Ten Facts about Congenital Syphilis

Congenital syphilis occurs when Treponema pallidum (a spirochete that is the cause of syphilis) is transmitted from mother to child during pregnancy¹ and can result in significant infant and childhood morbidity (which can include skeletal deformities, blindness, deafness, seizures, and developmental delay). In mothers with early untreated syphilis, there is an up-to-40% death rate in the unborn offspring in the forms of still birth, miscarriage, and early infant death.^1,2 Cases of congenital syphilis based on hospital diagnostic code review and cases reported to the Mississippi State Department of Health have also increased dramatically in recent years within the state of Mississippi, with estimates showing an 1100 percent over the past five years.³

1. Congenital syphilis is a preventable disease. Prenatal care reduces the risk of congenital syphilis by 97%,⁴ and penicillin treatment of mothers infected with syphilis has 98% efficacy in preventing congenital syphilis.⁵ However, despite evidence-based prevention, congenital syphilis is a resurging public health problem in the United States, with Mississippi now ranked fourth in the nation for congenital syphilis cases.⁶ Concerningly, Mississippi is one of the few states that had not mandated maternal syphilis screening⁷ up until recently.⁸ Of note, risk-stratification of screening mothers for syphilis has been shown to lack correlation in identifying cases.^9,10

2. Racial minorities and mothers with social vulnerabilities also bear a disproportionate burden of disease.^6,11–13 A recent CDC report from Georgia and Alabama demonstrated that from 2018-2021, pregnant mothers had twice the prevalence of substance use in those who had congenital syphilis compared with those who did not (48.1% vs. 24.6%). Half of these mothers who had a baby with congenital syphilis and had drug abuse also had “late or no prenatal care.” CDC also reports that cases in non-whites are uniformly higher, although rates in whites are also increasing.¹⁴ Barriers to health care access as encountered in southern states must be addressed for mothers to reduce the incidence of this preventable disease.¹⁵ Given that this population at risk for giving birth to babies with congenital syphilis with poor access to care, it is imperative to also screen mothers for other sexually transmitted infections, such as HIV and Hepatitis B, for which there are mother-to-child prevention measures available.

3. Severity and likelihood of infection depends on stage of maternal infection and gestation. Transmission from mother to baby is 60-100% for primary and secondary syphilis infection, and can occur intrauterine or by contact with lesions during birth.¹ Transmission also increases if mothers are infected later in gestation or co-infected with HIV.¹ Breastfeeding is not linked to transmission, however (in contrast to HIV), unless mothers have breast (chancre) lesions.¹ Syphilis screening in the first trimester with rescreening in the third trimester and at delivery as well as confirmation of mother and baby syphilis status before hospital discharge are recommended by CDC, and Mississippi has just adopted this guidance.⁸ Multiple analyses have shown screening and treatment of mothers reduces congenital syphilis-associated morbidity and mortality and is also cost effective.^5,9,16–18

4. Symptom severity and onset ranges and may be present at birth or within the first few months of birth, although most (60-90%) of infants are asymptomatic at birth¹⁹: symptoms may include hepatosplenomegaly, jaundice, snuffles (nasal secretions), rash (which may appear maculopapular and can be more severe on the hands and feet), lymphadenopathy, skeletal abnormalities (osteochondritis, periostitis, and “pseudo paralysis of Parrot” may also occur due to the pain from bone abnormalities), and hematologic abnormalities (hemolytic anemia or thrombocytopenia). Severe presentations with non-immune hydrops fetalis, pneumonia, central nervous system infection, and even myocarditis may occur.^1,2,20 Symptoms present before 2 years of age are considered consistent with “early” congenital syphilis. Untreated infants, including those asymptomatic at birth, may develop “late” congenital syphilis manifestations, manifesting after 2 years, and which may also include involvement of the central nervous system (CNS), as well as bones and joint (anterior bowing of the shins, frontal bossing, and Clutton joints or bilateral and painless knee swelling), or even tooth abnormalities (Hutchinson teeth, or “peg-shaped, notched central incisors” and mulberry molars, or molar deformity). Blindness (e.g., interstitial keratitis) and deafness (eighth cranial nerve deafness)x may also occur and not be evident until well after birth. Other phenotypic manifestations include saddle nose (depression of the nose bridge) and underdevelopment of the mandible, rhagades (perioral fissures). CNS manifestations may include asymptomatic abnormalities of CSF detected during an evaluation for congenital syphilis, or acute (consider especially in infants with aseptic meningitis, especially with lack of other explanation, during the first year or life) or chronic meningitis.^1,2

5. Understanding treponemal and non-treponemal test results in both mother and infant are important in diagnosis and evaluation of an infant with possible congenital syphilis. The American Academy of Pediatrics Red Book provides algorithms for testing strategies for congenital syphilis, including for both traditional (screen with non-treponemal test followed by confirmatory treponemal testing) and the reverse sequence (testing for syphilis antibodies followed by a non-treponemal test) algorithms.¹ For the former, confirmatory testing aids in diagnosis. For the latter, nontreponemal testing is needed as it is compared with the mother’s result. Nontreponemal testing is also used for monitoring of treatment success (importantly, two nontreponemal tests are needed when there is a “discordance” between syphilis antibody and nontreponemal test).

6. Understanding what constitutes adequate treatment in mothers is essential in determining treatment in infants. Infants are at risk for congenital syphilis if his or her mother was not treated or was inadequately treated (including dosing of penicillin and documentation of treatment response by fall in titers), or if there is no documentation of treatment, or if mother was treated with a nonpenicillin G regimen or received treatment less than 4 weeks before delivery. Treatment of syphilis in pregnancy and infants must be with penicillin, and desensitization may be indicated if allergy is suspected, whenever possible. Maternal and infant treatment must be with penicillin, and, if mothers are treated with a non-penicillin agent, this puts the infant in a higher risk category for congenital syphilis evaluation (cases of congenital syphilis have been reported in such situations).^1,2 Pediatric infectious disease specialists consider 3 doses of penicillin G administered to mothers, each one week apart, as adequate treatment in most cases (for late latent syphilis), especially in Mississippi where prevalence is so high, unless the diagnosis of primary or secondary syphilis is certain or the duration of latent infection is known (e.g. negative syphilis test had been documented within a year).^1,2,14 Providers’ knowledge about adequate treatment for syphilis is particularly important in states with high prevalence like Mississippi.

7. Treatment of the infant^[1] is indicated in situations in which the risk of congenital syphilis is high or there is physical or laboratory exam evidence of disease. Infant evaluation in suspected cases includes complete blood cell count and differential/platelet, cerebrospinal fluid analysis (for VDRL, cell count, and protein) and other tests as clinically indicated (chest radiographs, long bones radiographs, liver function tests, and neuroimaging). In addition, ophthalmologic and audiology evaluations must be completed.^1,2 If ten days of intravenous penicillin are indicated for the infant (that is, if mothers have not been adequately treated as above, and/or if any part of the congenital syphilis work-up is abnormal or incomplete, or if maternal/infant serology dictate treatment per AAP algorithms¹), ampicillin doses should not be counted, nor is ampicillin considered sufficient treatment as a substitute for penicillin.^1,2 Of note, if more than one dose is missed, the entire regimen needs to be restarted.² A single dose of intramuscular benthazine penicillin (long-acting) is only used in cases in which congenital syphilis may be very much less likely or possible, and only if maternal treatment has been deemed sufficient with all laboratory and physical exam components are normal (including CSF) and with follow-up assured.

8. Testing for other infectious diseases and infection prevention measures specific to mother and infant should be considered with close follow-up, including but not limited to reporting of every case of infants with suspected syphilis to the Mississippi State Department of Health. If a mother has syphilis, other sexually transmitted diseases must be thoroughly evaluated for in both mother and baby. Standard precaution is appropriate in most infants with suspected or confirmed congenital syphilis, but contact precautions should be employed in cases of congenital syphilis with skin and mucous membrane lesions until the first 24 hours of treatment have been completed. Infants with congenital syphilis must be followed carefully at 2, 4, 6, and 12 months of age with repeat nontreponemal serological testing every 2-3 months. If titers do not decrease or increase, re-evaluation (including CSF re-examination) and retreatment with 10 days of penicillin G are necessary. Repeat CSF examination is not necessary in infants who had initial abnormal results unless titers remain positive after 6-12 months. Neonates born to mothers with negative non-treponemal tests at delivery whose mothers were positive (seroreactive) at the time should have retesting at 3 months to rule out infection, as an infant may be seronegative at birth if the mother was infected late in pregnancy.^1,2 If a baby is diagnosed with congenital syphilis, evaluation of siblings (if not already completed) may need to be considered. Treponemal tests are not used to evaluate treatment efficacy or response as they may remain positive, or an infant may have evidence of positivity due to maternal antibody transfer, but a positive treponemal test after 18 months of age is diagnostic of congenital syphilis.

9. Routine screening for syphilis is not currently mandated for teens. The Mississippi Division of Medicaid requires routine screening for HIV to be done once between the ages of 15-18 per EPSDT guidelines.²¹ It does not stipulate screening for syphilis with an RPR. Pediatricians and family physicians should consider routine screening with and RPR when drawing an HIV given the increasing prevalence of disease in the state. The Mississippi Chapter of the American Academy of Pediatrics is investigating the feasibility of adding routine RPR testing to the AAP Bright Futures Periodicity Table.²²

10. Barriers to prenatal care or treatment are directly correlated to increased disease, and early identification and treatment in pregnancy is critical for preventing congenital syphilis. Lack of timely screening and prenatal care have been identified as factors associated with congenital syphilis.¹⁷ As such, we advocate for presumptive eligibility for pregnant moms who are eligible for Medicaid: currently it takes the Division of Medicaid an average of 4 weeks to process a completed application. Then it may take another 4-6 weeks for moms in some areas to get appointments with an obstetrician during which screening is now mandated.^8,22 We, therefore, advocate for presumptive eligibility to facilitate early entry into medical care while Medicaid coverage is pending.²³