Act Feb 2023 Congenital Syphilis Management and Outcome

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Official reprint from UpToDate®

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Congenital syphilis: Management and outcome

Author: Antonio C Arrieta, MD, FIDSA, FPIDS
Section Editor: Sheldon L Kaplan, 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: Feb 2023. | This topic last updated: Feb 14, 2023.
INTRODUCTION
Congenital syphilis occurs when the spirochete Treponema pallidum is transmitted

transplacentally from a pregnant individual to the fetus or, occasionally, through direct contact
with infectious lesions during birth. Infection can result in stillbirth, prematurity, or a wide
spectrum of clinical manifestations; only severe cases are clinically apparent at birth [1].
The management and outcome of congenital syphilis will be discussed here. The clinical
features, evaluation, and diagnosis of congenital syphilis; syphilis in pregnancy; and acquired
syphilis are discussed separately:
● (See "Congenital syphilis: Clinical manifestations, evaluation, and diagnosis".)

● (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".)
LIKELIHOOD OF INFECTION
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The diagnosis of congenital syphilis should be suspected in all infants whose mothers have
reactive nontreponemal and treponemal tests for syphilis. (See "Syphilis in pregnancy" and
"Congenital syphilis: Clinical manifestations, evaluation, and diagnosis", section on 'Clinical
suspicion'.)
To maximize treatment of children potentially infected with T. pallidum, the American Academy
of Pediatrics (AAP) categorizes congenital syphilis infection in the neonate as "proven or highly
probable," "possible," "less likely," and "unlikely" based upon identification of spirochetes in
tissue or body fluids, maternal and infant serologies, maternal treatment history, and the
neonate's clinical findings ( table 1). The diagnostic evaluation and approach to determining
the likelihood of infection are summarized in the algorithm ( algorithm 1) and discussed in
detail separately. (See "Congenital syphilis: Clinical manifestations, evaluation, and diagnosis",
section on 'Evaluation and diagnosis'.)
The categories of "possible" and "less likely" include infants with normal physical examination
and serological results not meeting diagnostic criteria but who nevertheless are still at risk of
congenital syphilis. The inclusion of these at-risk infants helps to ensure that all possible cases
are treated; however, not all at-risk infants are truly infected [2].
The vagaries of the maternal history of syphilis, inconsistent physical findings in the newborn,
and challenges of interpreting serologic tests in combination with the potential consequences
of delayed or missed diagnosis of congenital syphilis demand a "safety first" approach to both
diagnosis and treatment [3,4]. Our suggested approach described in the following sections is
generally consistent with guidelines of the United States Centers for Disease Control and
Prevention (CDC) and the AAP [5,6]. Similar guidance is provided by the World Health
Organization [7]. (See 'Society guideline links' below.)
TREATMENT ACCORDING TO DIAGNOSTIC CATEGORY
The following sections outline the approach to determining appropriate treatment based upon
likelihood of infection ( table 1 and algorithm 1). Additional details about penicillin therapy
are provided below. (See 'Penicillin therapy' below.)
● Proven or highly probable disease – For neonates with proven or highly probable
congenital syphilis, we recommend a 10-day course of intravenous (IV) aqueous crystalline
penicillin G or intramuscular (IM) procaine penicillin G ( table 1 and algorithm 1) [5,6].
(See '10-day regimen' below.)
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To prevent long-term morbidity, all neonates with proven or highly probable syphilis are
treated for presumed central nervous system syphilis. Although cerebrospinal fluid (CSF)
results do not alter the treatment, examination of the CSF is necessary since it may inform
prognosis and subsequent follow-up. (See 'Follow-up evaluations' below.)
● Possible congenital syphilis – Treatment of neonates with possible congenital syphilis is

as follows ( table 1 and algorithm 1) [5,6]:
• Neonates at higher risk – Neonates in the "possible" category who have a higher risk
of infection (ie, maternal risk of untreated syphilis is high or neonate's nontreponemal
titer is reactive) should undergo additional evaluation to assess the extent (if any) of
organ involvement. This is discussed separately. (See "Congenital syphilis: Clinical
manifestations, evaluation, and diagnosis", section on 'Evaluation for extent of organ
involvement'.)
- Any abnormality on evaluation – If there are any abnormalities on the evaluation

(eg, reactive CSF Venereal Disease Research Laboratory [VDRL], CSF pleocytosis,
elevated CSF protein, bony abnormalities), we recommend treatment with IV
aqueous crystalline penicillin G or IM procaine penicillin G for 10 days. (See '10-day
regimen' below.)
- No abnormalities on evaluation – If the results of the evaluation are normal and

follow-up of the infant is assured, we suggest a single IM dose of long-acting
penicillin (ie, benzathine penicillin). This approach requires that all components of
the evaluation have been completed and results are normal. Treatment failures
with single-dose therapy have been reported among infants who had incomplete
evaluation [8,9]. The frequency of such treatment failures is unknown but appears
to be low. (See 'Single-dose regimen' below.)
If evaluation is not performed or is not interpretable (traumatic lumbar puncture)

or if follow-up cannot be assured, we suggest a 10-day course of IV aqueous
crystalline penicillin G or IM procaine penicillin G. (See '10-day regimen' below.)
• Neonates at lower risk – Neonates in the "possible" category who have a lower risk of
infection (ie, maternal risk of untreated syphilis is low and neonate's nontreponemal
titer is nonreactive) do not require additional evaluation. For these neonates, we
suggest a single IM dose of benzathine penicillin [10]. (See 'Single-dose regimen'
below.)
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● Congenital syphilis less likely – For neonates in this category, further evaluation is not
necessary. We suggest a single IM dose of benzathine penicillin ( table 1 and
algorithm 1) [5,6]. (See 'Single-dose regimen' below.)
The rationale for treatment in this setting is that 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 [11-14]; higher rates
are more frequent in mothers with secondary syphilis. Treating the neonate at birth may
prevent the development of clinical disease if maternal therapy during pregnancy did not
prevent fetal infection [15,16].
Alternatively, some specialists opt not to treat such infants if close follow-up is certain (see
'Follow-up serology' below). If the infant's titers do not decline as expected for
transplacentally acquired antibody, treatment should be provided. (See '>1 month of age'
below.)
● Congenital syphilis unlikely – Newborns in this category do not require treatment or

further evaluation ( table 1 and algorithm 1) [5,6]. However, if follow-up is uncertain,
some experts would provide a single IM dose of benzathine penicillin to protect the infant
in the unlikely event that the mother was reinfected. (See 'Single-dose regimen' below.)
● Infants and children >1 month of age – Children who are diagnosed with congenital
syphilis after one month of age (including those with previously untreated late congenital
syphilis) require parenteral penicillin therapy, as discussed below. (See '>1 month of age'
below.)
PENICILLIN THERAPY
Parenteral penicillin is the drug of choice for the treatment of congenital syphilis for the
following reasons [5,6]:
● Penicillin is the only drug with documented efficacy.

● It has minimal toxicity.
● T. pallidum is extremely sensitive to penicillin, as demonstrated in animal studies [3].
● There is no evidence of increasing spirochete resistance to penicillin, but such evidence
would come only from the recognition of therapeutic failures.
The minimal inhibitory concentration (MIC) for penicillin is approximately 0.0005 mcg/mL [17].
Effective treatment of neurosyphilis requires maintaining a concentration of 0.018 mcg/mL in
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the cerebrospinal fluid (CSF) for 7 to 10 days [18]. 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 — For the single-dose regimen, long-acting benzathine penicillin G is

used.
Dosing is as follows:
● Benzathine penicillin G 50,000 units/kg, intramuscularly (IM) as a single dose
Two randomized trials have evaluated the efficacy of single-dose penicillin therapy in
preventing/treating congenital syphilis in asymptomatic infants born to mothers with no
treatment or inadequate/suboptimal treatment for syphilis during pregnancy [15,16]. One trial
compared single-dose benzathine penicillin G with no therapy in asymptomatic infants at high
risk of congenital syphilis (untreated mothers with Venereal Disease Research Laboratory test
[VDRL] ≥1:32) [15]. None of 11 infants in the treatment group developed congenital syphilis,
compared with four of eight infants who were not treated [15]. In the second trial, 169
asymptomatic neonates (normal physical examination, normal CSF evaluation, normal long-
bone radiographs, and no visceral abnormalities) were randomly assigned to treatment with a
single dose of benzathine penicillin G or 10 days of IM procaine penicillin G [16]. There were no
treatment failures in either group.
10-day regimen — The 10-day penicillin regimen is generally given intravenously (IV) with
aqueous crystalline penicillin G [5,6]:
● Aqueous crystalline penicillin G 50,000 units/kg IV every 12 hours (for neonates ≤7 days of
age) or every 8 hours (for neonates >7 days of age) for a total of 10 days
Alternatively, if IV access is not available, treatment can be given with daily IM injections using
procaine penicillin G, in which case the dosing is as follows:
● Procaine penicillin G 50,000 units/kg 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 [19]. However, the clinical significance of this observation is
unclear, since there have been no treatment failures reported after treatment with procaine
penicillin [6].
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If the newborn received antibiotics other than penicillin for other reasons (eg, neonates
undergoing evaluation for possible early-onset sepsis), this does not change the required
treatment for congenital syphilis. A full 10-day course of penicillin should still be administered
[5,6]. If more than one day of penicillin therapy is missed, the entire course should be restarted.
(See 'Missed doses' below.)
>1 month of age — For infants and children diagnosed with syphilis after one month of age,
including those with late congenital syphilis and children with acquired syphilis, treatment is as
follows [5,6]:
● Symptomatic patients – Patients with clinical or radiologic findings consistent congenital

syphilis are treated with a 10-day course of aqueous crystalline penicillin G (50,000
units/kg IV every four to six hours). If it is likely that the infection has been present for >1
year (eg, children with late congenital syphilis who are diagnosed after infancy), we
suggest providing a single dose of IM benzathine penicillin G (50,000 units/kg) after
completion of the 10-day IV course [5]. The rationale for the additional dose of IM
benzathine penicillin G in this setting is that the 10-day treatment course may not be
sufficient to treat late syphilis. (See "Syphilis: Treatment and monitoring", section on
'Preferred regimens'.)
● Asymptomatic patients – For infants and children with positive syphilis serology but
without any clinical or radiologic manifestations of disease and with normal CSF studies,
we suggest treatment with three weekly doses of IM benzathine penicillin G (50,000
units/kg) [5,6]. The treatment regimen should not exceed the adult regimen. A shorter
treatment course (ie, one or two doses of IM benzathine penicillin G) can be considered if
late syphilis is unlikely (eg, infants with congenital syphilis who are diagnosed within the
first year of life) [5]. (See "Syphilis: Treatment and monitoring", section on 'Late latent
syphilis'.)
Adverse effects — Penicillin G is generally safe and well tolerated in newborns. Potential
adverse effects include local reactions at the injection site and the possibility of a rare adverse
reaction (the Jarisch-Herxheimer reaction). The Jarisch-Herxheimer is characterized by onset of
fever 2 to 12 hours after initiation of therapy for active syphilis [20]. Rarely, cardiovascular
collapse, seizures, and death also have been reported [21]. 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. (See
"Syphilis: Treatment and monitoring", section on 'Jarisch-Herxheimer reaction'.)
Special circumstances
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Missed doses — If more than one day of penicillin therapy is missed, the entire course should
be restarted [5,6]. Effective treatment of neurosyphilis requires maintaining a concentration of
0.018 mcg/mL of penicillin in 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 [5,6]. (See "Penicillin
allergy: Immediate reactions", section on 'Desensitization'.)
If a nonpenicillin agent is used, close serologic and CSF follow-up are necessary. (See 'Follow-up
evaluations' below.)
Maternal coinfection with HIV — Infants born to mothers who are coinfected with syphilis
and human immunodeficiency virus (HIV) should receive the same evaluation and treatment for
syphilis as those whose mothers do not have HIV infection [5]. There is insufficient evidence to
determine whether such infants require different evaluation, treatment, or follow-up.
Evaluation and management of infants born to mothers with HIV are discussed separately. (See
"Diagnostic testing for HIV infection in infants and children younger than 18 months" and
"Intrapartum and postpartum management of pregnant women with HIV and infant
prophylaxis in resource-rich settings", section on 'Infant prophylaxis'.)
FOLLOW-UP EVALUATIONS
Infants who were treated should be monitored to assure adequate treatment response. Follow-
up evaluations are warranted for all infants and children who have reactive serologic tests for
syphilis and/or were born to mothers who were seroreactive at delivery [5,6,22-24].
Examination — During regularly scheduled well-child care visits, the clinician should carefully
assess for manifestations of congenital syphilis during the first year (for manifestations of early
congenital syphilis) ( table 2) and beyond (for manifestations of late congenital syphilis)
( table 3) [5,6].
Developmental surveillance and sensory screening — Routine surveillance should include:
● Yearly hearing evaluation (see "Hearing loss in children: Screening and evaluation")
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● Yearly vision screening and eye examination (see "Vision screening and assessment in
infants and children")
● Serial developmental assessments throughout infancy and childhood to ensure that the
infant is reaching expected developmental milestones (see "Developmental-behavioral
surveillance and screening in primary care")
In one study, children born to mothers with reactive syphilis serology during pregnancy were at
increased risk of neurodevelopmental impairment or speech delays regardless of whether they
were infected [25].
Follow-up serology — Reactive serology in the newborn does not differentiate between the
newborn's antibody response to infection and transplacentally acquired maternal antibody.
Serial monitoring of the infant's serology is necessary for the following reasons:
● In infants treated with penicillin, serial monitoring is necessary to ensure an appropriate

treatment response.
● In untreated infants (ie, those in the "unlikely congenital syphilis" category), serial
monitoring is necessary to definitively exclude congenital syphilis.
Thus, all infants born to mothers with syphilis require follow-up serologic monitoring,
regardless of whether the infant was seropositive or seronegative at birth and regardless of
whether the infant was treated with penicillin.
● Timing of testing – Follow-up serologic testing should be performed every two to three
months. Serology should be repeated until the test becomes nonreactive or the titer has
decreased fourfold (equivalent to two dilutions) [5,26,27].
● Tests to perform – Follow-up serologic monitoring should be performed with

nontreponemal tests (ie, quantitative Venereal Disease Research Laboratory [VDRL] or
rapid plasma reagin [RPR] titers). Ideally, follow-up testing should be performed with the
same test as was used in the newborn period. Additional details about these tests are
provided separately. (See "Congenital syphilis: Clinical manifestations, evaluation, and
diagnosis", section on 'Nontreponemal tests'.)
Treponemal tests should not be used to evaluate treatment response because they can
remain positive despite effective treatment [5,28].
However, in instances when the diagnosis is uncertain, treponemal tests can be used later
in infancy or childhood to help establish the diagnosis of congenital syphilis. This is
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discussed separately. (See "Congenital syphilis: Clinical manifestations, evaluation, and

diagnosis", section on 'Treponemal tests'.)
● Expected response – 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 initial reactive test in the newborn period was due to passive transfer of
maternal immunoglobulin G [IgG] antibody) [5,29,30]. The response may be slower in
infants and children treated after one month of age.
● Treatment failure – Treatment failure, or failure of maternal treatment to prevent

congenital syphilis, is indicated by:
• Failure of the VDRL or RPR titers to decline, or

• Increase in the VDRL or RPR after 6 to 12 months of age (or 6 to 12 months after
completing treatment in children treated after the neonatal period)
In such circumstances, the infant/child should undergo a lumbar puncture (LP) to obtain
cerebrospinal fluid (CSF) for VDRL, cell count, and protein, and be treated with an
extended course of parenteral penicillin, even if the infant/child was treated previously
[5,6]. (See '>1 month of age' above and "Congenital syphilis: Clinical manifestations,
evaluation, and diagnosis", section on 'Lumbar puncture'.)
Cerebrospinal fluid evaluation — Repeat CSF evaluations are generally not necessary unless
the infant has persistently positive nontreponemal titers at 6 to 12 months [6].
If repeat LP is performed and is abnormal (ie, reactive CSF VDRL or abnormal CSF white blood
cell count or protein that cannot be attributed to other ongoing illnesses), the infant should be
retreated with an extended course of parenteral penicillin therapy [5,6]. (See '>1 month of age'
above.)
Neuroimaging studies may be warranted in children with persistently reactive CSF VDRL,
elevated CSF cell count, and/or elevated CSF protein [6].
OUTCOME
In the United States, the case fatality rate for congenital syphilis is between 6 and 8 percent
[31,32]. Approximately 90 percent of fatal cases are associated with lack of prenatal care or
inadequate prenatal care.
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Appropriate treatment of early congenital syphilis within the first three months after birth
prevents some, but not all, of the late manifestations of congenital syphilis [30,33,34].
Interstitial keratitis ( picture 1) and anterior tibial bowing ("saber shins") ( picture 2) may
occur or progress despite appropriate therapy [35].
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 [36]. Active
disease after reinfection is common, regardless of nontreponemal antibody reactivity.
PREVENTION
Measures to prevent congenital syphilis include:
● Screening during pregnancy – Most cases of congenital syphilis are preventable with
routine prenatal care, screening for syphilis in pregnant individuals, penicillin treatment of
infected individuals and their sexual partners, and appropriate monitoring and
interpretation of treatment response [14,37-42]. Screening and treatment of syphilis
during pregnancy are discussed separately. (See "Syphilis in pregnancy", section on
'Maternal screening'.)
● International adoptees – Syphilis testing is recommended as part of the evaluation of

internationally adopted children, as discussed separately. (See "International adoption:
Infectious disease aspects", section on 'Syphilis'.)
● Infection control measures
• Standard precautions – Standard precautions are recommended for infants with

suspected or proven congenital syphilis [6]. (See "Infection prevention: Precautions for
preventing transmission of infection", section on 'Standard precautions'.)
In addition, gloves should be worn when caring for infants with skin or mucous
membrane lesions until 24 hours of treatment have been completed [43]. Moist open
lesions, secretions, and body fluids (eg, cerebrospinal fluid [CSF], blood) contain
spirochetes and are infectious [22]. (See "Infection prevention: Precautions for
preventing transmission of infection", section on 'Gloves'.)
• Management of exposures – Persons, including hospital personnel, who had close

unprotected contact with an infant or child with active early syphilis before the patient
was diagnosed or during the first 24 hours of treatment should be examined for
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syphilitic lesions (ie, chancre) two to three weeks after contact [6]. 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.
In 2007, the World Health Organization 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 [44].
Considerable progress has been made toward these goals, particularly with regards to [45]:
● 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 that 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 [46].
Prevention of acquired syphilis is discussed in greater detail separately. (See "Syphilis:

Treatment and monitoring", section on 'Treatment after an exposure' and "Syphilis:
Epidemiology, pathophysiology, and clinical manifestations in patients without HIV", section on
'Epidemiology'.)
SOCIETY GUIDELINE LINKS
Links to society and government-sponsored guidelines from selected countries and regions
around the world are provided separately.
● (See "Society guideline links: TORCH infections".)

● (See "Society guideline links: Sexually transmitted infections".)
INFORMATION FOR PATIENTS
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UpToDate offers two types of patient education materials, "The Basics" and "Beyond the
Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th 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, more
sophisticated, and more detailed. These articles are written at the 10th to 12th 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 (see "Patient education: Congenital syphilis (The Basics)")
SUMMARY AND RECOMMENDATIONS
● Likelihood of infection – 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 diagnosis and
treatment. Congenital syphilis should be suspected in all newborn infants whose mothers
have reactive nontreponemal and treponemal tests for syphilis. The diagnostic evaluation
and approach to determining the likelihood of infection are summarized in the table and
figure ( table 1 and algorithm 1) and discussed in detail separately. (See "Congenital
syphilis: Clinical manifestations, evaluation, and diagnosis", section on 'Evaluation and
diagnosis'.)
● Treatment – Penicillin is the treatment of choice for congenital syphilis. The treatment
regimen depends on the likelihood of infection ( table 1 and algorithm 1) (see
'Treatment according to diagnostic category' above):
• Proven or highly probable disease – For neonates in this category, we recommend an

extended course of penicillin (Grade 1A). These neonates are presumed to have central
nervous system syphilis. Treatment consists of aqueous crystalline penicillin G 50,000
units/kg intravenously (IV) every 12 hours (for infants ≤7 days of age) or every 8 hours
(for infants >7 days of age) for a total of 10 days. If IV access is not available, treatment
can be given with daily intramuscular (IM) injections of procaine penicillin G 50,000
units/kg as a single daily dose for 10 days. (See '10-day regimen' above.)
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• Possible congenital syphilis – For neonates in this category who have reactive
nontreponemal serologies and any abnormality on additional diagnostic evaluation
(eg, reactive cerebrospinal fluid [CSF], Venereal Disease Research Laboratory [VDRL],
CSF pleocytosis, elevated CSF protein, bony abnormalities), we recommend an
extended course of penicillin (Grade 1B). Treatment is the same as for newborns with
proven or highly probable congenital syphilis. (See '10-day regimen' above.)
For neonates in this category who have reactive nontreponemal serologies and no
other abnormalities on evaluation and those with nonreactive nontreponemal
serologies, we suggest a single IM dose of long-acting penicillin rather than an
extended treatment course (Grade 2B). Treatment consists of benzathine penicillin G
50,000 units/kg given as a single IM dose. (See 'Single-dose regimen' above.)
• Congenital syphilis less likely – For neonates in this category, we suggest a single
dose of IM benzathine penicillin G rather than an extended treatment course or no
treatment (Grade 2C). (See 'Single-dose regimen' above.)
• Congenital syphilis unlikely – Neonates in this category generally do not require

treatment. However, some experts would provide a single IM dose of benzathine
penicillin G if follow-up is uncertain. (See 'Single-dose regimen' above.)
• Late diagnosis – For symptomatic infants and children diagnosed with syphilis after
one month of age, we suggest an extended treatment course rather than single-dose
therapy (Grade 2C). For asymptomatic children, we suggest three weekly doses of IM
benzathine penicillin G rather than other regimens (Grade 2C). (See '>1 month of age'
above.)
● Follow-up – Follow-up evaluations are warranted for all infants and children who have
reactive serologic tests for syphilis and/or were born to mothers who were seroreactive at
delivery. Follow-up includes (see 'Follow-up evaluations' above):
• Physical examination to assess for manifestations of congenital syphilis. (See

'Examination' above and "Congenital syphilis: Clinical manifestations, evaluation, and
diagnosis", section on 'Clinical manifestations'.)
• Yearly hearing evaluation. (See "Hearing loss in children: Screening and evaluation".)
• Yearly vision screening and eye examination. (See "Vision screening and assessment in
infants and children".)
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• Serial developmental assessments throughout infancy and childhood to ensure that

the infant is reaching expected developmental milestones. (See "Developmental-
behavioral surveillance and screening in primary care".)
• Follow-up serologic testing with nontreponemal tests (ie, quantitative VDRL or rapid
plasma reagin [RPR]) performed every two to three months until the test becomes
nonreactive or the titer has decreased fourfold. (See 'Follow-up serology' above.)
• Follow-up lumbar puncture (LP) is warranted only if the infant has persistently positive
nontreponemal titers at 6 to 12 months. (See 'Cerebrospinal fluid evaluation' above.)
● Treatment failure – Treatment failure, or failure of maternal treatment to prevent

congenital syphilis, is indicated by:
• Failure of the VDRL or RPR titers to decline, or

• Increase in the VDRL or RPR after 6 to 12 months of age (or 6 to 12 months after
completing treatment in children treated after the neonatal period)
In such circumstances, the infant/child should undergo a full evaluation (including LP) and
should be treated with an extended course of penicillin. (See 'Follow-up serology' above
and '>1 month of age' above.)
● Outcome – The case fatality rate for congenital syphilis is between 6 and 8 percent.
Appropriate treatment of early congenital syphilis within the first three months after birth
prevents some, but not all, of the late manifestations of congenital syphilis. (See 'Outcome'
above.)
ACKNOWLEDGMENT
The editorial staff at UpToDate would like to acknowledge Simon R Dobson, MD, FRCP(C), who
contributed to an earlier version of this topic review.
Use of UpToDate is subject to the Terms of Use.
REFERENCES
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4. 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.
5. Workowski KA, Bolan GA, Centers for Disease Control and Prevention. Sexually transmitted
diseases treatment guidelines, 2015. MMWR Recomm Rep 2015; 64:1.
6. American Academy of Pediatrics. Syphilis. In: Red Book: 2021-2024 Report of the Committe
e on Infectious Diseases, 32nd ed, Kimberlin DW, Barnett ED, Lynfield R, Sawyer MH (Eds), A
merican Academy of Pediatrics, Itasca, IL 2021. p.729.
7. WHO guidelines for the treatment of Treponema pallidum (syphilis). 2016. Available at: htt
p://apps.who.int/iris/bitstream/10665/249572/1/9789241549806-eng.pdf?ua=1 (Accessed o
n September 15, 2016).
8. Beck-Sague C, Alexander ER. Failure of benzathine penicillin G treatment in early congenital
syphilis. Pediatr Infect Dis J 1987; 6:1061.
9. Woolf A, Wilfert CM, Kelsey DB. Childhood syphilis in North Carolina. N C Med J 1980;
41:443.
10. Wozniak PS, Cantey JB, Zeray F, et al. Congenital syphilis in neonates with nonreactive
nontreponemal test results. J Perinatol 2017; 37:1112.
11. Alexander JM, Sheffield JS, Sanchez PJ, et al. Efficacy of treatment for syphilis in pregnancy.
Obstet Gynecol 1999; 93:5.
12. 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.
13. Sheffield JS, Sánchez PJ, Morris G, et al. Congenital syphilis after maternal treatment for
syphilis during pregnancy. Am J Obstet Gynecol 2002; 186:569.
14. McFarlin BL, Bottoms SF, Dock BS, Isada NB. Epidemic syphilis: maternal factors associated
with congenital infection. Am J Obstet Gynecol 1994; 170:535.
15. 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.
16. Paryani SG, Vaughn AJ, Crosby M, Lawrence S. Treatment of asymptomatic congenital
syphilis: benzathine versus procaine penicillin G therapy. J Pediatr 1994; 125:471.
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17. Norris SJ, Edmondson DG. In vitro culture system to determine MICs and MBCs of
antimicrobial agents against Treponema pallidum subsp. pallidum (Nichols strain).
Antimicrob Agents Chemother 1988; 32:68.
18. Tramont EC. Persistence of Treponema pallidum following penicillin G therapy. Report of
two cases. JAMA 1976; 236:2206.
19. 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.
20. Woods CR. Syphilis in children: congenital and acquired. Semin Pediatr Infect Dis 2005;
16:245.
21. HOLZEL A. Jarisch-Herxheimer reaction following penicillin treatment of early congenital
syphilis. Br J Vener Dis 1956; 32:175.
22. Kollmann TR, Dobson S. Syphilis. In: Infectious Diseases of the Fetus and Newborn Infant, 7
th, Remington JS, Klein JO, Wilson CB, et al (Eds), Elsevier Saunders, Philadelphia 2011. p.52
4.
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. Verghese VP, Hendson L, Singh A, et al. Early Childhood Neurodevelopmental Outcomes in
Infants Exposed to Infectious Syphilis In Utero. Pediatr Infect Dis J 2018; 37:576.
26. Hardy JB, Hardy PH, Oppenheimer EH, et al. Failure of penicillin in a newborn with
congenital syphilis. JAMA 1970; 212:1345.
27. 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.
28. 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.
29. 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.
30. Lago EG, Vaccari A, Fiori RM. Clinical features and follow-up of congenital syphilis. Sex
Transm Dis 2013; 40:85.
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2008. MMWR Morb Mortal Wkly Rep 2010; 59:413.
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32. Gust DA, Levine WC, St Louis ME, et al. Mortality associated with congenital syphilis in the
United States, 1992-1998. Pediatrics 2002; 109:E79.
33. PUTKONEN T. Does early treatment prevent dental changes in congenital syphilis? Acta
Derm Venereol 1963; 43:240.
34. Stamos JK, Rowley AH. Timely diagnosis of congenital infections. Pediatr Clin North Am
1994; 41:1017.
35. OKSALA A. Interstitial keratitis after adequate penicillin therapy; a case report. Br J Vener
Dis 1957; 33:113.
36. Pavithran K. Acquired syphilis in a patient with late congenital syphilis. Sex Transm Dis
1987; 14:119.
37. 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.
38. Mascola L, Pelosi R, Blount JH, et al. Congenital syphilis. Why is it still occurring? JAMA 1984;
252:1719.
39. 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.
40. Webber MP, Lambert G, Bateman DA, Hauser WA. Maternal risk factors for congenital
syphilis: a case-control study. Am J Epidemiol 1993; 137:415.
41. 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.
42. 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.
43. 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.
44. The World Health Organization. The global elimination of congenital syphillis: Rationale an
d strategy for action. http://www.who.int/reproductivehealth/publications/rtis/9789241595
858/en/ (Accessed on December 20, 2016).
45. 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.who.int/r
eproductivehealth/publications/rtis/9789241505888/en/ (Accessed on December 20, 2016).
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46. 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.
Topic 15400 Version 33.0
3/30/23, 2:32 PM 15400
GRAPHICS
Likelihood of congenital syphilis infection in newborn infants born to

mothers with reactive nontreponemal and treponemal tests during
pregnancy
Additional Follow-up tes

Category Definition evaluation to Treatment (applies to
perform categories
Proven or Mother diagnosed with LP for CSF cell 10 days of Monitor clinic
highly syphilis during count, protein, parenteral examination f
probable pregnancy (reactive and CSF VDRL penicillin development
nontreponemal and CBC with new concerni
treponemal tests), differential and findings
regardless of platelet count Perform follow
treatment received LFTs serologic test
Plus Long-bone For infant
radiographs with react
Newborn has ANY of
ABR nontrepon
the following:
serologies
Clinical findings Eye examination
Perform s
consistent with Other tests as
serologic
congenital syphilis* clinically
testing wi
Infant serum VDRL indicated:
VDRL or R
or RPR titer ≥4-fold Chest (use same
maternal titer ¶ radiograph if
as for initi
Positive darkfield there are
testing) at
microscopy, DFA, or pulmonary
4, 6, and 1
PCR of skin lesions, findings
months o
body fluid(s), Neuroimaging nonreactiv
placenta, or if there are nontrepon
umbilical cord Δ concerning tests are s
neurologic positive at
findings months, t
Abdominal infant sho
imaging if be re-eval
there is (including
significant and treate
organomegaly with an
extended
Possible ALL of the following: We further classify newborns in the
course of
Mother diagnosed with "possible" category as higher or lower risk:
parentera
syphilis during penicillin.
3/30/23, 2:32 PM 15400
pregnancy (reactive Higher risk: Neonate's VDRL or RPR is For infant

nontreponemal and reactive or maternal risk of untreated with
treponemal tests) syphilis is high nonreact
Mother did not receive Lower risk: Neonate's VDRL or RPR is nontrepon
treatment, or received nonreactive and maternal risk of serologies
inadequate/suboptimal untreated syphilis is low Recheck V
treatment, or had or RPR (us
evidence of relapse or Higher risk: Higher risk: same test
reinfection ◊ Perform same If any part of for initial
Infant physical evaluation as for the additional testing) at
examination is normal the "proven or evaluation is 3 months
highly probable" abnormal, not confirm in
Infant serum VDRL or
category (see performed, or remains
RPR titer <4-fold
above) § uninterpretable seronegat
maternal titer ¶
(eg, traumatic
LP) or if follow-
up is uncertain:
10 days of
parenteral
penicillin
If all tests in
the additional
evaluation are
performed and
are normal:
Single dose of
IM penicillin
benzathine
Lower risk: Lower risk:

Additional Single dose of
evaluation is not IM benzathine
necessary penicillin
Less likely ALL of the following: Not required Single dose of IM

Mother diagnosed with penicillin
syphilis during benzathine ¥
pregnancy (reactive
nontreponemal and
treponemal tests)
Mother received
appropriate treatment
during pregnancy (at
least 4 weeks before
delivery) ◊
3/30/23, 2:32 PM 15400
Mother has no
evidence of reinfection
or relapse ◊
Infant physical
examination is normal
RPR titer <4-fold
maternal titer ¶
Unlikely ALL of the following: Not required Not required ‡

Mother had reactive
nontreponemal and
treponemal tests
during pregnancy
Mother received
appropriate treatment
before pregnancy ◊
Mother's titers
remained low (VDRL
<1:2; RPR <1:4) and
stable before and
during pregnancy and
at delivery
Infant physical
examination is normal
RPR titer <4-fold
maternal titer ¶
This table summarizes the likelihood of congenital syphilis infection based upon maternal and
newborn serologies, adequacy of maternal treatment, clinical findings in the infant, and other
findings. Evaluation for congenital syphilis is warranted in all newborns born to mothers who have
reactive nontreponemal and treponemal tests for syphilis during pregnancy. For mothers screened
with the traditional approach, the treponemal test is necessary to exclude a false-positive
nontreponemal result. When reverse sequencing is used, the nontreponemal test is still necessary
for comparison with the mother's result and for monitoring of treatment success (two
nontreponemal tests are needed when there is discordance between syphilis antibody and
nontreponemal test during reverse sequencing). Refer to UpToDate's topics on syphilis during
pregnancy and congenital syphilis for additional details.
VDRL: venereal disease research laboratory; RPR: rapid plasma regain; DFA: direct fluorescent
antibody; PCR: polymerase chain reaction; LP: lumbar puncture; CBC: complete blood count; LFTs:
liver function tests; ABR: auditory brainstem response; CDC: Centers for Disease Control and
Prevention; CSF: cerebrospinal fluid; IM: intramuscular.
3/30/23, 2:32 PM 15400
* Findings of congenital syphilis may include hepatosplenomegaly, rash, condyloma lata, snuffles,
jaundice (nonviral hepatitis), pseudoparalysis, pallor (anemia), or edema (nephrotic syndrome
and/or malnutrition). Refer to UpToDate topic on congenital syphilis for additional details.
¶ A 4-fold titer is equivalent to two dilutions (eg, newborn's titer 1:32 if maternal titer is 1:8).
Δ These tests are not available in many clinical settings.
◊ Adequate treatment is defined as completion of a penicillin-based regimen, in accordance with

CDC treatment guidelines, appropriate for stage of infection and initiated ≥4 weeks before delivery.
Relapse or reinfection after treatment is suggested by a 4-fold increase of maternal VDRL or RPR
titers after treatment. Inadequate/suboptimal therapy includes any of the following:
Treatment with a nonpenicillin antibiotic
Treatment given <4 weeks before delivery
Inappropriate dose for stage of disease
Inadequate documentation of maternal treatment
Inadequate response to therapy (ie, maternal VDRL or RPR titers did not decline at least 4-fold
after treatment)
§ The CDC guidelines include a caveat that additional evaluation may not be necessary for neonates
in the "possible" category if a 10-day treatment course is planned. Nevertheless, we suggest
performing the evaluation in higher-risk neonates (as defined above) since the evaluation may
inform decisions regarding treatment and follow-up.
¥ Some specialists opt not to treat infants in this category and instead provide close (ie, monthly)
serologic follow-up. If this approach is chosen, treatment should be provided if the infant's titers do
not decline as expected over the first few months after birth.
‡ If follow-up is uncertain, some specialists would provide a single dose of IM benzathine penicillin
to protect the infant in the unlikely event that the mother was reinfected.
Graphic 140142 Version 1.0
3/30/23, 2:32 PM 15400
Approach to evaluation and management of newborns born to mothers who te

syphilis during pregnancy
This figure summarizes our suggested approach to evaluating and treating infants with suspected congenit
based upon maternal and infant serologies, adequacy of maternal treatment, clinical findings in the infant,
3/30/23, 2:32 PM 15400
Evaluation for congenital syphilis is warranted in all infants born to mothers who have reactive nontreponem
tests for syphilis during pregnancy. For mothers screened with the traditional approach, the treponemal tes
exclude a false-positive nontreponemal result. When reverse sequencing is used, the nontreponemal test is
comparison with the mother's result and for monitoring of treatment success (two nontreponemal tests are
there is discordance between syphilis antibody and nontreponemal test during reverse sequencing). Refer t
on syphilis during pregnancy and congenital syphilis for additional details.
VDRL: venereal disease research laboratory; RPR: rapid plasma regain; DFA: direct fluorescent antibody; PCR
reaction; LP: lumbar puncture; CBC: complete blood count; LFTs: liver function tests; ABR: auditory brainstem
Centers for Disease Control and Prevention; CSF: cerebrospinal fluid; IM: intramuscular; IV: intravascular.
* Findings of congenital syphilis may include hepatosplenomegaly, rash, condyloma lata, snuffles, jaundice
pseudoparalysis, pallor (anemia), or edema (nephrotic syndrome and/or malnutrition). Refer to UpToDate to
syphilis for additional details.
¶ A 4-fold titer is equivalent to two dilutions (eg, infant's titer 1:32 if maternal titer is 1:8).
Δ These tests are not available in most clinical settings.
◊ Additional testing may include neuroimaging if there are concerning neurologic findings, chest radiograp
pulmonary findings, or abdominal imaging if there is significant organomegaly.
§ Adequate treatment is defined as completion of a penicillin-based regimen, in accordance with CDC treatm
appropriate for stage of infection and initiated ≥4 weeks before delivery. Relapse or reinfection after treatm
a 4-fold increase maternal VDRL or RPR titers after treatment. Inadequate/suboptimal therapy includes any
Treatment with a nonpenicillin antibiotic
Treatment given <4 weeks before delivery
Inappropriate dose for stage of disease
Inadequate documentation of maternal treatment
Inadequate response to therapy (ie, maternal VDRL or RPR titers did not decline at least 4-fold after tr
¥ The CDC guidelines include a caveat that additional evaluation may not be necessary for neonates in the "
if a 10-day treatment course is planned. Nevertheless, we suggest performing the evaluation in higher-risk n
defined above) since the evaluation may inform decisions regarding treatment and follow-up.
‡ All neonates with reactive nontreponemal serologies should be monitored with follow-up examinations an
testing with VDRL or RPR (use same test as for initial testing) at 1, 2, 4, 6, and 12 months or until nonreactive
tests are still positive at 6-12 months, the infant should be re-evaluated (including LP) and treated with an ex
parenteral penicillin. Infants with nonreactive nontreponemal serologies at birth should be retested at 3 mo
that the infant remains seronegative.
† For infants in the "less likely" category, some specialists opt not to treat and instead provide close (ie, mon
follow-up. If this approach is chosen, treatment should be provided if the infant's titers do not decline as exp
few months after birth.
** If follow-up is uncertain, some specialists would provide a single dose of IM penicillin G benzathine to pro
the unlikely event that the mother was reinfected.
3/30/23, 2:32 PM 15400
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 lymphadenopathy May be as large as 1 cm; generally nontender and firm
Failure to thrive
Edema Due to anemia/hydrops fetalis, nephrotic syndrome,

malnutrition
Mucocutaneous
Syphilitic rhinitis ("snuffles") Can be an early feature, developing after the first week of
life; 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 (pemphigus May be present at birth, most often develops in first four
syphiliticus) weeks; widely disseminated; vesicular fluid contains
spirochetes and is infectious (use contact precautions)
3/30/23, 2:32 PM 15400
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 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 Parrot Lack of movement of an extremity because of pain
associated with bone lesion; affects upper extremities more
often than lower; usually unilateral; rarely present at birth;
poorly correlated with radiographic abnormalities
Radiographic abnormalities: Most frequent abnormality in untreated early congenital

syphilis; 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 leptomeningitis Onset during the first year of life, usually between 3 and 6
months; presentation similar to bacterial meningitis but
CSF findings more consistent with aseptic meningitis
(mononuclear predominance); responds to penicillin
therapy
3/30/23, 2:32 PM 15400
Chronic meningovascular syphilis Onset toward the end of the first year; hydrocephalus;
cranial nerve palsies; intellectual/neurodevelopmental
deterioration; cerebral infarction; protracted course
Miscellaneous
Pneumonia/pneumonitis/respiratory Complete opacification of both lung fields on chest
distress radiograph
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.
3/30/23, 2:32 PM 15400
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, juvenile
system 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.
3/30/23, 2:32 PM 15400
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.
3/30/23, 2:32 PM 15400
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.
3/30/23, 2:32 PM 15400
Contributor Disclosures
Antonio C Arrieta, MD, FIDSA, FPIDS 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. 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.
Conflict of interest policy

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Congenital syphilis: Management and outcome

Congenital syphilis occurs when the spirochete Treponema pallidum is transmitted

● (See "Congenital syphilis: Clinical manifestations, evaluation, and diagnosis".)

TREATMENT ACCORDING TO DIAGNOSTIC CATEGORY

● Possible congenital syphilis – Treatment of neonates with possible congenital syphilis is

- Any abnormality on evaluation – If there are any abnormalities on the evaluation

- No abnormalities on evaluation – If the results of the evaluation are normal and

If evaluation is not performed or is not interpretable (traumatic lumbar puncture)

● Congenital syphilis unlikely – Newborns in this category do not require treatment or

● Penicillin is the only drug with documented efficacy.

<1 month of age

Single-dose regimen — For the single-dose regimen, long-acting benzathine penicillin G is

● Benzathine penicillin G 50,000 units/kg, intramuscularly (IM) as a single dose

● Procaine penicillin G 50,000 units/kg IM as a single daily dose for 10 days

● Symptomatic patients – Patients with clinical or radiologic findings consistent congenital

Developmental surveillance and sensory screening — Routine surveillance should include:

● In infants treated with penicillin, serial monitoring is necessary to ensure an appropriate

● Tests to perform – Follow-up serologic monitoring should be performed with

discussed separately. (See "Congenital syphilis: Clinical manifestations, evaluation, and

● Treatment failure – Treatment failure, or failure of maternal treatment to prevent

• Failure of the VDRL or RPR titers to decline, or

Measures to prevent congenital syphilis include:

● International adoptees – Syphilis testing is recommended as part of the evaluation of

● Infection control measures

• Standard precautions – Standard precautions are recommended for infants with

• Management of exposures – Persons, including hospital personnel, who had close

● Increasing access to maternal and newborn services

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

SOCIETY GUIDELINE LINKS

● (See "Society guideline links: TORCH infections".)

INFORMATION FOR PATIENTS

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

SUMMARY AND RECOMMENDATIONS

• Proven or highly probable disease – For neonates in this category, we recommend an

• Congenital syphilis unlikely – Neonates in this category generally do not require

• Physical examination to assess for manifestations of congenital syphilis. (See

• Serial developmental assessments throughout infancy and childhood to ensure that

● Treatment failure – Treatment failure, or failure of maternal treatment to prevent

• Failure of the VDRL or RPR titers to decline, or

Use of UpToDate is subject to the Terms of Use.

Likelihood of congenital syphilis infection in newborn infants born to

Additional Follow-up tes

pregnancy (reactive Higher risk: Neonate's VDRL or RPR is For infant

Lower risk: Lower risk:

Less likely ALL of the following: Not required Single dose of IM

Unlikely ALL of the following: Not required Not required ‡

Δ These tests are not available in many clinical settings.

◊ Adequate treatment is defined as completion of a penicillin-based regimen, in accordance with

Graphic 140142 Version 1.0

Approach to evaluation and management of newborns born to mothers who te

Δ These tests are not available in most clinical settings.

Graphic 140138 Version 1.0

Clinical manifestations of early congenital syphilis*

Birth weight <2500 g

Nonimmune hydrops fetalis

Placenta Large, thick, pale (send for pathologic/histologic

Umbilical cord Inflamed with abscess-like foci of necrosis within Wharton's

Fever May be more prominent in infants born to mothers who

Hepatomegaly Splenomegaly occurs in approximately one-half of patients

Generalized lymphadenopathy May be as large as 1 cm; generally nontender and firm

Edema Due to anemia/hydrops fetalis, nephrotic syndrome,