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Congenital syphilis: Evaluation, management, and

prevention
Author: Simon R Dobson, MD, FRCP(C)
Section Editors: Sheldon L Kaplan, MD, Leonard E Weisman, MD
Deputy Editor: Carrie Armsby, MD, MPH
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Jun 2022. | This topic last updated: Mar 26, 2021.
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 evaluation, management, and prevention of congenital syphilis will be discussed here.
The clinical features and diagnosis of congenital syphilis are discussed separately. (See
"Congenital syphilis: Clinical features and diagnosis".)
Syphilis in pregnancy and acquired syphilis also are discussed separately:
● (See "Syphilis in pregnancy".)

● (See "Syphilis: Epidemiology, pathophysiology, and clinical manifestations in patients
without HIV".)
● (See "Syphilis: Epidemiology, pathophysiology, and clinical manifestations in patients
without HIV", section on 'Clinical manifestations'.)
● (See "Syphilis: Treatment and monitoring".)
● (See "Neurosyphilis".)
● (See "Syphilis: Screening and diagnostic testing".)
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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 [2,3]. The United
States Centers for Disease Control and Prevention (CDC) and the American Academy of
Pediatrics (AAP) Committee on Infectious Diseases provide guidelines for the evaluation and
management of congenital syphilis ( algorithm 1 and table 1) [4,5]. Similar guidelines
are provided by the World Health Organization [6].
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 [4,5]:
● 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) [4,5]:
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● 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
'Prevalence').
● 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) [7].
Proven or highly probable disease — Congenital syphilis is proven or highly probable if

the infant has at least one of the following [4,5]:
● 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
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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 [4,5]. (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 'Cerebrospinal fluid 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) [4,5]:
● 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 [4,5]. (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
[4,5] (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 [4,5] (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 [4,8,9]. (See 'Cerebrospinal fluid 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):
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● 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) [4,5] (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 [7,10-12]; 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 [13,14].
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 before pregnancy, provided that all of the following
criteria are met [4]:
● 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 accordance with the AAP and CDC, we suggest that infants in this category do not require
treatment with penicillin ( algorithm 1 and table 1) [4,5]. 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'
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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) [5]. Some experts would also opt to treat such infants even if their
mothers were adequately treated [2,4,15]. 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 [1,16].
The evaluation of such children may include [4,5]:
● 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
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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 [4,5].
(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 [17].
PENICILLIN THERAPY
Parenteral penicillin is the drug of choice for the treatment of congenital syphilis [4,5].
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 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
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treatment or inadequate/suboptimal treatment for syphilis during pregnancy ( table 3)

[13,14]. One compared single-dose penicillin G benzathine with no therapy in asymptomatic
infants at high risk of congenital syphilis (untreated mothers with Venereal Disease Research
Laboratory test [VDRL] ≥1:32) [13]. None of 11 infants in the treatment group developed
congenital syphilis (defined by immunoglobulin M (IgM) Western blots and VDRL titers),
compared with four of eight infants who were not treated [13]. In the second trial, treatment
of asymptomatic infants (normal physical examination, normal cerebrospinal fluid [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 rapid plasma reagin (RPR)
by at least fourfold [14].
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; complete blood count [CBC] with
differential and platelet count; and long-bone radiographs) and has completely normal
results [4,5]. The evaluation is necessary to exclude central nervous system (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 [18,19]. 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 [4,5]:
● 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 [20]. However, the clinical significance of this observation is
unclear, since there have been no treatment failures reported after treatment with procaine
penicillin [5].
A full 10-day course of penicillin should be administered, even if the infant initially received
ampicillin for possible sepsis [4,5]. If more than one day of penicillin therapy is missed, the
entire course should be restarted.
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>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 IV every four to six hours for 10 days)
[4,5]. In addition, for children with congenital syphilis or findings compatible with CNS
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 IM).
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 IM) [4,5].
Adverse effects
Jarisch-Herxheimer reaction — The Jarisch-Herxheimer reaction generally consists of fever

2 to 12 hours after initiation of therapy for active syphilis [21]. However, cardiovascular
collapse, seizures, and death also have been reported [22]. 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 [4,5]. Effective treatment of syphilis requires maintenance of a minimal
inhibitory concentration (MIC) of 0.03 units/mL of penicillin in serum (or CSF) 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 United
States Centers for Disease Control and Prevention (CDC) and the American Academy of
Pediatrics (AAP) recommend desensitization and then treatment with penicillin [4,5]. (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 HIV should receive the same evaluation and treatment as those whose mothers do not
have HIV infection [4]. There is insufficient evidence to determine whether such infants
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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 [4,5,15,23,24].
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) [4,5].
Evaluation for hearing loss, ophthalmologic abnormalities, and neurodevelopmental
problems should occur yearly [2]. (See "Hearing loss in children: Screening and evaluation"
and "Vision screening and assessment in infants and children" and "Developmental-
behavioral surveillance and screening in primary care".)
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)
[4,25,26].
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 immunoglobulin G [IgG] antibody) [4,27,28]. 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
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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 [4,5]. (See 'Cerebrospinal fluid
evaluation' below and 'Penicillin therapy' above.)
Treponemal tests — 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]) should not be used to evaluate treatment response because they can remain positive
despite effective treatment [4,29].
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 [2,15]. 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 [2,26]. 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.)
Cerebrospinal fluid evaluation — Serial 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) [4]. 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 [4,5] (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 [5].
OUTCOME
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In the United States, the case fatality rate for congenital syphilis is between 6 and 8 percent
[30,31]. 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 [28,32,33].
Interstitial keratitis ( picture 2) and anterior tibial bowing ("saber shins") ( picture 3) may
occur or progress despite appropriate therapy [34].
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 [35]. 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.
In 2007, the World Health Organization (WHO) launched an initiative to eliminate congenital
syphilis that set targets of at least 90 percent of pregnant women being tested for syphilis
and at least 90 percent of seropositive pregnant women receiving adequate treatment by
2015 [36]. Considerable progress has been made toward these goals, particularly with
regards to [37]:
● Increasing access to maternal and newborn services

● Screening and treating pregnant women and their partners
● Establishing surveillance, monitoring, and evaluation systems
● Ensuring advocacy and sustained political commitment
Linking the efforts for global elimination of congenital syphilis to an integrated strategy of
eliminating mother-to-child HIV transmission affords the opportunity of synergistic benefits.
In a 2015 report the included data from 58 countries, the median proportion of pregnant
women receiving at least one antenatal care visit was 90 percent, and there were notable
successes in declaring some countries free of mother-to-child transmission of syphilis [38].
Prevention of acquired syphilis is discussed in greater detail separately. (See "Syphilis:
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Treatment and monitoring", section on 'Treatment after an exposure' and "Syphilis:

Epidemiology, pathophysiology, and clinical manifestations in patients without HIV", 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
[7,39-44]. Screening and treatment of syphilis during pregnancy are discussed separately.
(See "Syphilis in pregnancy" and "Syphilis in pregnancy", section on 'Maternal screening'.)
However, current screening practices have limitations. Lack of prenatal care is the most
important. Among the 431 cases of congenital syphilis reported to the United States Centers
for Disease Control and Prevention (CDC) in 2008, approximately one-third were born to
mothers who did not receive prenatal care [30]. Although the CDC and the American
Academy of Pediatrics (AAP) 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 [4,5,45].
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 [46,47]. 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 [21]. Congenital syphilis may be undiagnosed or
inadequately treated in developing countries [48]. (See "International adoption: Infectious
disease aspects", section on 'Syphilis'.)
Isolation precautions — Standard precautions are recommended for infants with suspected

or proven congenital syphilis [5]. (See "Infection prevention: Precautions for preventing
transmission of infection", section on 'Standard precautions'.) In addition, gloves should be
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worn when caring for infants with skin or mucous membrane lesions until 24 hours of
treatment have been completed [49]. Moist open lesions, secretions, and body fluids (eg,
cerebrospinal fluid, blood) contain spirochetes and are infectious [15].
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 [5]. 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 [50]. 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.
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● Basics topic (see "Patient education: Congenital syphilis (The Basics)")
SUMMARY AND RECOMMENDATIONS
● The United States 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 1). (See
'Evaluation and management of infants <1 month of age' above.)
● The diagnosis of congenital syphilis should be suspected in all infants born to women
who have reactive nontreponemal and treponemal tests for syphilis and
infants/children with clinical findings compatible with congenital syphilis ( table 2).
The initial evaluation of infants <1 month of age should include (see 'Initial evaluation'
above):
• Venereal Disease Research Laboratory (VDRL) or rapid plasma reagin (RPR) titers (the
same test that was performed on the mother)
• Physical examination for evidence of congenital syphilis with darkfield microscopic

examination or direct fluorescent antibody (DFA) staining of suspicious lesions or
body fluids (eg, nasal discharge); and
• Pathologic examination of the placenta and umbilical cord with specific fluorescent
antitreponemal antibody staining (if possible)
Additional evaluation depends upon the findings from the initial evaluation ( table 1).
(See 'Subsequent evaluation and management' above.)
● Congenital syphilis is proven or highly probable if the infant has examination findings
compatible with congenital syphilis ( table 2); VDRL or RPR titer that is ≥fourfold the
corresponding maternal titer; or a positive darkfield ( picture 1) or fluorescent
antibody test of body fluid(s), placenta, or umbilical cord. Such infants should be
evaluated with cerebrospinal fluid (CSF) VDRL, cell count, and protein; complete blood
count with differential and platelet count; and additional tests as clinically indicated (
table 1). (See 'Proven or highly probable disease' above.)
● For infants with proven or highly probable congenital syphilis, we recommend

treatment with 10 days of parenteral penicillin (Grade 1A). (See 'Ten-day regimens'
above.)
15 de 35 28/07/22 16:05
● Infants born to women with syphilis or a history of syphilis remain at risk for syphilis
even if the infant has a normal physical examination and VDRL or RPR that is
nonreactive or less than fourfold the maternal titer. The evaluation and treatment of at-
risk neonates varies depending upon the mother's history of syphilis and syphilis
treatment and the treatment plan for the infant ( algorithm 1 and table 1). (See
'Possible congenital syphilis' above and 'Congenital syphilis less likely' above.)
● For infants who are at risk for congenital syphilis, we recommend treatment with
parenteral penicillin (Grade 1A). The regimen varies depending upon the clinical
circumstances ( table 1). (See 'Penicillin therapy' above.)
● Infants and children who have reactive serologic tests for syphilis or were born to
mothers who were seroreactive at delivery should undergo monitoring for clinical
manifestations of congenital syphilis at well-child care visits throughout childhood.
VDRL or RPR should be repeated every two to three months until the test becomes
nonreactive or the titer has decreased fourfold. Serial CSF evaluation is necessary for
infants and children whose initial CSF evaluation was abnormal without an alternative
explanation. (See 'Follow-up evaluations' above.)
● 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. (See
'Prevention' above.)
Use of UpToDate is subject to the Terms of Use.
REFERENCES
1. Centers for Disease Control and Prevention. Syphilis (Treponema pallidum) 2018 Case De
finition. https://ndc.services.cdc.gov/case-definitions/syphilis-2018/ (Accessed on June 1
7, 2021).
2. Dobson SR, Sanchez PJ. Syphilis. In: Feigin and Cherry’s Textbook of Pediatric Infectious
Diseases, 8th Ed, Cherry JD, Harrison GJ, Kaplan SL, Steinbach, WJ, Hotez, PJ (Eds), Elsevie
r, Philadelphia, PA 2019. p.1268.
3. Kimball A, Torrone E, Miele K, et al. Missed Opportunities for Prevention of Congenital

Syphilis - United States, 2018. MMWR Morb Mortal Wkly Rep 2020; 69:661.
4. Workowski KA, Bolan GA, Centers for Disease Control and Prevention. Sexually
16 de 35 28/07/22 16:05
transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep 2015; 64:1.
5. American Academy of Pediatrics. Syphilis. In: Red Book: 2021-2024 Report of the Commit
tee on Infectious Diseases, 32nd ed, Kimberlin DW, Barnett ED, Lynfield R, Sawyer MH (E
ds), American Academy of Pediatrics, Itasca, IL 2021. p.729.
6. WHO guidelines for the treatment of Treponema pallidum (syphilis). 2016. Available at: h
ttp://apps.who.int/iris/bitstream/10665/249572/1/9789241549806-eng.pdf?ua=1 (Access
ed on September 15, 2016).
7. McFarlin BL, Bottoms SF, Dock BS, Isada NB. Epidemic syphilis: maternal factors
associated with congenital infection. Am J Obstet Gynecol 1994; 170:535.
8. Beeram MR, Chopde N, Dawood Y, et al. Lumbar puncture in the evaluation of possible
asymptomatic congenital syphilis in neonates. J Pediatr 1996; 128:125.
9. Moyer VA, Schneider V, Yetman R, et al. Contribution of long-bone radiographs to the

management of congenital syphilis in the newborn infant. Arch Pediatr Adolesc Med
1998; 152:353.
10. Alexander JM, Sheffield JS, Sanchez PJ, et al. Efficacy of treatment for syphilis in
pregnancy. Obstet Gynecol 1999; 93:5.
11. Conover CS, Rend CA, Miller GB Jr, Schmid GP. Congenital syphilis after treatment of
maternal syphilis with a penicillin regimen exceeding CDC guidelines. Infect Dis Obstet
Gynecol 1998; 6:134.
12. Sheffield JS, Sánchez PJ, Morris G, et al. Congenital syphilis after maternal treatment for
syphilis during pregnancy. Am J Obstet Gynecol 2002; 186:569.
13. Radcliffe M, Meyer M, Roditi D, Malan A. Single-dose benzathine penicillin in infants at

risk of congenital syphilis--results of a randomised study. S Afr Med J 1997; 87:62.
14. Paryani SG, Vaughn AJ, Crosby M, Lawrence S. Treatment of asymptomatic congenital
syphilis: benzathine versus procaine penicillin G therapy. J Pediatr 1994; 125:471.
15. Kollmann TR, Dobson S. Syphilis. In: Infectious Diseases of the Fetus and Newborn Infan
t, 7th, Remington JS, Klein JO, Wilson CB, et al (Eds), Elsevier Saunders, Philadelphia 2011.
p.524.
16. Christian CW, Lavelle J, Bell LM. Preschoolers with syphilis. Pediatrics 1999; 103:E4.
17. Chakraborty R, Luck S. Syphilis is on the increase: the implications for child health. Arch
Dis Child 2008; 93:105.
18. Beck-Sague C, Alexander ER. Failure of benzathine penicillin G treatment in early

congenital syphilis. Pediatr Infect Dis J 1987; 6:1061.
17 de 35 28/07/22 16:05
19. Woolf A, Wilfert CM, Kelsey DB. Childhood syphilis in North Carolina. N C Med J 1980;
41:443.
20. Azimi PH, Janner D, Berne P, et al. Concentrations of procaine and aqueous penicillin in
the cerebrospinal fluid of infants treated for congenital syphilis. J Pediatr 1994; 124:649.
21. Woods CR. Syphilis in children: congenital and acquired. Semin Pediatr Infect Dis 2005;
16:245.
22. HOLZEL A. Jarisch-Herxheimer reaction following penicillin treatment of early congenital

syphilis. Br J Vener Dis 1956; 32:175.
23. Ikeda MK, Jenson HB. Evaluation and treatment of congenital syphilis. J Pediatr 1990;
117:843.
24. Rathbun KC. Congenital syphilis: a proposal for improved surveillance, diagnosis, and
treatment. Sex Transm Dis 1983; 10:102.
25. Hardy JB, Hardy PH, Oppenheimer EH, et al. Failure of penicillin in a newborn with
congenital syphilis. JAMA 1970; 212:1345.
26. Rawstron SA, Mehta S, Marcellino L, et al. Congenital syphilis and fluorescent
treponemal antibody test reactivity after the age of 1 year. Sex Transm Dis 2001; 28:412.
27. Chang SN, Chung KY, Lee MG, Lee JB. Seroreversion of the serological tests for syphilis in
the newborns born to treated syphilitic mothers. Genitourin Med 1995; 71:68.
28. Lago EG, Vaccari A, Fiori RM. Clinical features and follow-up of congenital syphilis. Sex
Transm Dis 2013; 40:85.
29. Singh AE, Guenette T, Gratrix J, et al. Seroreversion of treponemal tests in infants
meeting canadian surveillance criteria for confirmed early congenital syphilis. Pediatr
Infect Dis J 2013; 32:199.
30. Centers for Disease Control and Prevention (CDC). Congenital syphilis - United States,
2003-2008. MMWR Morb Mortal Wkly Rep 2010; 59:413.
31. Gust DA, Levine WC, St Louis ME, et al. Mortality associated with congenital syphilis in
the United States, 1992-1998. Pediatrics 2002; 109:E79.
32. PUTKONEN T. Does early treatment prevent dental changes in congenital syphilis? Acta
Derm Venereol 1963; 43:240.
33. Stamos JK, Rowley AH. Timely diagnosis of congenital infections. Pediatr Clin North Am
1994; 41:1017.
34. OKSALA A. Interstitial keratitis after adequate penicillin therapy; a case report. Br J Vener
Dis 1957; 33:113.
18 de 35 28/07/22 16:05
35. Pavithran K. Acquired syphilis in a patient with late congenital syphilis. Sex Transm Dis
1987; 14:119.
36. The World Health Organization. The global elimination of congenital syphillis: Rationale
and strategy for action. http://www.who.int/reproductivehealth/publications/rtis/978924
1595858/en/ (Accessed on December 20, 2016).
37. The World Health Organization. Elimination of mother-to-child transmission (EMTCT) of

HIV and syphilis: Global guidance on criteria and processes for validation. http://www.w
ho.int/reproductivehealth/publications/rtis/9789241505888/en/ (Accessed on December
20, 2016).
38. Kiarie J, Mishra CK, Temmerman M, Newman L. Accelerating the dual elimination of
mother-to-child transmission of syphilis and HIV: Why now? Int J Gynaecol Obstet 2015;
130 Suppl 1:S1.
39. Coles FB, Hipp SS, Silberstein GS, Chen JH. Congenital syphilis surveillance in upstate
New York, 1989-1992: implications for prevention and clinical management. J Infect Dis
1995; 171:732.
40. Mascola L, Pelosi R, Blount JH, et al. Congenital syphilis. Why is it still occurring? JAMA
1984; 252:1719.
41. Desenclos JC, Scaggs M, Wroten JE. Characteristics of mothers of live infants with
congenital syphilis in Florida, 1987-1989. Am J Epidemiol 1992; 136:657.
42. Webber MP, Lambert G, Bateman DA, Hauser WA. Maternal risk factors for congenital
syphilis: a case-control study. Am J Epidemiol 1993; 137:415.
43. Southwick KL, Guidry HM, Weldon MM, et al. An epidemic of congenital syphilis in
Jefferson County, Texas, 1994-1995: inadequate prenatal syphilis testing after an
outbreak in adults. Am J Public Health 1999; 89:557.
44. Warner L, Rochat RW, Fichtner RR, et al. Missed opportunities for congenital syphilis
prevention in an urban southeastern hospital. Sex Transm Dis 2001; 28:92.
45. Martin D, Bertrand J, McKegney C, et al. Congenital syphilis surveillance and newborn
evaluation in a low-incidence state. Arch Pediatr Adolesc Med 2001; 155:140.
46. Dorfman DH, Glaser JH. Congenital syphilis presenting in infants after the newborn
period. N Engl J Med 1990; 323:1299.
47. Sánchez PJ, Wendel GD, Norgard MV. Congenital syphilis associated with negative results
of maternal serologic tests at delivery. Am J Dis Child 1991; 145:967.
48. Staat MA. Infectious disease issues in internationally adopted children. Pediatr Infect Dis
19 de 35 28/07/22 16:05
J 2002; 21:257.
49. TUCKER HA, ROBINSON RC. Disappearance time of Treponema pallidum from lesions of
early syphilis following administration of crystalline penicillin G. Bull Johns Hopkins Hosp
1947; 80:169.
50. Centers for Disease Control and Prevention. National Notifiable Diseases Surveillance Sy
stem. http://www.cdc.gov/osels/ph_surveillance/nndss/phs/infdis.htm (Accessed on Aug
ust 12, 2011).
Topic 15400 Version 30.0
20 de 35 28/07/22 16:05
GRAPHICS
Congenital syphilis: Evaluation and management
21 de 35 28/07/22 16:05
RPR: rapid plasma reagin; VDRL: Venereal Disease Research Laboratory; TP-PA: Treponema pallidum particle agglut
antibody absorption; TP-EIA: T. pallidum enzyme immunoassay; MHA-TP: microhemagglutination test for antibodie
* This algorithm does not apply if maternal samples are screened in reverse order (ie, treponemal test is performe
of interpretation of reverse sequence testing, please refer to the UpToDate topic on diagnosis of syphilis.
¶ TP-PA, FTA-ABS, TP-EIA, or MHA-TP.
Δ Test for HIV antibody. Infants of HIV-infected mothers do not require different evaluation or treatment.
◊ A fourfold change in titer is the same as a change of 2 dilutions. For example, a titer of 1:64 is fourfold greater t
fourfold lower than a titer of 1:16.
§ Women who maintain a VDRL titer 1:2 or less or an RPR 1:4 or less beyond 1 year after successful treatment are
¥ Complete blood cell and platelet count; CSF examination for cell count, protein, and quantitative VDRL; other tes
radiographs, long-bone radiographs, eye examination, liver function tests, neuroimaging, and auditory brainstem
‡ Some experts would consider a single intramuscular injection of benzathine penicillin (treatment option 2), parti
† Treatment (option 1 or option 2, above) with many experts recommending treatment option 1. If a single dose o
infant must be fully evaluated, full evaluation must be normal, and follow-up must be certain. If any part of the inf
performed, or if the CSF analysis is rendered uninterpretable, then a 10-day course of penicillin is required.
From: American Academy of Pediatrics. Syphilis. In: Red Book: 2012 Report of the Committee on Infectious Diseases, 29 th ed, Pickering LK (Ed
Village, IL 2012. Copyright © 2012 American Academy of Pediatrics. Used with permission. The contents of this figure remain unchanged in t
Infectious Diseases, 31 st ed.
Graphic 51559 Version 19.0
22 de 35 28/07/22 16:05
Evaluation and management of neonates (<1 month) born to women with

syphilis or history of syphilis*
Initial neonatal
Maternal treatment Subsequent
evaluation Treatment
neonatal
of neonate
Neonate Neonate evaluation
Timing Type
VDRL/RPR evaluation
Any result Examination Any Any or none ▪ CSF VDRL, 10 days of

compatible cell count, parenteral
with protein penicillin ◊
congenital ▪ CBC with
syphilis or differential
visualization and platelet
of spirochete count
in clinical ▪ Additional
specimen ¶ tests as
clinically
indicated Δ
≥ Fourfold Any Any Any ▪ CSF VDRL, 10 days of

maternal cell count, parenteral
titer protein penicillin ◊
▪ CBC with
differential
and platelet
count
▪ Additional
tests as
clinically
indicated Δ
< Fourfold Normal During None, ▪ CSF VDRL, If the entire

maternal titer physical pregnancy inadequate, cell count, evaluation is
examination suboptimal ‡ protein performed
▪ CBC with and normal † :
differential Single dose
and platelet IM
count benzathine
▪ Additional penicillin ¥ ;
tests as some experts
clinically would treat
indicated Δ with 10 days
of parenteral
23 de 35 28/07/22 16:05
penicillin ◊
If any portion
of the
evaluation is
abnormal, not
performed, or
not
interpretable:
10 days of
parenteral
penicillin ◊
< Fourfold Normal Before Evidence of ▪ CSF VDRL, If the entire

maternal titer physical pregnancy reinfection or cell count, evaluation is
examination relapse (≥ protein performed
fourfold ▪ CBC with and normal:
increase in differential Single dose
post- and platelet IM
treatment count benzathine
titer) ▪ Additional penicillin ¥
tests as If any portion
clinically of the
indicated Δ evaluation is
abnormal,
not
performed, or
not
interpretable:
10 days of
parenteral
penicillin ◊
< Fourfold Normal During Adequate § None Single dose

maternal titer physical pregnancy IM
examination benzathine
penicillin ¥ ;
some experts
would not
treat but
provide close
serologic
follow-up
< Fourfold Normal Before Adequate § None None; some

maternal titer physical pregnancy experts
examination would treat
24 de 35 28/07/22 16:05
with a single
dose of IM
benzathine
penicillin ¥
Nonreactive Normal During None, None Single dose

physical pregnancy inadequate, IM
examination suboptimal ‡ benzathine
penicillin ¥
Nonreactive Normal During Adequate § None None; some

physical pregnancy experts
examination would treat
with a single
dose of IM
benzathine
penicillin ¥
Neonate characteristics in bold text indicate proven or highly probable congenital syphilis
disease in the infant.
VDRL: Venereal Disease Research Laboratory serologic test for syphilis; RPR: rapid plasma reagin
serologic test for syphilis; CSF: cerebrospinal fluid; CBC: complete blood count; IM: intramuscular;
IV: intravenous.
* Mother with reactive nontreponemal (VDRL or RPR) and treponemal (microhemagglutination

test for T. pallidum [MHA-TP] or fluorescent treponemal antibody absorption [FTA-ABS]) serologic
tests for syphilis. All such infants require clinical and serologic follow-up (see text for details).
¶ Examination findings compatible with early congenital syphilis may include (but are not limited
to) hepatomegaly/hepatosplenomegaly; rash; condyloma lata; snuffles; jaundice;
pseudoparalysis; anemia; and edema.
Δ Additional tests may include: Long-bone radiographs, chest radiograph, liver function tests,
cranial ultrasonography, ophthalmologic examination, and auditory brainstem response.
◊ There are two alternate regimens: Aqueous penicillin G (50,000 units/kg IV every 12 hours [for
infants ≤7 days of age] and every 8 hours [>7 days of age] for a total of 10 days); or procaine
penicillin G 50,000 units/kg IM as a single daily dose for 10 days.
§ Adequate therapy encompasses treatment with penicillin more than four weeks before delivery;
appropriate dose for the stage of disease; documentation of treatment response (fourfold decline
in titer for early syphilis and titer remained stable or low [VDRL ≤1:2; RPR ≤1:4] for late syphilis);
no evidence of reinfection or relapse (fourfold increase in titer after treatment).
¥ Benzathine penicillin G (50,000 units/kg intramuscularly as a single dose).
‡ Inadequate or suboptimal maternal therapy encompasses: Treatment with a nonpenicillin

antibiotic; treatment less than four weeks before delivery; inappropriate dose for the stage of
disease; no documentation of maternal therapy; maternal titers did not decline at least fourfold
25 de 35 28/07/22 16:05
after treatment for early syphilis or did not remain stable and low [VDRL ≤1:2; RPR ≤1:4] for late
syphilis; or maternal titers increased by fourfold after treatment (suggesting reinfection or
relapse).
† Normal CSF is generally defined by nonreactive VDRL, CSF WBC <25 cells/microL, and CSF
protein <150 mg/dL for term infants and <170 mg/dL for preterm infants; however, some experts
define normal CSF WBC as <5 cells/microL and normal CSF protein as <40 mg/dL.
References:
1. Workowski KA, Bolan GA. Sexually Transmitted Diseases Treatment Guidelines, 2015. MMWR Recomm Rep 2015;
64:1.
2. American Academy of Pediatrics. Syphilis. In: Red Book: 2018 Report of the Committee on Infectious Diseases, 31st
ed, Kimberlin DW, Brady MT, Jackson MA, Long SS (Eds), American Academy of Pediatrics, Itasca, IL 2018. p.773.
3. Dobson SR, Sanchez PJ. Syphilis. In: Feigin and Cherry’s Textbook of Pediatric Infectious Diseases, 8th ed, Cherry
JD, Harrison GJ, Kaplan SL, et al (Eds), Elsevier Saunders, Philadelphia 2019. p.1268.
4. Kollmann TR, Dobson SD. Syphilis. In: Infectious Diseases of the Fetus and Newborn infant, 7th edition, Remington
JS, Klein JO, Wilson CB, et al (Eds), Elsevier Saunders, Philadelphia 2011. p.524.
26 de 35 28/07/22 16:05
Clinical manifestations of early congenital syphilis*
Gestational/perinatal
Stillbirth
Prematurity
Birth weight <2500 g
Nonimmune hydrops
fetalis
Placenta Large, thick, pale (send for pathologic/histologic evaluation)
Umbilical cord Inflamed with abscess-like foci of necrosis within Wharton's jelly,
centered around the umbilical vessels (necrotizing funisitis); barber-
pole appearance (send for pathologic/histologic evaluation)
Systemic
Fever May be more prominent in infants born to mothers who are
affected late in pregnancy and whose serology is negative at
delivery
Hepatomegaly Splenomegaly occurs in approximately one-half of patients with

hepatomegaly—isolated splenomegaly does not occur
Generalized May be as large as 1 cm; generally nontender and firm

lymphadenopathy
Failure to thrive
Edema Due to anemia/hydrops fetalis, nephrotic syndrome, malnutrition
Mucocutaneous
Syphilitic rhinitis Can be an early feature, developing after the first week of life;
("snuffles") contains spirochetes and is infectious (use contact precautions)
Maculopapular rash Usually appears one to two weeks after rhinitis. Oval lesions, initially
red or pink and then coppery brown; may be associated with
superficial desquamation or scaling, particularly on the palms or
soles; more common on the buttocks, back, posterior thighs, and
soles; contains spirochetes and is infectious (use contact
precautions).
Vesicular rash May be present at birth, most often develops in first four weeks;
(pemphigus syphiliticus) widely disseminated; vesicular fluid contains spirochetes and is
infectious (use contact precautions)
Condylomata lata Single or multiple, flat, wartlike, moist lesions around the mouth,
nares, and anus and other areas of the skin where there is moisture
27 de 35 28/07/22 16:05
or friction; lesions contain spirochetes and are infectious (use

contact precautions); frequently present without other signs of
infection
Jaundice Hyperbilirubinemia secondary to syphilitic hepatitis and/or

hemolysis
Hematologic
Anemia Newborn period: Hemolytic (Coomb's test [direct antiglobulin test]
negative); may persist after effective treatment
After one month of age: May be chronic and nonhemolytic
Thrombocytopenia May be associated with bleeding or petechiae; can be the only

manifestation of congenital infection
Leukopenia
Leukocytosis
Musculoskeletal
Pseudoparalysis of Lack of movement of an extremity because of pain associated with
Parrot bone lesion; affects upper extremities more often than lower;
usually unilateral; rarely present at birth; poorly correlated with
radiographic abnormalities
Radiographic Most frequent abnormality in untreated early congenital syphilis;

abnormalities: not usually clinically discernible; typically multiple and symmetric
Periostitis Irregular periosteal thickening; usually present at birth, but may

appear in the first few weeks of life
Wegner sign Metaphyseal serration or "sawtooth metaphysis"
Wimberger sign Demineralization and osseous destruction of the upper medial tibial
Neurologic
CSF abnormalities Reactive CSF VDRL; elevated CSF white blood cell count; elevated CSF
protein
Acute syphilitic Onset during the first year of life, usually between 3 and 6 months;
leptomeningitis presentation similar to bacterial meningitis but CSF findings more
consistent with aseptic meningitis (mononuclear predominance);
responds to penicillin therapy
Chronic Onset toward the end of the first year; hydrocephalus; cranial nerve
meningovascular palsies; intellectual/neurodevelopmental deterioration; cerebral
syphilis infarction; protracted course
Miscellaneous
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Pneumonia/pneumonitis Complete opacification of both lung fields on chest radiograph

/respiratory distress
Nephrotic syndrome Usually occurs at two to three months of age and manifests with
generalized edema and ascites
CSF: cerebrospinal fluid; VDRL: Venereal Disease Research Laboratory test.
* All of these findings may occur in other congenital infections; none is specific for congenital
syphilis.
Data from:
1. Ingall D, Sanchez PJ, Baker CH. Syphilis. In: Infectious Diseases of the Fetus and Newborn infant, 6th edition,
Remington JS, Klein JO, Wilson CB, Baker CJ (Eds), Elsevier Saunders, Philadelphia 2006. p.545.
2. Dobson SR, Sanchez PJ. Syphilis. In: Feigin and Cherry's Textbook of Pediatric Infectious Diseases, 7th, Cherry JD,
Harrison GJ, Kaplan SL, et al. (Eds), Elsevier Saunders, Philadelphia 2014. p.1761.
3. Woods CR. Syphilis in children: congenital and acquired. Semin Pediatr Infect Dis 2005; 16:245.
4. Saloojee H, Velaphi S, Goga Y, et al. The prevention and management of congenital syphilis: an overview and
recommendations. Bull World Health Organ 2004; 82:424.
5. Chakraborty R, Luck S. Syphilis is on the increase: the implications for child health. Arch Dis Child 2008; 93:105.
6. Rawstron SA. Treponema pallidum (Syphilis). In: Principles and Practice of Pediatric Infectious Diseases, 3rd
edition, Long SS, Pickering LK, Prober CG (Eds), Churchill Livingstone Elsevier, Philadelphia 2008. p.930.
29 de 35 28/07/22 16:05
Treponema pallidum spirochetes depicted with

darkfield microscopy
Using a darkfield microscopy technique, this photomicrograph

revealed the presence of Treponema pallidum spirochetes, which are
the bacterial agents that cause syphilis.
Courtesy of the Centers for Disease Control and Prevention/Schwartz WF.
30 de 35 28/07/22 16:05
Inadequate or suboptimal treatment of maternal syphilis
Inadequate therapy
Treatment with a nonpenicillin antibiotic
Treatment less than four weeks before delivery (including treatment with penicillin)
Inappropriate dose for stage of disease
Inadequate documentation of maternal treatment

Lack of performance of serial non-treponemal* antibody titers after maternal treatment
Maternal therapy was not documented
Inadequate response to therapy

Maternal non-treponemal antibody titers did not decline at least fourfold (two dilutions) after
treatment
Maternal non-treponemal antibody titers suggest reinfection or relapse (ie, fourfold increase)
* Non-treponemal test: Rapid plasma reagin (RPR) test or Venereal Disease Research Laboratory
(VDRL) test.
References:
1. Centers for Disease Control and Prevention. Syphilis (Treponema pallidum) 2018 Case Definition.
https://ndc.services.cdc.gov/case-definitions/syphilis-2018/ (Accessed on June 17, 2021).
2. American Academy of Pediatrics. Syphilis. In: Red Book: 2021-2024 Report of the Committee on Infectious
Diseases, 32nd ed, Kimberlin DW, Barnett ED, Lynfield R, Sawyer MH (Eds), American Academy of Pediatrics, Itasca,
IL 2021. p.729.
3. Workowski KA, Bolan GA. Sexually Transmitted Diseases Treatment Guidelines, 2015. MMWR Recomm Rep 2015;
64:1.
31 de 35 28/07/22 16:05
Stigmata of late congenital syphilis
Facial features Frontal bossing, saddle nose, short maxilla, protuberant mandible
Ophthalmologic Interstitial keratitis, chorioretinitis, secondary glaucoma, corneal scarring,

optic atrophy
Ears Sensorineural hearing loss
Oropharynx Hutchinson teeth, mulberry molars, perforation of hard palate
Cutaneous Rhagades, gummas
Central nervous Intellectual disability, arrested hydrocephalus, seizures, optic atrophy,

system juvenile general paresis
Skeletal Saber shins (anterior bowing of the tibia), Higoumenakis sign (enlargement
of the sternoclavicular portion of the clavicle), Clutton joints (painless
arthritis), scaphoid scapula
Data from:
1. Ingall D, Sanchez PJ, Baker CH. Syphilis. In: Infectious Diseases of the Fetus and Newborn infant, 6th edition,
Remington JS, Klein JO, Wilson CB, Baker CJ (Eds), Elsevier Saunders, Philadelphia 2006. p.545.
2. Dobson SR, Sanchez PJ. Syphilis. In: Feigin and Cherry’s Textbook of Pediatric Infectious Diseases, 7th, Cherry JD,
Harrison GJ, Kaplan SL, et al. (Eds), Elsevier Saunders, Philadelphia 2014. p.1761.
3. Woods CR. Syphilis in children: congenital and acquired. Semin Pediatr Infect Dis 2005; 16:245.
4. Chakraborty R, Luck S. Syphilis is on the increase: the implications for child health. Arch Dis Child 2008; 93:105.
32 de 35 28/07/22 16:05
Congenital syphilis: Interstitial keratitis
This photograph shows a stromal haze in both eyes of this child due
to interstitial keratitis, a manifestation of late congenital syphilis.
Interstitial keratitis is an inflammation of the connective tissue
structure of the cornea. It usually is bilateral.
Reproduced from: the Public Health Image Library, Centers for Disease Control and
Prevention. Photo by Susan Lindsley.
33 de 35 28/07/22 16:05
Congenital syphilis: Saber shins
Reproduced with permission from: Sweet RL, Gibbs RS. Atlas of Infectious Diseases of
the Female Genital Tract. Lippincott Williams & Wilkins, Philadelphia 2005. Copyright
© 2005 Lippincott Williams & Wilkins.
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Contributor Disclosures
Simon R Dobson, MD, FRCP(C) No relevant financial relationship(s) with ineligible companies to
disclose. Sheldon L Kaplan, MD Grant/Research/Clinical Trial Support: MeMed Diagnostics [Bacterial
and viral infections];Merck [Staphylococcus aureus];Pfizer [Streptococcus pneumoniae].
Consultant/Advisory Boards: MeMed Advisory Board [Diagnostics bacterial and viral infections]. Other
Financial Interest: Elsevier [Pediatric infectious diseases];Pfizer [PCV13]. All of the relevant financial
relationships listed have been mitigated. Leonard E Weisman, MD Equity Ownership/Stock Options:
Vax-Immune [Ureaplasma diagnosis, vaccines, antibodies, other medical diagnostics and pre-analytical
devices]. Patent Holder: Baylor College of Medicine [Ureaplasma diagnosis, vaccines, antibodies,
process for preparing biological samples]. All of the relevant financial relationships listed have been
mitigated. Carrie Armsby, MD, MPH No relevant financial relationship(s) with ineligible companies to
disclose.
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these
are addressed by vetting through a multi-level review process, and through requirements for
references to be provided to support the content. Appropriately referenced content is required of all
authors and must conform to UpToDate standards of evidence.
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Congenital Syphilis Evaluation, Management, and Prevention - UpToDate

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Congenital syphilis: Evaluation, management, and

Syphilis in pregnancy and acquired syphilis also are discussed separately:

● (See "Syphilis in pregnancy".)

EVALUATION AND MANAGEMENT OF INFANTS <1 MONTH OF AGE

Initial evaluation — The diagnosis of congenital syphilis should be suspected in all infants

● A quantitative nontreponemal test (Venereal Disease Research Laboratory test [VDRL]

● Physical examination for evidence of congenital syphilis ( table 2) and darkfield

● Pathologic examination of the placenta or umbilical cord with specific fluorescent

Subsequent evaluation and management — The subsequent evaluation depends upon

● If the mother has been treated for syphilis:

• The adequacy of therapy ( table 3).

• The likelihood of failure of maternal therapy to prevent congenital disease (higher

Proven or highly probable disease — Congenital syphilis is proven or highly probable if

● An abnormal physical examination that is consistent with congenital syphilis ( table 2

● A positive darkfield ( picture 1) or fluorescent antibody test of body fluid(s), placenta,

● Complete blood count (CBC) with differential and platelet count.

● Additional tests as clinically indicated: long-bone radiographs (for lack of movement of

tests (for hepatomegaly, jaundice), cranial ultrasound (for neurologic manifestations),

To prevent long-term morbidity, central nervous system syphilis is presumed in neonates

● CSF VDRL, cell count, and protein

Congenital syphilis less likely — No additional evaluation is necessary for the

● The infant has a normal physical examination.

● Mother was treated more than four weeks before delivery.

● Mother has no evidence of relapse or reinfection; relapse or reinfection are indicated by

Congenital syphilis unlikely — No additional evaluation is necessary for the asymptomatic

● The infant has a normal physical examination

EVALUATION AND MANAGEMENT OF CHILDREN >1 MONTH OF AGE

The evaluation of such children may include [4,5]:

● Complete blood count (CBC) with differential and platelet count.

● Evaluation and testing for HIV infection.

features and diagnosis", section on 'Long-bone radiographs'.)

Effective treatment of syphilis requires maintenance of a MIC of 0.03 units/mL of penicillin in

<1 month of age

Single-dose regimen — The single-dose regimen for treatment of congenital syphilis is as

● Penicillin G benzathine (50,000 units/kg, intramuscularly [IM] as a single dose)

treatment or inadequate/suboptimal treatment for syphilis during pregnancy ( table 3)

Single-dose therapy is contraindicated for asymptomatic infants born to women with

Jarisch-Herxheimer reaction — The Jarisch-Herxheimer reaction generally consists of fever

require different evaluation, treatment, or follow-up.

Nontreponemal tests — Quantitative Venereal Disease Research Laboratory test (VDRL) or

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

In such circumstances, the infant/child should undergo a lumbar puncture to obtain

Treponemal tests — Treponemal tests (eg, fluorescent treponemal antibody absorption

However, treponemal tests can be helpful in establishing a diagnosis of congenital syphilis. A

Measures to prevent congenital syphilis include screening of pregnant women and

● Increasing access to maternal and newborn services

Prevention of acquired syphilis is discussed in greater detail separately. (See "Syphilis:

Treatment and monitoring", section on 'Treatment after an exposure' and "Syphilis:

The possibility of false negative results of nontreponemal serology is another important

International adoptees — Syphilis testing is recommended as part of the evaluation of

Isolation precautions — Standard precautions are recommended for infants with suspected

INFORMATION FOR PATIENTS

● Basics topic (see "Patient education: Congenital syphilis (The Basics)")

SUMMARY AND RECOMMENDATIONS