Version May 2024
INTRODUCTION — Congenital syphilis occurs when the spirochete Treponema pallidum is transmitted from a pregnant individual to the fetus. Infection can result in stillbirth, prematurity, or a wide spectrum of clinical manifestations; only severe cases are clinically apparent at birth [1].
The clinical features, evaluation, and diagnosis of congenital syphilis will be discussed here. The management and prevention of congenital syphilis, syphilis in pregnancy, and acquired syphilis are discussed separately:
●(See "Congenital syphilis: Management and outcome".)
●(See "Syphilis in pregnancy".)
●(See "Syphilis: Epidemiology, pathophysiology, and clinical manifestations in patients without HIV".)
●(See "Syphilis: Treatment and monitoring".)
●(See "Neurosyphilis".)
●(See "Syphilis: Screening and diagnostic testing".)
EPIDEMIOLOGY
●Incidence – Congenital syphilis is a significant public health problem, complicating an estimated one million pregnancies per year throughout the world [2,3]. The incidence of congenital syphilis reflects the rate of syphilis in women of childbearing age [4]. (See "Syphilis: Epidemiology, pathophysiology, and clinical manifestations in patients without HIV", section on 'Epidemiology'.)
Most cases develop because the mother received no prenatal care or insufficient treatment for syphilis before or during pregnancy (table 1) [5-7]. Among women with untreated early syphilis, 40 percent of pregnancies result in spontaneous abortion [8]. (See "Syphilis in pregnancy", section on 'Prevalence'.)
Rates of congenital syphilis in the United States have risen steadily since 2012 [9,10]. In 2020, there were a total of 2152 reported cases of congenital syphilis in the United States, including 122 syphilitic stillbirths and 29 infant deaths [10,11]. The 2020 case rate (57 cases per 100,000 live births) represents the highest reported rate since 1991. As is expected, the increase in rates of congenital syphilis parallels increases in primary and secondary syphilis among women during this period (figure 1) [9,10,12].
Syphilis in pregnancy is commonly associated with adverse pregnancy outcomes (fetal loss, stillbirth, neonatal death, prematurity, and low birth weight), as discussed separately. (See "Syphilis in pregnancy", section on 'Potential adverse pregnancy outcomes'.)
●Risk factors – Poor access to prenatal care is an important risk factor for congenital syphilis. Among the 458 cases of congenital syphilis reported to the Centers for Disease Control and Prevention (CDC) in 2014, nearly one-quarter were born to mothers who did not receive prenatal care [9]. Among the 314 cases in which the mother received prenatal care, 135 (43 percent) received no treatment for syphilis during the pregnancy and 94 (30 percent) received inadequate treatment.
Social vulnerabilities including homelessness, substance abuse, and incarceration were found to be barriers to timely diagnosis and treatment of syphilis in pregnant women in a review of congenital cases in Indiana [13].
The rate of congenital syphilis is increased among infants born to mothers with human immunodeficiency virus (HIV) infection. However, the contribution of maternal coinfection with syphilis and HIV to vertical transmission of either syphilis or HIV is not completely understood. (See "Syphilis in patients with HIV", section on 'Effect of syphilis on HIV'.)
The rate of congenital syphilis is generally low among children adopted internationally; however, it is relatively increased among those adopted from Africa (table 2). Given the difficulty in confirming adequate treatment/treatment response of the birth mother and the risk of long-term sequelae in untreated children, we recommend screening international adoptees for congenital syphilis (regardless of the country of origin). (See "International adoption: Infectious disease aspects", section on 'Syphilis'.)
●Missed opportunities – The most common missed opportunity for prevention of congenital syphilis is lack of adequate maternal treatment despite a timely diagnosis, which accounts for approximately 30 to 40 percent of cases [9,10]. Other missed opportunities include lack of prenatal care (20 to 30 percent of cases), failure to perform timely syphilis testing (10 to 15 percent of cases), and late identification of seroconversion during pregnancy (approximately 10 percent of cases) [10,11,14]. In studies conducted in New York, Florida, and Louisiana, repeat early testing during the third trimester is an effective intervention for preventing congenital syphilis [15,16].
TRANSMISSION — Humans are the only natural host of T. pallidum [17]. Congenital syphilis generally is acquired through transplacental transmission during maternal spirochetemia or, occasionally, through direct contact with an infectious lesion during birth [18-20]. (See "Syphilis in pregnancy", section on 'Vertical transmission (congenital syphilis)'.)
Transplacental transmission of T. pallidum can occur at any time during gestation but occurs with increasing frequency as gestation advances. Women with untreated primary or secondary syphilis are more likely to transmit syphilis to their fetuses than women with latent disease (60 to 90 versus 40 percent in early latent and <10 percent in late latent syphilis) [21,22]. The risk of transmission decreases with increasing time since primary or secondary infection and is only 2 percent after four years.
T. pallidum is not transferred in breast milk, but transmission may occur if the mother has an infectious lesion (eg, chancre) on her breast [23].
PATHOGENESIS — At the onset of congenital syphilis, T. pallidum is liberated directly into the circulation of the fetus, resulting in spirochetemia with widespread dissemination to almost all organs. Clinical manifestations are the result of inflammation in the affected organs. Bones, liver, pancreas, intestine, kidney, and spleen are most frequently and severely involved. The severity of illness is variable and can range from isolated laboratory or radiographic abnormalities to fulminant involvement of multiple organ systems. Overt infection can manifest in the fetus, the newborn, or later in childhood (if the newborn/infant is not treated appropriately and timely) [24].
The pathophysiology of and immune response to acquired syphilis infection are discussed separately. (See "Syphilis: Epidemiology, pathophysiology, and clinical manifestations in patients without HIV".)
CLINICAL MANIFESTATIONS
Early congenital syphilis — Early congenital syphilis is arbitrarily defined by clinical manifestations with onset before two years of age [25].
Clinical findings — Clinical manifestations in untreated infants usually appear by three months of age, most often by five weeks [25,26].
Approximately 60 to 90 percent of live-born neonates with congenital syphilis are asymptomatic at birth [9,27]. The presence of signs at birth depends upon the timing of intrauterine infection and treatment [17]. Among symptomatic infants, the most common findings include [9,28]:
●Hepatomegaly
●Jaundice
●Nasal discharge ("snuffles")
●Rash
●Generalized lymphadenopathy
●Skeletal abnormalities
Clinical manifestations of early syphilis are varied and unpredictable (table 3) [1,17,23,25,29,30]. Common clinical findings are reviewed here:
●Placenta and umbilical cord – The placenta of neonates with congenital syphilis is often large, thick, and pale. The umbilical cord is edematous and may resemble a "barber's pole" with spiral stripes of red and light blue discoloration alternating with streaks of chalky white. It may be significantly inflamed with abscess-like foci of necrosis within Wharton jelly, centered around the umbilical vessels (necrotizing funisitis) [31,32]. (See "Care of the umbilicus and management of umbilical disorders", section on 'Funisitis'.)
●Hepatomegaly – Hepatomegaly occurs in almost all infants with congenital syphilis [7,23]. Hepatomegaly may or may not be associated with splenomegaly, but isolated splenomegaly does not occur. When noted on fetal ultrasonography, hepatomegaly may indicate failure of maternal treatment to prevent fetal infection [33]. Hepatomegaly is associated with jaundice and cholestasis. Spirochetes can be seen on liver biopsy (if one is performed). (See 'Laboratory abnormalities' below.)
●Rhinitis – Syphilitic rhinitis ("snuffles") (picture 1) may herald the onset of congenital syphilis. It usually develops during the first week after birth and seldom after the third month. The nasal discharge is white and may be bloody (secondary to mucosal erosion) or purulent if there is secondary bacterial infection. It is more severe and persistent than the nasal discharge typical of most childhood viral upper respiratory infections. The nasal discharge contains spirochetes, is contagious, and can transmit infection by direct contact.
●Rash – The rash of congenital syphilis usually appears one to two weeks after the rhinitis. It is maculopapular and consists of small, initially red or pink spots. The lesions may occur anywhere, but are more prominent on the back, buttocks, posterior thighs, palms, and soles (picture 2). The rash generally progresses over one to three weeks, followed by desquamation and crusting. As it fades, the lesions become dusky red or copper-colored, and the pigmentation may persist. If present at birth, the rash may be widely disseminated and bullous (pemphigus syphiliticus). Ulcerative lesions and bullous fluid contain spirochetes, are contagious, and can transmit infection by direct contact.
Other characteristic, but uncommon, cutaneous lesions of congenital syphilis include fissures, mucous patches, and condylomata lata (picture 3A-B). The fissures occur around the lips, nares, and anus. They bleed easily and heal with scarring. The mucous patches may occur on any mucous membrane, particularly those in the mouth and genitalia. Condylomata lata are flat, wart-like, moist lesions around the mouth, nares, anus, and other areas of the skin where there is moisture or friction (picture 3A-B). They contain spirochetes and can transmit infection.
●Generalized lymphadenopathy – Generalized, nontender lymphadenopathy is a common manifestation. Palpable epitrochlear lymphadenopathy in an infant is highly suggestive of congenital syphilis [23].
●Other manifestations – Other manifestations of early congenital syphilis may include [1,7,17,23,25,29,30]:
•Nonimmune fetal hydrops
•Fever (may be more prominent in infants born to mothers who are affected late in pregnancy and whose serology is negative at delivery)
•Myocarditis
•Pneumonia
•Failure to move an extremity secondary to painful periostitis ("pseudoparalysis of Parrot")
•Sepsis due to other bacteria (eg, Escherichia coli, group B streptococci, Yersinia species) (see "Clinical features, evaluation, and diagnosis of sepsis in term and late preterm neonates")
•Ophthalmologic manifestations – Loss of eyebrows, chorioretinitis, uveitis, cataract, glaucoma, and chancre of the eyelid
•Gastrointestinal manifestations – Rectal bleeding (from ileitis), necrotizing enterocolitis, malabsorption
•Nephrotic syndrome (immune complex mediated; responsive to penicillin) [34-37] (see "Congenital nephrotic syndrome", section on 'Infectious causes')
●Central nervous system (CNS) findings – CNS syphilis in children with congenital infection may be asymptomatic or symptomatic.
Asymptomatic CNS syphilis is indicated by abnormalities in the cerebrospinal fluid (CSF) (see 'Laboratory abnormalities' below). Asymptomatic CNS syphilis occurs in approximately 40 percent of infants who have clinical, laboratory, or radiographic abnormalities of congenital syphilis, but is infrequent in infants without such manifestations [17,38-42].
Symptomatic CNS involvement is rare among infants with congenital syphilis in the era of penicillin therapy but may develop from ongoing dissemination in infants who are not treated in the neonatal period [17]. Symptomatic CNS syphilis in infants has two overlapping presentations:
•Acute syphilitic leptomeningitis typically manifests during the first year of life, usually between three and six months. The clinical findings are suggestive of bacterial meningitis (eg, vomiting, bulging fontanelle, increased head circumference, splitting of the cranial sutures), but the CSF findings are consistent with aseptic meningitis (predominance of mononuclear cells, modest increase in protein, normal glucose) [17,23]. Congenital syphilis should be considered in febrile infants with unexplained aseptic meningitis. Acute syphilitic leptomeningitis generally responds to parenteral penicillin therapy. (See "Congenital syphilis: Management and outcome", section on 'Penicillin therapy'.)
•Chronic meningovascular syphilis typically manifests toward the end of the first year [17]. The clinical findings include signs of progressive hydrocephalus, cranial nerve palsies, papilledema, optic atrophy, neurodevelopmental regression, and seizures. Syphilitic endarteritis may cause cerebral infarction in the second year of life.
In addition, pituitary gland involvement may manifest with persistent hypoglycemia or diabetes insipidus [43,44].
Radiographic abnormalities
●Bony abnormalities – Bony abnormalities are a common manifestation of early congenital syphilis (occurring in 60 to 80 percent of cases) and may be the sole manifestation in infants born to mothers with untreated syphilis [45,46]. The changes usually are present at birth but may appear in the first few weeks after birth. Bone abnormalities may be associated with pathologic fractures or pain, which may limit movement of the involved extremity, giving the appearance of paralysis ("pseudoparalysis of Parrot") [47].
The radiographic abnormalities characteristically are bilateral, symmetric, and polyostotic; the femur, humerus, and tibia are most frequently involved. Findings may include [47-49]:
•Metaphyseal lucent bands (this finding may occur in response to other systemic illnesses) (image 1A).
•Symmetric localized demineralization and osseous destruction of the medial portion of the proximal tibial metaphysis (Wimberger sign), which also may occur in neonatal hyperparathyroidism and osteomyelitis.
•Metaphyseal serration ("sawtooth metaphysis").
•Diaphyseal periostitis with new bone formation (may occur in other conditions including nonaccidental trauma) (image 1B).
•Irregular areas of increased density and rarefaction ("moth-eaten" appearance) (image 1C and image 1D).
●Pulmonary findings – Complete opacification of both lung fields ("pneumonia alba") is the classic radiographic appearance of pneumonia in infants with congenital syphilis. However, a fluffy, diffuse infiltrate involving all lung areas is more common in the era of penicillin therapy.
Laboratory abnormalities
●Hematologic studies – Hematologic abnormalities of early congenital syphilis may include [7,50,51]:
•Anemia – In the newborn period, the characteristic finding is direct antiglobulin test (DAT; also called Coombs) negative hemolytic anemia. Hemolysis is often accompanied by cryoglobulinemia, immune complex formation, and macroglobulinemia [23]. It may last for weeks. Chronic DAT-negative anemia may persist beyond the neonatal period and may be accentuated by the onset of physiologic anemia of infancy.
•Thrombocytopenia.
•Leukopenia or leukocytosis.
●Abnormal liver function tests (LFT) – This may include elevated aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and direct bilirubin. Delayed prothrombin time may be seen if liver synthetic function is impaired. LFT abnormalities may be exacerbated by penicillin therapy before improving [52]. Transaminitis generally resolves slowly, even after adequate therapy.
●CSF abnormalities – Findings that indicate CNS involvement include [1,7,53,54]:
•Reactive CSF VDRL – A reactive CSF Venereal Disease Research Laboratory (VDRL) test supports the diagnosis of CNS syphilis. However, false positives can occur from maternal nontreponemal antibodies crossing the placenta and diffusing into the fetal CSF or through contamination of the CSF with blood from a traumatic lumbar puncture. False negatives can also occur.
•CSF pleocytosis – The CSF white blood cell (WBC) count can be difficult to interpret since normal values in newborns vary by gestational and postnatal age. Some experts define CSF pleocytosis as >5 WBCs/microL [1,42]; others accept values as high as 20 WBCs/microL to be normal [55]. We generally consider a CSF WBC >15/microL in a term newborn to be abnormal; a higher threshold is used in preterm neonates. After the age of one month, CSF pleocytosis is defined as WBC >5 microL.
•Elevated CSF protein – As with WBCs, the definition of elevated CSF protein in newborns is variably defined, ranging from >45 mg/dL to as high as 150 mg/dL (or 170 mg/dL in premature infants). After the age of one month, elevated CSF protein is defined as ≥45 mg/dL.
However, none of these findings is highly sensitive or specific [40,42]. In an observational study that used the rabbit infectivity test as the reference standard for identification of spirochetes in the CSF, the sensitivity and specificity of these findings were as follows [40]:
•Reactive CSF VDRL – Sensitivity 54 percent, specificity 90 percent
•Elevated CSF WBC count – Sensitivity 38 percent, specificity 88 percent
•Elevated CSF protein – Sensitivity 56 percent, specificity 78 percent
Examination of the CSF for T. pallidum deoxyribonucleic acid (DNA) by polymerase chain reaction (PCR) may prove more useful for definitive diagnosis of congenital neurosyphilis [18,40,41], but this test is not widely available. (See 'Other tests' below.)
Late congenital syphilis — Late congenital syphilis is arbitrarily defined by clinical manifestations with onset after two years of age [25]. Manifestations of late congenital syphilis are related to scarring or persistent inflammation from early infection and are characterized by gumma formation in various tissues [56]. Late congenital syphilis develops in approximately 40 percent of infants born to women with untreated syphilis during pregnancy. Most manifestations of late congenital syphilis are prevented by appropriate treatment of the mother during pregnancy or by treatment of the infant within the first three months of life [57,58]. However, other manifestations (eg, keratitis, saber shins) may occur or progress despite appropriate therapy [59].
Manifestations of late congenital syphilis include (table 4) [1,23,58,60,61]:
●Facial features – Frontal bossing (picture 4), saddle nose, short maxilla, protuberant mandible.
●Ophthalmologic – Interstitial keratitis (picture 5) (bilateral, usually occurs around puberty but can occur anytime between 4 and 30 years), secondary glaucoma, corneal scarring, optic atrophy.
●Hearing – Sensorineural hearing loss associated with late congenital syphilis typically develops suddenly at 8 to 10 years of age and often accompanies interstitial keratitis. The higher frequencies are affected first; normal conversational tones are affected later. Syphilis-associated hearing loss may respond to long-term glucocorticoid therapy [62].
●Oropharynx – Hutchinson teeth (hypoplastic, notched, widely spaced permanent teeth [upper central incisors most commonly affected] (picture 6); before eruption, Hutchinson teeth are visible on dental radiographs), mulberry molars (maldevelopment of the cusps of the first molars) (picture 7), and perforation of the hard palate (virtually pathognomonic for congenital syphilis) (picture 8).
●Cutaneous – Rhagades (perioral fissures or a cluster of scars radiating around the mouth) (picture 9), gummas (granulomatous inflammatory response to spirochetes) in the skin or mucous membranes.
●Neurologic – Intellectual disability, arrested hydrocephalus, cranial nerve palsies.
●Skeletal – Anterior bowing of the shins ("saber shins") (picture 10), enlargement of the sternoclavicular portion of the clavicle (Higoumenakis sign), painless arthritis of the knees ("Clutton joints") (picture 11), and, rarely, other joints.
●Hematologic – Paroxysmal cold hemoglobinuria. (See "Paroxysmal cold hemoglobinuria".)
Among these manifestations, Hutchinson triad (Hutchinson teeth, interstitial keratitis, and sensorineural hearing loss), mulberry molars, and Clutton joints are relatively specific for congenital syphilis [23,60].
EVALUATION AND DIAGNOSIS — 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 [10,63]. 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 [53,54]. Similar guidelines are provided by the World Health Organization [64]. (See 'Society guideline links' below.)
The CDC and AAP guidelines continue to recommend that maternal samples be screened according to the traditional algorithm (ie, a nontreponemal test followed when positive by a confirmatory treponemal test) [53,54]. However, both organizations recognize that due to practical and cost considerations, many antenatal care providers screen pregnant individuals in reverse sequence (testing initially for syphilis antibodies, typically by enzyme immunoassay [EIA] or chemiluminescence immunoassay [CIA], followed by nontreponemal test if EIA/CIA is positive). The CDC has provided guidance for interpreting results, which is particularly important when the initial EIA/CIA treponemal test is discordant with the subsequent nontreponemal test [65]. Interpretation of maternal screening results with the traditional and reverse sequence screening algorithms is discussed separately. (See "Syphilis in pregnancy", section on 'Diagnosis' and "Syphilis: Screening and diagnostic testing", section on 'Serologic testing algorithms'.)
Clinical suspicion — The diagnosis of congenital syphilis may be suspected based upon any of the following:
●Maternal syphilis during pregnancy – Evaluation for early congenital syphilis is warranted in all newborns born to mothers who have reactive nontreponemal and treponemal tests for syphilis during pregnancy. (See "Syphilis in pregnancy", section on 'Diagnosis'.)
●Maternal syphilis during first three months after delivery – This includes infants born to women who are identified clinically or through contact tracing [25].
●Concerning clinical findings – The possibility of congenital syphilis should be considered in all newborn infants with concerning clinical findings. This is particularly important when there is prior history or risk factors for syphilis in the mother (eg, inadequate prenatal care, other sexually transmitted diseases, homelessness or unstable housing, drug abuse, incarceration, having sex in conjunction with drug use or transactional sex). Maternal risk factors for syphilis are discussed separately. (See "Syphilis in pregnancy", section on 'Epidemiology'.)
Clinical findings that may raise concern for congenital syphilis in this setting include the following; however, these are nonspecific findings:
•Unexplained prematurity (<37 weeks gestation)
•Unexplained hydrops fetalis
•Enlarged placenta
•Failure to move an extremity ("pseudoparalysis")
•Persistent rhinitis (picture 1)
•Maculopapular or papulosquamous rash (picture 2), particularly in the diaper area, palms, and soles
•Jaundice, hepatomegaly
•Neonatal pneumonia
•Generalized lymphadenopathy
•Anemia (direct antiglobulin test negative)
•Thrombocytopenia
●Infants and children who are adopted internationally – This is discussed separately. (See "International adoption: Infectious disease aspects", section on 'Syphilis'.)
Initial evaluation
Neonates — Diagnostic testing for congenital syphilis is warranted in all newborn infants whose mothers have reactive nontreponemal and treponemal tests for syphilis. 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). (See "Syphilis in pregnancy", section on 'Diagnosis'.)
The initial evaluation of newborns born to mothers who tested positive for syphilis during pregnancy should include all of the following (algorithm 1) [53,54]:
●Quantitative nontreponemal test (Venereal Disease Research Laboratory [VDRL] test or rapid plasma reagin [RPR]) on infant serum (umbilical cord blood should not be used for testing since false positive results can occur if the sample is contaminated with maternal blood). The nontreponemal test performed in the newborn should be the same as was used for the mother so that the newborn's titers can be compared with the mother's. (See 'Nontreponemal tests' below.)
●Physical examination for evidence of congenital syphilis (table 3). (See 'Clinical findings' above.)
●Where available, testing for T. pallidum with direct fluorescent antibody (DFA) staining, darkfield microscopic examination, and/or polymerase chain reaction (PCR) can be performed on any concerning skin lesions or nasal discharge. However, these tests are not available in many clinical settings. (See 'Other tests' below.)
●If possible, pathologic examination of the placenta or umbilical cord can be performed using specific fluorescent antitreponemal antibody staining [20,32,66]. Characteristic histopathologic features are described separately. (See "Care of the umbilicus and management of umbilical disorders", section on 'Funisitis'.)
●Additional evaluation should be performed based upon the findings from the initial evaluation, as discussed below. (See 'Evaluation for extent of organ involvement' below.)
Older than one month — The initial evaluation of infants and children older than one month of age with clinical, radiographic, or laboratory manifestations compatible with congenital syphilis should include [53,54]:
●Quantitative VDRL or RPR (see 'Nontreponemal tests' below)
●Physical examination
●Darkfield microscopic examination or DFA staining of concerning skin lesions or nasal discharge (if available) (see 'Other tests' below)
●Cerebrospinal fluid (CSF) analysis for VDRL, white blood cell (WBC) count, and protein measurement (see 'Lumbar puncture' below)
●Complete blood count (CBC) with differential and platelet count
●Liver function tests
●Skeletal radiographs (see 'Skeletal survey' below)
●Hearing evaluation (see 'Hearing evaluation' below)
●Ophthalmologic examination (see 'Eye examination' below)
●Other tests as clinically indicated (eg, chest radiograph, abdominal ultrasonography, and neuroimaging studies) (see 'Other assessments' below)
Infants and children who are found to have reactive serologic tests for syphilis when they are older than one month of age should have maternal serology and records reviewed to assess whether the child has congenital or acquired syphilis, although this distinction may be difficult [1,24].
In addition to the above testing, any child at risk for congenital syphilis should also undergo testing for HIV [1]. (See "Diagnostic testing for HIV infection in infants and children younger than 18 months" and "Screening and diagnostic testing for HIV infection".)
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 abnormalities on long-bone radiographs are strongly supportive of congenital syphilis. (See 'Congenital versus acquired syphilis' below and 'Radiographic abnormalities' above.)
In a young child, the possibility of sexual abuse should be considered as a cause of acquired syphilis [24]. (See "Evaluation of sexual abuse in children and adolescents", section on 'Sexually transmitted infections'.)
Children who are diagnosed with syphilis after one month of age (including those with previously untreated congenital syphilis) require parenteral penicillin therapy, as discussed separately. (See "Congenital syphilis: Management and outcome", section on '>1 month of age'.)
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 [56].
Diagnostic tests — The diagnosis of syphilis is challenging because T. pallidum cannot be cultured in the laboratory. The diagnosis of syphilis may be established by:
●Demonstration of serologic reactions typical of syphilis (see 'Interpretation' below)
●Detection of T. pallidum in infected body fluids, skin lesions, placenta, or umbilical cord by any of the following (see 'Other tests' below):
•Direct visualization on darkfield microscopy (picture 12)
•DFA, or
•PCR
●Demonstration of the T. pallidum by special stains (picture 13) or histopathologic examination [67,68]
Other tests that involve animal inoculation (eg, rabbit infectivity test [RIT]) are used mostly in research settings.
These testing methods are briefly summarized here and are discussed in detail separately. (See "Syphilis: Screening and diagnostic testing", section on 'Diagnostic tests'.)
Serologic tests — Serologic tests include:
●Nontreponemal tests – These include VDRL and RPR. (See 'Nontreponemal tests' below.)
●Treponemal tests – These include EIA and CIA, which are the two tests used for maternal reverse sequencing, as discussed above (see 'Evaluation and diagnosis' above). Other treponemal tests include fluorescent treponemal antibody absorption (FTA-ABS), T. pallidum particle agglutination (TP-PA), and microhemagglutination test for T. pallidum (MHA-TP). (See 'Treponemal tests' below.)
Nontreponemal tests — Nontreponemal tests are inexpensive and rapidly performed. They are sensitive, but not specific. Nontreponemal tests generally are used in the evaluation of neonates with possible congenital syphilis because they provide semiquantitative results, which can be compared with simultaneously obtained maternal results to categorize the likelihood of neonatal infection (table 5) [54]. Interpretation of the results is discussed below. (See 'Interpretation' below.)
Positive nontreponemal tests are reported as a titer of antibody (eg, 1:32, which represents the detection of antibody in serum diluted 32-fold). The neonate's titer usually is one to two dilutions less than mother's [69]. When the mother's titer is low, the neonate may have nonreactive serology but remains at risk for congenital syphilis. If testing is performed early after maternal infection, both the mother and newborn may have negative nontreponemal tests [70]. (See 'Congenital syphilis less likely' below.)
When congenital syphilis is suspected and the nontreponemal test is negative, evaluation for prozone phenomenon (excess antibody) evaluation should be requested (test at dilution 1:512 and if that dilution is negative, test at 1:1024 dilution).
Nontreponemal titers are also useful for monitoring during treatment since successful treatment is associated with a decline in the titer. (See "Congenital syphilis: Management and outcome", section on 'Follow-up serology'.)
A disadvantage of serologic tests for syphilis is that they detect immunoglobulin G [IgG] antibodies and do not differentiate between passively acquired maternal antibody and endogenous antibody produced by the fetus/neonate. Thus, it is necessary to compare the infant's titer with the mother's to determine the likelihood of congenital infection. It would be more desirable if testing detected only immunoglobulin M [IgM] antibodies, which do not cross the placenta, since this theoretically would be more accurate in confirming congenital infection. Unfortunately, a sufficiently sensitive and specific IgM assay is not available for routine use in the assessment of congenital syphilis [53]. The fluorescent antitreponemal IgM antibody test (IgM FTA-ABS) was used in the past, but because of lack of sensitivity, the CDC suspended its use for diagnostic testing of infants [71,72].
For maternal testing during pregnancy, rapid point-of-care serologic tests are available that can be used as an alternative to laboratory testing, particularly in resource-limited settings. These tests do not require the laboratory infrastructure necessary for conventional tests and can be performed on finger-stick blood samples. They are easy to perform, it is easy to interpret their results, and they have a quick turnaround time (approximately 20 minutes). They have good sensitivity and specificity, comparable to those of conventional treponemal and nontreponemal tests [73,74]. However, they do not provide quantitative results and therefore are not appropriate for testing the neonate. Rapid serologic tests are discussed in greater detail separately. (See "Syphilis: Screening and diagnostic testing", section on 'Rapid serologic tests'.)
Treponemal tests — Treponemal tests (eg, FTA-ABS, TP-PA, EIA, CIA, MHA-TP) are not used in the evaluation of newborns with suspected congenital syphilis when maternal treponemal test results are available.
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. In infants known to have had reactive nontreponemal serologic tests for syphilis as newborns or born to mothers who were seroreactive at delivery, a treponemal test can be performed after 12 to 15 months of age [23,63]. 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 [63,75]. 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 "Congenital syphilis: Management and outcome", section on 'Penicillin therapy'.)
Treponemal tests are discussed in greater detail separately. (See "Syphilis: Screening and diagnostic testing", section on 'Treponemal tests'.)
Other tests
●Darkfield microscopy and DFA – Darkfield microscopy and DFA testing can be used to detect the organism (picture 12); however, these tests are not routinely available in many clinical settings because they require special equipment to perform and considerable experience and expertise to properly interpret the results. Thus, for most clinicians, these tests are now viewed as alternative diagnostic tools.
Where available, darkfield microscopy can be performed on body fluids (eg, nasal discharge) or moist skin lesions [76]. Darkfield microscopy enables demonstration of thin, delicate, corkscrew-shaped organisms with rigid, tightly wound spirals (picture 12). A positive darkfield slide illustrates the characteristic motility associated with T. pallidum: a forward and backward motion with rotation about the longitudinal axis [76]. Soft side-to-side bending and twisting may also be seen. Failure to identify spirochetes with darkfield microscopy does not exclude the diagnosis of syphilis. Darkfield microscopy depends upon the direct visualization of live, active spirochetes, characteristics that are rapidly destroyed by the previous use of antibiotics.
●PCR – PCR has been used on neonatal blood and CSF for diagnosis of congenital syphilis, but these tests are not widely available [18,40,41,77,78]. Compared with isolation of the spirochetes by rabbit infectivity testing, the sensitivity and specificity of PCR on cerebrospinal fluid was 65 to 71 percent and 97 to 100 percent, respectively [40,41]. Among 17 infants who had spirochetes detected in CSF by rabbit inoculation, blood PCR was the best predictor of central nervous system infection with T. pallidum [40].
●Rabbit infectivity test – The RIT, which involves the inoculation of CSF or other body fluids into rabbits to determine the presence of viable T. pallidum, is the reference standard test for congenital syphilis [23,26,56]. However, routine use of RIT is not practical because it involves animal testing and is not widely available.
Interpretation — To maximize treatment of newborns potentially infected with T. pallidum, the AAP categorizes congenital syphilis infection as "proven or highly probable," "possible," "less likely," and "unlikely" (table 5). 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 [53].
The following factors are considered when determining the likelihood of congenital infection:
●Whether the neonate has clinical findings that are consistent with congenital syphilis. (See 'Early congenital syphilis' above.)
●The neonate's syphilis serology, which must be compared with maternal titers. A titer that is ≥4-fold (two dilutions) higher than the maternal titer is indicative of infection (for example, a neonatal titer ≥1:32 when the maternal titer is 1:8). Lower titers in the newborn do not exclude congenital syphilis. (See 'Nontreponemal tests' above.)
●The mother's syphilis serology (in relation to previous tests and/or treatment and in relation to the neonate's titers).
●Maternal treatment for syphilis, including:
•Whether the mother received treatment.
•The timing of completion of treatment (before or during pregnancy; more or less than four weeks before delivery).
•Whether treatment was adequate (table 1).
•The likelihood of failure of maternal therapy to prevent congenital disease – Higher maternal titers and unknown duration of maternal syphilis are associated with increased risk of treatment failure [79].
Proven or highly probable congenital syphilis — For newborns born to women who tested positive for syphilis during pregnancy, the diagnosis of congenital syphilis is proven or highly probable if the neonate has any of the following findings [53]:
●Physical examination findings consistent with congenital syphilis.
●Serum VDRL or RPR titer that is ≥4-fold the corresponding maternal titer (which is equivalent to two dilutions [eg, neonate's titer ≥1:32 and maternal titer 1:8]).
●Positive darkfield microscopy (picture 12), DFA or PCR of lesions, body fluid(s), placenta, or umbilical cord (these tests are not be available in many clinical settings).
Neonates with proven or highly probable congenital syphilis should undergo further evaluation to assess the extent of organ involvement, as summarized in the table (table 5) and discussed below. (See 'Evaluation for extent of organ involvement' below.)
Regardless of the results of additional evaluation, neonates in this category should receive a 10-day course of IV penicillin, as summarized in the table and figure (table 5 and algorithm 1) and discussed in detail separately. (See "Congenital syphilis: Management and outcome", section on '10-day regimen'.)
Possible congenital syphilis — Neonates who meet all of the following criteria are considered to have possible congenital syphilis [53,54]:
●Mother was diagnosed with syphilis during pregnancy (reactive nontreponemal and treponemal tests)
●Mother was not treated, received inadequate/suboptimal therapy, or had evidence of relapse or reinfection (table 1)
●Infant physical examination is normal
●Infant serum VDRL or RPR titer <4-fold maternal titer
Some experts would also consider a newborn to have possible congenital syphilis if the mother had sexual contact with a person with primary or secondary syphilis within 90 days before delivery and was not treated or was inadequately treated, even if the mother had nonreactive serology [25,80].
For neonates in the "possible" congenital syphilis category, the need for additional evaluation and choice of treatment regimen are as follows (table 5 and algorithm 1):
●Neonates at higher risk – For 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), we suggest performing further evaluation to assess the extent of organ involvement, as summarized in the table (table 5) and discussed below. (See 'Evaluation for extent of organ involvement' below.)
If any part of the additional evaluation is abnormal, not performed, or uninterpretable (eg, traumatic lumbar puncture) or if follow-up is uncertain, the neonate should receive a 10-day course of IV penicillin, as summarized in the table and figure (table 5 and algorithm 1) and discussed in detail separately. (See "Congenital syphilis: Management and outcome", section on '10-day regimen'.)
If the additional evaluation is performed and is completely normal and if follow-up is assured, the neonate is treated with a single dose of long-acting intramuscular (IM) penicillin (ie, penicillin G benzathine). (See "Congenital syphilis: Management and outcome", section on 'Single-dose regimen'.)
●Neonates at lower risk – For 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), no additional evaluation is required, and the neonate can be treated with a single dose of IM penicillin G benzathine. (See "Congenital syphilis: Management and outcome", section on 'Single-dose regimen'.)
The CDC and AAP 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 [53,54]. Nevertheless, we suggest performing the evaluation in higher-risk neonates (as defined above) since the evaluation may inform decisions regarding treatment and follow-up.
Congenital syphilis less likely — Infection is less likely if all of the following criteria are met [53,54]:
●Mother was diagnosed with syphilis during pregnancy (reactive nontreponemal and treponemal tests)
●Mother completed appropriate treatment ≥4 weeks before delivery
●Mother has no evidence of reinfection or relapse
●Newborn's physical examination is normal
●Newborn's serum VDRL or RPR titers are <4-fold the maternal titer
Neonates who meet these criteria do not require additional evaluation [53,54]. However, these neonates are at risk and should receive treatment with a single dose of IM penicillin G benzathine, as summarized in the table and algorithm (table 5 and algorithm 1) and discussed in detail separately. (See "Congenital syphilis: Management and outcome", section on 'Single-dose regimen'.)
Congenital syphilis unlikely — The diagnosis of congenital syphilis is unlikely if all of the following criteria are met [53,54]:
●Mother had reactive nontreponemal and treponemal tests
●Mother completed appropriate treatment before pregnancy
●Mother's nontreponemal titers remained low (VDRL <1:2; RPR <1:4) and stable before and during pregnancy and at delivery (ie, serofast)
●Newborn's physical examination is normal
●Newborn's serum VDRL or RPR titers are <4-fold the maternal titer
These newborns generally do not require any additional evaluation or treatment (except in instances when follow-up cannot be assured, in which case a single dose of IM benzathine penicillin is sufficient). (See "Congenital syphilis: Management and outcome", section on 'Treatment according to diagnostic category'.)
Congenital versus acquired syphilis — In children who are found to have reactive serologic tests for syphilis after infancy, the distinction between congenital and acquired syphilis can be difficult [1]. The ultimate diagnosis may rest upon maternal history and clinical judgment [1]. Radiographic abnormalities of the long bones are more suggestive of congenital than acquired syphilis. (See 'Radiographic abnormalities' above.)
In a young child with reactive serologic tests for syphilis, the possibility of sexual abuse should be considered. (See "Evaluation of sexual abuse in children and adolescents", section on 'Sexually transmitted infections'.)
CASE DEFINITION — The Centers for Disease Control and Prevention (CDC) case definition for congenital syphilis is provided in the table (table 6) [1]. Other case definitions may differ slightly from the CDC definition [81].
In general, case definitions for congenital syphilis require only one of two criteria:
●The infant or child has physical, laboratory, or radiographic signs of congenital syphilis (confirmed/highly probable congenital syphilis), or
●The infant or child was born to a mother with untreated, inadequately, or suboptimally treated syphilis (presumed congenital syphilis) (table 1)
EVALUATION FOR EXTENT OF ORGAN INVOLVEMENT — For neonates in the "proven or highly probably" category and those in the "possible" category who have a higher risk of infection (ie, high risk of maternal untreated syphilis or neonate's nontreponemal titer is reactive), we suggest performing all of the following additional tests to evaluate for the extent of organ involvement (table 5) [53,54]. Details about these tests are provided in the sections below.
●Lumbar puncture (LP) for cerebrospinal fluid (CSF) analysis. (See 'Lumbar puncture' below.)
●Complete blood count (CBC) with differential and platelet count. (See 'Blood tests' below.)
●Liver function tests (LFTs, including serum bilirubin and liver enzymes); if LFTs are grossly abnormal, coagulation tests should also be obtained. (See 'Blood tests' below.)
●Skeletal survey. (See 'Skeletal survey' below.)
●Hearing evaluation and ophthalmologic examination – Our practice is to routinely perform these evaluations in all newborns who are undergoing evaluation for extent of organ involvement. This practice differs from the Centers for Disease Control and Prevention (CDC) and American Academy of Pediatrics (AAP) guidelines, which do not recommend routinely performing these assessments since retinitis and hearing loss are rare in newborns with early congenital syphilis [53,54]. However, in affected infants, hearing and vision problems may not be clinically apparent until later in childhood, and there can be serious developmental consequences if these problems are not diagnosed and treated in a timely manner. Thus, we suggest routinely performing these assessments in the neonatal period. (See 'Hearing evaluation' below and 'Eye examination' below.)
●Other tests as clinically indicated (eg, neuroimaging if there are concerning neurologic findings, chest radiograph if there are pulmonary findings). (See 'Other assessments' below.)
The CDC and AAP guidelines include a caveat that the above evaluation is not necessary for neonates in the "possible" category who will be treated with a 10-day course of parenteral penicillin [53,54]. Nevertheless, we suggest performing the evaluation in neonates in this category who are at higher risk for infection (as defined above) since the evaluation may inform treatment and follow-up decisions. (See 'Possible congenital syphilis' above.)
No additional evaluation is necessary for neonates in the "possible" category who have a lower risk of infection (ie, low risk of maternal untreated syphilis and neonate's nontreponemal titer is nonreactive) and those in the "less likely" and "unlikely" categories.
Lumbar puncture — If LP is performed, CSF analysis should include [53,54]:
●Cell count with differential
●CSF protein and glucose
●CSF Venereal Disease Research Laboratory (VDRL)
Ideally, the LP is nontraumatic since results of traumatic taps are not interpretable in this setting.
CSF analysis may help to establish the diagnosis in some infants and it informs decisions about the need for long-term CSF follow-up [42,45]. However, the diagnosis of congenital central nervous system (CNS) syphilis can be difficult to establish. Given the lack of a widely available laboratory test with high sensitivity and specificity for CNS syphilis and the potential consequences of untreated CNS syphilis, the diagnosis of CNS syphilis usually is presumed in children with clinical, radiographic, and laboratory abnormalities compatible with congenital syphilis. (See "Neurosyphilis".)
Blood tests — Routine blood tests performed in infants undergoing evaluation for congenital syphilis include:
●CBC with differential and platelet count to assess for anemia and other hematologic manifestations
●LFTs, including serum bilirubin and liver enzymes, to assess for liver involvement, which is common in symptomatic newborns
●If LFTs are grossly abnormal, coagulation tests should also be obtained
Skeletal survey — Radiographic evaluation to detect bony abnormalities should be performed in all neonates who warrant evaluation for extent of organ involvement. The CDC and AAP guidelines suggest limiting the radiographic evaluation to the long bones (femur, tibia/fibular, humerus, and radius/ulna) since these are the sites most frequently involved [53,54]. However, we generally perform a full skeletal survey since bony abnormalities are occasionally noted in other locations (eg, ribs, clavicles, hands, and feet) [82].
A skeletal survey (or long-bone radiographs) can also be helpful if there is uncertainty as to whether the infant or child has congenital versus acquired syphilis. Bony abnormalities are suggestive of congenital infection, as discussed above. (See 'Congenital versus acquired syphilis' above.)
Radiographic abnormalities characteristically are bilateral, symmetric, and polyostotic (image 1A-D); the femur, humerus, and tibia are most frequently involved, as described above. (See 'Radiographic abnormalities' above.)
Hearing evaluation — All infants and children with proven or highly probable congenital syphilis should undergo formal hearing assessment, typically with auditory brainstem response (ABR). This is best accomplished while the newborn is still in the hospital but can be done in the outpatient setting if follow-up is assured. (See "Hearing loss in children: Screening and evaluation", section on 'Formal audiology'.)
In many settings, all newborns routinely undergo hearing screening prior to discharge from the birth hospitalization. Otoacoustic emissions (OAE) screening is often used for this purpose. OAE is generally less sensitive compared with ABR (ie, higher false negative rate). Thus, in infants with congenital syphilis, formal audiologic evaluation with ABR is generally warranted even if the newborn passes the initial OAE screen. Newborns who pass a screening performed with automated ABR do not require formal audiology. (See "Screening the newborn for hearing loss".)
Eye examination — All infants and children with proven or highly probable congenital syphilis should have formal vision assessment and dilated eye examination performed by a pediatric eye care specialist. This is best accomplished while the newborn is still in the hospital but can be done in the outpatient setting if follow-up is assured. (See "Vision screening and assessment in infants and children".)
Other assessments — Additional testing is guided by the clinical findings and may include:
●Neuroimaging if there are concerning neurologic findings
●Chest radiograph if there are pulmonary findings
●Abdominal imaging if there is significant organomegaly or other concerning findings
DIFFERENTIAL DIAGNOSIS — The differential diagnosis for congenital syphilis includes:
●Other congenital and neonatal infections, including (table 7):
•Toxoplasmosis infection (see "Toxoplasmosis and pregnancy", section on 'Fetal infection' and "Congenital toxoplasmosis: Clinical features and diagnosis", section on 'Clinical features')
•Rubella virus infection (see "Congenital rubella", section on 'Evaluation')
•Cytomegalovirus infection (see "Congenital cytomegalovirus infection: Clinical features and diagnosis", section on 'Clinical manifestations')
•Herpes simplex virus infection (see "Neonatal herpes simplex virus infection: Clinical features and diagnosis", section on 'Evaluation and diagnosis')
•Congenital lymphocytic choriomeningitis virus infection (see "Viral meningitis in children: Epidemiology, pathogenesis, and etiology", section on 'Lymphocytic choriomeningitis virus')
•Neonatal sepsis (see "Clinical features, evaluation, and diagnosis of sepsis in term and late preterm neonates", section on 'Evaluation and initial management')
●Other causes of neonatal jaundice, hepatomegaly, and cholestasis, which are summarized in the table (table 8) and reviewed in detail separately. (See "Causes of cholestasis in neonates and young infants".)
●Other causes of long-bone abnormalities (eg, osteomyelitis, rickets, physical abuse) or failure to move an extremity. (See "Differential diagnosis of the orthopedic manifestations of child abuse" and "Brachial plexus syndromes", section on 'Neonatal brachial plexus palsy'.)
●Other causes of vesicular lesions in neonates, which are summarized in the table (table 9), and reviewed in detail separately. (See "Vesicular, pustular, and bullous lesions in the newborn and infant".)
Historical features, associated findings, and/or laboratory testing usually differentiate these conditions from congenital syphilis.
REPORTING REQUIREMENTS — In the United States, congenital syphilis is a national notifiable disease [83]. However, reporting requirements vary by state. Reporting to the Centers for Disease Control and Prevention by the states is voluntary. For reporting purposes, congenital syphilis includes stillbirths due to syphilis, cases of congenital syphilis detected in newborns, and cases of congenitally acquired syphilis in infants and children [1].
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 — 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 email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient education" and the keyword[s] of interest.)
●Basics topic (see "Patient education: Congenital syphilis (The Basics)")
SUMMARY AND RECOMMENDATIONS
●Transmission and epidemiology – Congenital syphilis is acquired through transplacental transmission of spirochetes. Pregnant individuals with untreated primary or secondary syphilis are at highest risk of transmitting syphilis to the fetus. Treponema pallidum is not transferred in breast milk. In the United States, reported cases of congenital syphilis have increased dramatically since 2012 (figure 1). (See 'Transmission' above and 'Epidemiology' above.)
●Clinical features
•Early congenital syphilis – Early congenital syphilis is arbitrarily defined by clinical manifestations with onset before two years of age. Manifestations of early congenital syphilis are varied and unpredictable, as summarized in the table (table 3). (See 'Early congenital syphilis' above.)
•Late congenital syphilis – Late congenital syphilis is arbitrarily defined by clinical manifestations with onset after two years of age. Manifestations of late congenital syphilis are summarized in the table (table 4); most are related to scarring or persistent inflammation from early infection.
●Clinical suspicion – The diagnosis of congenital syphilis should be suspected in all infants born to mothers who have reactive nontreponemal and treponemal tests for syphilis during pregnancy and infants/children with clinical findings compatible with congenital syphilis (table 3 and table 4). (See 'Clinical suspicion' above.)
●Evaluation – The initial evaluation for congenital syphilis includes the following (see 'Initial evaluation' above):
•Venereal Disease Research Laboratory (VDRL) or rapid plasma reagin (RPR) titer; titers should be measured in both the newborn and the mother using the same test. (See 'Nontreponemal tests' above.)
•Physical examination for evidence of congenital syphilis (table 3). (See 'Clinical findings' above.)
•Where available, testing for T. pallidum can be performed with direct fluorescent antibody (DFA) staining, darkfield microscopy, and/or polymerase chain reaction (PCR) of nasal discharge and/or swabs of skin lesions; however, these tests are not available in many clinical settings. (See 'Other tests' above.)
•If possible, pathologic examination of the placenta and umbilical cord with specific staining.
●Diagnosis – The diagnosis of congenital syphilis may be established by any of the following (table 6):
•Demonstration of serologic reactions typical of syphilis in relation to mother's serology
•Detection of T. pallidum by darkfield microscopy (picture 12), DFA or PCR of infected body fluids or lesions, placenta, or umbilical cord
•Demonstration of the T. pallidum by special stains (picture 13) or histopathologic examination
Based upon the physical examination, maternal and infant VDRL or RPR titers, maternal treatment history, and other findings, the likelihood of congenital syphilis can be categorized as "proven or highly probable," "possible," "less likely," and "unlikely" (algorithm 1 and table 5). (See 'Interpretation' above.)
●Further evaluation – For neonates in the "proven or highly probably" category and those in the "possible" category who have a higher risk of infection (ie, high risk of maternal untreated syphilis or neonate's nontreponemal titer is reactive), we suggest performing all of the following additional tests to evaluate for the extent of organ involvement (table 5) (see 'Evaluation for extent of organ involvement' above):
•Lumbar puncture for cerebrospinal fluid (CSF) analysis (see 'Lumbar puncture' above)
•Complete blood count (CBC) with differential and platelet count (see 'Blood tests' above)
•Liver function tests (LFTs) (see 'Blood tests' above)
•Skeletal survey (see 'Skeletal survey' above)
•Hearing evaluation and ophthalmologic examination (see 'Hearing evaluation' above and 'Eye examination' above)
•Other tests as clinically indicated (eg, neuroimaging if there are concerning neurologic findings, chest radiograph if there are pulmonary findings) (see 'Other assessments' above)
No additional evaluation is necessary for neonates in the "possible" category who have a lower risk of infection (ie, low risk of maternal untreated syphilis and neonate's nontreponemal titer is nonreactive) and those in the "less likely" and "unlikely" categories.
●Differential diagnosis – The differential diagnosis of congenital syphilis includes other congenital infections (table 7); neonatal sepsis; and other causes of neonatal hepatitis, hydrops fetalis, long-bone abnormalities, and cutaneous lesions. Historical features, associated clinical findings, and/or laboratory testing usually differentiate these conditions from congenital syphilis. (See 'Differential diagnosis' 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.
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