Congenital syphilis: Clinical features and diagnosis

Author
Simon R Dobson, MD, FRCP(C

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.

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].
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].

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.
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/treatmentresponse 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).

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].

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..

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. 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].
●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). The nasal discharge contains spirochetes and can transmit infection by direct
contact. It should be examined by darkfield microscopy to confirm the diagnosis.
●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.

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].

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. 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)
●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).

●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).

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).

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.

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
●Renal – 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)
●Rubella virus infection
●Cytomegalovirus infection)
●Herpes simplex virus)
●Neonatal sepsis)
●Neonatal hepatitis)
●Hydrops fetalis ()
●Long-bone abnormalities (eg, osteomyelitis, rickets, physical abuse) or failure to move an
extremity
●Vesicular lesions

Historical features, additional findings, and/orlaboratory 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

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 ofproven/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.

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.

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). 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:

●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.

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).
●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.

Additional evaluation depends upon the findings from the initial evaluation and is discussed
separately. ()

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.

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.
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
receivedinadequate/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.

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) benzathine penicillin [47,48,67]. No additional evaluation is needed [47].

Management of infants in whom congenital syphilis is less likely is discussed separately. (

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.

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 1 and table 6) [47,48]..)

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]..)

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.

The possibility of sexual abuse must be considered in children who are determined to have
acquired syphilis.

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].

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at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might
have about a given condition. These articles are best for patients who want a general overview and
who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer,
th th
more sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading
level and are best for patients who want in-depth information and are comfortable with some
medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or
e-mail these topics to your patients. (You can also locate patient education articles on a variety of
subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topic)

SUMMARY AND RECOMMENDATIONS

●Congenital syphilis is acquired through transplacental transmission of spirochetes. Women

with untreated primary or secondary syphilis are more likely to transmit syphilis to their fetuses
than women with latent disease. Treponema pallidum is not transferred in breast milk.
●Early congenital syphilis is arbitrarily defined by clinical manifestations with onset before two
years of age. Manifestations of early clinical syphilis are varied and unpredictable (table 4).
●Late congenital syphilis is arbitrarily defined by clinical manifestations with onset after two
years of age. Manifestations of late congenital syphilis are related to scarring or persistent
inflammation from early infection (table 5
●The differential diagnosis of congenital syphilis in neonates includes other congenital
infections (toxoplasmosis, rubella, cytomegalovirus, herpes simplex virus, neonatal sepsis),
and other causes of neonatal hepatitis, hydrops fetalis, long-bone abnormalities, and
cutaneous lesions. Historical features, additional clinical findings, and/or laboratory testing
usually differentiate these conditions from congenital syphilis
●The Centers for Disease Control and Prevention and the American Academy of Pediatrics
Committee on Infectious Diseases provide guidelines for the evaluation and management of
congenital syphilis (algorithm 1 and table 6).
●The diagnosis of congenital syphilis should be suspected in all infants born to women who
have reactive nontreponemal and treponemal tests for syphilis andinfants/children with clinical
findings compatible with congenital syphilis (table 4and table 5). (
●The initial evaluation for congenital syphilis in infants and children should include a
quantitative Venereal Disease Research Laboratory (VDRL) or rapid plasma reagin (RPR) titer
(for infants <1 month of age, the test should be the same as that which was performed on the
mother); physical examination for evidence of congenital syphilis; darkfield microscopic
examination or direct fluorescent antibody staining of suspicious lesions or body fluids (eg,
nasal discharge); and, for newborns, pathologic examination of the placenta and umbilical
cord with specific fluorescent antitreponemal antibody staining (if possible).
●The diagnosis of syphilis may be established by direct visualization of T. pallidum in clinical
specimens (picture 11and picture 12) or serologic reactions typical of syphilis. To prevent
long-term morbidity, it is also important to identify (and treat) infants at risk for clinical syphilis.
●The treatment of congenital syphilis is discussed separately.