The Jarisch-Herxheimer reaction generally consists of fever 2
to 12 hours after initiation of therapy for active syphilis [19]. However, cardiovascular collapse,
seizures, and death also have been reported [20]. The Jarisch-Herxheimer reaction is thought to
be produced by the release of endotoxin-like compounds during penicillin-mediated lysis of T.
pallidum. It is rare in newborns but can occur in older infants and children.
Special circumstances
Missed doses If more than one day of penicillin therapy is missed, the entire course should be
restarted [3,4]. Effective treatment of syphilis requires maintenance of a minimal inhibitory
concentration (MIC) of 0.03 units/mL of penicillin in serum (or cerebrospinal fluid) for 7 to 10 days.
(See'Penicillin therapy' above.)
Penicillin allergy Penicillin is the treatment of choice for congenital syphilis. There are
insufficient data regarding the adequacy of treatment with agents other than penicillins
(eg, ceftriaxone). For the infant/child who requires treatment for syphilis but has a penicillin
allergy or develops an allergic reaction that is presumed to be due to penicillin, the US Centers
for Disease Control and Prevention and the American Academy of Pediatrics recommend
desensitization and then treatment with penicillin [3,4]. (See "Penicillin allergy: Immediate

reactions", section on 'Desensitization'.) If a nonpenicillin agent is used, close serologic and CSF
follow-up are necessary. (See 'Follow-up evaluations' below.)
Maternal coinfection with HIV Infants born to mothers who are coinfected with syphilis and
human immunodeficiency virus (HIV) should receive the same evaluation and treatment as those
whose mothers do not have HIV infection [3]. There is insufficient evidence to determine whether
such infants require different evaluation, treatment, or follow-up.
FOLLOW-UP EVALUATIONS Infants and children who have reactive serologic tests for
syphilis or were born to mothers who were seroreactive at delivery should be monitored for
clinical or serologic manifestations of congenital syphilis; those who were treated should be
monitored to assure adequate treatment response [3,4,13,21,22].
Examination Infants who have reactive serologic tests for syphilis or were born to mothers
who were seroreactive at delivery should undergo evaluation for manifestations of congenital
syphilis during regularly scheduled well-child care visits during the first year and beyond (for
manifestations of late congenital syphilis) (table 2 and table 4) [3,4]. Evaluation for hearing loss,
ophthalmologic abnormalities, and neurodevelopmental problems should occur yearly [2].
(See "Hearing impairment in children: Evaluation" and "Visual development and vision
assessment in infants and children" and "Developmental-behavioral surveillance and screening in
primary care", section on 'When to perform developmental-behavioral screening'.)
Serology Reactive serology in the infant does not differentiate between the infant's antibody
response to infection and transplacentally acquired maternal antibody. Serial monitoring of the
infant's serology is necessary to ensure an appropriate treatment response or exclude congenital
syphilis. In children diagnosed with congenital syphilis after infancy, serial monitoring of serology
is necessary to ensure appropriate treatment response.
Nontreponemal tests Quantitative Venereal Disease Research Laboratory test (VDRL) or
rapid plasma reagin (RPR) should be performed every two to three months in infants born to
mothers with syphilis, including infants who were seronegative at birth whose mothers acquired
syphilis late in gestation (whether or not the infant was treated with penicillin), and in children
treated for congenital syphilis after infancy. Serology should be repeated until the test becomes
nonreactive or the titer has decreased fourfold (equivalent to two dilutions) [3,23,24].
The infant's VDRL or RPR titers should decline by three months of age and be nonreactive by six
months of age if the infant was successfully treated or not infected (ie, if the reactive test was
caused by passive transfer of maternal IgG antibody) [3,25,26]. The response may be slower in
infants and children treated after one month of age.
Treatment failure Treatment failure, or failure of maternal treatment to prevent congenital
syphilis, is indicated by:
Failure of the VDRL or RPR titers to decline, or
Increase in the VDRL or RPR after 6 to 12 months of age (or treatment in children treated
after the neonatal period)
In such circumstances, the infant/child should undergo a lumbar puncture to obtain cerebrospinal
fluid (CSF) for VDRL, cell count, and protein, and be treated with 10 days of parenteral penicillin,

even if he or she was treated previously [3,4]. (See 'CSF evaluation' below and 'Penicillin
therapy'above.)
Treponemal tests Treponemal tests (eg, fluorescent treponemal antibody absorption [FTAABS], T. pallidum particle agglutination [TP-PA], enzyme immunoassay [EIA],
chemiluminescence immunoassay [CIA], microhemagglutination test for T. pallidum [MHA-TP])
should not be used to evaluate treatment response because they can remain positive despite
effective treatment [3,27].
However, treponemal tests can be helpful in establishing a diagnosis of congenital syphilis. A
treponemal test should be performed after 12 to 15 months of age in infants who had reactive
serologic tests for syphilis or were born to mothers who were seroreactive at delivery [2,13]. If the
treponemal test is reactive, it should be repeated at 18 and 24 months of age. A positive
treponemal test at 18 months of age (after the disappearance of passively acquired maternal
antibody) confirms the diagnosis of congenital syphilis [2,24]. Children who have a positive
treponemal test for syphilis at 18 months of age and did not previously receive treatment should
undergo full evaluation and treatment. (See'Evaluation and management of children >1 month of
age' above.)
CSF evaluation Serial cerebrospinal fluid (CSF) evaluation is necessary for infants and
children whose initial CSF evaluation was abnormal (ie, reactive CSF VDRL or elevated CSF
white blood cell count or protein without an alternative explanation) [3]. CSF should be evaluated
every six months until the results are normal. A reactive CSF VDRL or abnormal CSF white blood
cell count or protein that cannot be attributed to other ongoing illnesses requires retreatment for
possible neurosyphilis with 10 days of parenteral penicillin therapy [3,4]. (See 'Penicillin
therapy' above.) Neuroimaging studies may be warranted in children with persistently reactive
CSF VDRL, elevated CSF cell count, and/or elevated CSF protein [4].
OUTCOME In the United States, the case fatality rate for congenital syphilis is between 6 and
8 percent [28,29]. Approximately 90 percent of fatal cases are associated with lack of prenatal
care or inadequate prenatal care.
Appropriate treatment of early congenital syphilis within the first three months of life prevents
some, but not all, of the late manifestations of congenital syphilis [26,30,31]. Interstitial keratitis
(picture 2) and anterior tibial bowing ("saber shins") (picture 3) may occur or progress despite
appropriate therapy [32].
Syphilis infection may persist for life. Treponemes appear to persist in extracellular loci with little
or no inflammatory response elicited. A history of syphilis or treatment for syphilis provides
relatively minor and unreliable protection against subsequent infection [33]. Active disease after
reinfection is common, regardless of nontreponemal antibody reactivity.
PREVENTION Measures to prevent congenital syphilis include screening of pregnant women
and international adoptees, contact tracing, contact precautions, and monitoring of close contacts
of infectious patients for clinical or serologic evidence of disease.
Prevention of acquired syphilis is discussed separately. (See "Syphilis: Treatment and
monitoring", section on 'Prevention' and "Syphilis: Epidemiology, pathophysiology, and clinical
manifestations in HIV-uninfected patients", section on 'Epidemiology'.)

Screening Most cases of congenital syphilis are preventable with routine prenatal care,
screening of pregnant women for syphilis, penicillin treatment of infected women and their sexual
partners, and appropriate monitoring and interpretation of treatment response [5,34-39].
Screening and treatment of syphilis during pregnancy are discussed separately. (See "Syphilis in
pregnancy" and "Syphilis in pregnancy", section on 'Maternal screening' and "Syphilis in
pregnancy", section on 'Maternal treatment'.)
However, current screening practices have limitations. Lack of prenatal care is the most
important. Among the 431 cases of congenital syphilis reported to the US Centers for Disease
Control and Prevention (CDC) in 2008, approximately one-third were born to mothers who did not
receive prenatal care [28]. Although the CDC and the American Academy of Pediatrics
recommend that newborn infants remain hospitalized until there is documentation of the mother's
syphilis serology (at least once during pregnancy and ideally again at delivery), adherence to this
recommendation may be difficult, particularly when an early discharge is planned [3,4,40].
The possibility of false negative results of nontreponemal serology is another important limitation
(see "Syphilis: Screening and diagnostic testing", section on 'Negative nontreponemal test in
early syphilis'). A negative maternal nontreponemal test at delivery does not exclude incubating
syphilis or primary syphilis if it is too early for maternal antibodies to have reached detectable
concentrations [41,42]. Infants born in such circumstances continue to escape detection until they
become symptomatic, typically at 3 to 14 weeks of age [2]. Repeat maternal screening at the first
postpartum visit may be warranted for mothers who engage in high-risk behaviors or reside in
areas with high prevalence of syphilis.
International adoptees Syphilis testing is recommended as part of the evaluation of
internationally adopted children, even if they are reported to have received evaluation and
treatment in their home country [19]. Congenital syphilis may be undiagnosed or inadequately
treated in developing countries [43]. (See "International adoption: Infectious disease aspects",
section on 'Syphilis'.)
Isolation precautions Standard precautions are recommended for infants with suspected or
proven congenital syphilis [4]. (See "General principles of infection control", section on 'Standard
precautions'.) In addition, gloves should be worn when caring for infants with skin or mucous
membrane lesions until 24 hours of treatment have been completed [44]. Moist open lesions,
secretions, and body fluids (eg, CSF, blood) contain spirochetes and are infectious [13].
Close contacts Persons, including hospital personnel, who had close unprotected contact
with a child with early congenital syphilis before the child was diagnosed or during the first 24
hours of treatment should be examined for syphilitic lesions (ie, chancre) two to three weeks after
contact [4]. Serologic testing should be performed and repeated three months after exposure, or
sooner if symptoms develop. Immediate treatment (penicillin G
benzathine 50,000 units/kg intramuscularly as a single dose; maximum dose 2.4 million units)
may be warranted if the degree of exposure was substantial.
REPORTING REQUIREMENTS In the United States, congenital syphilis is a national notifiable
disease [45]. However, reporting requirements vary by state. Reporting to the US Centers for
Disease Control and Prevention by the states is voluntary. For reporting purposes, congenital
syphilis includes stillbirths due to syphilis, cases of congenital syphilis detected in newborns, and

cases of congenitally acquired syphilis in infants and children [1]. Reporting of syphilis to state or
local health departments permits contact investigation, appropriate follow-up, and identification of
populations at increased risk.