Congenital syphilis: Management and outcome

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 — 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 (table 1 and algorithm 1) [5,6]. (See '10-day regimen' below.)

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 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 intramuscular (IM) dose of long-acting penicillin (ie, penicillin G benzathine). 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. (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 long-acting penicillin (ie, penicillin G benzathine) [10]. (See 'Single-dose regimen' below.)

●Congenital syphilis less likely – For neonates in this category, further evaluation is not necessary. We suggest a single IM dose of penicillin G benzathine (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 penicillin G benzathine 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 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 intramuscular (IM) penicillin G benzathine is used.

Dosing is as follows:

●Penicillin G benzathine 50,000 units/kg given 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 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) [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 IM benzathine penicillin or 10 days of parenteral penicillin G [16]. There were no treatment failures in either group.

10-day regimen — The 10-day penicillin regimen is 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

An alternative option for infants without IV access is to treat with daily IM injections of penicillin G procaine (intermediate-acting penicillin). However, procaine penicillin is no longer available in the United States and many other parts of the world.

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 penicillin G benzathine (50,000 units/kg) after completion of the 10-day IV course [5]. The rationale for the additional dose of long-acting IM benzathine penicillin 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 long-acting IM penicillin G benzathine (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 penicillin G benzathine) 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 [19]. Rarely, cardiovascular collapse, seizures, and death also have been reported [20]. The Jarisch-Herxheimer reaction is thought to be produced by the release of endotoxin-like compounds during penicillin-mediated lysis of T. pallidum. It is rare in newborns but can occur in older infants and children. (See "Syphilis: Treatment and monitoring", section on 'Jarisch-Herxheimer reaction'.)

Special circumstances

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 [5,6,21-23].

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")

●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 [24].

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) [5,25,26].

●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 [5,27].

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 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) [5,28,29]. 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 [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 after birth prevents some, but not all, of the late manifestations of congenital syphilis [29,32,33]. Interstitial keratitis (picture 1) and anterior tibial bowing ("saber shins") (picture 2) 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 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 [14,36-41]. 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 [42]. Moist open lesions, secretions, and body fluids (eg, cerebrospinal fluid [CSF], blood) contain spirochetes and are infectious [21]. (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 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 [43]. Considerable progress has been made toward these goals, particularly with regards to [44]:

●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 [45].

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".)

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●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. (See '10-day regimen' above.)

•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 a 10-day 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 intramuscular (IM) dose of long-acting penicillin rather than an extended treatment course (Grade 2B). Treatment consists of penicillin G benzathine 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 penicillin G benzathine 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 penicillin G benzathine 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".)

•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.